Acid and salt compound and preparation method thereof

Abstract

A complex comprising 3-hydroxybutyric acid; and one or more of potassium 3-hydroxybutyrate, calcium 3-hydroxybutyrate, or magnesium 3-hydroxybutyrate. A complex having anions including 3-hydroxyvalerate and cations including sodium and hydrogen. The composite has suitable hygroscopicity and stability. When the dosage is proper, the compound has a good ketogenic effect.

Description

A complex of acid and salt and preparation method thereof Technical Field

[0001] The present invention belongs to the technical field of dietary or nutritional supplements, and in particular relates to a complex of an acid and a salt and a preparation method thereof. Background Art

[0002] Currently, there is a growing demand for dietary or nutritional supplements aimed at improving individual health and reducing disease risk; athletes also use dietary or nutritional supplements to improve strength and performance.

[0003] Normally the human body relies on glucose for energy, but when the supply of glucose is insufficient to meet the body's energy needs, such as during prolonged exercise, hunger, or a lack of dietary carbohydrates, the body turns to consuming fat as fuel. Because the brain and central nervous system cannot directly use fat for energy, the liver produces ketone bodies from fatty acids as an alternative fuel, which are then released into the blood / plasma. Ketone bodies not only provide fuel for the brain, but are also used by skeletal and cardiac muscles. The metabolism of ketone bodies is associated with several beneficial effects, including anticonvulsant effects, enhanced brain metabolism, neuroprotection, muscle protection, and improved cognitive and physical performance. Based on the science-based improvement in the efficiency of cellular metabolism, managed through ketone supplementation, it can have beneficial effects on physical, cognitive and mental health, and have long-term effects on health against common avoidable diseases such as obesity, cardiovascular disease, neurodegenerative diseases, diabetes and cancer.

[0004] Despite the many health advantages of pursuing a ketogenic diet or lifestyle and maintaining a state of nutritional ketosis, significant barriers exist to achieving and maintaining ketosis. One of these barriers is the difficulty of transitioning to ketosis. The fastest endogenous pathway to ketosis, through depletion of the body's glucose reserves, is through fasting and exercise. This is physically and emotionally demanding, making it challenging for even the most motivated and disciplined individuals.

[0005] Numerous studies on exogenous ketones have shown that the ingestion of compounds that increase blood ketone body levels can provide various clinical benefits, including enhanced physical and cognitive performance and the treatment of cardiovascular disease, diabetes, neurodegenerative diseases, and epilepsy. Therefore, it is desirable to directly provide ketone bodies to humans or animals as an energy source. Dietary or nutritional supplements may contain carboxylic acids, such as β-hydroxybutyrate (also known as 3-hydroxybutyrate or BHB), which is one of the three major ketone bodies (i.e., acetoacetate, acetone, and BHB).

[0006] However, the existing known ingestible exogenous ketone bodies have disadvantages that limit their use. β-Hydroxybutyrate is a source of exogenous ketones, and its well-known problem is that it is extremely acidic. Due to this acidity, the amount and concentration of β-Hydroxybutyrate used in an ingestible form are limited. The acidity problem of D-BHB acid has been solved in some applications by forming β-Hydroxybutyrate into sodium, magnesium, calcium and potassium salts. However, while salts can solve the acidity problem, the use of ketone salts is also limited to very small amounts due to the accompanying salt overload and the tendency to cause electrolyte imbalance. In addition to small doses, the taste is also unpleasant. The above problems still exist when simply physically mixing the carboxylic acid and the salt, and it is difficult to achieve a uniform mix.

[0007] Therefore, in order to solve the problems of strong acidity and high hygroscopicity of existing acids and high salt load, gastrointestinal side effects, and unpleasant taste of existing salts, it is necessary to further find substances that can effectively avoid or balance the above problems so that they can be better used as ketogenic substances in diets or nutritional supplements, which is particularly beneficial for the process preparation of solid particles and the application of granules.

[0008] Summary of the Invention

[0009] In one aspect, the present invention provides a complex comprising 3-hydroxybutyric acid; and one or more of potassium 3-hydroxybutyrate, calcium 3-hydroxybutyrate, or magnesium 3-hydroxybutyrate.

[0010] In some embodiments, the anions in the structure of the complex include 3-hydroxybutyrate anions; and the cations include one or more of potassium ions, calcium ions, magnesium ions, and hydrogen ions.

[0011] In some embodiments, the ratio of 3-hydroxybutyric acid to one or more of potassium 3-hydroxybutyrate, or calcium 3-hydroxybutyrate, or magnesium 3-hydroxybutyrate is 1:10 to 10:1.

[0012] In some embodiments, the complex comprises no less than 50% of the R configuration and no more than 50% of the S configuration; or more than 50% of the S configuration and less than 50% of the R configuration.

[0013] In some embodiments, the complex is 3-hydroxybutyric acid·potassium 3-hydroxybutyrate or 3-hydroxybutyric acid·calcium 3-hydroxybutyrate or 3-hydroxybutyric acid·magnesium 3-hydroxybutyrate or a mixture thereof.

[0014] In some embodiments, the complex has the following structure:

[0015] or a mixture thereof.

[0016] In one aspect, the present invention provides a 3-hydroxybutyric acid·3-hydroxybutyrate complex, wherein the salt is a potassium salt, a calcium salt and / or a magnesium salt.

[0017] In some embodiments, the complex is R-3-hydroxybutyric acid·R-3-hydroxybutyrate and / or S-3-hydroxybutyric acid·S-3-hydroxybutyrate.

[0018] In some embodiments, the complex comprises not less than 50% R-3-hydroxybutyric acid·R-3-hydroxybutyrate, not more than 50% S-3-hydroxybutyric acid·S-3-hydroxybutyrate, or more than 50% S-3-hydroxybutyric acid·S-3-hydroxybutyrate, and less than 50% R-3-hydroxybutyric acid·R-3-hydroxybutyrate.

[0019] In some embodiments, the complex has the following structure:

[0020] In some embodiments, the complex is in crystalline form.

[0021] In some embodiments, the potassium salt complex has an X-ray powder diffraction pattern comprising peaks at diffraction angles (2θ) of 6.7±0.2°, 19.6±0.2°, 24.9±0.2°, and 27.1±0.2°.

[0022] In some embodiments, the potassium salt complex has an X-ray powder diffraction pattern further comprising one or more peaks at diffraction angles (2θ) of 13.4±0.2°, 21.4±0.2°, 26.0±0.2°, 32.5±0.2°.

[0023] In some embodiments, the potassium salt complex further comprises an X-ray powder diffraction pattern comprising one or more peaks at diffraction angles (2θ) of 20.2±0.2°, 23.4±0.2°, 28.2±0.2°, or 34.0±0.2°.

[0024] In some embodiments, the potassium salt complex has an X-ray powder diffraction pattern as shown in FIG1 .

[0025] In some embodiments, the potassium salt complex has the following absorption bands in the infrared spectrum, expressed as the inverse of the wavelength (cm -1 )(±2cm -1 ): 2972, 2933, 1715, 1574, 1304, 1196, 1126, 1065, 951, 854, 474.

[0026] In some embodiments, the infrared spectrum of the calcium salt complex has the following absorption bands, expressed as the inverse of the wavelength (cm -1 )(±2cm -1): 2974, 2936, 1715, 1558, 1506, 1300, 1196, 1126, 1065, 951, 854, 422.

[0027] In some embodiments, the infrared spectrum of the magnesium salt complex has the following absorption bands, expressed as the inverse of the wavelength (cm -1 )(±2cm -1 ): 2976, 2936, 1713, 1321, 1207, 1088, 957, 912, 826, 625, 554, 411.

[0028] In some embodiments, the complex is prepared as a food, beverage, supplement, or pharmaceutical formulation.

[0029] In another aspect, the present invention provides a 3-hydroxybutyric acid·3-hydroxybutyrate complex, which is obtained by the following method:

[0030] (1) obtaining substance B by one of the following methods: mixing 3-hydroxybutyric acid and a salt of 3-hydroxybutyric acid; or adding 3-hydroxybutyric acid to an aqueous solution of an alkaline compound, stirring and removing water, and evaporating to near dryness; or heating a 3-hydroxybutyric acid alkyl ester with water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness;

[0031] (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance B obtained in step (1), stirring and cooling to precipitate a solid;

[0032] (3) The solid is filtered out and dried to obtain a composite.

[0033] In some embodiments, the complex is R-3-hydroxybutyric acid·R-3-hydroxybutyrate and / or S-3-hydroxybutyric acid·S-3-hydroxybutyrate.

[0034] In some embodiments, the complex is in crystalline form.

[0035] In another aspect, the present invention provides a method for preparing the above-mentioned composite, comprising the following steps:

[0036] (1) obtaining substance B by one of the following methods: mixing 3-hydroxybutyric acid and a salt of 3-hydroxybutyric acid; or adding 3-hydroxybutyric acid to an aqueous solution of an alkaline compound, stirring and removing water, and evaporating to near dryness; or heating a 3-hydroxybutyric acid alkyl ester with water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness;

[0037] (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance B obtained in step (1), stirring and cooling to precipitate a solid;

[0038] (3) The solid is filtered out and dried to obtain a composite.

[0039] In some embodiments, in step (2), the alcohol is methanol, ethanol, isopropanol, or n-butanol; the halogenated hydrocarbon is chlorobenzene, dichlorobenzene, or dichloromethane; the ketone is acetone, methyl butyl ketone, or methyl isobutyl ketone; and the ester is ethyl acetate, isopropyl acetate, n-butyl acetate, or isobutyl acetate.

[0040] In some embodiments, the alkaline compound in step (1) is hydroxide, carbonate, bicarbonate, methoxide, acetate or formate of potassium, calcium or magnesium; the alkyl 3-hydroxybutyrate is methyl 3-hydroxybutyrate, ethyl 3-hydroxybutyrate, propyl 3-hydroxybutyrate, isopropyl 3-hydroxybutyrate, butyl 3-hydroxybutyrate or isobutyl 3-hydroxybutyrate.

[0041] In another aspect, the present invention provides a composition comprising an effective amount of the above-mentioned complex and a pharmaceutically acceptable carrier.

[0042] In some embodiments, the composition is used as a ketogenic substance.

[0043] In some embodiments, the composition is prepared as a food, beverage, supplement, or pharmaceutical formulation.

[0044] In another aspect, the present invention provides use of the complex in preparing a ketogenic substance for increasing or maintaining blood ketone levels in a subject.

[0045] In some embodiments, the ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

[0046] In another aspect, the present invention provides use of a composition for preparing a ketogenic substance for increasing or maintaining blood ketone levels in a subject, wherein the composition comprises the complex of the present invention and a pharmaceutically acceptable carrier.

[0047] In some embodiments, the ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

[0048] In another aspect, the present invention provides a complex of an acid and a salt, wherein the acid includes propionic acid, butyric acid, valeric acid, hexanoic acid, and hydroxycarboxylic acid, and the salt includes sodium salt, potassium salt, calcium salt and / or magnesium salt.

[0049] In some embodiments, the hydroxycarboxylic acid is 3-hydroxyvaleric acid (BHP).

[0050] In some embodiments, the anion in the structure of the complex includes a 3-hydroxyvalerate anion, and the cation includes a sodium ion and a hydrogen ion.

[0051] In some embodiments, the ratio of 3-hydroxyvaleric acid to sodium 3-hydroxyvalerate is 1:10 to 10:1.

[0052] In some embodiments, the complex comprises no less than 50% of the R configuration and no more than 50% of the S configuration; or more than 50% of the S configuration and less than 50% of the R configuration.

[0053] In some embodiments, the complex has the following structure:

[0054] In some embodiments, the complex is in crystalline form.

[0055] In some embodiments, the complex is R-3-hydroxyvaleric acid·sodium R-3-hydroxyvalerate and / or S-3-hydroxyvaleric acid·sodium S-3-hydroxyvalerate.

[0056] In some embodiments, the complex contains not less than 50% R-3-hydroxyvaleric acid·R-3-hydroxyvalerate sodium, not more than 50% S-3-hydroxyvaleric acid·S-3-hydroxyvalerate sodium; or more than 50% S-3-hydroxyvaleric acid·S-3-hydroxyvalerate sodium, less than 50% R-3-hydroxyvaleric acid·R-3-hydroxyvalerate sodium.

[0057] In some embodiments, the complex has the following structure: and / or

[0058] In some embodiments, the infrared spectrum of the composite has the following absorption bands, expressed as the inverse of the wavelength (cm -1 )(±2cm -1 ): 2968, 2880, 1715, 1558, 1404, 1065, 982, 912, 874, 783, 473, 426.

[0059] In some embodiments, the complex is prepared as a food, beverage, supplement, or pharmaceutical formulation.

[0060] In another aspect, the present invention provides a complex of an acid and a salt, which is obtained by the following method:

[0061] (1) obtaining substance C by one of the following methods: mixing an acid and a corresponding salt; or adding an acid to an aqueous solution of a basic compound, stirring and removing water, and evaporating to near dryness; or reacting an alkyl ester of the acid with water by heating in the presence of a catalyst, cooling and filtering, adding an aqueous solution of a basic compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness;

[0062] (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance C obtained in step (1), stirring and cooling to precipitate a solid;

[0063] (3) The solid is filtered out and dried to obtain a composite.

[0064] In some embodiments, the complex is propionic acid·propionic acid sodium salt, propionic acid·propionic acid potassium salt, propionic acid·propionic acid calcium salt, propionic acid·propionic acid magnesium salt, butyric acid·butyric acid sodium salt, butyric acid·butyric acid potassium salt, butyric acid·butyric acid calcium salt, butyric acid·butyric acid magnesium salt, valeric acid·valeric acid sodium salt, valeric acid·valeric acid potassium salt, valeric acid·valeric acid calcium salt, valeric acid·valeric acid magnesium salt, hexanoic acid·hexanoic acid sodium salt, hexanoic acid·hexanoic acid potassium salt, hexanoic acid·hexanoic acid calcium salt, hexanoic acid·hexanoic acid magnesium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid sodium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid potassium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid calcium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid magnesium salt.

[0065] In some embodiments, the complex is in crystalline form.

[0066] In another aspect, the present invention provides a method for preparing the above-mentioned composite, comprising the following steps:

[0067] (1) obtaining substance C by one of the following methods: mixing an acid and a corresponding salt; or adding an acid to an aqueous solution of a basic compound, stirring and removing water, and evaporating to near dryness; or reacting an alkyl ester of the acid with water by heating in the presence of a catalyst, cooling and filtering, adding an aqueous solution of a basic compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness;

[0068] (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance C obtained in step (1), stirring and cooling to precipitate a solid;

[0069] (3) The solid is filtered out and dried to obtain a composite.

[0070] In some embodiments, in step (2), the alcohol is methanol, ethanol, isopropanol, or n-butanol; the halogenated hydrocarbon is chlorobenzene, dichlorobenzene, or dichloromethane; the ketone is acetone, methyl butyl ketone, or methyl isobutyl ketone; and the ester is ethyl acetate, isopropyl acetate, n-butyl acetate, or isobutyl acetate.

[0071] In some embodiments, the basic compound in step (1) is hydroxide, carbonate, bicarbonate, methoxide, acetate or formate of sodium, potassium, calcium or magnesium; the alkyl ester of the acid is methyl, ethyl, propyl, isopropyl, butyl or isobutyl ester of the acid.

[0072] In another aspect, the present invention provides a composition comprising an effective amount of the above-mentioned complex and a pharmaceutically acceptable carrier.

[0073] >In some embodiments, the composition is used as a ketogenic substance.

[0074] In some embodiments, the composition is prepared as a food, beverage, supplement, or pharmaceutical formulation.

[0075] In another aspect, the present invention provides use of the above-mentioned complex in preparing a ketogenic substance for increasing or maintaining the blood ketone level of a subject.

[0076] In some embodiments, the ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

[0077] In another aspect, the present invention provides a use of a composition for preparing a ketogenic substance for increasing or maintaining the blood ketone level of a subject, wherein the composition comprises the above-mentioned complex and a pharmaceutically acceptable carrier.

[0078] In some embodiments, the ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

[0079] Compared to existing technologies, the complex of the present invention offers the following benefits: it is odorless and effectively avoids issues such as acidity, hygroscopicity, salt loading, intestinal side effects, and electrolyte imbalance; and it exhibits superior adaptability compared to other exogenous ketones. When administered to a subject, the complex exhibits a superior overall effect compared to either acid or salt alone, or simply physically mixed components. On one hand, the complex of the present invention addresses the strong acidity, intestinal side effects, and high hygroscopicity of acids, while simultaneously addressing the electrolyte imbalance caused by the high salt loading of salts, and eliminating the uneven mixing associated with physical mixing. Therefore, the complex has broad application prospects as a ketogenic substance in dietary supplements or food products. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] FIG1 is an XRPD pattern of the 3-hydroxybutyric acid·potassium 3-hydroxybutyrate complex (Complex I) of the present invention.

[0081] FIG2A is an infrared spectrum (IR) of the 3-hydroxybutyric acid·potassium 3-hydroxybutyrate complex (Complex I) of the present invention.

[0082] FIG2B is an infrared spectrum (IR) of the 3-hydroxybutyric acid·3-hydroxybutyrate calcium complex (Complex II) of the present invention.

[0083] FIG2C is an infrared spectrum (IR) of the 3-hydroxybutyric acid·3-hydroxybutyrate magnesium complex (Complex III) of the present invention.

[0084] 2D is an infrared spectrum (IR) of the 3-hydroxyvaleric acid·sodium 3-hydroxyvalerate complex (Complex IV) of the present invention.

[0085] FIG3 is a Raman spectrum of the 3-hydroxybutyric acid·potassium 3-hydroxybutyrate complex (complex I) of the present invention.

[0086] FIG4A is a TGA chart of the 3-hydroxybutyric acid·potassium 3-hydroxybutyrate complex (Complex I) of the present invention.

[0087] [Corrected 12.10.2023 according to Rule 91] Figures 4B-1 to 4B-3 are TGA charts of the 3-hydroxybutyric acid and calcium 3-hydroxybutyrate complex (Complex II) of the present invention.

[0088] [Corrected 12.10.2023 according to Rule 91] Figures 4C-1 to 4C-3 are TGA charts of the 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex (Complex III) of the present invention.

[0089] FIG4D is a TGA chart of the 3-hydroxyvaleric acid·sodium 3-hydroxyvalerate complex (Complex IV) of the present invention.

[0090] FIG5 is a DSC spectrum of the 3-hydroxybutyric acid·potassium 3-hydroxybutyrate complex (Complex I) of the present invention. DETAILED DESCRIPTION

[0091] The preferred embodiments of the present invention will now be described in detail with reference to the embodiments thereof. Although the present invention will be described in conjunction with the preferred embodiments, it should be understood that they are not intended to limit the present invention to these embodiments. On the contrary, the present invention is intended to cover substitutions, modifications and equivalents, which may be included within the spirit and scope of the present invention as defined in the claims. In addition, in the detailed description of the present invention, many specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be apparent to one of ordinary skill in the art that the present invention can be practiced without these specific details. In other cases, well-known methods, procedures, components and other features are not described in detail to avoid unnecessarily obscuring various aspects of the present invention.

[0092] The 3-hydroxybutyric acid·3-hydroxybutyrate complex of the present invention comprises 3-hydroxybutyric acid and 3-hydroxybutyrate in any suitable ratio, and the complex can be a hydrate, an anhydrate, and corresponding crystalline forms at a fixed water content ratio. The acid·salt complex of the present invention comprises 3-hydroxyvaleric acid (BHP), propionic acid, butyric acid, valeric acid, and / or hexanoic acid with a sodium salt, potassium salt, calcium salt, and / or magnesium salt in any suitable ratio, and the complex can be a hydrate, an anhydrate, and corresponding crystalline forms at a fixed water content ratio.

[0093] As used herein, the term "or" is intended to include "and" and "or." In other words, the term "or" can also be replaced with "and / or."

[0094] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0095] As used herein, the term "comprises" or "includes" or variations thereof refers to instances where the term is used in its non-limiting sense, meaning that items following the term are included, but items not specifically mentioned are not excluded. It also includes the more restrictive verbs 'consisting essentially of' and 'consisting of.'

[0096] As used herein, the terms "about" and "approximately" provide that a given value may be "slightly above"

[0097] The flexibility of this term can be determined by the specific variable and is within the knowledge of those skilled in the art to determine based on experience and the relevant description herein.

[0098] "β-Hydroxybutyrate," also known as 3-hydroxybutyric acid, βHB, or BHB, refers to a compound with the general formula: CH3CH2OHCH2COOH. "β-Hydroxybutyrate derivatives" refer to compounds with the following chemical structure: wherein X is hydrogen, a metal ion, an amino cation (e.g., an amino acid), or the like.

[0099] When X is hydrogen, the compound is β-hydroxybutyric acid. When X is a metal ion or an amino cation, the compound is β-hydroxybutyrate. The aforementioned compound can be in any desired physical form, such as crystals, powders, solids, liquids, solutions, suspensions, or gels.

[0100] As used herein, the term "administer" refers to the process of delivering a disclosed complex or active ingredient to a subject. The complexes of the present invention can be administered by various suitable means to achieve the desired effect, including oral, intragastric, and parenteral (referring to intravenous and intraarterial and other suitable parenteral routes), etc. The complexes of the present invention can be administered to a subject at a therapeutically effective dose and / or at a frequency to induce or maintain ketosis. In some embodiments, a single dose will include an amount of about 1-50 grams, or about 2-40 grams, or about 5-30 grams, or about 10-20 grams, about 0.5-25 grams, or about 0.75-20 grams, or about 1-15 grams, or about 1.5-12 grams. In some embodiments, multiple doses of the complex are administered over a period of time. The frequency of administration of the complex can vary depending on any of a variety of factors, such as the time since the previous treatment, the purpose of the treatment, etc. The duration of complex administration (e.g., the time period over which the agent is administered) can vary depending on any of a variety of factors, including the subject's response, the desired therapeutic effect, etc.

[0101] As used herein, the term "effective amount" refers to the amount required to achieve the effects taught herein. The amount to be administered can vary depending on factors such as individual sensitivity, individual age, sex, and weight, individual idiosyncrasies, and the like. In accordance with the present disclosure, a suitable single dose size is a dose that, when administered one or more times over an appropriate time period, achieves the effects described above.

[0102] As used herein, the term "pharmaceutically acceptable" refers to pharmaceutically, physiologically, dietary and / or nutritionally acceptable, and refers to those compositions or agents, materials or combinations of compositions and / or dosage forms thereof that are within the scope of sound medical judgment, suitable for contact with the tissues of humans and animals, compatible with the other ingredients of the composition, without excessive toxicity, irritation, allergic response or other problems or complications, and commensurate with a reasonable benefit / risk ratio.

[0103] In some embodiments, the β-hydroxybutyrate can be R-β-hydroxybutyrate, which is endogenously produced by mammals during ketosis, so that administering R-β-hydroxybutyrate to a subject provides additional amounts and / or increased plasma levels that can be immediately used by the body, e.g., for energy production (e.g., as an alternative energy source to glucose).

[0104] The complexes and / or compositions of the present invention can be used to prepare ketogenic substances for increasing or maintaining blood ketone levels in a subject, increasing ketone body levels in a subject, including inducing and / or maintaining elevated ketone body levels (e.g., ketosis) at a desired level in a subject to which it is administered. "Ketosis" refers to a subject's blood ketone level in the range of about 0.5 mmol / L to about 16 mmol / L. Ketosis can improve mitochondrial function, reduce the production of reactive oxygen species, reduce inflammation, and increase the activity of neurotrophic factors. "Keto adaptation" refers to long-term nutritional ketosis (>1 week) to achieve sustained, non-pathological "mild ketosis" or "therapeutic ketosis." In some cases, "elevated ketone body levels" may not mean that the subject is in a state of "clinical ketosis," but still has an elevated ketone supply for producing energy and / or achieving other beneficial effects of ketone bodies.

[0105] Administration of the complexes and / or compositions of the present invention can increase or maintain blood ketone levels in a subject, acting as a ketogenic substance, and produce one or more desired effects, including but not limited to appetite suppression, weight loss, fat loss, lowered blood sugar levels, improved mental alertness, increased physical energy, improved cognitive function, reduced traumatic brain injury, reduced effects of diabetes, improved neurological disorders, reduced cancer, reduced inflammation, anti-aging, anti-glycation, reduced seizures, improved mood, increased strength, increased muscle mass, or improved body composition.

[0106] In some embodiments, the complex of the present invention can be prepared as a composition together with a dietary or pharmaceutically acceptable carrier. In the present invention, the administration form of the composition involves a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be "acceptable" in the sense that it is compatible with the other ingredients of the composition and is harmless to the subject, i.e., suitable for consumption or nutritionally acceptable. The above-mentioned carriers include those non-toxic compatible substances commonly used in health foods and dietary supplements and pharmaceutical preparations, such as sugars, starches, cellulose and its derivatives, powdered tragacanth gum, malt, gelatin, talc, oils, glycols, polyols, esters, agar, alginic acid, pyrogen-free water, isotonic saline, etc.

[0107] In some embodiments, the complexes of the present invention can be administered with other supplements, such as vitamins, minerals, nootropics, and other supplements known in the art. Examples of vitamins, minerals, and herbal supplements that can be added to the ketogenic composition include one or more of vitamin A, vitamin C, vitamin D3, vitamin E, niacin, vitamin B6, folic acid, 5-MTHF, vitamin B12, iodine, zinc, copper, manganese, chromium, caffeine, theobromine, theophylline, methyltaxine, huperzine A, epicatechin, and enzymes.

[0108] In some embodiments, the complexes of the present invention can be provided in solid or powder form. Such solid compositions can be formulated to provide sufficient ease of handling and manufacturability. The complexes can be provided in liquid form, such as an injection or oral spray for rapid delivery and absorption. The liquid form can include one or more liquid carriers, such as water, ethanol, glycerol, propylene glycol, 1,3-propanediol, and the like.

[0109] In some embodiments, the complexes of the present invention can be administered as suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, alcohol, tinctures, tonics, liquid suspensions, or syrups.

[0110] The complexes and / or compositions of the present invention can be prepared into food and beverage products for human consumption, as well as nutritional supplements, energy treatments, medical treatments, or strength and / or endurance sports supplements, as ketogenic substances, thereby providing a dietary source of exogenous ketones to increase or maintain blood ketone levels in a subject. The resulting products can exhibit reduced acidity, lower hygroscopicity, improved taste, better palatability, a uniform appearance, and a well-balanced ketogenic effect, without intestinal side effects, electrolyte imbalance, or high salt load.

[0111] The following examples are illustrative of selected embodiments of the present invention and are not intended to limit the scope of the invention.

[0112] Preparation of the complex of the present invention

[0113] Example 1. Preparation of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate complex (complex I)

[0114] Add 110 g of R-3-hydroxybutyric acid, 110 g of potassium R-3-hydroxybutyrate, and 440 mL of dichloromethane into a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 160 g of R-3-hydroxybutyric acid·potassium R-3-hydroxybutyrate complex.

[0115] Example 2. Preparation of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate complex (complex I)

[0116] Add 104 g of R-3-hydroxybutyric acid, 142 g of potassium R-3-hydroxybutyrate, and 440 mL of acetone to a 1 L reaction flask, heat to 60°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 200 g of R-3-hydroxybutyric acid·potassium R-3-hydroxybutyrate complex.

[0117] Example 3. Preparation of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate complex (complex I)

[0118] Add 200 mL of water and 28 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 104 g of R-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 80 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate potassium complex.

[0119] Example 4. Preparation of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate complex (complex I)

[0120] Add 200 mL of water and 28 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 104 g of R-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 100 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate potassium complex.

[0121] Example 5. Preparation of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate complex (complex I)

[0122] In a 1 L reaction flask, 60 g of methyl R-3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with a 50 mL aqueous solution of 13 g of potassium hydroxide. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 45 g of an R-3-hydroxybutyric acid·potassium R-3-hydroxybutyrate complex.

[0123] Example 6. Preparation of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate complex (complex I)

[0124] 60 g of methyl R-3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added to a 1 L reaction flask. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The filtrate was cooled to room temperature, and the catalyst was filtered off. A 50 mL aqueous solution of 13 g of potassium hydroxide was added to the filtrate. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 55° C. to obtain 52 g of an R-3-hydroxybutyric acid·potassium R-3-hydroxybutyrate complex.

[0125] Example 7. Preparation of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex (Complex I)

[0126] In a 1 L reaction flask, 110 g of 3-hydroxybutyric acid, 110 g of potassium 3-hydroxybutyrate, and 440 mL of dichloromethane were added, heated to 40°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 40°C to obtain 152 g of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex.

[0127] Example 8. Preparation of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex (Complex I)

[0128] In a 1 L reaction flask, 104 g of 3-hydroxybutyric acid, 142 g of potassium 3-hydroxybutyrate, and 440 mL of acetone were added, heated to 60°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 55°C to obtain 170 g of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex.

[0129] Example 9. Preparation of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex (Complex I)

[0130] Add 200 mL of water and 28 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 104 g of 3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 98 g of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex.

[0131] Example 10. Preparation of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex (Complex I)

[0132] Add 200 mL of water and 28 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 104 g of 3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 82 g of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex.

[0133] Example 11. Preparation of 3-Hydroxybutyric Acid and Potassium 3-Hydroxybutyrate Complex (Complex I)

[0134] In a 1L reaction flask, 60 g of methyl 3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-100°C for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with a 50 mL aqueous solution of 13 g of potassium hydroxide. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10°C. The solid precipitated, filtered, and dried at 40°C to obtain 48 g of a 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex.

[0135] Example 12. Preparation of 3-Hydroxybutyric Acid and Potassium 3-Hydroxybutyrate Complex (Complex I)

[0136] In a 1L reaction flask, 60 g of methyl 3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95°C for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with a 50 mL aqueous solution of 13 g of potassium hydroxide. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10°C. The solid precipitated, filtered, and dried at 55°C to obtain 58 g of a 3-hydroxybutyric acid and potassium 3-hydroxybutyrate complex.

[0137] Example 13. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate potassium complex (Complex I)

[0138] Add 110 g of S-3-hydroxybutyric acid, 110 g of potassium S-3-hydroxybutyrate, and 440 mL of dichloromethane to a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 162 g of S-3-hydroxybutyric acid·potassium S-3-hydroxybutyrate complex.

[0139] Example 14. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate potassium complex (Complex I)

[0140] Add 104 g of S-3-hydroxybutyric acid, 142 g of potassium S-3-hydroxybutyrate, and 440 mL of acetone to a 1 L reaction flask, heat to 60°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 186 g of S-3-hydroxybutyric acid·potassium S-3-hydroxybutyrate complex.

[0141] Example 15. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate potassium complex (Complex I)

[0142] Add 200 mL of water and 28 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 104 g of S-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 78 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate potassium complex.

[0143] Example 16. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate potassium complex (Complex I)

[0144] Add 200 mL of water and 28 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 104 g of S-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 90 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate potassium complex.

[0145] Example 17. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate potassium complex (Complex I)

[0146] In a 1 L reaction flask, 60 g of methyl S-3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with a 50 mL aqueous solution of 13 g of potassium hydroxide. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 48 g of a S-3-hydroxybutyric acid·potassium S-3-hydroxybutyrate complex.

[0147] Example 18. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate potassium complex (Complex I)

[0148] In a 1 L reaction flask, 60 g of methyl S-3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with a 50 mL aqueous solution of 13 g of potassium hydroxide. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 55° C. to obtain 55 g of a S-3-hydroxybutyric acid·potassium S-3-hydroxybutyrate complex.

[0149] Example 19. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyrate calcium complex (Complex II)

[0150] Add 100 g of R-3-hydroxybutyric acid, 120 g of R-3-hydroxybutyrate calcium, and 440 mL of dichloromethane to a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 150 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate calcium complex.

[0151] Example 20. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyrate calcium complex (Complex II)

[0152] Add 104 g of R-3-hydroxybutyric acid, 125 g of R-3-hydroxybutyrate calcium, and 480 mL of acetone to a 1 L reaction flask, heat to 60°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 140 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate calcium complex.

[0153] Example 21. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyrate calcium complex (Complex II)

[0154] Add 200 mL of water and 14 g of calcium oxide to a 1 L reaction flask, stir, heat to 55°C, then add 104 g of R-3-hydroxybutyric acid dropwise. After stirring for half an hour, remove water by distillation under reduced pressure. After evaporation to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 65 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate calcium complex.

[0155] Example 22. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyrate calcium complex (Complex II)

[0156] Add 200 mL of water and 14 g of calcium oxide to a 1 L reaction flask, stir, heat to 55°C, add 104 g of R-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 88 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate calcium complex.

[0157] Example 23. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyrate calcium complex (Complex II)

[0158] 60 g of methyl R-3-hydroxybutyrate, 360 mL of water, and 24 g of catalyst were added to a 1 L reaction flask. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The filtrate was cooled to room temperature, and the catalyst was filtered out. 7 g of solid calcium oxide was added to the filtrate. Water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 32 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate calcium complex.

[0159] Example 24. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyrate calcium complex (Complex II)

[0160] 60 g of methyl R-3-hydroxybutyrate, 360 mL of water, and 24 g of catalyst were added to a 1 L reaction flask. The mixture was heated at 90-95° C. for 24 hours until the reaction was complete. The mixture was cooled to room temperature and the catalyst was filtered off. 7 g of solid calcium oxide was added to the filtrate. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added. The mixture was stirred and cooled to 0-10° C. The solid was precipitated, filtered, and dried at 55° C. to obtain 35 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate calcium complex.

[0161] Example 25. Preparation of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate complex (Complex II)

[0162] Add 100 g of 3-hydroxybutyric acid, 120 g of calcium 3-hydroxybutyrate, and 440 mL of dichloromethane to a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 143 g of 3-hydroxybutyric acid·calcium 3-hydroxybutyrate complex.

[0163] Example 26. Preparation of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate complex (Complex II)

[0164] In a 1 L reaction flask, 104 g of 3-hydroxybutyric acid, 125 g of calcium 3-hydroxybutyrate, and 480 mL of acetone were added, heated to 60°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 55°C to obtain 132 g of 3-hydroxybutyric acid·calcium 3-hydroxybutyrate complex.

[0165] Example 27. Preparation of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate complex (Complex II)

[0166] Add 200 mL of water and 14 g of calcium oxide to a 1 L reaction flask, stir, heat to 55 ° C, add 104 g of 3-hydroxybutyric acid dropwise, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10 ° C, precipitate solid, filter, and dry at 40 ° C to obtain 69 g of 3-hydroxybutyric acid·3-hydroxybutyrate calcium complex.

[0167] Example 28. Preparation of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate complex (Complex II)

[0168] Add 200 mL of water and 14 g of calcium oxide to a 1 L reaction flask, stir, heat to 55 ° C, add 104 g of 3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10 ° C, precipitate solid, filter, and dry at 55 ° C to obtain 85 g of 3-hydroxybutyric acid·3-hydroxybutyrate calcium complex.

[0169] Example 29. Preparation of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate complex (Complex II)

[0170] In a 1 L reaction flask, 60 g of methyl 3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95°C for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. 7 g of solid calcium oxide was added to the filtrate. Water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10°C. The solid precipitated, filtered, and dried at 40°C to obtain 37 g of a 3-hydroxybutyric acid-3-hydroxybutyrate calcium complex.

[0171] Example 30. Preparation of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate complex (Complex II)

[0172] In a 1 L reaction flask, 60 g of methyl 3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. 7 g of solid calcium oxide was added to the filtrate. Water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 55° C. to obtain 34 g of a 3-hydroxybutyric acid·R-3-hydroxybutyrate calcium complex.

[0173] Example 31. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate calcium complex (Complex II)

[0174] Add 100 g of S-3-hydroxybutyric acid, 120 g of S-3-hydroxybutyrate calcium, and 440 mL of dichloromethane to a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 148 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate calcium complex.

[0175] Example 32. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate calcium complex (Complex II)

[0176] Add 104 g of S-3-hydroxybutyric acid, 125 g of S-3-hydroxybutyric acid calcium, and 480 mL of acetone to a 1 L reaction flask, heat to 60°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 143 g of S-3-hydroxybutyric acid·S-3-hydroxybutyric acid calcium complex.

[0177] Example 33. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate calcium complex (Complex II)

[0178] Add 200 mL of water and 14 g of calcium oxide to a 1 L reaction flask, stir, heat to 55°C, and then dropwise add 104 g of S-3-hydroxybutyric acid. After stirring for half an hour, remove water by distillation under reduced pressure. After evaporation to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 59 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate calcium complex.

[0179] Example 34. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate calcium complex (Complex II)

[0180] Add 200 mL of water and 14 g of calcium oxide to a 1 L reaction flask, stir, heat to 55°C, add 104 g of S-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 83 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate calcium complex.

[0181] Example 35. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate calcium complex (Complex II)

[0182] In a 1 L reaction flask, 60 g of methyl S-3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. 7 g of solid calcium oxide was added to the filtrate. Water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 30 g of a S-3-hydroxybutyric acid·S-3-hydroxybutyrate calcium complex.

[0183] Example 36. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyrate calcium complex (Complex II)

[0184] 60 g of methyl S-3-hydroxybutyrate, 360 mL of water, and 24 g of catalyst were added to a 1 L reaction flask. The reaction was heated at 90-95°C for 24 hours until the reaction was complete. The filtrate was cooled to room temperature, and the catalyst was filtered out. 7 g of solid calcium oxide was added to the filtrate. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10°C. The solid was precipitated, filtered, and dried at 55°C to obtain 32 g of S-3-hydroxybutyric acid and S-3-hydroxybutyrate calcium complex.

[0185] Example 37. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyric acid magnesium complex (Complex III)

[0186] Add 100 g of R-3-hydroxybutyric acid, 110 g of R-3-hydroxybutyric acid magnesium, and 440 mL of dichloromethane to a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 148 g of R-3-hydroxybutyric acid·R-3-hydroxybutyric acid magnesium complex.

[0187] Example 38. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyric acid magnesium complex (Complex III)

[0188] 104 g of R-3-hydroxybutyric acid, 116 g of magnesium R-3-hydroxybutyrate, and 480 mL of acetone were added to a 1 L reaction flask, heated to 60°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 55°C to obtain 140 g of R-3-hydroxybutyric acid·magnesium R-3-hydroxybutyrate complex.

[0189] Example 39. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyric acid magnesium complex (Complex III)

[0190] Add 200 mL of water and 12 g of magnesium oxide to a 1 L reaction flask, stir, heat to 55°C, add 104 g of R-3-hydroxybutyric acid dropwise, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 62 g of R-3-hydroxybutyric acid·R-3-hydroxybutyrate magnesium complex.

[0191] Example 40. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyric acid magnesium complex (Complex III)

[0192] Add 200 mL of water and 12 g of magnesium oxide to a 1 L reaction flask, stir, heat to 55°C, add 104 g of R-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 82 g of R-3-hydroxybutyric acid·R-3-hydroxybutyric acid magnesium complex.

[0193] Example 41. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyric acid magnesium complex (Complex III)

[0194] 60 g of methyl R-3-hydroxybutyrate, 360 mL of water, and 24 g of catalyst were added to a 1 L reaction flask. The mixture was heated at 90-95° C. for 24 hours until the reaction was complete. The mixture was cooled to room temperature and the catalyst was filtered off. 7 g of solid magnesium oxide was added to the filtrate. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added. The mixture was stirred and cooled to 0-10° C. The solid was precipitated, filtered, and dried at 40° C. to obtain 32 g of R-3-hydroxybutyric acid·R-3-hydroxybutyric acid magnesium complex.

[0195] Example 42. Preparation of R-3-hydroxybutyric acid and R-3-hydroxybutyric acid magnesium complex (Complex III)

[0196] 60 g of methyl R-3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added to a 1 L reaction flask. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The filtrate was cooled to room temperature, and the catalyst was filtered out. 7 g of solid magnesium oxide was added to the filtrate. Water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10° C. The solid was precipitated, filtered, and dried at 55° C. to obtain 35 g of an R-3-hydroxybutyric acid and R-3-hydroxybutyric acid magnesium complex.

[0197] Example 43. Preparation of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex (Complex III)

[0198] Add 100 g of 3-hydroxybutyric acid, 110 g of magnesium 3-hydroxybutyrate, and 440 mL of dichloromethane to a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 145 g of 3-hydroxybutyric acid·magnesium 3-hydroxybutyrate complex.

[0199] Example 44. Preparation of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex (Complex III)

[0200] In a 1 L reaction flask, 104 g of 3-hydroxybutyric acid, 116 g of magnesium 3-hydroxybutyrate, and 480 mL of acetone were added, heated to 60°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 55°C to obtain 148 g of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex.

[0201] Example 45. Preparation of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex (Complex III)

[0202] Add 200 mL of water and 12 g of magnesium oxide to a 1 L reaction flask, stir, heat to 55 ° C, add 104 g of 3-hydroxybutyric acid dropwise, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10 ° C, precipitate solid, filter, and dry at 40 ° C to obtain 67 g of 3-hydroxybutyric acid·3-hydroxybutyrate magnesium complex.

[0203] Example 46. Preparation of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex (Complex III)

[0204] Add 200 mL of water and 12 g of magnesium oxide to a 1 L reaction flask, stir, heat to 55°C, add 104 g of 3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 76 g of 3-hydroxybutyric acid·3-hydroxybutyrate magnesium complex.

[0205] Example 47. Preparation of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex (Complex III)

[0206] In a 1L reaction flask, 60 g of methyl 3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95°C for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. 7 g of solid magnesium oxide was added to the filtrate. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10°C. The solid was precipitated, filtered, and dried at 40°C to obtain 35 g of a 3-hydroxybutyric acid-3-hydroxybutyrate magnesium complex.

[0207] Example 48. Preparation of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate complex (Complex III)

[0208] 60 g of methyl 3-hydroxybutyrate, 360 mL of water, and 24 g of catalyst were added to a 1 L reaction flask. The mixture was heated at 90-95° C. for 24 hours until the reaction was complete. The mixture was cooled to room temperature and the catalyst was filtered off. 7 g of solid magnesium oxide was added to the filtrate. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added. The mixture was stirred and cooled to 0-10° C. The solid was precipitated, filtered, and dried at 55° C. to obtain 36 g of 3-hydroxybutyric acid and 3-hydroxybutyrate magnesium complex.

[0209] Example 49. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyric acid magnesium complex (Complex III)

[0210] Add 100 g of S-3-hydroxybutyric acid, 110 g of S-3-hydroxybutyric acid magnesium, and 440 mL of dichloromethane to a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 145 g of S-3-hydroxybutyric acid·S-3-hydroxybutyric acid magnesium complex.

[0211] Example 50. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyric acid magnesium complex (Complex III)

[0212] 104 g of S-3-hydroxybutyric acid, 116 g of magnesium S-3-hydroxybutyrate, and 480 mL of acetone were added to a 1 L reaction flask, heated to 60°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 55°C to obtain 138 g of S-3-hydroxybutyric acid and magnesium S-3-hydroxybutyrate complex.

[0213] Example 51. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyric acid magnesium complex (Complex III)

[0214] Add 200 mL of water and 12 g of magnesium oxide to a 1 L reaction flask, stir, heat to 55 ° C, add 104 g of S-3-hydroxybutyric acid dropwise, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10 ° C, precipitate solid, filter, and dry at 40 ° C to obtain 58 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate magnesium complex.

[0215] Example 52. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyric acid magnesium complex (Complex III)

[0216] Add 200 mL of water and 12 g of magnesium oxide to a 1 L reaction flask, stir, heat to 55°C, add 104 g of S-3-hydroxybutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 83 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate magnesium complex.

[0217] Example 53. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyric acid magnesium complex (Complex III)

[0218] In a 1 L reaction flask, 60 g of methyl S-3-hydroxybutyrate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. 7 g of solid magnesium oxide was added to the filtrate. Water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 34 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate magnesium complex.

[0219] Example 54. Preparation of S-3-hydroxybutyric acid and S-3-hydroxybutyric acid magnesium complex (Complex III)

[0220] 60 g of methyl S-3-hydroxybutyrate, 360 mL of water, and 24 g of catalyst were added to a 1 L reaction flask. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The filtrate was cooled to room temperature, and the catalyst was filtered out. 7 g of solid magnesium oxide was added to the filtrate. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10° C. The solid was precipitated, filtered, and dried at 55° C. to obtain 36 g of S-3-hydroxybutyric acid·S-3-hydroxybutyrate magnesium complex.

[0221] Example 55. Preparation of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex (Complex IV)

[0222] Add 118 g of R-3-hydroxyvaleric acid, 140 g of sodium R-3-hydroxyvalerate, and 450 mL of dichloromethane into a 1 L reaction flask, heat to 40°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 148 g of R-3-hydroxyvaleric acid·sodium R-3-hydroxyvalerate complex.

[0223] Example 56. Preparation of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex (Complex IV)

[0224] Add 118 g of 3-hydroxyvaleric acid, 140 g of sodium 3-hydroxyvalerate, and 480 mL of acetone to a 1 L reaction flask, heat to 60°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 140 g of R-3-hydroxyvaleric acid·Sodium 3-hydroxyvalerate complex.

[0225] Example 57. Preparation of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex (Complex IV)

[0226] Add 200 mL of water and 20 g of sodium hydroxide into a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 120 g of R-3-hydroxyvaleric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 75 g of R-3-hydroxyvaleric acid·R-3-hydroxyvalerate sodium complex.

[0227] Example 58. Preparation of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex (Complex IV)

[0228] Add 200 mL of water and 20 g of sodium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 120 g of R-3-hydroxyvaleric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 98 g of R-3-hydroxyvaleric acid·R-3-hydroxyvalerate sodium complex.

[0229] Example 59. Preparation of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex (Complex IV)

[0230] In a 1 L reaction flask, 65 g of methyl R-3-hydroxyvalerate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with 9 g of sodium hydroxide in 50 mL of an aqueous solution. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 40 g of an R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex.

[0231] Example 60. Preparation of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex (Complex IV)

[0232] In a 1 L reaction flask, 65 g of methyl R-3-hydroxyvalerate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with a 50 mL aqueous solution of 9 g of sodium hydroxide. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 55° C. to obtain 50 g of an R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate complex.

[0233] Example 61. Preparation of 3-Hydroxyvaleric Acid and Sodium 3-Hydroxyvalerate Complex (Complex IV)

[0234] In a 1 L reaction flask, 118 g of 3-hydroxyvaleric acid, 140 g of sodium 3-hydroxyvalerate, and 450 mL of dichloromethane were added, heated to 40°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 40°C to obtain 139 g of 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate complex.

[0235] Example 62. Preparation of 3-Hydroxyvaleric Acid and Sodium 3-Hydroxyvalerate Complex (Complex IV)

[0236] In a 1 L reaction flask, 118 g of 3-hydroxyvaleric acid, 140 g of sodium 3-hydroxyvalerate, and 480 mL of acetone were added, heated to 60°C, stirred to dissolve, cooled to 0-10°C, the solid precipitated, filtered, and dried at 55°C to obtain 124 g of 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate complex.

[0237] Example 63. Preparation of 3-Hydroxyvaleric Acid and Sodium 3-Hydroxyvalerate Complex (Complex IV)

[0238] Add 200 mL of water and 20 g of sodium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 120 g of 3-hydroxyvaleric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 72 g of 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate complex.

[0239] Example 64. Preparation of 3-Hydroxyvaleric Acid and Sodium 3-Hydroxyvalerate Complex (Complex IV)

[0240] Add 200 mL of water and 20 g of sodium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 120 g of 3-hydroxyvaleric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 68 g of 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate complex.

[0241] Example 65. Preparation of 3-Hydroxyvaleric Acid and Sodium 3-Hydroxyvalerate Complex (Complex IV)

[0242] In a 1 L reaction flask, 65 g of methyl 3-hydroxyvalerate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with 9 g of sodium hydroxide in 50 mL of an aqueous solution. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 45 g of a 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate complex.

[0243] Example 66. Preparation of 3-Hydroxyvaleric Acid and Sodium 3-Hydroxyvalerate Complex (Complex IV)

[0244] In a 1L reaction flask, 65 g of methyl 3-hydroxyvalerate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95°C for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with 9 g of sodium hydroxide in 50 mL of an aqueous solution. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10°C. The solid precipitated, filtered, and dried at 55°C to obtain 46 g of a 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate complex.

[0245] Example 67. Preparation of S-3-hydroxyvaleric acid and S-3-hydroxyvalerate sodium complex (Complex IV)

[0246] In a 1 L reaction flask, add 118 g of S-3-hydroxyvaleric acid, 140 g of sodium S-3-hydroxyvalerate, and 450 mL of dichloromethane. Heat to 40°C, stir to dissolve, and cool to 0-10°C to precipitate a solid. Filter and dry at 40°C to obtain 147 g of a complex of S-3-hydroxyvaleric acid and sodium S-3-hydroxyvalerate.

[0247] Example 68. Preparation of S-3-hydroxyvaleric acid and S-3-hydroxyvalerate sodium complex (Complex IV)

[0248] In a 1 L reaction flask, add 118 g of S-3-hydroxyvaleric acid, 140 g of sodium S-3-hydroxyvalerate, and 480 mL of acetone, heat to 60°C, stir to dissolve, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 138 g of S-3-hydroxyvaleric acid·sodium S-3-hydroxyvalerate complex.

[0249] Example 69. Preparation of S-3-hydroxyvaleric acid and S-3-hydroxyvalerate sodium complex (Complex IV)

[0250] Add 200 mL of water and 20 g of sodium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 120 g of S-3-hydroxyvaleric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 40°C to obtain 68 g of S-3-hydroxyvaleric acid·S-3-hydroxyvalerate sodium complex.

[0251] Example 70. Preparation of S-3-hydroxyvaleric acid and S-3-hydroxyvalerate sodium complex (Complex IV)

[0252] Add 200 mL of water and 20 g of sodium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 120 g of S-3-hydroxyvaleric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 200 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 92 g of S-3-hydroxyvaleric acid·S-3-hydroxyvalerate sodium complex.

[0253] Example 71. Preparation of S-3-hydroxyvaleric acid and S-3-hydroxyvalerate sodium complex (Complex IV)

[0254] In a 1 L reaction flask, 65 g of methyl S-3-hydroxyvalerate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95° C. for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with 9 g of sodium hydroxide in 50 mL of an aqueous solution. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of dichloromethane was added, stirred, and cooled to 0-10° C. The solid precipitated, filtered, and dried at 40° C. to obtain 41 g of a complex of S-3-hydroxyvaleric acid and sodium S-3-hydroxyvalerate.

[0255] Example 72. Preparation of S-3-hydroxyvaleric acid and S-3-hydroxyvalerate sodium complex (Complex IV)

[0256] In a 1L reaction flask, 65 g of methyl S-3-hydroxyvalerate, 360 mL of water, and 24 g of a catalyst were added. The reaction was heated at 90-95°C for 24 hours until the reaction was complete. The reaction was cooled to room temperature, and the catalyst was filtered off. The filtrate was added with 9 g of sodium hydroxide in 50 mL of an aqueous solution. The water was removed by distillation under reduced pressure. After evaporation to near dryness, 100 mL of acetone was added, stirred, and cooled to 0-10°C. The solid precipitated, filtered, and dried at 55°C to obtain 48 g of a complex of S-3-hydroxyvaleric acid and sodium S-3-hydroxyvalerate.

[0257] The acid·sodium salt complex, acid·potassium salt complex, acid·calcium salt complex and acid·magnesium salt complex of the present invention are prepared by the same method as that of complexes I-IV.

[0258] Characterization of the complex of the present invention

[0259] The composites prepared in the examples were subjected to tests such as X-ray diffraction (XRD), elemental analysis, Raman spectroscopy (Raman), infrared spectroscopy (IR), TGA, DSC, and DVS.

[0260] Example 73. X-ray diffraction

[0261] X-ray powder diffraction patterns were obtained using a SmartLab 3KW X-ray powder diffractometer under the following conditions: diffraction line: Cu_K-beta (40 kV, 40 mA), scan rate: 20.00 deg / min, scan range: 3° to 60°. The XRPD pattern of the 3-hydroxybutyric acid / potassium 3-hydroxybutyrate complex (Complex I) obtained in Example 1 is shown in Figure 1, and the XRPD data obtained in Example 1 are shown in Table 1.

[0262] Table 1

[0263] The XRPD results of the complexes prepared in Examples 2-6 were basically consistent with those in Example 1.

[0264] Example 74. Infrared spectroscopy

[0265] The composite I of Example 1 was analyzed by infrared spectroscopy using a Shimadzu Fourier transform attenuated total reflection infrared spectrometer. FIG2A is an infrared spectrum (IR) diagram of the composite I of Example 1. As can be seen from FIG2A , the composite I has a peak at 2972 ​​cm -1 、2933cm -1 、1715cm -1 、1574cm -1 、1304cm -1 、1196cm -1 、1126cm -1 、1065cm -1 、951cm -1 、854cm -1 、474cm -1 The IR results of the complexes prepared in Examples 2-18 are basically consistent with those in Example 1. The complex II of Example 19 was subjected to infrared spectroscopy analysis. FIG2B is an infrared spectrum (IR) diagram of the complex II of Example 19. It can be seen from FIG2B that the complex II has a characteristic absorption peak at 2974 cm -1 、2936cm -1 、1715cm -1 、1558cm - 1 、1506cm -1 , 1300cm -1 、1196cm -1 、1126cm -1 、1065cm -1 、951cm -1 、854cm -1 422cm -1 The IR results of the complexes prepared in Examples 20-36 are basically consistent with those in Example 19. The complex III of Example 37 was subjected to infrared spectroscopy analysis. FIG2C is an infrared spectrum (IR) diagram of the complex III of Example 37. It can be seen from FIG2C that the complex III has a characteristic absorption peak at 2976 cm -1 、2936cm - 1 、1713cm -1 、1321cm -1 、1207cm -1 、1088cm -1 、957cm -1 、912cm -1 、826cm -1 、625cm -1 、554cm -1、411cm -1 The IR results of the complexes prepared in Examples 38-54 are basically consistent with those in Example 37. The complex IV of Example 55 was subjected to infrared spectroscopy analysis. FIG2D is an infrared spectrum (IR) diagram of the complex IV of Example 55. It can be seen from FIG2D that the complex IV has a characteristic absorption peak at 2968 cm -1 、2880cm -1 、1715cm -1 、1558cm -1 、1404cm -1 、1065cm -1 , 982cm - 1 、912cm -1 、874cm -1 、783cm -1 、473cm -1 、426cm -1 There is a characteristic absorption peak at; the IR results of the complexes prepared in Examples 56-72 are basically consistent with those in Example 55.

[0266] Example 75. NMR ( 1 H / 13 C) Determination

[0267] The complex I of Example 1 was recorded in an AVIII-HD-400 spectrometer. 1 H NMR and 13 C NMR spectrum: 1 H NMR (400MHz, DMSO-d6) δ7.61 (s, 1H), 3.89 (dt, J = 7.1, 5.9Hz, 1H), 2.20–2.06 (m, 2H), 1.04 (d, J = 6.2Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 175.58, 64.24, 45.69, 23.80. NMR of the complex I prepared in Example 2-18 ( 1 H / 13 C) The results are basically consistent with those in Example 1. 1 H NMR spectrum: 1 H NMR (400 MHz, D2O) δ 4.06 (h, J = 6.4 Hz, 1H), 2.32 (d, J = 6.6 Hz, 2H), 1.09 (d, J = 6.3 Hz, 3H). 1 H) The results are basically consistent with those in Example 19.1 H NMR spectrum: 1 H NMR (400 MHz, DMSO-d6) δ 3.68–3.53 (m, 1H), 2.17 (dd, J = 14.8, 4.3 Hz, 1H), 2.03 (dd, J = 14.8, 8.5 Hz, 1H), 1.40–1.26 (m, 2H), 0.84 (t, J = 7.4 Hz, 3H). 1 H) The results are basically consistent with those in Example 55.

[0268] Example 76. Determination of Metal Ion Content and BHB / BHP Content

[0269] The potassium content of the complex I of Examples 1, 7, and 13, the calcium content of the complex II of Examples 19, 25, and 31, and the magnesium content of the complex III of Examples 37, 43, and 49 were measured, and the 3-hydroxybutyric acid content of each complex was determined by HPLC. The test results were consistent with the structure of the complex, and the specific data are shown in Table 2-1 below. The potassium content and 3-hydroxybutyric acid content of the complex I prepared in Examples 2-6, 8-12, and 14-18 were consistent with those of Examples 1, 7, and 13, respectively; the calcium content and 3-hydroxybutyric acid content of the complex II prepared in Examples 20-24, 26-30, and 32-36 were consistent with those of Examples 19, 25, and 31, respectively; and the magnesium content and 3-hydroxybutyric acid content of the complex III prepared in Examples 38-42, 44-48, and 50-54 were consistent with those of Examples 37, 43, and 49, respectively. The sodium content of Complex IV of Examples 55, 61, and 67 was measured, and the 3-hydroxyvaleric acid content of the complex was determined by HPLC. The test results were consistent with the structure of the complex, as shown in Table 2-2 below. The sodium content and 3-hydroxyvaleric acid content of Complex IV prepared in Examples 56-60, 62-66, and 68-72 were consistent with those of Examples 55, 61, and 67, respectively.

[0270] Table 2-1

[0271] Table 2-2

[0272] Example 77. Elemental Analysis

[0273] Elemental analysis of Complex I from Example 1 revealed C 39.1% and H 6.1%. The elemental analysis results for Examples 2-18 were also consistent with those of Example 1, consistent with the structure of a 3-hydroxybutyric acid·potassium 3-hydroxybutyrate complex. Elemental analysis of Complex II from Example 19 revealed C 42.2% and H 6.6%. The elemental analysis results for Examples 20-36 were also consistent with those of Example 19, consistent with the structure of a 3-hydroxybutyric acid·calcium 3-hydroxybutyrate complex. Elemental analysis of Complex III from Example 37 revealed C 43.8% and H 6.9%. The elemental analysis results for Examples 38-54 were also consistent with those of Example 37, consistent with the structure of a 3-hydroxybutyric acid·magnesium 3-hydroxybutyrate complex. Elemental analysis of Complex IV from Example 55 revealed C 46.5% and H 7.3%. The elemental analysis results for Examples 56-72 were also consistent with those of Example 55, consistent with the structure of a 3-hydroxyvaleric acid·sodium 3-hydroxyvaleric acid complex.

[0274] Example 78. Raman spectroscopy

[0275] The characteristic Raman spectrum of the complex can be obtained by Raman spectroscopy analysis. FIG3 is the Raman spectrum of the complex I of Example 1. The Raman spectrum of the complex I of Example 1 is at 3358.49 cm -1 、2974.54cm -1 、2962.49cm -1 、2922.50cm -1 、2888.89cm -1 、2712.38cm -1 、1451.91cm -1 、1312.00cm -1 、1067.72cm -1 、912.01cm -1 、856.19cm -1 、752.02cm -1 There are characteristic absorption peaks at ±2cm - 1 The Raman spectra of the composites prepared in Examples 2-18 were basically consistent with those in Example 1.

[0276] Example 79 Thermogravimetric Analysis (TGA)

[0277] Figure 4A is a TGA chart of Complex I of Example 1, which exhibited a 61.51% weight loss when heated from 30°C to 299°C. The TGA results of the complexes prepared in Examples 2-18 were substantially consistent with those of Example 1. Figure 4B-1 is a TGA chart of Complex II of Example 19, which exhibited a 2.18% weight loss when heated from 23.5°C to 100.0°C. The TGA results of the complexes prepared in Examples 20-24 were substantially consistent with those of Example 19. Figure 4B-2 is a TGA chart of Complex II of Example 25, which exhibited a 1.22% weight loss when heated from 26.8°C to 100.0°C. The TGA results of the complexes prepared in Examples 26-30 were substantially consistent with those of Example 25. Figure 4B-3 is a TGA chart of Complex II of Example 31. This complex exhibited a weight loss of 1.47% when heated from 27.2°C to 100.0°C. The TGA results of the complexes prepared in Examples 32-36 were substantially consistent with those of Example 31. Figure 4C-1 is a TGA chart of Complex III of Example 37. This complex exhibited a weight loss of 2.47% when heated from 26.2°C to 100.0°C. The TGA results of the complexes prepared in Examples 38-42 were substantially consistent with those of Example 37. Figure 4C-2 is a TGA chart of Complex III of Example 43. This complex exhibited a weight loss of 2.78% when heated from 26.9°C to 100.0°C. The TGA results of the complexes prepared in Examples 44-48 were substantially consistent with those of Example 43. Figure 4C-3 is a TGA chart of Complex III of Example 49, which exhibited a 3.59% weight loss when heated from 26.6°C to 100.0°C. The TGA results of the complexes prepared in Examples 50-54 were substantially consistent with those of Example 49. Figure 4D is a TGA chart of Complex IV of Example 55, which exhibited a 2.74% weight loss when heated from 24.2°C to 120.0°C. The TGA results of the complexes prepared in Examples 56-72 were substantially consistent with those of Example 55.

[0278] Example 80. Differential Scanning Calorimetry (DSC)

[0279] FIG5 is a DSC spectrum of the complex I of Example 1, which includes an endothermic peak at 251.24° C.±3° C. The DSC spectrum results of the complexes prepared in Examples 2-18 are basically consistent with those of Example 1.

[0280] Determination of properties of the complex of the present invention

[0281] Example 81. Determination of moisture content of the composite of the present invention

[0282] R-3-hydroxybutyric acid, potassium R-3-hydroxybutyrate, a mixture of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate, and the R-3-hydroxybutyric acid / potassium R-3-hydroxybutyrate complex of Example 1 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3A-1.

[0283] Table 3A-1

[0284] 3-hydroxybutyric acid, potassium 3-hydroxybutyrate, a mixture of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate, and the 3-hydroxybutyric acid / potassium 3-hydroxybutyrate complex of Example 7 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3A-2.

[0285] Table 3A-2

[0286] S-3-hydroxybutyric acid, potassium S-3-hydroxybutyrate, a mixture of S-3-hydroxybutyric acid and potassium S-3-hydroxybutyrate, and the S-3-hydroxybutyric acid / potassium S-3-hydroxybutyrate complex of Example 13 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3A-3.

[0287] Table 3A-3

[0288] R-3-hydroxybutyric acid, calcium R-3-hydroxybutyrate, a mixture of R-3-hydroxybutyric acid and calcium R-3-hydroxybutyrate, and the R-3-hydroxybutyric acid / calcium R-3-hydroxybutyrate complex of Example 19 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3B-1.

[0289] Table 3B-1

[0290] 3-hydroxybutyric acid, calcium 3-hydroxybutyrate, a mixture of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate, and the 3-hydroxybutyric acid / calcium 3-hydroxybutyrate complex of Example 25 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3B-2.

[0291] Table 3B-2

[0292] S-3-hydroxybutyric acid, calcium S-3-hydroxybutyrate, a mixture of S-3-hydroxybutyric acid and calcium S-3-hydroxybutyrate, and the S-3-hydroxybutyric acid / calcium S-3-hydroxybutyrate complex of Example 31 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3B-3.

[0293] Table 3B-3

[0294] R-3-hydroxybutyric acid, magnesium R-3-hydroxybutyrate, a mixture of R-3-hydroxybutyric acid and magnesium R-3-hydroxybutyrate, and the R-3-hydroxybutyric acid / magnesium R-3-hydroxybutyrate complex of Example 37 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3C-1.

[0295] Table 3C-1

[0296] 3-hydroxybutyric acid, magnesium 3-hydroxybutyrate, a mixture of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate, and the 3-hydroxybutyric acid / magnesium 3-hydroxybutyrate complex of Example 43 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3C-2.

[0297] Table 3C-2

[0298] S-3-hydroxybutyric acid, magnesium S-3-hydroxybutyrate, a mixture of S-3-hydroxybutyric acid and magnesium S-3-hydroxybutyrate, and the S-3-hydroxybutyric acid / magnesium S-3-hydroxybutyrate complex of Example 49 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3C-3.

[0299] Table 3C-3

[0300] R-3-hydroxyvaleric acid, sodium R-3-hydroxyvalerate, a mixture of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate, and the R-3-hydroxyvaleric acid / sodium R-3-hydroxyvalerate complex of Example 55 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3D-1.

[0301] Table 3D-1

[0302] 3-Hydroxyvaleric acid, sodium 3-hydroxyvalerate, a mixture of 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate, and the 3-hydroxyvaleric acid / sodium 3-hydroxyvalerate complex of Example 61 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3D-2.

[0303] Table 3D-2

[0304] S-3-hydroxyvaleric acid, sodium S-3-hydroxyvalerate, a mixture of S-3-hydroxyvaleric acid and sodium S-3-hydroxyvalerate, and the S-3-hydroxyvaleric acid / sodium S-3-hydroxyvalerate complex of Example 67 were tested for moisture content at different times using a KF moisture meter under certain sample placement conditions. The experimental results are shown in Table 3D-3.

[0305] Table 3D-3

[0306] The above results show that the moisture content of the present complexes I-IV is significantly lower than that of the corresponding acids, salts, and acid-salt mixtures, which can expand the application scenarios of the complex products. Because acid solids are highly hygroscopic and easily deliquesce, they are not well suited for use in solid formulations, which greatly limits their application in solid nutritional products and dietary supplements. However, the water absorption properties of the present complexes I-IV are significantly better than those of the corresponding acids, salts, and acid-salt mixtures. Furthermore, simple acid-salt mixtures are prone to uneven mixing, which broadens the application range of the complexes and makes them particularly suitable for the preparation and use of solid formulations.

[0307] Example 82. Stability of the complex of the present invention

[0308] The stability of R-3-hydroxybutyric acid, potassium R-3-hydroxybutyrate, a mixture of R-3-hydroxybutyric acid and potassium R-3-hydroxybutyrate, and the R-3-hydroxybutyric acid / potassium R-3-hydroxybutyrate complex of Example 1 was measured at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C. The experimental results are shown in Table 4A-1.

[0309] Table 4A-1

[0310] The stability of 3-hydroxybutyric acid, potassium 3-hydroxybutyrate, a mixture of 3-hydroxybutyric acid and potassium 3-hydroxybutyrate, and the 3-hydroxybutyric acid / potassium 3-hydroxybutyrate complex of Example 7 at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C was measured. The experimental results are shown in Table 4A-2.

[0311] Table 4A-2

[0312] The stability of S-3-hydroxybutyric acid, potassium S-3-hydroxybutyrate, a mixture of S-3-hydroxybutyric acid and potassium S-3-hydroxybutyrate, and the S-3-hydroxybutyric acid·potassium S-3-hydroxybutyrate complex of Example 13 at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C was measured. The experimental results are shown in Table 4A-3.

[0313] Table 4A-3

[0314] The stability of R-3-hydroxybutyric acid, R-3-hydroxybutyric acid calcium, a mixture of R-3-hydroxybutyric acid and R-3-hydroxybutyric acid calcium, and the R-3-hydroxybutyric acid·R-3-hydroxybutyric acid calcium complex of Example 19 was measured at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C. The experimental results are shown in Table 4B-1.

[0315] Table 4B-1

[0316] The stability of 3-hydroxybutyric acid, calcium 3-hydroxybutyrate, a mixture of 3-hydroxybutyric acid and calcium 3-hydroxybutyrate, and the 3-hydroxybutyric acid / calcium 3-hydroxybutyrate complex of Example 25 at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C was measured. The experimental results are shown in Table 4B-2.

[0317] Table 4B-2

[0318] The stability of S-3-hydroxybutyric acid, calcium S-3-hydroxybutyrate, a mixture of S-3-hydroxybutyric acid and calcium S-3-hydroxybutyrate, and the S-3-hydroxybutyric acid·calcium S-3-hydroxybutyrate complex of Example 31 was measured at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C. The experimental results are shown in Table 4B-3.

[0319] Table 4B-3

[0320] The stability of R-3-hydroxybutyric acid, magnesium R-3-hydroxybutyrate, a mixture of R-3-hydroxybutyric acid and magnesium R-3-hydroxybutyrate, and the R-3-hydroxybutyric acid·magnesium R-3-hydroxybutyrate complex of Example 37 at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C was measured. The experimental results are shown in Table 4C-1.

[0321] Table 4C-1

[0322] The stability of 3-hydroxybutyric acid, magnesium 3-hydroxybutyrate, a mixture of 3-hydroxybutyric acid and magnesium 3-hydroxybutyrate, and the 3-hydroxybutyric acid-magnesium 3-hydroxybutyrate complex of Example 43 at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C was measured. The experimental results are shown in Table 4C-2.

[0323] Table 4C-2

[0324] The stability of S-3-hydroxybutyric acid, magnesium S-3-hydroxybutyrate, a mixture of S-3-hydroxybutyric acid and magnesium S-3-hydroxybutyrate, and the S-3-hydroxybutyric acid·magnesium S-3-hydroxybutyrate complex of Example 49 was measured at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C. The experimental results are shown in Table 4C-3.

[0325] Table 4C-3

[0326] The stability of R-3-hydroxyvaleric acid, sodium R-3-hydroxyvalerate, a mixture of R-3-hydroxyvaleric acid and sodium R-3-hydroxyvalerate, and the R-3-hydroxyvaleric acid·sodium R-3-hydroxyvalerate complex of Example 55 were tested at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C. The experimental results are shown in Table 4D-1.

[0327] Table 4D-1

[0328] The stability of 3-hydroxyvaleric acid, sodium 3-hydroxyvalerate, a mixture of 3-hydroxyvaleric acid and sodium 3-hydroxyvalerate, and the 3-hydroxyvaleric acid·sodium 3-hydroxyvalerate complex of Example 61 was tested at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C. The experimental results are shown in Table 4D-2.

[0329] Table 4D-2

[0330] The stability of S-3-hydroxyvaleric acid, sodium S-3-hydroxyvalerate, a mixture of S-3-hydroxyvaleric acid and sodium S-3-hydroxyvalerate, and the S-3-hydroxyvaleric acid·sodium S-3-hydroxyvalerate complex of Example 67 were tested at temperatures of 30°C, 40°C, 60°C, 70°C, and 80°C. The experimental results are shown in Table 4D-3.

[0331] Table 4D-3

[0332] The above results show that the stability of the complex I-IV of the present invention is very high, significantly better than that of the corresponding acid and the mixture of acid and salt.

[0333] This invention addresses the issues of strong acidity, intestinal side effects, high hygroscopicity, and poor stability associated with BHB and BHP acids. It also addresses the electrolyte imbalance caused by the high salt load of BHB and BHP salts. The complex exhibits a superior overall effect compared to individual acids or salts, or simply physically mixed components, and possesses suitable hygroscopicity and stability, making it particularly suitable for the preparation of solid dosage forms. At appropriate dosages, the complex exhibits a strong ketogenic effect. Furthermore, the complex produced by this invention exhibits high purity, uniform particle size distribution, good fluidity, low agglomeration, and good bioavailability. The preparation process is controllable, cost-effective, and environmentally friendly.

[0334] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any person skilled in the art may make various changes, modifications, substitutions and variations to these embodiments without departing from the principles and purpose of the present invention. The scope of the present invention is defined by the claims and their equivalents.

Claims

1. A composite, characterized in that The complex comprises 3-hydroxybutyric acid; and one or more of potassium 3-hydroxybutyrate, calcium 3-hydroxybutyrate, or magnesium 3-hydroxybutyrate.

2. The composite according to claim 1, characterized in that The anions in the structure of the complex include 3-hydroxybutyrate anions; the cations include one or more of potassium ions, calcium ions, magnesium ions, and hydrogen ions.

3. The composite according to claim 1 or 2, characterized in that The ratio of the 3-hydroxybutyric acid to one or more of potassium 3-hydroxybutyrate, calcium 3-hydroxybutyrate, or magnesium 3-hydroxybutyrate is 1:10 to 10:

1.

4. The composite according to any one of claims 1 to 3, characterized in that The complex contains not less than 50% of the R configuration and not more than 50% of the S configuration; or more than 50% of the S configuration and less than 50% of the R configuration.

5. The composite according to any one of claims 1 to 4, characterized in that The complex is 3-hydroxybutyric acid·potassium 3-hydroxybutyrate or 3-hydroxybutyric acid·calcium 3-hydroxybutyrate or 3-hydroxybutyric acid·magnesium 3-hydroxybutyrate or a mixture thereof.

6. The composite according to any one of claims 1 to 5, characterized in that The complex has the following structure: or a mixture thereof.

7. 3-Hydroxybutyric acid·3-hydroxybutyrate complex, characterized in that The salt is a potassium salt, a calcium salt and / or a magnesium salt.

8. The composite according to any one of claims 1 to 7, characterized in that The complex is R-3-hydroxybutyric acid·R-3-hydroxybutyrate and / or S-3-hydroxybutyric acid·S-3-hydroxybutyrate.

9. The composite according to any one of claims 1 to 7, characterized in that The complex contains not less than 50% of R-3-hydroxybutyric acid·R-3-hydroxybutyrate and not more than 50% of S-3-hydroxybutyric acid·S-3-hydroxybutyrate, or more than 50% of S-3-hydroxybutyric acid·S-3-hydroxybutyrate and less than 50% of R-3-hydroxybutyric acid·R-3-hydroxybutyrate.

10. The composite according to claim 8 or 9, characterized in that The complex has the following structure:

11. The composite according to any one of claims 1 to 10, characterized in that The complex is in crystalline form.

12. The composite according to any one of claims 1 to 11, characterized in that The X-ray powder diffraction pattern of the potassium salt complex includes peaks at diffraction angles (2θ) of 6.7±0.2°, 19.6±0.2°, 24.9±0.2°, and 27.1±0.2°.

13. The composite according to claim 12, characterized in that The X-ray powder diffraction pattern of the potassium salt complex further includes one or more peaks located at diffraction angles (2θ) of 13.4±0.2°, 21.4±0.2°, 26.0±0.2°, and 32.5±0.2°.

14. The composite according to claim 12 or 13, characterized in that The X-ray powder diffraction pattern of the potassium salt complex further includes one or more peaks located at diffraction angles (2θ) of 20.2±0.2°, 23.4±0.2°, 28.2±0.2°, and 34.0±0.2°.

15. The composite according to any one of claims 1 to 14, characterized in that The X-ray powder diffraction pattern of the potassium salt complex is shown in FIG1 .

16. The composite according to any one of claims 1 to 15, characterized in that The infrared spectrum of the potassium salt complex has the following absorption bands, expressed as the reciprocal of the wavelength (cm -1 )(±2cm -1 ): 2972, 2933, 1715, 1574, 1304, 1196, 1126, 1065, 951, 854.

17. The composite according to any one of claims 1 to 11, characterized in that The infrared spectrum of the calcium salt complex has the following absorption bands, expressed as the inverse of the wavelength (cm -1 )(±2cm -1 ): 2974, 2936, 1715, 1558, 1506, 1300, 1196, 1126, 1065, 951, 854.

18. The composite according to any one of claims 1 to 11, characterized in that The infrared spectrum of the magnesium salt complex has the following absorption bands, expressed as the reciprocal of the wavelength (cm -1 )(±2cm -1 ): 2976, 2936, 1713, 1321, 1207, 1088, 957, 912, 826.

19. The composite according to any one of claims 1 to 18, characterized in that The complex is prepared as a food, a beverage, a supplement or a pharmaceutical preparation.

20. A 3-hydroxybutyric acid / 3-hydroxybutyrate complex, characterized in that: The complex is obtained by the following method: (1) obtaining substance B by one of the following methods: mixing 3-hydroxybutyric acid and a salt of 3-hydroxybutyric acid; or adding 3-hydroxybutyric acid to an aqueous solution of an alkaline compound, stirring and removing water, and evaporating to near dryness; or heating a 3-hydroxybutyric acid alkyl ester with water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness; (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance B obtained in step (1), stirring and cooling to precipitate a solid; (3) filtering out the solid and drying it to obtain the composite.

21. The composite according to claim 20, characterized in that The complex is R-3-hydroxybutyric acid·R-3-hydroxybutyrate and / or S-3-hydroxybutyric acid·S-3-hydroxybutyrate.

22. The composite according to claim 20 or 21, characterized in that The complex is in crystalline form.

23. A method for preparing the composite according to any one of claims 1 to 11, characterized in that: The method comprises the following steps: (1) obtaining substance B by one of the following methods: mixing 3-hydroxybutyric acid and a salt of 3-hydroxybutyric acid; or adding 3-hydroxybutyric acid to an aqueous solution of an alkaline compound, stirring and removing water, and evaporating to near dryness; or heating a 3-hydroxybutyric acid alkyl ester with water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness; (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance B obtained in step (1), stirring and cooling to precipitate a solid; (3) filtering out the solid and drying it to obtain the composite.

24. The method according to claim 23, wherein In step (2), the alcohols are methanol, ethanol, isopropanol, and n-butanol; the halogenated hydrocarbons are chlorobenzene, dichlorobenzene, and dichloromethane; the ketones are acetone, methyl butyl ketone, and methyl isobutyl ketone; and the esters are ethyl acetate, isopropyl acetate, n-butyl acetate, and isobutyl acetate.

25. The method according to claim 23 or 24, characterized in that The alkaline compound in step (1) is a hydroxide, carbonate, bicarbonate, methoxide, acetate or formate of potassium, calcium or magnesium; the alkyl 3-hydroxybutyrate is methyl 3-hydroxybutyrate, ethyl 3-hydroxybutyrate, propyl 3-hydroxybutyrate, isopropyl 3-hydroxybutyrate, butyl 3-hydroxybutyrate or isobutyl 3-hydroxybutyrate.

26. A composition, characterized in that The composition comprises an effective amount of the complex according to any one of claims 1 to 22, and a pharmaceutically acceptable carrier.

27. The composition according to claim 26, characterized in that The composition is used as a ketogenic substance.

28. The composition according to claim 26 or 27, characterized in that The composition is prepared as food, beverage, supplement or pharmaceutical preparation.

29. Use of the complex according to any one of claims 1 to 22, characterized in that Use of the complex in preparing a ketogenic substance for increasing or maintaining the blood ketone level of a subject.

30. The use according to claim 29, characterized in that The ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

31. Use of a composition for preparing a ketogenic substance for increasing or maintaining blood ketone levels in a subject, characterized in that: The composition comprises the complex according to any one of claims 1 to 22, and a pharmaceutically acceptable carrier.

32. The use according to claim 31, characterized in that The ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

33. A complex of an acid and a salt, characterized in that: The acids include propionic acid, butyric acid, valeric acid, hexanoic acid, and hydroxycarboxylic acids, and the salts include sodium salts, potassium salts, calcium salts, and / or magnesium salts.

34. The composite according to claim 33, characterized in that The hydroxycarboxylic acid is 3-hydroxyvaleric acid (BHP).

35. The composite according to claim 33 or 34, characterized in that The anions in the structure of the complex include 3-hydroxyvaleric acid anions, and the cations include sodium ions and hydrogen ions.

36. The composite according to claim 35, characterized in that The ratio of 3-hydroxyvaleric acid to sodium 3-hydroxyvalerate is 1:10 to 10:

1.

37. The composite according to any one of claims 33 to 36, characterized in that The complex contains not less than 50% of the R configuration and not more than 50% of the S configuration; or more than 50% of the S configuration and less than 50% of the R configuration.

38. The complex according to any one of claims 33 to 37, characterized in that The complex has the following structure:

39. The composite according to any one of claims 33 to 38, characterized in that The complex is in crystalline form.

40. The complex according to any one of claims 33 to 39, characterized in that The complex is R-3-hydroxyvaleric acid·R-3-hydroxyvaleric acid sodium and / or S-3-hydroxyvaleric acid·S-3-hydroxyvaleric acid sodium.

41. The composite according to any one of claims 33 to 40, characterized in that The complex contains not less than 50% of R-3-hydroxyvaleric acid·R-3-hydroxyvalerate sodium and not more than 50% of S-3-hydroxyvaleric acid·S-3-hydroxyvalerate sodium; or more than 50% of S-3-hydroxyvaleric acid·S-3-hydroxyvalerate sodium and less than 50% of R-3-hydroxyvaleric acid·R-3-hydroxyvalerate sodium.

42. The composite according to claim 40 or 41, characterized in that The complex has the following structure:

43. The composite according to any one of claims 33 to 42, characterized in that The infrared spectrum of the composite has the following absorption bands, expressed as the reciprocal of the wavelength (cm -1 )(±2cm -1 ): 2968, 2880, 1715, 1558, 1404, 1065, 982, 912, 874, 783,.

44. The complex according to any one of claims 33 to 43, characterized in that The complex is prepared as a food, a beverage, a supplement or a pharmaceutical preparation.

45. A complex of an acid and a salt, characterized in that: The complex is obtained by the following method: (1) obtaining substance C by one of the following methods: mixing an acid and a corresponding salt; or adding an acid to an aqueous solution of a basic compound, stirring and removing water, and evaporating to near dryness; or reacting an alkyl ester of the acid with water by heating in the presence of a catalyst, cooling and filtering, adding an aqueous solution of a basic compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness; (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance C obtained in step (1), stirring and cooling to precipitate a solid; (3) filtering out the solid and drying it to obtain the composite.

46. ​​The composite according to claim 45, characterized in that The complex is propionic acid·propionic acid sodium salt, propionic acid·propionic acid potassium salt, propionic acid·propionic acid calcium salt, propionic acid·propionic acid magnesium salt, butyric acid·butyric acid sodium salt, butyric acid·butyric acid potassium salt, butyric acid·butyric acid calcium salt, butyric acid·butyric acid magnesium salt, valeric acid·valeric acid sodium salt, valeric acid·valeric acid potassium salt, valeric acid·valeric acid calcium salt, valeric acid·valeric acid magnesium salt, hexanoic acid·hexanoic acid sodium salt, hexanoic acid·hexanoic acid potassium salt, hexanoic acid·hexanoic acid calcium salt, hexanoic acid·hexanoic acid magnesium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid sodium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid potassium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid calcium salt, 3-hydroxyvaleric acid·3-hydroxyvaleric acid magnesium salt.

47. The complex according to claim 45 or 46, characterized in that The complex is in crystalline form.

48. A method for preparing the composite of claim 33, characterized in that: The method comprises the following steps: (1) obtaining substance C by one of the following methods: mixing an acid and a corresponding salt; or adding an acid to an aqueous solution of a basic compound, stirring and removing water, and evaporating to near dryness; or reacting an alkyl ester of the acid with water by heating in the presence of a catalyst, cooling and filtering, adding an aqueous solution of a basic compound to the filtrate, removing water by distillation under reduced pressure, and evaporating to near dryness; (2) adding one or more solvents selected from the group consisting of water, THF, DMF, DMSO, DMAC, alcohols, halogenated hydrocarbons, ketones, and esters to the substance C obtained in step (1), stirring and cooling to precipitate a solid; (3) filtering out the solid and drying it to obtain the composite.

49. The method according to claim 48, characterized in that In step (2), the alcohols are methanol, ethanol, isopropanol, and n-butanol; the halogenated hydrocarbons are chlorobenzene, dichlorobenzene, and dichloromethane; the ketones are acetone, methyl butyl ketone, and methyl isobutyl ketone; and the esters are ethyl acetate, isopropyl acetate, n-butyl acetate, and isobutyl acetate.

50. The method according to claim 48 or 49, characterized in that The alkaline compound in step (1) is a hydroxide, carbonate, bicarbonate, methoxide, acetate or formate of sodium, potassium, calcium or magnesium; the alkyl ester of the acid is a methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester or isobutyl ester of the acid.

51. A composition, characterized in that The composition comprises an effective amount of the complex according to any one of claims 33 to 47, and a pharmaceutically acceptable carrier.

52. The composition according to claim 51, characterized in that The composition is used as a ketogenic substance.

53. The composition according to claim 51 or 52, characterized in that The composition is prepared as food, beverage, supplement or pharmaceutical preparation.

54. Use of the complex according to any one of claims 33 to 47, characterized in that Use of the complex in preparing a ketogenic substance for increasing or maintaining the blood ketone level of a subject.

55. The use according to claim 54, characterized in that The ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

56. Use of a composition in preparing a ketogenic substance for increasing or maintaining blood ketone levels in a subject, characterized in that: The composition comprises the complex according to any one of claims 33 to 47, and a pharmaceutically acceptable carrier.

57. The use according to claim 56, characterized in that The ketogenic substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

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