RU2789509C1 - APPLICATION OF A COMPOUND BASED ON γ-QUATERNARY AMMONIUM BUTYRATE IN OBTAINING A FEED ADDITIVE FOR ANIMALS - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to the field of biotechnology. Disclosed is the use of a compound based on γ-quaternary ammonium butyrate represented by formula (I) as a feed additive to improve the growth rates of farm animals.

Formula (I)

Compound (I) is applied by adding to the daily diet of animals, which leads to an increase in weight gain in animals and a decrease in the feed conversion rate.

EFFECT: invention expands the arsenal of means for use as a feed additive to improve the growth rates of farm animals.

3 cl, 2 tbl, 4 ex

Description

FIELD OF TECHNOLOGY

The present invention relates to the field of animal feed additives, in particular to the use of compounds based on γ-quaternary ammonium butyrate in the preparation of animal feed additives or animal feed.

BACKGROUND OF THE INVENTION

Carnitine is an amino acid species belonging to a complex containing a quaternary ammonium cation, and is an amino acid widely distributed in the liver and, in particular, has the highest content in the myocardium and skeletal muscle. Most of the carnitine components required by the body come from meat and dairy products in the diet, or are synthesized from the two amino acids, lysine and methionine, through biosynthetic pathways. Carnitine is a type of amino acid that helps convert fat into energy. Red meat is the main source of L-carnitine with no toxic side effects. Carnitine has two stereoisomers, including the biologically active L-carnitine and the biologically inactive enantiomer D-carnitine. Studies have shown that L-carnitine is involved in β-oxidation of fatty acids, promotes fat catabolism and is capable of eliminating acyl substances in muscle tissue, and protects muscle cells from the destruction of acyl residues, thereby eliminating lactic acids in muscles and alleviating muscle fatigue and spasms. Additional research has shown that L-carnitine intake can lead to a decrease in body fat and weight without a decrease in water and muscle mass. In 2003, L-carnitine was recognized as the safest dietary supplement for weight loss with no side effects by the International Health Organization for the Fight against Obesity.

L-carnitine is widely used in animal husbandry and is mainly used to reduce the fat content in animal meat, reduce weight, or prevent diseases of the liver or biliary tract in animals. Research has shown that puffed dog food supplemented with L-carnitine can effectively reduce fat in obese dogs and keep them healthy. The results of other studies have shown that bile acids and L-carnitine play an important role in fat metabolism and can effectively prevent nutrition-related diseases of the liver and biliary tract in farm animals. Other studies have shown that betaine and saccharicterpenine can be used to synergistically enhance the action of L-carnitine tartrate to accelerate fat oxidation and breakdown in chickens and increase the percentage of lean meat. Research results have also been published showing that adding carnitine to the diet of cattle or sheep can effectively combat ammonia toxicity associated with high protein levels. In the field of medicine, carnitine is a widely used lipid-lowering drug for hemodialysis patients. Although many studies have shown that carnitine has biological effects in breeding ruminants such as cattle or sheep at various stages of growth, the effect on milk production and growth performance is almost always less than expected. On December 13, 2018, Dong-Liang Lu studied the effect of L-carnitine on tilapia cultivation performance. Compared with the intact control group, the rate of weight gain of tilapia fed a basic diet supplemented with L-carnitine was reduced by 1.2% in the experimental group.

By itself, carnitine is a complex containing a quaternary ammonium cation, which is usually characterized by hygroscopicity. In the 1970s, research found that the fatty acid ester derivatives of the carboxyl group of carnitine are a chemical that is physically and chemically stable and does not absorb moisture. Such carnitine derivatives are used as intermediates in the chemical industry as a protection scheme for the carboxyl group in the production of carnitine or prodrugs formed by combining carnitine as a drug ligand with drugs. Such carnitine derivatives can also be used as surfactants in the field of cosmetics, food or medicine.

Feed additives refer to small or trace amounts of substances added during the processing, preparation and use of feed and include nutritional feed additives and conventional feed additives. General feed additives refer to small or trace amounts of substances added to feed to provide or improve feed quality and feed efficiency. At present, commonly used conventional feed additives that can effectively and stably improve feed utilization efficiency and improve animal rearing performance mainly include high copper content, high zinc content, feed antibiotics, chemically synthesized antimicrobial agents, etc. .d. However, long-term use of these substances in animal husbandry has significant side effects, such as the disadvantages of animal liver and kidney toxicity, growth suppression, kidney dysfunction, urinary tract disorders, teratogenicity, mutagenesis, drug resistance, drug residues in the body. and environmental pollution or the like. In order to protect animal health and improve production efficiency in livestock production, it is necessary to develop a new, effective, stable and safe feed additive with the ability to improve the performance of animal rearing.

BRIEF DESCRIPTION OF THE INVENTION

In view of the foregoing, it is an object of the present invention to provide the use of a γ-quaternary ammonium butyrate compound or its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt in the preparation of animal feed additives or animal feed, wherein the compound based on γ-quaternary ammonium butyrate can improve the performance of growing farm animals.

In order to achieve the above object, the present invention provides for the use of a γ-quaternary ammonium butyrate compound represented by formula (I), or a racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt thereof, in the preparation of animal feed additives,

where A is an anion; R is C ₁ -C ₂₀ alkyl or C _{1 -C 20} alkyl optionally substituted with one, two, three, four or five R ³ , or C ₆ -C ₁₂ aryl, or C ₄ -C ₁₂ heteroaryl, or (C ₁ -C ₄ alkylene) -C ₆ -C ₁₂ aryl, or (C ₁ -C ₄ alkylene) -C ₄ -C ₁₂ heteroaryl, or C ₆ -C ₁₂ aryl, C ₄ -C ₁₂ heteroaryl, (C ₁ - C ₄ alkylene)-C ₆ -C ₁₂ aryl, (C ₁ -C ₄ alkylene)-C ₄ -C ₁₂ heteroaryl, each of which is optionally substituted with one, two, three, four or five R ⁴ ; R ³ is -OH, -NH ₂ , -CN, -SH or X ₁ where X ₁ is F, Cl, Br or I; R ⁴ is -OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl substituted with X ₂ , where X ₂ represents F, Cl, Br or I.

The present invention further provides a feed composition comprising at least one of the γ-quaternary ammonium butyrate compounds or a racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt thereof described above as main components.

The present invention further provides for the use of the feed composition as described above in the preparation of animal feed or animal feed additives.

Based on the above technical solutions, the present invention has the following effects.

The present invention provides for the use of a γ-quaternary ammonium butyrate compound represented by formula (I), or a racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt thereof, in the preparation of animal feed additives. The compound is added to the daily diet of animals in a certain concentration ratio so as to increase the average daily weight gain of animals under the same feed intake conditions without significantly affecting the daily feed intake of animals, thereby reducing the feed conversion rate. It can be seen that the γ-quaternary ammonium butyrate compound or its racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt of the present invention can effectively increase the rate of daily weight gain in animals and improve the growth performance of animals, when It has no side effects on animals and is stable and safe, and improves production efficiency in animal husbandry while ensuring animal health.

DETAILED DESCRIPTION OF EMBODIMENTS

In order to provide a better understanding of the present invention, hereinafter the present invention will be described more fully with reference to embodiments; the following are preferred embodiments of the present invention. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein. Such embodiments are provided in order to make the understanding of the disclosure of the present invention more complete and complete. It should be understood that experimental methods for which specific conditions are not indicated in the following embodiments are generally carried out in accordance with the usual conditions or in accordance with the conditions recommended by the manufacturer. All of the various conventional reagents used in the embodiments are commercially available products.

Unless otherwise indicated, all technical and scientific terms used in this document have the same meaning as is generally understood by specialists in the field to which the present invention pertains. The terms used in the description of the present invention serve to describe specific embodiments only and are not intended to limit the present invention. As used herein, the conjunction "and/or" includes any and all combinations of one or more of the respective listed entities.

This document will describe in detail some embodiments of the present invention, examples of which are shown using the accompanying structural formulas and chemical formulas. The present invention is intended to cover all substituted, modified and equivalent technical solutions, all of which are included within the scope of the present invention as defined by the claims. In addition, certain technical features of the present invention are described separately in a variety of independent embodiments for the sake of clarity, however, they may also be provided in combination or any suitable subcombination in one example.

Connections

The present invention relates to the use of a γ-quaternary ammonium butyrate compound represented by formula (I), or a racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt thereof, in the preparation of animal feed additives,

where A is an anion, and the relationship between an anion and a cation shown in formula (I) only means that the compound is an ionic compound, and does not mean that the sums of the positive and negative charges of the ions are equal.

R is substituted or unsubstituted C ₁ -C ₂₀ alkyl, if R is substituted C ₁ -C ₂₀ alkyl, it is optionally substituted with one, two, three, four or five R ³ , R ³ is -OH, -NH ₂ , -CN, -SH or X ₁ where X ₁ is F, Cl, Br or I; or R is substituted or unsubstituted C ₆ -C ₁₂ aryl, C ₄ -C ₁₂ heteroaryl, (C ₁ -C ₄ alkylene) -C ₆ -C ₁₂ aryl, (C ₁ -C ₄ alkylene) -C ₄ -C ₁₂ heteroaryl, if R is a substituted C ₆ -C ₁₂ aryl, C ₄ -C ₁₂ heteroaryl, (C ₁ -C ₄ alkylene) -C ₆ -C ₁₂ aryl, (C ₁ -C ₄ alkylene) -C ₄ - C ₁₂ heteroaryl, it is optionally substituted with one, two, three, four or five R ⁴ , R ⁴ is -OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , C ₁ -C ₅ alkoxy , C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl substituted with X ₂ where X ₂ is F, Cl, Br or I.

Typically, the term "substituted" means that one or more hydrogen atoms that may be substituted in a given structure are replaced by specific substituents. A substituted group may be formed by substituting one substituent group at each substitutable group position. If more than one position in a given structural formula can be substituted by one or more specific substituents, they can be substituted by groups of substituents the same or differently at each position.

In the present invention, the term "C _a -C _b alkyl" means a linear or branched saturated alkyl containing from a to b carbon atoms, such as methyl, ethyl, propyl, isopropyl, etc. For example, the term "C ₁ -C ₅ alkyl" means a linear or branched saturated alkyl containing 15 carbon atoms. The term "C ₃ -C ₇ cycloalkyl" means a cyclic alkyl containing 3-7 carbon atoms, which contains only two elements of carbon and hydrogen, for example, cyclopropyl, 2-methylcyclopropyl, cyclopentyl, etc. The term "C ₁ -C ₅ alkoxy" means a group containing 15 carbon atoms and one oxygen atom, such as methoxy, ethoxy, propoxy, isopropoxy, etc. The term "C ₆ -C ₁₂ aryl" means a cyclic group containing 6-12 carbon atoms having aromaticity, such as a benzene ring, etc. The term "C ₄ -C ₁₂ heteroaryl" means a cyclic group containing 4-12 carbon atoms and at least one heteroatom (including, without limitation, an oxygen atom (O), a sulfur atom (S), a nitrogen atom (N)), aromatic, such as pyrrolidinyl, pyridinyl, etc. The term "C _n -C _m alkylene" means alkyl containing n or m methylene groups, eg CH ₂ , (CH ₂ ) ₂ and the like.

In some embodiments, R in the γ-quaternary ammonium butyrate compound represented by formula (I) is substituted or unsubstituted C ₆ -C ₁₂ aryl.

In additional embodiments, unsubstituted C ₆ -C ₁₂ aryl includes, without limitation, phenyl or naphthyl.

.In some embodiments, R is

.

In addition, if R is a substituted C ₆ -C ₁₂ aryl, then C ₆ -C ₁₂ aryl is a C ₆ -C ₁₂ aryl optionally substituted with one, two, three, four or five R ⁴ , R ⁴ is - OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl substituted with X ₂ where X ₂ is F, Cl, Br, or I.

In additional embodiments, the substituted C ₆ -C ₁₂ aryl is preferably a substituted C ₆ aryl.

In particular, substituted phenyl is optionally substituted with one, two, three, four or five R ⁴ , R ⁴ is -OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , C ₁ -C ₅ alkoxy , C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl substituted with X ₂ where X ₂ is F, Cl, Br or L

In some embodiments, R is selected from the group consisting of

In some embodiments, R in the γ-quaternary ammonium butyrate compound represented by formula (I) is substituted or unsubstituted (C ₁ -C ₄ alkylene)-C ₆ -C ₁₂ aryl.

In additional embodiments, if R is unsubstituted (C ₁ -C ₄ alkylene)-C ₆ -C ₁₂ aryl, then C ₆ -C ₁₂ aryl includes, but is not limited to, phenyl or naphthyl, and alkylene is preferably methylene.

(бензил).In some embodiments, R is

(benzyl).

In addition, if R is substituted -(C ₁ -C ₄ alkylene) -C ₆ -C ₁₂ aryl, then C ₆ -C ₁₂ aryl is C ₆ -C ₁₂ aryl, optionally substituted with one, two, three, four or five R ⁴ , R ⁴ is -OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl , substituted by X ₂ where X ₂ is F, Cl, Br or I.

In additional embodiments, C ₆ -C ₁₂ aryl is preferably C ₆ aryl.

In particular, R is a substituted benzyl which is optionally substituted with one, two, three, four, or five R ⁴ , R ⁴ is -OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl substituted with X ₂ where X ₂ is F, Cl, Br or I.

In some embodiments, R is selected from the group consisting of

In some embodiments, R in the γ-quaternary ammonium butyrate compound represented by formula (I) is substituted or unsubstituted C ₄ -C ₁₂ heteroaryl.

In additional embodiments, if R is unsubstituted C ₄ -C ₁₂ heteroaryl, then C ₄ -C ₁₂ heteroaryl includes, but is not limited to, pyrrolidinyl, pyrazolyl, or pyridyl.

In some embodiments, R is selected from the group consisting of

In addition, if R is substituted with C₄-WITH₁₂heteroaryl, C₄-WITH₁₂heteroaryl optionally substituted with one, two, three, four or five R⁴, R⁴ represents -OH, -NH₂, -NO₂, -CN, -SH, -X₂, WITH₁-WITH₅alkoxy, C₁- WITH₅alkyl or C₁-WITH₅alkyl substituted X₂, where X₂ is F, Cl, Br or I.

In further embodiments, the C ₄ -C ₁₂ heteroaryl is preferably pyrrolidinyl, pyrazolyl, or pyridyl.

In some embodiments, the C ₄ -C ₁₂ heteroaryl is selected from the group consisting of

In some embodiments, R in the γ-quaternary ammonium butyrate compound represented by formula (I) is substituted or unsubstituted (C ₁ -C ₄ alkylene)-C ₄ -C ₁₂ heteroaryl.

In additional embodiments, C ₄ -C _{12 g} heteroaryl is unsubstituted (C ₁ -C ₄ alkylene)-C ₄ -C ₁₂ heteroaryl, C ₄ -C ₁₂ heteroaryl includes, but is not limited to, pyrrolidinyl, pyrazolyl, or pyridyl, and C ₁ -C ₄ alkylene is preferably methylene.

In some embodiments, R is selected from the group consisting of

In addition, if R is substituted (C ₁ -C ₄ alkylene)-C ₄ -C ₁₂ heteroaryl, then C ₄ -C ₁₂ heteroaryl is optionally substituted with one, two, three, four, or five R ⁴ , R ⁴ is - OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , C ₁ -C ₅ alkoxy, C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl substituted with X ₂ where X ₂ is F, Cl, Br or L

In additional embodiments, C ₄ -C ₁₂ heteroaryl is preferably pyrrolidinyl, pyrazolyl, or pyridyl, and C ₁ -C ₄ alkylene is preferably methylene.

In some embodiments, R is selected from the group consisting of

In some embodiments, R in the γ-quaternary ammonium butyrate compound represented by formula (I) is substituted or unsubstituted C ₁ -C ₂₀ alkyl; if R is substituted C ₁ -C ₂₀ alkyl then substituted C ₁ -C ₂₀ alkyl is C ₁ -C ₂₀ alkyl optionally substituted with one, two, three, four or five R ³ , R ³ is -OH, -NH ₂ , -CN, -SH or X ₁ where X ₁ is F, Cl, Br or I;

Optionally, R is preferably linear C ₁ -C ₂₀ alkyl.

In additional embodiments, R is preferably linear C ₁ -C ₁₁ alkyl.

In particular, linear C ₁ -C ₁₁ alkyl is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n- decyl and n-undecyl.

In some embodiments, R is methyl.

In other embodiments, R is ethyl.

In other embodiments, R is n-propyl.

Optionally, R is branched C ₁ -C ₂₀ alkyl.

In some embodiments, R is preferably isopropyl or tert-butyl.

In some embodiments, anion A is a negative monovalent anion.

Optionally, the negative monovalent anion includes, without limitation, chloride, bromide, iodide, or perchlorate ions.

In some embodiments, anion A is a negative divalent anion.

Optionally, the negative divalent anion includes, without limitation, a sulfate ion or a carbonate ion.

In some embodiments, anion A is an organic acid ion.

Optionally, the organic acid ion includes, but is not limited to, acetate ion, fumarate ion, maleate ion, and the like.

In some specific embodiments, the γ-quaternary ammonium butyrate compound of the present invention comprises one of the following structures and the corresponding racemates, stereoisomers, geometric isomers, tautomers, solvates, and edible salts of the above compounds:

Getting and Cleaning Connections

The production method of the γ-quaternary ammonium butyrate compound represented by formula (I) of the present invention is as shown in equation (II), wherein carnitine is used as a starting material and the main reaction involved is a displacement reaction.

For clarity, "solv." in equation (II) denotes a reaction solvent, and "A" denotes heating.

In some embodiments, the γ-quaternary ammonium butyrate compound is a chiral compound that is derived from chiral carnitine (as shown in formula (III)) or its racemate. The γ-quaternary ammonium butyrate compound of the present invention is selected from stereoisomers such as levorotatory isomer, which is an L-(-)-γ-quaternary ammonium butyrate compound (the structure is represented by formula (IV)), dextrorotatory isomer, which is a D-(+)-γ-quaternary ammonium butyrate compound (the structure is represented by formula (V)), a racemate which is a DL-(±)-γ-quaternary ammonium butyrate compound, and the like.

In some embodiments, chiral stereoisomers of a γ-quaternary ammonium butyrate compound can undergo a stereoconfigurational transformation under suitable conditions, e.g., a stereoconfiguration of a γ-quaternary ammonium butyrate compound is interconverted to form a tautomer, and the method of interconversion is shown in equation (VI).

If the corresponding γ-quaternary ammonium butyrate compound obtained from the reaction of the involved reactants has a rigid structure, the reaction substrate can produce various geometric isomeric products during the course of the reaction.

The above stereoisomer, geometric isomer and tautomer are also included within the scope of the present invention.

As used in the present invention, the term "stereoisomer" refers to a compound having the same chemical structure but a different arrangement of atoms or groups in space, including enantiomer, diastereomer, conformational isomer, geometric isomer and atropisomer, and the like. The term "enantiomer" refers to two isomers of a compound that cannot overlap but are mirror images of each other. The term "diastereomer" refers to a stereoisomer that contains two or more chiral centers and its molecules are not mirror images of each other and have different physical properties such as melting point, boiling point, spectral properties and reactivity. Mixtures of diastereoisomers can be separated using high resolution analysis operations such as electrophoresis or chromatography. The term "tautomer" refers to structural isomers with different energies, which can be converted into each other due to the low energy barrier.

In some embodiments, the process for preparing a γ-quaternary ammonium butyrate compound of the present invention also includes a process for separating, purifying, or recrystallizing the reaction products. The reaction products can be obtained as crude products from the reaction system by a solvent removal process. In order to obtain solids with a higher chemical purity and lower impurity content, the crude products are dissolved, crystallized, or precipitated, or recrystallized and separated in an alcoholic solvent, an alcohol-water mixed solvent, or other organic solvents that can be used to recrystallize the products in conditions of suitable temperature, lighting and mechanical vibration, to obtain a compound based on γ-quaternary ammonium butyrate in a certain crystalline state. The γ-quaternary ammonium butyrate compound in a defined crystalline state is a crystal of the γ-quaternary ammonium butyrate compound or a solvate of the γ-quaternary ammonium butyrate compound. The solvate of the γ-quaternary ammonium butyrate compound can be selected from hydrates of the γ-quaternary ammonium butyrate compound or ethanol solvates of the γ-quaternary ammonium butyrate compound.

As used in the present invention, the term "solvate" refers to an associated eutectic compound formed by binding chemically equivalent solvent molecules or solvent molecules that are not chemically equivalent to a compound of the present invention through non-covalent intermolecular forces under external conditions and internal conditions during contact between the compound according to the present invention and solvent molecules.

Solvents for forming solvates include, without limitation, solvents such as water, acetone, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and isopropanol, or the like. The term "hydrate" refers to the associated compound or crystal formed when the solvent molecule is water, i.e. a compound formed by the binding of chemically equivalent water or water that is not chemically equivalent through non-covalent intermolecular forces.

In order to obtain solids with a higher chemical purity and a lower impurity content, the process for producing a γ-quaternary ammonium butyrate compound of the present invention may further include a post-treatment by a desalting method. The desalination method is a process for precipitating salts of a γ-quaternary ammonium butyrate compound and a corresponding organic base, inorganic base, organic acid, or inorganic acid using the principle of an acid-base neutralization method, an acid-base coordination method, or an acid-base complexation method to obtain edible salts. Inorganic acids include, without limitation, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, nitric acid, or combinations thereof. The organic base includes, without limitation, ammonia or triethylamine. The inorganic base includes, without limitation, sodium hydroxide, potassium hydroxide, magnesium hydroxide, or calcium hydroxide.

Edible salts are those formed by the γ-quaternary ammonium butyrate compound of the present invention and an organic base, an inorganic base, an organic acid, or an inorganic acid, which are non-toxic to animals. The expression "edible" means that the substance or composition must be chemically or toxicologically suitable, and it refers to the feed to be received, or the process of eating it by farm animals.

In some embodiments, the γ-quaternary ammonium butyrate compound of the present invention is an ionic compound that forms an acid-base coordination salt and/or an acid-base chelate salt with an inorganic acid or organic acid during the precipitation of salts in a post-treatment. The organic acid includes, without limitation, acetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, malic acid, 2-hydroxypropionic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, glucuronic acid, galactitol acid, citric acid, tartaric acid, aspartic acid, glutamic acid, benzoic acid, p-methylbenzoic acid, cinnamic acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, triflate acid, or a combination thereof. The inorganic acid includes, without limitation, sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, and the like.

Use of the γ-Quaternary Ammonium Butyrate Compound Involved in the Present Invention

The γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt are used in the preparation of animal feed additives.

As used in the present invention, the term "animal" refers to humans or farm animals that are unable to synthesize organic matter from inorganic matter and can only use organic matter as food for life activities such as swallowing, digesting, absorbing, breathing, circulating, excreting , sensation, movement and reproduction. The term "farm animals" includes poultry, livestock, aquatic animals, and other animals that are artificially fed and legally captured, including pets such as cats and dogs. The term "livestock" refers to any of, for example, pigs, cattle, horses, goats, sheep, deer, and many beneficial rodents. The term "poultry" includes, for example, chickens, ducks, geese, quails, pigeons, and the like. The term "aquatic animals" includes, for example, fish, shrimp, turtles, amide, and the like.

A γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt of the present invention are used to provide nutritional supplements for improving the rearing performance of animals at various growth stages. Animals may be selected from livestock, poultry, aquatic animals, or domestic animals in various stages of growth.

In addition, livestock includes, but is not limited to, pigs, cattle, sheep, horses, rabbits, minks, or donkeys, poultry includes, but is not limited to, chickens, turkeys, ducks, geese, quails, or pigeons, and aquatic animals include without limitation, fish, shrimp, turtles, crabs, amides, bullfrogs, eels or bats, and domestic animals include, without limitation, dogs or cats of various subspecies.

In one embodiment, a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt of the present invention are used to make feed additives for improving the rearing performance of slaughter pigs, which have a beneficial effect on average daily weight gain and feed conversion efficiency in fattening pigs.

In another embodiment, a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt of the present invention are used to provide feed additives having the ability to significantly improve the performance of broilers or laying hens.

Feed composition according to the present invention

The feed composition contains at least one of a compound based on γ-quaternary ammonium butyrate and its racemate, a stereoisomer, a geometric isomer, a tautomer, a solvate, or an edible salt, and a feed aid. A feed aid is a carrier, diluent, adjuvant and solvent that are suitable for consumption, or a combination thereof.

As used in the present invention, the term "feed" refers to an industrially processed and manufactured product for animal consumption.

Used in the present invention, the term "composition" refers to a group of compounds, including one or more compounds as effective ingredients.

As used in the present invention, the term "comprising" is an open-ended term that includes the content explicitly stated in the present invention, but does not exclude other content.

The term "carrier" as used in the present invention refers to an edible substance having the ability to carry active ingredients, improve their dispersibility, and have high chemical stability and adsorption rate, and includes an organic carrier and an inorganic carrier. An organic carrier is a material containing many crude fibers, including, but not limited to, corn flour, corn cob flour, wheat bran, rice bran flour, defatted rice bran, rice bran and husk, corn stalk meal, peanut husk meal and so on. The inorganic carrier is a mineral mainly divided into calcium salts and silicas, which is used to prepare a trace element premix, including, but not limited to, calcium carbonate, silicate, vermiculite, zeolite, sepiolite, and the like.

As used in the present invention, the term "diluent" refers to a substance that evenly distributes additional raw materials in the material, diluting highly concentrated additional raw materials into a low-strength premix or premix that can separate trace components from each other and reduce interaction between active ingredients. , thereby increasing the stability of the active ingredients without affecting the physical and chemical properties of the associated substances, and includes an organic diluent or an inorganic diluent. The organic diluent includes, but is not limited to, corn flour, hulled corn flour, dextrose (glucose), sucrose, bran semolina, roasted soy flour, medium grade flour, corn gluten meal, and the like. The inorganic diluent includes, without limitation, limestone, calcium dihydrogen phosphate, eggshell powder, kaolin (porcellanite), table salt, and sodium sulfate.

An excipient is a wetting agent that causes the intrinsic viscosity of a substance, a binder that binds substances together, a disintegrant that breaks the entire layer of substance into many small particles, a retention agent that reduces friction between particles, or an anti-adhesive that prevents adhesion material, including but not limited to magnesium stearate, talc, vegetable oil, magnesium lauryl sulfate, starch, starch slurry, water, inorganic salt, dextrin, powdered sugar, and the like.

As used in the present invention, the term "solvent" refers to a solvent required to dissolve or disperse solids, including, but not limited to, water, ethanol, glycerin, and the like.

In some embodiments, the feed composition further comprises an additional animal feed additive and/or animal feed material.

The animal feed additive is a nutritional feed additive, a general feed additive, or a therapeutic feed additive.

Nutritional feed additive refers to a small or trace amount of a substance that is added to compound feed to balance the nutrients in the feed, improve the feed utilization rate and directly affect the nutrition of animals, it includes amino acid, amino acid salt and its analogs, vitamin and vitamins, mineral element and its complexes (chelates), microbial enzyme preparation or non-protein nitrogen.

Ordinary feed additive is also called non-nutritional additive, it refers to some non-nutritional substances that are added to feed to improve feed utilization rate, ensure feed quality, and which are beneficial to animal health or metabolism, it includes a growth promoter, insect repellent and health care agent, fragrance and attraction agent, feed texturizer, feed modulator, feed storage agent and Chinese medicine herbal supplement.

More specifically, the non-nutritional additive is a growth promoter, including but not limited to butyric acid, calcium butyrate, sodium butyrate, tannic acid, p-thymol, p-thymol ester, p-thymol salt, 2-hydroxybenzoic acid, β-acid, β-acid ester, β-acid salt, hexahydro-β-acid, hexahydro-β-acid ester, hexahydro-β-acid salt, benzoic acid or calcium benzoate, zinc oxide, zinc sulfate and zinc chloride .

In one embodiment, the non-nutritional additive is calcium butyrate.

In another embodiment, the non-nutritional additive is tannic acid.

The therapeutic feed additive includes, without limitation, premixed veterinary drug materials that have the function of preventing diseases in animals and promoting growth of animals, and can also be added to feed for a long time and mixed with carriers or diluents.

In particular, the therapeutic feed additive is a feed antibiotic, including, but not limited to, polymyxin, salinomycin, avilamycin, bacitracin, virginiamycin, nosigeptide, flavomycin, enramycin, kitasamycin, olaquindox, oxytetracycline, or aureomycin.

In some embodiments, a composition comprising a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt further comprises one or more nutritional feed additives, conventional feed additives, and therapeutic feed additives. additives.

In some embodiments, the animal feed material is a feed material such as grains and their processed products, oilseeds and their processed products, legume seeds and their processed products, tubers, root crops and their processed products, other seeds and fruits and their processed foods, forage grass, roughage and their processed products, other plants, algae and their processed products, dairy products and their by-products, terrestrial animal products and their by-products, fish, other aquatic organisms and their by-products, minerals, products microbiological fermentation and by-products and other food products or the like.

Application of feed composition

The present invention relates to the use of the aforementioned feed composition comprising a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt.

In some embodiments, the aforementioned feed composition comprising a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt is used in the preparation of animal feed additives.

Animal feed additives obtained using a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt are livestock feed additives, feed additives for poultry, feed additives for aquatic animals, or feed additives for pets.

In particular, a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt is used to produce feed supplements for livestock. Livestock includes, without limitation, pigs, cattle, sheep, horses, rabbits, minks, and the like in various growth stages.

In particular, a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt is used to produce feed additives for poultry. Poultry includes, without limitation, chickens, ducks, geese, pigeons, and the like. at various stages of growth.

In particular, a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt is used to produce pet food additives. Pets include, without limitation, artificially fed dogs or cats.

In some embodiments, animal feed additives made using a composition comprising a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt are premixes, multipremixes, aqueous solutions or granules.

In some embodiments, the aforementioned food composition comprising a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt is used in the manufacture of animal feed.

Animal feeds made using a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt are livestock feeds, poultry feeds , aquatic animal feed or pet food.

In particular, a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt is used in the production of livestock feed. Livestock includes, without limitation, pigs, cattle, sheep, horses, rabbits, minks, and the like in various growth stages.

In particular, a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate or edible salt is used to produce poultry feed. Poultry includes, without limitation, chickens, ducks, geese, pigeons, and the like. at various stages of growth.

In particular, a food composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt is used in the production of pet food. Pets include, without limitation, artificially fed dogs or cats.

In some embodiments, foods made using a food composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt are single-element foods, concentrated foods, compound foods , multi-premixes or concentrated additives.

In particular, compound feed is a complete formulated feed.

A method for improving the performance of growing farm animals.

In some feeding embodiments, a farmer feeds animals feed additives containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt, in combination with the feed, which may significantly improve the performance of animal rearing.

In some embodiments, the feed additives are premixes, multi-premixes, granules, or aqueous solutions that are mixed with animal feeds to feed animals.

The animal is livestock, poultry, aquatic animals or pets.

In particular, livestock includes, without limitation, pigs, cattle, sheep, horses, rabbits, minks, and the like. at various stages of growth. Poultry includes, without limitation, chickens, ducks, geese, pigeons, and the like. at various stages of growth. Aquatic animals include, but are not limited to, fish, shrimp, crabs, amide, eels, and the like. at various stages of growth. Pets include, without limitation, artificially fed cats and dogs.

In one embodiment, the farmer feeds feed additives containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt in combination with feed to significantly increase average daily weight gain and feed conversion efficiency in weaned piglets.

In one embodiment, the farmer feeds broilers feed supplements containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt in combination with the feed, which significantly reduces the feed conversion rate. in broilers and improves feed conversion efficiency.

In one embodiment, a farmer feeds puppies a dietary supplement containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt, in combination with the diet.

In other feeding embodiments, a farmer feeds animals a feed composition containing a γ-quaternary ammonium butyrate compound and its racemate, stereoisomer, geometric isomer, tautomer, solvate, or edible salt, which can significantly improve animal rearing performance. .

Optionally, the feed composition is a feed additive premix, a feed additive multipremix, a granule, or an aqueous solution that is fed to animals in combination with feed.

In one embodiment, the feed composition is a feed additive premix.

In one embodiment, the feed composition is a multi-premix feed additive.

Optionally, the feed composition is a concentrated feed, compound feed, multi-premix or concentrated supplement that is directly fed to animals as animal feed.

In one embodiment, the food composition is a complete formulated food.

The present invention will be described in detail below in combination with specific examples.

The method for producing the γ-quaternary ammonium butyrate compound is described in detail using the method for producing ethyl-L-carnitine chloride and benzyl-L-carnitine chloride as examples only.

Example 1 Preparation of ethyl-(R)-3-hydroxy-4-(trimethylammonium)butyrate bromide (abbreviated as ethyl-L-carnitine bromide)

400 g of L-carnitine was weighed into a 2000 ml three-necked flask, 500 ml of acetonitrile was added, and the mixture was thoroughly stirred. Then, a condensate return tube and a drying tube were added and the oil bath was heated to 40°C, then 450 g of bromoethane was added dropwise, and the mixture was stirred at 85°C. If the absence of starting material was confirmed by observation by thin layer chromatography (TLC), the reaction mixture was filtered and the filter cake was dried at 70°C to obtain 590 g of ethyl-L-carnitine bromide with a yield of 88.86%.

Example 2 Preparation of ethyl-(R)-3-hydroxy-4-(trimethylammonium)butyrate chloride (abbreviated benzyl-L-carnitine chloride)

400 g of L-carnitine was weighed into a 3000 ml three-necked flask, 1000 ml of acetonitrile was added, and the mixture was thoroughly stirred. Then, a condensate return tube and a drying tube were added, and the oil bath was heated to 70°C, then 400 g of benzyl chloride was added dropwise, and the mixture was stirred at 90°C. If the absence of starting material was confirmed by observation by thin layer chromatography (TLC), the reaction mixture was filtered and the filter cake was washed with ethanol and dried at 85°C to give 610 g of benzyl-L-carnitine chloride as a white solid in a yield of 86.16 %.

Animal rearing test

Example 3 Effect of a γ-quaternary ammonium butyrate compound on rearing performance of pigs fattened for slaughter

90 heads of pigs of the three-breed "Duroc × Landrace × Large Yorkshire)) lean type with similar weight, having an average weight of 80 kg, were randomly divided into 3 treatment groups, each group had 3 replications, and each replication had 10 pigs , half males and half females. The pigsties and devices were sterilized before testing. During the trial, the piglets were fed in separate pens with the same feeding and care conditions in the same pigsty. During the test, the study pigs had free access to food and water, they received food twice a day. Each study group was a control group (Group I) and study groups II-III, respectively. While the control group received only the basal diet, and the study groups II-III received a diet that was supplemented with 1000 ppm of various compounds based on γ-quaternary ammonium butyrate based on the basal diet, in particular, as shown in table 1.

During the entire feeding process, no additional antioxidant components or growth promoters were added for each study group. The duration of the trial was 28 days, with each repetition counted as one, the pigs were weighed on the 28th day of the trial after they stopped feeding, but continued to give water for 12 hours, to calculate the average daily feed intake (ADFI, g/day * head), average daily weight gain (ADG, g/day*head) and feed conversion rate (FCR) for each study group. The formulas for the calculation are as follows:

average daily feed intake = (total feed - remaining feed)/(test days × number of pigs per repetition);

average daily weight gain = (average weight at end of trial - average weight at start of trial)/days of trial;

feed conversion rate = average daily feed intake/average daily weight gain.

The test results are shown in Table 1.

From the results in Table 1, it can be seen that during this experiment, the effect of the test products on the rearing performance of the test pigs was compared and evaluated in three aspects: feed intake, weight gain, and feed conversion efficiency.

In particular, the γ-quaternary ammonium butyrate compounds used had no significant effect on feed intake in each study group; the average daily weight gain of the studied pigs in each group increased compared to the control group; and the feed conversion rate in each study group was relatively reduced by approximately 11.72% to 9.26%.

It can be seen that the γ-quaternary ammonium butyrate compounds of the present invention can effectively improve growth performance in fattening pigs.

Example 4 Effect of a γ-Quaternary Ammonium Butyrate Compound on Broiler Growth Performance

The trial used a single-factor randomized design. 360 one-day-old Chinese yellow-feathered broiler chickens with a similar average weight of 50 g were randomly divided into 3 treatment groups, each group having 6 replicates, half male and half female, and each replicate had 20 Chinese chickens. broilers with yellow plumage. The chicken coops and devices were sterilized before testing. During the trial, cage culture was carried out in the same coop with the same feeding and care conditions. The base diet consisted mainly of corn and soybean meal, and no additional antioxidant components or growth promoters were added during the entire feeding process. Each study group was a control group (Group I) and study groups II-III, respectively. While the control group received only the basic diet, and the study groups II-III received the basic diet, which was supplemented with 600 ppm of various compounds based on γ-quaternary ammonium butyrate. The division into groups is shown in Table 2.

The total duration of the test was 20 days. The studied broilers had free access to food and water, they received food twice a day. Each replication was taken as a unit of the study broilers were weighed at the age of 21 days (after feeding was stopped for 12 hours, but continued to give water) to calculate the feed intake of the study broilers, calculate the average daily feed intake (ADFI, g/day*number of broilers), average daily weight gain (ADG, g/day*number of broilers) and feed conversion rate (FCR) of each group of broilers studied. The formulas for the calculation are as follows:

feed conversion rate (FCR) = average daily feed intake/average daily weight gain.

The test results are shown in Table 2.

From the results in Table 3 it can be seen that the test samples do not affect the feed intake of the test broilers. From the average daily weight gain and feed conversion rate of each study group, it can be seen that compared to the control group, the study group treated with the γ-quaternary ammonium butyrate compound of the present invention showed a significant improvement in weight gain and feed conversion rate. feed in the broilers studied, and the feed conversion rate decreased by 5.86% to 6.64%.

It can be seen that the γ-quaternary ammonium butyrate compounds provided by the present invention can effectively improve the growth performance of broilers.

Each of the technical features of the above embodiments can be combined randomly. To simplify the description, not all possible combinations of each technical feature in the above embodiments are described. However, all combinations of such technical features are to be considered as being within the scope of the present invention, unless such combinations are in conflict with each other.

The above embodiments are merely illustrative of several embodiments of the present invention, which are described specifically and in detail, but should not be construed as limiting the scope of the present invention. It should be noted that several variations and improvements can be made by those skilled in the art without departing from the spirit of the present invention, all of which are within the scope of the present invention. Therefore, the scope of legal protection of the present invention will be determined by the appended claims.

Claims (8)

1. Use of a γ-quaternary ammonium butyrate compound represented by formula (I) as a feed additive for improving the growth performance of farm animals

Formula (I), where A represents a chloride ion or a bromide ion; R is linear C ₁ -C ₃ alkyl, phenyl, or (C ₁ -C ₄ alkylene)phenyl, with phenyl and (C ₁ -C ₄ alkylene)phenyl each optionally substituted with one, two, three, four, or five R ⁴ ; R ⁴ is -OH, -NH ₂ , -NO ₂ , -CN, -SH, -X ₂ , -C ₁ -C ₅ alkoxy, -C ₁ -C ₅ alkyl or C ₁ -C ₅ alkyl substituted with X ₂ where X ₂ is F, Cl, Br or I. 2. Use according to claim 1, wherein the γ-quaternary ammonium butyrate compound represented by formula (I) is characterized by the structural formula

or

. 3. Use according to claim 1, wherein the γ-quaternary ammonium butyrate compound represented by formula (I) is used in combination with at least one animal feed additive.