JP2023148376A - Hydroxyalkanoate composition - Google Patents

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

The present invention relates to hydroxyalkanoate compositions.

Hydroxyalkanoic acids, represented by 3-hydroxybutyric acid (hereinafter also simply referred to as "3HB"), are substances that originally exist in the human body, and are attracting attention as an innovative energy source that can replace carbohydrates. .

When hydroxyalkanoic acids such as 3HB are ingested, for example, medium chain fatty acids (MCT) contained in coconut oil, etc., they are metabolized in the body, enter the bloodstream, and are converted into energy. In this process, carbohydrates are converted into energy more quickly than through glycolysis. In other words, by ingesting hydroxyalkanoic acids such as 3HB from the outside, they are converted into energy more quickly than carbohydrates that go through the glycolytic system.

Furthermore, hydroxyalkanoic acids such as 3HB have the effect of suppressing the absorption of fat and sugar by cells. In other words, external intake of hydroxyalkanoic acids such as 3HB has a dieting effect that suppresses sugar absorption and promotes fat burning.

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

In view of the functions of hydroxyalkanoic acids such as 3HB, the application of hydroxyalkanoic acids such as 3HB as energy substances or diet/health foods for athletes is being considered.

Since hydroxyalkanoic acids such as 3HB have high hygroscopicity, it is difficult to handle them as they are. In addition, it has a strong sour taste, which causes discomfort when ingested orally. In order to improve the handling of hydroxyalkanoic acids, it is possible to add silicon dioxide, calcium silicate, dextrin, etc. as anti-caking agents, but there are upper limit intakes for these ingredients, and there are restrictions on sugar content. Therefore, it is not preferred 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, and as the neutralized salts, Patent Document 1 describes sodium salts, which have a large intake tolerance for the human body as minerals, Examples using potassium salts, calcium salts, magnesium salts, etc. are given.

US Patent No. 10736861

However, with the above-mentioned neutralized salt, there is a concern about excessive intake, so-called salt overload. Among minerals, sodium and potassium have a high permissible intake, but sodium is often ingested as salt in regular meals, and there are restrictions on its intake outside of meals.

Therefore, in order to increase the intake of hydroxyalkanoic acids such as 3HB, intake in the form of potassium salt is required. However, potassium salt is a compound that exhibits a behavior in which the amount of water vapor adsorbed significantly increases in a water vapor adsorption isotherm in a low humidity environment of about 35% relative humidity, and is extremely hygroscopic. For this reason, potassium salts are difficult to manufacture, and at present they are hardly distributed.

In addition, sodium salt is also a compound that exhibits hygroscopicity, and the amount of water vapor adsorbed increases significantly in an environment with a relative humidity of approximately 45%. It is not as hygroscopic as potassium salts, so although it is available on the market, it is difficult to manufacture in high humidity environments and is not suitable for storage.

From the above, there is a need to reduce the hygroscopicity of hydroxyalkanoate compositions containing 3HB potassium salt and the like. Therefore, the main object of the present invention is to provide a hydroxyalkanoate composition with low hygroscopicity.

As a result of intensive research to achieve the above object, the present inventors have found that while hydroxyalkanoic acid is a mixed salt of an alkali metal salt and an alkaline earth metal salt, it contains an alkali metal salt and an alkaline earth metal salt. When the amount is set within a predetermined range, for example, by drying, the crystallinity of the hydroxyalkanoate composition can be reduced and the hydroxyalkanoate composition can be made amorphous, and its hygroscopicity can be reduced. The present invention has been completed. That is, the present invention includes the following configurations.

Item 1. A hydroxyalkanoate composition comprising an alkali metal salt of hydroxyalkanoate and an alkaline earth metal salt of hydroxyalkanoate, the composition comprising:
When the total amount of the alkali metal and alkaline earth metal is 100 mol%, the content of the hydroxyalkanoic acid alkali metal salt is 1 to 70 mol% in terms of the amount of alkali metal,
The content of the hydroxyalkanoic acid alkaline earth metal salt is 30 to 99 mol% in terms of alkaline earth metal amount, and
is amorphous,
Hydroxyalkanoate composition.

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

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

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

Item 5. In the X-ray diffraction pattern by CuKα rays, within the tolerance range of ±0.5°, there is no peak with a full width at half maximum of 0.50° or less at the position of diffraction angle 2θ = 6.38°, or the diffraction angle 2θ = The hydroxyalkanoic acid according to any one of items 1 to 4, which does not have a peak with a full width at half maximum of 0.50° or less at positions 6.70° and 7.08°, or has only a halo. salt composition.

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

Section 7. The hydroxyalkanoate composition according to any one of items 1 to 6, which is a hydroxyalkanoate composition for oral intake.

Section 8. A nutritional supplement containing the hydroxyalkanoate composition according to any one of items 1 to 7.

Item 9. A method for producing the hydroxyalkanoate composition according to any one of Items 1 to 7 or the nutritional supplement according to Item 8,
comprising a step of mixing a hydroxyalkanoic acid and an alkali metal and an alkaline earth metal in a solution,
The content of the alkali metal in the mixed solution is 1 to 70 mol%, and the content of the alkaline earth metal salt in the mixed solution is 30 to 70 mol%, assuming that the total amount of the alkali metal and alkaline earth metal is 100 mol%. A manufacturing method in which the content is adjusted to 99 mol%.

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

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

Item 12. After said mixing,
Item 12. The manufacturing method according to any one of Items 9 to 11, comprising a step of concentrating and/or drying the obtained mixture.

Item 13. Item 13. The manufacturing method according to item 12, wherein the drying is dry powdering by spray drying.

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.

In particular, according to the present invention, salts containing potassium, which have been extremely difficult to produce, can be produced by including alkaline earth metal salts, and salts containing potassium that have a specific composition and are amorphous can be produced. A high quality hydroxyalkanoate composition can be obtained, and such a composition can reduce hygroscopicity.

These are the results of the hygroscopicity test of Test Example 1 of the powders obtained in Examples 1 to 2 and Comparative Examples 1 to 5. These are the results of the hygroscopicity test of Test Example 2 of the powders obtained in Examples 2 to 5 and Comparative Examples 1, 3, and 6. These are the results of water vapor moisture absorption isotherms of Test Example 3 for the powders obtained in Examples 1 to 2 and Comparative Example 1. These are the results of water vapor moisture absorption isotherms of Test Example 3 for the powders obtained in Examples 6 to 7 and Comparative Examples 4 to 5.

In this specification, "contain" is a concept that includes all of "comprise," "consist essentially of," and "consist of."

Furthermore, in this specification, when a numerical range is expressed as "A to B", it means greater than or equal to A and less than or equal to B.

Embodiments of the present invention will be described below, but various changes in form and details can be made without departing from the spirit and scope of the claims.

1. Hydroxyalkanoate Composition The hydroxyalkanoate composition of the present invention contains an alkali metal salt of hydroxyalkanoate and an alkaline earth metal salt of hydroxyalkanoate,
When the total amount of alkali metals and alkaline earth metals in the hydroxyalkanoate composition is 100 mol%, the content of the hydroxyalkanoic acid alkali metal salt is 1 to 70 mol% in terms of the amount of alkali metal, The content of the alkaline earth metal salt of hydroxyalkanoic acid is 30 to 99 mol% in terms of alkaline earth metal amount, and it is amorphous.

(1-1) Alkali metal salt of hydroxyalkanoic acid Examples of the hydroxyalkanoic acid in the alkali metal salt of hydroxyalkanoic acid include hydroxyacetic acid, 3-hydroxypropionic acid, 3-hydroxybutyric acid (3HB), 4-hydroxybutyric acid, 3- Examples include 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 these, 3-hydroxyalkanes with 3 to 12 carbon atoms are considered to be easy to use as an energy source, easy to suppress fat and sugar absorption, easy to improve cognitive function and long-term memory function, and easy to prevent Alzheimer's disease. Acids 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. .

Examples of the alkali metal salts in the alkali metal hydroxyalkanoic acid salts include sodium salts, potassium salts, lithium salts, and the like. These alkali metal salts can be used alone or in combination of two or more. Any alkali metal salt alone has a relative humidity point in its water vapor adsorption isotherm at which the amount of water vapor adsorbed increases significantly (e.g., 45% for the sodium salt, 35% for the potassium salt). ), making it difficult to manufacture in a high-humidity environment and unsuitable for storage. However, as in the present invention, it is possible to create a mixed salt with an alkaline earth metal salt, set the content within a specific range, and make it amorphous. As a result, there is no relative humidity point at which the amount of water vapor adsorption significantly increases, making production and storage possible.

Furthermore, when using a potassium salt, it was difficult to produce it alone due to its extremely high hygroscopicity, but as in the present invention, the content can be reduced by creating a mixed salt with an alkaline earth metal salt. By setting it within a specific range, it is particularly useful in that manufacturing and storage are possible with reduced hygroscopicity, and potassium salts, which have a large recommended intake amount of minerals, are effectively used, and the intake of hydroxyalkanoic acids is particularly increased. Easy to do.

From the above, as the alkali metal salt, sodium salt, potassium salt, etc. are preferable, and potassium salt is more preferable.

The alkali metal salts of hydroxyalkanoates can be used alone or in combination of two or more.

The steric structure of the hydroxyalkanoic acid alkali metal salt may be the R configuration (R configuration) or the S configuration (S configuration), or both steric structures may be mixed in any proportion. good. From the viewpoints that it is easy to use as an energy source, easy to suppress absorption of fat and sugar, easy to improve cognitive function and long-term memory function, and easy to prevent Alzheimer's disease, R configuration (R form) is preferable. It is more preferable to contain 95 to 100 mol% of

The method for producing the alkali metal salt of hydroxyalkanoic acid used in the present invention is not particularly limited, and hydroxyalkanoic acid is produced by a conventionally known method, and further, a conventionally used salt forming process, desalting process, A hydroxyalkanoic acid alkali metal salt can be produced by a salt exchange process or the like.

In the hydroxyalkanoate composition of the present invention, the content of the alkali metal salt of hydroxyalkanoate is the amount of alkali metal, with the total amount of alkali metals and alkaline earth metals in the hydroxyalkanoate composition of the present invention being 100 mol%. The amount is 1 to 70 mol%, preferably 5 to 65 mol%, and more preferably 10 to 60 mol%. In this range, the hydroxyalkanoate composition does not crystallize and becomes an amorphous material, so that hygroscopicity can be reduced. If the content of the hydroxyalkanoic acid alkali metal salt is made as large as possible while satisfying this range, that is, 20 mol% or more, especially 30 mol% or more, further 40 mol% or more, and even more particularly 50 mol% or more, etc. Since the recommended intake amount of hydroxyalkanoic acid alkali metal salts is large, it is possible to increase the intake amount of hydroxyalkanoic acid. Note that if the content of the alkali metal salt of hydroxyalkanoic acid is less than 1 mol %, the amount of intake of hydroxyalkanoic acid cannot be increased because the content of the alkali metal salt of hydroxyalkanoic acid is small. On the other hand, when the content of the alkali metal salt of hydroxyalkanoate exceeds 70 mol%, the hydroxyalkanoate composition becomes a crystalline material and has high hygroscopicity, making it difficult to manufacture and difficult to store.

(1-2) Alkaline earth metal salt of hydroxyalkanoic acid As the hydroxyalkanoic acid in the alkaline earth metal salt of hydroxyalkanoic acid, the same hydroxyalkanoic acid as in the alkali metal salt of hydroxyalkanoic acid described above can be used. , you can also use different ones.

Examples of the hydroxyalkanoic acid in the alkali metal hydroxyalkanoic acid salt include hydroxyacetic acid, 3-hydroxypropionic acid, 3-hydroxybutyric acid (3HB), 4-hydroxybutyric acid, 3-hydroxyvaleric acid, 3-hydroxyisovaleric acid, Examples include 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 these, 3-hydroxyalkanes with 3 to 12 carbon atoms are considered to be easy to use as an energy source, easy to suppress fat and sugar absorption, easy to improve cognitive function and long-term memory function, and easy to prevent Alzheimer's disease. Acids 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.

Examples of alkaline earth metal salts in the alkaline earth metal hydroxyalkanoic acid salts include magnesium salts, calcium salts, barium salts, and the like. These alkaline earth metal salts can be used alone or in combination of two or more. For any alkaline earth metal salt, by mixing the salt with an alkali metal salt and keeping the content within a specific range, it is possible to reduce the amount of adsorption compared to the case of using an alkali metal salt alone. There is no relative humidity point at which the amount of adsorption increases significantly, it can be produced and stored even in high-humidity environments, and it can increase the uptake of hydroxyalkanoic acids because it contains alkali metal salts. Can be done.

Among these, as the alkaline earth metal salt, magnesium salts, calcium salts, etc. are preferable, and magnesium salts are more preferable.

The alkaline earth metal salts of hydroxyalkanoates can be used alone or in combination of two or more.

The steric structure of the alkaline earth metal hydroxyalkanoic acid salt may be an R configuration (R configuration) or an S configuration (S configuration), and both tertiary structures may be mixed in an arbitrary ratio. It's okay. From the viewpoints that it is easy to use as an energy source, easy to suppress absorption of fat and sugar, easy to improve cognitive function and long-term memory function, and easy to prevent Alzheimer's disease, R configuration (R form) is preferable. It is more preferable to contain 95 to 100 mol% of

The method for producing the alkaline earth metal salt of hydroxyalkanoic acid used in the present invention is not particularly limited, and the hydroxyalkanoic acid is produced by a conventionally known method, and furthermore, a conventional salt-forming process and a desalting process are carried out. A hydroxyalkanoic acid alkaline earth metal salt can be produced by a process such as a salt exchange process or the like.

In the hydroxyalkanoate composition of the present invention, the content of the alkaline earth metal salt of hydroxyalkanoate is 30% by mole, with the total amount of alkali metal and alkaline earth metal in the hydroxyalkanoate composition of the present invention being 100% by mole. ~99 mol%, preferably 35-95 mol%, more preferably 40-90 mol%. While satisfying this range, the content of the alkaline earth metal salt of hydroxyalkanoate should be as small as possible, that is, 80 mol% or less, especially 70 mol% or less, further 60 mol% or less, even more especially 50 mol% or less, etc. If so, it is possible to relatively increase the content of the alkali metal salt of hydroxyalkanoic acid, which has a large recommended intake amount, and it is possible to increase the intake amount of hydroxyalkanoic acid. If the content of the alkali metal salt of hydroxyalkanoate is less than 30 mol%, the hydroxyalkanoate composition becomes a crystalline material and has high hygroscopicity, making it difficult to manufacture and difficult to store. When the content of alkaline earth metal salt of hydroxyalkanoic acid exceeds 99 mol%, the amount of intake of hydroxyalkanoic acid cannot be increased because the content of alkali metal salt of hydroxyalkanoic acid is small.

(1-3) Other components It is also preferable that the hydroxyalkanoate composition of the present invention contains other components as appropriate to the extent that the objects and effects of the present invention are not impaired. Such other components are not particularly limited as long as they are edible, and include, for example, edible oils and fats, proteins, carbohydrates, dietary fibers, and the like.

There are no particular restrictions on the edible oil and fat, and a wide variety of edible fats and oils can be used.

Examples of edible oils include 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; lard; and animal fats and oils such as fish oil.

Note that these edible fats and oils include fats and oils synthesized from glycerin and fatty acids, fractionated oils thereof, transesterified oils, hydrogenated oils, and the like.

Examples of fats and oils synthesized from glycerin and fatty acids include medium chain fatty acid triglyceride (MCT) fats and oils.

Examples of the fractionated oil include fractionated oils of palm oil such as palm olein, palm superolein, palm stearin, and palm midfraction.

As transesterified oils, for example, transesterified oils of the above-mentioned fats and oils or their fractionated oils and other liquid fats and oils, or transesterified oils of medium chain fatty acid triglyceride (MCT) fats and vegetable oils, etc. can be used. can.

Examples of hydrogenated oils include hydrogenated oils such as the above-mentioned fats and oils and their fractionated oils, as well as hydrogenated oils such as transesterified oils.

In addition, these edible fats and oils include refined fats and oils, and when using refined fats and oils, there are no particular restrictions on the method of refining the fats and oils, but for example, chemical refining, physical refining, etc. refining), etc. Chemical refining is a method of refining crude oil compressed and extracted from raw materials by subjecting it to degumming, deacidification, decolorization, dewaxing, deodorization, and the like. Physical refining is a method of refining crude oil compressed from raw materials by subjecting it to degumming, decoloring, deoxidizing, deodorizing, etc.

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

Further, the shape of these edible fats and oils is not particularly limited, as long as the composition is solid.

There are no particular restrictions on the protein, and any of whey protein, casein protein, soy protein, pea protein, wheat protein, egg protein, rice protein, etc. can be used. In the present invention, it is possible to improve the water dispersibility of not only water-soluble whey proteins such as whey protein but also water-insoluble proteins while suppressing the deliquescence and acidity of 3HB. Among these, whey protein, casein protein, soy protein (soybean protein), etc. are preferred, and whey protein is more preferred, from the viewpoint of water dispersibility, deliquescence suppression, sourness suppression, and the like.

These proteins may be partially decomposed products in order to easily improve water dispersibility and absorbability. Specific examples of such partial decomposition products include water-soluble protein decomposition products obtained by partially decomposing the proteins contained in protein raw materials using proteolytic enzymes, acids, etc. It will be done.

Preferably, the protein is in powder form when used. The form of the protein includes so-called pulverized form, powder form, powder form, flake form, granule form, granule form, etc., and the individual form is not strictly limited.

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

Carbohydrates usually refer to carbohydrates other than dietary fiber. Examples of carbohydrates include edible sugars such as monosaccharides, disaccharides, oligosaccharides, sugar alcohols, isomerized sugars, and starch decomposition products. More specifically, glucose (monosaccharide), sugar, maltose (maltose), lactose, trehalose (disaccharide), maltitol, palatinit (sugar alcohol), high-fructose corn syrup, high-fructose corn syrup Examples include sugar (hereinafter referred to as isomerized sugar), starch syrup (a mixture of glucose, maltose, and dextrin), dextrin (starch decomposition product), and the like.

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

When these other components are included, their content is preferably within a range that does not impair the objects and effects of the present invention. However, the present invention enables the production and storage of hydroxyalkanoate compositions with reduced hygroscopicity without using other ingredients, and the content of alkali metal salts of hydroxyalkanoates, which has a high recommended intake amount, Since it is expected that the intake of hydroxyalkanoic acid will be increased by increasing the amount of hydroxyalkanoic acid as much as possible, it is preferable that the content of these other components be as small as possible. For example, the content of other components other than the hydroxyalkanoate composition of the present invention is determined from the viewpoints of hygroscopicity, suppression of deliquescence, suppression of acidity, intake of hydroxyalkanoic acid, etc. The total amount of is 100% by mass, preferably 0 to 10% by mass, more preferably 0.01 to 5% by mass.

(1-4) Hydroxyalkanoate composition The hydroxyalkanoate composition of the present invention having the above components is an amorphous material, unlike the case of an alkali metal salt of hydroxyalkanoate alone. I can do it.

In the present invention, the fact that the hydroxyalkanoate composition is an amorphous material means that it does not have a peak characteristic of an alkali metal hydroxyalkanoate salt in an X-ray diffraction pattern using CuKα rays. Specifically, with a tolerance of ±0.5° (preferably ±0.3°, more preferably ±0.2°), for example, in the case of potassium 3-hydroxybutyrate, the diffraction angle 2θ = 6.38. In the case of sodium 3-hydroxybutyrate, the peak at a diffraction angle of 2θ = 6.70, the full width at half maximum of the peak at a position of 7.08° 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°).

In addition, in the present invention, the fact that the hydroxyalkanoate composition is an amorphous material means that in the X-ray diffraction pattern using CuKα rays, the area of the halo in the range of 5 to 85 degrees (S1) exceeds the halo. When the area of the peak derived from the hydroxyalkanoate composition in the crystalline state of the part is (S2),
Formula: [(S2)/(S1)+(S2)]×100
It is preferable that the ratio calculated by is 0 to 5%, particularly 0 to 3%, and even more preferably 0 to 2%.

Further, in the present invention, it is preferable that only a halo exists in the range of 5 to 85 degrees in the X-ray diffraction pattern using CuKα rays. In this case, it is possible to reduce the crystallinity (increase in amorphousness) of the composition, and in turn, it is possible to reduce the adsorptivity of the composition.

The hydroxyalkanoate composition of the present invention can be either solid or liquid (aqueous dispersion). That is, it can be stored as a solid such as a powder and taken orally as it is or in combination with water, or it can be taken orally as an aqueous dispersion in water.

In any case, hygroscopicity can be reduced and it can be stored without being highly monitored, so it is suitable for oral consumption and is a good way to ingest hydroxyalkanoic acid, which is an energy source. Therefore, it is useful as a nutritional supplement.

2. Method for producing a hydroxyalkanoate composition The method for producing a hydroxyalkanoate composition of the present invention includes:
A step of mixing a hydroxyalkanoic acid and an alkali metal and an alkaline earth metal in a solution, wherein the total amount of the alkali metal and the alkaline earth metal is 100 mol%, and the content of the alkali metal in the mixed solution is 1. The content of the alkaline earth metal salt in the mixed solution is adjusted to 30 to 99 mol%.

In this case, the liquid component of the solution when mixing the hydroxyalkanoic acid and the alkali metal and alkaline earth metal includes various solvents (preferably polar solvents, more preferably water) such as water and alcohol (ethanol etc.). One type or two or more types can be used without any particular restriction.

There are no particular limitations on the mixing method, and any known method may be used. For example, a method of mechanical mixing using a mixer or a mill can be exemplified.

Furthermore, there are no particular restrictions when mixing a hydroxyalkanoic acid, an alkali metal, and an alkaline earth metal in a solution; for example, a hydroxyalkanoic acid solution and a mixed solution of an alkali metal and an alkaline earth metal Can be mixed. 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 hydroxyalkanoic acid solution), or an alkali metal A hydroxyalkanoic acid solution (preferably a hydroxyalkanoic acid aqueous solution) can also be added dropwise to a solution containing an alkaline earth metal (preferably an aqueous solution containing an alkali metal and an alkaline earth metal).

When the hydroxyalkanoate composition of the present invention is a solid, the solvent can be removed and the solid can be taken out by concentrating and/or drying by a conventional method. Examples include evaporating (volatilizing) the solvent remaining in the mixture using an evaporator, spray dryer, freeze dryer, etc., filtering the obtained solid, drying under reduced pressure, etc., but there are no particular limitations. Not done.

On the other hand, the method for producing the hydroxyalkanoate composition of the present invention includes:
a step of melting a mixture containing a solid hydroxyalkanoic acid alkali metal salt and a hydroxyalkaline earth metal salt, the alkali metal content of the mixture being 100 mol%, The content of the alkaline earth metal salt in the mixture can be adjusted to 30 to 99 mol%.

In this case, the melting can be carried out in the presence or absence of a trace amount (approximately 1 to 20 parts by mass per 100 parts by mass of the mixture) of one or more various solvents such as water or alcohol (ethanol, etc.). .

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.

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

The mixing method is not particularly limited and may be mixed by any known method. For example, a method of mechanical mixing using a mixer or a mill can be exemplified.

Although the embodiments of the present invention have been described above, the present invention is not limited to these examples at all, and it goes without saying that the present invention can be implemented in various forms without departing from the gist of the present invention.

Hereinafter, embodiments of the present invention will be described in more detail based on Examples, but the present invention is not limited thereto.

In the following examples, (R)-3-hydroxybutyric acid was obtained by preparing an R-3-hydroxybutyric acid aqueous solution prepared according to the method described in Example 1 of JP 2019-176839 A at 70°C. The mixture was concentrated using an evaporator that was heated until no water came out, and seed crystals of ethyl acetate and R-3-hydroxybutyric acid were added thereto in an amount of 30% by weight based on the weight of the concentrated liquid, and the mixture was left at 4°C overnight. In the following examples, this was filtered and dried.

<Analysis method>
・Powder X-ray diffraction measurement Using a fully automatic multi-purpose horizontal powder X-ray diffraction device SmartLab (manufactured by Rigaku Co., Ltd.), CuKα (λ = 1.542 Å) was used as the radiation source, output 1.2 kW, operating angle 5-85. Measured under the conditions of °.

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

From the powder X-ray diffraction pattern of the obtained sample, the following diffraction peaks derived from the potassium salt crystals of R-3HB were observed:
Diffraction angle 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°.

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

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

Comparative example 4: 3HB-Na
The base used in Comparative Example 1 was changed from potassium hydroxide to sodium hydroxide, and a 20% by mass solution with a pH of 7 was similarly prepared and dried to obtain a powder of the sodium salt of R-3HB. From the powder X-ray diffraction pattern of the obtained sample, the following diffraction peaks derived from the crystals of the sodium salt of R-3HB were observed:
Diffraction angle 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°.

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

From the powder X-ray diffraction pattern of the obtained sample, no diffraction derived from crystals was observed, and only the following halo, which is characteristic of amorphous and derived from the potassium and calcium mixed salt of R-3HB, was observed:
Diffraction angle 2θ = 6.90° (full width at half maximum 2.22°), 21.30° (full width at half maximum 8.98°).

Example 2: 3HB-KMg1:1
By changing the calcium hydroxide used in Example 1 to magnesium oxide and similarly preparing a 20% by mass solution with a pH of 9 and drying it, a mixed salt of potassium and magnesium of R-3HB was obtained. A powder with a molar ratio of 1:1 was obtained.

From the powder X-ray diffraction pattern of the obtained sample, no diffraction derived from crystals was observed, and only the following halo, which is characteristic of amorphous and derived from the potassium and magnesium mixed salt of R-3HB, was observed. :
Diffraction angle 2θ = 6.90° (full width at half maximum 3.18°), 21.36° (full width at half maximum 13.54°).

Comparative example 5: 3HB-KNa
By changing the calcium hydroxide used in Example 1 to sodium hydroxide and preparing a 20% by mass solution with a pH of 9 and drying it, a mixed salt of potassium and sodium of R-3HB was obtained. A powder having a molar ratio of 1:1 was obtained.

From the powder X-ray diffraction pattern of the obtained sample, the following diffraction peaks derived from the crystals of the mixed salt of potassium and sodium of R-3HB were observed:
Diffraction angle 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°.

Example 3: 3HB-KMg1:4
By changing the calcium hydroxide used in Example 1 to magnesium hydroxide and preparing a 20% by mass solution with a pH of 9 and drying it, a mixed salt of potassium and magnesium of R-3HB was obtained. A powder having a molar ratio of 1:4 was obtained.

From the powder X-ray diffraction pattern of the obtained sample, no diffraction originating from crystals was observed, and only a halo characteristic of amorphous originating from the potassium and magnesium mixed salt of R-3HB was observed.

Example 4: 3HB-KMg2:3
By changing the calcium hydroxide used in Example 1 to magnesium hydroxide and preparing a 20% by mass solution with a pH of 9 and drying it, a mixed salt of potassium and magnesium of R-3HB was obtained. A powder having a molar ratio of 2:3 was obtained.

From the powder X-ray diffraction pattern of the obtained sample, no diffraction originating from crystals was observed, and only a halo characteristic of amorphous originating from the potassium and magnesium mixed salt of R-3HB was observed.

Example 5: 3HB-KMg3:2
By changing the calcium hydroxide used in Example 1 to magnesium hydroxide and preparing a 20% by mass solution with a pH of 9 and drying it, a mixed salt of potassium and magnesium of R-3HB was obtained. A powder having a molar ratio of 3:2 was obtained.

From the powder X-ray diffraction pattern of the obtained sample, no diffraction originating from crystals was observed, and only a halo characteristic of amorphous originating from the potassium and magnesium mixed salt of R-3HB was observed.

Comparative example 6:3HB-KMg4:1
By changing the calcium hydroxide used in Example 1 to magnesium hydroxide and preparing a 20% by mass solution with a pH of 9 and drying it, a mixed salt of potassium and magnesium of R-3HB was obtained. A powder with a molar ratio of 4:1 was obtained.

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

Example 6: 3HB-NaCa
By changing the potassium hydroxide used in Example 1 to sodium hydroxide and preparing a 20% by mass solution with a pH of 9 and drying it, a mixed salt of sodium and calcium of R-3HB was obtained. A powder having a molar ratio of 1:1 was obtained.

From the powder X-ray diffraction pattern of the obtained sample, no diffraction originating from crystals was observed, and only a halo characteristic of amorphous originating from the mixed salt of sodium and calcium of R-3HB was observed.

Example 7: 3HB-NaMg
The potassium hydroxide used in Example 1 was changed to sodium hydroxide, the calcium hydroxide was changed to magnesium hydroxide, and a 20% by mass solution with a pH of 9 was similarly prepared and dried to obtain sodium and R-3HB. A powder was obtained which is a mixed salt of magnesium and has a molar ratio of sodium and magnesium of 1:1.

From the powder X-ray diffraction pattern of the obtained sample, no diffraction originating from crystals was observed, and only a halo characteristic of amorphous originating from the mixed salt of sodium and magnesium of R-3HB was observed.

Test example 1: Hygroscopicity test (part 1)
1 g of each of the powders obtained in Examples 1 to 2 and Comparative Examples 1 to 5 was stored in a constant temperature and humidity machine at 25°C and 40% humidity for 20 hours, the weight increase rate was measured, and the hygroscopicity was compared. did. The results are shown in Figure 1.

As a result, it can be seen that the potassium salt of Comparative Example 1 has high hygroscopicity and is not suitable for storage. In addition, although the sodium salt alone in Comparative Example 4 had low hygroscopicity, the hygroscopicity was high when mixed with potassium, so even if potassium and sodium were mixed, no effect of reducing hygroscopicity could be obtained. There wasn't. On the other hand, in Examples 1 and 2, a mixed salt of potassium and magnesium or calcium, that is, a mixed salt of an alkali metal and an alkaline earth metal, is used, so it has a higher hygroscopicity than a potassium salt alone. was able to be significantly reduced. In particular, in the mixed salt of potassium and calcium of Example 1, the hygroscopicity was able to be reduced to the same level or more than that of the single calcium salt and the single magnesium salt of Comparative Examples 2 and 3. For this reason, the present invention uses a mixed salt of alkali metals and alkaline earth metals, which can significantly reduce hygroscopicity, making it suitable for manufacturing and storage, and with a high intake amount. Since it contains alkali metal salts, it can be expected to increase the intake of hydroxyalkanoic acids.

Test example 2: Hygroscopicity 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 constant temperature and humidity chamber at 25°C and 40% humidity for 20 hours, and the weight increase rate was measured. compared gender. The results are shown in Figure 2.

As a result, in Examples 2 to 5, the hygroscopicity was similarly reduced because the magnesium content was sufficient, but in Comparative Example 6, the magnesium content was insufficient, so The effect of reducing hygroscopicity could not be said to be sufficient. Therefore, in the present invention, since the content of alkali metals and alkaline earth metals is within a predetermined range, hygroscopicity can be significantly reduced, making it suitable for manufacturing and storage, and also suitable for alkali metals, which have a large intake amount. Since it contains metal salts, it can be expected to increase the intake of hydroxyalkanoic acids.

Test Example 3: Water vapor adsorption isotherm Using a high-precision vapor adsorption measurement device BELSORP-aqua3 (manufactured by Microtrac Bell Co., Ltd.), Examples 1 to 2 and 6 to 7, and Comparative Examples 1 and 4 to 5 The water vapor adsorption isotherm of the powder obtained was measured at 25°C and an equilibrium waiting time of 300 seconds. The results are shown in Figures 3 and 4.

As a result, in Comparative Examples 1, 4, and 5, there is a relative humidity point at which the amount of adsorption increases significantly, but in Examples 1 to 2 and 6 to 7, there is no such tendency, and the amount of adsorption increases gradually. did. 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 (13)

A hydroxyalkanoate composition comprising an alkali metal salt of hydroxyalkanoate and an alkaline earth metal salt of hydroxyalkanoate, the composition comprising:
When the total amount of the alkali metal and alkaline earth metal is 100 mol%, the content of the hydroxyalkanoic acid alkali metal salt is 1 to 70 mol% in terms of the amount of alkali metal,
The content of the hydroxyalkanoic acid alkaline earth metal salt is 30 to 99 mol% in terms of alkaline earth metal amount, and
is amorphous,
Hydroxyalkanoate composition. The hydroxyalkanoate composition according to claim 1, wherein the alkali metal salt of hydroxyalkanoic acid is at least one selected from the group consisting of sodium salt, potassium salt, and lithium salt of hydroxyalkanoic acid. The hydroxyalkanoate composition according to claim 1 or 2, wherein the alkaline earth metal salt of hydroxyalkanoic acid is at least one selected from the group consisting of magnesium salt, calcium salt, and barium salt of hydroxyalkanoic acid. The hydroxyalkanoate composition according to any one of claims 1 to 3, wherein the hydroxyalkanoic acid is 3-hydroxybutyric acid. In the X-ray diffraction pattern of CuKα rays, within the tolerance range of ±0.5°, there is no peak with a full width at half maximum of 0.50° or less at the diffraction angle 2θ = 6.38°, or the diffraction angle 2θ = The hydroxyalkane according to any one of claims 1 to 4, which does not have a peak with a full width at half maximum of 0.50° or less at positions of 6.70° and 7.08°, or has only a halo. Acid composition. The hydroxyalkanoate composition according to any one of claims 1 to 5, wherein the alkali metal salt of hydroxyalkanoate and the alkaline earth metal salt of hydroxyalkanoate contain an R configuration. The hydroxyalkanoate composition according to any one of claims 1 to 6, which is a hydroxyalkanoate composition for oral intake. A nutritional supplement containing the hydroxyalkanoate composition according to any one of claims 1 to 7. A method for producing the hydroxyalkanoate composition according to any one of claims 1 to 7 or the nutritional supplement according to claim 8, comprising:
comprising a step of mixing a hydroxyalkanoic acid and an alkali metal and an alkaline earth metal in a solution,
The content of the alkali metal in the mixed aqueous solution is 1 to 70 mol%, and the content of the alkaline earth metal salt in the mixed solution is 30 to 70 mol%, assuming that the total amount of the alkali metal and alkaline earth metal is 100 mol%. A manufacturing method in which the content is adjusted to 99 mol%. The manufacturing method according to claim 9, wherein the solvent constituting the solution is a polar solvent. The manufacturing method according to claim 9 or 10, wherein the solvent constituting the solution is water. After said mixing,
The manufacturing method according to any one of claims 9 to 11, comprising a step of concentrating and/or drying the obtained mixture. The manufacturing method according to claim 12, wherein the drying is dry powdering by spray drying.

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