Agents for maintaining blood ketone body levels, and agents for reducing body fat.

Abstract

The present invention can provide a new agent for maintaining blood ketone body concentration and an agent for reducing body fat. [Solution] A blood ketone body concentration maintenance agent and a body fat reduction agent.

Description

Technical Field

[0001] The present invention relates to a blood ketone body concentration-maintaining agent and a body fat-reducing agent.

Background Art

[0002] Patent Document 1 discloses a ketone body production-promoting agent formed by combining a medium-chain fatty acid oil or fat with at least one casein compound selected from the group consisting of casein and salts thereof.

[0003] Patent Document 2 discloses a visceral fat-reducing agent comprising R-3-hydroxybutyric acid and / or a salt thereof as an active ingredient.

[0004] Non-Patent Document 1 discloses that an oral D-beta-hydroxybutyrate (D-BHB) supplement is rapidly absorbed and metabolized in the human body, and increases blood ketone bodies to a millimolar level.

[0005] Non-Patent Document 2 discloses the bioenergetic effects and pleiotropic effects of ketone bodies that may potentially contribute to effects on the cardiovascular system, based on evidence obtained from animal and human studies.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Non-Patent Documents

[0007]

Non-Patent Document 1

Non-Patent Document 2

[0008] The present invention aims to provide a new agent for maintaining blood ketone body concentration and an agent for reducing body fat. [Means for solving the problem]

[0009] Beta-hydroxybutyric acid (hereinafter also simply referred to as "BHB"; also known as 3-hydroxybutyric acid (3HB)) is a substance that naturally exists in the human body and is attracting attention as a groundbreaking energy source that can replace carbohydrates.

[0010] BHB, for example, is obtained by ingesting medium-chain triglycerides (MCTs) found in coconut oil, which are then metabolized in the body, enter the bloodstream, and converted into energy. This process converts to energy more quickly than carbohydrates, which are converted via glycolysis.

[0011] Furthermore, when 1,3-butanediol and acetoacetic acid are ingested, they are converted into BHB in the body and then converted into energy, similar to MCTs.

[0012] BHB has the effect of inhibiting the absorption of fat and sugar by cells. In other words, by ingesting BHB from external sources, it has a weight-loss effect by suppressing sugar absorption and promoting fat burning. Furthermore, BHB is said to have not only the role of an energy source, but also the effect of improving cognitive function and long-term memory, as well as a preventive effect against Alzheimer's disease.

[0013] Low-carbohydrate diets, which restrict the intake of sugars and carbohydrates, are attracting attention in the field of weight loss. A low-carbohydrate diet breaks down body fat and produces ketones. Ketones are a collective term for three types: acetone, acetoacetic acid, and β-hydroxybutyrate (BHB). Recently, it has become clear that ketones produced in the body through a low-carbohydrate diet are effective not only for weight loss but also as a dietary therapy for heart disease, Alzheimer's disease, epilepsy, and other conditions.

[0014] In addition to a carbohydrate-restricted diet, the intake of ketone body donors such as medium-chain triglyceride oil (MCT) and BHB is effective in increasing blood ketone body levels (Non-patent documents 1 and 2, and Patent Document 1). Ketone body donors do not require carbohydrate restriction, making it easier to increase blood ketone body levels.

[0015] Furthermore, when ketone body donors such as MCTs and BHBs are ingested, the concentration of ketone bodies in the blood generally reaches its peak about one hour after ingestion and is completely metabolized after three hours (Non-Patent Literature 1).

[0016] In terms of fat breakdown, carbohydrate-restricted diets break down fat and increase blood ketone body levels, but the challenge is that they result in an unbalanced diet. On the other hand, MCTs have the challenge of being difficult to consume continuously due to their low palatability caused by their unique taste and gastrointestinal discomfort. There was room for improvement in these areas.

[0017] Patent Document 1 discloses a visceral fat reducing agent that can reduce visceral fat by ingesting BHB every morning, which is the technology of the present inventors.

[0018] The present invention aims to develop a method that can be easily maintained to keep blood ketone body levels without requiring a restrictive diet such as a carbohydrate-restricted diet.

[0019] The present invention includes the following agents for maintaining blood ketone body concentration and agents for reducing body fat.

[0020] Section 1. A reducing agent for reducing human body fat through oral ingestion, comprising β-hydroxybutyric acid (BHB) and / or a salt thereof as an active ingredient, the body fat reducing agent for oral ingestion.

[0021] Claim 2. The body fat reducing agent according to claim 1, wherein the daily intake of BHB and / or the salt thereof is 0.01 g to 0.5 g per 1 kg of body weight in terms of the active ingredient.

[0022] Claim 3. The body fat reducing agent according to claim 1, wherein the proportion of the BHB and / or the salt thereof is 80% by mass or more.

[0023] Claim 4. The body fat reducing agent according to claim 1, wherein the active ingredient is a mixture of BHB and a salt of BHB.

[0024] Claim 5. The body fat reducing agent according to any one of claims 1 to 4, which is a body fat reducing agent for facilitating easy decomposition of body fat.

[0025] Claim 6. The body fat reducing agent according to any one of claims 1 to 4, which is a body fat reducing agent for facilitating easy decomposition of body fat during sleep.

[0026] Claim 7. The body fat reducing agent according to any one of claims 1 to 4, which is a body fat reducing agent for promoting the production of BHB from body fat.

[0027] Claim 8. The body fat reducing agent according to any one of claims 1 to 4, which is a body fat reducing agent for promoting the production of BHB from body fat during sleep.

[0028] Claim 9. A composition for reducing human body fat through oral ingestion, comprising β-hydroxybutyric acid (BHB) and / or a salt thereof as an active ingredient, the composition for reducing body fat for oral ingestion.

[0029] Section 10. The body fat reduction composition according to item 9, wherein the daily intake of BHB and / or its salt is 0.01 g to 0.5 g per kg of body weight in terms of active ingredients.

[0030] Section 11. The body fat reduction composition according to item 9, wherein the active ingredient comprises BHB, and the composition is liquid.

[0031] Section 12. The body fat reduction composition according to item 9, wherein the active ingredient comprises a salt of BHB, and the composition is in a solid or semi-solid state.

[0032] Section 13. A body fat reduction composition according to any one of items 9 to 12 above, which is a functional food composition or pharmaceutical composition for oral intake by humans.

[0033] Section 14. A body fat reduction composition according to any one of items 9 to 12, which is a composition for reducing body fat without exercise or dietary restrictions.

[0034] Section 15. A body fat reduction composition according to any one of items 9 to 12, which is a composition for preferentially reducing visceral fat over subcutaneous fat.

[0035] Section 16. A composition for reducing body fat, as described in any one of items 9 to 12 above, which is a composition for preventing or improving lifestyle-related diseases.

[0036] Section 17. A method for reducing body fat by orally ingesting β-hydroxybutyric acid (BHB) and / or its salt as an active ingredient.

[0037] Section 18. The method for reducing visceral fat as described in item 17, wherein the daily intake of BHB and / or its salt is 0.01g to 0.5g per kg of body weight in terms of active ingredients.

[0038] Section 19. A method for reducing body fat as described in item 17 above, which reduces body fat without exercise or dietary restrictions.

[0039] Section 20. A method for reducing body fat as described in item 17 above, wherein visceral fat is reduced preferentially over subcutaneous fat.

[0040] In the specification and claims, the term "ingestion" includes the meanings of "taking" and "administering."

[0041] According to the present invention, it is possible to maintain blood ketone body levels without requiring a restrictive diet such as a carbohydrate-restricted diet, and this method can be easily continued.

[0042] In this invention, since the active ingredient of the body fat reducing agent is BHB and / or its salt, body fat can be reduced without dietary restrictions, exercise, etc. [Effects of the Invention]

[0043] The present invention can provide a new agent for maintaining blood ketone body concentration and a fat-reducing agent. [Modes for carrying out the invention]

[0044] The present invention will be described in detail below. The embodiments representing the present invention are intended to provide a better understanding of the spirit of the invention and do not limit the scope of the invention unless otherwise specified. It goes without saying that the present invention can be implemented in various forms without departing from the spirit of the invention.

[0045] In this specification, "contains" and "include" are concepts that encompass all of the following: "comprise," "consist essentially of," and "consist of."

[0046] In this specification, when a numerical range is indicated as "A to B", it means "greater than or equal to A and less than or equal to B".

[0047] In this specification, when using indications such as parts, percentages, etc., they represent parts by mass, parts by weight, mass%, or weight% (wt%).

[0048] [1] Body fat reducing agent The body fat reducing agent of the present invention is a body fat reducing agent that reduces human body fat when taken orally, and contains β-hydroxybutyric acid (BHB) and / or its salt as an active ingredient, and is a body fat reducing agent for oral intake.

[0049] The body fat reducing agent of the present invention preferably has a daily intake of BHB and / or its salt equivalent to 0.01g to 0.5g per kg of body weight in terms of active ingredients.

[0050] The body fat reducing agent of the present invention preferably has a proportion of BHB and / or its salt of 80% by mass or more.

[0051] The body fat reducing agent of the present invention preferably has as its active ingredient a mixture of BHB and a salt of BHB.

[0052] The present invention includes an embodiment in which the body fat reducing agent of the present invention is used as a blood ketone body concentration maintaining agent.

[0053] The body fat reducing agent (body fat reducing composition) of the present invention can reduce body fat without diet or exercise. The body fat reducing agent (body fat reducing composition) of the present invention contributes to the healthy prevention of lifestyle-related diseases.

[0054] The body fat reducing agent (body fat reducing composition) of the present invention can efficiently reduce body fat, preferably by using the R-isomer of BHB [R-BHB], and can reduce body fat even with a small amount of R-BHB intake (administered).

[0055] The body fat reducing agent (blood ketone body concentration maintaining agent) of the present invention contains β-hydroxybutyrate (BHB) and / or its salt (hereinafter sometimes collectively referred to as "BHB (salt)"). BHB (also known as 3-hydroxybutyrate (3HB)) is a compound represented by the following formula.

[0056] [ka]

[0057] The three-dimensional structure of BHB may be either the R configuration (R-isomer) or the S configuration (S-isomer). From the viewpoint of energy absorption into the body, water dispersibility, deliquescence inhibition, and acidity inhibition, the R configuration (R-isomer) (hereinafter sometimes collectively referred to as "R-BHB (salt)") is preferred.

[0058] When acetoacetic acid, 1,3-butanediol, short-chain, medium-chain (MCT), and long-chain fatty acids, and their salts and esters are ingested, they are converted into BHB in the body. The BHB converted in the body is also converted into energy, similar to medium-chain triglyceride (MCT).

[0059] The present invention encompasses compositions comprising at least one derivative selected from the group consisting of acetoacetic acid, 1,3-butanediol, short-chain fatty acids, medium-chain fatty acids (MCTs), long-chain fatty acids, and salts or esters thereof.

[0060] (R-BHB (salt) as the active ingredient) R-BHB(salt) may be in crystalline or amorphous form. Of these, R-BHB(salt) in a solid or semi-solid composition may be in crystalline form.

[0061] Examples of salts include alkali metal salts such as sodium salts, potassium salts, and lithium salts; alkaline earth metal salts such as magnesium salts and calcium salts; and ammonium salts. These R-BHB salts can be used individually or in combination of two or more. Of these, alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as magnesium salts and calcium salts are preferred, alkali metal salts are more preferred, potassium salts are particularly preferred because they can suppress excessive salt intake, and sodium salts are particularly preferred because the balance of various properties can be easily adjusted.

[0062] R-BHB (salt) as a body fat reducing agent may be R-BHB (salt) alone, a mixture of R-BHB and R-BHB salt, or R-BHB salt alone. When a body fat reducing agent (active ingredient) is incorporated into a liquid composition, it may contain R-BHB, and when a body fat reducing agent (active ingredient) is incorporated into a solid or semi-solid composition, it may contain R-BHB salt.

[0063] While R-BHB (salt) exhibits a strong sour taste and is difficult to take in its acidic form, it is easier to take in its salt form. However, this results in salt intake, and from the perspective of preventing and treating lifestyle-related diseases such as hypertension, it is desirable to limit salt intake. Therefore, it is preferable to adjust the form of R-BHB according to the form of use and application.

[0064] In applications where it is necessary to suppress salt intake, such as when used for the prevention or treatment of lifestyle-related diseases such as hypertension, it is preferable that the active ingredient [R-BHB (salt)] has a reduced proportion of salt and contains R-BHB as the main component. Specifically, the proportion of R-BHB may be 50% by mass or more of the active ingredient, preferably 80% by mass or more, more preferably 90% by mass or more, more preferably 95% by mass or more, and most preferably 100% by mass.

[0065] For applications where ease of administration is important, it is preferable that the active ingredient contains a reduced proportion of R-BHB and includes a salt of R-BHB as the main component. Specifically, the proportion of R-BHB salt may be 50% by mass or more of the active ingredient, preferably 80% by mass or more, more preferably 90% by mass or more, more preferably 95% by mass or more, and most preferably 100% by mass.

[0066] On the other hand, unlike the ketogenic diet, the body fat reducing agent of the present invention does not require a reduction in carbohydrates. Therefore, by combining it with sugars, it is easy to adjust its palatability, and body fat can be reduced with a small dose. For this reason, even in the form of an acid, the body fat reducing agent of the present invention can easily suppress extreme sourness. Furthermore, because body fat can be reduced with a small dose, even in the form of a salt, the amount of salt can be kept to a minimum.

[0067] From this viewpoint, the body fat reducing agent of the present invention is preferably in the form of an acid and a salt. The mass ratio of R-BHB to R-BHB salt is former / latter = 99 / 1 to 1 / 99, preferably 90 / 10 to 5 / 95, more preferably 80 / 20 to 10 / 90, more preferably 70 / 30 to 20 / 80, and most preferably 50 / 50 to 30 / 70. If the proportion of R-BHB is too low, there is a risk of excessive salt intake, and conversely, if it is too high, there is a risk of decreased palatability. In particular, when the body fat reducing agent of the present invention is incorporated into a liquid composition, the combination of the acid and salt forms is preferred.

[0068] The R-BHB (salt) is preferably at least one selected from the group consisting of R-BHB, sodium salt of R-BHB, potassium salt of R-BHB, magnesium salt of R-BHB, and calcium salt of R-BHB, with R-BHB alone, a combination of R-BHB and sodium salt of R-BHB, and potassium salt of R-BHB alone being particularly preferred. Furthermore, the active ingredient is preferably in a form containing a salt of R-BHB from the viewpoint of handling, a combination of R-BHB and an alkali metal salt of R-BHB is preferred from the viewpoint of being able to easily adjust the balance of various properties, and a combination of R-BHB and sodium salt of R-BHB is particularly preferred from the viewpoint of being able to easily adjust the balance of various properties.

[0069] The proportion of R-BHB (salt) in the body fat reducing agent may be 10% by mass or more, preferably 50% by mass or more, more preferably 80% by mass or more, more preferably 90% by mass or more, and most preferably 100% by mass.

[0070] (S-BHB (salt)) The body fat reducing agent of the present invention may further contain, in addition to the active ingredient which is the R-isomer, the S-isomer, which is an optical isomer of the R-isomer, i.e., the S-configuration (S-isomer) (hereinafter sometimes collectively referred to as "S-BHB (salt)").

[0071] In the body fat reducing agent of the present invention, BHB (salt) may contain R-BHB (salt) and may be a racemic mixture. However, if the proportion of S-BHB (salt) is too high, biocompatibility decreases, so it is preferable that the proportion of S-BHB (salt) be low, and it is particularly preferable that it be included in a proportion that is unavoidable.

[0072] The mass percentage of the R-isomer in BHB (salt) may be 10% by mass or more, preferably 50% by mass or more, more preferably 80% by mass or more, more preferably 90% by mass or more, and most preferably 100% by mass. The optical purity (enantiomer or optical isomer excess) of the R-isomer in BHB (salt) is, for example, 50%ee or more (e.g., 80%ee or more), preferably 90%ee or more (e.g., 95%ee to 100%ee), and more preferably 98%ee to 100%ee (e.g., 99%ee to 100%ee, especially substantially 100%ee).

[0073] The method for producing R-BHB (salt) is not particularly limited. R-BHB (salt) can be produced by conventionally known methods. Furthermore, R-BHB salt can be produced by processes such as salt production, desalination, and salt exchange.

[0074] BHB(salt) containing R-BHB(salt) may be a commercially available product. Examples of commercially available products include chemically synthesized BHB(salt) and BHB(salt) produced by fermentation using microorganisms. Of these, fermentation-produced BHB(salt) is preferred due to its high purity of the R-isomer, and R-BHB(salt) produced by fermentation using microorganisms with biomass raw materials (biologically derived resources) is particularly preferred.

[0075] R-BHB (salt) (D-β-hydroxybutyric acid (D-BHB)) can be produced using BHB (naturally derived ketone body, fermented ketone body) produced from Halomonas bacteria by Osaka Gas Co., Ltd. R-BHB (salt) (D-BHB (salt)) can also be produced using R-BHB (salt) fermented with Halomonas bacteria, based on the disclosure of Japanese Patent Application Publication No. 2019-176839.

[0076] (BHB oligomers) The body fat reducing agent of the present invention may further contain BHB oligomers. The average degree of polymerization of the BHB oligomers should be 2 or higher, but for example, 2 to 100, preferably 2 to 10, more preferably 2 to 5, more preferably 2 to 4.5, and most preferably 2 to 4. The BHB oligomers may be oligomers that are inevitably mixed in during the BHB manufacturing process, etc. Alternatively, PHB (average degree of polymerization 1000-10000), which is a BHB oligomer produced by microorganisms, can also be used.

[0077] The proportion of BHB oligomer may be 10 parts by mass or less per 100 parts by mass of the active ingredient, preferably 5 parts by mass or less, more preferably 3 parts by mass or less, and most preferably 1 part by mass or less. The body fat reducing agent does not need to substantially contain BHB oligomer, and it is particularly preferable that it does not contain BHB oligomer, but it is also possible to consist only of BHB oligomer.

[0078] (Characteristics of body fat reducing agents) The body fat reducing agent of the present invention can be used to reduce body fat in mammals such as humans, and is preferably used to reduce body fat in medium-sized or large mammals (especially humans).

[0079] The body fat reducing agent of the present invention can reduce body fat while retaining subcutaneous fat, which has functions such as maintaining body temperature and protecting internal organs and bones. Therefore, it can be used not only for weight loss purposes but also to prevent or improve lifestyle-related diseases in humans.

[0080] The body fat reducing agent of the present invention may be administered orally or parenterally. Oral administration may be in the form of a liquid, solid, or semi-solid preparation. Parenteral administration may be by inhalation, injection, transdermal administration, or nasal administration. Of these, oral administration is preferred.

[0081] The body fat reducing agent of the present invention can reduce body fat in medium-sized or large mammals such as humans, even with small doses. In particular, by using the R-isomer as BHB (salt), body fat can be efficiently reduced with small doses, and unlike conventional ketogenic diets, body fat can be reduced without exercise or dietary restrictions.

[0082] The body fat reducing agent of the present invention is highly safe and can be taken in relatively large amounts. For example, it may be taken orally at a dose of 2g or more (e.g., 2g to 10g) per kg of body weight per day in terms of the active ingredient [BHB (salt)]. However, since it can reduce body fat even in small amounts, the daily dose is preferably 2g or less per kg of body weight. Specifically, a preferred daily dose can be selected from a range of approximately 0.005g to 2g (particularly 0.005g to 1g) per kg of body weight in terms of the active ingredient [BHB (salt)]. For example, 0.01g to 0.5g, preferably 0.015g to 0.3g, more preferably 0.02g to 0.1g, more preferably 0.03g to 0.08g, and most preferably 0.04g to 0.06g.

[0083] The body fat reducing agent of the present invention includes a body fat reducing agent that makes body fat easier to break down. By ingesting the body fat reducing agent (body fat reducing composition) of the present invention, body fat becomes easier to break down thereafter.

[0084] The body fat reducing agent of the present invention includes a body fat reducing agent for promoting the production of BHB from body fat during sleep. By taking the body fat reducing agent (composition for reducing visceral fat) of the present invention before dinner, the production of BHB from body fat during sleep thereafter is promoted.

[0085] The intake (administration, taking) schedule (number of intakes per day) of the body fat reducing agent of the present invention is not particularly limited and may be once a day or multiple times a day, for example 1 to 5 times, preferably 1 to 3 times, more preferably 1 to 2 times, and more preferably once a day. When taking multiple times a day, it is preferable to take them at intervals of 3 hours, 6 hours, 8 hours, or 12 hours, depending on the number of intakes.

[0086] The administration schedule for the body fat reducing agent of the present invention allows for an increase in blood ketone body concentration by ingesting BHB (salt), thereby reducing body fat, etc. The administration schedule for the body fat reducing agent of the present invention involves ingesting BHB (salt) before dinner, which allows fat to be broken down into ketone bodies during sleep.

[0087] According to the present invention, it is possible to maintain blood ketone body levels without requiring a restrictive diet such as a carbohydrate-restricted diet, and this method can be easily continued.

[0088] The intake (administration, taking) schedule for the body fat reducing agent of the present invention is preferably one in which the agent is taken continuously for a certain period (daily intake), and more preferably for two weeks or more, six weeks or more, or twelve weeks or more, with daily intake. This is the most efficient way to increase blood ketone body concentration and reduce body fat, etc.

[0089] [2] Composition for reducing body fat The body fat reduction composition of the present invention is a composition for reducing human body fat when taken orally, and contains β-hydroxybutyric acid (BHB) and / or its salt as an active ingredient, and is a body fat reduction composition for oral intake.

[0090] The body fat reduction composition of the present invention preferably has a daily intake of BHB and / or its salts of 0.01g to 0.5g per kg of body weight in terms of active ingredients.

[0091] The body fat reduction composition of the present invention preferably contains BHB as an active ingredient, and the composition is in liquid form.

[0092] The body fat reduction composition of the present invention preferably contains a salt of BHB as an active ingredient, and the composition is in a solid or semi-solid form.

[0093] The body fat reduction composition of the present invention is preferably a functional food composition or pharmaceutical composition for oral intake by humans.

[0094] The body fat reduction composition of the present invention is preferably a composition for reducing body fat without exercise or dietary restrictions.

[0095] The body fat reduction composition of the present invention is preferably a composition that preferentially reduces visceral fat over subcutaneous fat.

[0096] The body fat reduction composition of the present invention is preferably a composition for preventing or improving lifestyle-related diseases.

[0097] The present invention includes an embodiment in which the body fat reduction composition of the present invention is used as a composition for maintaining blood ketone body concentration.

[0098] When preparing a liquid composition (body fat reduction composition) of the body fat reducing agent of the present invention, R-BHB takes the form of an acid, resulting in a strong sour taste.

[0099] In this invention, even with the intake of a small amount of BHB (preferably R-BHB), body fat can be reduced. Furthermore, by using the R-isomer, the dosage of R-BHB can be reduced, thereby improving palatability.

[0100] When preparing the body fat reducing agent of the present invention as a solid or semi-solid composition (body fat reducing composition), R-BHB is included in the form of salt, making it easy to consume excessive amounts of salt. When preparing it as a solid composition such as a powder, it is necessary to add an excessive amount of alkaline components to completely neutralize it, which makes it even easier to consume excessive amounts of salt.

[0101] In this invention, even with the intake of a small amount of BHB (preferably R-BHB), body fat can be reduced, and by using the R-isomer, salt intake can be reduced, as can the amount of R-BHB administered, thereby suppressing salt intake and contributing to the prevention of lifestyle-related diseases.

[0102] The body fat reduction composition (composition for maintaining blood ketone body concentration) of the present invention contains BHB (salt) (preferably R-BHB (salt)) as an active ingredient.

[0103] The body fat reduction composition of the present invention may be a liquid composition (liquid), a solid composition (solid agent), or a semi-solid composition (semi-solid agent). In the body fat reduction composition of the present invention, R-BHB (salt) is incorporated into the liquid composition, solid composition, or semi-solid composition as the aforementioned body fat reduction agent. The active ingredient in the composition is the same as the active ingredient described as the body fat reduction agent, including in preferred embodiments.

[0104] The proportion of the active ingredient [R-BHB (salt)] can be selected from a range of approximately 0.01% to 99% by mass in the composition, preferably 0.1% to 95% by mass, and more preferably 0.5% to 90% by mass. The proportion of the active ingredient may also be selected depending on the form of the composition.

[0105] When the body fat reduction composition of the present invention is a liquid composition, the proportion of the active ingredient can be selected from a range of about 0.01% to 50% by mass in the liquid composition, for example, 0.05% to 30% by mass, preferably 0.1% to 20% by mass, more preferably 0.5% to 10% by mass, more preferably 1% to 8% by mass, and most preferably 2% to 5% by mass. If the proportion of the active ingredient is too high, the acidity may become strong and the palatability may decrease, and if it is too low, the volume and mass of the liquid composition may increase, which may decrease the palatability and portability.

[0106] When the body fat reduction composition of the present invention is a solid composition or a semi-solid composition, the proportion of the active ingredient can be selected from a range of approximately 0.1% to 99% by mass in the solid composition or semi-solid composition, for example, 1% to 90% by mass, preferably 3% to 80% by mass, more preferably 5% to 70% by mass, more preferably 8% to 50% by mass, and most preferably 10% to 30% by mass. If the proportion of the active ingredient is too high, the palatability may decrease, and if it is too low, the volume and mass of the composition may increase, which may decrease the palatability and portability.

[0107] (Ingredients contained in body fat reduction compositions) The body fat reduction composition of the present invention may contain other components as appropriate, provided that they do not impair the purpose and effects of the present invention. The other components are not particularly limited as long as they are edible.

[0108] The body fat reduction composition of the present invention may also preferably contain other components such as edible oils and fats, protein, dietary fiber, carbohydrates (in powder form), emulsifiers, flavorings, skim milk powder, whole milk powder, cocoa powder, sugar, dextrin, sweeteners, colorings, flavorings, vitamins, minerals, and binders.

[0109] (Sugars) The body fat reduction composition of the present invention may further contain sugars.

[0110] R-BHB (salt) is a substance that naturally exists in the human body and is expected to be a groundbreaking energy source that can replace carbohydrates. Therefore, as mentioned above, the ketogenic diet focuses on using R-BHB (salt) as an energy source, and aims to limit the intake of carbohydrates, which are easily converted into fat in the body and lead to weight gain.

[0111] Unlike the ketogenic diet, the body fat reducing agent of the present invention does not require a reduction in carbohydrates, and therefore may be combined with sugars. By combining it with sugars that also function as sweeteners, the palatability can be easily adjusted. In particular, when the composition is a liquid composition such as a beverage, it is preferable to include sugars in order to suppress strong acidity and improve palatability.

[0112] R-BHB (salt) functions as an energy source in addition to its body fat reduction function, but sugars may be added as an energy source to enhance its function as an energy source in the composition of the present invention.

[0113] Examples of sugars include pentoses such as arabinose and xylose; hexoses such as glucose, fructose, galactose, mannose, and sorbose; rare sugars represented by psicose; monosaccharides such as honey; disaccharides such as sucrose (e.g., white sugar, refined white sugar, powdered sugar, granulated sugar, cane sugar, brown sugar, light brown sugar, etc.); oligosaccharides (oligosaccharides of three or more saccharides) such as maltotriose, isomaltoriose, panose, and starch hydrolysates (dextrin); and sugar alcohols such as xylitol, erythritol, sorbitol, mannitol, reduced maltose syrup (maltitol), reduced starch hydrolysates, reduced palatinose, and reduced lactose (lactitol).

[0114] These sugars can be used individually or in combination of two or more. Of these, monosaccharides such as glucose and fructose; disaccharides such as sucrose and lactose; and sugar alcohols such as xylitol and erythritol are preferred. Furthermore, when sugars are added primarily to improve palatability, sugar alcohols such as erythritol are preferred, and when sugars are added as an energy source in addition to palatability, monosaccharides and disaccharides are preferred.

[0115] The proportion of sugars may be 1,000 parts by mass or less per 100 parts by mass of the active ingredient, for example, 10 to 1,000 parts by mass, preferably 30 to 500 parts by mass, more preferably 50 to 300 parts by mass, more preferably 100 to 250 parts by mass, and most preferably 150 to 200 parts by mass. If the proportion of sugars is too low, the function of the sugars may not be expressed, and if it is too high, the volume and mass of the composition may become too large, which may reduce its palatability and portability.

[0116] (Sweetener) The body fat reduction composition of the present invention may further contain a sweetener (non-carbohydrate sweetener) in addition to, or in place of, the aforementioned sugars, which also function as sweeteners, in order to improve palatability.

[0117] Examples of sweeteners include natural sweeteners such as stevia, licorice, and hydrangea; and artificial sweeteners such as saccharin, sodium saccharin, aspartame, acesulfame potassium, sucralose, and neotame. These sweeteners can be used individually or in combination of two or more.

[0118] Of these, artificial sweeteners such as acesulfame potassium and sucralose are preferred because they easily improve palatability. Furthermore, these sweeteners are preferably used in combination with the sugars mentioned above because they easily allow for adjustment of palatability.

[0119] The proportion of the sweetener is, for example, 0.01 to 20 parts by mass, preferably 0.1 to 15 parts by mass, more preferably 0.5 to 10 parts by mass, more preferably 1 to 8 parts by mass, and most preferably 2 to 5 parts by mass, per 100 parts by mass of the active ingredient. If the proportion of the sweetener is too low, the effect of improving palatability may not be achieved, and if it is too high, the sweetness may be too strong and the palatability may decrease.

[0120] (Acidifier) The body fat reduction composition of the present invention may further contain an acidulant. Because the active ingredient R-BHB has a very strong sour taste, the sourness may be adjusted not only with the sugars and / or sweeteners but also by combining it with an acidulant. In particular, in the case of a liquid composition, the sourness may be adjusted by adjusting the pH by using an alkaline component as an acidulant, or by changing at least a portion of the R-BHB into a salt form.

[0121] Organic acids are typically used as acidulants. Examples of organic acids include saturated monocarboxylic acids such as acetic acid; saturated dicarboxylic acids such as malonic acid, succinic acid, succinic anhydride, and glutaric acid; unsaturated polycarboxylic acids such as maleic acid and fumaric acid; hydroxy monocarboxylic acids such as lactic acid; hydroxy polycarboxylic acids such as malic acid, tartaric acid, and citric acid; and ascorbic acid and gluconic acid. These organic acids can be used individually or in combination of two or more.

[0122] These organic acids may also be in the form of salts. Examples of salts include alkali metal salts such as sodium salts, potassium salts, and lithium salts; alkaline earth metal salts such as magnesium salts and calcium salts; and ammonium salts. These salts can be used individually or in combination of two or more types.

[0123] The acidulants can be used alone or in combination of two or more. Of the acidulants, saturated carboxylic acids such as acetic acid or their salts; hydroxypolycarboxylic acids such as malic acid, tartaric acid, and citric acid or their salts; ascorbic acid or its salts are preferred, and saturated monocarboxylate salts such as sodium acetate; and hydroxypolycarboxylate salts such as potassium bitartrate, sodium bitartrate, and sodium citrate are even more preferred.

[0124] When the body fat reduction composition of the present invention is a liquid composition, alkali metal salts or alkaline earth metal salts of organic acids such as sodium citrate are preferred, and alkali metal salts of hydroxypolycarboxylic acids are particularly preferred, in order to allow for adjustment of the sourness.

[0125] The proportion of the acidulant is, for example, 1 to 50 parts by mass, preferably 3 to 40 parts by mass, more preferably 5 to 30 parts by mass, more preferably 8 to 20 parts by mass, and most preferably 10 to 15 parts by mass, per 100 parts by mass of the active ingredient. If the proportion of the acidulant is too low, the effect of improving palatability may not be achieved, and if it is too high, the volume and mass of the composition may become too large, reducing palatability and portability.

[0126] (amino acid) The body fat reduction composition of the present invention may further contain amino acids to act as an energy source or to impart flavoring or functionality.

[0127] Various types of amino acids can be used. Amino acids exist in both L-enantiomer and D-enantiomer forms.

[0128] Preferably, the amino acids used are L-alanine (Ala), L-arginine (Arg), L-asparagine (Asn), L-aspartic acid (Asp), L-cysteine ​​(Cys), L-glutamic acid (Glu), L-glutamine (Gln), glycine (Gly), L-histidine (His), L-isoleucine (Ile), L-leucine (Leu), L-lysine (Lys), L-methionine (Met), L-phenylalanine (Phe), L-proline (Pro), L-serine (Ser), L-threonine (Thr), L-tryptophan (Trp), L-tyrosine (Tyr), L-valine (Val), etc. More preferably, the amino acids used are L-alanine (Ala), L-histidine (His), etc.

[0129] Examples of amino acids include neutral amino acids such as glycine, alanine, valine, isoleucine, proline, methionine, tryptophan, tyrosine, and glutamine; acidic amino acids such as aspartic acid and glutamic acid; and basic amino acids such as lysine, arginine, and ornithine.

[0130] Amino acids can also be added as salts. Preferably, alkali metal salts such as sodium salts, potassium salts, and lithium salts; and alkaline earth metal salts such as magnesium salts and calcium salts are used. Sodium glutamate may be added instead of glutamic acid, or sodium aspartate may be added instead of aspartic acid.

[0131] These amino acids can be used individually or in combination of two or more. Among these amino acids, neutral amino acids such as alanine are preferred because they function as an energy source and also have excellent flavor-enhancing properties.

[0132] The proportion of amino acids is, for example, 1 to 100 parts by mass, preferably 5 to 80 parts by mass, more preferably 10 to 50 parts by mass, more preferably 15 to 40 parts by mass, and most preferably 20 to 30 parts by mass, per 100 parts by mass of the active ingredient. If the proportion of amino acids is too low, the effect of the amino acids may not be exhibited, and if it is too high, the volume and mass of the composition may become too large, reducing its palatability and portability.

[0133] (fragrance) The body fat reduction composition of the present invention may further contain a fragrance to improve palatability. The fragrance may be a natural fragrance or a synthetic fragrance.

[0134] Examples of natural fragrances include fruit essences or oils such as strawberry, blueberry, apple, plum, lime, vanilla, and pepper; peel essences or oils such as orange, white grape, grapefruit, and lemon; tree bark essences or oils such as cinnamon; tree bark powders such as cinnamon powder; root vegetable essences or oils such as ginger; root vegetable powders such as ginger powder; seed powders such as vanilla beans and cocoa powder; branch and leaf essences or oils such as peppermint, spearmint, and rosemary; branch and leaf powders such as peppermint powder; and flower essences or oils such as jasmine, lavender, rose, rosemary, and hyacinth.

[0135] Examples of synthetic fragrances include benzyl acetate, linalyl acetate, citral, citronellal, citronellol, cis-jasmine, cis-3-hexenol, and menthol.

[0136] These fragrances can be used individually or in combination of two or more, depending on the application.

[0137] The proportion of fragrance is, for example, 1 to 50 parts by mass, preferably 3 to 40 parts by mass, more preferably 5 to 30 parts by mass, more preferably 8 to 20 parts by mass, and most preferably 10 to 15 parts by mass, per 100 parts by mass of the active ingredient. If the proportion of fragrance is too low, the effect of improving palatability may not be achieved, and if it is too high, the total volume and mass of the composition may become too large, which may reduce palatability.

[0138] (oils and fats) The body fat reduction composition of the present invention may further contain oils and fats. The oils and fats are not particularly limited as long as they are edible oils and fats, and may be vegetable oils, animal oils and fats, or processed oils and fats.

[0139] Examples of vegetable oils include soybean oil, cottonseed oil, linseed oil, castor oil, safflower oil, rice bran oil, germinated rice oil, corn oil, sesame oil, sunflower oil, rice bran oil, rapeseed oil such as canola oil, peanut oil, palm kernel oil, olive oil, grapeseed oil, and other vegetable oils (salad oil, refined oil); palm oil such as coconut oil and carotino oil, and vegetable fats such as cocoa butter.

[0140] Examples of animal fats include butter, beef tallow, milk fat, lard, and fish oil.

[0141] Examples of processed oils and fats include margarine, shortening, coconut milk, and medium-chain triglycerides (MCTs) such as C8-10 fatty acid triglycerides.

[0142] These oils and fats may be fractionated oils, transesterified oils, or hydrogenated oils. These oils and fats can be used individually or in combination of two or more types.

[0143] The proportion of oils and fats may be 100 parts by mass or less per 100 parts by mass of the active ingredient, preferably 30 parts by mass or less, more preferably 10 parts by mass or less, more preferably 5 parts by mass or less, and most preferably 1 part by mass or less.

[0144] (edible fats and oils) There are no particular restrictions on edible oils and fats. Preferably, vegetable oils such as milk fat, shea butter, olive oil, soybean oil, safflower oil, corn oil, sunflower oil, rapeseed oil, coconut oil, palm oil, palm kernel oil, and fractionated palm oil are used as edible oils and fats; animal oils such as suet, lard, and fish oil are also used.

[0145] Edible oils and fats include oils and fats synthesized from glycerin and fatty acids, as well as fractionated oils, transesterified oils, hydrogenated oils, and the like.

[0146] The oils and fats synthesized from glycerin and fatty acids include monoglycerides, diglycerides, and triglycerides, and preferably medium-chain triglyceride (MCT) oils and fats.

[0147] Preferably, fractionated oils are used from palm oil (long chain) such as palm olein, palm superolein, palm stearin, and palm mid-fraction, and from palm kernel oil (short chain).

[0148] Preferably, the transesterified oil used is a transesterified oil of the aforementioned oil or its fractionated oil and other liquid oils, or a transesterified oil of medium-chain triglyceride (MCT) oil and vegetable oil, etc.

[0149] As hydrogenated oil, hydrogenated oils of the aforementioned oils and fats, hydrogenated oils of fractionated oils thereof, hydrogenated oils of transesterified oils, etc. are used. Furthermore, hydrogenated oils contain trans fatty acids.

[0150] Edible oils and fats include refined oils and fats. When refined oils and fats are used as edible oils and fats, there are no particular restrictions on the refining method. Preferably, chemical refining, physical refining, etc., are employed as the refining method for oils and fats.

[0151] Chemical refining is a method of refining oils and fats by subjecting crude oil, which has been pressed and extracted from raw materials, to degumming, deacidification, decolorization, dewaxing, deodorization, etc. Physical refining is a method of refining oils and fats by subjecting crude oil, which has been pressed from raw materials, to degumming, decolorization, deacidification, deodorization, etc.

[0152] There are no particular restrictions on the form of edible oils and fats. They may be solid or liquid.

[0153] The body fat reduction composition of the present invention can be used by using these edible oils and fats individually or in combination of two or more types.

[0154] The body fat reduction composition of the present invention may contain oils and fats, but since elevated triglyceride levels also have an adverse effect on lifestyle-related diseases, it is preferable to limit the intake of oils and fats from the viewpoint of preventing and treating lifestyle-related diseases. For this reason, the body fat reduction composition of the present invention preferably contains a small amount of oils and fats, more preferably substantially free of oils and fats, and most preferably completely free of oils and fats.

[0155] (protein) The body fat reduction composition of the present invention may further contain protein. Examples of protein include whey protein, casein protein, soy protein, pea protein, wheat protein, egg protein, and rice protein. These proteins can be used individually or in combination of two or more.

[0156] Proteins can suppress the deliquescence and acidity of BHB, not only water-soluble whey protein but also non-water-soluble proteins. Among the proteins used, whey protein, casein protein, soy protein (soybean protein), etc. are preferred from the viewpoint of suppressing deliquescence and acidity, and whey protein is preferred.

[0157] From the viewpoint of easily improving water dispersibility and absorption, the protein may be a partially hydrolyzed protein. Preferably, as the partially hydrolyzed protein, a water-soluble protein hydrolyzed product obtained by partially breaking down the protein contained therein in the protein raw material using proteolytic enzymes, acids, etc., is used.

[0158] When using protein, it is preferable to use protein in powder form. Protein can be in the form of crushed, powdered, flakes, granules, or granules.

[0159] The proportion of protein may be, for example, 3,000 parts by mass or less per 100 parts by mass of active ingredient, for example, 1,000 parts by mass or less (e.g., 1 to 1,000 parts by mass), preferably 800 parts by mass or less (e.g., 10 to 800 parts by mass), and more preferably 500 parts by mass or less (e.g., 100 to 500 parts by mass). If the proportion of protein is too low, the effect of incorporating protein may not be realized, and conversely, if it is too high, the volume and mass of the composition may increase, reducing its palatability and portability.

[0160] (R-BHB oligomers) The body fat reduction composition of the present invention may further contain R-BHB oligomers. The average degree of polymerization of the R-BHB oligomers should be 2 or more, but for example, 2 to 100, preferably 2 to 10, more preferably 2 to 5, more preferably 2 to 4.5, and most preferably 2 to 4. The R-BHB oligomers may be oligomers that are inevitably mixed in during the manufacturing process of the composition. The proportion of R-BHB oligomers may be 10 parts by mass or less per 100 parts by mass of the active ingredient, preferably 5 parts by mass or less, more preferably 3 parts by mass or less, and most preferably 1 part by mass or less.

[0161] (Other ingredients) The body fat reduction composition of the present invention may further contain other components. Examples of other components include conventional additives used in the fields of health foods (functional foods) and pharmaceuticals.

[0162] Common additives include, for example, ketone esters (e.g., ketone ester of BHB and 1,3-butanediol), vitamins (e.g., vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin B12, etc.), dietary fiber (e.g., wheat bran, corn bran, oat bran, corn fiber, soy fiber, beet fiber, crystalline cellulose, agar, chitosan, chitin, hemicellulose) Examples of additives include loin, lignin, glucan, etc., coloring agents (food colorants such as Yellow No. 5, Red No. 2, Blue No. 2; lake colorants; red iron oxide, etc.), seasonings, leavening agents or foaming agents (such as baking soda), thickening stabilizers or water-retaining emulsifying stabilizers (such as pectin and cellulose), pH adjusters (such as inorganic salts like baking soda, trisodium phosphate, and potassium dihydrogen phosphate), preservatives (such as antiseptics and antibacterial agents), defoaming agents, emulsifiers, antioxidants, light stabilizers, and brewing agents. These additives can be used individually or in combination of two or more.

[0163] The proportion of other components (total proportion) can be selected from a range of approximately 0.01 parts by mass to 50 parts by mass per 100 parts by mass of the active ingredient, for example, 0.01 parts by mass to 10 parts by mass, preferably 0.1 parts by mass to 5 parts by mass, and more preferably 0.2 parts by mass to 3 parts by mass.

[0164] (water) If the body fat reduction composition of the present invention is a liquid composition, it is preferable to further contain water. The proportion of water is, for example, 100 to 10,000 parts by mass, preferably 500 to 8,000 parts by mass, more preferably 1,000 to 5,000 parts by mass, and more preferably 2,000 to 4,000 parts by mass, per 100 parts by mass of the active ingredient.

[0165] The body fat reduction composition of the present invention may contain, for the expectation of a synergistic effect, physiologically active substances such as berberines, vasodilators, stimulants, stimulants, nootropic substances, and energy-enhancing compositions, including nootropic substances, energy-enhancing compositions, and tranquilizers. The BHB-containing composition may further contain or encapsulate complex phytosomes, liposomes, cytochrome P450 inhibitors, etc., in order to promote their uptake into the body.

[0166] (Physiologically active substance) The vasodilator components include nitric oxide promoter, arginase inhibitor, and nitric oxide synthase promoter, quercetin, L-citrulline, L-citrulline salt, L-arginine, L-arginine salt, agmatine, agmatine salt, nitrate, gallic acid, coenzyme Q10 (CoQ10), trimethylglycine, niacin, theanine, theobromine, garlic, magnesium, grape seed extract, and green It contains at least one component selected from the group consisting of tea extract, cocoa, proanthocyanidin, gallolylated proanthocyanidin, L-norvaline, β-alanine, niacin, theanine, catechin, or epicatechin, epicatechin-(4-8)-epicatechin-(4-8)-epicatechin or epicatechin-(4-8)-epicatechin-gallate, cocaine, glutathione, and taurine.

[0167] The vasodilator component includes at least one component selected from the group consisting of mucunapruriene, tyrosine, L-DOPA (i.e., L-3,4-dihydroxyphenylalanine), huperzine-A, dimethylaminoethanol, phenylalanine, phenylethylamine, choline, α-glycerophosphocholine, uridine, citicoline, tryptophan, 5-hydroxytryptophan (5-HTP), D-serine, phosphatidylserine, ginseng, ginkgo biloba, rhodiola rosea, polygala tenuifolia, muira puama, huperzia serrata, eshshordia californica, convolvulus pluricalis, Centella asiatica, Evolvulus alsinoides, Bacopa monnieri, Epimedium herb, Ashwagandha herb, forskolin, and vinpocetine.

[0168] The stimulant component comprises at least one component selected from the group consisting of adenosine receptor antagonists, phosphodiesterase inhibitors, epinephrine and / or norepinephrine promoters, caffeine, theacrine, theobromine, theophylline, methylriverine, and caffeine analogs.

[0169] The stimulant component includes at least one component selected from the group consisting of caffeine, theacrine, theobromine, theophylline, methylriverine, and paraxanthine.

[0170] The nootropic component includes at least one component selected from the group consisting of methylriverine, theacrine, mucunapruriene, tyrosine, L-DOPA (i.e., L-3,4-dihydroxyphenylalanine), huperzine-A, dimethylaminoethanol, phenylalanine, phenylethylamine, choline, α-glycerophosphocholine, uridine, citicoline, and racetam.

[0171] The energy-enhancing composition comprises at least one component selected from the group consisting of tryptophan, 5-hydroxytryptophan (5-HTP), D-serine, phosphatidylserine, ginseng, ginkgo biloba, ginkgo biloba, Rhodiola rosea, Polygala tenuifolia, Muira puama, Huperzia serrata, Eschscholzia californica, Convolvulus pluricaulis, Centella asiatica, Evolvulus alsinoides, Bacopa monnieri, Epimedium herb, ashwagandha, forskolin, and vinpocetine.

[0172] The energy-enhancing composition comprises at least one component selected from the group consisting of methylriverine, adenosine receptor antagonists, phosphodiesterase inhibitors, epinephrine and / or norepinephrine promoters, and xanthan alkaloids.

[0173] The tranquilizer contains at least one component selected from the group consisting of THC (tetrahydrocannabidiol) below the standard value, a THC compound having BHB or acetacetate bonded to THC via an ester bond, cannabidiol (CBD), and a CBD compound having BHB or acetacetate bonded to a CBD compound via an ester bond.

[0174] CBD compounds contain at least one component selected from the group consisting of one or more β-hydroxybutyrate (BHB) salts, cannabidiol (CBD), tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabidivarin (CBDV), cannabichromene (CBC), cannabinol (CBN), cannabiersoin (CBE), tetrahydrocannabinol (THC), iso-THC, cannabicyclolol (CBL), cannabicitran (CBT), cannabivarin (CBV), cannabichromarin THC (CBCV), cannabigerovarin (CBGV), and cannabigerol monomethyl ether (CBGM).

[0175] (Properties of compositions for reducing body fat) The body fat reduction composition of the present invention may be a composition for reducing body fat in mammals such as humans, and is preferably a composition for reducing body fat in medium-sized or large mammals (especially humans).

[0176] The body fat reducing agent of the present invention can reduce body fat while retaining subcutaneous fat, which has functions such as maintaining body temperature and protecting internal organs and bones. Therefore, it is particularly preferable that the composition be used not for weight loss purposes, but for preventing or improving lifestyle-related diseases in humans.

[0177] The body fat reduction composition of the present invention may be either a food composition or a pharmaceutical composition, but it is preferably a functional food composition.

[0178] The body fat reduction composition of the present invention may take the form of a liquid composition, a solid composition, or a semi-solid composition. Examples of liquid compositions (liquid preparations) include drinks, suspensions, emulsions, syrups, and injections. Examples of solid compositions (solid preparations) include powders, fine granules, granules, pills, tablets, flakes, cakes, gummies, nougat, films, and capsules. Examples of semi-solid compositions (semi-solid preparations) include gels, creams, slurries, and pastes. Of these, liquid compositions and solid compositions are preferred, with liquid preparations such as drinks and solid preparations such as powders and tablets being preferred, and drinks being particularly preferred.

[0179] The method of ingesting or administering the body fat reducing agent of the present invention may be parenteral administration such as injection, but oral administration in the form of a drink or powder is preferred.

[0180] When the body fat reduction composition of the present invention is a solid or semi-solid composition, the active ingredient, R-BHB (salt), may be in the form of a salt. The R-BHB salt in the form of a salt may be granular (or powdery). Examples of the shape of granular R-BHB salt include spherical, ellipsoidal, polyhedral, plate-like, fibrous, and irregular shapes. Of these shapes, a spherical shape, such as a nearly spherical shape, is preferred.

[0181] The average particle size (effective diameter) of the granular R-BHB salt is, for example, 0.1 μm to 1,000 μm, preferably 0.3 μm to 500 μm, more preferably 0.5 μm to 100 μm, and more preferably 1 μm to 50 μm. If the average particle size of the granular R-BHB salt is too small, handling may be impaired, and conversely, if it is too large, productivity may decrease.

[0182] In the specification and claims, the average particle size (effective diameter) is the central particle size (D50: measured particle size at 50% of the cumulative value in the particle size distribution), and can be measured by wet measurement using a particle size distribution analyzer (manufactured by Nikkiso Co., Ltd., device name: Microtrac MT3300ExII) on a volume basis, in accordance with the laser diffraction scattering method (ISO133201 and ISO9276-1).

[0183] When the body fat reduction composition of the present invention is a liquid composition, the liquid composition may contain R-BHB, and a mixture of R-BHB and a salt of R-BHB is particularly preferred as the active ingredient in the liquid composition, in order to maintain palatability and suppress salt intake. The pH of the liquid composition may be 7 or less, for example, 3 to 7, and from the viewpoint of productivity, it may be 4.5 or less, preferably 3 to 4.5, and more preferably 3 to 4. If the pH of the liquid composition is too low, there is a risk that it will be too sour.

[0184] In the specification and claims, pH can be measured by conventional methods, for example, using a commercially available pH meter.

[0185] When the body fat reduction composition of the present invention is a liquid composition, the acidity of the liquid composition (converted to the mass of citric acid) is, for example, 1% to 20% by mass, preferably 1% to 10% by mass, and more preferably 1% to 5% by mass.

[0186] (Method for manufacturing a body fat reduction composition) The body fat reduction composition of the present invention can be manufactured by conventional manufacturing methods depending on its form. When the body fat reduction composition of the present invention is a liquid composition, if R-BHB (salt) is in the form of an acid, the acidity is too strong, so it is preferable to manufacture the liquid body fat reduction composition by mixing R-BHB with an alkaline component. In this manufacturing method, the acidity can be suppressed by increasing the pH of the liquid composition by using an alkaline component as a raw material, or by changing R-BHB into the form of a salt.

[0187] There are no particular restrictions on the method of mixing each component. Any known mixing method can be used to mix each component, and preferably, a method of mechanically mixing each component using a mixer, mill, etc. is employed. Alternatively, after mixing and grinding each component, the remaining moisture in the mixture may be evaporated (volatilized) using an evaporator, etc.

[0188] The alkaline component is not particularly limited as long as it is an alkaline component commonly used in food and pharmaceuticals, but alkali metal compounds, alkaline earth metal compounds, basic amino acids, etc. are commonly used, and alkali metal compounds or alkaline earth metal compounds as acidulants or pH adjusters are preferred, with alkali metal compounds as acidulants being particularly preferred.

[0189] When alkali metal compounds or alkaline earth metal compounds are used as the alkaline component, acidity can be suppressed by converting at least a portion of R-BHB into salt form, but the intake of salt, which is a cause of lifestyle-related diseases, increases. Therefore, it is preferable to adjust the amount of alkaline component so that the mass ratio of R-BHB to R-BHB salt falls within the range described in the section on body fat reducing agents mentioned above.

[0190] (Nutritional supplement) The body fat reduction composition of the present invention can be in solid form or liquid form (aqueous dispersion). The body fat reduction composition can be stored as a solid such as a powder and taken orally as is or in combination with water, or it can be taken orally as an aqueous dispersion obtained by dispersing the body fat reduction composition in water.

[0191] The body fat reduction composition is suitable for oral intake and allows for the appropriate intake of BHB, which is an energy source, making it useful as a nutritional supplement.

[0192] The body fat reduction composition can be applied to foods and food products containing BHB (salt) for oral intake. Preferably, the body fat reduction composition can be applied to food supplements, functional foods, food additives, diet foods, power snacks, appetite suppressants, and sports supplements.

[0193] By using a body fat reduction composition and taking BHB (salt) (preferably R-BHB (salt)) as a supplement, the ketone body cycle for fat breakdown is activated, and blood ketone body concentration can be maintained.

[0194] According to this invention, by ingesting BHB (salt), it is possible to increase the blood ketone body concentration and reduce body fat, etc. According to this invention, by ingesting BHB (salt) before dinner, fat is broken down into ketone bodies during sleep.

[0195] According to the present invention, it is possible to maintain blood ketone body levels without requiring a restrictive diet such as a carbohydrate-restricted diet, and this method can be easily continued.

[0196] The intake (administration, taking) schedule for the body fat reduction composition of the present invention is preferably one in which the composition is taken continuously for a certain period (daily intake), and more preferably for two weeks or more, six weeks or more, or twelve weeks or more, and taken continuously every day. This is the most efficient way to increase the blood ketone body concentration the following morning and reduce body fat, etc.

[0197] By ingesting a composition for reducing body fat, it is possible to increase blood ketone body concentration and reduce body fat, as well as regulate weight loss, weight maintenance, increased blood ketone concentration (induction of ketosis, increase in blood BHB concentration) and maintenance (maintenance of ketosis), decreased and maintained blood glucose concentration, improved mental strength, improved concentration, improved energy, improved cognitive function, reduced traumatic brain injury, improved diabetes, reduced neuropathy, improved inflammatory state, anti-aging, improved diabetes, improved epilepsy, improved depression, improved and increased muscle mass, decreased fat mass, improved body composition, improved metabolism, fat loss, fatty acid conversion, improved motor function, increased muscle mass, and improved mental state and mood.

[0198] [3] Methods to reduce body fat The present invention provides a method for reducing body fat by orally ingesting β-hydroxybutyric acid (BHB) and / or its salt as an active ingredient.

[0199] The method for reducing body fat according to the present invention preferably involves a daily intake of BHB and / or its salts of 0.01g to 0.5g per kg of body weight in terms of active ingredients.

[0200] The present invention provides a method for reducing body fat, preferably one that reduces body fat without exercise or dietary restrictions.

[0201] The method for reducing body fat according to the present invention is preferably a method for reducing body fat that prioritizes the reduction of visceral fat over subcutaneous fat.

[0202] The present invention includes an embodiment in which the method for reducing body fat according to the present invention is a method for maintaining blood ketone body concentration.

[0203] The method of ingesting or administering the body fat reducing agent and body fat reducing composition of the present invention may be parenteral administration such as injection, but oral administration in the form of a drink or powder is preferred.

[0204] According to the present invention, the intake of BHB (salt) activates the ketone body cycle for fat breakdown, thereby maintaining blood ketone body levels.

[0205] According to this invention, by ingesting BHB (salt), it is possible to increase the blood ketone body concentration and reduce body fat, etc. According to this invention, by ingesting BHB before dinner, fat is broken down into ketone bodies during sleep.

[0206] According to the present invention, it is possible to maintain blood ketone body levels without requiring a restrictive diet such as a carbohydrate-restricted diet, and this method can be easily continued.

[0207] The method for reducing body fat (maintaining blood ketone body concentration) of the present invention preferably involves continuously ingesting (taking or administering) the body fat reducing agent and body fat reducing composition of the present invention for a certain period of time (daily continuous intake), and more preferably continuously ingesting (taking or administering) them for 2 weeks or more, 6 weeks or more, or 12 weeks or more (daily continuous intake). This method most efficiently increases blood ketone body concentration and reduces body fat, etc.

[0208] In the present invention's body fat reducing agent, body fat reducing composition, and method for reducing body fat, "dinner" refers to a meal taken in the evening or at night, and is also called "evening meal," "dinner," "supper," "evening meal," or "evening meal." "Dinner" refers to a meal eaten with about 2 to 5 hours before going to bed, and means a meal taken around sunset (evening).

[0209] The body fat reducing agent, body fat reducing composition, and method for reducing body fat of the present invention include a mode in which the body fat reducing agent and body fat reducing composition of the present invention are taken (drank) before dinner, followed by dinner, and then going to bed.

[0210] Although embodiments of the present invention have been described above, the present invention is not limited in any way to these examples, and can be implemented in various forms without departing from the spirit of the invention. [Examples]

[0211] The embodiments of the present invention will be described in more detail below based on the examples. The present invention is not limited to these examples.

[0212] [1] BHB's effect on maintaining blood ketone body concentration D-β-hydroxybutyrate (D-BHB, R-β-hydroxybutyrate) Osaka Gas Co., Ltd. produces BHB (naturally derived ketone bodies, fermented ketone bodies) from Halomonas bacteria. D-BHB can also be produced by fermentation using Halomonas bacteria, based on the disclosures in Japanese Patent Publication No. 2019-176839.

[0213] (method) Target participants: Japanese men and women aged 20 and over with a BMI of 23 kg / m². 2 More than 30kg / m 2 Those under the age of 18. Healthy individuals. Number of cases: 90. 30 cases in the BHB 2.9g group. 30 cases in the BHB 1.5g group. 30 cases in the placebo group. Test food: Test food group: BHB-containing beverage (2.9g / day or 1.5g / day of BHB) Placebo group: BHB-free beverage Intervention period: 12 weeks

[0214] (Evaluation method) (1) For 12 weeks, subjects were given either a BHB-containing beverage (2.9g / day or 1.5g / day of BHB) or a placebo food (BHB-free beverage) to take before dinner (daily and continuously) before going to bed. (2) The total ketone body concentration, acetoacetate concentration, and BHB concentration in the subjects' blood were measured the following morning.

[0215] (result)

[0216] [Table 1]

[0217] In the group receiving the test food (BHB-containing beverage), the change in blood ketone body concentration before and after the test was significantly greater compared to the placebo group.

[0218] The experimental results suggest that by continuously taking BHB before dinner for a certain period (12 weeks) (daily and continuous intake), the ketone body cycle for fat breakdown is activated, and blood ketone body levels are maintained.

[0219] [2] Body fat reduction effect of BHB (result)

[0220] [Table 2]

[0221] The experimental results showed that continuous daily intake of BHB before dinner for a certain period (12 weeks) increased blood ketone body levels the following morning and reduced visceral fat, suggesting that fat is broken down and converted into ketone bodies.

[0222] [2] Industrial applicability According to the present invention, it is possible to maintain blood ketone body levels without requiring a restrictive diet such as a carbohydrate-restricted diet, and this method can be easily continued.

Claims

1. A body fat reducing agent that is taken orally to reduce human body fat, The active ingredient is β-hydroxybutyric acid (BHB) and / or its salt. A body fat-reducing agent for oral administration.

2. The body fat reducing agent according to claim 1, wherein the daily intake of BHB and / or its salt is 0.01g to 0.5g per kg of body weight in terms of active ingredients.

3. The body fat reducing agent according to claim 1, wherein the proportion of BHB and / or its salt is 80% by mass or more.

4. The body fat reducing agent according to claim 1, wherein the active ingredient is a mixture of BHB and a salt of BHB.

5. A body fat reducing agent according to any one of claims 1 to 4, which is a body fat reducing agent that makes body fat easier to break down.

6. A body fat reducing agent according to any one of claims 1 to 4, which makes it easier for body fat to be broken down during sleep.

7. A body fat reducing agent according to any one of claims 1 to 4, which is a body fat reducing agent for promoting the production of BHB from body fat.

8. A body fat reducing agent according to any one of claims 1 to 4, which promotes the production of BHB from body fat during sleep.

9. A composition that reduces human body fat when taken orally, The active ingredient is β-hydroxybutyric acid (BHB) and / or its salt. A composition for reducing body fat, intended for oral intake.

10. The body fat reduction composition according to claim 9, wherein the daily intake of BHB and / or its salt is 0.01 g to 0.5 g per kg of body weight in terms of active ingredients.

11. The body fat reduction composition according to claim 9, wherein the active ingredient comprises BHB, and the composition is liquid.

12. The body fat reduction composition according to claim 9, wherein the active ingredient comprises a salt of BHB, and the composition is in a solid or semi-solid state.

13. A body fat reduction composition according to any one of claims 9 to 12, which is a functional food composition or pharmaceutical composition for oral intake by humans.

14. A body fat reduction composition according to any one of claims 9 to 12, which is a composition for reducing body fat without exercise or dietary restrictions.

15. A body fat reduction composition according to any one of claims 9 to 12, which is a composition for preferentially reducing visceral fat over subcutaneous fat.

16. A body fat reduction composition according to any one of claims 9 to 12, which is a composition for preventing or improving lifestyle-related diseases.

17. A method for reducing body fat by orally ingesting β-hydroxybutyric acid (BHB) and / or its salt as an active ingredient.

18. The method for reducing visceral fat according to claim 17, wherein the daily intake of BHB and / or its salt is 0.01g to 0.5g per kg of body weight in terms of active ingredients.

19. A method for reducing body fat according to claim 17, which reduces body fat without exercise or dietary restrictions.

20. A method for reducing body fat according to claim 17, wherein visceral fat is reduced in priority over subcutaneous fat.

Images