US20200323816A1 - Kaempferol analog-containing composition - Google Patents

Kaempferol analog-containing composition Download PDF

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US20200323816A1
US20200323816A1 US16/642,189 US201816642189A US2020323816A1 US 20200323816 A1 US20200323816 A1 US 20200323816A1 US 201816642189 A US201816642189 A US 201816642189A US 2020323816 A1 US2020323816 A1 US 2020323816A1
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kaempferol
composition
glycoside
residue
och
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Yasutaka IKEDA
tsubasa MIZOKAMI
Yasuhiro Abiru
Minoru Akiyama
Ayuko OYAMA
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Otsuka Pharmaceutical Co Ltd
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Otsuka Pharmaceutical Co Ltd
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Assigned to OTSUKA PHARMACEUTICAL CO., LTD. reassignment OTSUKA PHARMACEUTICAL CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ABIRU, YASUHIRO, AKIYAMA, MINORU, OYAMA, Ayuko, IKEDA, YASUTAKA, MIZOKAMI, Tsubasa
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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A23L29/035—Organic compounds containing oxygen as heteroatom
    • 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
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • 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
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
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    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/31—Foods, ingredients or supplements having a functional effect on health having an effect on comfort perception and well-being
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A23V2250/2116—Flavonoids, isoflavones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present application relates to a composition for improvement in physical activity efficiency, a composition for reducing fatigue, and a composition for improving dynamic/kinetic visual acuity.
  • Improvement of physical activity efficiency, reduction of fatigue, and improvement in dynamic/kinetic visual acuity are very important not only in athletes with intense training but also in ordinary people's daily work (e.g. housework, baggage handling, stair climbing).
  • Oxygen consumption is an indicator of energy production, and improving oxygen consumption efficiency is key to achieving a sustained “physical activity” in sports and daily life without feeling tired or breathlessness.
  • Non-Patent Document 1 Arterial oxygen saturation (at rest) is about 97% in people in their 20s, but this value decreases with age, reaching about 93% in people in their 60s (Non-Patent Document 2).
  • the decline in oxygen status may also occur in the daily lives of ordinary people due to aging, labor, bad weather (atmospheric depression), apnea syndrome and the like.
  • Kaempferol is a kind of natural flavonoid contained in various edible plants, such as tea, broccoli, grapefruit, cabbage, kale, beans, Cichorium endivia , leek, tomato, strawberry, grape, Brussels sprouts, apple, quinua, and horseradish.
  • Natural flavonoids including kaempferol
  • kaempferol have been studied with a focus on their diverse physiological effects, including the involvement of kaempferol in mitochondrial function (Patent Document 1, Patent Document 2, and Non-Patent Document 3) and the effects of kaempferol on cellular energy expenditure and thyroid hormone (Non-Patent Document 4), all of which relate to in vitro studies.
  • Patent Document 3 discloses the effect of quercetin on lactic acid concentration, but there is no specific disclosure using other flavonoids.
  • An object of the present application is to provide a composition which can improve oxygen consumption efficiency (that is, the ability to use oxygen can be enhanced.), and thereby can suppress a decrease in physical activity efficiency, improve physical activity efficiency, or reduce fatigue, or which can suppress a decrease in dynamic/kinetic visual acuity, or improve dynamic/kinetic visual acuity, even at the lowered oxygen state in addition to the normal oxygen state.
  • the present inventors have been intensively studied to solve the above problems, and have found that oral administration of a kaempferol-containing composition to a human increases oxygen consumption efficiency, improves physical activity efficiency, reduces fatigue feeling, and improves dynamic/kinetic visual acuity, in a wide range of an exercise ranging from mild exercise of the level of daily work to an exercise of the level of intense sports, thereby reaching the present invention.
  • the present invention provides the following:
  • composition for improvement in physical activity efficiency comprising a kaempferol analog of Formula I:
  • R 1 is —OH, or —OCH 3 ;
  • R 2 is H, or —OH
  • R 3 is H, —OH, or —OCH 3 ;
  • R 4 is —OH, or —OCH 3 ;
  • R 5 is H, or —OH
  • R 6 is H, —OH, or —OCH 3 ;
  • composition for reducing fatigue comprising a kaempferol analog of Formula I:
  • R 1 is —OH, or —OCH 3 ;
  • R 2 is H, or —OH
  • R 3 is H, —OH, or —OCH 3 ;
  • R 4 is —OH, or —OCH 3 ;
  • R 5 is H, or —OH
  • R 6 is H, —OH, or —OCH 3 ;
  • composition for improving dynamic/kinetic visual acuity comprising a kaempferol analog of Formula I:
  • R 1 is —OH, or —OCH 3 ;
  • R 2 is H, or —OH
  • R 3 is H, —OH, or —OCH 3 ;
  • R 4 is —OH, or —OCH 3 ;
  • R 5 is H, or —OH
  • R 6 is H, —OH, or —OCH 3 ;
  • R 1 , R 2 , R 4 , and R 6 is independently selected from —OR 7 , —OR 7 R 8 , and —OR 7 R 8 R 9 ;
  • R 7 is a glucose residue
  • R 8 and R 9 are independently selected from a glucose residue, a mannose residue, a galactose residue, a fucose residue, a rhamnose residue, an arabinose residue, a xylose residue, a fructose residue, a glucuronic acid residue, and an apiose residue.
  • composition according to any one of [1] to [15], wherein said composition is a food and drink.
  • the present invention provides use of a kaempferol analog or a glycoside thereof in the manufacture of a composition for improvement in physical activity efficiency, a composition for reducing fatigue, or a composition for improving dynamic/kinetic visual acuity.
  • the present invention provides a method for improvement in physical activity efficiency, a method for reducing fatigue, or a method for improving dynamic/kinetic visual acuity, comprising administering a kaempferol analog or a glycoside thereof.
  • the present invention provides a kaempferol analog or a glycoside thereof for use in improvement in physical activity efficiency, reducing fatigue, or improving dynamic/kinetic visual acuity.
  • the composition of the present invention may improve oxygen consumption efficiency (an ability to utilize oxygen), thereby allowing for increased efficiency in any “physical activity” including daily activities and sports.
  • the composition of the present invention may allow for an exercise with a reduced breathlessness or an improved endurance.
  • the composition of the present invention may also be used as a composition for reducing breathlessness or a composition for improving endurance.
  • the composition of the present invention may reduce fatigue, and may allow for performing sports, daily housework, etc. without feeling fatigue.
  • the composition of the present invention may improve dynamic/kinetic visual acuity and may contribute to an improved outcome, for example in sports.
  • FIG. 1 depicts a graph showing the oxygen consumption (VO 2 ) at each exercise intensity.
  • FIG. 2 depicts a graph showing the oxygen consumption efficiency (VO 2 /VE) after initiation of incremental loading exercise.
  • FIG. 3 depicts a graph showing the oxygen uptake efficiency slope (OUES) for each of the dosages in incremental loading exercise.
  • FIG. 4 depicts a graph showing the maximum oxygen consumption (VO 2peak ) for each of the dosages in incremental loading exercise.
  • FIG. 5 depicts a graph showing the maximum exercise load for each of the dosages in incremental loading exercise.
  • FIG. 6-1 depicts a graph showing the exercise intensity (% HR) and the rating of perceived exertion (RPE) at the oxygen consumption equivalent to the level of climbing stairs.
  • FIG. 6-2 depicts a graph showing the exercise intensity (% HR) and the rating of perceived exertion (RPE) at the oxygen consumption equivalent to the level of jogging.
  • FIG. 7 depicts a graph showing the dynamic visual acuity (DVA) before and after incremental loading exercise.
  • FIG. 8 depicts a graph showing the effect of each compound on ATP production in a hypoxic environment.
  • FIG. 9-1 depicts a graph showing the ATP content in the soleus muscle (Sol).
  • FIG. 9-2 depicts a graph showing the ATP content in the whole brain.
  • FIG. 10 depicts a graph showing the time changes for the 1st and 2nd 400 m runs.
  • FIG. 11 depicts a graph showing the respiratory rate during 400 m runs.
  • FIG. 12 depicts a graph showing the exercise intensity during sprints.
  • FIG. 13 depicts a graph showing the changes in expiratory mouth pressures.
  • FIG. 14 depicts a graph showing the changes in heart rates.
  • the invention relates to a composition for improvement in physical activity efficiency, a composition for reducing fatigue, or a composition for improving dynamic/kinetic visual acuity, comprising a kaempferol analog or a glycoside thereof.
  • a kaempferol analog is a compound of Formula I:
  • R 1 is —OH, or —OCH 3 ;
  • R 2 is H, or —OH
  • R 3 is H, —OH, or —OCH 3 ;
  • R 4 is —OH, or —OCH 3 ;
  • R 5 is H, or —OH
  • R 6 is H, —OH, or —OCH 3 ;
  • composition of the present invention may comprise glycoside(s) of the kaempferol analog(s). Since the glycoside(s) of the kaempferol analog(s) may be converted into their aglycone(s) in vivo, they may have the same activity as the aglycone(s).
  • a glycoside of a kaempferol analogue means a compound in which a sugar chain having at least 1 (preferably 1 to 3, more preferably 1) sugar residue is glycosidically bonded to at least 1 (preferably 1 to 2, more preferably 1) hydroxy group of the kaempferol analogue.
  • the sugar residue(s) include a glucose residue, a mannose residue, a galactose residue, a fucose residue, a rhamnose residue, an arabinose residue, a xylose residue, a fructose residue, a glucuronic acid residue, and an apiose residue.
  • glycoside(s) of the kaempferol analog(s) include compound(s) of Formula I, wherein
  • R 1 , R 2 , R 4 , and R 6 is independently selected from —OR 7 , —OR 7 R 8 , and —OR 7 R 8 R 9 ;
  • R 7 is a glucose residue
  • R 8 and R 9 are independently selected from a glucose residue, a mannose residue, a galactose residue, a fucose residue, a rhamnose residue, a arabinose residue, a xylose residue, a fructose residue, a glucuronic acid residue, and apiose residue.
  • kaempferol analog(s) and glycoside(s) thereof include the following kaempferol analog(s) and glycoside(s) thereof:
  • kaempferol analog(s) include kaempferol, and examples of its glycoside (s) include kaempferol 3-O-glucoside.
  • a kaempferol analog or a glycoside thereof may be a combination of kaempferol analog(s) and glycoside (s) of kaempferol analog(s).
  • a kaempferol analog may be a single kind of kaempferol analog or a combination of a plurality of kinds of kaempferol analog (s).
  • a glycoside of a kaempferol analogue may be a single kind of glycoside of a kaempferol analogue or a combination of a plurality of kinds of glycoside(s) of kaempferol analog(s).
  • a kaempferol analog or a glycoside thereof used in the composition of the present invention is not limited in any way by its form, method of production or the like.
  • an extract from a plant known to contain a large amount of kaempferol, prepared by a known method may be used as it is, or a synthetic product may be used.
  • the glycoside(s) of the kaempferol analogue(s) derived from such plant may be used as it is or may be converted into aglycone(s) (kaempferol analogue(s)), by a known method (For example, by enzymatic treatment).
  • a product with a higher content obtained by a process such as concentration or purification
  • a process such as concentration or purification
  • a known method of concentration or of purification can be used.
  • kaempferol analog equivalent value means a value obtained by converting the amount of the glycoside of the kaempferol analog into the amount of the kaempferol analog as its aglycone. Specifically, the kaempferol analog equivalent value can be calculated by multiplying the amount of substance of the glycoside, which is obtained by dividing the amount of the glycoside by its molecular weight, by the molecular weight of the aglycone.
  • the amount of kaempferol analog(s) or glycoside (s) thereof contained in the composition of the present invention (food and drink, pharmaceutical composition, etc.), the amount of kaempferol analog(s) or glycoside(s) thereof administered per administration, and the amount of kaempferol analog(s) or glycoside(s) thereof administered per day are not particularly limited as long as they are within the range in which the intended effect is exerted, and may be selected according to the form of the composition, the number of administrations, the health condition of the subject, etc.
  • the administration period of the composition of the present invention is not particularly limited as long as it is within the range in which the intended effect is exerted, and may be administered as a single dose or continuously.
  • composition of the present invention may be desirably administered continuously over a long period of time, for example, 2 days, 3 days, 1 week, 10 days, 1 month, or 3 months or more.
  • Examples of the amount of kaempferol analog(s) or glycoside(s) thereof comprised in the composition of the present invention includes 0.1 mg to 200 mg, preferably 0.5 mg to 100 mg, more preferably 1 mg to 30 mg, and most preferably 2 mg to 10 mg, which may vary depending on the total weight of the composition.
  • Examples of the lower limit of the amount of the kaempferol analog equivalent value include 0.1 mg, 0.5 mg, 1 mg, 2 mg, and 2.5 mg, and examples of the upper limit include 200 mg, 150 mg, 100 mg, 50 mg, 30 mg, 25 mg, 15 mg, 10 mg, 5 mg, 3 mg, and 2.5 mg, and a preferred range of the amount of the kaempferol analog equivalent value may be indicated by a combination of the upper and lower limits.
  • compositions of the present invention may be such that kaempferol analog(s) or glycoside(s) thereof are administered, for example, 0.1 mg to 200 mg per administration, preferably 0.5 mg to 100 mg per administration, more preferably 1 mg to 30 mg per administration, and most preferably 2 mg to 10 mg per administration, as a kaempferol analog equivalent value.
  • Examples of the lower limit of the dose of the kaempferol analog equivalent value per administration include 0.1 mg, 0.5 mg, 1 mg, 2 mg, and 2.5 mg, and examples of the upper limit include 200 mg, 150 mg, 100 mg, 50 mg, 30 mg, 25 mg, 15 mg, 10 mg, 5 mg, 3 mg, and 2.5 mg, and a preferred range of the dose of the kaempferol analog equivalent value per administration can be indicated by a combination of the upper and lower limits.
  • kaempferol analog(s) or glycoside(s) thereof may be administered, for example, from 0.1 mg to 600 mg per day, preferably from 0.5 mg to 200 mg per day, more preferably from 1 mg to 100 mg per day, as a kaempferol analog equivalent value.
  • Examples of the lower limit of the dose of the kaempferol analog equivalent value per day include 0.1 mg, 0.5 mg, 1 mg, 2 mg, and 2.5 mg, and examples of the upper limit include 600, 300, 200 mg, 150 mg, 100 mg, 50 mg, 30 mg, 25 mg, 15 mg, 10 mg, 5 mg, 3 mg, and 2.5 mg, and a preferred range of the dose of the kaempferol analog equivalent value per day may be indicated by a combination of the upper and lower limits.
  • the dose of kaempferol analog(s) or glycoside(s) thereof which may be administered per day may be administered in a single dose or in multiple divided doses (for example, twice, three times, four times, and five times).
  • composition of the present invention is preferably formulated as oral dosage forms, and the form is not particularly limited, but may be conventional food forms such as tablets, granules, capsules, powders, chewable tablets, sweets (cookies, biscuits, chocolate confectioneries, chips, cakes, gums, candies, gummies, buns, yokan (sweet bean jelly), puddings, jellies, yogurt, ice cream, sherbet, etc.), breads, noodles, rice, cereal foods, beverages (liquid preparations, soft drinks, carbonated drinks, nutritional drinks, powdered drinks, fruit drinks, milk drinks, jelly drinks, etc.), soups (powder, freeze-dry), miso soups (powder, freeze-dry), and the like.
  • the composition of the present invention may be a food and drink or a pharmaceutical composition, and may be used as a food and drink, for example Foods with Functional Claims, Food for specified health uses, a health food, a nutritional supplement (supplement), a food for medical use, etc.
  • compositions of the invention may be formulated into orally administered formulations by adding pharmaceutically acceptable base(s), carrier(s), and/or additive(s) usable in foods, etc., in addition to kaempferol analog(s) or glycoside(s) thereof. It is desirable that ingredients other than kaempferol analog(s) or glycoside (s) thereof used in the composition of the present invention do not impair the stability of the kaempferol analog(s), and that they do not impair the intended effect(s) of the composition of the present invention (for example, improved oxygen consumption, improved physical activity efficiency, reduced fatigue, or improved dynamic/kinetic visual acuity).
  • “improvement of oxygen consumption efficiency” means an increased ability to utilize oxygen. Specific examples include an increase in the oxygen consumption efficiency (VO 2 /VE) described in the present Examples, and under a given exercise intensity an increase in oxygen consumption (VO 2 ), an increase in oxygen uptake efficiency slope (increase in OUES), and an increase in maximum oxygen consumption (VO 2peak ).
  • physical activity means a moving the body and includes any movements, for example daily housework, baggage handling, stair climbing, sports, and the like.
  • “improvement in physical activity efficiency” means that the body can be moved more easily in any kinds of physical activities.
  • improvement in physical activity efficiency includes continuing a physical activity for a long time in a more comfortable state by improving endurance, or doing a physical activity more easily in a state of reduced breathlessness.
  • indices of improvement in physical activity efficiency include under a given exercise intensity, increased oxygen consumption (VO 2 ), increased oxygen consumption efficiency (VO 2 /VE), increased oxygen uptake efficiency slope (increased OUES), increased maximum oxygen consumption (VO 2peak ), increased maximum exercise load, decreased exercise intensity at a given oxygen consumption (VO 2 ), or decrease in rating of perceived exertion (these terms are described in Examples).
  • the dosage and the number of doses are not particularly limited, and the composition may be administered in the dosage, the number of doses and the period of administration exemplified above.
  • the term “reducing fatigue” means that any physical activity can be done while suppressing fatigue.
  • indices of fatigue reduction include decreased exercise intensity or decrease in rating of perceived exertion (these terms are described in Examples).
  • the dosage and the number of doses are not particularly limited, and may be administered, for example, at the dose, the number of doses and the period of administration exemplified above.
  • improvement of dynamic/kinetic visual acuity means prevention of reduction of dynamic/kinetic visual acuity or improvement of dynamic/kinetic visual acuity.
  • the dosage and the number of doses are not particularly limited, and the composition may be administered in the dosage, the number of doses and the period of administration exemplified above.
  • the composition of the present invention may have an effect of improving oxygen consumption efficiency (That is, the ability to use oxygen increases.). Therefore, the composition of the present invention may also be used for improving oxygen consumption efficiency.
  • the “hypoxic” state means a state in which oxygen level in the body is insufficient, for example, a state in which arterial oxygen saturation is less than 95%. Since the composition of the present invention may have an effect of improving oxygen consumption efficiency even in a subject in a hypoxic state, the composition of the present invention may contribute to improvement of physical activity efficiency, reduction of fatigue, and improvement of dynamic/kinetic visual acuity even in the subject in the hypoxic state.
  • the subject of administration of the composition of the present invention is not particularly limited, but is preferably human. It is preferable to administer the composition before and after sports, before and after outdoor work, before and after daily work (going up and down stairs, doing housework, etc.), when the subject feels that daily fatigue cannot be relieved, when the subject wants to work efficiently, or when the subject feels that the physical movement has become dull due to aging.
  • Cookies (kaempferol content: 2.5 mg) Quinua extract* 37 wt % Maple syrup 22 wt % Milk 22 wt % Salted butter 15 wt % Granulated sugar 4 wt % Total 100 wt %
  • Quinua extract* an Quinua extract wherein kaempferol glycosides were degraded into kaempferol aglycones by an enzymatic treatment.
  • Capsule-shaped food (kaempferol content: 2.5 mg) Ethanol-extracted and enzyme-treated quinoa powder** 48 wt % Gelatin Capsule 52 wt % Total 100 wt %
  • Gelatin Capsule was filled with Ethanol-extracted and enzyme-treated quinoa powder** to give the capsule food.
  • the amount of kaempferol contained in one capsule was 2.5 mg (HPLC).
  • Ethanol-extracted and enzyme-treated quinoa powder** prepared by process comprising: extracting quinua grains with a 50% ethanol to give kaempferol glycosides, and then treating enzymatically to degrade the kaempferol glycosides into kaempferol aglycones.
  • kaempferol-containing cookie-shaped foods containing 2.5 mg, 10 mg, or 25 mg of kaempferol, respectively
  • a placebo cookie-shaped food kaempferol-free
  • 3 hours after a test food ingestion on day 1 (Single ingestion) and on day 8 (Consecutive ingestion) an incremental loading exercise with bicycle was performed while sampling the exhaled gas to determine the oxygen consumption.
  • the Heart rate and the rating of perceived exertion were monitored during exercise. Dynamic/kinetic visual acuity was measured before and after the exercise. Details of each endpoint are given below.
  • Oxygen consumption (VO 2 ) (mL/min/kg) was calculated from the difference between the amount of oxygen in the inhaled gas (atmosphere) and the amount of oxygen in the exhaled gas.
  • HR heart rate
  • the increase in heart rate from the resting heart rate to the maximum heart rate was defined as 100% of exercise intensity, and the oxygen consumption (VO 2 ) was plotted at each exercise intensity.
  • an exercise intensity of 50% HR is calculated by the following equation:
  • oxygen consumption (VO 2 ) in which the heart rate is the “x” means “oxygen consumption (VO 2 ) at an exercise intensity of 50% HR”.
  • Oxygen consumption efficiency was calculated by the following equation.
  • Oxygen consumption efficiency (VO 2 /VE) oxygen consumption/ventilation
  • the oxygen uptake efficiency slope was calculated using the ventilation and VO 2 every 1 min from the beginning of the incremental loading exercise. Specifically, a graph of linearity was obtained by plotting “logarithmic value of ventilation (VE)” on the horizontal axis and “VO 2 ” on the vertical axis, and the slope of the linear function graph was defined as OUES. For details, see Non-Patent Document 5.
  • Oxygen consumption (VO 2 ) during stair climbing and jogging has been reported to be generally 14 mL/min/kg and 24.5 mL/min/kg, respectively.
  • the calculation methods for oxygen consumption (VO 2 ) and exercise intensity (% HR) are the same as those described above.
  • the perceived exertion was rated by the subject according to the following table at 1-minute intervals from the beginning of the incremental loading exercise, and the scales rated by each subject were averaged to give the rating of perceived exertion (RPE).
  • RPE perceived exertion
  • ingesting the kaempferol-containing food increased the oxygen consumption and the oxygen consumption efficiency at the same exercise intensities.
  • the maximum exercise load increased.
  • the heart rate was decreased, which suggests that the subjects could exercise more comfortably with less breathlessness due to increased endurance.
  • This improvement in physical activity efficiency may also reduce the fatigue of the subject.
  • the ingestion of kaempferol-containing foods reduced perceived exertion and reduced breathlessness and fatigue. Therefore, it is suggested that the composition may be used for reducing breathlessness, and/or an enhancing endurance and/or improving oxygen consumption.
  • DVA dynamic visual acuity
  • KVA kinetic visual acuity
  • the fastest visible speed of Landolt's ring moving horizontally on the arc was measured with the subject as the center.
  • the target automatically decelerated gradually as it rotated, and when the subject detected the break in Landolt's ring, the subject pressed a switch on his/her hand to indicate the direction (up and down, and left and right) of the break.
  • the number of revolutions at the time of the digital display was recorded on the recording paper and used as the inspection result. The results are shown in FIG. 7 .
  • C 2 C 12 skeletal muscle cells differentiated with horse serum were obtained, and various compounds (Final concentration of 20 ⁇ M) or dimethyl sulfoxide (DMSO) as a negative control were added thereto.
  • DMSO dimethyl sulfoxide
  • the ATP content in the cells was determined using a kit (luciferase luminescence assay) manufactured by TOYO B-Net Co., Ltd.
  • the ATP content of the negative control treated with DMSO was defined as 100%, and the activity value of the test compounds was calculated as a percentage based on the value of DMSO.
  • mice at 9 weeks of age were orally administered kaempferol (KMP; 1.0 mg/kg body weight) or kaempferol 3-O-glucoside (K3G; 0.1, 0.2, or 1 mg/kg body weight (KMP aglycone equivalent value)) once a day for 8 consecutive days at 9 AM (reared in 21% oxygen).
  • KMP kaempferol
  • K3G kaempferol 3-O-glucoside
  • K3G 0.1, 0.2, or 1 mg/kg body weight
  • KMP aglycone equivalent value 1 mg/kg body weight
  • a two-group and two-phase crossover study (single ingestion) was conducted for 13 healthy male adults.
  • a kaempferol-containing capsule-shaped food (SNR 14) wherein the aglycone equivalent value is 10 mg; and a placebo capsule-shaped food: Placebo (kaempferol free) were used as test foods.
  • FIG. 10 depicts a graph showing the time change between the 1st and 2nd 400 m runs.
  • the mean time change of the placebo group was ⁇ 0.11 seconds and the mean time change of the kaempferol-Ingestion group was ⁇ 0.77 seconds.
  • FIG. 11 depicts a graph showing the respiratory rate during the run.
  • the total number of breaths during the run was significantly lower in the kaempferol-containing food group compared with the placebo food group, and the respiratory rate (times per minute) every 50 m was also significantly lower in the kaempferol-containing food group.
  • FIG. 12 depicts a graph showing the exercise intensity during the runs.
  • the exercise intensity during the run was significantly lower in the kaempferol-containing food group compared with the placebo food group.
  • FIG. 13 shows a graph showing the changes in expiratory mouth pressure. As shown in FIG. 13 , the decrease in expiratory mouth pressure was significantly suppressed in the kaempferol-containing food group compared with the placebo food group.
  • FIG. 14 depicts a graph showing the changes in heart rate. As shown in FIG. 14 , the heart rate was significantly lower at 200-250 m during the 1st run and at 0 (start)-150 m in the 2nd run in the kaempferol-containing food group compared with the placebo food group.
  • the kaempferol-containing food may improve exercise performance while giving the feeling of “comfort”, “recover quickly” etc.

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