JP2022520560A - Beta-Hydroxybutyrate Mixed Salt-Acid Composition and Usage - Google Patents

Abstract

A ketogenic composition comprising a beta-hydroxybutyrate mixed salt-acid is formulated to induce or maintain ketosis in a subject to which the ketogenic composition is administered. The beta-hydroxybutyrate mixed salt-acid provides a biologically balanced set and is formulated to avoid the harmful health effects associated with an unbalanced electrolyte ratio. The ketogenic composition comprises beta-hydroxybutyric acid and at least two beta-hydroxybutyrate salts selected from sodium, potassium, calcium, and magnesium. The beta-hydroxybutyric acid fraction of the mixed hydrochloric acid composition can be absorbed and utilized more quickly, can improve the taste, does not require citric acid or other edible acids, and provides a lower pH composition. Can be done. The beta-hydroxybutyrate composition is a transition metal cation (eg, zinc or iron), one or more beta-hydroxybutyrate-amino acid salts, short chain-, medium chain-, or long chain fatty acid source, vitamin D3, It may contain flavoring agents and excipients.

Description

Disclosed herein are mixed beta-hydroxybutyrate salt-acid compositions and methods that result in elevated blood levels of ketone bodies in a subject.

During periods of fasting, strenuous exercise, and / or low carbohydrate consumption, glucose and glycogen stores in the body are rapidly consumed and can be rapidly depleted. Failure to replenish the glucose stores associated with their depletion leads to a metabolic shift in the body's production of ketone bodies for energy (“ketosis”). Ketone bodies can be used in almost every cell of the body as an alternative fuel to meet the body's energy needs, including the needs of the brain and heart. For example, long-term fasting can increase blood ketone levels to 2 or 3 mmol / L or higher. When blood ketones rise above 0.5 mmol / L, the heart, brain, and peripheral tissues have traditionally used ketone bodies (beta-hydroxybutyrate, and acetoacetate) as their primary fuel source. It is understood. This state is called ketosis. A condition in which blood levels are between 1.0 mmol / L and 3.0 mmol / L is called "nutritional ketosis".

During the transition to ketosis, the body uses dietary fat and body fat as the primary source of energy during ketogenic metabolism in the liver. During ketosis, body fat can be reduced by controlling dietary fat intake and reducing carbohydrate intake to maintain ketosis. During ketosis, the body is in a state of ketogenesis and burns fat as the main fuel. In the body, fat is broken down into fatty acids and glycerol, which are converted to acetyl-CoA molecules, which are the water-soluble ketone bodies in the liver via ketone production, beta-hydroxybutyrate, acetoacetate, and It is finally converted to acetone. Beta-hydroxybutyrate and acetoacetate are used as energy in the body, and acetone is removed and excreted as a by-product of keto production.

Ketone body metabolism is associated with several beneficial effects, including anticonvulsant effects, promotion of brain metabolism, neuroprotection, muscle-sparing properties, and improved cognitive and physical fitness. Scientific improvements in the efficiency of cell metabolism, controlled by ketone supplementation, have beneficial effects on physical, cognitive, and psychological health, including obesity, cardiovascular disease, neurodegenerative disease, diabetes, And may have long-term health effects on common avoidable diseases such as cancer.

While pursuing a ketogenic diet and lifestyle and maintaining a state of nutritional ketosis has many health benefits, there remain significant barriers to pursuing and maintaining a ketogenic state. One of the barriers is the difficulty of transitioning to a ketogenic state. The fastest intrinsic method of transitioning to ketosis through the depletion of glucose stores in the body is by fasting combined with exercise. This is very difficult, even for the most ambitious and disciplined person, with strict physical and mental demands.

In addition, the transition to ketosis is often accompanied by hypoglycemia, which can lead to lethargy and lightheadedness, resulting in an unpleasant physical and mental condition commonly referred to as a "low-carbohydrate cold." Sometimes. Also, as the body goes into an "energy saving" mode, many people experience downregulation in metabolism. Some argue that these transient symptoms can last for as long as 2-3 weeks. During this transition period, if a diet or light meal consisting of more carbohydrates than the limit is ingested, ketone production ends immediately, the body escapes from ketosis, and the body uses glucose as the main fuel. And the transition to ketosis must be started again.

If a subject succeeds in establishing ketosis, maintaining ketosis is equally or even more difficult, as the ratio of carbohydrates and proteins to fat must be strictly maintained during the diet. It is further complicated by the disruption of normal electrolyte imbalance that often occurs when transitioning to and maintaining a ketogenic state. The depletion and reduction of glycogen storage in the liver and muscles reduces the body's ability to retain water, increasing the frequency of urination, which results in the loss of more electrolytes. Also, the decrease in insulin levels due to ketosis affects the rate at which certain electrolytes are excreted by the kidneys, further reducing electrolyte levels in the body.

Electrolyte imbalances lead to fatigue, muscle spasms, headaches, dizziness, depression, constipation, skin problems, weakness, and irritability, and other often associated with entering and maintaining a ketogenic state. It exacerbates harmful psychological and physiological effects and thus further increases the difficulty of promoting and / or maintaining ketosis. In more extreme cases, electrolyte imbalances can cause serious health problems such as palpitation, dyspnea, involuntary muscle spasms, and arrhythmias.

(Overview)
As used herein, a ketogenic diet containing a beta-hydroxybutyrate mixed salt-acid composition formulated to induce and / or sustain ketosis of interest while promoting or maintaining a beneficial electrolyte balance. The composition is disclosed.

For example, the ketogenic composition does not overdeliver total electrolytes into the body, or oversupply certain electrolytes that can be unhealthy, such as excesses of sodium, potassium, magnesium and / or calcium (ie). , Not to exceed the RDA of a particular electrolyte, or by a predetermined amount), may function to induce and / or sustain ketosis in the subject. This allows the ketogenic composition to induce or sustain ketosis while limiting, preventing or ameliorating electrolyte imbalances in the subject.

In some embodiments, the beta-hydroxybutyrate mixed salt-acid composition for promoting and / or sustaining ketosis in a subject is formed from a plurality of different cations and an amount of free beta-hydroxybutyric acid. Contains a beta-hydroxybutyrate mixed salt. The cation can be selected from alkali metals, alkaline earth metals, transition metals, amines, and amino acids. When used in combination with cations and certain amounts of free beta-hydroxybutyric acid, beta-hydroxybutyrate while maintaining or promoting electrolyte balance and / or without causing electrolyte imbalance or overload. Will be able to be administered in a larger amount.

In some embodiments, the beta-hydroxybutyrate mixed salt-acid composition for promoting and / or sustaining ketosis in a subject comprises a plurality of beta-hydroxybutyrate salts formulated from a plurality of cations. In some cases, anions other than beta-hydroxybutyrate may be excluded from the mixed beta-hydroxybutyrate salt-acid composition. The cations are formulated to provide a biologically balanced set of cationic electrolytes upon administration to the subject. The mixed salt-acid composition comprises a beta-hydroxybutyrate lithium salt, a beta-hydroxybutyrate potassium salt, a beta-hydroxybutyrate sodium salt (eg, by weight less than or equal to the weight of the beta-hydroxybutyrate potassium salt). It may contain at least two of a beta-hydroxybutyrate magnesium salt and a beta-hydroxybutyrate calcium salt (eg, by weight less than or equal to the weight of the beta-hydroxybutyrate magnesium salt).

Some embodiments include one or more transition metal salts, such as, but not limited to beta-hydroxybutyrate salts, such as zinc salts, iron salts, copper salts, manganese salts, and chromium salts. Examples of other beta-hydroxybutyrate and non-beta-hydroxybutyrate salts include selenium salts and amino acid salts.

By limiting the total amount of single electrolyte salt in the ketogenic composition, substantially the total amount of beta-hydroxybutyrate delivered to the body without delivering an excessive or unhealthy amount of single electrolyte. It is possible to increase. The use of multiple beta-hydroxybutyrate salts in combination with free beta-hydroxybutyric acid can be used to maintain an appropriate electrolyte balance.

In some embodiments, the ketogenic composition is used as a weight loss supplement, as a therapeutic agent for hyperglycemia or type II diabetes, as a brain health agent, as an athletic performance enhancer, for metabolic dysfunction, mitochondrial deficiency, insulin resistance. It is useful as a prophylactic, as an adjunct to the ketogenic diet, as an anti-aging supplement, and for other uses related to improving metabolic health.

In a preferred embodiment, the ketogenic composition is provided in the form of a solid or powder rather than a liquid or gel. In addition to providing the beneficial ketogenic and electrolyte balancing effects described herein, such solid form ketogenic compositions preferably provide ease of handling and manufacture. Be prescribed. Alternatively, the composition may be in the form of a liquid mouse spray for rapid delivery and uptake. In some embodiments, beneficial ketogenic and electrolyte effects are achieved without interfering with or unduely affecting the manufacturability or ease of handling of the composition.

Further features and advantages are described in part in the description below, some of which may be clarified by the description or learned by practicing the embodiments disclosed herein. It should be understood that both the brief overview described above and the detailed description below are for purposes of illustration and illustration only and do not limit the scope of the embodiments or claims described herein. Is.

（式中、
Ｘは、水素、金属イオン、アミノ酸からなどのアミノカチオン、アルキル、アルケニル、アリール、またはアシルであってもよい。） (Detailed explanation)
1. 1. Introduction The compound "beta-hydroxybutyrate", also known as β-hydroxybutyrate, 3-hydroxybutyrate, βHB, BHB, or beta-hydroxybutyrate, has the general formula CH ₃ CH ₂ OHCH ₂ COOH. It is a deprotonated form of beta-hydroxybutyric acid, which is a hydroxycarboxylic acid having. The deprotonated form present at typical biological pH levels is CH ₃ CH ₂ OHCH ₂ ^COO- . The general chemical structure shown below represents a beta-hydroxybutyrate compound that can be utilized in the disclosed compositions.

(During the ceremony,
X may be an amino cation such as from hydrogen, metal ion, amino acid, alkyl, alkenyl, aryl, or acyl. )

When X is hydrogen, the compound is beta-hydroxybutyric acid. If X is a metal ion or amino cation, the compound is a beta-hydroxybutyrate salt. If X is an alkyl, alkenyl, aryl, or acyl, the compound is a beta-hydroxybutyrate ester. The aforementioned compounds can be in any desired physical form such as crystals, powders, solids, liquids, solutions, suspensions, or gels.

Unless otherwise specified, the term "salt" is any of crystals, powders, and other solid forms that dissolve in water to form a solution and then disperse in a liquid to form a suspension or gel. Does not mean or imply any particular physical condition of. The salt may be obtained by at least partially neutralizing beta-hydroxybutyric acid with a strong or weak base such as a hydroxide, carbonate, or bicarbonate, basic amino acid of an alkali metal or alkaline earth metal. Can be formed in solution.

The beta-hydroxybutyrate mixed salt-acid composition may include a mixture of beta-hydroxybutyrate salt and beta-hydroxybutyric acid. Providing beta-hydroxybutyrate in its acid form may be beneficial as the absorption response time is much faster compared to the salt form. Nonetheless, the amount of beta-hydroxybutyric acid is made or combined with the salt form, even though the acid form itself is a liquid with extremely low pH and unpalatable taste. When relatively small, the composition may still form a typical solid, powder or other form in salt form. In such cases, the salt-acid combination form of beta-hydroxybutyrate has acceptable pH and taste. BHB compositions containing both salt and acid forms provide improved absorption, improved bioavailability, reduced electrolyte load, ease of production, significantly improved taste, neutral or acidic pH compositions. Benefits include reducing the need for citric acid or other edible acids to obtain. It will also be appreciated that the use of mixtures of beta-hydroxybutyrate salts and / or esters with the acid form of BHB will also provide beneficial effects.

The term "free beta-hydroxybutyric acid" means the sum of the deprotonated beta-hydroxybutyric acid molecule and the deprotonated beta-hydroxybutyric acid molecule. Deprotonated beta-hydroxybutyric acid molecules generally mean molecules that have released protons to form hydronium ions (H ₃ O +) and beta-hydroxybutyrate anions (eg, dissolved in water). ..

Free beta-hydroxybutyric acid molecules are typically not significantly deprotonated when included in dry powder or other solid forms of beta-hydroxybutyrate mixed hydrochloric acid compositions. In such cases, the fractional amount of free beta-hydroxybutyric acid in the beta-hydroxybutyrate mixed salt-acid composition on a weight basis is the weight of free beta-hydroxybutyric acid, free beta-hydroxybutyric acid. And beta-hydroxybutyrate salt divided by the total weight. On a molar basis, the fraction of free beta-hydroxybutyric acid in the beta-hydroxybutyrate mixed hydrochloric acid composition is provided by the molar equivalent of free beta-hydroxybutyric acid, free beta-hydroxybutyric acid and the beta-hydroxybutyrate salt. It is divided by the total molar equivalent with the beta-hydroxybutyrate anion.

When dissolved in water, some of the beta-hydroxybutyric acid typically dissociates into beta-hydroxybutyrate anions and hydronium ions ( _H3O +). As a result, the beta-hydroxybutyric acid molecule can exchange protons and cations with the dissolved beta-hydroxybutyrate salt. Dissociation of beta-hydroxybutyric acid molecules and exchange of protons and cations is beta-hydroxy for the purpose of defining the relative amounts of beta-hydroxybutyric acid and beta-hydroxybutyrate salts in the beta-hydroxybutyrate mixed salt-acid composition. It is not understood to alter the molar ratio of free beta-hydroxybutyric acid to beta-hydroxybutyrate anions from butyrate salts. The total amount of free beta-hydroxybutyric acid molecules in solution is the sum of the undeprotonated dissolved beta-hydroxybutyric acid molecules and the beta-hydroxybutyrate anions formed by the deprotonation of the beta-hydroxybutyric acid molecules. Is.

In other words, the total molar equivalent of beta-hydroxybutyric acid in solution is (i) the molar equivalent of non-deprotonated beta-hydroxybutyric acid molecules in solution, whether or not it is deprotonated. The total molar equivalents of beta-hydroxybutyrate anions (from all sources) and (ii) the total molar equivalents of the cation charge provided by the cations from the beta-hydroxybutyrate salt compound (which is beta-hydroxybutyrate). Equal to the total molar equivalent of beta-hydroxybutyrate anion provided by the rate salt). Alkali metal cations such as sodium and potassium provide 1 mol of cation charge per mol of metal cation. On the other hand, cations of alkaline earth metals such as magnesium and calcium provide 2 mol of cation charge per mol of metal cation. One mol of deprotonated beta-hydroxybutyric acid molecule provides 1 mol of anionic charge and 1 mol of cationic charge.

From the above, the mole fraction of beta-hydroxybutyric acid in solution with respect to the total number of moles of beta-hydroxybutyrate molecules from the beta-hydroxybutyrate mixed salt-acid composition in solution is [(i)-. (Ii) ÷ (i)], and the mole fraction of the beta-hydroxybutyrate molecule from the beta-hydroxybutyrate salt in the solution is [(ii) ÷ (i)]. Multiply each mole fraction by 100 to get each percentage in solution.

As an example, if the beta-hydroxybutyrate mixed salt-acid composition in the dry powder state contains 5% free non-deprotonated beta-hydroxybutyric acid and 95% beta-hydroxybutyrate salt on a mol basis, it is substantially. There will be 5 molar equivalents of beta-hydroxybutyric acid molecule and 95 molar equivalents of beta-hydroxybutyrate anion. If there is enough water to dissolve all beta-hydroxybutyrate salts and some of the beta-hydroxybutyric acid molecules are deprotonated, the molar equivalent of non-deprotonated beta-hydroxybutyric acid is 5%. Less than, the molar equivalent of beta-hydroxybutyrate anion will be greater than 95%. The degree of deprotonation of beta-hydroxybutyric acid in solution is related to the pH of the solution.

Beta-hydroxybutyrate can be utilized by the patient's body as a fuel source when glucose levels in the subject are low or when the patient's body is supplemented with a usable form of beta-hydroxybutyrate. Beta-hydroxybutyrate is commonly referred to as a "ketone body".

As used herein, "ketogenic composition" refers to a mixed beta-hydroxybutyrate salt-acid composition. The composition raises ketone body levels in the subject, including inducing and / or sustaining elevated ketone body levels at desired levels, such as ketosis, in the subject to which it is administered, while simultaneously providing an electrolyte in the subject. Prescribed to promote or maintain balance.

As used herein, the term "mixed salt" or "polysalt" is used to describe some of the ketogenic compositions containing multiple beta-hydroxybutyrate salts. The mixed BHB salt comprises multiple cationic forms of the BHB salt (eg, 2, 3, 4, or more), the salt being relatively distributed to promote the benefits of the electrolyte in the subject. There is.

As used herein, "subject" or "patient" refers to members of the animal kingdom, including, but not limited to, humans and other primates, rodents, fish, reptiles, and birds. And so on. The subject may be any animal in need of treatment, treatment or prevention, or any animal suspected of needing treatment, treatment or prevention. Prevention means that it is done to prevent events that may occur, such as when high glucose or diabetes is present. "Patient" and "subject" are used interchangeably herein.

The term "unit dose" refers to a dosage form configured to deliver a composition or component thereof in a particular amount or dose. Examples of dosage forms are tablets, capsules, powders, foods, food additives, beverages (flavored, vitamin-enriched, or non-alcoholic, etc.), beverage additives (flavored, vitamin-enriched, or non-alcoholic, etc.), candy. , Stick candy, pastilles, dietary supplements, nutritionally acceptable sprays (such as flavored mouth sprays), injections (such as alcohol-free injections), and suppositories. , Not limited to these. Such dosage forms may be configured to provide a complete unit dose or fraction thereof (eg, 1/2, 1/3, or 1/4 of a unit dose).

Another dosage form that can be used to provide a unit dose of the composition or its ingredients is a unit dose measuring device such as a cup, scoop, syringe, dropper, spoon, spatula, or colonic irrigation device, which is a complete unit. It is configured to retain in it a measured amount of composition equal to a dose or fraction thereof (eg, 1/2, 1/3, or 1/4 of a unit dose). For example, bulk containers such as cartons, boxes, cans, jars, bags, pouches, bottles, jugs, or barrels containing several unit dose compositions (eg, 5 to 250 or 10 to 150 unit doses) may be composed. It may be provided to the user with a unit dose measuring device configured to provide a unit dose or fraction thereof of the substance or its components.

The kits used to provide the compositions disclosed herein in bulk form, while providing a unit dose of said composition, include a bulk container that holds an amount of the composition therein. It may include a unit dose measuring device configured to provide a unit dose or fraction thereof of the composition or its components. One or more unit dose measuring devices may be placed inside the bulk container at the time of sale, attached to the outside of the bulk container, or pre-packaged with the bulk container in a larger package. It may be provided by the seller or manufacturer for use with one or more bulk containers.

The kit may include instructions regarding the size of the unit dose or fraction thereof, as well as the method and frequency of administration. The instructions may be written in a bulk container, pre-packaged with the bulk container, or placed in a packaging material sold with the bulk container. It may be provided by the seller or manufacturer (eg, websites, mailers, leaflets, product materials, etc.). The instructions for use may include references to how to use the unit dose measuring device to adequately provide the unit dose or fraction thereof. The instructions may, in an additional or alternative manner, include references to common unit dose measuring devices such as spoons, spatulas, cups, etc. that are not included with the bulk container (eg, provided unit doses). In case the measuring device is lost or misplaced). In such cases, the kit by the end user according to the instructions provided with the bulk container or the instructions provided by the seller on how to properly provide the unit dose or fraction thereof of the product, composition. Can be constructed.

As used herein, "ketosis" refers to a subject having a blood ketone level in the range of about 0.5 mmol / L to about 16 mmol / L. Ketosis can improve mitochondrial function, reduce reactive oxygen species production, reduce inflammation, and increase neurotrophic factor activity. As used herein, "ketogenic indication" refers to long-term nutritional ketosis (> 1 week) to obtain maintained, non-pathological "mild ketosis" or "therapeutic ketosis". ..

In some cases, "elevated ketone body levels" may not mean that the subject is in a "clinical ketosis" state, but nevertheless generate energy and / or other ketone bodies. It means an increase in the supply of ketones to exert beneficial effects. For example, subjects who are "ketone-adapted" may not necessarily have elevated ketone body serum levels, but are more rapidly compared to subjects who are not "ketone-adapted". , Available ketone bodies are available. In such cases, "elevated ketone body levels" can refer to the total amount and / or proportion of ketone bodies utilized by the subject, rather than the plasma levels themselves.

The term "short chain triglyceride" (SCT) refers to a molecule with a glycerol backbone with three medium chain fatty acids. Short chain fatty acids can range in length from 2 to 5 carbon atoms. Examples of short-chain fatty acids include acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid and the like. Examples of SCTs include tributyrin.

The term "medium chain triglyceride (MCT)" refers to a molecule with a glycerol skeleton with three medium chain fatty acids. Medium-chain fatty acids can range in length from 6 to 12 carbon atoms and are likely to range in length from 8 to 10 carbon atoms. Examples of fatty acids include caprylic acid, also known as octanoic acid, which has eight carbon molecules, and caprylic acid, also known as decanoic acid, which has ten carbon molecules. MCTs, medium chain fatty acids, as well as mono and diglycerides are ketone body precursors that can provide an additional source for the production of ketone bodies independent of beta-hydroxybutyrate.

The term "long chain triglyceride" (LCT) refers to a molecule with a glycerol backbone with three medium chain fatty acids. Long-chain fatty acids can have more than 12 carbon atoms in length.

The terms "administer" or "administer" as used herein are used to describe the process of delivering a mixed salt ketogenic composition to a subject. The composition can be administered in a variety of ways, including oral, gastric, and parenteral (intravenous and intraarterial, as well as other suitable parenteral routes), among others.

II. Ketogenic Beta-Hydroxybutyrate Mixed Salt-Acid Composition Administration of beta-hydroxybutyrate mixed salt-acid composition increases and sustains blood levels of ketone bodies, thereby sustained metabolic ketosis. And the physiological benefits are available. Subjects are compared to methods that aim to induce and maintain ketosis based solely on diet (eg, fasting and / or restricted carbohydrate intake) by increasing blood ketone body levels. You will be able to choose your meal more flexibly. For example, subjects receiving the appropriate amount of beta-hydroxybutyrate mixed salt-acid sometimes eat carbohydrate or sugar-based foods without endangering the ketogenic state and without returning to a glucose-based metabolic state. You will be able to take it. In addition, such administration facilitates the transition to ketosis and reduces or eliminates the typical adverse effects associated with transition to ketosis.

Subjects who enter or maintain a ketogenic state often become electrolyte imbalanced due to metabolic shifts associated with ketosis, including enhanced diuretic effects and altered insulin profile. Thus, administration of beta-hydroxybutyrate mixed salt-acids to promote or maintain ketosis in a subject has many advantages, but the resulting electrolyte imbalance and associated harmful effects. Physiological effects offset the benefits of ketosis and / or make it more difficult for the subject to maintain ketosis at the desired level or for the desired time.

In addition, beta-hydroxybutyrate can be administered in the form of a salt, where one or more beta-hydroxybutyrate molecules are anions to the selected cation, so the introduction of additional cation electrolytes in the subject. It can cause or exacerbate electrolyte imbalances. For example, a formulation having a particular form of beta-hydroxybutyrate salt at excessively high levels and / or excessively high proportions causes additional electrolyte imbalances and / or other harmful health effects. there is a possibility. In some situations, even if certain forms of beta-hydroxybutyrate salts alleviate electrolyte imbalances to some extent, they can have other negative and undesired health effects.

For example, formulations with too high and / or too high proportions of beta-hydroxybutyrate sodium increase sodium levels in the subject. Sodium is a necessary nutrient, but having levels outside the optimal range has detrimental effects. High levels of sodium are associated with hypertension and worsening cardiovascular health. In particular, higher levels of sodium compared to potassium promote hypertension and increase the risk of cardiovascular disease.

In another example, a formulation with too high or too high a proportion of beta-hydroxybutyrate calcium increases calcium levels in the subject. Calcium is also a necessary nutrient and is especially important for good bone health, but excess calcium is not well absorbed by bone and instead accumulates in soft tissues, causing harmful calcification and hardening of the tissues. It can result in increased risk of heart disease (eg, associated with hardened arteries), kidney stones, arthritis, and other problematic conditions. In particular, excessively high levels of calcium compared to magnesium can exacerbate these adverse effects. Magnesium functions by stimulating the hormone calcitonin and functions to convert vitamin D to its active form, thus promoting calcium absorption in bone as opposed to calcium deposition in soft tissues. Can be done.

Therefore, administration of beta-hydroxybutyrate salts in inappropriate amounts and ratios can cause or exacerbate adverse health effects. Moreover, for subjects seeking to maintain a ketogenic state, compensating for imbalances with other dietary options is not always easy or possible. For example, many foods known to be high in potassium and / or magnesium, such as whole grains, bananas, avocados, milk, yogurt, oatmeal, corn, pea, potatoes, and pumpkin, contain high levels of carbohydrates. It is incompatible with a strict ketogenic diet when ingested in significant amounts.

The embodiments disclosed herein provide a therapeutically effective amount of beta-hydroxybutyrate in the form of a beta-hydroxybutyrate mixed salt-acid. Advantageously, the beta-hydroxybutyrate mixed salt-acid is formulated to provide a biologically balanced set of cationic electrolytes. Therefore, one or more embodiments provide the advantage of initiating and / or sustaining ketosis while at the same time promoting a positive electrolyte effect.

In some embodiments, the beta-hydroxybutyrate mixed salt-acid may comprise one or more salts of alkali metals, alkaline earth metals, transition metals, amino acids, or amino acid metabolites. Examples include lithium salt, sodium salt, potassium salt, magnesium salt, calcium salt, zinc salt, iron salt (as iron (II) and / or iron (III)), chromium salt, manganese salt, cobalt salt, copper salt. , Molybdenum salt, selenium salt, arginine salt, lysine salt, leucine salt, isoleucine salt, histidine salt, ornithine salt, citrulin salt, glutamine salt, and creatine salt.

In some embodiments, the beta-hydroxybutyrate mixed salt-acid comprises a plurality of (eg, at least two, three or four) different cations, beta-hydroxybutyrate lithium, beta-hydroxybuty. It is allocated to contain at least two of rate sodium, beta-hydroxybutyrate potassium, beta-hydroxybutyrate calcium, or beta-hydroxybutyrate magnesium in acceptable amounts and ratios.

In some embodiments, beta-hydroxybutyrate sodium is about 5 to 70%, or about 6 to 50%, or about 8 to 40%, or about 10 to 10% by weight of the BHB mixed salt-acid. It is included in the range of 30%, or about 12-25%, or about 14-22%, or about 16-20%, or about 18%.

In some embodiments, beta-hydroxybutyrate potassium is about 5 to 70%, or about 6 to 50%, or about 8 to 40%, or about 10 to 10% by weight of the BHB mixed salt-acid. It is included in the range of 30%, or about 12-25%, or about 14-22%, or about 16-20%, or about 18%.

In some embodiments, beta-hydroxybutyrate calcium is about 5 to 70%, or about 6 to 60%, or about 8 to 50%, or about 10 to 10% by weight of the BHB mixed salt-acid. It is included in the range of 40%, or about 12-35%, or about 15-30%, or about 18-25%, or about 20-23%.

In some embodiments, beta-hydroxybutyrate magnesium is about 5 to 70%, or about 6 to 60%, or about 8 to 50%, or about 10 to 10% by weight of the BHB mixed salt-acid. It is included in the range of 40%, or about 12-35%, or about 15-30%, or about 18-25%, or about 20-23%.

In some embodiments, beta-hydroxybutyrate sodium is included by weight in an amount no greater than the amount of beta-hydroxybutyrate potassium in the composition. This allows the administration of the required sodium and potassium electrolytes, causing or exacerbating unwanted health effects associated with high sodium ratios to potassium (eg, hypertension, cardiovascular disease, and other unfavorable effects). It is possible to provide a beneficial electrolyte effect to the subject without causing it to occur.

In some embodiments, beta-hydroxybutyrate calcium is contained by weight in an amount no greater than the amount of beta-hydroxybutyrate magnesium. This allows the required calcium and magnesium electrolytes to be administered, with unfavorable health effects associated with high calcium ratios to magnesium (eg, tissue calcification, poor bone health, and other unfavorable effects). It can provide a beneficial electrolyte effect to the subject without causing or exacerbating it.

In some embodiments, the beta-hydroxybutyrate mixed salt-acid composition has a molar ratio of sodium ions to potassium ions not greater than 1 and / or a molar ratio of calcium ions to magnesium ions of 1. Can be prescribed not to exceed.

The beta-hydroxybutyrate mixed salt-acid composition disclosed herein comprises a plurality of beta-hydroxybutyrate salts and beta-hydroxybutyric acid. More specifically, the beta-hydroxybutyrate mixed salt-acid composition comprises less than 100% complex beta-hydroxybutyrate salt and more than 0% free beta-hydroxybutyric acid, eg, up to 99 in molar equivalents. 9.9%, 99.8%, 99.7%, 99.6%, 99.5%, 99.4%, 99.3%, 99.2%, 99.1%, 99%, 98.8. %, 98.65%, 98.5%, 98.35%, 98.2%, 98%, 97.75%, 97.5%, 97.25%, or 97%, and at least 75%, 80. %, 85%, 90%, 92%, 94%, 95%, 96%, or 97% complex beta-hydroxybutyrate salts, and molar equivalents of at least 0.1%, 0.2%, 0. 3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.2%, 1.35%, 1.5% , 1.65%, 1.8%, 2%, 2.25%, 2.5%, 2.75%, or 3%, 25%, 20%, 15%, 10%, 8%, Contains 6%, 5%, 4%, or less than 3% free hydroxybutyric acid.

In some embodiments, the ketogenic composition further comprises a therapeutically effective amount of vitamin D ₃ . Vitamin D ₃ works with magnesium and calcium to promote good bone health and prevent unwanted calcification of soft tissues. In a preferred embodiment, Vitamin D ₃ has an average daily dose of about 200 IU (“international unit”) to about 8000 IU, or about 400 IU to about 4000 IU, or about 600 IU to about 3000 IU. It is contained in an amount such that it contains ₃ . In some embodiments, vitamin D ₃ comprises vitamin D ₃ having an average daily dose of about 5 μg to about 200 μg, or about 10 μg to about 100 μg, or about 15 μg to about 75 μg. Included in quantity.

In some embodiments, the ketogenic composition may include or be administered with other supplements known in the art, such as vitamins, minerals, nootropics, and the like. Examples of vitamins, minerals and herbal supplements that can be added to the ketogenic composition include vitamin A, vitamin C, vitamin E, niacin, vitamin B6, folic acid, 5-MTH F, vitamin B12, iodine, zinc, copper. , Manganese, chromium, caffeine, theobromine, theacrin, methylliberin, fuperzine A, epicatechin, and one or more of the enzymes.

In some embodiments, it comprises one or more additional ketone precursors or supplements. These additional ketone precursors or supplements may contain acetoacetates, ketone esters, and / or other compounds that cause elevated blood ketone levels without adding more electrolytes into the bloodstream. Other additives include metabolites that enhance efficacy or promote the transport of ketone bodies to mitochondria, caffeine, theobromine, and nootropics such as L-alpha glyceryl phosphorylcholine (“alpha GPC”).

Some embodiments include an additional beta-hydroxybutyrate salt as part of the mixed salt of the ketogenic composition. For example, some embodiments include one or more transition metal beta-hydroxybutyrate salts. Suitable transition metal cations for use as BHB or other salts include lithium, chromium, manganese, cobalt, copper, zinc, iron, (eg, as iron (II) or iron (III) cations), molybdenum, etc. And selenium.

The ketogenic composition has an average daily dose of about 0.25 to about 10 times the recommended dietary intake standard (RDA) for at least one cation, or an RDA for at least one cation. It may be formulated to provide at least one of the cations of a certain amount of mixed salt, which is in the range of about 0.5-5 times, or about 0.75 to 2 times. For example, the mixed salt-acid composition may be formulated to consume an amount of cationic electrolyte within the range when the subject ingests the daily dose of the composition. In some embodiments, the mixed salt-acid composition is formulated such that at least one cationic electrolyte that falls within the aforementioned range after 1 day administration of the composition is potassium and / or magnesium. In some cases, RDA levels may be exceeded without necessarily experiencing toxicity or adverse health effects.

In some embodiments, the beta-hydroxybutyrate mixed salt-acid composition is one or more in which at least some of the cations have a net positive charge at the pH at which the beta-hydroxybutyrate salt is produced. It may contain one or more beta-hydroxybutyrate salts provided by amino acids or other organic compounds. Beta-hydroxybutyrate-amino acid salts can provide soluble forms of beta-hydroxybutyrate without providing an electrolyte such as sodium, potassium, calcium, or magnesium. This reduces the amount of electrolyte and / or more electrolyte when it is desired to deliver a larger amount of beta-hydroxybutyrate for therapeutic reasons, especially without further increasing the electrolyte load. It enables the production of beta-hydroxybutyrate salts in healthy amounts and / or with a healthier electrolyte balance. Amino acids suitable for this purpose may contain amino acids containing multiple amine groups that can be protonated to form a compound with a net positive charge, which is the pair to the beta-hydroxybutyrate anion. May provide cations. Examples include arginine, lysine, leucine, isoleucine, histidine, ornithine, citrulline, L-glutamine, or other suitable amino acids or amino acid metabolites (eg, creatine). Also, some amino acids are beneficial to your health. For example, L-arginine can increase nitric oxide in the blood, dilate blood vessels, and improve blood circulation in people with heart disease (may also be effective in men with erectile dysfunction). be).

In some embodiments, the ketogenic composition may comprise at least one short chain fatty acid, or at least one short chain fatty acid mono-, di- or triglyceride, wherein the short chain fatty acid is 6 Has less than one carbon. The composition may comprise at least one medium chain fatty acid, or mono-, di-, or triglyceride of the at least one medium chain fatty acid, wherein the medium chain fatty acid is preferably 6 to 12 carbons. Has 8 to 10 carbons. Although less preferred, the composition may comprise at least one long chain fatty acid or mono, di- or tri-glyceride of the at least one long chain fatty acid having more than 12 carbons.

Examples of short chain fatty acids include acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid. Examples of medium chain fatty acids include caproic acid, caprylic acid, capric acid, and lauric acid. Examples of long-chain fatty acids include myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cellotic acid, omega 3 fatty acid, omega 6 fatty acid, omega 7 fatty acid, and omega 9 fatty acid.

Examples and sources of such esters such as medium chain fatty acids, or medium chain triglycerides, include coconut oil, coconut milk powder, palm oil, palm oil, palm kernel oil, capric acid, capric acid, isolated medium chain fatty acids (single). (Isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, etc.), either medium-chain triglyceride in purified or natural form (such as coconut oil), and ester derivatives of medium-chain fatty acid ethoxylated triglycerides, enontriglycerides. , Aaldehyde triglyceride derivative, a monoglyceride derivative, a diglyceride derivative, and a triglyceride derivative, and a salt of the medium chain triglyceride. The ester derivative optionally comprises an alkyl ester derivative such as methyl, ethyl, propyl, butyl, hexyl and the like.

In some embodiments, the ketogenic composition may be provided in solid or powder form as opposed to liquid or gel form. Such solid-form ketogenic compositions are formulated to provide sufficient ease of handling and manufacture, in addition to promoting the beneficial ketogenic and electrolyte effects described herein. To. For example, in a mixed hydrochloric acid formulation of various beta-hydroxybutyrate salts, certain salts exhibit different material properties (eg, hygroscopicity), and the relative amount of different salts in the mixed salt formulation is the composition. May affect overall characteristics.

In another embodiment, the ketogenic composition may be provided as a liquid, such as in the form of a shot or mouse spray for rapid delivery and absorption. The liquid form may include one or more liquid carriers such as water, ethanol, glycerin, propylene glycol, 1,3-propanediol, in which the BHB mixed salt-acid composition is dissolved or dispersed. The composition may contain a flavoring agent that helps mask the taste of the beta-hydroxybutyrate compound. These include essential oils such as peppermint, natural and artificial sweeteners, and other flavors known in the art.

In the production of the mixed salt-acid formulations described herein, certain beta-hydroxybutyrate salts, especially beta-hydroxybutyrate potassium and beta-hydroxybutyrate magnesium, are more than other beta-hydroxybutyrate salts. It has been demonstrated to exhibit high hygroscopicity. If the ratio of beta-hydroxybutyrate salt is inappropriate, a formulation with poor fluidity and handleability will be produced, which will increase the production cost and improve the storage stability, stability and effectiveness of the ketogenic composition product. May decrease.

Accordingly, the compositions described herein provide the advantages and advantages of the ketogenic and electrolytes described above, while formulating and prescribing so as not to overly or unacceptably disrupt the manufacturability of the composition. Can be balanced. In at least some embodiments, sufficient BHB calcium and / or BHB sodium (typically manufacturability and handling) without excessive inclusion of these salts at excessively high levels that promote harmful health effects. Includes different beta-hydroxybutyrate salts in proportions that provide (promote). Similarly, in at least some embodiments, a sufficient amount of BHB potassium and / or BHB magnesium (typically hindering manufacturability and handling) to balance BHB calcium and / or BHB sodium. Includes, not excessive amounts.

In some embodiments, the beta-hydroxybutyrate mixed salt-acid composition comprises a dietetically or pharmaceutically acceptable carrier. Examples include powders, liquids, tablets, capsules, foods, food additives, beverages, vitamin-enriched beverages, beverage additives, candy, stick candy, troches, dietary supplements, sprays, injections, and suppositories. ..

In some embodiments, the ketogenic composition may further contain one or more additional components configured to reduce the hygroscopicity of the composition. For example, various anticaking agents, fluids, and / or hygroscopic agents may be contained in safe types and amounts for ingestion. Such additional components include aluminosilicates, ferrocyanides, carbonates or bicarbonates, silicates (eg, sodium silicate or calcium silicate), silica, phosphates (eg, diphosphate). It may contain one or more of calcium or tricalcium phosphate), talc, powdered cellulose, calcium carbonate and the like.

III. Administration The ketogenic compositions described herein may be administered to a subject in a therapeutically effective amount and / or at a frequency that induces or maintains ketosis. In some embodiments, the single dose is in an amount ranging from about 1 gram to 50 grams, or about 2 grams to 40 grams, or about 5 grams to 30 grams, or about 10 grams to 20 grams. Contains beta-hydroxybutyrate mixed salt-acid. In some embodiments, the ketogenic composition may include or be administered with the supplements or other additives described herein.

In some embodiments, the subject preferably follows a ketogenic diet that limits the intake of carbohydrates and proteins during the administration period of the composition. In one exemplary embodiment, the subject may limit dietary intake to a ratio of about 65% fat, about 25% protein, and about 10% carbohydrate. The resulting therapeutic ketosis provides rapid and sustained ketogenic adaptation as a metabolic therapy for a wide range of metabolic disorders, providing nutritional support for therapeutic fasting, weight loss, and performance improvement. Therefore, the composition is usually administered once daily, twice daily, or three times daily to subjects who wish to promote and / or maintain ketosis.

In some embodiments, the ketogenic composition is in powder form, such as a solid and / or powder mixture (eg, powder-filled gelatin capsule), strongly pressed tablets, dissolved in water or juice, or in the art. It is orally administered by other known oral routes of administration.

In some embodiments, the composition may be administered in multiple doses. The frequency of administration of the composition may vary depending on any of a variety of factors, including the timing of treatment from pretreatment, the purpose of treatment, and the like. The duration of administration of the composition (eg, the duration of administration of the drug) may vary depending on any of a variety of factors, including the response of the subject, the desired effect of the treatment, and the like.

The amount of said composition administered may vary depending on factors such as the degree of sensitivity of the individual, the age, sex and weight of the individual, and the idiosyncratic response of the individual. A "therapeutically effective amount" is an amount required to promote a therapeutically effective result (ie, therapeutic ketosis) in vivo. According to the present disclosure, a suitable single dose size is an amount that can prevent or alleviate (reduce or eliminate) symptoms in a patient when administered more than once over a suitable period of time.

The amount of composition administered is known to those of skill in the art as well as the efficacy, absorption, distribution, metabolism and excretion rate of beta-hydroxybutyrate and / or the corresponding electrolyte, the method of administration, the particular disorder being treated, and the person skilled in the art. Depends on other factors. Taking into account the severity of the alleviating condition, the dose shall be sufficient to influence the desired response, such as a therapeutic or prophylactic response to a particular disorder or condition. The composition may be administered once or in divided doses over time. It should be understood that the administration may be adjusted according to the individual need and the professional judgment of the person who administers the composition or supervises the administration of the composition.

IV. Examples The following is an exemplary beta-hydroxybutyrate mixed salt useful for inducing and / or sustaining a ketogenic state in an administered subject while simultaneously providing a balanced set of cationic electrolytes. -A description of the acid composition.

Example 1
A beta-hydroxybutyrate mixed salt-acid is prepared by mixing 23% by weight BHB sodium, 23% by weight BHB potassium, 27% by weight BHB calcium, and 27% by weight BHB magnesium. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 2
18% by weight BHB sodium, 18% by weight BHB potassium, 32% by weight BHB calcium, and 32% by weight BHB magnesium are mixed to prepare a beta-hydroxybutyrate mixed salt-acid. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 3
15% by weight of BHB sodium, 20% by weight of BHB potassium, 30% by weight of BHB calcium, and 35% by weight of BHB magnesium are mixed to prepare a beta-hydroxybutyrate mixed salt-acid. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 4
15% by weight BHB sodium, 15% by weight BHB potassium, 35% by weight BHB calcium, and 35% by weight BHB magnesium are mixed to prepare a beta-hydroxybutyrate mixed salt-acid. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 5
30% by weight BHB sodium, 30% by weight BHB potassium, 20% by weight BHB calcium, and 20% by weight BHB magnesium are mixed to prepare a beta-hydroxybutyrate mixed salt-acid. Vitamin D ₃ is added in an amount of 1200 IU (representing the average daily intake) per 15 g of BHB mixed salt-acid. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 6
Beta-hydroxy by mixing 15% by weight BHB sodium, 15% by weight BHB potassium, 18% by weight BHB calcium, 18% by weight BHB magnesium, 17% by weight BHB zinc, and 17% by weight BHB iron. Butyrate mixed salt-acid is prepared. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 7
20% by weight BHB sodium, 20% by weight BHB potassium, 20% by weight BHB calcium, 20% by weight BHB magnesium, and 20% by weight BHB zinc are mixed to form beta-hydroxybutyrate mixed salt-acid. Prepare. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 8
A beta-hydroxybutyrate mixed salt-acid is mixed with 15% by weight BHB sodium, 25% by weight BHB potassium, 20% by weight BHB calcium, 25% by weight BHB magnesium, and 15% by weight BHB iron. Prepare. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 9
Beta-mixed with 15% by weight BHB sodium, 15% by weight BHB potassium, 20% by weight BHB calcium, and 20% by weight BHB magnesium, 20% by weight BHB zinc, and 10% by weight BHB iron. Prepare a hydroxybutyrate mixed salt-acid. Vitamin D ₃ is added in an amount of 600 IU (representing the average daily intake) per 10 g of BHB mixed salt. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily as a ketogenic composition, for example in the form of a powder as a dietary supplement mixed with food or drink, in the form of one or more capsules or tablets, or in the form of a liquid such as a mouth spray or shot. Be administered.

Example 10
A beta-hydroxybutyrate mixed salt-acid is prepared by mixing 23% by weight BHB sodium, 23% by weight BHB potassium, 27% by weight BHB calcium, and 27% by weight BHB magnesium. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is readily administered as a ketogenic composition in powder form, for example as a dietary supplement mixed with food and drink, in the form of one or more capsules or tablets, or in liquid form such as mouth spray. To.

Example 11
A beta-hydroxybutyrate mixed salt-acid is prepared by mixing 25% by weight BHB sodium, 25% by weight BHB potassium, 25% by weight BHB calcium, and 25% by weight BHB magnesium. At least one of the beta-hydroxybutyrate salts contains an amount of free beta-hydroxybutyric acid and / or an additional amount of free beta-hydroxybutyric acid is added to the BHB mixed salt to free about 1-3% by weight. Beta-hydroxybutyric acid is provided. The BHB mixed salt-acid is mixed with an anticaking agent that is safe for human consumption in a 4: 1 ratio and is in powder form as a dietary supplement mixed with food and drink, or in one or more capsules or tablets. In form, it forms a ketogenic composition that is readily administered to the subject.

Example 12
Any of the above beta-hydroxybutyrate mixed salt-acid compositions is a medium chain fatty acid having 6 to 12 carbons, preferably 8 to 10 carbons, a monoglyceride of a medium chain fatty acid, a diglyceride of a medium chain fatty acid. , Or a ketogenic composition comprising at least one medium chain fatty acid source selected from medium chain fatty acid triglycerides, which provides ketosis over a longer period of time than provided by a given amount of BHB mixed salt-acid alone. .. The ratio of the medium chain fatty acid source to the BHB mixed salt-acid composition is 4: 1, 3: 1, 2: 1, 1: 1 or 1: 2.

Example 13
All of the beta-hydroxybutyrate mixed salt-acid compositions are cationic amino acids selected from amino acid metabolites such as arginine, lysine, leucine, isoleucine, histidine, ornithine, citrulline, L-glutamine, or creatin. Contains one or more BHB salts. The BHB-amino acid salt reduces the ratio of electrolyte to BHB anion in the composition.

Example 14
Any of the beta-hydroxybutyrate mixed salt-acid compositions may be derived from a short chain fatty acid having less than 6 carbons, a monoglyceride of the short chain fatty acid, a diglyceride of the short chain fatty acid, or a triglyceride of the short chain fatty acid. Combined with at least one short chain fatty acid source of choice.

Example 15
Any of the beta-hydroxybutyrate mixed salt-acid compositions may be derived from a long chain fatty acid having more than 12 carbons, a monoglyceride of the long chain fatty acid, a diglyceride of the long chain fatty acid, or a triglyceride of the long chain fatty acid. Combined with at least one long chain fatty acid source of choice.

The present invention may be embodied in other specific forms without departing from its spirit or essential features. The embodiments described are only exemplary in all embodiments and should be considered without limitation. Therefore, the scope of the present invention is indicated by the appended claims rather than the above description. Equal meaning of the claims and all modifications that fall within those scopes should be included within those scopes.

Claims (20)

A beta-hydroxybutyrate mixed acid-salt composition for increasing ketone levels in a subject.
Beta-hydroxybutyric acid and
Beta-hydroxybutyrate sodium,
Beta-hydroxybutyrate potassium,
Beta-hydroxybutyrate calcium, or
Beta-hydroxybutyrate magnesium, comprising a plurality of beta-hydroxybutyrate salts consisting of at least two of them,
A composition in which the composition is in solid or powder form. The composition
Beta-hydroxybutyrate sodium,
Beta-hydroxybutyrate potassium,
Beta-hydroxybutyrate calcium, or
The composition according to claim 1, which comprises at least three of beta-hydroxybutyrate magnesium. The composition
Beta-hydroxybutyrate sodium,
Beta-hydroxybutyrate potassium,
Beta-hydroxybutyrate calcium, and
The composition according to claim 1 or 2, which comprises beta-hydroxybutyrate magnesium. The composition in which the beta-hydroxybutyrate sodium, the beta-hydroxybutyrate potassium, the beta-hydroxybutyrate calcium, and the beta-hydroxybutyrate magnesium provide a recommended daily intake of calcium (RDA). The composition according to any one of claims 1 to 3, wherein the composition is contained in a relative ratio so that the amount of sodium, potassium, and magnesium does not exceed the respective RDAs of sodium, potassium, and magnesium. The composition according to any one of claims 1 to 4, wherein the composition contains 5 to 70% by weight of beta-hydroxybutyrate sodium. The composition according to any one of claims 1 to 5, wherein the composition comprises 5 to 70% by weight of beta-hydroxybutyrate potassium. The composition according to any one of claims 1 to 6, wherein the composition comprises 5 to 70% by weight of beta-hydroxybutyrate magnesium. The composition according to any one of claims 1 to 7, wherein the composition contains 5 to 70% by weight of beta-hydroxybutyrate calcium. Any of claims 1-8, wherein the composition comprises 90% to 99.9% molar equivalent of the complex beta-hydroxybutyrate salt and 10% to 0.1% molar equivalent of beta-hydroxybutyric acid. The composition according to item 1. Any of claims 1-9, wherein the composition comprises 94% to 99.5% molar equivalent of the complex beta-hydroxybutyrate salt and 6% to 0.5% molar equivalent of beta-hydroxybutyric acid. The composition according to item 1. 13. The composition described. The composition according to any one of claims 1 to 11, further comprising at least one short chain fatty acid having less than 6 carbons, or at least one short chain fatty acid mono-, di-, or tri-glyceride. thing. The composition according to any one of claims 1 to 12, further comprising at least one supplement selected from vitamins, minerals, nootropics, and herbal supplements. A beta-hydroxybutyrate mixed acid-salt composition for increasing ketone levels in a subject.
Beta-hydroxybutyric acid and
Beta-hydroxybutyrate sodium,
Beta-hydroxybutyrate potassium,
Beta-hydroxybutyrate calcium, or
Beta-hydroxybutyrate magnesium, comprising a plurality of beta-hydroxybutyrate salts consisting of at least two of them,
The composition comprises tablets, capsules, powders, foods, food additives, flavored beverages, vitamin-enriched beverages, non-alcoholic beverages, flavored beverage additives, vitamin-enriched beverage additives, non-alcoholic beverage additives, candies, sticks. Compositions provided as or in candy, troches, dietary supplements, flavored mouth sprays, or suppositories. 14. The composition of claim 14, wherein the composition comprises 94% to 99.5% molar equivalent of a complex beta-hydroxybutyrate salt and 6% to 0.5% molar equivalent of beta-hydroxybutyric acid. thing. The composition of claim 14 or 15, further comprising at least one supplement selected from vitamins, minerals, nootropics, and herbal supplements. A beta-hydroxybutyrate mixed acid-salt composition for increasing ketone levels in a subject.
Tablets, capsules, powders, foods, food additives, flavored beverages, vitamin-enriched beverages, non-alcoholic beverages, flavored beverage additives, vitamin-enriched beverage additives, non-alcoholic beverage additives, candies, candies with sticks, troches, With a foodally or pharmaceutically acceptable carrier selected from the group consisting of dietary supplements, flavored mouth sprays, and suppositories.
Beta-hydroxybutyric acid and
Beta-hydroxybutyrate sodium,
Beta-hydroxybutyrate potassium,
A composition comprising a plurality of beta-hydroxybutyrate salts consisting of at least two of beta-hydroxybutyrate calcium or beta-hydroxybutyrate magnesium. A kit for administering ketone bodies to a subject,
The beta-hydroxybutyrate mixed acid-salt composition according to claim 1 and
The container containing the composition and
A measuring device configured to retain a unit dose of the composition or a fraction thereof therein, wherein the unit dose of the composition comprises from about 1 g to about 50 g of the beta-hydroxybutyrate compound. A kit, including a measuring device. 18. The kit of claim 18, wherein the container is selected from the group consisting of cartons, boxes, cans, jars, bags, pouches, bottles, jugs, and barrels. The kit of claim 18 or 19, wherein the measuring device is selected from the group consisting of a cup, a scoop, a syringe, a dropper, a spatula, a spoon, and a colonic irrigation device.