Composition for suppressing cortisol production

Abstract

To provide a novel food ingredient for suppressing cortisol production and a composition incorporating the food ingredient.SOLUTION: A cortisol production-suppressing composition comprising a milk-derived phospholipid is provided.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to a composition for inhibiting cortisol production, etc. [Background technology]

[0002] Cortisol is a hormone produced by the adrenal cortex and is released in response to stress, etc. Excess cortisol can cause a variety of problems, including insomnia, muscle atrophy, hyperglycemia, and high blood pressure. Medications that suppress cortisol production have been developed, but they cannot be ingested on a daily basis like foods. Therefore, the development of foods that suppress cortisol production is thought to be of great significance in terms of preventing and improving problems caused by excess cortisol.

[0003] Glycerophosphatidylcholine (GPC), a derivative of phosphatidylcholine (PC), a type of milk-derived phospholipid, is known as a food ingredient that suppresses cortisol production (Non-Patent Document 1). However, there have been no reports that sphingomyelin (SM), a type of milk-derived phospholipid, suppresses cortisol production.

[0004] It has also been reported that special PC bound with DHA improves sleep rhythm. However, the mechanism is not mediated by the inhibition of cortisol production (Non-Patent Document 2). There have been no reports of SM improving sleep. Furthermore, there have been no reports of PC inhibiting muscle atrophy by inhibiting cortisol production. On the other hand, there have been many reports that SM is useful for maintaining muscle mass and improving motor function, but this is not mediated by its inhibitory effect on cortisol production (Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2016-121132 [Non-patent literature]

[0006] [Non-Patent Document 1] PM Kidd, PhD “GPC, Mind-Body Nutrient” Science&Ingredients April 2005 [Non-patent document 2] J. Lipid Nutr. Vol.22, No.1 (2013) Summary of the Invention [Problem to be solved by the invention]

[0007] As mentioned above, suppressing excessive cortisol production is beneficial for health, but there are limited ways to achieve this through inexpensive and safe food intake. GPC, derived from PC, has been reported to suppress cortisol production, but it is difficult to obtain because it is produced by enzymatically processing PC. Regarding sleep improvement effects, a challenge remains: only the rare, special DHA-bound PC found in fish eggs can be effective. Furthermore, improving the muscle atrophy-inhibiting effect of SM remains a challenge. In view of these circumstances, an objective of the present invention is to provide a new food ingredient that suppresses cortisol production and a composition containing the food ingredient. [Means for solving the problem]

[0008] The present inventors have conducted extensive research with the aim of obtaining a new food ingredient that suppresses cortisol production and a composition containing the food ingredient. As a result, they have discovered that milk-derived phospholipids have an inhibitory effect on cortisol production, and have found a means of suppressing cortisol production using milk-derived phospholipids that can be ingested as food. In particular, they have found that milk-derived phospholipids, which are not PC derivatives that require special processing, can be used alone. We have found that PC, which is commonly found in foods, has a cortisol production inhibitory effect. We have also found that SM, which is commonly found in foods, has a cortisol production inhibitory effect. Furthermore, we have suggested that combining PC with SM exerts a stronger cortisol production inhibitory effect than either substance alone. Based on these findings, we have completed the present invention.

[0009] That is, the gist of the present invention relates to the following. [1] A composition for suppressing cortisol production, comprising milk-derived phospholipids. In this specification, "for suppressing cortisol production" can be rephrased as "for suppressing cortisol production." The following aspects are also aspects 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 for suppressing cortisol production. [1-3] Use of milk-derived phospholipids for producing a composition for suppressing cortisol production. [2] The composition described in [1], wherein the phospholipid comprises one or more selected from sphingomyelin and phosphatidylcholine. [3] The composition described in [2], wherein the phospholipid comprises 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 this specification, "for improving sleep quality" can be rephrased as "for improving sleep quality." The following aspects are also aspects 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 phospholipids for the manufacture of a composition for improving sleep quality. [6] The composition according to any one of [1] to [4], which is for maintaining, inhibiting a decline in, or improving muscle mass and / or muscle strength. In this specification, "for maintaining, inhibiting a decline in, or improving muscle mass and / or muscle strength" can be rephrased as "for maintaining, inhibiting a decline in, or improving muscle mass and / or muscle strength." The following aspects are also aspects of the present invention. [6-1] A method for maintaining, inhibiting decline, or improving muscle mass and / or muscle strength, comprising administering milk-derived phospholipids to a subject. [6-2] Use of milk-derived phospholipids for maintaining, preventing loss of, or improving muscle mass and / or muscle strength. [6-3] Use of milk-derived phospholipids for the manufacture of a composition for maintaining, preventing loss of, or improving muscle mass and / or muscle strength. [7] The composition according to any one of [1] to [3], which is a pharmaceutical product. [8] The composition according to [7], which is administered for a disease and / or condition that can be prevented, treated, or ameliorated by suppressing cortisol production. In this specification, "a disease and / or condition that can be prevented, treated, or ameliorated by suppressing cortisol production" can be rephrased as "a disease and / or condition caused by excessive cortisol production." The following aspects are also aspects of the present invention. [8-1] A method for preventing, treating, or ameliorating diseases and / or conditions caused by excessive cortisol production, comprising administering milk-derived phospholipids to a subject. [8-2] Use of milk-derived phospholipids for the prevention, treatment, or amelioration of diseases and / or conditions caused by excessive cortisol production. [8-3] Use of milk-derived phospholipids for the manufacture of a composition for preventing, treating, or ameliorating diseases and / or conditions caused by excessive cortisol production. [9] The disease and / or condition is type 2 diabetes, impaired glucose tolerance, hyperglycemia, insulin resistance, [8] The composition according to [8], wherein the target disease is one or more selected from the group consisting of insulin resistance, muscle degradation, dyslipidemia, 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.

[10] A composition for improving sleep quality, comprising milk-derived phospholipids.

[11] A composition for maintaining, inhibiting the decline of, or improving muscle mass and / or muscle strength, comprising a milk-derived phospholipid, wherein the milk-derived phospholipid is phosphatidylcholine. The following aspects are also aspects of the present invention. [11-1] A method for maintaining, preventing a decline in, or improving muscle mass and / or muscle strength, 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, preventing a 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 manufacture of a composition for maintaining, preventing the decline of, or improving muscle mass and / or muscle strength, wherein the milk-derived phospholipid is phosphatidylcholine. [Effects of the Invention]

[0010] The present invention provides a safe and cost-effective means for suppressing cortisol production, and a means for improving sleep quality and suppressing muscle breakdown through the suppression of cortisol production. Furthermore, it is expected that the combination of PC and SM will be more effective than conventional techniques in improving sleep quality and suppressing muscle breakdown. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 shows the results of a test on the inhibition of cortisol production in HAC15 cells by a mixture of five types of phospholipids. [Figure 2] FIG. 2 shows the test results of the inhibition of cortisol production in HAC15 cells by each phospholipid. [Figure 3] FIG. 3 shows the results of a test on the inhibition of cortisol production in HAC15 cells by a combination of phospholipids (a combination of phosphatidylcholine and sphingomyelin, or a combination of phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS)). [Figure 4] FIG. 4 shows the results of a test on the inhibition of cortisol production in HAC15 cells by phosphatidylcholine at various concentrations and by sphingomyelin alone. DETAILED DESCRIPTION OF THE INVENTION

[0012] Hereinafter, embodiments of the present invention will be described. 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 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 "greater than or equal to" or "greater than."

[0013] 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 an individual developing a disease, symptom, or condition. Also, as used herein, "amelioration" refers to improving a disease, symptom, or condition, preventing, suppressing, or delaying the worsening of a disease, symptom, or condition, or reversing, preventing, suppressing, or delaying the progression of a disease, symptom, or condition.

[0014] <Composition for inhibiting cortisol production> One aspect of the present invention relates to a composition for inhibiting cortisol production, which comprises a milk-derived phospholipid (hereinafter, may be referred to as "the composition for inhibiting cortisol production of the present invention").

[0015] <Milk-derived phospholipids> The composition for inhibiting cortisol production of the present invention contains milk-derived phospholipids as an active ingredient. Here, "milk-derived phospholipids" refers to phospholipids originally contained in milk, and does not refer to the source of extraction. In other words, phospholipids that have the same structure as phospholipids contained in milk are included in the milk-derived phospholipids of the present invention. Furthermore, "milk-derived phospholipids" refers not only to phospholipids that have the same structure as phospholipids contained in milk, but also to derivatives that have a partial structure different from that of phospholipids contained in milk, as long as they maintain the activity required for the present invention.

[0016] Phospholipids contained in milk generally include sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine.

[0017] 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 bonded to sphingosine), but the types are not limited in the present invention. Typical examples of sphingomyelin include stearylsphingomyelin, palmitoylsphingomyelin, and tricosanylsphingomyelin, but the present invention is not limited to these. Note that, in this specification, the term "sphingomyelin" refers to one or more of the multiple types that exist depending on the fatty acid. The same applies to other milk-derived phospholipids.

[0018] There are several types of phosphatidylcholine depending on the type of two fatty acids ester-bonded to the glycerol backbone in the structure, but the type is not limited in the present invention. Typical examples of phosphatidylcholine include dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, egg phosphatidylcholine, and 1-palmitoyl-2-oleoylphosphatidylcholine, but the present invention is not limited thereto.

[0019] From the viewpoint of the cortisol production inhibitory effect, the milk-derived phospholipids used in the composition for inhibiting cortisol production of the present invention preferably contain one or more selected from sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, more preferably one or more selected from sphingomyelin and phosphatidylcholine, and even more preferably a combination of sphingomyelin and phosphatidylcholine.

[0020] As used herein, the phrase "comprising one or more selected from sphingomyelin and phosphatidylcholine" encompasses "an embodiment comprising one or more types of sphingomyelin and no phosphatidylcholine," "an embodiment comprising one or more types of phosphatidylcholine and no sphingomyelin," and "an embodiment comprising one or more types of sphingomyelin and one or more types of phosphatidylcholine."

[0021] Furthermore, in this specification, "comprising a combination of sphingomyelin and phosphatidylcholine" means "an embodiment comprising one or more types of sphingomyelin and one or more types of phosphatidylcholine."

[0022] The milk-derived phospholipids may be those derived from milk or those chemically synthesized from phospholipids originally contained in milk. As the milk-derived phospholipids, phospholipids derived from the milk of mammals such as cows, goats, sheep, and humans are preferred, and phospholipids derived from cow's milk are more preferred.

[0023] The milk-derived phospholipids used in the present invention can be prepared, for example, from raw milk (e.g., cow's milk) according to known methods. For example, in the case of milk-derived phospholipids, they can be prepared from buttermilk, a by-product of butter production, butter serum, a by-product of butter oil production from cream or butter, whey, a by-product of cheese production, a phospholipid-containing composition, a by-product of WPI (Whey Protein Isolate) production from whey, or skim milk, etc., by filtration, solvent extraction, fractionation by various chromatography methods, or a combination thereof, according to known methods. Furthermore, the milk-derived phospholipids used in the present invention do not necessarily need to be separated and purified as phospholipids. As long as they have the cortisol production inhibitory effect of the present invention, a mixture of milk-derived phospholipids or a milk-derived phospholipid-containing composition (a composition containing milk-derived phospholipids and other optional components) can also be used.

[0024] Commercially available milk-derived phospholipids and milk-derived phospholipid-containing compositions can also be used, including, but not limited to, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine (manufactured by Nagara Science Co., Ltd.), and a phospholipid-containing composition (Milei (registered trademark) 70 HPL; manufactured by Milei Co., Ltd.).

[0025] When the milk-derived phospholipid used in the composition for inhibiting cortisol production of the present invention contains multiple types of phospholipids, the ratios thereof are not limited and may be the composition ratios of phospholipids contained in milk or equivalent ratios. The phospholipid composition in the milk-derived phospholipids is, for example, 20-30% by mass of sphingomyelin, 20-35% by mass of phosphatidylcholine, 20-35% by mass of phosphatidylethanolamine, 3-10% by mass of phosphatidylinositol, and 3-15% by mass of phosphatidylserine, relative to the total mass of phospholipids. The sum of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine does not exceed 100% by mass relative to the total mass of phospholipids. For example, when the composition for inhibiting cortisol production of the present invention contains a combination of sphingomyelin and phosphatidylcholine, the ratio is not limited, but may be, for example, a mass ratio of 1:0.5 to 1:2, or 1:1 to 1:1.2, etc.

[0026] The composition for inhibiting cortisol production of the present invention may consist solely of milk-derived phospholipids, or may be in a form that also contains ingredients such as raw materials contained in foods, beverages, pharmaceuticals, etc. The content of milk-derived phospholipids in the composition for inhibiting cortisol production of the present invention is not particularly limited as long as it has the cortisol production inhibiting effect of the present invention, but the content of milk-derived phospholipids relative to the total composition may be 0.001 to 100 mass%, 0.01 to 90 mass%, 0.1 to 50 mass%, 1 to 30 mass%, or 5 to 10 mass%.

[0027] The composition for inhibiting cortisol production of the present invention may be in the form of a food or beverage, a medicine, etc., or may be in the form of an additive contained in a food or beverage, a medicine, etc. (this form can also be referred to as a "cortisol production inhibitor"). The composition for inhibiting cortisol production of the present invention may be administered orally or parenterally, but is usually administered orally. Parenteral administration includes transdermal administration, intravenous injection, rectal administration, inhalation, etc.

[0028] The content of milk-derived phospholipids when the composition for inhibiting cortisol production of the present invention is orally ingested (administered) may be the content in the entire composition as described above, or may be the content in the composition after appropriate dilution, etc. For example, the content of the milk-derived phospholipid relative to the total mass of the composition at the time of oral ingestion (administration) may be 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 mass. These may be in the range of contents typically used when distributed as oral compositions.

[0029] The intake (administration) amount of the composition for inhibiting cortisol production of the present invention is appropriately selected depending on the age (months), sex, condition, and other conditions of the subject to be ingested (administered). The intake (administration) amount of the composition for inhibiting cortisol production of the present invention is, for example, preferably 0.01 to 1000 mg / kg / day, more preferably 0.1 mg / kg / day, in terms of intake of milk-derived phospholipids. A dose in the range of 1 to 500 mg / kg / day, and more preferably 1 to 300 mg / kg / day, is recommended as a guideline. Regardless of the amount or period of ingestion (administration), the composition for inhibiting cortisol production of the present invention can be administered once a day or in divided doses.

[0030] The amount of cortisol produced after application of the composition for inhibiting cortisol production of the present invention may be 0.9-fold or less, 0.8-fold or less, 0.7-fold or less, 0.65-fold or less, 0.6-fold or less, or 0.55-fold or less compared to before application. The upper limit is not particularly limited, but may be less than 1-fold (the same amount as before application). Furthermore, the range may be any consistent combination of the above values, specifically 1-0.9-fold, 1-0.8-fold, 1-0.7-fold, 1-0.65-fold, 1-0.6-fold, or 1-0.55-fold. The amount of cortisol produced can be confirmed qualitatively or quantitatively by well-known methods, for example, by measuring the cortisol concentration in a sample by a standard method. For example, the method described in the Examples can be referred to.

[0031] <Food and beverages> When the composition for inhibiting cortisol production of the present invention is intended to be taken orally, it is preferably in the form of a food or drink (hereinafter, sometimes referred to as "food or drink of the present invention"). The composition for inhibiting cortisol production of the present invention inhibits cortisol production, and is therefore expected to prevent or improve various conditions caused by excess cortisol.

[0032] Various conditions caused by excess cortisol include, but are not limited to, decreased sleep quality, decreased muscle mass and / or muscle strength, etc. The food and drink of the present invention can be used to prevent or improve these conditions. More specifically, the food and drink of the present invention can be used to improve sleep quality, maintain, inhibit the decline of, or improve muscle mass and / or muscle strength.

[0033] Furthermore, the "improvement of sleep quality" achieved by the food and beverage of the present invention is expected to result in, more specifically, improvements in difficulty falling asleep, shortened awakening times during the night, improvements in early morning awakenings, and improvements in lack of a deep sleep. Here, "difficulty falling asleep" refers to the state in which it takes a long time to fall asleep (difficulty falling asleep). Furthermore, "awakening midway" refers to a state in which one wakes up between falling asleep and waking up, and the accumulated time spent awake is defined as the midway awakening time. Also, "early morning awakening" refers to the state of waking up early in the morning and not being able to fall back asleep despite still feeling sleepy. Furthermore, "feeling of deep sleep" refers to the satisfaction of having had a deep sleep, while lack of feeling of deep sleep refers to a state in which one wakes up feeling sleep deprived despite having had a sufficient amount of sleep.

[0034] Furthermore, by "maintaining, inhibiting decline, or improving muscle mass and / or muscle strength" using the food and beverage of the present invention, it is expected that, more specifically, walking function will be maintained, inhibited decline, and / or improved, and motor function will be maintained, inhibited decline, and / or improved, for example.

[0035] The form and properties of the food and beverage products are not particularly limited as long as they do not impair the effects of the present invention and can be taken orally, and they can be produced by conventional methods using raw materials normally used in food and beverage products, except that they contain milk-derived phospholipids.

[0036] Food and drink products include all foods and drinks, regardless of their form, such as liquid, paste, gel-like solid, powder, etc., including tablet confectionery; liquid food (nutritional food for tube feeding); wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, fried chicken powder, breadcrumbs, etc.; instant noodles, cup noodles, retort / prepared foods, canned foods, microwave foods, instant soup / stew, instant miso soup / cleaning liquid, canned soup, freeze-dried foods, other instant foods, etc.; canned agricultural products, canned fruit, jam, Agricultural processed products such as marmalades, pickles, boiled beans, dried agricultural goods, and cereals (processed grain products); canned seafood, fish ham and sausage, fish paste products, seafood delicacies, and tsukudani (fish stews) and other processed seafood products; canned livestock products and pastes, livestock ham and sausage, and other processed livestock products; dairy products such as processed milk, milk drinks, yogurt (fermented milk), lactic acid bacteria drinks, cheese, ice cream, cream, and other dairy products; butter, margarines, vegetable oils, and other fats and oils; soy sauce, miso, and sauces Basic seasonings such as processed tomato seasonings, mirin, vinegars, etc.; complex seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soups, spices, and other complex seasonings; frozen foods such as frozen ingredients, semi-cooked frozen foods, and cooked frozen foods; confectioneries such as caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice snacks, bean snacks, desserts, jellies, and other sweets. ; carbonated drinks, natural fruit juices, fruit juice drinks, soft drinks with fruit juice, fruit pulp drinks, fruit drinks with fruit particles, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic drinks, other beverages, and other commercially available foods such as baby food, furikake, and ochazuke nori seaweed; nutritional compositions such as supplements and infant formula (including powdered milk, liquid milk, etc.); enteral nutritional foods; functional foods (foods for specified health uses, foods with nutrient functions), etc.

[0037] When made into a supplement form as a food or drink, it can be formulated into solid preparations such as powders, granules, tablets, capsules, etc., which may be enteric-coated with an enteric coating, etc.; liquid preparations such as solutions, syrups, suspensions, emulsions, etc. When making such preparations, the ingredients, carriers, and methods for formulating pharmaceuticals described below can be followed.

[0038] Furthermore, one aspect of the food and drink product may be feed, such as pet food, livestock feed, and fish feed. The form of the feed is not particularly limited, and may contain, in addition to milk-derived phospholipids, for example, grains such as corn, wheat, barley, rye, and milo; vegetable oil cakes such as soybean oil cake, rapeseed oil cake, palm oil cake, and linseed oil cake; bran such as wheat bran, wheat bran, rice bran, and defatted rice bran; manufacturing residues such as corn gluten meal and corn jam meal; animal feeds such as fish meal, skim milk powder, whey, yellow grease, and tallow; yeasts such as torula yeast and brewer's yeast; mineral feeds such as calcium triphosphate and calcium carbonate; oils and fats; simple amino acids; and sugars.

[0039] When the composition for inhibiting cortisol production of the present invention is in the form of a food or drink (including feed), it can be provided or sold as a food or drink labeled with uses such as improving sleep quality, maintaining, inhibiting decline, or improving muscle mass and / or muscle strength, etc. Furthermore, the milk-derived phospholipids according to the present specification can be used for producing such foods, drinks, etc.

[0040] Such "indication" acts include all acts for informing consumers of the aforementioned uses, and any expression that can recall or infer the aforementioned uses falls under the category of "indication" acts in this invention, regardless of the purpose of the indication, the content of the indication, the object or medium on which it is displayed, etc. In addition, the "display" is made in a way that consumers can directly recognize the above-mentioned uses. Specifically, this includes acts such as transferring, delivering, displaying for the purpose of transferring or delivering, or importing food and beverage products or product packaging on which the above-mentioned uses are written, displaying or distributing advertisements, price lists, or transaction documents related to the products and including the above-mentioned uses, or providing information containing the above-mentioned uses by electromagnetic means (such as the Internet).

[0041] On the other hand, it is preferable that the content of the labeling be one approved by the government, etc. (for example, a labeling approved based on various systems established by the government and made in a manner based on such approval.) It is also preferable that such content of the labeling be affixed to promotional materials at the point of sale, such as packaging, containers, catalogs, pamphlets, POP displays, and other documents.

[0042] "Labeling" also includes labeling as health food, functional food, enteral nutritional food, special dietary food, health functional food, food for specified health uses, food with nutrient functions, food with functional claims, and quasi-drugs. Among these, labeling approved by the Consumer Affairs Agency, such as labeling approved under systems related to foods for specified health uses, foods with nutrient functions, or foods with functional claims, or similar systems, can be cited. Specific examples include labeling as a food for specified health uses, labeling as a conditional food for specified health uses, labeling claiming to affect the structure or function of the body, labeling claiming to reduce disease risk, and labeling claiming functionality based on scientific evidence. More specifically, typical examples include labeling as a food for specified health uses (especially labeling of health uses) and similar labeling as defined in the Cabinet Office Ordinance on Permission for Labeling for Special Uses Provided in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009). Examples of such claims include "suppresses excess cortisol production," "improves sleep quality," "supports sleep," "reduces fatigue upon waking," "regulates sleep-wake rhythm," "reduces drowsiness," "helps maintain muscle and muscle strength," "helps maintain walking function," and "helps reduce body fat."

[0043] <Pharmaceuticals> The composition for inhibiting cortisol production of the present invention can also be in the form of a pharmaceutical product (hereinafter, sometimes referred to as the "pharmaceutical product of the present invention"). The composition for inhibiting cortisol production of the present invention contains milk-derived phospholipids as an active ingredient and inhibits cortisol production, and is therefore expected to prevent, treat, or ameliorate various diseases and / or conditions caused by excess cortisol.

[0044] Therefore, the pharmaceutical agent of the present invention is preferably one that is 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 excessive cortisol production include, but are not limited to, type II diabetes, impaired glucose tolerance, hyperglycemia, insulin resistance, dyslipidemia, dyslipidemia, hyperlipidemia, hypertriglyceridemia, obesity, atherosclerosis, syndrome X, Cushing's syndrome, hypertension, cognitive impairment, memory impairment, depression, anxiety, dementia, Alzheimer's disease, osteoporosis, glaucoma, immune disorders, etc. The pharmaceutical product of the present invention can be administered for the prevention, treatment, or amelioration of these diseases, conditions, complications, etc.

[0045] The route of administration of pharmaceuticals may be either oral or parenteral, with oral being preferred. Parenteral administration includes transdermal, intravenous, rectal, and inhalation routes. The pharmaceutical form can be 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; or liquid preparations such as solutions, syrups, suspensions, and emulsions. It can also be formulated into an enteric-coated preparation by enteric coating. In the case of parenteral administration, it can be formulated into suppositories, ointments, injections, etc. It can be formulated. In formulating the formulation, in addition to milk-derived phospholipids, ingredients commonly used in formulations, such as excipients, pH adjusters, colorants, and flavoring agents, can be used. It is also possible to use other medicinal ingredients, or ingredients that have known or will be discovered in the future, which have a cortisol production inhibitory effect, in combination. In addition, formulation can be carried out by a known method as appropriate depending on the dosage form. When formulating, carriers commonly used in formulations may be appropriately blended to form the formulation. Such carriers include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, etc.

[0046] 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; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and carboxymethyl cellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; and sulfate derivatives such as calcium sulfate.

[0047] Examples of binders include gelatin, polyvinylpyrrolidone, macrogol, and the like, in addition to the above-mentioned excipients.

[0048] Examples of disintegrants include the above-mentioned excipients, as well as chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and cross-linked polyvinylpyrrolidone.

[0049] Examples of lubricants include talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; waxes such as veegum and gaelt; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylates 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; and starch derivatives.

[0050] Examples of stabilizers include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid; and the like.

[0051] Examples of flavoring agents include sweeteners, acidulants, and fragrances. In the case of a liquid preparation for oral administration, examples of the carrier to be used include solvents such as water.

[0052] The timing of taking the pharmaceutical of the present invention is not particularly limited, and may be before meals, after meals, between meals, or before going to bed.

[0053] The subject to which the composition for inhibiting 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.

[0054] Another aspect of the present invention is the use of milk-derived phospholipids in the manufacture of a composition for suppressing cortisol production. Another aspect of the present invention is the use of milk-derived phospholipids in suppressing cortisol production. Another aspect of the present invention is a milk-derived phospholipid used in a composition for suppressing cortisol production. Another aspect of the invention is a method for suppressing cortisol production, comprising administering milk-derived phospholipids to a subject.

[0055] Note that "administering milk-derived phospholipids to a subject" may be synonymous with "allowing a subject to ingest milk-derived phospholipids." Intake may be voluntary (free intake) or forced (forced intake). That is, the administration step may specifically be, for example, a step of adding milk-derived phospholipids to food, drink, or feed and supplying the mixture to the subject, thereby allowing the subject to freely ingest the milk-derived phospholipids.

[0056] The timing and duration of ingestion (administration) of the composition for inhibiting 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.

[0057] <Composition for improving sleep quality, composition for maintaining, preventing decline, or improving muscle mass and / or muscle strength> Another aspect of the present invention relates to a composition for improving sleep quality containing milk-derived phospholipids (hereinafter, sometimes referred to as the "composition for improving sleep quality of the present invention"). The composition for improving sleep quality of the present invention contains milk-derived phospholipids as an active ingredient, and is expected to improve sleep quality through the action of the milk-derived phospholipids. The matters explained above in the sections <Composition for inhibiting cortisol production>, <Food and drink>, and <Pharmaceuticals> all apply to the explanation of the composition for improving sleep quality of the present invention. Another aspect of the present invention relates to a composition for maintaining, inhibiting a decline in, or improving muscle mass and / or muscle strength, comprising a milk-derived phospholipid, wherein the milk-derived phospholipid is phosphatidylcholine (hereinafter, this composition may be referred to as the "composition for maintaining, inhibiting a decline in, or improving muscle mass and / or muscle strength of the present invention"). The composition for maintaining, inhibiting a decline in, or improving muscle mass and / or muscle strength of the present invention contains phosphatidylcholine as an active ingredient, and is expected to maintain, inhibit a decline in, or improve muscle mass and / or muscle strength through the action of phosphatidylcholine. The matters explained above in the sections "Composition for inhibiting cortisol production," "Food and drink," and "Pharmaceuticals" all apply to the description of the composition of the present invention for maintaining, inhibiting a decline in, or improving muscle mass and / or muscle strength. [Example]

[0058] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples as long as it does not depart from the gist of the invention.

[0059] [Example] (Adrenocortical carcinoma cell line culture) The adrenocortical carcinoma cell line (HAC15) was obtained from ATCC. The HAC15 cell line was pre-cultured for 11 days in 20 ml of DMEM:F12 (1:1) medium (Thermo Fisher Scientific) supplemented with 10% Cosmic Calf serum (Cytiva) and penicillin streptomycin (Fujifilm Wako Pure Chemical Industries, Ltd.). During the pre-culture, the cells were passaged on days 4 and 8 after seeding. On day 11 after seeding, the cells were treated with trypsin (Fujifilm Wako Pure Chemical Industries, Ltd.) and harvested. The harvested cells were suspended in the same DMEM:F12 (1:1) medium used for culture, supplemented with 0.1% Cosmic Calf serum and penicillin streptomycin. The cell suspension was then placed in a 48-well cell culture plate (Corning) at a cell density of 5x per well. 10 4 The seeds were sown so that each plant would have 1 plant.

[0060] Preparation of Phospholipid Solutions and Suspensions Five types of phospholipids: phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine (all from Nagara Science) (manufactured by Stanford University) was dissolved or suspended in ethanol to a concentration of 10 mg / ml.

[0061] (treatment with phospholipid mixture) Five types of phospholipids dissolved or suspended in ethanol were mixed in the ratios shown in Table 1, which correspond to the phospholipid composition of a typical whey protein / phospholipid concentrate. The mixed phospholipids were further diluted 2-fold and 4-fold with ethanol to prepare dilutions. The prepared phospholipid solutions and dilutions were added at 1 / 100 volume to wells seeded with HAC15 cells. The cells were then cultured for 24 hours in an incubator maintained at 37°C with 5% CO2, and the culture supernatant was collected. The culture supernatant was centrifuged at 2,000g for 10 minutes to remove insoluble components and stored at -80°C until analysis.

[0062] [Table 1]

[0063] (Treatment with each phospholipid) Phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine were suspended or dissolved in ethanol at the concentrations shown in Table 2. Each phospholipid solution or suspension was added at 1 / 100 volume to each well containing HAC15 cells. The cells were then cultured for 24 hours in an incubator maintained at 37°C with 5% CO2, 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°C until analysis.

[0064] [Table 2]

[0065] (Treatment with a combination of phosphatidylcholine and sphingomyelin) The concentrations of phosphatidylcholine and sphingomyelin are shown in Table 3, and those of phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine are shown in Table 4. The cells were suspended or dissolved in ethanol as indicated. 1 / 100 volume of each solution was added to each well containing HAC15 cells. After 24 hours of incubation in an incubator maintained at 37°C with 5% CO2, the culture supernatant was collected. The culture supernatant was centrifuged at 2,000g for 10 minutes to remove insoluble components and stored at -80°C until analysis.

[0066] [Table 3]

[0067] [Table 4]

[0068] (Treatment with multiple concentrations of phosphatidylcholine and sphingomyelin alone) Phosphatidylcholine and sphingomyelin were dissolved in ethanol to concentrations 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. Each solution was added at 1 / 100 volume to each well containing HAC15 cells. The cells were then cultured for 24 hours in an incubator maintained at 37°C with 5% CO2, 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°C until analysis.

[0069] (quantitation of cortisol) The frozen culture supernatant was thawed on ice and assayed according to the instructions provided with the Cortisol ELISA kit (Enzo). The sample was diluted 20-fold with the included assay buffer.

[0070] (result) A phospholipid mixture consisting of five phospholipids, namely phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine, inhibited cortisol production in HAC15 cells in a concentration-dependent manner (n=3 for each sample). Of the five phospholipids contained in the phospholipid mixture, phosphatidylcholine and sphingomyelin suppressed cortisol production in HAC15 cells (n = 3 for each sample) (Fig. 2). The combination of phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine did not inhibit cortisol production in HAC15 cells (n = 3 for each sample) (Fig. 3). The phosphatidylcholinesterase inhibitor inhibited the production of cortisol in the cells (n=3 for each sample) (Figure 4). The inhibition rates of cortisol production when phosphatidylcholine and sphingomyelin were applied at various concentrations were calculated (Table 5). Furthermore, the inhibition rates of cortisol production by the combination of phosphatidylcholine and sphingomyelin were calculated from the data shown in Figure 3 (Table 6). The inhibition rates of cortisol production were expressed as the percentage reduction in cortisol in the culture supernatant by each sample treatment compared to the control. The combination of phosphatidylcholine and sphingomyelin contained final concentrations of 26.9 μg / ml and 23.7 μg / ml, respectively, in the medium. The combined phospholipid concentration was 50.6 μg / ml, resulting in a cortisol production inhibition rate of 42%. On the other hand, the inhibition rates of cortisol production by phosphatidylcholine and sphingomyelin alone at a concentration of 50 μg / ml were 25% and 37%, respectively. Furthermore, even when phosphatidylcholine and sphingomyelin were used alone, the production inhibition rates were only 34% and 38%, respectively, even at concentrations up to 100 μg / ml, suggesting that the combination of phosphatidylcholine and sphingomyelin acts synergistically to more strongly inhibit cortisol production than either compound alone.

[0071] [Table 5]

[0072] [Table 6] [Industrial Applicability]

[0073] The present invention is useful in the fields of foods and beverages, health foods, functional foods, supplements, pharmaceuticals, and the like.

Claims

1. A composition for improving sleep quality, comprising milk-derived phospholipids.

2. The composition described in claim 1, wherein the phospholipid comprises one or more selected from sphingomyelin and phosphatidylcholine.

3. The composition described in claim 2, wherein the phospholipid comprises a combination of sphingomyelin and phosphatidylcholine.

4. A composition for maintaining, inhibiting decline in, or improving muscle mass and / or muscle strength, comprising a milk-derived phospholipid, wherein the milk-derived phospholipid is phosphatidylcholine.

5. A composition described in any one of claims 1 to 4, which is a food or beverage.

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