Complex of 3-hydroxy-3-methylbutyric acid and salt thereof and preparation method thereof

Abstract

The invention discloses a compound of 3-hydroxy-3-methylbutyric acid and salts thereof and a preparation method of the compound. The compound provided by the invention effectively solves the problems of low solubility, poor stability, acid / salt load, excessive intake of calcium and gastrointestinal side effects accompanied by the existing product, has good taste comfort, improves flavor, has better effects of increasing muscle weight, improving muscle performance, joint functions and body components or enhancing health and the like, and can be used as a health-care food. And the product can be better used as a dietary or nutritional supplement.

Description

Complex of 3-hydroxy-3-methylbutyric acid and its salt and preparation method thereof Technical Field

[0001] The present invention belongs to the technical field of dietary or nutritional supplements, and particularly relates to a complex of 3-hydroxy-3-methylbutyric acid and its salt and a preparation method thereof. Background Art

[0002] There is a growing demand for dietary or nutritional supplements to improve an individual's health and reduce the risk of disease.

[0003] Numerous studies on 3-hydroxy-3-methylbutyrate (HMB) have shown that HMB intake can improve muscle performance: increasing muscle strength, promoting muscle recovery, reducing muscle atrophy, minimizing muscle damage, maintaining myoglobin levels, improving muscle aerobic capacity, reducing or preventing the loss of contractile substances in muscle, and increasing the amount of hemoglobin in the blood. It also improves body composition: reducing body fat, increasing fat-free mass, increasing or maintaining lean body mass, and increasing lean tissue development or lean body mass; it also enhances or promotes lipolysis, reduces fat loss, increases fat oxidation in adipocytes, induces mitochondrial biogenesis in adipocytes and muscles, increases energy expenditure, and reduces total body weight. It also improves joint function and health: increasing joint stability and reducing joint stiffness. It also promotes or improves the recovery and healing of soft tissue injuries, improving and enhancing health in many ways.

[0004] Intake of HMB can also improve the perception of emotional states, enhance or improve cognitive ability or function. Reduce insulin resistance and improve glucose tolerance. Prevent or alleviate diarrhea or intestinal inflammatory conditions, chronic inflammatory diseases and accidental weight loss. Regulate autophagy and lipophagy; treat, prevent, inhibit, slow down or reduce autophagy-mediated conditions or diseases, including cardiovascular disease, type II diabetes, neurodegenerative diseases, metabolic syndrome, liver disease, reduced metabolic rate, muscle disease, osteoarthritis, sarcopenia, cancer, obesity and insulin resistance; treat, inhibit, reduce or slow down age-related diseases in mammals, including obesity, sarcopenia and / or sarcopenic obesity. Inhibit or alleviate depression, asthma, allergies and cancer. Promote nitrogen retention and improve protein nutrition. Reduce or eliminate microbial contamination in animal feed.

[0005] Commercially, HMB is available only in the form of a free acid or calcium salt. Calcium salts are primarily used for supplements and health foods, particularly in powdered form due to their ease of handling. However, existing products have drawbacks that limit their use. In the pharmaceutical field, calcium from calcium salts easily combines with other ingredients such as phosphoric acid to form insoluble salts, making it difficult to prepare high-concentration solutions. Reports indicate that excessive calcium intake increases the risk of death from cardiovascular disease and ischemic heart disease. HMB in its free acid form has these drawbacks.

[0006] Compared to existing HMB free acid or calcium salt products, the eutectic complex of the present invention effectively avoids or balances the aforementioned issues, enabling better inclusion or use as a dietary or nutritional supplement. The HMB acid-salt eutectic complex of the present invention effectively increases HMB utilization and accelerates its absorption. It also exhibits high solubility, avoids forming insoluble salts, and avoids inducing electrolyte abnormalities, offering numerous advantages. Furthermore, the HMB acid-salt eutectic complex of the present invention exhibits excellent palatability and flavor enhancement.

[0007] Summary of the Invention

[0008] In one aspect, the present invention provides a 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate complex and a composition thereof, wherein the salt is a sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt, or amino acid salt.

[0009] In some embodiments, the complex is in solid form.

[0010] In some embodiments, the complex is in crystalline form.

[0011] In some embodiments, the sodium salt complex has the following structure:

[0012] In some embodiments, the sodium salt complex has an X-ray powder diffraction pattern comprising peaks at diffraction angles (2θ) of 8.8±0.2°, 18.1±0.2°, 24.3±0.2°, and 35.6±0.2°.

[0013] In some embodiments, the sodium salt complex further comprises an X-ray powder diffraction pattern comprising one or more peaks at diffraction angles (2θ) of 7.9±0.2°, 19.0±0.2°, or 28.6±0.2°.

[0014] In some embodiments, the sodium salt complex further comprises an X-ray powder diffraction pattern comprising one or more peaks at diffraction angles (2θ) of 17.6±0.2°, 21.4±0.2°, or 36.7±0.2°.

[0015] In some embodiments, the sodium salt complex has an X-ray powder diffraction pattern as shown in FIG1 .

[0016] In some embodiments, the potassium salt complex has the following structure:

[0017] In some embodiments, the potassium salt complex has an X-ray powder diffraction pattern comprising peaks at diffraction angles (2θ) of 15.9±0.2°, 18.3±0.2°, 20.6±0.2°, and 34.7±0.2°.

[0018] 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 10.6±0.2°, 17.9±0.2°, or 22.6±0.2°.

[0019] 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 11.9±0.2°, 18.5±0.2°, or 30.7±0.2°.

[0020] In some embodiments, the potassium salt complex has an X-ray powder diffraction pattern as shown in FIG2 .

[0021] In some embodiments, the calcium salt complex has the following structure:

[0022] In some embodiments, the calcium salt complex has an X-ray powder diffraction pattern comprising peaks at diffraction angles (2θ) of 9.0±0.2°, 18.8±0.2°, 26.4±0.2°, and 30.3±0.2°.

[0023] In some embodiments, the X-ray powder diffraction pattern of the calcium salt complex further comprises one or more peaks at diffraction angles (2θ) of 8.1±0.2°, 13.1±0.2°, 20.4±0.2°.

[0024] In some embodiments, the X-ray powder diffraction pattern of the calcium salt complex further comprises one or more peaks at diffraction angles (2θ) of 16.5±0.2°, 25.4±0.2°, 34.2±0.2°.

[0025] In some embodiments, the X-ray powder diffraction pattern of the calcium salt complex is shown in FIG3 .

[0026] In some embodiments, the magnesium salt complex has the following structure:

[0027] In some embodiments, the magnesium salt complex has an X-ray powder diffraction pattern comprising peaks at diffraction angles (2θ) of 8.9±0.2°, 16.5±0.2°, 25.3±0.2°, and 37.4±0.2°.

[0028] In some embodiments, the magnesium salt complex has an X-ray powder diffraction pattern further comprising one or more peaks at diffraction angles (2θ) of 9.4±0.2°, 18.8±0.2°, and 30.2±0.2°.

[0029] In some embodiments, the magnesium salt complex has an X-ray powder diffraction pattern further comprising one or more peaks at diffraction angles (2θ) of 13.0±0.2°, 20.3±0.2°, or 34.1±0.2°.

[0030] In some embodiments, the X-ray powder diffraction pattern of the magnesium salt complex is shown in FIG4 .

[0031] In some embodiments, the complex is prepared as a food, beverage, supplement, nutraceutical, or pharmaceutical formulation.

[0032] In another aspect, the present invention provides a 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate complex, which is obtained by the following method:

[0033] (1) obtaining substance B by one of the following methods: mixing 3-hydroxy-3-methylbutyric acid and 3-hydroxy-3-methylbutyric acid salt; or adding 3-hydroxy-3-methylbutyric acid to an aqueous solution of an alkaline compound, stirring and removing water; or heating alkyl 3-hydroxy-3-methylbutyrate and water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, and removing water by distillation under reduced pressure;

[0034] (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;

[0035] (3) The solid is filtered out and dried to obtain a composite.

[0036] In some embodiments, the complex is in crystalline form.

[0037] In another aspect, the present invention provides a method for preparing the above-mentioned composite, comprising the following steps:

[0038] (1) obtaining substance B by one of the following methods: mixing 3-hydroxy-3-methylbutyric acid and 3-hydroxy-3-methylbutyric acid salt; or adding 3-hydroxy-3-methylbutyric acid to an aqueous solution of an alkaline compound, stirring and removing water; or heating alkyl 3-hydroxy-3-methylbutyrate and water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, and removing water by distillation under reduced pressure;

[0039] (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;

[0040] (3) The solid is filtered out and dried to obtain a composite.

[0041] 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.

[0042] In some embodiments, the alkaline compound in step (1) is a hydroxide, carbonate, bicarbonate, methoxide, acetate or formate of sodium, potassium, calcium or magnesium, aqueous ammonia, triethylamine, N,N-diisopropylethylamine; and the alkyl 3-hydroxy-3-methylbutyrate is methyl 3-hydroxy-3-methylbutyrate, ethyl 3-hydroxy-3-methylbutyrate, propyl 3-hydroxy-3-methylbutyrate, isopropyl 3-hydroxy-3-methylbutyrate, butyl 3-hydroxy-3-methylbutyrate or isobutyl 3-hydroxy-3-methylbutyrate.

[0043] In another aspect, the present invention provides a composition comprising an effective amount of the above-mentioned complex and a pharmaceutically acceptable carrier.

[0044] In some embodiments, the composition is used as a substance to improve muscle performance, joint function, body composition, or enhance health.

[0045] In some embodiments, the composition is prepared as a food, beverage, supplement, nutraceutical, or pharmaceutical formulation.

[0046] In another aspect, the present invention provides the use of the complex in the preparation of a substance for improving muscle performance, joint function, body composition or enhancing health.

[0047] In some embodiments, the 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 use of a composition for preparing a substance for improving muscle performance, joint function, body composition or enhancing health, wherein the composition comprises the complex of the present invention and a pharmaceutically acceptable carrier.

[0049] In some embodiments, the substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

[0050] Compared to existing technologies, the complexes of the present invention offer the following advantages: they effectively avoid the instability associated with HMB acid and the calcium and metal ion excesses associated with HMB calcium salts or other metal salts. When administered to a subject, the complexes exhibit superior overall efficacy compared to individual acids or salts, or simply physically mixed components. On one hand, the complexes of the present invention address the instability and poor handling characteristics of acids, while also addressing the electrolyte imbalances caused by the high salt load of HMB calcium salts or other metal salts. Furthermore, they avoid the uneven mixing associated with physical mixing, thus promising broad application prospects in dietary supplements and food products. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] FIG1 is an XRPD pattern of the 3-hydroxy-3-methylbutyric acid·sodium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0052] FIG2 is an XRPD pattern of the 3-hydroxy-3-methylbutyric acid·potassium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0053] FIG3 is an XRPD pattern of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate calcium complex of the present invention.

[0054] FIG4 is an XRPD pattern of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid magnesium complex of the present invention.

[0055] FIG5 is an IR graph of the 3-hydroxy-3-methylbutyric acid·sodium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0056] FIG6 is an IR spectrum of the 3-hydroxy-3-methylbutyric acid·potassium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0057] FIG7 is an IR spectrum of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate calcium complex of the present invention.

[0058] FIG8 is an IR spectrum of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid magnesium complex of the present invention.

[0059] FIG9 is a TGA chart of the 3-hydroxy-3-methylbutyric acid·sodium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0060] FIG10 is a TGA chart of the 3-hydroxy-3-methylbutyric acid·potassium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0061] FIG11 is a TGA chart of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate calcium complex of the present invention.

[0062] FIG12 is a TGA chart of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid magnesium complex of the present invention.

[0063] FIG13 is a Raman spectrum analysis diagram of the 3-hydroxy-3-methylbutyric acid·sodium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0064] FIG14 is a Raman spectrum analysis diagram of the 3-hydroxy-3-methylbutyric acid·potassium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0065] FIG15 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0066] FIG16 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid·potassium 3-hydroxy-3-methylbutyrate complex of the present invention.

[0067] FIG17 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate calcium complex of the present invention.

[0068] FIG18 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid magnesium complex of the present invention.

[0069] FIG19 is a graph showing the muscle weight of experimental mice at 7 weeks. DETAILED DESCRIPTION

[0070] 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.

[0071] The 3-hydroxy-3-methylbutyric acid / 3-hydroxy-3-methylbutyrate complex of the present invention comprises 3-hydroxy-3-methylbutyric acid and 3-hydroxy-3-methylbutyrate in any suitable ratio, and the complex may be a hydrate, an anhydrate, or a corresponding crystalline form with a fixed water content ratio. 3-Hydroxy-3-methylbutyrate may be a sodium salt, potassium salt, ammonium salt, amino acid salt, calcium salt, and / or magnesium salt, or other suitable salt. The amino acid salt is preferably a basic amino acid salt, particularly an arginine salt, a lysine salt, a histidine salt, or an ornithine salt.

[0072] 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."

[0073] 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.

[0074] 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.'

[0075] As used herein, the terms "about" and "approximately" provide flexibility in numerical values ​​by providing that a given value may be "slightly higher" or "less than" an endpoint. The flexibility of this term can be determined by the specific variables and is within the knowledge of those skilled in the art to determine based on experience and the relevant description herein.

[0076] 3-Hydroxy-3-methylbutyric acid, also known as β-hydroxy-β-methylbutyric acid, β-hydroxyisovaleric acid, 3-hydroxyisovaleric acid or HMB, has the general formula C5H 10 O3. HMB is a metabolite of the essential amino acid leucine. It is a beneficial compound that can reduce muscle damage during exercise, increase muscle mass and strength, improve recovery from muscle damage, improve the balance between muscle synthesis and breakdown, maintain muscle mass and strength, reduce body fat, tighten muscles, and increase basal metabolism. "3-Hydroxy-3-methylbutyric acid derivatives" refer to compounds with the following chemical structure: where X is hydrogen, a metal ion, ammonium, an amino cation (e.g., an amino acid), etc.

[0077] When X is hydrogen, the compound is 3-hydroxy-3-methylbutanoic acid. When X is a metal ion or an amino cation, the compound is 3-hydroxy-3-methylbutyrate. The aforementioned compound can be in any desired physical form, such as crystals, powders, solids, liquids, solutions, suspensions, or gels.

[0078] As used herein, the term "administer" refers to the process of delivering the disclosed complex or active ingredient to a subject. The complex 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 complex of the present invention can be administered to the subject in a therapeutically effective dose and / or at an effective frequency. In some embodiments, a single dose will include an amount of about 0.1-30 grams, about 0.2-25 grams, about 0.5-20 grams, about 1-10 grams, or about 2-6 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.

[0079] 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.

[0080] 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.

[0081] 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.

[0082] 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.

[0083] 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.

[0084] 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.

[0085] The complexes and / or compositions of the present invention can be formulated 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 substances for increasing muscle mass and reducing weight, as well as improving muscle performance, joint function, body composition, or enhancing health. The resulting products can exhibit a balanced combination of reduced acidity, lower hygroscopicity, improved flavor, better palatability, a uniform appearance, excellent stability, and a good solubility effect, without the problems of intestinal side effects, electrolyte imbalance, or high salt load.

[0086] The following examples are illustrative of selected embodiments of the invention and are not intended to limit the scope thereof.

[0087] Preparation of the complex of the present invention

[0088] Example 1. Preparation of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex

[0089] In a 1 L reaction flask, add 118 g of 3-hydroxy-3-methylbutyric acid, 140 g of sodium 3-hydroxy-3-methylbutyrate, and 500 mL of dichloromethane. Heat to 40°C, stir to dissolve, and cool to 0-10°C to precipitate a solid. Filter and dry at 55°C to obtain 180 g of a 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex.

[0090] Example 2. Preparation of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex

[0091] In a 1 L reaction flask, add 118 g of 3-hydroxy-3-methylbutyric acid, 140 g of sodium 3-hydroxy-3-methylbutyrate, and 500 mL of acetone. Heat to 60°C, stir to dissolve, and cool to 0-10°C to precipitate a solid. Filter and dry at 55°C to obtain 150 g of a 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex.

[0092] Example 3. Preparation of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex

[0093] Add 400 mL of water and 34 g of sodium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 200 g of 3-hydroxy-3-methylbutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 400 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 150 g of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex.

[0094] Example 4. Preparation of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex

[0095] Add 400 mL of water and 34 g of sodium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 200 g of 3-hydroxy-3-methylbutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 400 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 110 g of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex.

[0096] Example 5. Preparation of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex

[0097] In a 1 L reaction flask, 132 g of methyl 3-hydroxy-3-methylbutyrate, 360 mL of water, and 12 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 20 g of a 50 mL aqueous solution of sodium 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 55° C. to obtain 90 g of a 3-hydroxy-3-methylbutyric acid sodium 3-hydroxy-3-methylbutyrate complex.

[0098] Example 6. Preparation of 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex

[0099] In a 1 L reaction flask, 132 g of methyl 3-hydroxy-3-methylbutyrate, 360 mL of water, and 12 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 20 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 80 g of a 3-hydroxy-3-methylbutyric acid sodium 3-hydroxy-3-methylbutyrate complex.

[0100] Example 7. Preparation of 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex

[0101] In a 1 L reaction flask, add 118 g of 3-hydroxy-3-methylbutyric acid, 156 g of potassium 3-hydroxy-3-methylbutyrate, and 500 mL of dichloromethane. Heat to 40°C, stir to dissolve, and cool to 0-10°C to precipitate a solid. Filter and dry at 55°C to obtain 180 g of a 3-hydroxy-3-methylbutyric acid·potassium 3-hydroxy-3-methylbutyrate complex.

[0102] Example 8. Preparation of 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex

[0103] In a 1 L reaction flask, add 118 g of 3-hydroxy-3-methylbutyric acid, 156 g of potassium 3-hydroxy-3-methylbutyrate, and 500 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 150 g of 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex.

[0104] Example 9. Preparation of 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex

[0105] Add 400 mL of water and 112 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 200 g of 3-hydroxy-3-methylbutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 400 mL of dichloromethane, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 150 g of 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate potassium complex.

[0106] Example 10. Preparation of 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex

[0107] Add 400 mL of water and 112 g of potassium hydroxide to a 1 L reaction flask, stir and dissolve, cool to below 25°C, add 200 g of 3-hydroxy-3-methylbutyric acid, stir for half an hour, remove water by distillation under reduced pressure, evaporate to near dryness, add 400 mL of acetone, stir, cool to 0-10°C, precipitate solid, filter, and dry at 55°C to obtain 110 g of 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate potassium complex.

[0108] Example 11. Preparation of 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex

[0109] In a 1 L reaction flask, 132 g of methyl 3-hydroxy-3-methylbutyrate, 360 mL of water, and 12 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 33 g of potassium 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 55° C. to obtain 90 g of a 3-hydroxy-3-methylbutyric acid potassium 3-hydroxy-3-methylbutyrate complex.

[0110] Example 12. Preparation of 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex

[0111] In a 1 L reaction flask, 132 g of methyl 3-hydroxy-3-methylbutyrate, 360 mL of water, and 12 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 33 g of potassium 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 80 g of a 3-hydroxy-3-methylbutyric acid potassium 3-hydroxy-3-methylbutyrate complex.

[0112] The 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid calcium complex, the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid magnesium complex and other 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate salt complexes of the present invention are prepared by the same or similar method as the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid sodium complex and the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid potassium complex.

[0113] Characterization of the complex of the present invention

[0114] 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, NMR, IPC-MS, DSC, and DVS.

[0115] Example 13. X-ray diffraction

[0116] The X-ray powder diffraction pattern was obtained using a SmartLab 3KW X-ray powder diffractometer under the following conditions: diffraction line: Cu_K-beta (40KV, 40mA), scanning rate: 20.00deg / min, scanning range: 5°~40°.

[0117] The XRPD pattern of the 3-hydroxy-3-methylbutyric acid·sodium 3-hydroxy-3-methylbutyrate complex obtained in Example 1 is shown in FIG1 , and the XRPD data obtained in Example 1 are shown in Table 1.

[0118] Table 1

[0119] The XRPD results of the complexes prepared in Examples 2-6 were basically consistent with those in Example 1.

[0120] The XRPD pattern of the 3-hydroxy-3-methylbutyric acid·potassium 3-hydroxy-3-methylbutyrate complex obtained in Example 7 is shown in FIG2 , and the XRPD data obtained in Example 7 are shown in Table 2.

[0121] Table 2

[0122] The XRPD results of the complexes prepared in Examples 8-12 were basically consistent with those in Example 7.

[0123] The XRPD pattern of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate calcium complex of the present invention is shown in FIG3 , and the XRPD data are shown in Table 3.

[0124] Table 3

[0125] The XRPD pattern of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid magnesium complex of the present invention is shown in FIG4 , and the XRPD data are shown in Table 4.

[0126] Table 4

[0127] Example 14. Infrared Spectroscopy (IR)

[0128] The composite of Example 1 was analyzed by infrared spectroscopy using a Fourier transform attenuated total reflection infrared spectrometer. FIG5 is an infrared spectrum (IR) diagram of the composite of Example 1. It can be seen from FIG5 that the composite has a wavelength of 3449 cm -1 、2972cm -1 、2942cm -1 、2920cm-1 、1713cm -1 、1577cm -1 、1507cm -1 、1459cm -1 、1438cm -1 、1401cm -1 、1372cm -1 、1286cm -1 、1255cm -1 , 1220cm -1 、1152cm -1 , 987cm -1 、913cm -1 、891cm -1 , 860cm -1 、782cm -1 、705cm -1 、619cm - 1 、529cm -1 、502cm -1 、462cm -1 、413cm -1 The IR results of the composites prepared in Examples 2-6 are basically consistent with those in Example 1.

[0129] The composite of Example 7 was analyzed by infrared spectroscopy using a Fourier transform attenuated total reflection infrared spectrometer. FIG6 is an infrared spectrum (IR) diagram of the composite of Example 7. It can be seen from FIG6 that the composite has a wavelength of 3449 cm -1 、2985cm -1 、2973cm -1 、2943cm -1 、2920cm -1 、1717cm -1 、1577cm -1 、1507cm -1 、1472cm -1 、1458cm -1 、1438cm -1 、1401cm -1 、1372cm -1 、1359cm -1 、1284cm -1 、1266cm -1 , 1222cm -1 、1153cm -1 、1129cm -1 、1014cm -1 , 988cm -1, 890cm -1 、783cm -1 、704cm -1 、621cm -1 , 590cm -1 、528cm -1 、461cm -1 、419cm - 1 The IR results of the composites prepared in Examples 8-12 are basically consistent with those in Example 7.

[0130] The 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid calcium complex of the present invention was subjected to infrared spectroscopy analysis. FIG7 shows its infrared spectrum (IR) diagram. It can be seen that the complex has a peak at 2970 cm -1 、1713cm -1 、1591cm - 1 、1476cm -1 、1412cm -1 、1369cm -1 , 1200cm -1 、1132cm -1 , 989cm -1 、959cm -1 , 920cm -1 、897cm -1 、818cm -1 、793cm -1 、768cm -1 , 750cm -1 , 710cm -1 、633cm - 1 、546cm -1 、467cm -1 、430cm -1 There is a characteristic absorption peak.

[0131] The 3-hydroxy-3-methylbutyric acid and 3-hydroxy-3-methylbutyric acid magnesium complex of the present invention was subjected to infrared spectroscopy analysis. FIG8 shows its infrared spectrum (IR) diagram. It can be seen that the complex has a peak at 3343 cm -1 、2976cm -1 、2938cm - 1 、2608cm -1 、1709cm -1 、1572cm -1 、1406cm -1 、1387cm -1 , 1250cm-1 、1209cm - 1 、1152cm -1 , 989cm -1 , 935cm -1 , 910cm -1 、895cm -1 、806cm -1 , 750cm -1 、623cm -1 、538cm -1 、463cm -1 、413cm -1 There is a characteristic absorption peak.

[0132] Example 15. Thermogravimetric analysis (TGA)

[0133] The composite of Example 1 was subjected to thermogravimetric analysis (TGA), and its TGA curve is shown in Figure 9, which depicts the percentage weight loss of the sample as a function of temperature. The TGA results of the composites prepared in Examples 2-6 were substantially consistent with those of Example 1. The composite of Example 7 was subjected to thermogravimetric analysis (TGA), and its TGA curve is shown in Figure 10, which depicts the percentage weight loss of the sample as a function of temperature. The TGA results of the composites prepared in Examples 8-12 were substantially consistent with those of Example 7.

[0134] Thermogravimetric analysis of the 3-hydroxy-3-methylbutyric acid / calcium 3-hydroxy-3-methylbutyrate complex of the present invention revealed a TGA curve, as shown in FIG11 , showing a 2.98% weight loss upon heating from 24.2° C. to 100.0° C. Thermogravimetric analysis of the 3-hydroxy-3-methylbutyric acid / magnesium 3-hydroxy-3-methylbutyrate complex of the present invention revealed a 2.30% weight loss upon heating from 23.5° C. to 100.0° C., as shown in FIG12 .

[0135] Example 16. Elemental Analysis

[0136] Elemental analysis of the composite of Example 1 using an elemental analyzer revealed: C, 45.34%, H, 7.13%. Elemental analysis results for the composites prepared in Examples 2-6 were substantially consistent with those of Example 1. Elemental analysis of the composite of Example 7 using an elemental analyzer revealed: C, 46.73%, H, 7.43%. Elemental analysis results for the composites prepared in Examples 8-12 were substantially consistent with those of Example 7.

[0137] Example 17. Raman spectroscopy analysis

[0138] The composite of Example 1 was subjected to Raman spectroscopy analysis, and the results are shown in Figure 13. The Raman spectroscopy analysis results of the composites prepared in Examples 2-6 were substantially consistent with those of Example 1. The composite of Example 7 was subjected to Raman spectroscopy analysis, and the results are shown in Figure 14. The Raman spectroscopy analysis results of the composites prepared in Examples 8-12 were substantially consistent with those of Example 7.

[0139] Example 18. NMR measurement

[0140] The composite of Example 1 was recorded in a spectrometer. 1 H NMR spectrum: 1 H NMR (400 MHz, deuterium oxide) δ 2.36 (s, 2H), 1.20 (s, 6H). The NMR results of the complexes prepared in Examples 2-6 were basically consistent with those in Example 1. The complex of Example 7 was recorded in a spectrometer. 1 H NMR spectrum: 1 H NMR (400 MHz, deuterium oxide) δ 2.36 (s, 2H), 1.20 (s, 6H). The NMR results of the complexes prepared in Examples 8-12 were substantially consistent with those in Example 7. The NMR results of the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid calcium complex and the 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyric acid magnesium complex of the present invention were substantially consistent with those in Examples 1 and 7.

[0141] Example 19. Differential Scanning Calorimetry (DSC)

[0142] Figure 15 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid and sodium 3-hydroxy-3-methylbutyrate complex of the present invention, which includes an endothermic peak at 160.28°C ± 3°C. Figure 16 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid and potassium 3-hydroxy-3-methylbutyrate complex of the present invention, which includes an endothermic peak at 146.73°C ± 3°C. Figure 17 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid and calcium 3-hydroxy-3-methylbutyrate complex of the present invention, which includes an endothermic peak at 269.38°C ± 3°C. Figure 18 is a DSC spectrum of the 3-hydroxy-3-methylbutyric acid and magnesium 3-hydroxy-3-methylbutyrate complex of the present invention, which includes an endothermic peak at 252.26°C ± 3°C.

[0143] Example 20

[0144] For the composites of various examples, the 3-hydroxy-3-methylbutyric acid content and the metal ion content were measured. The results are shown in Table 5.

[0145] Table 5

[0146] Example 21

[0147] The solubility of various 3-hydroxy-3-methylbutyrates and the complexes of various examples was measured. The results are shown in Table 6. The solubility of the complexes of the present invention is significantly higher than that of the corresponding 3-hydroxy-3-methylbutyrate.

[0148] Table 6

[0149] Example 22

[0150] The stabilities of various 3-hydroxy-3-methylbutyrates and the complexes of the present invention were determined at 23° C. and 92.5% humidity. The results are shown in Table 7.

[0151] Table 7

[0152] Example 23

[0153] Thirty-two 24-month-old female C57BL / 6 mice were randomly divided into four groups of eight mice each: the NC group received oral administration of water; commercially available 3-hydroxy-3-methylbutyrate calcium (HMB calcium salt); the HMB-Na complex of the present invention; and the HMB-Ca complex of the present invention. Supplementation was continued once daily for approximately six weeks. Each group maintained a final HMB concentration of approximately 384 mg / kg. Hindlimb muscles were dissected and weighed at week seven, and data were recorded.

[0154] Figure 19 shows the muscle weight of experimental mice at 7 weeks. As shown in Figure 19, the muscle weight of mice administered with the complex of the present invention increased significantly compared to the existing HMB calcium salt product.

[0155] The complex provided by the present invention has a high HMB content, high solubility, and good stability, effectively solving the problems of low solubility, poor stability, acid / salt load, excessive calcium intake, and gastrointestinal side effects associated with existing products. It has a good mouthfeel and improved flavor. Moreover, due to the changes in properties such as solubility and stability, the complex of the present invention has better effects of increasing muscle mass and improving muscle performance, joint function, body composition, or health compared to existing HMB calcium salts, and can be better used as a dietary or nutritional supplement.

[0156] 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 3-hydroxy-3-methylbutyric acid·3-hydroxy-3-methylbutyrate complex and a composition thereof, characterized in that: The salt is sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt, and amino acid salt.

2. The composite according to claim 1, characterized in that The complex is in solid form.

3. The composite according to claim 1 or 2, characterized in that The complex is in crystalline form.

4. The composite according to any one of claims 1 to 3, characterized in that The sodium salt complex has the following structure:

5. The composite according to claim 4, characterized in that The X-ray powder diffraction pattern of the sodium salt complex includes peaks at diffraction angles (2θ) of 8.8±0.2°, 18.1±0.2°, 24.3±0.2°, and 35.6±0.2°.

6. The composite according to claim 5, characterized in that The X-ray powder diffraction pattern of the sodium salt complex further includes one or more peaks at diffraction angles (2θ) of 7.9±0.2°, 19.0±0.2°, and 28.6±0.2°.

7. The composite according to claim 5 or 6, characterized in that The X-ray powder diffraction pattern of the sodium salt complex further includes one or more peaks at diffraction angles (2θ) of 17.6±0.2°, 21.4±0.2°, and 36.7±0.2°.

8. The composite according to any one of claims 1 to 7, characterized in that The X-ray powder diffraction pattern of the sodium salt complex is shown in FIG1 .

9. The composite according to any one of claims 1 to 3, characterized in that The potassium salt complex has the following structure:

10. The composite according to claim 9, characterized in that The X-ray powder diffraction pattern of the potassium salt complex includes peaks at diffraction angles (2θ) of 15.9±0.2°, 18.3±0.2°, 20.6±0.2°, and 34.7±0.2°.

11. The composite according to claim 10, characterized in that The X-ray powder diffraction pattern of the potassium salt complex further includes one or more peaks at diffraction angles (2θ) of 10.6±0.2°, 17.9±0.2°, and 22.6±0.2°.

12. The composite according to claim 10 or 11, characterized in that The X-ray powder diffraction pattern of the potassium salt complex further includes one or more peaks at diffraction angles (2θ) of 11.9±0.2°, 18.5±0.2°, and 30.7±0.2°.

13. The composite according to any one of claims 1 to 3 and 9 to 12, characterized in that The X-ray powder diffraction pattern of the potassium salt complex is shown in FIG2 .

14. The composite according to any one of claims 1 to 3, characterized in that The calcium salt complex has the following structure:

15. The composite according to claim 14, characterized in that The X-ray powder diffraction pattern of the calcium salt complex includes peaks at diffraction angles (2θ) of 9.0±0.2°, 18.8±0.2°, 26.4±0.2°, and 30.3±0.2°.

16. The composite according to claim 15, characterized in that The X-ray powder diffraction pattern of the calcium salt complex further includes one or more peaks located at diffraction angles (2θ) of 8.1±0.2°, 13.1±0.2°, and 20.4±0.2°.

17. The composite according to claim 15 or 16, characterized in that The X-ray powder diffraction pattern of the calcium salt complex further includes one or more peaks at diffraction angles (2θ) of 16.5±0.2°, 25.4±0.2°, and 34.2±0.2°.

18. The composite according to any one of claims 1 to 3 and 14 to 17, characterized in that The X-ray powder diffraction pattern of the calcium salt complex is shown in FIG3 .

19. The composite according to any one of claims 1 to 3, characterized in that The magnesium salt complex has the following structure:

20. The composite according to claim 19, characterized in that The X-ray powder diffraction pattern of the magnesium salt complex includes peaks at diffraction angles (2θ) of 8.9±0.2°, 16.5±0.2°, 25.3±0.2°, and 37.4±0.2°.

21. The composite according to claim 20, characterized in that The X-ray powder diffraction pattern of the magnesium salt complex further includes one or more peaks at diffraction angles (2θ) of 9.4±0.2°, 18.8±0.2°, and 30.2±0.2°.

22. The composite according to claim 20 or 21, characterized in that The X-ray powder diffraction pattern of the magnesium salt complex further includes one or more peaks at diffraction angles (2θ) of 13.0±0.2°, 20.3±0.2°, and 34.1±0.2°.

23. The composite according to any one of claims 1 to 3 and 19 to 22, characterized in that The X-ray powder diffraction pattern of the magnesium salt complex is shown in FIG4 .

24. The composite according to any one of claims 1 to 23, characterized in that The complex is prepared as food, beverage, supplement, nutraceutical or pharmaceutical preparation.

25. A 3-hydroxy-3-methylbutyric acid / 3-hydroxy-3-methylbutyrate complex, characterized in that: The composite is obtained by the following method: (1) obtaining substance B by one of the following methods: mixing 3-hydroxy-3-methylbutyric acid and 3-hydroxy-3-methylbutyric acid salt; or adding 3-hydroxy-3-methylbutyric acid to an aqueous solution of an alkaline compound, stirring and removing water; or heating 3-hydroxy-3-methylbutyric acid alkyl ester and water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, and removing water by distillation under reduced pressure; (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.

26. The composite according to claim 25, characterized in that The complex is in crystalline form.

27. A method for preparing the composite according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: (1) obtaining substance B by one of the following methods: mixing 3-hydroxy-3-methylbutyric acid and 3-hydroxy-3-methylbutyric acid salt; or adding 3-hydroxy-3-methylbutyric acid to an aqueous solution of an alkaline compound, stirring and removing water; or heating 3-hydroxy-3-methylbutyric acid alkyl ester and water in the presence of a catalyst, cooling and filtering, adding an aqueous solution of an alkaline compound to the filtrate, and removing water by distillation under reduced pressure; (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.

28. The method according to claim 27, characterized in that In step (2), the alcohol is methanol, ethanol, isopropanol, or n-butanol; the halogenated hydrocarbons are chlorobenzene, dichlorobenzene, or dichloromethane; the ketones are acetone, methyl butyl ketone, or methyl isobutyl ketone; and the esters are ethyl acetate, isopropyl acetate, n-butyl acetate, or isobutyl acetate.

29. The method according to claim 28, characterized in that The alkaline compound in step (1) is a hydroxide, carbonate, bicarbonate, methoxide, acetate or formate of sodium, potassium, calcium or magnesium, aqueous ammonia, triethylamine or N,N-diisopropylethylamine; the alkyl 3-hydroxy-3-methylbutyrate is methyl 3-hydroxy-3-methylbutyrate, ethyl 3-hydroxy-3-methylbutyrate, propyl 3-hydroxy-3-methylbutyrate, isopropyl 3-hydroxy-3-methylbutyrate, butyl 3-hydroxy-3-methylbutyrate or isobutyl 3-hydroxy-3-methylbutyrate.

30. A composition, characterized in that The composition comprises an effective amount of the complex according to any one of claims 1 to 23, and a pharmaceutically acceptable carrier.

31. The composition according to claim 30, characterized in that The composition is used as a substance for improving muscle performance, joint function, body composition or enhancing health.

32. The composition according to claim 30 or 31, characterized in that The composition is prepared as food, beverage, supplement, nutraceutical or pharmaceutical preparation.

33. Use of the complex according to any one of claims 1 to 23, characterized in that The use of the complex in preparing a substance for improving muscle performance, joint function, body composition or enhancing health.

34. The use according to claim 33, characterized in that The substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

35. Use of a composition for preparing a substance for improving muscle performance, joint function, body composition or enhancing health, characterized in that: The composition comprises the complex according to any one of claims 1 to 23, and a pharmaceutically acceptable carrier.

36. The use according to claim 35, characterized in that The substance is a nutritional supplement, an energy treatment, a medical treatment, or a strength and / or endurance sports supplement.

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