WO2023190809A1 - Composition for inhibiting production of cortisol - Google Patents

Composition for inhibiting production of cortisol Download PDF

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Publication number
WO2023190809A1
WO2023190809A1 PCT/JP2023/013057 JP2023013057W WO2023190809A1 WO 2023190809 A1 WO2023190809 A1 WO 2023190809A1 JP 2023013057 W JP2023013057 W JP 2023013057W WO 2023190809 A1 WO2023190809 A1 WO 2023190809A1
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Prior art keywords
milk
composition
suppressing
derived
phosphatidylcholine
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PCT/JP2023/013057
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French (fr)
Japanese (ja)
Inventor
周太郎 久保
浩嗣 織田
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森永乳業株式会社
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Publication of WO2023190809A1 publication Critical patent/WO2023190809A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23JPROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
    • A23J7/00Phosphatide compositions for foodstuffs, e.g. lecithin
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115Fatty acids or derivatives thereof; Fats or oils
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/683Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20Milk; Whey; Colostrum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/20Hypnotics; Sedatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/38Drugs for disorders of the endocrine system of the suprarenal hormones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives

Definitions

  • the present invention relates to a composition for suppressing cortisol production.
  • Cortisol is one of the hormones produced by the adrenal cortex and is released in response to stress etc. Too much of it causes various problems such as insomnia, muscle atrophy, high blood sugar, and high blood pressure. Although medicines that suppress cortisol production have been developed, they are not something that can be taken on a daily basis like food. Therefore, the development of foods that suppress cortisol production is considered to be of great significance from the perspective of preventing and improving problems caused by excessive cortisol.
  • Glycerophosphatidylcholine which is a derivative of phosphatidylcholine (PC), which is a type of milk-derived phospholipid
  • PC phosphatidylcholine
  • Non-Patent Document 1 Glycerophosphatidylcholine
  • SM sphingomyelin
  • Non-Patent Document 2 Non-Patent Document 2
  • PC sleep-improving effects for SM.
  • PC there is no report on the effect of suppressing muscle atrophy due to suppression of cortisol production.
  • Patent Document 1 Although it has been reported that SM is useful for maintaining muscle mass and improving motor function, it is not mediated by the effect of suppressing cortisol production.
  • an object of the present invention is to provide a new food component that suppresses the production of cortisol and a composition containing the same food component.
  • the present inventors conducted extensive studies with the aim of obtaining a new food component that suppresses the production of cortisol and a composition containing the same food component. They also discovered that milk-derived phospholipids have a suppressive effect on cortisol production, and found a means to suppress cortisol production using milk-derived phospholipids that can be ingested as food. In particular, we found that cortisol production suppressive effects were found not in PC derivatives that require special processing, but in PC contained in common foods. We also found that SM contained in common foods suppresses cortisol production. Furthermore, it was suggested that the combination of PC and SM exerts a stronger cortisol production suppressing effect than either of them alone. The present invention was completed based on such knowledge.
  • the gist of the present invention relates to the following.
  • a composition for suppressing cortisol production containing a milk-derived phospholipid.
  • “for cortisol production suppression” can be rephrased as “for cortisol production suppression.”
  • the following embodiment is also an embodiment of the present invention.
  • [1-1] A method for suppressing cortisol production, comprising administering milk-derived phospholipids to a subject.
  • [1-2] Use of milk-derived phospholipids to suppress cortisol production.
  • [5-2] Use of milk-derived phospholipids to improve sleep quality.
  • [5-3] Use of milk-derived phospholipid for producing a composition for improving sleep quality.
  • [6] The composition according to any one of [1] to [4], which is used for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength.
  • "for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength” can also be translated as “for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength”. can.
  • the following embodiment is also an embodiment of the present invention.
  • [7] The composition according to any one of [1] to [3], which is a pharmaceutical.
  • a disease and/or condition that can be prevented, treated, or ameliorated by suppressing cortisol production can be referred to as "a disease and/or condition caused by cortisol overproduction.”
  • the following embodiment is also an embodiment of the present invention.
  • [8-1] A method for preventing, treating, or improving a disease and/or condition caused by cortisol overproduction, the method comprising administering a milk-derived phospholipid to a subject.
  • [8-3] Use of milk-derived phospholipids for the production of a composition for preventing, treating, or improving diseases and/or conditions caused by cortisol overproduction.
  • the disease and/or condition is type II diabetes, impaired glucose tolerance, hyperglycemia, insulin resistance, muscle breakdown, abnormal lipid metabolism, dyslipidemia, hyperlipidemia, hypertriglyceridemia, obesity. , atherosclerosis, syndrome X, Cushing's syndrome, hypertension, cognitive impairment, memory impairment, depression, insomnia, anxiety, dementia, Alzheimer's disease, osteoporosis, glaucoma, and immune diseases.
  • the composition according to [8] which is one or more types.
  • a composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength which contains a milk-derived phospholipid, and wherein the milk-derived phospholipid is phosphatidylcholine. Furthermore, the following embodiment is also an embodiment of the present invention.
  • the present invention it is possible to provide a highly safe and economical means for suppressing cortisol production, as well as a means for improving sleep quality and suppressing muscle breakdown through suppressing cortisol production. Furthermore, by combining PC and SM, it is expected that higher effects than conventional techniques can be obtained in terms of improving sleep quality and inhibiting muscle breakdown.
  • FIG. 1 is a diagram showing test results of inhibition of cortisol production in HAC15 cells by a mixture of five types of phospholipids.
  • FIG. 2 is a diagram showing test results of inhibition of cortisol production in HAC15 cells by each phospholipid.
  • Figure 3 shows test results of inhibition of cortisol production in HAC15 cells by combinations of phospholipids (combination of phosphatidylcholine and sphingomyelin, or combination of phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS)). It is a diagram.
  • FIG. 4 is a diagram showing the test results of inhibition of cortisol production in HAC15 cells using multiple concentrations of phosphatidylcholine and sphingomyelin alone.
  • prevention refers to preventing, suppressing, or delaying the onset of a disease, symptom, or condition in an individual, or reducing the risk of developing a disease, symptom, or condition in an individual.
  • improvement refers to improvement of a disease, symptom or condition, prevention, suppression or delay of deterioration of a disease, symptom or condition, or reversal, prevention, suppression or delay of the progression of a disease, symptom or condition. means.
  • composition for suppressing cortisol production of the present invention relates to a composition for suppressing cortisol production (hereinafter sometimes referred to as "composition for suppressing cortisol production of the present invention") containing a milk-derived phospholipid.
  • milk-derived phospholipids means phospholipids that are originally contained in milk, and does not mean the source from which they are collected. That is, phospholipids having the same structure as phospholipids contained in milk are included in the milk-derived phospholipids in the present invention.
  • milk-derived phospholipids include not only phospholipids that have the same structure as the phospholipids contained in milk, but also derivatives that have a partially different structure as long as they maintain the activity required for the present invention. It is a meaning that includes.
  • Phospholipids contained in milk generally include sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine.
  • sphingomyelin there are multiple types of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine depending on the type of fatty acid.
  • sphingomyelin depending on the type of fatty acid that constitutes the ceramide in its structure (amide bond to sphingosine), but the type is not limited in the present invention.
  • Typical examples of sphingomyelin include stearyl sphingomyelin, palmitoyl sphingomyelin, and tricosanylsphingomyelin, but the present invention is not limited thereto.
  • the term "sphingomyelin” refers to one containing one or more of a plurality of fatty acids. The same applies to other milk-derived phospholipids.
  • phosphatidylcholine There are multiple types of phosphatidylcholine depending on the types of two fatty acids that are ester-bonded to the glycerol skeleton in its structure, but the types are not limited in the present invention.
  • Typical examples of phosphatidylcholine include dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, eggphosphatidylcholine, and 1-palmitoyl-2-oleoylphosphatidylcholine.
  • the present invention is not limited to these.
  • the milk-derived phospholipids used in the composition for suppressing cortisol production of the present invention include one or more selected from sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine from the viewpoint of suppressing cortisol production. are preferred, those containing one or more selected from sphingomyelin and phosphatidylcholine are more preferred, and those containing a combination of sphingomyelin and phosphatidylcholine are even more preferred.
  • containing one or more selected from sphingomyelin and phosphatidylcholine refers to "an embodiment containing one or more types of sphingomyelin and not containing phosphatidylcholine” and "an embodiment containing one or more types of sphingomyelin and not containing phosphatidylcholine”. This includes embodiments including the above but not containing sphingomyelin, and embodiments containing one or more sphingomyelins and one or more phosphatidylcholines.
  • containing a combination of sphingomyelin and phosphatidylcholine means “an embodiment containing one or more types of sphingomyelin and one or more types of phosphatidylcholine.”
  • milk-derived phospholipids those derived from milk or those chemically synthesized from phospholipids originally contained in milk can be used.
  • milk-derived phospholipids phospholipids derived from milk of mammals such as cows, goats, sheep, and humans are preferred, and phospholipids derived from cow's milk are preferred.
  • the milk-derived phospholipid used in the present invention can be prepared, for example, from raw milk (eg, cow's milk) according to a known method.
  • raw milk eg, cow's milk
  • buttermilk is a by-product during butter production
  • butter serum is a by-product during butter oil production from cream or butter
  • whey is a by-product during cheese production
  • WPI from whey.
  • the phospholipid-containing composition produced as a by-product during the production, skim milk, etc. is subjected to filtration, solvent extraction, fractionation by various chromatography, or a combination thereof according to known methods.
  • milk-derived phospholipids used in the present invention do not necessarily have to be separated and purified as phospholipids, and milk-derived phospholipids such as a mixture of milk-derived phospholipids or milk-derived phospholipids may be used as long as they have the cortisol production suppressing effect of the present invention.
  • milk-containing compositions compositions containing milk-derived phospholipids and other optional components can also be used.
  • milk-derived phospholipids can also be used as milk-derived phospholipids and milk-derived phospholipid-containing compositions.
  • Commercially available products include, but are not limited to, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine (manufactured by Nagara Science), and phospholipid-containing composition (Milei (registered trademark) 70 HPL; manufactured by Milei). etc. are available.
  • the ratio is not limited, and the composition ratio of phospholipids contained in milk and ratios similar thereto, etc. It's good.
  • the composition of phospholipids in milk-derived phospholipids is, for example, based on the total weight of phospholipids, sphingomyelin is 20 to 30% by mass, phosphatidylcholine is 20 to 35% by mass, phosphatidylethanolamine is 20 to 35% by mass, and phosphatidylinositol. is 3 to 10% by mass, and phosphatidylserine is 3 to 15% by mass.
  • the sum of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine does not exceed 100% by mass based on the total mass of phospholipids.
  • the ratio is not limited, but for example, the mass ratio is 1:0.5 to 1:2, or 1:1 to It may be 1:1.2 etc.
  • the composition for suppressing cortisol production of the present invention may be composed only of milk-derived phospholipids, or may be in a form containing components such as raw materials to be included in foods, drinks, medicines, and the like.
  • the content of milk-derived phospholipids in the composition for suppressing cortisol production of the present invention is not particularly limited as long as it has the cortisol production-suppressing effect of the present invention, but the content of milk-derived phospholipids in the entire composition is 0. 001-100% by weight, 0.01-90% by weight, 0.1-50% by weight, 1-30% by weight, or 5-10% by weight.
  • the composition for suppressing cortisol production of the present invention may be in the form of food/beverage products, medicines, etc., or may be incorporated into food/beverage products, medicines, etc. as an additive (this form is referred to as a "cortisol production inhibitor"). (can also be expressed in other words).
  • the ingestion (administration) route of the composition for suppressing cortisol production of the present invention may be either oral or parenteral, but is usually oral.
  • parenteral ingestion (administration) include transdermal administration, intravenous injection, rectal administration, and inhalation.
  • the content of milk-derived phospholipids when orally ingesting (administering) the composition for suppressing cortisol production of the present invention may be the content in the entire composition described above, or may be diluted as appropriate.
  • the content of milk-derived phospholipids in the entire composition when ingested (administered) is 0.001 to 100% by mass, 0.01 to 90% by mass, 0.1 to 50% by mass, 1 to 30% by mass. %, or 5 to 10% by weight. These may be in the range of contents normally distributed as oral compositions.
  • the amount of the composition for suppressing cortisol production of the present invention to be ingested (administered) is appropriately selected depending on the age (age in months), sex, condition, and other conditions of the subject to be ingested (administered).
  • the intake (administration) amount of the composition for suppressing cortisol production of the present invention is, for example, preferably 0.01 to 1000 mg/kg/day, more preferably 0.1 to 500 mg/kg as the intake amount of milk-derived phospholipids. It is best to aim for an amount in the range of 1 to 300 mg/kg/day, more preferably 1 to 300 mg/kg/day. Note that, regardless of the amount and period of intake (administration), the composition for suppressing cortisol production of the present invention can be administered once a day or divided into multiple doses.
  • the amount of cortisol produced after application of the composition for suppressing cortisol production of the present invention is 0.9 times or less, 0.8 times or less, 0.7 times or less, 0.65 times or less, 0. It may be 6 times or less, or 0.55 times or less.
  • the upper limit is not particularly limited, but may be less than 1 times (same amount as before application).
  • the above numerical values may be in the range of non-contradictory combinations, specifically, 1 to 0.9 times, 1 to 0.8 times, 1 to 0.7 times, 1 to 0.65 times, 1 It may be ⁇ 0.6 times, or 1-0.55 times.
  • the amount of cortisol produced can be confirmed qualitatively or quantitatively by a well-known method, for example, by measuring the cortisol concentration in a sample by a standard method. For example, reference may be made to the methods described in the Examples.
  • composition for suppressing cortisol production of the present invention is used as a composition to be orally ingested, it is preferably in the form of a food or drink (hereinafter sometimes referred to as "the food or drink of the present invention"). Since the composition for suppressing cortisol production of the present invention suppresses cortisol production, it can be expected to prevent or improve various conditions caused by excessive cortisol.
  • Various conditions caused by excessive cortisol include, but are not limited to, decreased sleep quality, decreased muscle mass and/or muscle strength, and the like.
  • the food and drink products of the present invention can be used to prevent or improve these conditions. More specifically, the food or drink of the present invention can be used to improve the quality of sleep, maintain muscle mass and/or muscle strength, suppress decline, or improve it.
  • the food and drink of the present invention by “improving sleep quality" by the food and drink of the present invention, more specifically, for example, it is expected to improve poor sleep onset, shorten the time of waking up in the middle of the day, improve early morning awakening, and improve the lack of feeling of deep sleep. be done.
  • poor sleep onset refers to a condition in which it takes a long time to fall asleep (difficulty falling asleep).
  • mid-way awakening refers to a state of waking up between falling asleep and waking up, and the cumulative time of waking up is defined as the mid-way awakening time.
  • “early morning awakening” refers to a state in which a person wakes up early in the morning and is unable to fall asleep even though he or she is still sleepy.
  • feeling of deep sleep refers to a feeling of satisfaction from having slept soundly
  • lack of feeling of deep sleep refers to a state in which a person feels sleep deprivation upon waking up, without feeling satisfied that he or she has slept deeply, even though he or she has slept for a sufficient amount of time.
  • the form and properties of the food and drink are not particularly limited as long as they do not impair the effects of the present invention and can be ingested orally, and raw materials commonly used for food and drink may be used, except for containing milk-derived phospholipids. It can be manufactured by conventional methods.
  • Foods and beverages may be in the form of liquids, pastes, gel-like solids, powders, etc., such as tablets, liquid foods (nutritive foods for tube administration), bread, macaroni, spaghetti, noodles, cake mixes, etc.
  • Flour products such as fried flour and bread crumbs; instant noodles, cup noodles, retort and cooked foods, cooked canned foods, microwave foods, instant soups and stews, instant miso soup and soups, canned soups, freeze-dried foods, and other instant foods, etc.
  • Agricultural processed products such as canned agricultural products, canned fruits, jams and marmalade, pickles, boiled beans, dried agricultural products, cereals (processed grain products); Canned marine products, fish hams and sausages, seafood paste products, marine delicacies , Processed seafood products such as boiled fish; Processed livestock products such as canned livestock products, pastes, meat hams and sausages; Processed milk, milk drinks, yogurt (fermented milk), lactic acid bacteria drinks, cheese, ice cream, cream, Milk and dairy products such as other dairy products; Fats and oils such as butter, margarine, and vegetable oil; Basic seasonings such as soy sauce, miso, sauces, processed tomato seasonings, mirin, and vinegar; Cooking mixes, curry Complex seasonings and foods such as seasonings, sauces, dressings, noodle soups, spices, and other complex seasonings; Frozen foods such as raw frozen foods, semi-cooked frozen foods, and cooked frozen foods; Caramels, candy Confectionery such as
  • solid preparations such as powders, granules, tablets, capsules, etc. that may be enterically coated, solutions, syrups, suspensions, etc. It can be formulated into liquid formulations such as emulsions; Such formulation can be carried out in accordance with the explanations of components, carriers, and methods for formulating pharmaceuticals, which will be described later.
  • the feed can also be used as feed as one aspect of food and drink products.
  • the feed include pet food, livestock feed, and fish feed.
  • the form of the feed is not particularly limited, and in addition to milk-derived phospholipids, for example, grains such as corn, wheat, barley, rye, and milo; vegetable oil cakes such as soybean oil meal, rapeseed oil meal, coconut oil meal, and linseed oil meal; Bran such as bran, wheat bran, rice bran, and defatted rice bran; Manufactured lees such as corn gluten meal and corn jam meal; Animal feed such as fish meal, skim milk powder, whey, yellow grease, and tallow; Torula yeast and brewer's yeast Mineral feeds such as tricalcium phosphate and calcium carbonate; fats and oils; simple amino acids; sugars, etc. may be contained.
  • composition for suppressing cortisol production of the present invention is in the form of a food or drink (including feed), the food or drink is labeled with uses such as improving sleep quality, maintaining, inhibiting decline in, or improving muscle mass and/or muscle strength. It is possible to provide and sell it as a product. Furthermore, the milk-derived phospholipid according to the present specification can be used for producing these foods and drinks.
  • Such acts of "display” include all acts to inform the consumer of the above-mentioned use, and if the expression is such that it may remind or infer the above-mentioned use, the purpose of the display, the content of the display, Regardless of the object or medium to be displayed, all of them fall under the act of "display” in the present invention. Moreover, it is preferable that the "display” be performed using expressions that allow the consumer to directly recognize the above-mentioned use. Specifically, the act of transferring, handing over, displaying for transfer or delivery, or importing food and drink products or products with the above-mentioned usage written on their packaging, advertisements related to products, price lists, or transaction documents. Examples include acts of displaying or distributing information with the above-mentioned uses written thereon, or acts of writing the above-mentioned uses on information containing these items and providing it by electromagnetic (Internet, etc.) methods.
  • the display content is preferably a display approved by the government (for example, a display that has been approved based on various systems established by the government and is performed in a manner based on such approval). Further, it is preferable to attach such display contents to packaging, containers, catalogs, pamphlets, promotional materials at sales sites such as POP, and other documents.
  • labeling includes health foods, functional foods, enteral nutritional foods, special purpose foods, foods with health claims, foods for specified health uses, foods with nutritional function claims, foods with functional claims, quasi-drugs, etc. Display can also be mentioned.
  • labeling approved by the Consumer Affairs Agency for example, labeling approved under the system related to food for specified health uses, food with nutritional function claims, or food with functional claims, or a system similar to these, etc. can be mentioned.
  • labeling as a food for specified health uses labeling as a food for specified health uses with conditions, labeling that it affects the structure or function of the body, labeling to reduce disease risk, and labeling as a food for specified health uses based on scientific evidence.
  • Typical examples include labeling as food for specified health uses (especially labeling for health uses) and similar labeling as stipulated in Such claims include, for example, ⁇ suppresses excessive cortisol production,'' ⁇ increases sleep quality,'' ⁇ supports sleep,'' ⁇ reduces feeling of fatigue when waking up,'' and ⁇ regulates sleep/wake-up rhythm.''",”Reducessleepiness,””Helpful for maintaining muscle/strength,””Helpful for maintaining walking function,””Helpful for reducing body fat,” etc.
  • composition for suppressing cortisol production of the present invention can also be in the form of a pharmaceutical (hereinafter sometimes referred to as "the pharmaceutical of the present invention").
  • the composition for suppressing cortisol production of the present invention contains milk-derived phospholipids as an active ingredient and suppresses cortisol production, and therefore can prevent, treat, or improve various diseases and/or conditions caused by excessive cortisol. can be expected.
  • the pharmaceuticals of the present invention include those administered for diseases and/or conditions caused by cortisol overproduction, specifically diseases and/or conditions that can be prevented, treated, or ameliorated by cortisol overproduction.
  • Diseases and conditions caused by cortisol overproduction include, but are not limited to, type II diabetes, impaired glucose tolerance, hyperglycemia, insulin resistance, abnormal lipid metabolism, dyslipidemia, hyperlipidemia, and high triglycerides.
  • Diseases and conditions include blood pressure, obesity, atherosclerosis, syndrome X, Cushing's syndrome, hypertension, cognitive impairment, memory impairment, depression, anxiety, dementia, Alzheimer's disease, osteoporosis, glaucoma, and immune diseases. .
  • the pharmaceutical of the present invention can be administered to prevent, treat, or improve these diseases, conditions, complications, etc.
  • the route of administration of the drug may be either oral or parenteral, but oral is preferred.
  • parenteral ingestion examples include transdermal administration, intravenous injection, rectal administration, and inhalation.
  • the pharmaceutical form can be appropriately formulated into a desired dosage form depending on the administration method.
  • oral administration it can be formulated into solid preparations such as powders, granules, tablets, and capsules; liquid preparations such as solutions, syrups, suspensions, and emulsions.
  • it can also be made into an enteric agent by enteric coating or the like.
  • parenteral administration it can be formulated into suppositories, ointments, injections, etc.
  • formulation can be carried out by appropriately known methods depending on the dosage form.
  • carriers commonly used in formulation may be added as appropriate. Such carriers include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, and the like.
  • excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, ⁇ -starch, dextrin, and carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, Cellulose derivatives such as hydroxypropyl methylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light silicic anhydride, synthetic aluminum silicate, magnesium aluminate metasilicate; phosphate derivatives such as calcium phosphate; carbonic acid Examples include carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate.
  • binder examples include, in addition to the excipients mentioned above, gelatin; polyvinylpyrrolidone; macrogol, and the like.
  • disintegrant examples include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch, and crosslinked polyvinylpyrrolidone.
  • lubricants include talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as vegum and gay wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid. ; carboxylic acid sodium salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; starch derivatives, etc. It will be done.
  • the stabilizer examples include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; and sorbic acid.
  • flavoring agents include sweeteners, acidulants, fragrances, and the like.
  • carriers used in the case of liquid preparations for oral administration include solvents such as water.
  • the timing of ingesting the pharmaceutical of the present invention is not particularly limited, such as before meals, after meals, between meals, before going to bed, etc.
  • composition for suppressing cortisol production of the present invention is administered (ingested) is not particularly limited as long as it is an animal, but is usually a mammal, preferably a human.
  • Another aspect of the invention is the use of milk-derived phospholipids in the manufacture of a composition for inhibiting cortisol production. Another aspect of the invention is the use of milk-derived phospholipids in suppressing cortisol production. Another aspect of the present invention is a milk-derived phospholipid used for a composition for suppressing cortisol production. Another aspect of the invention is a method of suppressing cortisol production, which includes administering milk-derived phospholipids to a subject.
  • administering milk-derived phospholipids to a subject may be synonymous with “making a subject ingest milk-derived phospholipids.”
  • the intake may be voluntary (free intake) or forced (forced intake).
  • the administration step may be, for example, a step in which the milk-derived phospholipid is blended into a food/drink or feed and supplied to the subject, thereby allowing the subject to freely ingest the milk-derived phospholipid.
  • the intake (administration) timing and intake (administration) period of the composition for suppressing cortisol production of the present invention are not particularly limited, and can be appropriately selected depending on the condition of the subject to be administered.
  • composition for improving sleep quality of the present invention a composition for improving sleep quality (hereinafter sometimes referred to as "composition for improving sleep quality of the present invention") containing milk-derived phospholipids.
  • composition for improving sleep quality of the present invention contains milk-derived phospholipids as an active ingredient, and can be expected to improve sleep quality through the action of milk-derived phospholipids. Note that the matters explained in the above ⁇ Composition for suppressing cortisol production>, ⁇ Food and drink>, and ⁇ Pharmaceuticals> are all applicable to the description of the composition for improving sleep quality of the present invention.
  • composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength which comprises a milk-derived phospholipid, wherein the milk-derived phospholipid is phosphatidylcholine.
  • composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength of the present invention contains phosphatidylcholine as an active ingredient, and maintains, suppresses decline in, or improves muscle mass and/or muscle strength due to the action of phosphatidylcholine. We can expect it to improve.
  • composition for suppressing cortisol production> ⁇ Food and drink>, and ⁇ Pharmaceuticals> do not apply to the explanation of the composition for maintaining, inhibiting decline in, or improving muscle mass and/or muscle strength of the present invention. All apply.
  • Adrenocortical carcinoma cell line (HAC15) was obtained from ATCC.
  • HAC15 cell line is grown in 20 ml of DMEM:F12 (1:1) medium (Thermo Fisher Scientific) supplemented with 10% Cosmic Calf serum (Cytiva) and Penicillin Streptomycin (Fuji Film Wako Pure Chemical Industries). The cells were precultured for 11 days. During preculture, cells were passaged on the 4th and 8th day after seeding. Eleven days after seeding, the cells were treated with trypsin (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) and collected.
  • the collected cells were suspended in a DMEM:F12 (1:1) medium used for culture to which 0.1% Cosmic Calf serum and Penicillin Streptomycin were added.
  • the medium in which the cells were suspended was seeded in a 48-well cell culture plate (manufactured by CORNING) so that the number of cells per well was 5 x 104 .
  • Phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine were each suspended or dissolved in ethanol at the concentrations shown in Table 2.
  • 1/100 volume of each phospholipid solution or suspension was added to each well seeded with HAC15 cells. Thereafter, the cells were cultured for 24 hours in an incubator maintained at 37 degrees and 5% CO 2 , and the culture supernatant was collected. The culture supernatant was centrifuged at 2,000 g for 10 minutes to remove insoluble components and stored at -80 degrees until used for analysis.
  • Phosphatidylcholine and sphingomyelin were dissolved in ethanol to a concentration of 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1.25 mg/ml, 0.63 mg/ml, and 0.31 mg/ml, respectively. 1/100 volume was added to each well seeded with HAC15 cells. Thereafter, the cells were cultured for 24 hours in an incubator maintained at 37 degrees and 5% CO 2 , and the culture supernatant was collected. The culture supernatant was centrifuged at 2,000 g for 10 minutes to remove insoluble components and stored at -80 degrees until used for analysis.
  • cortisol production suppression rate by the combination of phosphatidylcholine and sphingomyelin was calculated from the data shown in FIG. 3 (Table 6).
  • the rate of inhibition of cortisol production was expressed as the percentage of decrease in cortisol in the culture supernatant by each sample treatment relative to the control.
  • the combination of phosphatidylcholine and sphingomyelin contains final concentrations of 26.9 ⁇ g/ml and 23.7 ⁇ g/ml, respectively, in the medium, so the combined phospholipid concentration is 50.6 ⁇ g/ml, and the cortisol production inhibition rate showed 42%.
  • phosphatidylcholine and sphingomyelin alone had a cortisol production suppression rate of 25% and 37%, respectively, at a concentration of 50 ⁇ g/ml. Furthermore, even when the concentration of phosphatidylcholine and sphingomyelin alone was increased to 100 ⁇ g/ml, the production inhibition rate was 34% and 38%, respectively.
  • the present invention is useful in the fields of food and beverages, health foods, functional foods, supplements, pharmaceuticals, etc.

Abstract

The present invention addresses the problem of providing: a new food component that inhibits production of cortisol; and a composition containing the food component. The present invention provides a composition that is for inhibiting production of cortisol, and that contains a milk-derived phospholipid.

Description

コルチゾール産生抑制用組成物Composition for suppressing cortisol production
 本発明は、コルチゾール産生抑制用組成物等に関する。 The present invention relates to a composition for suppressing cortisol production.
 コルチゾールは副腎皮質から産生されるホルモンの1つでストレス等に応答して放出される。その過多は不眠、筋委縮、高血糖、高血圧等、様々な問題を引き起こす。コルチゾールの産生を抑制する医薬品は開発されているが、食品のように日常的に摂取できるものではない。よって、コルチゾールの産生を抑制するような食品の開発は、コルチゾール過多に基づく問題の予防改善の側面から大きな意義があると考えられる。 Cortisol is one of the hormones produced by the adrenal cortex and is released in response to stress etc. Too much of it causes various problems such as insomnia, muscle atrophy, high blood sugar, and high blood pressure. Although medicines that suppress cortisol production have been developed, they are not something that can be taken on a daily basis like food. Therefore, the development of foods that suppress cortisol production is considered to be of great significance from the perspective of preventing and improving problems caused by excessive cortisol.
 コルチゾールの産生を抑制する食品成分として、乳由来リン脂質の1種であるホスファチジルコリン(PC)の誘導体であるグリセロホスファチジルコリン(GPC)が知られている(非特許文献1)。なお、乳由来リン脂質の1種であるスフィンゴミエリン(SM)についてはコルチゾール産生を抑制するとの報告はない。 Glycerophosphatidylcholine (GPC), which is a derivative of phosphatidylcholine (PC), which is a type of milk-derived phospholipid, is known as a food component that suppresses the production of cortisol (Non-Patent Document 1). Note that there is no report that sphingomyelin (SM), which is a type of milk-derived phospholipid, suppresses cortisol production.
 また、DHAが結合した特殊なPCでは睡眠リズムを改善することが報告されている。ただし、そのメカニズムはコルチゾール産生抑制を介したものではない(非特許文献2)。SMについては睡眠改善作用の報告はない。さらに、PCに関して、コルチゾールの産生抑制による筋委縮抑制作用の報告はない。一方、SMでは筋量の維持や運動機能の改善等に役立つことが多数報告されているが、コルチゾール産生抑制作用を介したものではない(特許文献1)。 Additionally, it has been reported that a special PC bound with DHA improves sleep rhythm. However, the mechanism is not mediated by suppression of cortisol production (Non-Patent Document 2). There are no reports of sleep-improving effects for SM. Furthermore, regarding PC, there is no report on the effect of suppressing muscle atrophy due to suppression of cortisol production. On the other hand, although it has been reported that SM is useful for maintaining muscle mass and improving motor function, it is not mediated by the effect of suppressing cortisol production (Patent Document 1).
特開2016-121132号公報Japanese Patent Application Publication No. 2016-121132
 上記のように、過度なコルチゾール産生を抑制することは健康上有益であるが、安価かつ安全性の高い食品の摂取で達成する方法は限られている。PCから誘導されるGPCでコルチゾール産生抑制作用が報告されているが、PCを酵素処理して製造するため容易に得ることが難しい。睡眠改善作用に関しても魚卵等に含まれる希少性が高く特殊なDHA結合型PCでなければ効果を得ることができない点が課題である。また、SMによる筋委縮抑制作用に関しては作用の向上が課題である。
 このような状況を鑑み、本発明は、コルチゾールの産生を抑制する新たな食品成分および同食品成分を含む組成物を提供することを課題とする。
As mentioned above, suppressing excessive cortisol production is beneficial for health, but there are limited ways to achieve this by consuming inexpensive and highly safe foods. It has been reported that GPC derived from PC has a cortisol production suppressing effect, but it is difficult to obtain because it is manufactured by treating PC with enzymes. Regarding the sleep-improving effect, the problem is that the effect can only be obtained with the rare and special DHA-binding PC contained in fish eggs and the like. Furthermore, with regard to the muscle atrophy suppressing effect of SM, it is a challenge to improve the effect.
In view of this situation, an object of the present invention is to provide a new food component that suppresses the production of cortisol and a composition containing the same food component.
 本発明者等は、コルチゾールの産生を抑制する新たな食品成分および同食品成分を含む組成物を得ることを目的として鋭意検討を行った。そして、乳由来リン脂質においてコルチゾール産生抑制作用を見出し、食品として摂取可能な乳由来リン脂質によりコルチゾールの産生を抑制する手段を見出した。特に、特殊な加工が必要なPC誘導体ではなく、一般的な食品に含まれるPCにおいてコルチゾール産生抑制作用を見出した。また、一般的な食品に含まれるSMにおいてコルチゾール産生抑制作用を見出した。さらに、PCに加えてSMを組み合わせることで、それぞれの単体よりも強いコルチゾール産生抑制作用を発揮することを示唆した。このような知見に基づいて本発明を完成した。 The present inventors conducted extensive studies with the aim of obtaining a new food component that suppresses the production of cortisol and a composition containing the same food component. They also discovered that milk-derived phospholipids have a suppressive effect on cortisol production, and found a means to suppress cortisol production using milk-derived phospholipids that can be ingested as food. In particular, we found that cortisol production suppressive effects were found not in PC derivatives that require special processing, but in PC contained in common foods. We also found that SM contained in common foods suppresses cortisol production. Furthermore, it was suggested that the combination of PC and SM exerts a stronger cortisol production suppressing effect than either of them alone. The present invention was completed based on such knowledge.
 すなわち、本発明の要旨は以下に関する。
[1] 乳由来リン脂質を含む、コルチゾール産生抑制用組成物。なお、本明細書において、「コルチゾール産生抑制用」は、「コルチゾール産生抑制のための」と換言することができる。
 また、以下の態様も本発明の一態様である。
[1-1] 乳由来リン脂質を対象に投与することを含む、コルチゾール産生抑制方法。
[1-2] 乳由来リン脂質の、コルチゾール産生抑制のための使用。
[1-3] 乳由来リン脂質の、コルチゾール産生抑制用組成物の製造のための使用。
[2] 前記リン脂質が、スフィンゴミエリンおよびホスファチジルコリンから選択される1種以上を含む、[1]に記載の組成物。
[3] 前記リン脂質が、スフィンゴミエリンおよびホスファチジルコリンの組み合わせを含む、[2]に記載の組成物。
[4] 飲食品である、[1]~[3]のいずれかに記載の組成物。
[5] 睡眠の質改善用である、[1]~[4]のいずれかに記載の組成物。なお、本明細書において、「睡眠の質改善用」は、「睡眠の質改善のための」と換言することができる。
 また、以下の態様も本発明の一態様である。
[5-1] 乳由来リン脂質を対象に投与することを含む、睡眠の質改善方法。
[5-2] 乳由来リン脂質の、睡眠の質改善のための使用。
[5-3] 乳由来リン脂質の、睡眠の質改善用組成物の製造のための使用。
[6] 筋肉量および/または筋力の維持、低下抑制、または改善用である、[1]~[4]のいずれかに記載の組成物。なお、本明細書において、「筋肉量および/または筋力の維持、低下抑制、または改善用」は、「筋肉量および/または筋力の維持、低下抑制、または改善のための」と換言することができる。
 また、以下の態様も本発明の一態様である。
[6-1] 乳由来リン脂質を対象に投与することを含む、筋肉量および/または筋力の維持、低下抑制、または改善方法。
[6-2] 乳由来リン脂質の、筋肉量および/または筋力の維持、低下抑制、または改善のための使用。
[6-3] 乳由来リン脂質の、筋肉量および/または筋力の維持、低下抑制、または改善用組成物の製造のための使用。
[7] 医薬品である、[1]~[3]のいずれかに記載の組成物。
[8] コルチゾール産生抑制により、予防、治療、または改善し得る疾患および/または状態のために投与される、[7]に記載の組成物。なお、本明細書において、「コルチゾール産生抑制により、予防、治療、または改善し得る疾患および/または状態」は、「コルチゾール過剰産生によって引き起こされる疾患および/または状態」と換言することができる。
 また、以下の態様も本発明の一態様である。
[8-1] 乳由来リン脂質を対象に投与することを含む、コルチゾール過剰産生によって引き起こされる疾患および/または状態の予防、治療、または改善方法。
[8-2] 乳由来リン脂質の、コルチゾール過剰産生によって引き起こされる疾患および/または状態の予防、治療、または改善のための使用。
[8-3] 乳由来リン脂質の、コルチゾール過剰産生によって引き起こされる疾患および/または状態の予防、治療、または改善用組成物の製造のための使用。
[9] 前記疾患および/または状態が、II型糖尿病、耐糖能異常、高血糖症、インスリン抵抗性、筋分解、脂質代謝異常、異脂肪血症、高脂血症、高トリグリセリド血症、肥満、アテローム性動脈硬化症、シンドロームX、クッシング症候群、高血圧、認識障害、記憶障害、うつ病、不眠症、不安症、痴呆症、アルツハイマー病、骨粗鬆症、緑内障、および免疫疾患からなる群から選択される1種以上である、[8]に記載の組成物。
[10] 乳由来リン脂質を含む、睡眠の質改善用組成物。
[11] 乳由来リン脂質を含む、筋肉量および/または筋力の維持、低下抑制、または改善用組成物であって、前記乳由来リン脂質が、ホスファチジルコリンである、組成物。
 また、以下の態様も本発明の一態様である。
[11-1] 乳由来リン脂質を対象に投与することを含む、筋肉量および/または筋力の維持、低下抑制、または改善方法であって、前記乳由来リン脂質が、ホスファチジルコリンである、方法。
[11-2] 乳由来リン脂質の、筋肉量および/または筋力の維持、低下抑制、または改善のための使用であって、前記乳由来リン脂質が、ホスファチジルコリンである、使用。
[11-3] 乳由来リン脂質の、筋肉量および/または筋力の維持、低下抑制、または改善用組成物の製造のための使用であって、前記乳由来リン脂質が、ホスファチジルコリンである、使用。
That is, the gist of the present invention relates to the following.
[1] A composition for suppressing cortisol production, containing a milk-derived phospholipid. In addition, in this specification, "for cortisol production suppression" can be rephrased as "for cortisol production suppression."
Furthermore, the following embodiment is also an embodiment of the present invention.
[1-1] A method for suppressing cortisol production, comprising administering milk-derived phospholipids to a subject.
[1-2] Use of milk-derived phospholipids to suppress cortisol production.
[1-3] Use of milk-derived phospholipid for producing a composition for suppressing cortisol production.
[2] The composition according to [1], wherein the phospholipid contains one or more selected from sphingomyelin and phosphatidylcholine.
[3] The composition according to [2], wherein the phospholipid includes a combination of sphingomyelin and phosphatidylcholine.
[4] The composition according to any one of [1] to [3], which is a food or drink.
[5] The composition according to any one of [1] to [4], which is for improving sleep quality. In addition, in this specification, "for improving the quality of sleep" can be rephrased as "for improving the quality of sleep".
Furthermore, the following embodiment is also an embodiment of the present invention.
[5-1] A method for improving sleep quality, comprising administering milk-derived phospholipids to a subject.
[5-2] Use of milk-derived phospholipids to improve sleep quality.
[5-3] Use of milk-derived phospholipid for producing a composition for improving sleep quality.
[6] The composition according to any one of [1] to [4], which is used for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength. In addition, in this specification, "for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength" can also be translated as "for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength". can.
Furthermore, the following embodiment is also an embodiment of the present invention.
[6-1] A method for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength, which comprises administering milk-derived phospholipids to a subject.
[6-2] Use of milk-derived phospholipids for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength.
[6-3] Use of milk-derived phospholipids for the production of a composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength.
[7] The composition according to any one of [1] to [3], which is a pharmaceutical.
[8] The composition according to [7], which is administered for diseases and/or conditions that can be prevented, treated, or ameliorated by suppressing cortisol production. Note that in this specification, "a disease and/or condition that can be prevented, treated, or ameliorated by suppressing cortisol production" can be referred to as "a disease and/or condition caused by cortisol overproduction."
Furthermore, the following embodiment is also an embodiment of the present invention.
[8-1] A method for preventing, treating, or improving a disease and/or condition caused by cortisol overproduction, the method comprising administering a milk-derived phospholipid to a subject.
[8-2] Use of milk-derived phospholipids for the prevention, treatment, or amelioration of diseases and/or conditions caused by cortisol overproduction.
[8-3] Use of milk-derived phospholipids for the production of a composition for preventing, treating, or improving diseases and/or conditions caused by cortisol overproduction.
[9] The disease and/or condition is type II diabetes, impaired glucose tolerance, hyperglycemia, insulin resistance, muscle breakdown, abnormal lipid metabolism, dyslipidemia, hyperlipidemia, hypertriglyceridemia, obesity. , atherosclerosis, syndrome X, Cushing's syndrome, hypertension, cognitive impairment, memory impairment, depression, insomnia, anxiety, dementia, Alzheimer's disease, osteoporosis, glaucoma, and immune diseases. The composition according to [8], which is one or more types.
[10] A composition for improving sleep quality containing a milk-derived phospholipid.
[11] A composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength, which contains a milk-derived phospholipid, and wherein the milk-derived phospholipid is phosphatidylcholine.
Furthermore, the following embodiment is also an embodiment of the present invention.
[11-1] A method for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength, the method comprising administering a milk-derived phospholipid to a subject, wherein the milk-derived phospholipid is phosphatidylcholine.
[11-2] Use of a milk-derived phospholipid for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength, wherein the milk-derived phospholipid is phosphatidylcholine.
[11-3] Use of a milk-derived phospholipid for the production of a composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength, wherein the milk-derived phospholipid is phosphatidylcholine. .
 本発明により、安全性が高く経済性にも優れたコルチゾール産生を抑制する手段、およびコルチゾール産生抑制を介した睡眠の質改善、筋分解を抑制する手段を提供できる。さらに、PCとSMを組み合わせることで睡眠の質改善、筋分解を抑制する作用について従来技術より高い効果を得ることができると期待される。 According to the present invention, it is possible to provide a highly safe and economical means for suppressing cortisol production, as well as a means for improving sleep quality and suppressing muscle breakdown through suppressing cortisol production. Furthermore, by combining PC and SM, it is expected that higher effects than conventional techniques can be obtained in terms of improving sleep quality and inhibiting muscle breakdown.
図1は、5種のリン脂質混合物によるHAC15細胞のコルチゾール産生抑制の試験結果を示す図である。FIG. 1 is a diagram showing test results of inhibition of cortisol production in HAC15 cells by a mixture of five types of phospholipids. 図2は、各リン脂質によるHAC15細胞のコルチゾール産生抑制の試験結果を示す図である。FIG. 2 is a diagram showing test results of inhibition of cortisol production in HAC15 cells by each phospholipid. 図3は、リン脂質の組み合わせ(ホスファチジルコリンおよびスフィンゴミエリンの組み合わせ、またはホスファチジルエタノールアミン(PE)、ホスファチジルイノシトール(PI)およびホスファチジルセリン(PS)の組み合わせ)によるHAC15細胞のコルチゾール産生抑制の試験結果を示す図である。Figure 3 shows test results of inhibition of cortisol production in HAC15 cells by combinations of phospholipids (combination of phosphatidylcholine and sphingomyelin, or combination of phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS)). It is a diagram. 図4は、複数の濃度のホスファチジルコリンとスフィンゴミエリン単体によるHAC15細胞のコルチゾール産生抑制の試験結果を示す図である。FIG. 4 is a diagram showing the test results of inhibition of cortisol production in HAC15 cells using multiple concentrations of phosphatidylcholine and sphingomyelin alone.
 以下、本発明の実施の形態について、説明する。ただし、本発明は以下の好ましい実施形態に限定されず、本発明の範囲内で自由に変更することができるものである。
 なお、本明細書において、数値範囲を「下限~上限」で表現するものに関しては、上限は「以下」であっても「未満」であってもよく、下限は「以上」であっても「超」であってもよい。
Embodiments of the present invention will be described below. However, the present invention is not limited to the following preferred embodiments, and can be freely modified within the scope of the present invention.
In addition, in this specification, when a numerical range is expressed as "lower limit to upper limit", the upper limit may be "less than or equal to" or "less than", and the lower limit may be "more than" or "more than". It may be "super".
 本明細書において、「予防」とは、個体における疾患、症状または状態の発症の防止、抑制または遅延、あるいは個体の疾患、症状または状態の発症の危険性を低下させることをいう。また本明細書において、「改善」とは、疾患、症状または状態の好転、疾患、症状または状態の悪化の防止、抑制または遅延、あるいは疾患、症状または状態の進行の逆転、防止、抑制または遅延をいう。 As used herein, "prevention" refers to preventing, suppressing, or delaying the onset of a disease, symptom, or condition in an individual, or reducing the risk of developing a disease, symptom, or condition in an individual. In addition, as used herein, "improvement" refers to improvement of a disease, symptom or condition, prevention, suppression or delay of deterioration of a disease, symptom or condition, or reversal, prevention, suppression or delay of the progression of a disease, symptom or condition. means.
<コルチゾール産生抑制用組成物>
 本発明の一態様は、乳由来リン脂質を含む、コルチゾール産生抑制用組成物(以下、「本発明のコルチゾール産生抑制用組成物」ということがある)に関する。
<Composition for suppressing cortisol production>
One aspect of the present invention relates to a composition for suppressing cortisol production (hereinafter sometimes referred to as "composition for suppressing cortisol production of the present invention") containing a milk-derived phospholipid.
≪乳由来リン脂質≫
 本発明のコルチゾール産生抑制用組成物は、乳由来リン脂質を有効成分として含む。ここで、「乳由来リン脂質」とは、元来乳に含まれているリン脂質を意味し、採取原を意味するものではない。すなわち、乳に含まれているリン脂質と構造が同一であるリン脂質は、本発明における乳由来リン脂質に包含される。また、「乳由来リン脂質」としては、乳に含まれているリン脂質と構造が同一であるリン脂質のみならず、本発明に必要な活性を維持している限り、一部構造が異なる誘導体を含む意味である。
≪Milk-derived phospholipids≫
The composition for suppressing cortisol production of the present invention contains milk-derived phospholipids as an active ingredient. Here, "milk-derived phospholipids" means phospholipids that are originally contained in milk, and does not mean the source from which they are collected. That is, phospholipids having the same structure as phospholipids contained in milk are included in the milk-derived phospholipids in the present invention. In addition, "milk-derived phospholipids" include not only phospholipids that have the same structure as the phospholipids contained in milk, but also derivatives that have a partially different structure as long as they maintain the activity required for the present invention. It is a meaning that includes.
 乳に含まれているリン脂質としては、一般的に、スフィンゴミエリン、ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、およびホスファチジルセリン等が挙げられる。 Phospholipids contained in milk generally include sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine.
 ここで、スフィンゴミエリン、ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、およびホスファチジルセリンには、脂肪酸の種類によって複数の種類が存在する。例えば、スフィンゴミエリンは、その構造中のセラミドを構成する(スフィンゴシンにアミド結合する)脂肪酸の種類により複数種が存在するが、本発明においてはその種類は限定されない。スフィンゴミエリンの典型的な例としては、ステアリルスフィンゴミエリン、パルミトイルスフィンゴミエリン、およびトリコサニルスフィンゴミエリン等が挙げられるが、本発明においては、これらに限定されない。なお、本明細書において、「スフィンゴミエリン」というときは、脂肪酸により存在する複数種のうちの1種または2種以上を含むものを意味する。その他の各乳由来リン脂質についても同様である。 Here, there are multiple types of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine depending on the type of fatty acid. For example, there are multiple types of sphingomyelin depending on the type of fatty acid that constitutes the ceramide in its structure (amide bond to sphingosine), but the type is not limited in the present invention. Typical examples of sphingomyelin include stearyl sphingomyelin, palmitoyl sphingomyelin, and tricosanylsphingomyelin, but the present invention is not limited thereto. In this specification, the term "sphingomyelin" refers to one containing one or more of a plurality of fatty acids. The same applies to other milk-derived phospholipids.
 ホスファチジルコリンは、その構造中のグリセロール骨格にエステル結合する2つの脂肪酸の種類により複数種が存在するが、本発明においてはその種類は限定されない。ホスファチジルコリンの典型的な例としては、ジミリストイルフォスファチジルコリン、ジパルミトイルフォスファチジルコリン、ジステアロイルフォスファチジルコリン、エッグフォスファチジルコリン、および1-パルミトイル-2-オレオイルフォスファチジルコリン等が挙げられるが、本発明においては、これらに限定されない。 There are multiple types of phosphatidylcholine depending on the types of two fatty acids that are ester-bonded to the glycerol skeleton in its structure, but the types are not limited in the present invention. Typical examples of phosphatidylcholine include dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, eggphosphatidylcholine, and 1-palmitoyl-2-oleoylphosphatidylcholine. However, the present invention is not limited to these.
 本発明のコルチゾール産生抑制用組成物に使用される乳由来リン脂質としては、コルチゾール産生抑制作用の観点から、スフィンゴミエリン、ホスファチジルコリン、ホスファチジルエタノールアミン、およびホスファチジルセリンから選択される1種以上を含むものが好ましく、スフィンゴミエリンおよびホスファチジルコリンから選択される1種以上を含むものがより好ましく、スフィンゴミエリンおよびホスファチジルコリンの組み合わせを含むものがさらに好ましい。 The milk-derived phospholipids used in the composition for suppressing cortisol production of the present invention include one or more selected from sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine from the viewpoint of suppressing cortisol production. are preferred, those containing one or more selected from sphingomyelin and phosphatidylcholine are more preferred, and those containing a combination of sphingomyelin and phosphatidylcholine are even more preferred.
 本明細書における「スフィンゴミエリンおよびホスファチジルコリンから選択される1種以上を含む」とは、「スフィンゴミエリンの1種または2種以上を含み、ホスファチジルコリンを含まない態様」、「ホスファチジルコリンの1種または2種以上を含み、スフィンゴミエリンを含まない態様」、および、「スフィンゴミエリンの1種または2種以上と、ホスファチジルコリンの1種または2種以上を含む態様」を包含するものである。 In the present specification, "containing one or more selected from sphingomyelin and phosphatidylcholine" refers to "an embodiment containing one or more types of sphingomyelin and not containing phosphatidylcholine" and "an embodiment containing one or more types of sphingomyelin and not containing phosphatidylcholine". This includes embodiments including the above but not containing sphingomyelin, and embodiments containing one or more sphingomyelins and one or more phosphatidylcholines.
 また、本明細書における「スフィンゴミエリンおよびホスファチジルコリンの組み合わせを含む」とは、「スフィンゴミエリンの1種または2種以上と、ホスファチジルコリンの1種または2種以上を含む態様」を意味するものである。 Further, in the present specification, "containing a combination of sphingomyelin and phosphatidylcholine" means "an embodiment containing one or more types of sphingomyelin and one or more types of phosphatidylcholine."
 乳由来リン脂質としては、乳由来のものや、元来乳に含まれているリン脂質を化学的に合成したものを使用可能である。乳由来リン脂質としては、ウシ、ヤギ、ヒツジ、ヒト等の哺乳類の乳由来のリン脂質が好ましく、牛乳由来のリン脂質が好ましい。 As milk-derived phospholipids, those derived from milk or those chemically synthesized from phospholipids originally contained in milk can be used. As milk-derived phospholipids, phospholipids derived from milk of mammals such as cows, goats, sheep, and humans are preferred, and phospholipids derived from cow's milk are preferred.
 本発明に用いられる乳由来リン脂質は、例えば、原料乳(例えば牛乳)から公知の方法に準じて、調製することができる。例えば、牛乳由来のリン脂質の場合、バター製造の際に副生するバターミルク、クリームまたはバターからバターオイル製造の際に副生するバターセラム、チーズ製造の際に副生するホエイ、ホエイからWPI(Whey Protein Isolate)製造の際に副生するリン脂質含有組成物、または脱脂乳等から、公知の方法に準じて、ろ過、溶媒抽出、各種クロマトグラフィーによる分画、またはそれらの組み合わせ等を行うことで調製することができる。また、本発明に用いられる乳由来リン脂質としては、必ずしもリン脂質として分離、精製されている必要はなく、本発明のコルチゾール産生抑制作用を有する限り、乳由来リン脂質の混合物や、乳由来リン脂質含有組成物(乳由来リン脂質およびそれ以外の任意成分を含む組成物)を用いることもできる。 The milk-derived phospholipid used in the present invention can be prepared, for example, from raw milk (eg, cow's milk) according to a known method. For example, in the case of milk-derived phospholipids, buttermilk is a by-product during butter production, butter serum is a by-product during butter oil production from cream or butter, whey is a by-product during cheese production, and WPI from whey. (Whey Protein Isolate) The phospholipid-containing composition produced as a by-product during the production, skim milk, etc. is subjected to filtration, solvent extraction, fractionation by various chromatography, or a combination thereof according to known methods. It can be prepared by In addition, the milk-derived phospholipids used in the present invention do not necessarily have to be separated and purified as phospholipids, and milk-derived phospholipids such as a mixture of milk-derived phospholipids or milk-derived phospholipids may be used as long as they have the cortisol production suppressing effect of the present invention. Lipid-containing compositions (compositions containing milk-derived phospholipids and other optional components) can also be used.
 また、乳由来リン脂質や乳由来リン脂質含有組成物としては、市販品を用いることもできる。市販品としては、限定されないが、例えば、スフィンゴミエリン、ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、ホスファチジルセリン(長良サイエンス社製)、リン脂質含有組成物(Milei(登録商標) 70 HPL;Milei社製)等が使用可能である。 Furthermore, commercially available products can also be used as milk-derived phospholipids and milk-derived phospholipid-containing compositions. Commercially available products include, but are not limited to, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine (manufactured by Nagara Science), and phospholipid-containing composition (Milei (registered trademark) 70 HPL; manufactured by Milei). etc. are available.
 本発明のコルチゾール産生抑制用組成物に使用される乳由来リン脂質として、複数種のリン脂質を含む場合、その比率は限定されず、乳に含まれるリン脂質の組成比およびそれに準ずる比等であってよい。乳由来リン脂質におけるリン脂質の組成は、例えば、リン脂質の総質量に対し、スフィンゴミエリンが20~30質量%、ホスファチジルコリンが20~35質量%、ホスファチジルエタノールアミンが20~35質量%、ホスファチジルイノシトールが3~10質量%、ホスファチジルセリンが3~15質量%である。ここで、スフィンゴミエリン、ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、およびホスファチジルセリンの和は、リン脂質の総質量に対して100質量%を超えない。
 例えば、本発明のコルチゾール産生抑制用組成物に、スフィンゴミエリンおよびホスファチジルコリンの組み合わせを含む場合、その比率は限定されないが、例えば、質量比で1:0.5~1:2、あるいは1:1~1:1.2等であってよい。
When the milk-derived phospholipids used in the composition for suppressing cortisol production of the present invention include multiple types of phospholipids, the ratio is not limited, and the composition ratio of phospholipids contained in milk and ratios similar thereto, etc. It's good. The composition of phospholipids in milk-derived phospholipids is, for example, based on the total weight of phospholipids, sphingomyelin is 20 to 30% by mass, phosphatidylcholine is 20 to 35% by mass, phosphatidylethanolamine is 20 to 35% by mass, and phosphatidylinositol. is 3 to 10% by mass, and phosphatidylserine is 3 to 15% by mass. Here, the sum of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine does not exceed 100% by mass based on the total mass of phospholipids.
For example, when the composition for suppressing cortisol production of the present invention contains a combination of sphingomyelin and phosphatidylcholine, the ratio is not limited, but for example, the mass ratio is 1:0.5 to 1:2, or 1:1 to It may be 1:1.2 etc.
 本発明のコルチゾール産生抑制用組成物は、乳由来リン脂質のみからなってもよく、飲食品や医薬品等に含有させる原料等の成分を含む形態であってもよい。
 本発明のコルチゾール産生抑制用組成物における乳由来リン脂質の含有量は、本発明のコルチゾール産生抑制作用を有する限り、特に限定されないが、組成物全体に対する乳由来リン脂質の含有量は、0.001~100質量%、0.01~90質量%、0.1~50質量%、1~30質量%、または5~10質量%であってよい。
The composition for suppressing cortisol production of the present invention may be composed only of milk-derived phospholipids, or may be in a form containing components such as raw materials to be included in foods, drinks, medicines, and the like.
The content of milk-derived phospholipids in the composition for suppressing cortisol production of the present invention is not particularly limited as long as it has the cortisol production-suppressing effect of the present invention, but the content of milk-derived phospholipids in the entire composition is 0. 001-100% by weight, 0.01-90% by weight, 0.1-50% by weight, 1-30% by weight, or 5-10% by weight.
 本発明のコルチゾール産生抑制用組成物は、それ自体を飲食品や医薬品等の形態としてもよいし、添加物として飲食品や医薬品等に含有させる形態(この形態について、「コルチゾール産生抑制剤」と換言することもできる)としてもよい。
 本発明のコルチゾール産生抑制用組成物の摂取(投与)経路は、経口または非経口のいずれでもよいが、通常は経口である。また、非経口摂取(投与)としては、経皮、静注、直腸投与、吸入等が挙げられる。
The composition for suppressing cortisol production of the present invention may be in the form of food/beverage products, medicines, etc., or may be incorporated into food/beverage products, medicines, etc. as an additive (this form is referred to as a "cortisol production inhibitor"). (can also be expressed in other words).
The ingestion (administration) route of the composition for suppressing cortisol production of the present invention may be either oral or parenteral, but is usually oral. In addition, examples of parenteral ingestion (administration) include transdermal administration, intravenous injection, rectal administration, and inhalation.
 本発明のコルチゾール産生抑制用組成物を経口摂取(投与)するときの乳由来リン脂質の含有量としては、前述した組成物全体における含有量としてもよいし、適宜希釈等してもよい。例えば、経口摂取(投与)時の乳由来リン脂質の組成物全体に対する含有量は、0.001~100質量%、0.01~90質量%、0.1~50質量%、1~30質量%、または5~10質量%であってよい。
 これらは、通常、経口組成物として流通するときの含有量の範囲であってよい。
The content of milk-derived phospholipids when orally ingesting (administering) the composition for suppressing cortisol production of the present invention may be the content in the entire composition described above, or may be diluted as appropriate. For example, the content of milk-derived phospholipids in the entire composition when ingested (administered) is 0.001 to 100% by mass, 0.01 to 90% by mass, 0.1 to 50% by mass, 1 to 30% by mass. %, or 5 to 10% by weight.
These may be in the range of contents normally distributed as oral compositions.
 本発明のコルチゾール産生抑制用組成物の摂取(投与)量は、摂取(投与)対象の年齢(月齢)、性別、状態、その他の条件等により適宜選択される。
 本発明のコルチゾール産生抑制用組成物の摂取(投与)量は、乳由来リン脂質の摂取量として、例えば、好ましくは0.01~1000mg/kg/日、より好ましくは0.1~500mg/kg/日、さらに好ましくは1~300mg/kg/日の範囲となる量を目安とするのがよい。
 なお、摂取(投与)の量や期間にかかわらず、本発明のコルチゾール産生抑制用組成物は1日1回または複数回に分けて投与することができる。
The amount of the composition for suppressing cortisol production of the present invention to be ingested (administered) is appropriately selected depending on the age (age in months), sex, condition, and other conditions of the subject to be ingested (administered).
The intake (administration) amount of the composition for suppressing cortisol production of the present invention is, for example, preferably 0.01 to 1000 mg/kg/day, more preferably 0.1 to 500 mg/kg as the intake amount of milk-derived phospholipids. It is best to aim for an amount in the range of 1 to 300 mg/kg/day, more preferably 1 to 300 mg/kg/day.
Note that, regardless of the amount and period of intake (administration), the composition for suppressing cortisol production of the present invention can be administered once a day or divided into multiple doses.
 本発明のコルチゾール産生抑制用組成物の適用後のコルチゾール産生量は、適用前に比べて、0.9倍以下、0.8倍以下、0.7倍以下、0.65倍以下、0.6倍以下、または0.55倍以下であってよい。上限値は、特に制限されないが、1倍(適用前と同量)未満であってよい。また、上記数値の矛盾しない組み合わせの範囲であってもよく、具体的には、1~0.9倍、1~0.8倍、1~0.7倍、1~0.65倍、1~0.6倍、または1~0.55倍であってよい。
 ここで、コルチゾール産生量は、周知の方法で定性的または定量的に確認することができ、例えば、試料中のコルチゾール濃度を定法により測定すること等により行うことができる。例えば、実施例に記載の方法を参照することができる。
The amount of cortisol produced after application of the composition for suppressing cortisol production of the present invention is 0.9 times or less, 0.8 times or less, 0.7 times or less, 0.65 times or less, 0. It may be 6 times or less, or 0.55 times or less. The upper limit is not particularly limited, but may be less than 1 times (same amount as before application). Furthermore, the above numerical values may be in the range of non-contradictory combinations, specifically, 1 to 0.9 times, 1 to 0.8 times, 1 to 0.7 times, 1 to 0.65 times, 1 It may be ~0.6 times, or 1-0.55 times.
Here, the amount of cortisol produced can be confirmed qualitatively or quantitatively by a well-known method, for example, by measuring the cortisol concentration in a sample by a standard method. For example, reference may be made to the methods described in the Examples.
<飲食品>
 本発明のコルチゾール産生抑制用組成物を経口摂取される組成物とする場合は、飲食品の態様とすることが好ましい(以下、「本発明の飲食品」ということがある)。
 本発明のコルチゾール産生抑制用組成物は、コルチゾール産生を抑制させることから、コルチゾール過多に起因する種々の状態を予防、または改善することが期待できる。
<Food and beverages>
When the composition for suppressing cortisol production of the present invention is used as a composition to be orally ingested, it is preferably in the form of a food or drink (hereinafter sometimes referred to as "the food or drink of the present invention").
Since the composition for suppressing cortisol production of the present invention suppresses cortisol production, it can be expected to prevent or improve various conditions caused by excessive cortisol.
 コルチゾール過多に起因する種々の状態としては、限定されないが、例えば、睡眠の質の低下、筋肉量および/または筋力の低下等が挙げられる。本発明の飲食品は、これらの状態の予防、または改善のための飲食品とすることができる。より具体的には、本発明の飲食品は、睡眠の質の改善、筋肉量および/または筋力の維持、低下抑制、または改善のための飲食品とすることができる。 Various conditions caused by excessive cortisol include, but are not limited to, decreased sleep quality, decreased muscle mass and/or muscle strength, and the like. The food and drink products of the present invention can be used to prevent or improve these conditions. More specifically, the food or drink of the present invention can be used to improve the quality of sleep, maintain muscle mass and/or muscle strength, suppress decline, or improve it.
 なお、本発明の飲食品による「睡眠の質の改善」により、より具体的には、例えば、入眠不良の改善、中途覚醒時間の短縮、早朝覚醒の改善、熟眠感の欠如の改善等が期待される。
 ここで、「入眠不良」は、入眠までに時間がかかる(寝つきが悪い)状態を指す。
 また、「中途覚醒」は、入眠から起床に至るまでの間に目が覚める状態を指し、目が覚めた時間の積算時間を中途覚醒時間とする。
 また、「早朝覚醒」は、早朝目覚めてしまい、まだ眠気があるにもかかわらず眠れない状態を指す。
 また、「熟眠感」は、熟眠したという満足感を指し、熟眠感の欠如は、睡眠時間は十分なのに熟眠したという満足感がない状態で、目覚め時に睡眠不足を感じる状態を指す。
In addition, by "improving sleep quality" by the food and drink of the present invention, more specifically, for example, it is expected to improve poor sleep onset, shorten the time of waking up in the middle of the day, improve early morning awakening, and improve the lack of feeling of deep sleep. be done.
Here, "poor sleep onset" refers to a condition in which it takes a long time to fall asleep (difficulty falling asleep).
Moreover, "mid-way awakening" refers to a state of waking up between falling asleep and waking up, and the cumulative time of waking up is defined as the mid-way awakening time.
Furthermore, "early morning awakening" refers to a state in which a person wakes up early in the morning and is unable to fall asleep even though he or she is still sleepy.
In addition, "feeling of deep sleep" refers to a feeling of satisfaction from having slept soundly, and lack of feeling of deep sleep refers to a state in which a person feels sleep deprivation upon waking up, without feeling satisfied that he or she has slept deeply, even though he or she has slept for a sufficient amount of time.
 なお、本発明の飲食品による「筋肉量および/または筋力の維持、低下抑制、または改善」により、より具体的には、例えば、歩行機能の維持、低下抑制および/または改善、運動機能の維持、低下抑制および/または改善等が期待される。 In addition, by "maintaining, suppressing decline, or improving muscle mass and/or muscle strength" by the food and drink of the present invention, more specifically, for example, maintaining, suppressing decline, and/or improving walking function, maintaining motor function , reduction suppression and/or improvement are expected.
 飲食品としては、本発明の効果を損なわず、経口摂取できるものであれば形態や性状は特に制限されず、乳由来リン脂質を含有させること以外は、通常飲食品に用いられる原料を用いて通常の方法によって製造することができる。 The form and properties of the food and drink are not particularly limited as long as they do not impair the effects of the present invention and can be ingested orally, and raw materials commonly used for food and drink may be used, except for containing milk-derived phospholipids. It can be manufactured by conventional methods.
 飲食品としては、液状、ペースト状、ゲル状固体、粉末等の形態を問わず、例えば、錠菓;流動食(経管摂取用栄養食);パン、マカロニ、スパゲッティ、めん類、ケーキミックス、から揚げ粉、パン粉等の小麦粉製品;即席めん、カップめん、レトルト・調理食品、調理缶詰め、電子レンジ食品、即席スープ・シチュー、即席みそ汁・吸い物、スープ缶詰め、フリーズ・ドライ食品、その他の即席食品等の即席食品類;農産缶詰め、果実缶詰め、ジャム・マーマレード類、漬物、煮豆類、農産乾物類、シリアル(穀物加工品)等の農産加工品;水産缶詰め、魚肉ハム・ソーセージ、水産練り製品、水産珍味類、つくだ煮類等の水産加工品;畜産缶詰め・ペースト類、畜肉ハム・ソーセージ等の畜産加工品;加工乳、乳飲料、ヨーグルト(発酵乳)類、乳酸菌飲料類、チーズ、アイスクリーム類、クリーム、その他の乳製品等の乳・乳製品;バター、マーガリン類、植物油等の油脂類;しょうゆ、みそ、ソース類、トマト加工調味料、みりん類、食酢類等の基礎調味料;調理ミックス、カレーの素類、たれ類、ドレッシング類、めんつゆ類、スパイス類、その他の複合調味料等の複合調味料・食品類;素材冷凍食品、半調理冷凍食品、調理済冷凍食品等の冷凍食品;キャラメル、キャンディー、チューインガム、チョコレート、クッキー、ビスケット、ケーキ、パイ、スナック、クラッカー、和菓子、米菓子、豆菓子、デザート菓子、ゼリー、その他の菓子等の菓子類;炭酸飲料、天然果汁、果汁飲料、果汁入り清涼飲料、果肉飲料、果粒入り果実飲料、野菜系飲料、豆乳、豆乳飲料、コーヒー飲料、お茶飲料、粉末飲料、濃縮飲料、スポーツ飲料、栄養飲料、アルコール飲料、その他の嗜好飲料等の嗜好飲料類、ベビーフード、ふりかけ、お茶漬けのり等のその他の市販食品等;サプリメント、調製乳(粉乳、液状乳等を含む)等の栄養組成物;経腸栄養食;機能性食品(特定保健用食品、栄養機能食品)等が挙げられる。 Foods and beverages may be in the form of liquids, pastes, gel-like solids, powders, etc., such as tablets, liquid foods (nutritive foods for tube administration), bread, macaroni, spaghetti, noodles, cake mixes, etc. Flour products such as fried flour and bread crumbs; instant noodles, cup noodles, retort and cooked foods, cooked canned foods, microwave foods, instant soups and stews, instant miso soup and soups, canned soups, freeze-dried foods, and other instant foods, etc. Instant foods; Agricultural processed products such as canned agricultural products, canned fruits, jams and marmalade, pickles, boiled beans, dried agricultural products, cereals (processed grain products); Canned marine products, fish hams and sausages, seafood paste products, marine delicacies , Processed seafood products such as boiled fish; Processed livestock products such as canned livestock products, pastes, meat hams and sausages; Processed milk, milk drinks, yogurt (fermented milk), lactic acid bacteria drinks, cheese, ice cream, cream, Milk and dairy products such as other dairy products; Fats and oils such as butter, margarine, and vegetable oil; Basic seasonings such as soy sauce, miso, sauces, processed tomato seasonings, mirin, and vinegar; Cooking mixes, curry Complex seasonings and foods such as seasonings, sauces, dressings, noodle soups, spices, and other complex seasonings; Frozen foods such as raw frozen foods, semi-cooked frozen foods, and cooked frozen foods; Caramels, candy Confectionery such as chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice sweets, bean sweets, dessert sweets, jellies, and other sweets; carbonated drinks, natural fruit juices, fruit juice drinks, and refreshing drinks with fruit juice. Beverages, pulp drinks, fruit drinks with fruit grains, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic drinks, and other recreational drinks. , baby food, furikake, other commercially available foods such as ochazuke nori; supplements, nutritional compositions such as formula milk (including powdered milk, liquid milk, etc.); enteral nutritional foods; functional foods (foods for specified health uses, nutritional supplements, etc.); functional foods), etc.
 なお、飲食品としてサプリメントの形態とする場合は、腸溶性コーティング等により腸溶処理されてもよい、散剤、顆粒剤、錠剤、カプセル剤等の固形製剤;溶液剤、シロップ剤、懸濁剤、乳剤等の液剤;等に製剤化することができる。かかる製剤化に際しては、後述する医薬品の製剤化に係る成分、担体、および方法の説明に準ずることができる。 In addition, when it is in the form of a supplement as a food or drink, solid preparations such as powders, granules, tablets, capsules, etc. that may be enterically coated, solutions, syrups, suspensions, etc. It can be formulated into liquid formulations such as emulsions; Such formulation can be carried out in accordance with the explanations of components, carriers, and methods for formulating pharmaceuticals, which will be described later.
 また、飲食品の一態様として飼料とすることもできる。飼料としては、ペットフード、家畜飼料、養魚飼料等が挙げられる。
 飼料の形態としては特に制限されず、乳由来リン脂質の他に例えば、トウモロコシ、小麦、大麦、ライ麦、マイロ等の穀類;大豆油粕、ナタネ油粕、ヤシ油粕、アマニ油粕等の植物性油粕類;フスマ、麦糠、米糠、脱脂米糠等の糠類;コーングルテンミール、コーンジャムミール等の製造粕類;魚粉、脱脂粉乳、ホエイ、イエローグリース、タロー等の動物性飼料類;トルラ酵母、ビール酵母等の酵母類;第三リン酸カルシウム、炭酸カルシウム等の鉱物質飼料;油脂類;単体アミノ酸;糖類等を含有するものであってよい。
Moreover, it can also be used as feed as one aspect of food and drink products. Examples of the feed include pet food, livestock feed, and fish feed.
The form of the feed is not particularly limited, and in addition to milk-derived phospholipids, for example, grains such as corn, wheat, barley, rye, and milo; vegetable oil cakes such as soybean oil meal, rapeseed oil meal, coconut oil meal, and linseed oil meal; Bran such as bran, wheat bran, rice bran, and defatted rice bran; Manufactured lees such as corn gluten meal and corn jam meal; Animal feed such as fish meal, skim milk powder, whey, yellow grease, and tallow; Torula yeast and brewer's yeast Mineral feeds such as tricalcium phosphate and calcium carbonate; fats and oils; simple amino acids; sugars, etc. may be contained.
 本発明のコルチゾール産生抑制用組成物が飲食品(飼料を含む)の態様である場合、睡眠の質改善、筋肉量および/または筋力の維持、低下抑制、または改善等の用途が表示された飲食品として提供・販売されることが可能である。また、本明細書に係る乳由来リン脂質は、これら飲食品等の製造のために使用可能である。 When the composition for suppressing cortisol production of the present invention is in the form of a food or drink (including feed), the food or drink is labeled with uses such as improving sleep quality, maintaining, inhibiting decline in, or improving muscle mass and/or muscle strength. It is possible to provide and sell it as a product. Furthermore, the milk-derived phospholipid according to the present specification can be used for producing these foods and drinks.
 かかる「表示」行為には、需要者に対して前記用途を知らしめるための全ての行為が含まれ、前記用途を想起・類推させうるような表現であれば、表示の目的、表示の内容、表示する対象物・媒体等の如何に拘わらず、全て本発明における「表示」行為に該当する。
 また、「表示」は、需要者が上記用途を直接的に認識できるような表現により行われることが好ましい。具体的には、飲食品に係る商品または商品の包装に前記用途を記載したものを譲渡し、引き渡し、譲渡もしくは引き渡しのために展示し、輸入する行為、商品に関する広告、価格表もしくは取引書類に上記用途を記載して展示し、もしくは頒布し、またはこれらを内容とする情報に上記用途を記載して電磁気的(インターネット等)方法により提供する行為等が挙げられる。
Such acts of "display" include all acts to inform the consumer of the above-mentioned use, and if the expression is such that it may remind or infer the above-mentioned use, the purpose of the display, the content of the display, Regardless of the object or medium to be displayed, all of them fall under the act of "display" in the present invention.
Moreover, it is preferable that the "display" be performed using expressions that allow the consumer to directly recognize the above-mentioned use. Specifically, the act of transferring, handing over, displaying for transfer or delivery, or importing food and drink products or products with the above-mentioned usage written on their packaging, advertisements related to products, price lists, or transaction documents. Examples include acts of displaying or distributing information with the above-mentioned uses written thereon, or acts of writing the above-mentioned uses on information containing these items and providing it by electromagnetic (Internet, etc.) methods.
 一方、表示内容としては、行政等によって認可された表示(例えば、行政が定める各種制度に基づいて認可を受け、そのような認可に基づいた態様で行う表示等)であることが好ましい。また、そのような表示内容を、包装、容器、カタログ、パンフレット、POP等の販売現場における宣伝材、その他の書類等へ付することが好ましい。 On the other hand, the display content is preferably a display approved by the government (for example, a display that has been approved based on various systems established by the government and is performed in a manner based on such approval). Further, it is preferable to attach such display contents to packaging, containers, catalogs, pamphlets, promotional materials at sales sites such as POP, and other documents.
 また、「表示」には、健康食品、機能性食品、経腸栄養食品、特別用途食品、保健機能食品、特定保健用食品、栄養機能食品、機能性表示食品、医薬用部外品等としての表示も挙げられる。この中でも特に、消費者庁によって認可される表示、例えば、特定保健用食品、栄養機能食品、もしくは機能性表示食品に係る制度、またはこれらに類似する制度にて認可される表示等が挙げられる。具体的には、特定保健用食品としての表示、条件付き特定保健用食品としての表示、身体の構造や機能に影響を与える旨の表示、疾病リスク減少表示、科学的根拠に基づいた機能性の表示等を挙げることができ、より具体的には、健康増進法に規定する特別用途表示の許可等に関する内閣府令(平成二十一年八月三十一日内閣府令第五十七号)に定められた特定保健用食品としての表示(特に保健の用途の表示)およびこれに類する表示が典型的な例である。
 かかる表示としては、例えば、「過剰なコルチゾールの産生を抑制する」、「睡眠の質を高める」、「睡眠をサポート」、「起床時の疲労感を軽減する」、「就寝・起床リズムを整える」、「眠気を軽減する」、「筋肉・筋力の維持に役立つ」、「歩行機能の維持に役立つ」、「体脂肪の減少に役立つ」等と表示することが挙げられる。
In addition, "labeling" includes health foods, functional foods, enteral nutritional foods, special purpose foods, foods with health claims, foods for specified health uses, foods with nutritional function claims, foods with functional claims, quasi-drugs, etc. Display can also be mentioned. Among these, in particular, labeling approved by the Consumer Affairs Agency, for example, labeling approved under the system related to food for specified health uses, food with nutritional function claims, or food with functional claims, or a system similar to these, etc. can be mentioned. Specifically, labeling as a food for specified health uses, labeling as a food for specified health uses with conditions, labeling that it affects the structure or function of the body, labeling to reduce disease risk, and labeling as a food for specified health uses based on scientific evidence. More specifically, the Cabinet Office Ordinance on Permission for Special Purpose Labeling as stipulated in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009) Typical examples include labeling as food for specified health uses (especially labeling for health uses) and similar labeling as stipulated in
Such claims include, for example, ``suppresses excessive cortisol production,'' ``increases sleep quality,'' ``supports sleep,'' ``reduces feeling of fatigue when waking up,'' and ``regulates sleep/wake-up rhythm.''","Reducessleepiness,""Helpful for maintaining muscle/strength,""Helpful for maintaining walking function,""Helpful for reducing body fat," etc.
<医薬品>
 本発明のコルチゾール産生抑制用組成物は、医薬品の態様とすることもできる(以下、「本発明の医薬品」ということがある)。
 本発明のコルチゾール産生抑制用組成物は、有効成分として乳由来リン脂質を含み、コルチゾール産生を抑制させることから、コルチゾール過多に起因する種々の疾患および/または状態を予防、治療、または改善することが期待できる。
<Medicinal products>
The composition for suppressing cortisol production of the present invention can also be in the form of a pharmaceutical (hereinafter sometimes referred to as "the pharmaceutical of the present invention").
The composition for suppressing cortisol production of the present invention contains milk-derived phospholipids as an active ingredient and suppresses cortisol production, and therefore can prevent, treat, or improve various diseases and/or conditions caused by excessive cortisol. can be expected.
 したがって、本発明の医薬品としては、コルチゾール過剰産生に起因する疾患および/または状態、具体的にはコルチゾール過剰産生により予防、治療、または改善し得る疾患および/または状態のために投与されるものが好ましい。
 コルチゾール過剰産生によって引き起こされる疾患・状態としては、限定されないが、例えば、II型糖尿病、耐糖能異常、高血糖症、インスリン抵抗性、脂質代謝異常、異脂肪血症、高脂血症、高トリグリセリド血症、肥満、アテローム性動脈硬化症、シンドロームX、クッシング症候群、高血圧、認識障害、記憶障害、鬱病、不安症、痴呆症、アルツハイマー病、骨粗鬆症、緑内障、免疫疾患等の疾病・状態が挙げられる。本発明の医薬品は、これらの疾病・状態・合併症等の予防・治療・改善のために投与される医薬品とすることができる。
Therefore, the pharmaceuticals of the present invention include those administered for diseases and/or conditions caused by cortisol overproduction, specifically diseases and/or conditions that can be prevented, treated, or ameliorated by cortisol overproduction. preferable.
Diseases and conditions caused by cortisol overproduction include, but are not limited to, type II diabetes, impaired glucose tolerance, hyperglycemia, insulin resistance, abnormal lipid metabolism, dyslipidemia, hyperlipidemia, and high triglycerides. Diseases and conditions include blood pressure, obesity, atherosclerosis, syndrome X, Cushing's syndrome, hypertension, cognitive impairment, memory impairment, depression, anxiety, dementia, Alzheimer's disease, osteoporosis, glaucoma, and immune diseases. . The pharmaceutical of the present invention can be administered to prevent, treat, or improve these diseases, conditions, complications, etc.
 医薬品の投与経路は、経口または非経口のいずれでもよいが経口が好ましい。また、非経口摂取(投与)としては、経皮、静注、直腸投与、吸入等が挙げられる。
 医薬品の形態としては、投与方法に応じて、適宜所望の剤形に製剤化することができる。例えば、経口投与の場合、散剤、顆粒剤、錠剤、カプセル剤等の固形製剤;溶液剤、シロップ剤、懸濁剤、乳剤等の液剤等に製剤化することができる。また、腸溶性コーティング等により、腸溶剤とすることもできる。非経口投与の場合、座剤、軟膏剤、注射剤等に製剤化することができる。
 製剤化に際しては、乳由来リン脂質の他に、通常製剤化に用いられている賦形剤、pH調整剤、着色剤、矯味剤等の成分を用いることができる。また、他の薬効成分や、公知のまたは将来的に見出されるコルチゾール産生抑制作用を有する成分等を併用することも可能である。
 加えて、製剤化は剤形に応じて適宜公知の方法により実施できる。製剤化に際しては、適宜、通常製剤化に用いる担体を配合して製剤化してもよい。かかる担体としては、賦形剤、結合剤、崩壊剤、滑沢剤、安定剤、矯味矯臭剤等が挙げられる。
The route of administration of the drug may be either oral or parenteral, but oral is preferred. In addition, examples of parenteral ingestion (administration) include transdermal administration, intravenous injection, rectal administration, and inhalation.
The pharmaceutical form can be appropriately formulated into a desired dosage form depending on the administration method. For example, in the case of oral administration, it can be formulated into solid preparations such as powders, granules, tablets, and capsules; liquid preparations such as solutions, syrups, suspensions, and emulsions. Moreover, it can also be made into an enteric agent by enteric coating or the like. For parenteral administration, it can be formulated into suppositories, ointments, injections, etc.
When formulating, in addition to the milk-derived phospholipid, components such as excipients, pH adjusters, coloring agents, and flavoring agents that are commonly used in formulating can be used. In addition, it is also possible to use other medicinal ingredients and ingredients that are known or will be discovered in the future and have a cortisol production suppressing effect.
In addition, formulation can be carried out by appropriately known methods depending on the dosage form. During formulation, carriers commonly used in formulation may be added as appropriate. Such carriers include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, and the like.
 賦形剤としては、例えば、乳糖、白糖、ブドウ糖、マンニット、ソルビット等の糖誘導体;トウモロコシデンプン、馬鈴薯デンプン、α-デンプン、デキストリン、カルボキシメチルデンプン等のデンプン誘導体;結晶セルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースカルシウム等のセルロース誘導体;アラビアゴム;デキストラン;プルラン;軽質無水珪酸、合成珪酸アルミニウム、メタ珪酸アルミン酸マグネシウム等の珪酸塩誘導体;リン酸カルシウム等のリン酸塩誘導体;炭酸カルシウム等の炭酸塩誘導体;硫酸カルシウム等の硫酸塩誘導体等が挙げられる。 Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, Cellulose derivatives such as hydroxypropyl methylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light silicic anhydride, synthetic aluminum silicate, magnesium aluminate metasilicate; phosphate derivatives such as calcium phosphate; carbonic acid Examples include carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate.
 結合剤としては、例えば、上記賦形剤の他、ゼラチン;ポリビニルピロリドン;マクロゴール等が挙げられる。 Examples of the binder include, in addition to the excipients mentioned above, gelatin; polyvinylpyrrolidone; macrogol, and the like.
 崩壊剤としては、例えば、上記賦形剤の他、クロスカルメロースナトリウム、カルボキシメチルスターチナトリウム、架橋ポリビニルピロリドン等の化学修飾されたデンプンまたはセルロース誘導体等が挙げられる。 Examples of the disintegrant include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch, and crosslinked polyvinylpyrrolidone.
 滑沢剤としては、例えば、タルク;ステアリン酸;ステアリン酸カルシウム、ステアリン酸マグネシウム等のステアリン酸金属塩;コロイドシリカ;ビーガム、ゲイロウ等のワックス類;硼酸;グリコール;フマル酸、アジピン酸等のカルボン酸類;安息香酸ナトリウム等のカルボン酸ナトリウム塩;硫酸ナトリウム等の硫酸塩類;ロイシン;ラウリル硫酸ナトリウム、ラウリル硫酸マグネシウム等のラウリル硫酸塩;無水珪酸、珪酸水和物等の珪酸類;デンプン誘導体等が挙げられる。 Examples of lubricants include talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as vegum and gay wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid. ; carboxylic acid sodium salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; starch derivatives, etc. It will be done.
 安定剤としては、例えば、メチルパラベン、プロピルパラベン等のパラオキシ安息香酸エステル類;クロロブタノール、ベンジルアルコール、フェニルエチルアルコール等のアルコール類;塩化ベンザルコニウム;無水酢酸;ソルビン酸等が挙げられる。 Examples of the stabilizer include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; and sorbic acid.
 矯味矯臭剤としては、例えば、甘味料、酸味料、香料等が挙げられる。
 なお、経口投与用の液剤の場合に使用する担体としては、水等の溶剤等が挙げられる。
Examples of flavoring agents include sweeteners, acidulants, fragrances, and the like.
In addition, examples of carriers used in the case of liquid preparations for oral administration include solvents such as water.
 本発明の医薬品を摂取するタイミングは、例えば食前、食後、食間、就寝前等特に限定されない。 The timing of ingesting the pharmaceutical of the present invention is not particularly limited, such as before meals, after meals, between meals, before going to bed, etc.
 本発明のコルチゾール産生抑制用組成物を投与する(摂取させる)対象は、動物であれば特に限定されないが、通常は哺乳動物であり、ヒトが好ましい。 The subject to whom the composition for suppressing cortisol production of the present invention is administered (ingested) is not particularly limited as long as it is an animal, but is usually a mammal, preferably a human.
 本発明の別の側面は、コルチゾール産生抑制用組成物の製造における、乳由来リン脂質の使用である。
 本発明の別の側面は、コルチゾール産生抑制における、乳由来リン脂質の使用である。
 本発明の別の側面は、コルチゾール産生抑制用組成物のために用いられる、乳由来リン脂質である。
 本発明の別の側面は、乳由来リン脂質を対象に投与することを含む、コルチゾールの産生を抑制する方法である。
Another aspect of the invention is the use of milk-derived phospholipids in the manufacture of a composition for inhibiting cortisol production.
Another aspect of the invention is the use of milk-derived phospholipids in suppressing cortisol production.
Another aspect of the present invention is a milk-derived phospholipid used for a composition for suppressing cortisol production.
Another aspect of the invention is a method of suppressing cortisol production, which includes administering milk-derived phospholipids to a subject.
 なお、「乳由来リン脂質を対象に投与すること」は、「乳由来リン脂質を対象に摂取させること」と同義であってよい。摂取は、自発的なもの(自由摂取)であってもよく、強制的なもの(強制摂取)であってもよい。すなわち、投与工程は、具体的には、例えば、乳由来リン脂質を飲食品や飼料に配合して対象に供給し、以て対象に乳由来リン脂質を自由摂取させる工程であってもよい。 Note that "administering milk-derived phospholipids to a subject" may be synonymous with "making a subject ingest milk-derived phospholipids." The intake may be voluntary (free intake) or forced (forced intake). Specifically, the administration step may be, for example, a step in which the milk-derived phospholipid is blended into a food/drink or feed and supplied to the subject, thereby allowing the subject to freely ingest the milk-derived phospholipid.
 本発明のコルチゾール産生抑制用組成物の摂取(投与)時期や摂取(投与)期間は、特に限定されず、投与対象の状態に応じて適宜選択することができる。 The intake (administration) timing and intake (administration) period of the composition for suppressing cortisol production of the present invention are not particularly limited, and can be appropriately selected depending on the condition of the subject to be administered.
<睡眠の質改善用組成物、筋肉量および/または筋力の維持、低下抑制、または改善用組成物>
 本発明の別の一態様は、乳由来リン脂質を含む、睡眠の質改善用組成物(以下、「本発明の睡眠の質改善用組成物」ということがある)に関する。本発明の睡眠の質改善用組成物は、乳由来リン脂質を有効成分として含むものであり、乳由来リン脂質の作用により睡眠の質を改善することが期待できる。
 なお、上記<コルチゾール産生抑制用組成物>、<飲食品>、<医薬品>において説明された事項は、本発明の睡眠の質改善用組成物の説明に全て適用される。
 また、本発明の別の一態様は、乳由来リン脂質を含む、筋肉量および/または筋力の維持、低下抑制、または改善用組成物であって、前記乳由来リン脂質が、ホスファチジルコリンである、組成物(以下、「本発明の筋肉量および/または筋力の維持、低下抑制、または改善用組成物」ということがある)に関する。本発明の筋肉量および/または筋力の維持、低下抑制、または改善用組成物は、ホスファチジルコリンを有効成分として含むものであり、ホスファチジルコリンの作用により、筋肉量および/または筋力の維持、低下抑制、または改善することが期待できる。
 なお、上記<コルチゾール産生抑制用組成物>、<飲食品>、<医薬品>において説明された事項は、本発明の筋肉量および/または筋力の維持、低下抑制、または改善用組成物の説明に全て適用される。
<Composition for improving sleep quality, composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength>
Another aspect of the present invention relates to a composition for improving sleep quality (hereinafter sometimes referred to as "composition for improving sleep quality of the present invention") containing milk-derived phospholipids. The composition for improving sleep quality of the present invention contains milk-derived phospholipids as an active ingredient, and can be expected to improve sleep quality through the action of milk-derived phospholipids.
Note that the matters explained in the above <Composition for suppressing cortisol production>, <Food and drink>, and <Pharmaceuticals> are all applicable to the description of the composition for improving sleep quality of the present invention.
Another aspect of the present invention is a composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength, which comprises a milk-derived phospholipid, wherein the milk-derived phospholipid is phosphatidylcholine. The present invention relates to a composition (hereinafter sometimes referred to as "composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength of the present invention"). The composition for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength of the present invention contains phosphatidylcholine as an active ingredient, and maintains, suppresses decline in, or improves muscle mass and/or muscle strength due to the action of phosphatidylcholine. We can expect it to improve.
Note that the matters explained in the above <Composition for suppressing cortisol production>, <Food and drink>, and <Pharmaceuticals> do not apply to the explanation of the composition for maintaining, inhibiting decline in, or improving muscle mass and/or muscle strength of the present invention. All apply.
 以下、実施例により、本発明をさらに具体的に説明するが、本発明はその要旨を超えない限り、これらの実施例に限定されるものではない。 Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples unless the gist thereof is exceeded.
[実施例]
(副腎皮質癌細胞株の培養)
 副腎皮質癌細胞株(HAC15)をATCCから入手した。HAC15細胞株は20mlのDMEM:F12(1:1)培地(Thermo Fisher Scientific 社製)に10%のCosmic Calf serum(Cytiva社製)とPenicillin Streptomycin (富士フィルム和光純薬社製)を添加した培地で11日間前培養した。前培養の間、播種後4日目、8日目に細胞を継代した。播種後11日目にトリプシン(富士フィルム和光純薬社製)で処理し、細胞を回収した。回収した細胞は培養に用いたDMEM:F12(1:1)培地に0.1%のCosmic Calf serumとPenicillin Streptomycinを添加した培地を用いて懸濁した。細胞を懸濁した培地を48穴細胞培養用プレート(CORNING社製)に1ウェルあたりの細胞数が5×10個となるよう播種した。
[Example]
(Culture of adrenocortical carcinoma cell line)
Adrenocortical carcinoma cell line (HAC15) was obtained from ATCC. HAC15 cell line is grown in 20 ml of DMEM:F12 (1:1) medium (Thermo Fisher Scientific) supplemented with 10% Cosmic Calf serum (Cytiva) and Penicillin Streptomycin (Fuji Film Wako Pure Chemical Industries). The cells were precultured for 11 days. During preculture, cells were passaged on the 4th and 8th day after seeding. Eleven days after seeding, the cells were treated with trypsin (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) and collected. The collected cells were suspended in a DMEM:F12 (1:1) medium used for culture to which 0.1% Cosmic Calf serum and Penicillin Streptomycin were added. The medium in which the cells were suspended was seeded in a 48-well cell culture plate (manufactured by CORNING) so that the number of cells per well was 5 x 104 .
(リン脂質溶液および懸濁液の調製)
 ホスファチジルコリン、スフィンゴミエリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、ホスファチジルセリンの5種類のリン脂質(全て長良サイエンス社製)を10mg/mlの濃度となるようエタノールに溶解または懸濁させた。
(Preparation of phospholipid solutions and suspensions)
Five types of phospholipids (all manufactured by Nagara Science), phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine, were dissolved or suspended in ethanol to a concentration of 10 mg/ml.
(リン脂質混合物での処理)
 エタノールに溶解または懸濁させた5種類のリン脂質を、一般的なホエイタンパク・リン脂質濃縮物に含まれるリン脂質の組成に合わせて、(表1)に示す割合で混合した。混合したリン脂質をエタノールでさらに2倍、4倍に希釈した希釈液もあわせて調製した。調製したリン脂質溶液および希釈液を、HAC15細胞を播種したウェルに1/100体積添加した。その後、5%CO、37度に保ったインキュベーターで24時間培養し、培養上清を回収した。培養上清は2,000gで10分間遠心分離し不溶成分を取り除き、解析に供するまで-80度で保存した。
(Treatment with phospholipid mixture)
Five types of phospholipids dissolved or suspended in ethanol were mixed in the proportions shown in Table 1 in accordance with the composition of phospholipids contained in common whey protein/phospholipid concentrates. A diluted solution in which the mixed phospholipids were further diluted 2 times and 4 times with ethanol was also prepared. The prepared phospholipid solution and diluted solution were added at 1/100 volume to the wells in which HAC15 cells were seeded. Thereafter, the cells were cultured for 24 hours in an incubator maintained at 37 degrees and 5% CO 2 , and the culture supernatant was collected. The culture supernatant was centrifuged at 2,000 g for 10 minutes to remove insoluble components and stored at -80 degrees until used for analysis.
(各リン脂質での処理)
 ホスファチジルコリン、スフィンゴミエリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、ホスファチジルセリンをそれぞれ(表2)に示す濃度でエタノールに懸濁または溶解した。各リン脂質の溶液または懸濁液を、HAC15細胞を播種した各ウェルに1/100体積添加した。その後、5%CO、37度に保ったインキュベーターで24時間培養し、培養上清を回収した。培養上清は2,000gで10分間遠心分離し不溶成分を取り除き、解析に供するまで-80度で保存した。
(Treatment with each phospholipid)
Phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine were each suspended or dissolved in ethanol at the concentrations shown in Table 2. 1/100 volume of each phospholipid solution or suspension was added to each well seeded with HAC15 cells. Thereafter, the cells were cultured for 24 hours in an incubator maintained at 37 degrees and 5% CO 2 , and the culture supernatant was collected. The culture supernatant was centrifuged at 2,000 g for 10 minutes to remove insoluble components and stored at -80 degrees until used for analysis.
(ホスファチジルコリンとスフィンゴミエリンの組み合わせによる処理)
 ホスファチジルコリン、スフィンゴミエリンを(表3)、ホスファチジルエタノールアミン、ホスファチジルイノシトール、ホスファチジルセリンを(表4)に示す濃度となるようにエタノールに懸濁または溶解した。それぞれHAC15細胞を播種した各ウェルに1/100体積添加した。その後、5%CO、37度に保ったインキュベーターで24時間培養し、培養上清を回収した。培養上清は2,000gで10分間遠心分離し不溶成分を取り除き、解析に供するまで-80度で保存した。
(Treatment using a combination of phosphatidylcholine and sphingomyelin)
Phosphatidylcholine and sphingomyelin (Table 3), phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine were suspended or dissolved in ethanol to the concentrations shown in Table 4. 1/100 volume was added to each well seeded with HAC15 cells. Thereafter, the cells were cultured for 24 hours in an incubator maintained at 37 degrees and 5% CO 2 , and the culture supernatant was collected. The culture supernatant was centrifuged at 2,000 g for 10 minutes to remove insoluble components and stored at -80 degrees until used for analysis.
(複数の濃度のホスファチジルコリンとスフィンゴミエリン単体での処理)
 ホスファチジルコリン、スフィンゴミエリンそれぞれ、10mg/ml、5mg/ml、2.5mg/ml、1.25mg/ml、0.63mg/ml、0.31mg/mlの濃度となるようエタノールで溶解した。それぞれHAC15細胞を播種した各ウェルに1/100体積添加した。その後、5%CO、37度に保ったインキュベーターで24時間培養し、培養上清を回収した。培養上清は2,000gで10分間遠心分離し不溶成分を取り除き、解析に供するまで-80度で保存した。
(Treatment with multiple concentrations of phosphatidylcholine and sphingomyelin alone)
Phosphatidylcholine and sphingomyelin were dissolved in ethanol to a concentration of 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1.25 mg/ml, 0.63 mg/ml, and 0.31 mg/ml, respectively. 1/100 volume was added to each well seeded with HAC15 cells. Thereafter, the cells were cultured for 24 hours in an incubator maintained at 37 degrees and 5% CO 2 , and the culture supernatant was collected. The culture supernatant was centrifuged at 2,000 g for 10 minutes to remove insoluble components and stored at -80 degrees until used for analysis.
(コルチゾールの定量)
 凍結した培養上清を氷上で解凍し、Cortisol ELISA kit(Enzo社)の提供するマニュアルに従って測定を行った。サンプルは付属のアッセイバッファーで20倍に希釈して測定した。
(quantification of cortisol)
The frozen culture supernatant was thawed on ice and measured according to the manual provided by Cortisol ELISA kit (Enzo). The sample was diluted 20 times with the attached assay buffer and measured.
(結果)
 ホスファチジルコリン、スフィンゴミエリン、ホスファチジルエタノールアミン、ホスファチジルイノシトール、ホスファチジルセリンの5種のリン脂質からなるリン脂質混合物は濃度依存的にHAC15細胞のコルチゾール産生を抑制した(各試料につき、n=3)(図1)。リン脂質混合物に含まれる5種類のリン脂質のうち、ホスファチジルコリン、スフィンゴミエリンがHAC15細胞のコルチゾール産生を抑制した(各試料につき、n=3)(図2)。ホスファチジルコリン、スフィンゴミエリンの組み合わせはHAC15細胞のコルチゾール産生を抑制したが、ホスファチジルエタノールアミン、ホスファチジルイノシトール、ホスファチジルセリンの組み合わせは抑制しなかった(各試料につき、n=3)(図3)。ホスファチジルコリン、スフィンゴミエリンは濃度依存的にHAC15細胞のコルチゾール産生を抑制した(各試料につき、n=3)(図4)。ホスファチジルコリンおよびスフィンゴミエリンを各濃度で作用させた場合のコルチゾール産生抑制率を算出した(表5)。さらに、(図3)に示したデータよりホスファチジルコリン、スフィンゴミエリンの組み合わせによるコルチゾール産生抑制率を算出した(表6)。コルチゾール産生抑制率はコントロールに対する各サンプル処理による培養上清中のコルチゾールの減少量の百分率であらわした。ホスファチジルコリン、スフィンゴミエリンの組み合わせでは培地中に各々終濃度として26.9μg/ml、23.7μg/mlを含むため、これらを合算したリン脂質の濃度は50.6μg/mlであり、コルチゾール産生抑制率は42%を示した。一方で、ホスファチジルコリン、スフィンゴミエリン単体は各々50μg/mlの濃度でコルチゾール産生抑制率はそれぞれ25%、37%であった。さらに、ホスファチジルコリン、スフィンゴミエリンの単体は100μg/mlまで濃度を高めても産生抑制率はそれぞれ34%、38%であった。これらはホスファチジルコリンとスフィンゴミエリンの組み合わせが、相乗的に作用し各々単体に比べて強力にコルチゾールの産生を抑制することを示唆する。
(result)
A phospholipid mixture consisting of five types of phospholipids: phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine suppressed cortisol production in HAC15 cells in a concentration-dependent manner (n = 3 for each sample) (Figure 1 ). Among the five types of phospholipids contained in the phospholipid mixture, phosphatidylcholine and sphingomyelin suppressed cortisol production in HAC15 cells (n=3 for each sample) (Figure 2). The combination of phosphatidylcholine and sphingomyelin suppressed cortisol production in HAC15 cells, but the combination of phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine did not (n=3 for each sample) (Figure 3). Phosphatidylcholine and sphingomyelin suppressed cortisol production in HAC15 cells in a concentration-dependent manner (n=3 for each sample) (FIG. 4). The inhibition rate of cortisol production when phosphatidylcholine and sphingomyelin were applied at each concentration was calculated (Table 5). Furthermore, the cortisol production suppression rate by the combination of phosphatidylcholine and sphingomyelin was calculated from the data shown in FIG. 3 (Table 6). The rate of inhibition of cortisol production was expressed as the percentage of decrease in cortisol in the culture supernatant by each sample treatment relative to the control. The combination of phosphatidylcholine and sphingomyelin contains final concentrations of 26.9 μg/ml and 23.7 μg/ml, respectively, in the medium, so the combined phospholipid concentration is 50.6 μg/ml, and the cortisol production inhibition rate showed 42%. On the other hand, phosphatidylcholine and sphingomyelin alone had a cortisol production suppression rate of 25% and 37%, respectively, at a concentration of 50 μg/ml. Furthermore, even when the concentration of phosphatidylcholine and sphingomyelin alone was increased to 100 μg/ml, the production inhibition rate was 34% and 38%, respectively. These results suggest that the combination of phosphatidylcholine and sphingomyelin acts synergistically to suppress cortisol production more strongly than either agent alone.
 本発明は、飲食品、健康食品、機能性食品、サプリメント、医薬品等の分野で有用である。 The present invention is useful in the fields of food and beverages, health foods, functional foods, supplements, pharmaceuticals, etc.

Claims (11)

  1.  乳由来リン脂質を含む、コルチゾール産生抑制用組成物。 A composition for suppressing cortisol production containing milk-derived phospholipids.
  2.  前記リン脂質が、スフィンゴミエリンおよびホスファチジルコリンから選択される1種以上を含む、請求項1に記載の組成物。 The composition according to claim 1, wherein the phospholipid contains one or more selected from sphingomyelin and phosphatidylcholine.
  3.  前記リン脂質が、スフィンゴミエリンおよびホスファチジルコリンの組み合わせを含む、請求項2に記載の組成物。 3. The composition of claim 2, wherein the phospholipid comprises a combination of sphingomyelin and phosphatidylcholine.
  4.  飲食品である、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, which is a food or drink.
  5.  睡眠の質改善用である、請求項1~4のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 4, which is used to improve sleep quality.
  6.  筋肉量および/または筋力の維持、低下抑制、または改善用である、請求項1~4のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 4, which is used for maintaining, suppressing decline in, or improving muscle mass and/or muscle strength.
  7.  医薬品である、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, which is a pharmaceutical.
  8.  コルチゾール産生抑制により、予防、治療、または改善し得る疾患および/または状態のために投与される、請求項7に記載の組成物。 The composition according to claim 7, which is administered for diseases and/or conditions that can be prevented, treated, or ameliorated by suppressing cortisol production.
  9.  前記疾患および/または状態が、II型糖尿病、耐糖能異常、高血糖症、インスリン抵抗性、筋分解、脂質代謝異常、異脂肪血症、高脂血症、高トリグリセリド血症、肥満、アテローム性動脈硬化症、シンドロームX、クッシング症候群、高血圧、認識障害、記憶障害、うつ病、不眠症、不安症、痴呆症、アルツハイマー病、骨粗鬆症、緑内障、および免疫疾患からなる群から選択される1種以上である、請求項8に記載の組成物。 The disease and/or condition is type II diabetes, impaired glucose tolerance, hyperglycemia, insulin resistance, muscle breakdown, abnormal lipid metabolism, dyslipidemia, hyperlipidemia, hypertriglyceridemia, obesity, atherosclerosis. One or more types selected from the group consisting of arteriosclerosis, syndrome X, Cushing's syndrome, hypertension, cognitive impairment, memory impairment, depression, insomnia, anxiety, dementia, Alzheimer's disease, osteoporosis, glaucoma, and immune diseases The composition according to claim 8.
  10.  乳由来リン脂質を含む、睡眠の質改善用組成物。 A composition for improving sleep quality containing milk-derived phospholipids.
  11.  乳由来リン脂質を含む、筋肉量および/または筋力の維持、低下抑制、または改善用組成物であって、前記乳由来リン脂質が、ホスファチジルコリンである、組成物。 A composition for maintaining, inhibiting decline in, or improving muscle mass and/or muscle strength, which contains a milk-derived phospholipid, and the milk-derived phospholipid is phosphatidylcholine.
PCT/JP2023/013057 2022-03-30 2023-03-30 Composition for inhibiting production of cortisol WO2023190809A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101606942A (en) * 2009-07-09 2009-12-23 北京康比特体育科技股份有限公司 A kind of nutritional supplement of relieving sports fatigue
JP2017171595A (en) * 2016-03-22 2017-09-28 雪印メグミルク株式会社 Bdnf production promoting agent
US20200397842A1 (en) * 2019-06-20 2020-12-24 Steven Adler Plant-based compositions and methods for reducing cortisol levels

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101606942A (en) * 2009-07-09 2009-12-23 北京康比特体育科技股份有限公司 A kind of nutritional supplement of relieving sports fatigue
JP2017171595A (en) * 2016-03-22 2017-09-28 雪印メグミルク株式会社 Bdnf production promoting agent
US20200397842A1 (en) * 2019-06-20 2020-12-24 Steven Adler Plant-based compositions and methods for reducing cortisol levels

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