Hydroxyalkanoate Composition

Abstract

To provide a hydroxyalkanoate composition in which hygroscopicity of alkali metal salts of hydroxyalkanoic acids such as 3HB is further reduced.SOLUTION: There is provided a hydroxyalkanoate composition which contains alkali metal salts of hydroxyalkanoic acids and alkaline earth metal salts of hydroxyalkanoic acids and is amorphous. When the total amount of alkali metals and alkaline earth metals in the hydroxyalkanoate composition is 100 mol%, the content of alkali metal salts of hydroxyalkanoates is 1 to 70 mol% in terms of alkali metal content, and the content of alkaline earth metal salts of hydroxyalkanoates is 30 to 99 mol% in terms of alkaline earth metal content.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to hydroxyalkanoate compositions. [Background technology]

[0002] Hydroxyalkanoic acids, such as 3-hydroxybutyric acid (hereinafter simply referred to as "3HB"), are substances that are naturally present in the human body and are attracting attention as an innovative energy source that can replace carbohydrates.

[0003] When ingested, hydroxyalkanoic acids such as 3HB are metabolized in the body via medium-chain fatty acids (MCTs), found in coconut oil, for example, and then transported to the bloodstream where they are converted into energy. This process allows for faster energy conversion than carbohydrates via the glycolytic pathway. In other words, when ingested externally, hydroxyalkanoic acids such as 3HB are converted into energy more quickly than carbohydrates via the glycolytic pathway.

[0004] Furthermore, hydroxyalkanoic acids such as 3HB have the effect of suppressing the absorption of fat and sugar by cells. In other words, by taking hydroxyalkanoic acids such as 3HB from an external source, it has the effect of suppressing sugar absorption and promoting fat burning, which is a dietary effect.

[0005] In addition, hydroxyalkanoic acids such as 3HB not only serve as an energy source, but have also been shown to be effective in improving cognitive function and long-term memory function, as well as preventing Alzheimer's disease.

[0006] In light of the functions of hydroxyalkanoic acids such as 3HB, their use as energy substances or diet and health foods for athletes is being considered.

[0007] Hydroxyalkanoic acids such as 3HB are highly hygroscopic, making them difficult to handle in their original state. Furthermore, their strong sour taste makes oral ingestion unpleasant. To improve the handleability of hydroxyalkanoic acids, it is conceivable to add anti-caking agents such as silicon dioxide, calcium silicate, or dextrin. However, these ingredients have upper intake limits and contain carbohydrates, making them undesirable in combination with hydroxyalkanoic acids such as 3HB. For this reason, hydroxyalkanoic acids such as 3HB are generally provided as powders in the form of neutralized salts. Patent Document 1 cites examples of such neutralized salts, including sodium salts, potassium salts, calcium salts, and magnesium salts, which are minerals with a high tolerance for human intake. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] U.S. Patent No. 10,736,861 Summary of the Invention [Problem to be solved by the invention]

[0009] However, there are concerns about excessive intake of the above-mentioned neutralized salts, or so-called excessive salt intake. Although sodium and potassium have a high intake tolerance among minerals, sodium is often ingested as table salt in a normal diet, and intake outside of meals is limited.

[0010] Therefore, to increase the intake of hydroxyalkanoic acids such as 3HB, potassium salts are required. However, potassium salts are highly hygroscopic compounds, exhibiting a significantly increased amount of water vapor adsorption in low-humidity environments (relative humidity of approximately 35%) in their water vapor adsorption isotherms. For this reason, potassium salts are difficult to manufacture, and are currently rarely available.

[0011] The sodium salt is also a hygroscopic compound, with its water vapor adsorption rate increasing significantly in an environment with a relative humidity of approximately 45%. Although it is commercially available, it is difficult to manufacture and is not suitable for storage in high-humidity environments because its hygroscopicity is not as high as that of the potassium salt.

[0012] For these reasons, it is desirable to reduce the hygroscopicity of hydroxyalkanoate compositions containing 3HB potassium salts, etc. Therefore, a primary object of the present invention is to provide a hydroxyalkanoate composition with low hygroscopicity. [Means for solving the problem]

[0013] As a result of extensive research conducted by the present inventors to achieve the above-mentioned object, they discovered that when a hydroxyalkanoic acid is prepared as a mixed salt of an alkali metal salt and an alkaline earth metal salt, and the contents of the alkali metal salt and the alkaline earth metal salt are set within a predetermined range, the crystallinity of the hydroxyalkanoic acid salt composition can be reduced by, for example, drying, thereby making it possible to exhibit amorphous properties, and ultimately to reduce its hygroscopicity, thereby completing the present invention.

[0014] Item 1. A hydroxyalkanoate composition containing an alkali metal hydroxyalkanoate and an alkaline earth metal hydroxyalkanoate, the content of the alkali metal hydroxyalkanoate salt is 1 to 70 mol % in terms of the amount of alkali metal, with the total amount of the alkali metal and alkaline earth metal being 100 mol %, The content of the alkaline earth metal salt of hydroxyalkanoic acid is 30 to 99 mol % in terms of the amount of alkaline earth metal, and It is amorphous, Hydroxyalkanoate compositions.

[0015] Item 2. The hydroxyalkanoate composition according to Item 1, wherein the alkali metal hydroxyalkanoate is at least one selected from the group consisting of sodium salts, potassium salts, and lithium salts of hydroxyalkanoic acid.

[0016] Item 3. The hydroxyalkanoate composition according to Item 1 or 2, wherein the alkaline earth metal hydroxyalkanoate is at least one selected from the group consisting of magnesium salts, calcium salts, and barium salts of hydroxyalkanoic acid.

[0017] Item 4. The hydroxyalkanoate composition according to any one of Items 1 to 3, wherein the hydroxyalkanoic acid is 3-hydroxybutyric acid.

[0018] Item 5. The hydroxyalkanoate composition according to any one of Items 1 to 4, wherein, in an X-ray diffraction pattern using CuKα radiation, there is no peak at a diffraction angle 2θ=6.38° with a full width at half maximum of 0.50° or less, or there are no peaks at diffraction angles 2θ=6.70° and 7.08° with a full width at half maximum of 0.50° or less, within a tolerance of ±0.5°. Alternatively, there is only a halo.

[0019] Item 6. The hydroxyalkanoate composition according to any one of Items 1 to 5, wherein the alkali metal hydroxyalkanoate and alkaline earth metal hydroxyalkanoate have an R configuration.

[0020] Item 7. The hydroxyalkanoate composition according to any one of Items 1 to 6, which is an orally ingested hydroxyalkanoate composition.

[0021] Item 8. A nutritional supplement comprising the hydroxyalkanoate composition according to any one of items 1 to 7.

[0022] Item 9. A method for producing the hydroxyalkanoate composition according to any one of items 1 to 7 or the dietary supplement according to item 8, mixing the hydroxyalkanoic acid with an alkali metal and an alkaline earth metal in solution; Equipped with The production method includes adjusting the content of alkali metal in the mixed solution to 1 to 70 mol % and the content of alkaline earth metal salt in the mixed solution to 30 to 99 mol %, where the total amount of alkali metal and alkaline earth metal is 100 mol %.

[0023] Item 10. The method according to Item 9, wherein the solvent constituting the solution is a polar solvent.

[0024] Item 11. The method according to Item 9 or 10, wherein the solvent constituting the solution is water.

[0025] Item 12. After the mixing, concentrating and / or drying the resulting mixture. Item 12. The manufacturing method according to any one of items 9 to 11, comprising:

[0026] Item 13. The method according to Item 12, wherein the drying is carried out by spray drying to obtain a powder. [Effects of the Invention]

[0027] According to the present invention, it is possible to provide a hydroxyalkanoate composition in which the hygroscopicity of an alkali metal salt of a hydroxyalkanoic acid such as 3HB is further reduced.

[0028] In particular, according to the present invention, it is possible to produce salts containing potassium, which have been extremely difficult to produce, by incorporating an alkaline earth metal salt, and it is also possible to obtain an amorphous hydroxyalkanoate composition having a specific composition, and such a composition can have reduced hygroscopicity. [Brief explanation of the drawings]

[0029] [Figure 1] 1 shows the results of a moisture absorption test in Test Example 1 for the powders obtained in Examples 1 and 2 and Comparative Examples 1 to 5. [Figure 2] 1 shows the results of a moisture absorption test in Test Example 2 for the powders obtained in Examples 2 to 5 and Comparative Examples 1, 3 and 6. [Figure 3]1 shows the results of moisture vapor absorption isotherms of Test Example 3 for the powders obtained in Examples 1 and 2 and Comparative Example 1. [Figure 4] 1 shows the results of moisture vapor absorption isotherms of Test Example 3 for the powders obtained in Examples 6 to 7 and Comparative Examples 4 to 5. DETAILED DESCRIPTION OF THE INVENTION

[0030] In this specification, the term "containing" is a concept that encompasses all of "comprise," "consist essentially of," and "consist only of."

[0031] In addition, in this specification, when a numerical range is expressed as "A to B," it means A or more and B or less.

[0032] Although the embodiments of the present invention will be described below, various modifications of the form and details are possible without departing from the spirit and scope of the claims.

[0033] 1. Hydroxyalkanoate composition The hydroxyalkanoate composition of the present invention contains an alkali metal hydroxyalkanoate and an alkaline earth metal hydroxyalkanoate, The hydroxyalkanoate composition has a content of the alkali metal hydroxyalkanoate of 1 to 70 mol % in terms of the amount of alkali metal, and a content of the alkaline earth metal hydroxyalkanoate of 30 to 99 mol % in terms of the amount of alkaline earth metal, where the total amount of alkali metal and alkaline earth metal in the hydroxyalkanoate composition is 100 mol %, and the composition is amorphous.

[0034] (1-1) Alkali metal hydroxyalkanoates Examples of hydroxyalkanoic acids in the alkali metal hydroxyalkanoate salts include hydroxyacetic acid, 3-hydroxypropionic acid, 3-hydroxybutyric acid (3HB), 4-hydroxybutyric acid, 3-hydroxyvaleric acid, 3-hydroxyisovaleric acid, 3-hydroxyhexanoic acid, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, and 3-hydroxydecanoic acid. These hydroxyalkanoic acids can be used alone or in combination of two or more. Among them, from the viewpoints of ease of use as an energy source, ease of suppressing fat and sugar absorption, ease of improving cognitive function and long-term memory function, and ease of preventing Alzheimer's disease, 3-hydroxyalkanoic acids having 3 to 12 carbon atoms are preferred, 3-hydroxyalkanoic acids having 3 to 8 carbon atoms are more preferred, 3-hydroxyalkanoic acids having 4 to 6 carbon atoms are even more preferred, and 3-hydroxybutyric acid (3HB) represented by the following formula is most preferred.

[0035] [ka]

[0036] Examples of alkali metal salts in alkali metal hydroxyalkanoates include sodium salts, potassium salts, and lithium salts. These alkali metal salts can be used alone or in combination of two or more. Each alkali metal salt has a relative humidity point at which the amount of adsorbed water vapor increases significantly in its water vapor adsorption isotherm (for example, 45% for sodium salts and 35% for potassium salts), making it difficult to produce in a high-humidity environment and unsuitable for storage. However, by using a mixed salt with an alkaline earth metal salt in a specific range and making it amorphous as in the present invention, the relative humidity point at which the amount of adsorbed water vapor increases significantly does not exist, making it possible to produce and store the salt.

[0037] Furthermore, when potassium salts are used alone, they are extremely hygroscopic and therefore difficult to produce. However, by using a mixed salt with an alkaline earth metal salt and setting the content within a specific range, as in the present invention, hygroscopicity is reduced, making it possible to produce and store the product, which is particularly useful. Potassium salts, which account for a large amount of the recommended intake of minerals, are effectively utilized, making it particularly easy to increase the intake of hydroxyalkanoic acids.

[0038] From the above, preferred alkali metal salts are sodium salts, potassium salts, etc., and potassium salts are more preferred.

[0039] The alkali metal hydroxyalkanoates may be used alone or in combination of two or more.

[0040] The steric structure of the alkali metal hydroxyalkanoate may be the R-configuration (R-isomer) or the S-configuration (S-isomer), or both steric structures may be mixed in any ratio. From the viewpoints of ease of use as an energy source, ease of suppressing the absorption of fat and sugar, ease of improving cognitive function and long-term memory function, and ease of preventing Alzheimer's disease, the R-configuration (R-isomer) is preferred, and it is more preferred that the R-configuration (R-isomer) is contained in an amount of 95 to 100 mol%.

[0041] The method for producing the alkali metal hydroxyalkanoate used in the present invention is not particularly limited, and a hydroxyalkanoic acid can be produced by a conventionally known method, and then the alkali metal hydroxyalkanoate can be produced by a conventionally used salt formation step, desalting step, salt exchange step, etc.

[0042] In the hydroxyalkanoate composition of the present invention, the content of the alkali metal hydroxyalkanoate is 1 to 70 mol%, preferably 5 to 65 mol%, and more preferably 10 to 60 mol%, calculated as the alkali metal amount, with the total amount of alkali metal and alkaline earth metal in the hydroxyalkanoate composition being 100 mol%. Within this range, the hydroxyalkanoate composition does not crystallize and becomes an amorphous material, thereby reducing hygroscopicity. By increasing the content of the alkali metal hydroxyalkanoate as much as possible while satisfying this range, i.e., 20 mol% or more, particularly 30 mol% or more, further 40 mol% or more, and even more particularly 50 mol% or more, it is possible to increase the intake of hydroxyalkanoic acid because the recommended intake of alkali metal hydroxyalkanoate is high. Note that if the content of alkali metal hydroxyalkanoate is less than 1 mol%, the content of alkali metal hydroxyalkanoate is low, making it impossible to increase the intake of hydroxyalkanoic acid. On the other hand, if the content of the alkali metal hydroxyalkanoate exceeds 70 mol %, the hydroxyalkanoate composition becomes a crystalline material, which is highly hygroscopic and therefore difficult to produce and store.

[0043] (1-2) Alkaline earth metal hydroxyalkanoates The hydroxyalkanoic acid in the alkaline earth metal hydroxyalkanoate may be the same as or different from the hydroxyalkanoic acid in the alkali metal hydroxyalkanoate described above.

[0044] Examples of hydroxyalkanoic acids in the alkali metal hydroxyalkanoate salts include hydroxyacetic acid, 3-hydroxypropionic acid, 3-hydroxybutyric acid (3HB), 4-hydroxybutyric acid, 3-hydroxyvaleric acid, 3-hydroxyisovaleric acid, 3-hydroxyhexanoic acid, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, and 3-hydroxydecanoic acid. These hydroxyalkanoic acids can be used alone or in combination of two or more. Among them, from the viewpoints of ease of use as an energy source, ease of suppressing fat and sugar absorption, ease of improving cognitive function and long-term memory function, and ease of preventing Alzheimer's disease, 3-hydroxyalkanoic acids having 3 to 12 carbon atoms are preferred, 3-hydroxyalkanoic acids having 3 to 8 carbon atoms are more preferred, 3-hydroxyalkanoic acids having 4 to 6 carbon atoms are even more preferred, and 3-hydroxybutyric acid (3HB) is most preferred.

[0045] Examples of alkaline earth metal salts in alkaline earth metal hydroxyalkanoates include magnesium salts, calcium salts, barium salts, etc. These alkaline earth metal salts can be used alone or in combination of two or more. In any alkaline earth metal salt, by forming a mixed salt with an alkali metal salt and setting the content within a specific range, the amount of adsorption can be reduced compared to the case of the alkali metal salt alone, there is no relative humidity point at which the amount of adsorption of water vapor increases significantly, it can be produced and stored even in a high humidity environment, and the inclusion of an alkali metal salt can increase the intake of hydroxyalkanoic acid.

[0046] Of these, the alkaline earth metal salts are preferably magnesium salts, calcium salts, etc., and more preferably magnesium salts.

[0047] The alkaline earth metal hydroxyalkanoates may be used alone or in combination of two or more.

[0048] The steric structure of the alkaline earth metal hydroxyalkanoate may be the R-configuration (R-isomer) or the S-configuration (S-isomer), or both configurations may be mixed in any ratio. From the viewpoints of ease of use as an energy source, ease of suppressing the absorption of fat and sugar, ease of improving cognitive function and long-term memory function, and ease of preventing Alzheimer's disease, the R-configuration (R-isomer) is preferred, and it is more preferred that the R-configuration (R-isomer) is contained in an amount of 95 to 100 mol%.

[0049] The method for producing the alkaline earth metal hydroxyalkanoate used in the present invention is not particularly limited, and a hydroxyalkanoic acid can be produced by a conventionally known method, and then the alkaline earth metal hydroxyalkanoate can be produced by a conventionally used salt formation step, desalting step, salt exchange step, etc.

[0050] In the hydroxyalkanoate composition of the present invention, the content of the alkaline earth metal hydroxyalkanoate is 30 to 99 mol%, preferably 35 to 95 mol%, and more preferably 40 to 90 mol%, based on 100 mol% of the total amount of alkali metal and alkaline earth metal in the hydroxyalkanoate composition. By minimizing the content of the alkaline earth metal hydroxyalkanoate within this range, i.e., 80 mol% or less, particularly 70 mol% or less, further 60 mol% or less, and even more particularly 50 mol% or less, the content of the alkali metal hydroxyalkanoate, which has a high recommended intake, can be relatively increased, thereby increasing the intake of hydroxyalkanoic acid. Note that if the content of the alkali metal hydroxyalkanoate is less than 30 mol%, the hydroxyalkanoate composition becomes a crystalline material, which is highly hygroscopic and therefore difficult to manufacture and store. If the content of alkaline earth metal hydroxyalkanoate exceeds 99 mol %, the content of alkali metal hydroxyalkanoate is so low that the intake of hydroxyalkanoic acid cannot be increased.

[0051] (1-3) Other ingredients The hydroxyalkanoate composition of the present invention preferably contains other components as appropriate within the scope of not impairing the objects and effects of the present invention. Such other components are not particularly limited as long as they are edible, and examples thereof include edible oils and fats, proteins, carbohydrates, dietary fiber, etc.

[0052] There are no particular limitations on the edible oils and fats, and a wide variety of oils and fats can be used.

[0053] Examples of edible fats and oils include vegetable fats and 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; and animal fats and oils such as lard and fish oil.

[0054] These edible oils and fats also include oils and fats synthesized from glycerin and fatty acids, fractionated oils thereof, interesterified oils, hydrogenated oils, and the like.

[0055] Examples of fats and oils synthesized from glycerin and fatty acids include medium-chain triglyceride (MCT) fats and oils.

[0056] Examples of fractionated oils include fractionated palm oils such as palm olein, palm superolein, palm stearin, and palm midfraction.

[0057] As interesterified oils, for example, interesterified oils of the above-mentioned oils and fats or fractionated oils thereof with other liquid oils and fats, or interesterified oils of medium-chain fatty acid triglyceride (MCT) oils and vegetable oils, etc. can be used.

[0058] Examples of the hydrogenated oil include hydrogenated oils of the above-mentioned fats and oils and fractionated oils thereof, as well as hydrogenated oils of interesterified oils.

[0059] These edible oils and fats also include refined oils and fats, and the refining method for the refined oils and fats when using refined oils and fats is not particularly limited, but examples include chemical refining, physical refining, etc. Chemical refining is a method of refining crude oil that has been pressed and extracted from a raw material by subjecting it to degumming, deacidification, bleaching, dewaxing, deodorization, etc. Physical refining is a method of refining crude oil that has been pressed from a raw material by subjecting it to degumming, bleaching, deacidification, deodorization, etc.

[0060] These edible oils and fats can be used alone or in combination of two or more.

[0061] The form of these edible oils and fats is not particularly limited as long as the composition is solid.

[0062] The protein is not particularly limited, and whey protein, casein protein, soy protein (soybean protein), pea protein, wheat protein, egg protein, rice protein, etc. can all be used. In the present invention, not only water-soluble whey proteins such as whey protein, but also water-insoluble proteins can improve the water dispersibility of 3HB while suppressing deliquescence and sourness. Among these, whey protein, casein protein, soy protein (soybean protein), etc. are preferred, and whey protein is more preferred, from the viewpoints of water dispersibility, suppression of deliquescence, suppression of sourness, etc.

[0063] These proteins may be partially hydrolyzed to facilitate improvement of water dispersibility and absorbability, and specific examples of such partially hydrolyzed proteins include water-soluble protein hydrolyzates obtained by partially hydrolyzing proteins contained in a protein raw material using a protease, acid, or the like.

[0064] The protein is preferably in powder form when used. The form of the protein may be so-called pulverized, powdered, powdered, flake, granular, or particulate, and the individual form is not strictly limited.

[0065] The above proteins are not particularly limited, and known or commercially available products can be used.

[0066] Carbohydrates usually refer to carbohydrates other than dietary fiber. Examples of carbohydrates include edible sugars such as monosaccharides, disaccharides, oligosaccharides, sugar alcohols, isomerized sugar, and starch hydrolysates. More specific examples include glucose (monosaccharide), table sugar, maltose, lactose, trehalose (all disaccharides), maltitol, palatinit (all sugar alcohols), glucose-fructose syrup, fructose-glucose syrup (all isomerized sugar), starch syrup (a mixture of glucose, maltose, and dextrin), and dextrin (a starch hydrolysate).

[0067] Examples of dietary fiber include wheat bran, corn bran, oat bran, cellulose-based fibers extracted from plants (e.g., corn fiber, soybean dietary fiber, beet fiber, etc.), cellulose, crystalline cellulose, agar, chitosan, chitin, hemicellulose, lignin, glucan, etc.

[0068] When these other components are included, the content thereof is preferably within a range that does not impair the objects and effects of the present invention. However, since the present invention allows the production and storage of a hydroxyalkanoate composition with reduced hygroscopicity without using other components, and since it is expected that the intake of hydroxyalkanoic acid will be increased by increasing the content of hydroxyalkanoic acid alkali metal salts, which have a high recommended intake amount, as much as possible, it is preferable that the content of these other components be as low as possible. For example, the content of other components other than the hydroxyalkanoic acid salt composition of the present invention is preferably 0 to 10% by mass, more preferably 0.01 to 5% by mass, based on 100% by mass of the total amount of the hydroxyalkanoic acid salt composition of the present invention, from the viewpoints of hygroscopicity, deliquescence suppression, sourness suppression, hydroxyalkanoic acid intake, etc.

[0069] (1-4) Hydroxyalkanoate composition The hydroxyalkanoate composition of the present invention having the above-mentioned components can be made into an amorphous material, unlike the case of an alkali metal hydroxyalkanoate alone.

[0070] In the present invention, the hydroxyalkanoate composition being an amorphous material means that the X-ray diffraction pattern using CuKα radiation does not have peaks characteristic of alkali metal hydroxyalkanoates. Specifically, it is preferable that the composition does not have a peak at a diffraction angle 2θ=6.38° in the case of potassium 3-hydroxybutyrate, or a peak at diffraction angles 2θ=6.70° and 7.08° in the case of sodium 3-hydroxybutyrate, whose full width at half maximum is 0.50° or less (preferably 0.01 to 0.50°, more preferably 0.03 to 0.40°, and even more preferably 0.05 to 0.25°) within an allowable range of ±0.5° (preferably ±0.3°, more preferably ±0.2°).

[0071] In the present invention, the hydroxyalkanoate composition is an amorphous material when, in an X-ray diffraction pattern using CuKα rays, the area of ​​the halo in the range of 5 to 85° is defined as (S1), and the area of ​​the peak beyond the halo, which is attributable to the hydroxyalkanoate composition in a crystalline state, is defined as (S2). Formula: [(S2) / (S1)+(S2)]×100 It is preferable that the ratio calculated by the above formula is 0 to 5%, particularly 0 to 3%, and further preferably 0 to 2%.

[0072] In the present invention, it is also preferred that only a halo is present in the range of 5 to 85° in the X-ray diffraction pattern using CuKα radiation, which can reduce the crystallinity of the composition (increase the amorphousness), and thus reduce the adsorptivity of the composition.

[0073] The hydroxyalkanoate composition of the present invention can be in the form of a solid or a liquid (aqueous dispersion). That is, it can be stored as a solid such as a powder and orally ingested as is or in combination with water, or it can be dispersed in water to form an aqueous dispersion and orally ingested.

[0074] In any case, since the hygroscopicity can be reduced and it can be stored without strict monitoring, it is suitable for oral intake, and since it allows the hydroxyalkanoic acid, which is an energy source, to be suitably ingested, it is useful as a nutritional supplement (supplement), etc.

[0075] 2. Method for producing hydroxyalkanoate composition The method for producing the hydroxyalkanoate composition of the present invention comprises: mixing the hydroxyalkanoic acid with an alkali metal and an alkaline earth metal in solution; The mixed solution is adjusted so that the content of alkali metal in the mixed solution is 1 to 70 mol % and the content of alkaline earth metal salt in the mixed solution is 30 to 99 mol %, where the total amount of alkali metal and alkaline earth metal is 100 mol %.

[0076] In this case, the liquid component of the solution when mixing the hydroxyalkanoic acid with the alkali metal and alkaline earth metal is not particularly limited, and one or more of various solvents such as water and alcohol (e.g., ethanol) (preferably a polar solvent, more preferably water) can be used.

[0077] The mixing method is not particularly limited, and any known method can be used, such as mechanical mixing using a mixer or mill.

[0078] Furthermore, when mixing a hydroxyalkanoic acid with an alkali metal and an alkaline earth metal in a solution, there is no particular limitation, and for example, a hydroxyalkanoic acid solution can be mixed with a mixed solution of an alkali metal and an alkaline earth metal. For example, a solution containing an alkali metal and an alkaline earth metal (preferably an aqueous solution containing an alkali metal and an alkaline earth metal) can be added dropwise to a hydroxyalkanoic acid solution (preferably an aqueous solution of a hydroxyalkanoic acid), or a hydroxyalkanoic acid solution (preferably an aqueous solution of a hydroxyalkanoic acid) can be added dropwise to a solution containing an alkali metal and an alkaline earth metal (preferably an aqueous solution containing an alkali metal and an alkaline earth metal).

[0079] When the hydroxyalkanoate composition of the present invention is a solid, the solvent can be removed and the solid can be extracted by a conventional method of concentration and / or drying, such as by evaporating (volatilizing) the solvent remaining in the mixture using an evaporator, spray dryer, freeze dryer, etc., and then filtering the obtained solid, or drying under reduced pressure, but this is not particularly limited.

[0080] On the other hand, the method for producing a hydroxyalkanoate composition of the present invention comprises the steps of: The method may also include a step of melting a mixture containing a solid hydroxyalkanoic acid alkali metal salt and a solid hydroxyalkanoic acid alkaline earth metal salt, and adjusting the alkali metal content of the mixture to 1 to 70 mol % and the alkaline earth metal salt content to 30 to 99 mol %, where the total amount of the alkali metal and alkaline earth metal is 100 mol %.

[0081] In this case, the mixture can be melted in the presence or absence of one or more kinds of solvents such as a small amount (about 1 to 20 parts by mass per 100 parts by mass of the mixture) of water or alcohol (ethanol, etc.).

[0082] The mixture used as a raw material may further contain a hydroxyalkanoic acid. In this case, it is preferable to adjust the final composition to be the same as the hydroxyalkanoate composition of the present invention.

[0083] It is also possible to mix the hydroxyalkanoic acid alkali metal salt solid and the hydroxyalkanoic acid alkaline earth metal salt solid in advance before melting.

[0084] The mixing method is not particularly limited, and any known method can be used, such as mechanical mixing using a mixer or mill.

[0085] Although the embodiments of the present invention have been described above, the present invention is not limited to these examples, and it goes without saying that the present invention can be embodied in various forms without departing from the spirit of the present invention. [Example]

[0086] Hereinafter, the embodiments of the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

[0087] In the following examples, (R)-3-hydroxybutyric acid was obtained by concentrating an aqueous solution of R-3-hydroxybutyric acid produced according to the method described in Example 1 of JP 2019-176839 A in an evaporator set at 70° C. until no water was released, adding 30% by mass of ethyl acetate and seed crystals of R-3-hydroxybutyric acid relative to the weight of the concentrated solution, and leaving it overnight at 4° C. This was filtered and dried and used in the following examples.

[0088] <Analysis method> Powder X-ray diffraction measurement Measurements were performed using a fully automated multipurpose horizontal powder X-ray diffractometer, SmartLab (Rigaku Corporation), with CuKα (λ=1.542 Å) as the radiation source, at an output of 1.2 kW and an operating angle of 5 to 85°.

[0089] Comparative example 1:3HB-K 20 g (0.19 mol) of R-3-hydroxybutyric acid (R-3HB) and 30 g of distilled water were mixed in a beaker to prepare an R-3HB aqueous solution. 20 g of distilled water was placed in a separate beaker, and 10.7 g (0.20 mol) of potassium hydroxide was added and mixed. The potassium hydroxide aqueous solution was added dropwise to the R-3HB aqueous solution to adjust the pH to 9. Distilled water was added to the R-3HB aqueous solution to a weight of 136.1 g and a solids content of approximately 20% by mass. This was dried in a spray dryer to obtain a powder of the potassium salt of R-3HB. A B-290 spray dryer manufactured by Nippon Buchi was used.

[0090] The powder X-ray diffraction pattern of the obtained sample showed the following diffraction peaks derived from the crystals of the potassium salt of R-3HB: Diffraction angles 2θ = 6.38° (full width at half maximum 0.10°), 7.14°, 12.76°, 18.20°, 19.26°, 19.52°, 20.82°, 22.46°, 25.76°, 26.78°, 30.02°, 31.10°, 31.84°, 32.28°, 32.38°, 35.12°.

[0091] Comparative example 2: 3HB-Ca In Comparative Example 1, the base was changed from potassium hydroxide to calcium hydroxide, and a 20% by mass solution at pH 7 was prepared and dried in the same manner to obtain a powder of calcium salt of R-3HB. The powder X-ray diffraction pattern of the obtained sample showed only the following halo, which is characteristic of an amorphous substance and is derived from the calcium salt of R-3HB: Diffraction angle 2θ = 7.16° (full width at half maximum 2.62°), 21.46° (full width at half maximum 12.56°).

[0092] Comparative example 3: 3HB-Mg In Comparative Example 1, the base was changed from potassium hydroxide to magnesium oxide, and a 20% by mass solution at pH 7 was prepared and dried in the same manner to obtain a powder of the magnesium salt of R-3HB. The powder X-ray diffraction pattern of the obtained sample showed only the following halo, which is characteristic of an amorphous substance and is derived from the magnesium salt of R-3HB: Diffraction angle 2θ = 8.00° (full width at half maximum 3.70°), 21.14° (full width at half maximum 13.00°).

[0093] Comparative example 4: 3HB-Na In Comparative Example 1, the base was changed from potassium hydroxide to sodium hydroxide, and a 20% by mass solution at pH 7 was similarly prepared and dried to obtain a powder of the sodium salt of R-3HB. The powder X-ray diffraction pattern of the obtained sample showed the following diffraction peaks derived from crystals of the sodium salt of R-3HB: Diffraction angles 2θ = 6.70° (full width at half maximum 0.18°), 7.08° (full width at half maximum 0.18°), 8.34°, 11.68°, 12.08°, 16.86°, 18.76°, 20.20°, 20.64°, 20.68°, 22.08°, 22.44°, 23.14°, 23.44°, 27.60°, 28.80°, 28.88°, 29.40°, 30.00°, 30.20°, 30.26°, 30.50°, 33.18°, 37.06°.

[0094] Example 1: 3HB-KCa 20 g (0.19 mol) of R-3-hydroxybutyric acid (R-3HB) and 30 g of distilled water were mixed in a beaker to prepare an R-3HB aqueous solution. 20 g of distilled water was placed in a separate beaker, and 4.88 g (0.066 mol) of calcium hydroxide and 3.70 g (0.066 mol) of potassium hydroxide were added and mixed. A mixed aqueous solution of potassium hydroxide and calcium hydroxide was added dropwise to the R-3HB aqueous solution to adjust the pH to 9. Distilled water was added to the R-3HB aqueous solution to a weight of 124.3 g and a solids content of approximately 20% by mass. This was dried in a spray dryer to obtain a powder of a potassium and calcium mixed salt of R-3HB with a potassium to calcium molar ratio of 1:1. A B-290 spray dryer manufactured by Nippon Buchi was used.

[0095] The powder X-ray diffraction pattern of the obtained sample showed no diffraction due to crystals, and only the following halo characteristic of an amorphous substance, which is due to the potassium and calcium mixed salt of R-3HB: Diffraction angle 2θ = 6.90° (full width at half maximum 2.22°), 21.30° (full width at half maximum 8.98°).

[0096] Example 2: 3HB-KMg 1:1 The calcium hydroxide used in Example 1 was changed to magnesium oxide, and a 20% by mass solution at pH 9 was similarly prepared and dried to obtain a powder of a mixed salt of potassium and magnesium of R-3HB, with a potassium to magnesium molar ratio of 1:1.

[0097] The powder X-ray diffraction pattern of the obtained sample showed no diffraction due to crystals, and only the following halo characteristic of amorphous material, which is due to the potassium and magnesium mixed salt of R-3HB: Diffraction angle 2θ = 6.90° (full width at half maximum 3.18°), 21.36° (full width at half maximum 13.54°).

[0098] Comparative example 5: 3HB-KNa The calcium hydroxide used in Example 1 was replaced with sodium hydroxide, and a 20% by mass solution at pH 9 was similarly prepared and dried to obtain a powder of a mixed salt of potassium and sodium of R-3HB, with a potassium to sodium molar ratio of 1:1.

[0099] The powder X-ray diffraction pattern of the obtained sample showed the following diffraction peaks derived from the crystals of a mixed salt of potassium and sodium R-3HB: Diffraction angles 2θ = 6.54° (full width at half maximum 0.18°), 6.80° (full width at half maximum 0.10°), 13.62°, 13.80°, 18.26°, 18.80°, 19.98°, 20.42°, 20.78°, 21.56°, 21.90°, 22.56°, 23.36°, 23.58°, 24.38°, 24.90°, 25.76°, 25.96°, 26.32°, 26.36°, 26.42°, 26.52°, 27.08°, 27.16°, 27.40°, 27.72°, 29.20°, 29.82°, 29.86°, 29.94°, 30.08°, 31.18°, 31.26°, 31.32°, 31.48°, 31.80°, 31.90°, 32.02°, 32.06°, 32.1°, 32.18°, 32.32°, 33.82°, 33.90°, 34.00°, 34.06°, 34.42°, 37.02°, 37.54°, 38.22°.

[0100] Example 3: 3HB-KMg 1:4 The calcium hydroxide used in Example 1 was changed to magnesium hydroxide, and a 20% by mass solution at pH 9 was similarly prepared and dried to obtain a powder of a mixed salt of potassium and magnesium of R-3HB, with a potassium to magnesium molar ratio of 1:4.

[0101] The powder X-ray diffraction pattern of the obtained sample showed no diffraction due to crystals, and only a halo characteristic of amorphous material due to the potassium and magnesium mixed salt of R-3HB was observed.

[0102] Example 4: 3HB-KMg 2:3 The calcium hydroxide used in Example 1 was changed to magnesium hydroxide, and a 20% by mass solution at pH 9 was similarly prepared and dried to obtain a powder of a mixed salt of potassium and magnesium of R-3HB, with a potassium to magnesium molar ratio of 2:3.

[0103] The powder X-ray diffraction pattern of the obtained sample showed no diffraction due to crystals, and only a halo characteristic of amorphous material due to the potassium and magnesium mixed salt of R-3HB was observed.

[0104] Example 5: 3HB-KMg3:2 The calcium hydroxide used in Example 1 was changed to magnesium hydroxide, and a 20% by mass solution at pH 9 was similarly prepared and dried to obtain a powder of a mixed salt of potassium and magnesium of R-3HB, with a potassium to magnesium molar ratio of 3:2.

[0105] The powder X-ray diffraction pattern of the obtained sample showed no diffraction due to crystals, and only a halo characteristic of amorphous material due to the potassium and magnesium mixed salt of R-3HB was observed.

[0106] Comparative example 6:3HB-KMg4:1 The calcium hydroxide used in Example 1 was changed to magnesium hydroxide, and a 20% by mass solution at pH 9 was similarly prepared and dried to obtain a powder of a mixed salt of potassium and magnesium of R-3HB, with a potassium to magnesium molar ratio of 4:1.

[0107] The powder X-ray diffraction pattern of the obtained sample showed the following diffraction peaks derived from the crystals of the potassium and magnesium mixed salt of R-3HB: Diffraction angle 2θ = 6.38° (full width at half maximum 0.22°), 6.60° (full width at half maximum 0.14°).

[0108] Example 6: 3HB-NaCa The potassium hydroxide used in Example 1 was changed to sodium hydroxide, and a 20% by mass solution at pH 9 was similarly prepared and dried to obtain a powder of a mixed salt of sodium and calcium of R-3HB, with a molar ratio of sodium to calcium of 1:1.

[0109] The powder X-ray diffraction pattern of the obtained sample showed no diffraction due to crystals, and only a halo characteristic of amorphous matter, which was due to the sodium and calcium mixed salt of R-3HB, was observed.

[0110] Example 7: 3HB-NaMg The potassium hydroxide used in Example 1 was changed to sodium hydroxide, and the calcium hydroxide was changed to magnesium hydroxide. Similarly, a 20% by mass solution at pH 9 was prepared and dried, thereby obtaining a powder of a mixed salt of sodium and magnesium of R-3HB, in which the molar ratio of sodium to magnesium was 1:1.

[0111] The powder X-ray diffraction pattern of the obtained sample showed no diffraction due to crystals, and only a halo characteristic of amorphous matter, which was due to the sodium and magnesium mixed salt of R-3HB, was observed.

[0112] Test Example 1: Moisture absorption test (part 1) 1 g of each of the powders obtained in Examples 1 and 2 and Comparative Examples 1 to 5 was stored in a thermo-hygrostat at 25°C and 40% humidity for 20 hours, and the weight gain was measured to compare the hygroscopicity. The results are shown in Figure 1.

[0113] As a result, it can be seen that the potassium salt of Comparative Example 1 is highly hygroscopic and unsuitable for storage. Furthermore, although the sodium salt of Comparative Example 4 had low hygroscopicity, its mixed salt with potassium exhibited high hygroscopicity, and therefore, mixing potassium and sodium did not result in a reduction in hygroscopicity. In contrast, Examples 1 and 2 employed mixed salts of potassium and magnesium or calcium, i.e., mixed salts of alkali metals and alkaline earth metals, which enabled a significant reduction in hygroscopicity compared to potassium salt alone. In particular, the potassium and calcium mixed salt of Example 1 was able to reduce hygroscopicity to the same level or even greater than that of the calcium salt and magnesium salt of Comparative Examples 2 and 3. Therefore, the present invention, which employs mixed salts of alkali metals and alkaline earth metals, significantly reduces hygroscopicity and is suitable for production and storage, and is expected to increase the intake of hydroxyalkanoic acid because it contains alkali metal salts with a high recommended intake.

[0114] Test Example 2: Moisture absorption test (part 2) 1 g of each of the powders obtained in Examples 2 to 5 and Comparative Examples 1, 3, and 6 was stored in a thermo-hygrostat at 25°C and 40% humidity for 20 hours, and the weight gain was measured to compare the hygroscopicity. The results are shown in Figure 2.

[0115] As a result, in Examples 2 to 5, the magnesium content was sufficient and thus hygroscopicity could be similarly reduced, but in Comparative Example 6, the magnesium content was insufficient and therefore the effect of reducing hygroscopicity was not sufficient. Therefore, in the present invention, the contents of alkali metals and alkaline earth metals are set within a predetermined range, thereby significantly reducing hygroscopicity, making it suitable for production and storage, and since it contains alkali metal salts with a high recommended intake amount, it is expected that the intake of hydroxyalkanoic acid will be increased.

[0116] Test Example 3: Water Vapor Adsorption Isotherm Using a high-precision vapor adsorption analyzer BELSORP-aqua3 (manufactured by Microtrack-Bell Corporation), water vapor adsorption isotherms were measured at 25°C with an equilibrium waiting time of 300 seconds for the powders obtained in Examples 1 to 2, 6 to 7, and Comparative Examples 1, 4 and 5. The results are shown in Figures 3 and 4.

[0117] As a result, in Comparative Examples 1, 4, and 5, there existed a relative humidity point at which the amount of adsorption increased significantly, whereas in Examples 1 to 2 and 6 to 7, such a tendency was not observed and the amount of adsorption increased gradually. Therefore, the present invention is suitable for production and storage even in a high humidity environment, and is expected to increase the intake of hydroxyalkanoic acid because it contains an alkali metal salt with a high recommended intake amount.

Claims

1. A 3-hydroxybutyrate composition containing an alkali metal salt of 3-hydroxybutyrate and an alkaline earth metal salt of 3-hydroxybutyrate, The content of the alkali metal salt of 3-hydroxybutyric acid is 20 to 60 mol % in terms of the amount of alkali metal, and the content of the alkaline earth metal salt of 3-hydroxybutyric acid is 40 to 80 mol % in terms of the amount of alkaline earth metal, where the total amount of the alkali metal and alkaline earth metal is 100 mol %; and It is amorphous, 3-hydroxybutyrate composition.

2. 2. The 3-hydroxybutyrate composition according to claim 1, wherein the alkali metal 3-hydroxybutyrate is at least one selected from the group consisting of sodium, potassium, and lithium salts of 3-hydroxybutyrate.

3. 3. The 3-hydroxybutyrate composition according to claim 1, wherein the alkaline earth metal salt of 3-hydroxybutyric acid is at least one selected from the group consisting of magnesium salt, calcium salt, and barium salt of 3-hydroxybutyric acid.

4. The 3-hydroxybutyrate composition according to any one of claims 1 to 3, wherein, in an X-ray diffraction pattern using CuKα radiation, there is no peak at a diffraction angle 2θ = 6.38° with a full width at half maximum of 0.50° or less, or there are no peaks at diffraction angles 2θ = 6.70° and 7.08° with a full width at half maximum of 0.50° or less, within a tolerance range of ±0.5°. Alternatively, there is only a halo.

5. The 3-hydroxybutyrate composition according to any one of claims 1 to 4, wherein the alkali metal 3-hydroxybutyrate and the alkaline earth metal 3-hydroxybutyrate contain an R configuration.

6. The 3-hydroxybutyrate composition according to any one of claims 1 to 5, which is a 3-hydroxybutyrate composition for oral administration.

7. A nutritional supplement comprising the 3-hydroxybutyrate composition according to any one of claims 1 to 6.

8. A method for producing the 3-hydroxybutyrate composition according to any one of claims 1 to 6 or the dietary supplement according to claim 7, comprising: The method comprises the step of mixing 3-hydroxybutyric acid with an alkali metal and an alkaline earth metal in a solution, the mixed aqueous solution is adjusted so that the content of the alkali metal in the mixed aqueous solution is 20 to 60 mol % and the content of the alkaline earth metal salt in the mixed solution is 40 to 80 mol %, where the total amount of the alkali metal and alkaline earth metal is 100 mol %.

9. The method according to claim 8 , wherein the solvent constituting the solution is a polar solvent.

10. The method according to claim 8 or 9, wherein the solvent constituting the solution is water.

11. After said mixing, concentrating and / or drying the resulting mixture. The manufacturing method according to any one of claims 8 to 10, comprising:

12. The method according to claim 11, wherein the drying is carried out by spray drying to obtain a dry powder.

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