Use of N-carbamoyl-DL-aspartic acid in the preparation of animal feed additives, feed compositions and use of feed compositions in the preparation of animal feeds

Abstract

The present invention discloses the use of an aspartic acid derivative having a structure represented by formula (I) or its racemate, stereoisomer, geometric isomer, tautomer, solvate or feed-acceptable salt in the preparation of an animal feed additive, which has a good effect on improving the productivity of farmed animals. [Formula 1] TIFF2022506755000019.tif40170 However, Y and X are C1-C independently. 20 alkyl or -H, R 1 is R 1a C(=O) or H, and R 2 is R 2a C(=O), and R 1a and R 2a are each independently (A)(B)N-(CH2) 0-5 - A and B are each independently selected from C1-C 20 is selected from alkyl or -H.

Description

Technical Field

[0001] The present invention belongs to the field of additives for animal feed, and specifically relates to the use of aspartic acid derivatives in the preparation of animal feed additives, as well as feed compositions containing aspartic acid derivatives and their use in the preparation of animal feed additives and animal feed.

Background Art

[0002] N-carbamoyl aspartic acid is an endogenous product in the animal body. When exposed to acid outside the body, it becomes unstable and can form a hydantoin to form a cyclic ureido substance, and is used in the preparation of orotic acid intermediates in the field of chemical fine chemicals. N-carbamoyl aspartic acid is one of the components of cosmetics, has a whitening effect and a nutritional supplement effect, and can promote the absorption of dipeptide drugs as an absorption carrier in the preparation of dipeptide drugs. In addition, Japanese Patent Publication No. 2010-504171, which is a patent document as a prior art document, discloses the use of N-carbamoyl aspartic acid in lung drugs.

Summary of the Invention

[0003] The present invention provides the use of N-carbamoyl aspartic acid and its derivatives (hereinafter both are referred to as aspartic acid derivatives), or their racemates, stereoisomers, geometric isomers, tautomers, solvates and salts acceptable in feed in the preparation of animal feed additives. Further, the present invention provides a feed composition containing the aspartic acid derivative or its racemate, stereoisomer, geometric isomer, tautomer, solvate and salt acceptable in feed, and the use of the composition in the preparation of animal feed additives and animal feed.

[0004] On the other hand, the present invention provides an aspartic acid derivative having a structure represented by formula (I).

Chemical Formula

[0005] In some technical solutions, R 1 is R 1a C(=O)- or -H, and R 2is R 2a is C(=O)-, and said R 1a and R 2a each independently is (A)(B)N-(CH2) 0-5 - wherein said A and B are each independently selected from C1-C 20 alkyl or -H, and Y and X are each independently selected from C1-C 20 alkyl or -H.

[0006] In some technical solutions, R of the aspartic acid derivative 1 is -H.

[0007] In some technical solutions, A and B of the aspartic acid derivative are both -H at the same time.

[0008] In some technical solutions, Y and X of the aspartic acid derivative are -H.

[0009] In some technical solutions, Y and X of the aspartic acid derivative are each independently selected from C1-C 20 alkyl or -H, and are not -H at the same time.

[0010] In some technical solutions, Y and X of the aspartic acid derivative are each independently selected from C1-C4 alkyl or -H, and are not -H at the same time.

[0011] In some technical solutions, the feed-acceptable salt of the aspartic acid derivative is a metal ion salt.

[0012] In some technical solutions, the feed-acceptable salt of the aspartic acid derivative is preferably a sodium ion salt, a zinc ion salt, a copper ion salt, an iron ion salt or a calcium ion salt.

[0013] On the other hand, the present invention provides the use of the aspartic acid derivative of the present invention or its racemate, stereoisomer, geometric isomer, tautomer, solvate or feed-acceptable salt in the preparation of an animal feed additive or animal feed.

[0014] On the other hand, the present invention provides a feed composition comprising at least one of the aspartic acid derivative provided by the present invention or its racemate, stereoisomer, geometric isomer, tautomer, solvate or feed-acceptable salt, and at least one feed auxiliary material.

[0015] The feed auxiliary material is selected from a carrier for feed, a diluent, an excipient, a solvent or a combination thereof.

[0016] In some technical solutions, the feed composition further comprises an animal feed raw material.

[0017] In some technical solutions, the feed composition further comprises an additional animal feed additive.

[0018] In some technical solutions, the feed composition further comprises an animal feed raw material and an additional animal feed additive.

[0019] In some technical solutions, the additional animal feed additive is selected from a nutritional feed additive and / or a general feed additive and / or a pharmaceutical feed additive.

[0020] On the other hand, the present invention provides the use of the feed composition in the preparation of an animal feed additive.

[0021] On the other hand, the present invention provides the use of the feed composition in the preparation of animal feed.

[0022] On the other hand, the present invention further provides a method for improving the production capacity of farmed animals.

Advantages of the Invention

[0023] The beneficial effects of the present invention are as follows.

[0024] As can be seen from the results of animal breeding experiments, the aspartic acid derivative or its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable in feed provided by the present invention is applied as an animal feed additive, and the effect of improving the production capacity of animals is enhanced.

[0025] Any embodiment of any aspect of the present invention can be combined with other embodiments as long as there is no contradiction between them. Also, in any embodiment of any aspect of the present invention, any technical feature can be applied to the technical features in other embodiments as long as there is no contradiction between them.

[0026] The above content only outlines certain aspects of the present invention and is not limited to these aspects. The above related content and the content of other aspects will be further described in detail below.

[0027] The present invention will be described in more detail.

[0028] Here, an embodiment of the present invention will be described in detail, and its examples are shown by the accompanying structural formulas and chemical formulas. The present invention encompasses all alternatives, modifications, and equivalent technical solutions, all of which are intended to be included within the scope of the present invention as defined by the claims. Note that the specific technical features of the present invention can be clearly seen and are separately described in a plurality of independent embodiments, but they can also be provided in a combined form in a single embodiment or in any appropriate sub-combination form.

[0029] Compound. The compound according to the present invention is an aspartic acid derivative having a structure represented by formula (I),

Chemical formula

[0030] Generally, "substituted" means that one or more of the hydrogen atoms that can be substituted in a given structure are substituted with a specific substituent, and the substituent can have a substituent at each substitutable position of the group, and can be substituted with one or more substituents of a specific group at one or more positions of a given structural formula, and the substituents at each position can be the same or different.

[0031] In the present invention, "C1-C 20 alkyl" means a saturated alkyl containing 1 to 20 carbon atoms, for example, methyl, ethyl, propyl, isopropyl,..., and includes linear or branched alkyls containing 20 carbon atoms, "(CH2) 0-5 " means containing 0 to 5 methylene groups, and "(A)(B)N" means an amino group in which a hydrogen atom is substituted with a substituent A and a substituent B.

[0032] Optionally, R 1 is R 1a C(=O)-, and R 2 is R 2a C(=O)-, and the said R 1a and R 2a are each independently (A)(B)N-(CH2) 0-5 -selected from, wherein A and B are each independently C1-C 20 alkyl or -H.

[0033] Optionally, R 1 is -H, R 2 is R 2a C(=O)-, and R 2a is (A)(B)N-(CH2) 0-5 - wherein A and B are each independently C1-C 20 alkyl or -H.

[0034] Optionally, when A and B of said (A)(B)N-(CH2) 0-5 - are both -H, (A)(B)N-(CH2) 0-5 - is NH2(CH2) 0-5 - .

[0035] Optionally, A and B of said (A)(B)N-(CH2) 0-5 - are each independently selected from C1-C 20 alkyl or -H, but not both -H at the same time.

[0036] Furthermore, R 2a is (A)(B)N-(CH2) 0-5 - wherein all of A and B are C1-C 20 alkyl.

[0037] Still further, R 2a is (A)(B)N-(CH2) 0-5 - wherein all of A and B are C1-C4 alkyl.

[0038] Specifically, said R 2a is (A)(B)N-(CH2) 0-5 - wherein all of A and B are linear C1-C4 alkyl.

[0039] In some embodiments, R 2a is (CH3)2N-, (N,N'-dimethyl)N-(CH2)-, (N,N'-dimethyl)N-(CH2)2-, (N,N'-dimethyl)N-(CH2)3-, (N,N'-dimethyl)N-(CH2)4- or (N,N'-dimethyl)N-(CH2)5-.

[0040] In other embodiments, R 2a is N,N'-di-n-butylamino, (N,N'-di-n-butyl)N-(CH2)-, (N,N'-di-n-butyl)N-(CH2)2-, (N,N'-di-n-butyl)N-(CH2)3-, (N,N'-di-n-butyl)N-(CH2)4- or (N,N'-di-n-butyl)N-(CH2)5-.

[0041] Specifically, said R 2a is (A)(B)N-(CH2) 0-5 - wherein A and B are both branched C1-C4 alkyls.

[0042] In some embodiments, R 2a is N,N'-diisopropylamino, (N,N'-diisopropyl)N-(CH2)-, (N,N'-diisopropyl)N-(CH2)2-, (N,N'-diisopropyl)N-(CH2)3-, (N,N'-diisopropyl)N-(CH2)4- or (N,N'-diisopropyl)N-(CH2)5-.

[0043] In other embodiments, R 2a is N,N'-diisobutylamino, (N,N'-diisobutyl)N-(CH2)-, (N,N'-diisobutyl)N-(CH2)2-, (N,N'-diisobutyl)N-(CH2)3-, (N,N'-diisobutyl)N-(CH2)4- or N,N'-diisobutyl)N-(CH2)5-.

[0044] Furthermore, R 2a is (A)(B)N-(CH2) 0-5- and when said A is C1-C 20 alkyl, B is simultaneously H.

[0045] Furthermore, R 2a is (A)(B)N-(CH2) 0-5 - and when said A is C1-C4 alkyl, B is simultaneously H.

[0046] Specifically, R 2a is (A)(B)N-(CH2) 0-5 - and when said A is linear C1-C4 alkyl, B is simultaneously H.

[0047] In some embodiments, R 2a is N-methylamino, (N'-1H-N-methyl)N-(CH2)-, (N'-1H-N-methyl)N-(CH2)2-, (N'-1H-N-methyl)N-(CH2)3-, (N'-1H-N-methyl)N-(CH2)4- or (N'-1H-N-methyl)N-(CH2)5-.

[0048] In other embodiments, R 2a is N-n-butylamino, (N'-1H-N-n-butyl)N-(CH2)-, (N'-1H-N-n-butyl)N-(CH2)2-, (N'-1H-N-n-butyl)N-(CH2)3-, (N'-1H-N-n-butyl)N-(CH2)4- or (N'-1H-N-n-butyl)N-(CH2)5-.

[0049] Specifically, R 2a is (A)(B)N-(CH2) 0-5 - and when said A is branched C1-C4 alkyl, B is simultaneously H.

[0050] In some embodiments, R 2ais N-isopropylamino, (N'-1H-N-isopropyl)N-(CH2)-, (N'-1H-N-isopropyl)N-(CH2)2-, (N'-1H-N-isopropyl)N-(CH2)3-, (N'-1H-N-isopropyl)N-(CH2)4- or (N'-1H-N-isopropyl)N-(CH2)5-.

[0051] In other embodiments, R 2a is N-isobutylamino, (N'-1H-N-isobutyl)N-(CH2)-, (N'-1H-N-isobutyl)N-(CH2)2-, (N'-1H-N-isobutyl)N-(CH2)3-, (N'-1H-N-isobutyl)N-(CH2)4- or (N'-1H-N-isobutyl)N-(CH2)5-.

[0052] Optionally, Y and X are simultaneously -H.

[0053] Optionally, Y and X are each independently selected from C1-C 20 alkyl or -H, and are not simultaneously -H.

[0054] Specifically, Y and X are simultaneously C1-C 20 alkyl, or are each one of C1-C 20 alkyl and -H.

[0055] Optionally, the C1-C 20 alkyl is a straight-chain alkyl.

[0056] In some embodiments, the straight-chain alkyl is methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-octadecyl.

[0057] Optionally, the C1-C 20 alkyl is a branched-chain alkyl.

[0058] In some embodiments, the branched alkyl is isopropyl or t-butyl.

[0059] Optionally, the C1-C 20 alkyl is cycloalkyl.

[0060] In some embodiments, the cycloalkyl is cyclopropyl, cyclopentyl or cyclohexyl.

[0061] In some embodiments, the aspartic acid derivative having the structure represented by the formula (I) is a salt acceptable for feed.

[0062] Furthermore, the salt acceptable for feed is a metal ion salt, and the metal ion salt is a substance formed by the combination of a metal ion and an acid donor aspartic acid derivative according to the charge conservation rule, and is a chelate compound formed by a metal ion bond and a complexation of the aspartic acid derivative or a chelate bond through the electrical properties of the metal ion and the aspartic acid derivative.

[0063] Optionally, the metal ion is a monovalent metal ion, a divalent metal ion or a trivalent metal ion.

[0064] Specifically, the monovalent metal ions include, but are not limited to, sodium ion, potassium ion, lithium ion, ammonium ion, the divalent metal ions include, but are not limited to, calcium ion, magnesium ion, zinc ion, copper ion, ferrous ion, manganese ion, and the trivalent metal ions include, but are not limited to, iron ion, nickel ion, chromium ion, aluminum ion.

[0065] In some embodiments, the metal ion is zinc ion.

[0066] In other embodiments, the metal ion is copper ion.

[0067] In other embodiments, the metal ion is a sodium ion.

[0068] In other embodiments, the metal ion is a calcium ion.

[0069] In other embodiments, the metal ion is an iron ion.

[0070] Preparation and purification of the compound. When using aspartic acid (Asp) as the starting material, the main chemical reactions involved in the preparation method of the aspartic acid derivative represented by formula (I) according to the present invention mainly include acylation of amino, esterification of carboxyl, and hydrolysis of carboxyl ester.

[0071] In some embodiments, Y and X of formula (I) are C1-C 20 alkyl or H, but not H at the same time. The preparation method of the aspartic acid derivative represented by formula (I) includes two reactions of esterification of carboxyl and acylation of amino, as shown in formula (II).

Chemical formula

[0072] For clarity, X and R in formula (II) 1 only represent substituents. When the substances represented by the raw materials X-OH and R 1 -OH are not single substances, X or R 1 should be understood as a set of substituents. R 1 -OH in formula (II) and the following various formulas is H2N-(CH2) 0-5 (C=O)OH, when the amino group contained therein is protected by a t-butoxycarbonyl protecting group (Boc-), and the Boc protecting group is removed under trifluoroacetate (F3CCOOH) or other de-substitution conditions after the reaction is completed. In addition, SOC l2is thionyl chloride, rt. indicates room temperature, EtN(Pr-i)2 indicates diisopropylethylamine, DMF indicates N,N-dimethylformamide, and HBTU indicates O-benzotriazole-tetramethylurea hexafluorophosphate (coupling agent).

[0073] In some embodiments, Y and X are both -H at the same time, and the method for synthesizing the aspartic acid derivative is represented by formula (III) using di-t-butyl aspartate (t-Bu-Asp) as a raw material.

Chemical formula

[0074] For clarity, R in formula (III) 1 only represents a substituent. When the raw material R 1 -OH is not a single substance, R on the target product (TM) 1 should be understood as a set of substituents. t-Bu indicates t-butyl as a protecting group for the carboxyl group, DCM indicates dichloromethane, NaOH indicates sodium hydroxide, and F3CCOOH indicates trifluoroacetate.

[0075] Furthermore, when Y and X are both -H at the same time, or each is one of C1-C 20 alkyl and -H, the aspartic acid derivative reacts with a metal chloride or metal bromide under alkaline conditions to produce a metal ion salt of the aspartic acid derivative, such as a metal ion salt according to the present invention, such as a zinc salt, copper salt, calcium salt, iron salt, or sodium salt.

[0076] In some embodiments, the di-t-butyl aspartate is a chiral compound, and the di-t-butyl aspartate of the present invention is selected from L-(-)-di-t-butyl aspartate (the structure is shown in formula (IV)), D-(+)-di-t-butyl aspartate (the structure is shown in formula (V)), or racemic-DL-(±)-di-t-butyl aspartate, and reacts with the participating alcohol and carboxylic acid derivative to obtain a stereoisomer or racemate of an aspartic acid derivative having a chiral center.

Chemical formula

[0077] In some embodiments, the chiral stereoisomers of the di-t-butyl aspartate and the stereoisomers of the aspartic acid derivative undergo a conformational conversion such as the tautomerism of the three-dimensional conformation of t-Bu-aspartic acid or the aspartic acid derivative under appropriate conditions. For example, the tautomerism process of the three-dimensional conformation of t-Bu-aspartic acid is shown in formula (VI):

Chemical formula

[0078] When the participating reactants react with di-t-butyl aspartate and the like to generate a corresponding aspartic acid derivative with a rigid structure, the reaction substrate may generate different geometric isomer products during the reaction.

[0079] The above-mentioned stereoisomers, geometric isomers, and tautomers are also included within the scope of the present invention.

[0080] The "stereoisomers" according to the present invention refer to compounds having the same chemical structure but different arrangements of atoms or groups in space, including enantiomers, diastereomers, conformational isomers, geometric isomers, atropisomers, etc. "Enantiomers" refer to two isomers of a compound that cannot be superimposed but are mirror images of each other. "Diastereomers" refer to stereoisomers having two or more chiral centers, where the molecules are not mirror images of each other and have different physical properties such as melting point, boiling point, spectral characteristics, reactivity, etc. A mixture of diastereomers can be separated by high-resolution analytical operations such as electrophoresis and chromatography. "Tautomers" refer to structural isomers with different energies that can be converted into each other via a low energy barrier.

[0081] In some embodiments, the preparation process of the aspartic acid derivative provided by the present invention also includes the separation, purification, or recrystallization process of the reaction product. The reaction product can be obtained as a crude product from the reaction system by a solvent removal method. In order to obtain a solid with high chemical purity and low impurity content, the crude product is dissolved, crystallized, or precipitated or recrystallized and separated under appropriate temperature, light, and mechanical vibration through an alcohol solvent, an alcohol-water mixed solvent, or other organic solvents that can be used for the recrystallization of the product to obtain an aspartic acid derivative having a specific crystalline state. The aspartic acid derivative having the specific crystalline state is an aspartic acid derivative crystal or a solvate of the aspartic acid derivative. The solvate of the aspartic acid derivative can be selected from a hydrate of the aspartic acid derivative or an ethanolate of the aspartic acid derivative.

[0082] The "solvate" according to the present invention is a eutectic compound formed by bonding solvent molecules that are chemically equivalent or non-chemically equivalent by non-covalent intermolecular forces under external and internal conditions during the contact between the compound of the invention and the solvent molecules. Solvents that form solvates include, but are not limited to, solvents such as water, acetone, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, isopropanol, etc. "Hydrate" refers to a compound or crystal formed by solvent molecules that are water, that is, a compound to which water that is chemically equivalent or non-chemically equivalent is bonded via non-covalent intermolecular forces.

[0083] The preparation of the aspartic acid derivative provided by the present invention can be processed by the salting-out method in order to obtain higher chemical purity and lower impurity solids. The salting-out method uses the principles of the acid-base neutralization method, the acid-base coordination method, or the acid-base chelation method to obtain a salt acceptable for feed through the precipitation process of the aspartic acid derivative and the corresponding organic base, inorganic base, organic acid, or inorganic acid salt.

[0084] The salt acceptable for feed is a salt formed by the aspartic acid derivative of the present invention and an organic base, inorganic base, organic acid, or inorganic acid that is non-toxic to animals. The term "acceptable for feed" means that the substance or composition must be chemically or toxicologically appropriate and is related to the composition of feed or edible farm animals.

[0085] In some embodiments, the aspartic acid derivative is a diester or a mixed ester (i.e., Y and X are simultaneously the same or different C1-C 20is (alkyl), and the post-treatment salting-out precipitation process generates an acid-base coordination salt and / or an acid-base chelate salt with an inorganic acid or an organic acid. The organic acids include, but are not limited to, 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-toluic acid, cinnamic acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, or combinations thereof. The inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, nitric acid, or combinations thereof.

[0086] In some embodiments, the aspartic acid derivative is a monoester (i.e., Y and X are each C1-C 20 alkyl and one of -H), and the post-treatment salting-out precipitation process generates an acid-base coordination salt and / or an acid-base chelate salt with an organic acid or an inorganic acid, or generates an acidic salt with an organic base or an inorganic base. The organic acids include, but are not limited to, 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-toluic acid, cinnamic acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, or combinations thereof. The inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, nitric acid, or combinations thereof. The organic bases include, but are not limited to, ammonia or triethylamine. The inorganic bases include, but are not limited to, sodium hydroxide, potassium hydroxide, magnesium hydroxide, or calcium hydroxide.

[0087] Study on the stability of aspartic acid derivatives.

[0088] The aspartic acid derivative or its racemate, stereoisomer, geometric isomer, tautomer, solvate or feed-acceptable salt provided by the present invention has its compound stability measured under the condition of 60°C, with an experimental period of 10 days, and the content of the compound does not change significantly with the passage of time during the experimental period.

[0089] The present invention relates to the use of aspartic acid derivatives.

[0090] The aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or feed-acceptable salt provided by the present invention are applied to the preparation of animal feed additives.

[0091] The "animal" according to the present invention refers to a human or a farmed animal that cannot synthesize inorganic substances into organic substances and conducts life activities such as ingestion, digestion, absorption, respiration, circulation, excretion, sensation, movement and reproduction. "Farmed animals" include other animals that are legally farmed, including poultry, livestock, aquaculture animals, and pets such as cats and dogs. The term "livestock" is any one of, for example, pigs, cows, horses, goats, sheep, deer and many useful rodents. The term "poultry" is, for example, chickens, ducks, geese, quails, pigeons, etc. The term "aquaculture animals" is fish, shrimps, turtles, soft-shelled turtles, etc.

[0092] The "feed additive" according to the present invention refers to a small amount or trace amount of substances added during the processes of feed processing, manufacturing, and use, and is divided into nutritional feed additives and general feed additives (also called non-nutritional feed additives). Nutritional feed additives refer to small amounts or trace amounts of substances added to compound feeds to balance feed nutrients, improve feed utilization, and directly exert nutritional effects on animals, such as vitamins, trace elements, amino acids, small peptides, non-protein nitrogen, etc. General feed additives, also called non-nutritional additives, refer to some non-nutritional substances added to feeds to improve feed utilization and ensure feed quality and quality, including growth promoters, insect repellents, and other health care additives, feed additives, feed storage agents, and traditional Chinese medicine additives beneficial to animal health and metabolism.

[0093] By applying the aspartic acid derivative or its racemate, stereoisomer, geometric isomer, tautomer, solvate or salt acceptable in feed provided by the present invention, a non-nutritional additive for improving the production capacity of animals at each growth stage is prepared, and the animals are selected from livestock, poultry, aquaculture animals or pets at each growth stage.

[0094] Furthermore, the livestock includes, but is not limited to, pigs, cows, sheep, horses, rabbits, minks or donkeys; the poultry includes, but is not limited to, chickens, turkeys, ducks, geese, quails or pigeons; the aquaculture animals includes, but is not limited to, fish, shrimps, turtles, crabs, soft-shell turtles, bullfrogs, eels or loaches; and the pets includes various subspecies of dogs or cats, but is not limited thereto.

[0095] In one embodiment, by applying the aspartic acid derivative or its racemate, stereoisomer, geometric isomer, tautomer, solvate or salt acceptable in feed provided by the present invention, a feed additive for weaned pigs is prepared, which can improve the average daily weight gain of weaned pigs and improve the feed conversion rate without affecting the feed intake.

[0096] In another embodiment, the aspartic acid derivative or its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt provided by the present invention is applied to prepare a feed additive for laying hens, which can effectively improve the egg - laying rate of laying hens, increase the egg weight and reduce the feed - to - egg ratio of laying hens.

[0097] In another embodiment, the feed additive prepared by applying the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt provided by the present invention can significantly improve the production capacity of broilers.

[0098] In yet another embodiment, the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt provided by the present invention are applied to prepare a feed additive for improving the production capacity of fish.

[0099] In one embodiment, the aspartic acid derivative is a zinc salt, and a feed additive for animals is prepared as a substitute for high - dose inorganic zinc for animals.

[0100] In another embodiment, the aspartic acid derivative is a copper salt, and a feed additive for animals is prepared as a substitute for high - dose inorganic copper for animals.

[0101] A feed composition according to the present invention. Provided is a feed composition comprising at least one of an aspartic acid derivative or its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt and a feed auxiliary material, wherein the feed auxiliary material is a feed carrier, diluent, adjuvant, solvent or a combination thereof.

[0102] The feed according to the present invention refers to a product industrially processed and manufactured for animal consumption.

[0103] The "composition" according to the present invention refers to a group of compounds containing one or more compounds as active ingredients.

[0104] The "including" in the present invention is an open expression that includes the content explicitly mentioned in the present invention but does not exclude other aspects.

[0105] The "carrier" according to the present invention refers to a substance that can carry the active ingredient, improve its dispersibility, and has good chemical stability and adsorbability, and it includes organic carriers and inorganic carriers. The organic carrier is a material containing a large amount of coarse fibers, including but not limited to corn flour, corn cob powder, wheat bran, rice husk powder, defatted rice bran, rice bran, corn stalk powder, peanut shell powder, etc. The inorganic carrier is mainly a mineral divided into calcium salts and silicon oxides, which is used in the production of trace element premixes, including but not limited to calcium carbonate, silicate, vermiculite, zeolite, sepiolite, etc.

[0106] The "diluent" according to the present invention refers to a substance that evenly distributes the additive raw material in the material, dilutes the high-concentration additive raw material into a low-concentration premix or premix, separates trace components from each other, reduces the interaction between active ingredients, and enhances the stability of the active ingredients without affecting the physical and chemical properties of related substances, and includes organic diluents and inorganic diluents. Organic diluents include but are not limited to corn flour, germinated corn flour, dextrose (glucose), sucrose, semolina flour with bran, fried soybean powder, wheat middling, corn gluten meal, etc. Inorganic diluents include but are not limited to limestone, calcium dihydrogen phosphate, shell powder, kaolin (white clay), table salt, and sodium sulfate.

[0107] The auxiliary agent is a wetting agent that induces the intrinsic viscosity of the substance, an adhesive that binds the substance, a disintegrant that decomposes the whole sheet of the substance into many fine particles and reduces the particle size, a retention aid for reducing the frictional force between particles, or an anti-adhesive for preventing the adhesion of the material, and includes but is not limited to magnesium stearate, talc, vegetable oil, magnesium lauryl sulfate, starch, starch slurry, water, inorganic salts, dextrin, powdered sugar, etc.

[0108] The "solvent" according to the present invention refers to a solvent necessary for dissolving or dispersing a solid, and includes, but is not limited to, water, ethanol, glycerin, etc.

[0109] In some embodiments, the feed composition further comprises an additional animal feed additive and / or an animal feed raw material.

[0110] The animal feed additive is a nutritional feed additive, a general feed additive or a pharmaceutical feed additive.

[0111] The nutritional feed additive refers to a small amount or trace amount of substances added to compound feeds to balance feed nutrients, improve feed utilization, and directly exert a nutritional effect on animals, and includes amino acids, amino acid salts and their analogs, vitamins, and retinoid vitamins, mineral elements and their complexes (chelates), microbial enzyme preparations or non-protein nitrogen.

[0112] The general feed additive is also called a non-nutritional additive, and refers to some non-nutritional substances added to feeds to improve feed utilization, ensure feed quality and quality, and be beneficial to animal health and metabolism, including growth promoters, healthcare agents, flavors and attractants, feed additives, feed additives, probiotics, prebiotics, feed storage agents and traditional Chinese medicine additives in China.

[0113] More specifically, the non-nutritional additive is a growth promoter, and includes, but is not limited to, butyric acid, calcium butyrate, sodium butyrate, tannic acid, p-cymene, p-cymene ester, p-cymene 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, zinc chloride.

[0114] In one example, the non-nutritional additive is calcium butyrate.

[0115] In another embodiment, the non-nutritive additive is tannic acid.

[0116] Specifically, the pharmaceutical feed additive includes, but is not limited to, animal pharmaceutical premix substances that can prevent animal diseases and promote animal growth and can be added to feed for a long time to incorporate carriers or diluents.

[0117] More specifically, the pharmaceutical feed additive is an antibiotic for feed, and the antibiotics for feed include, but are not limited to, polymyxin, salinomycin, avilamycin, bacitracin, virginiamycin, nosiheptide, flavomycin, enramycin, kitasamycin, olaquindox, oxytetracycline or chlortetracycline.

[0118] In some embodiments, a composition comprising an aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable in feed further comprises one or more of a nutritional feed additive, a general feed additive and a pharmaceutical feed additive.

[0119] In some embodiments, the animal feed raw materials are grains and their processed products, oilseed grains and their processed products, legal crops and their processed products, tubers, tubers and their processed products, other seeds and fruit products, and their processed products, feeds, roughages 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, microbial fermentation products and their by-products, other feed materials and other feed materials.

[0120] Use of the feed composition. The present invention relates to the use of a feed composition comprising the above-mentioned aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable in feed.

[0121] In some embodiments, the feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt thereof is applied to the preparation of animal feed additives.

[0122] The animal feed additive prepared by applying the feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt thereof is a livestock feed additive, a poultry feed additive, an aquaculture animal feed additive or a pet feed additive.

[0123] Specifically, a livestock feed additive is prepared by applying the feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt thereof. The livestock includes, but is not limited to, pigs, cows, sheep, horses, rabbits, minks, etc. at each growth stage.

[0124] Specifically, a poultry feed additive is prepared by applying the feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt thereof. The poultry includes, but is not limited to, chickens, ducks, geese, pigeons, etc. at each growth stage.

[0125] Specifically, an aquaculture animal feed additive is prepared by applying the feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt thereof. The aquaculture animals include, but is not limited to, fish, shrimps, crabs, turtles, eels, etc. at each growth stage.

[0126] Specifically, a pet feed additive is prepared by applying the feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt thereof. The pets include, but are not limited to, artificially - raised dogs or cats.

[0127] In some embodiments, the animal feed additive prepared by applying a composition comprising the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt is a premix, compound premix, aqueous agent or granule.

[0128] In some embodiments, the feed composition comprising the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt is applied to the preparation of animal feed.

[0129] The animal feed prepared by applying the feed composition comprising the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt is livestock feed, poultry feed, aquaculture animal feed or pet feed.

[0130] Specifically, a livestock feed is prepared by applying the feed composition comprising the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt, and the livestock includes, but is not limited to, pigs, cows, sheep, horses, rabbits, minks, etc. at each growth stage.

[0131] Specifically, a poultry feed is prepared by applying the feed composition comprising the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt, and the poultry includes, but is not limited to, chickens, ducks, geese, pigeons, etc. at each growth stage.

[0132] Specifically, an aquaculture animal feed is prepared by applying the feed composition comprising the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed - acceptable salt, and the aquaculture animals includes, but is not limited to, fish, shrimps, crabs, turtles, eels, etc. at each growth stage.

[0133] Specifically, a pet feed is prepared by applying a feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable for feed, and the pets include, but are not limited to, artificially raised dogs or cats.

[0134] In some embodiments, the feed prepared by applying a feed composition containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable for feed is a single feed, concentrated feed, compound feed, compound premix or concentrated supplementary feed.

[0135] Specifically, the compound feed is a complete compound feed.

[0136] A method for improving the production capacity of farmed animals. In some feeding examples, farmers can effectively improve the production capacity of animals by feeding the animals with a feed additive or feed containing the aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable for feed.

[0137] In some embodiments, the feed additive or feed is a premix, compound premix, granule or aqueous agent, and is uniformly mixed with the animal feed and fed to the animals.

[0138] The animals are livestock, poultry, aquaculture animals or pets.

[0139] Specifically, the livestock include, but are not limited to, pigs, cows, sheep, horses, rabbits, minks, etc. at each growth stage; the poultry include, but are not limited to, chickens, ducks, geese, pigeons, etc. at each growth stage; the aquaculture animals include, but are not limited to, fish, shrimps, crabs, turtles, eels, etc. at each growth stage; and the pets include, but are not limited to, artificially raised dogs or cats.

[0140] In some embodiments, the farmer feeds a feed additive or feed containing an aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed-acceptable salt to weaned pigs, which can significantly improve the feed intake and average daily weight gain of the weaned pigs, and effectively improve the feed conversion rate.

[0141] In a specific embodiment, the aspartic acid derivative contained in the feed additive or feed fed to weaned pigs by the farmer together with the feed is zinc N-carbamoyl-aspartate, which can significantly improve the feed intake and average daily weight gain of the weaned pigs, effectively increase the feed conversion rate, and the improvement of the production capacity of weaned pigs by the feed additive reaches the level of high-dose inorganic zinc.

[0142] In another specific embodiment, the aspartic acid derivative contained in the feed additive or feed fed to weaned pigs by the farmer together with the feed is copper N-carbamoyl-aspartate, which can significantly improve the average daily weight gain of the weaned pigs, effectively increase the feed conversion rate, and the improvement of the production capacity of weaned pigs by the feed additive reaches the level of high-dose inorganic copper.

[0143] In one embodiment, the farmer feeds a feed additive or feed containing an aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed-acceptable salt to broilers, which can effectively improve the weight gain, significantly reduce the feed-to-meat ratio of the broilers, and increase the feed conversion rate.

[0144] In one embodiment, the farmer feeds a feed additive or feed containing an aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed-acceptable salt to laying hens, which can significantly improve the laying rate, increase the egg weight and reduce the feed-to-egg ratio.

[0145] In one embodiment, the farmer feeds a feed additive or feed containing an aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a feed-acceptable salt to fish.

[0146] In one embodiment, the breeder feeds a puppy with a feed additive or feed containing an aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable in the feed.

[0147] In another feeding embodiment, the breeder feeds an animal with a composition for feed containing an aspartic acid derivative and its racemate, stereoisomer, geometric isomer, tautomer, solvate or a salt acceptable in the feed, and significantly improves the production capacity of the animal.

[0148] Optionally, the composition for feed is a feed additive premix, a compound feed additive premix, a granule or an aqueous agent, and is fed to the animal together with the feed.

[0149] In one embodiment, the composition for feed is a feed additive premix.

[0150] In one embodiment, the composition for feed is a compound feed additive premix.

[0151] Optionally, the composition for feed is a concentrated feed, a compound feed, a compound premix or a concentrated supplementary feed, and is directly fed to the animal as animal feed.

[0152] In one embodiment, the composition for feed is a complete compound feed.

[0153] Here, certain embodiments of the present invention will be described in detail, and the examples thereof are shown by the accompanying structural formulas and chemical formulas. The present invention is intended to cover all alternatives, modifications, and equivalent technical solutions, all of which are included in the scope of the present invention defined by the claims. It should be noted that the specific technical features of the present invention can be clearly seen and are separately described in a plurality of independent embodiments, but can also be provided in a combined form in a single embodiment or in any suitable sub-combination form.

Embodiments for Carrying out the Invention

[0154] To make the objectives, technical solutions, and advantages of the present invention clearer, the compounds, compositions, and uses of the present invention will be further described in more detail below through examples. It should be understood that the specific examples described herein are only used to illustrate the present invention and are not used to limit the present invention.

[0155] Example 1: Preparation of a Compound Example 1.1 Preparation of N-carbamoyl-DL-aspartic acid

Chemical formula

[0156] 1 HNMR (500 MHz, DMSO-d6) δ: 12.48 (s, 2H), 6.28 (d, 1H), 5.72 (s, 2H5), 4.35 - 4.38 (m, 1H), 2.56 - 2.67 (m, 2H).

[0157] Example 2 Preparation of N-glycyl-DL-aspartic acid

Chemical formula

[0158] 1.5 g of N-(N-Boc-glycyl)-aspartic acid di-t-butyl obtained by the above procedure was dissolved in 100 ml of dry dichloromethane, 8 ml of trifluoroacetate was added, and the mixture was stirred and reacted at room temperature for 24 hours, washed with water (50 ml × 3 times), concentrated under reduced pressure to remove the solvent, and the obtained crude product was recrystallized from ethyl acetate to obtain 0.6 g of N-glycyl-DL-aspartic acid with a yield of 72.7%.

[0159] Example 3: Thermal Stability Study Experiment of Compounds The aspartic acid derivative raw material and its 2% mass fraction premix (hereinafter abbreviated as 2% premix) were respectively examined for the change over time in the content of its main component under the 60 °C stability experiment conditions.

[0160] Experimental equipment: Pharmaceutical stability incubator, Waters high performance liquid chromatography (HPLC), etc.

[0161] Test samples: N-carbamoyl-DL-aspartic acid (Compound 1), N-carbamoyl-DL-aspartic acid diethyl ester (Compound 2), sodium N-carbamoyl-DL-aspartate (Compound 3), calcium N-carbamoyl-DL-aspartate (Compound 4), zinc N-carbamoyl-DL-aspartate (Compound 5), copper N-carbamoyl-DL-aspartate (Compound 6), iron N-carbamoyl-DL-aspartate (Compound 7), N-glycyl-DL-aspartic acid (Compound 8), N-(4-aminobutyryl)-DL-aspartic acid (Compound 9), N-(10-aminodecanoyl)-DL-aspartic acid (Compound 10), N-(14-aminomyristoyl)-DL-aspartic acid (Compound 11).

[0162] Experimental reagents: methanol (chromatography grade), phosphoric acid (analytical grade).

[0163] Experimental procedures: Preparation of standard solution: Accurately weigh 50 mg of the raw material of the test sample, add 50 mL of water, and dissolve it by ultrasonic wave to prepare a working stock solution. Take an appropriate amount of the working stock solution and dilute it with water to working solutions with concentrations of 125 ppm, 250 ppm, 500 ppm, and 1000 ppm respectively, and measure by HPLC. Confirm whether the sample concentration and the HPLC peak area response value are linear, and prepare a calibration curve.

[0164] Preparation of test sample solution: Add an appropriate amount of water to an appropriate amount of the test sample raw material and a 2% premix (hereinafter abbreviated as 2% premix) with a test sample mass fraction, dissolve it by ultrasonic wave to obtain a 1000 ppm solution, filter it with a 0.22 μm filter membrane, and then perform HPLC analysis.

[0165] HPLC detection conditions: Chromatography column: watersC 18Column (250 mm × 4.6 mm, 5 μm), mobile phase: 0.05% phosphoric acid: methanol = 95:5 (V:V) (raw material), 0.05% phosphoric acid: methanol (gradient elution), methanol: 5% → 40% (0 - 15 min) curve 6, 40% → 5% (15 - 16 min) curve 1, 5% (16 - 23 min) curve 1, (premix, feed), detection wavelength: 210 nm, column temperature: 25 °C, sample size: 20 μL, flow rate: 1 ml / min.

[0166] Experimental method: The test sample raw material and its 2% premix were placed in a petri dish, spread into a thin layer of ≤5 mm, left at 60 °C, and HPLC detection samples were collected on the 5th and 10th days. Each sample was collected in parallel 3 times.

[0167] Experimental results: The experimental results are expressed as "average values" and shown in Table 1. As can be seen from the experimental results, except that the content of iron N-carbamoyl-DL-aspartate decreased to 94.98% on the 10th day during the 0 - 10-day experimental period, the contents of the raw materials of each test sample and its 2% premix did not change significantly under the high-temperature condition of 60 °C, indicating excellent stability.

Table 1

[0168] Example 4: Breeding experiment Example 4.1 Influence of derivatives of aspartic acid and their salts on the production capacity of weaned piglets From 95 litters of weaned piglets of the three - breed cross “Duroc×Landrace×Yorkshire” at 28±2 days of age, 360 pigs of similar body weight were selected as test pigs and randomly divided into 12 groups, with 3 replicates in each group. In each replicate, there were 5 male and 5 female pigs, for a total of 10 pigs. The piglets started attracting feed at 7 days of age. The weaned pigsty at 28 days of age had a cement floor, steel bar fences, good ventilation, and appropriate temperature. Before the experiment, the pigsty and cooking utensils were sterilized. During the experimental period, the experimental pigs were housed separately in the same feeding and management conditions, with the same feeding and drinking. The pigsty was cleaned once a day, the floor was washed once every 3 days to maintain a clean and hygienic state, and the feed was provided 3 times a day. Each experimental group was divided into a control group and an experimental group. Group I was the control group, and the piglets were given a basic feed. In experimental groups II - VII, the feed given to the piglets was the basic feed with 50 ppm of aspartic acid derivative added respectively, as shown in Table 2. In groups VIII - XII, the feed given to the piglets was the basic feed with 1000 ppm of aspartic acid derivative metal ion salt added respectively, as shown in Table 2. Throughout the feeding process, no other antioxidant components or growth promoters were added to each experimental group. The experimental period was 40 days.

[0169] The body weights of the experimental pigs were measured from 7:00 to 9:00 am on day 0 and day 40 after the start of the experiment. During the experimental period, the feed intake and health status of the piglets were observed daily, the remaining feed was weighed, the feed consumption was recorded, and the average daily feed intake (ADFI, g / d*head), average daily weight gain (ADG, g / d*head), and feed - to - meat ratio (FCR) were calculated. They were calculated by the following formulas: Average daily feed intake=(total feed amount - remaining amount) / (number of experimental days×number of replicated pigs), Average daily weight gain=(average weight at the end of the experiment - average weight at the beginning of the experiment) / number of experimental days, Feed - to - meat ratio=average daily feed intake / average daily weight gain.

[0170] The experimental data were statistically analyzed by SPSS 18 software. First, the data were analyzed by one-way analysis of variance (ANOVA). When the difference between treatments was significant, multiple comparisons were performed by Duncan's method, and the significance level was 0.05. The experimental results were presented as "mean ± standard error", and the experimental results are shown in Table 2.

[0171] As can be seen from the feeding experiment results of weaned piglets, when comparing each experimental group with the control group, except for diethyl N-carbamoyl-DL-aspartate, sodium N-carbamoyl-DL-aspartate, and zinc N-carbamoyl-DL-aspartate, other test samples had no obvious effect on the feed intake of weaned pigs. Regarding the average daily weight gain, the experimental pigs increased by 7.0%, 5.2%, and 8.1% respectively with N-carbamoyl-DL-aspartic acid, N-glycyl-DL-aspartic acid, and N-(4-aminobutyryl)-DL-aspartic acid, but the effect was not significant compared with the control group. In other experimental groups, the average daily weight gain of the experimental pigs showed a significant improvement effect compared with the control group. Regarding the feed conversion rate, each experimental group decreased by 4.8% - 7.8%, and no significant improvement effect was observed compared with the control group.

Table 2

[0172] Example 4.2 Effect of Aspartic Acid Derivatives on the Production Capacity of Laying Hens In the experiment, a single-factor randomized design was adopted. 420 Beijing White laying hens at 147 days old and with similar body weights were selected and randomly divided into 7 treatment groups, with each group replicated 3 times. There were an equal number of males and females, and each replication had 20 Beijing White laying hens. Before the experiment, the chicken coop and cooking utensils were sterilized. During the experimental period, the hens were raised in cages under the same feeding and management conditions in the same chicken coop. The basal diet mainly consisted of corn-soybean meal, and no other antioxidant components or growth promoters were added throughout the feeding process. Each experimental group was the control group, and experimental groups I - VII respectively. Experimental group I was the control group, fed only the basal diet, and experimental groups II - VII had different aspartic acid derivatives added to the basal diet at 500 ppm each. The details are shown in Table 3. A 10-day pre-feeding period was conducted, the experimental period was 158 days, and the experimental hens had free access to water and feed and were fed twice a day.

[0173] Parameter statistics: During the experimental period, the daily egg production number, egg production amount, and feed intake were recorded daily in units of replication. The egg production rate (EPR), average daily feed intake (ADFI, g / d), egg weight (EW, g), and feed-to-egg ratio (FER) of the laying hens during the experimental period were calculated. They were calculated by the following formulas: Egg production rate (%) = average total daily egg number / number of hens × 100, Egg weight (g) = average total daily egg weight / average total daily egg number, Feed-to-egg ratio = average daily feed intake / egg weight.

[0174] The experimental data were statistically analyzed using SPSS 18 software. First, the data were analyzed by one-way analysis of variance (ANOVA). If the difference between treatments was significant, multiple comparisons were made by Duncan's method. The significance level was 0.05. The experimental results were presented as "mean ± standard error", and the experimental results are shown in Table 4.

[0175] As can be seen from the results, the effects of the test samples on the egg production rate and feed-to-egg ratio of experimental chickens were not significantly improved compared with the control group, but different degrees of improvement effects occurred. The egg production rate increased by 2.7% - 4.4%, the feed-to-egg ratio decreased by 5.9% - 7.6%, the test samples did not affect the feed intake of experimental chickens, but the egg weights of all other groups except N-glycyl-DL-aspartic acid increased significantly.

Table 3

Table 4

[0176] Example 4.3 Influence of Aspartic Acid Derivatives on the Production Capacity of Broilers The experiment adopted a single-factor random design. 420 yellow-feathered broilers with an average body weight of 50 g and the same body weight at 1 day old were selected and randomly divided into 7 treatment groups, with each group replicated 3 times, half male and half female, and each replication had 20 yellow-feathered broilers. Before the experiment, the chicken coop and cooking utensils were sterilized. During the experimental period, they were raised in cages under the same feeding and management conditions in the same chicken coop. The basal diet mainly consisted of corn-soybean meal, and no other antioxidant components or growth promoters were added throughout the feeding process. Each experimental group was the control group, Experimental Groups I - VII respectively. Experimental Group I was the control group, fed only with the basal diet, and Experimental Groups II - VII were added with different aspartic acid derivatives of 300 ppm to the basal diet respectively, and the details are shown in Table 5. The experimental period was 20 days, and the experimental chickens were allowed to drink and eat feed freely, and fed twice a day. Taking each replication as a unit, the body weight was measured on the 21st day (without feeding for 12 hours, only given water), the feed consumption of the experimental chickens was counted, and the average daily feed intake (ADFI, g / d*bird), average daily weight gain (ADG, g / d*bird) and feed-to-meat ratio (FCR) of the experimental chickens in each group were calculated. Calculated by the following formula: Feed-to-meat ratio (FCR) = Average daily feed intake / Average daily weight gain in one day.

[0177] The experimental data were statistically analyzed using SPSS 18 software. First, the data were analyzed by one-way analysis of variance (ANOVA). If the difference between treatments was significant, multiple comparisons were performed by Duncan's method, and the significance level was 0.05. The experimental results were presented as "mean ± standard error" and are shown in Table 5.

[0178] As can be seen from the results, in the test samples of aspartic acid derivatives, each experimental group had a different degree of increasing effect on feed intake compared with the control group. Compared with the control group, the average daily weight gain of the experimental chickens in each experimental group all increased. Among them, the effects of N-carbamoyl-DL-aspartic acid and N-carbamoyl-DL-aspartic acid diethyl ester were the most significant. Regarding feed efficiency, compared with the control group, the feed-to-meat ratio in each experimental group decreased by about 3.1% - 7.0%, and some of the experimental groups showed a significant improvement effect. Overall, the aspartic acid derivatives used in the experiment had an excellent improvement effect on the production capacity of broilers in terms of average daily weight gain and feed efficiency.

Table 5

[0179] Example 4.4 Use of Aspartic Acid Derivatives in Fish Feed 1) Experimental Materials Experimental fish: The experimental fish used were healthy and lively carp of the same size. Before being used in a formal breeding experiment, they were reared in a large cage (4×2×1.5 m 3 ) for 4 weeks. The experimental system was a floating cage (specification 1.1×1.1×1.1 m 3 ). Each small cage was equipped with one air pump and aerated for 24 hours a day. All small cages and the temporary rearing cage were located at 3500 m in the experimental site 2It is installed in a pond with a pond depth of about 1.5 m, and the water in the pond is completely aerated to the bottom. 560 hungry carp were randomly divided into 7 groups in one day, with 4 replicates for each group, 20 fish in each replicate. Each replicate was weighed by weight and placed in 28 cages, and experimental feeds containing different test samples with the same content were given to each.

[0180] Experimental feed: The experimental feed was self-prepared according to the recipe in Table 6, and different test samples were given to different experimental groups with the same content according to Table 7. After the feed raw materials used were ground into extremely fine powder, they were passed through a Jiangsu MUYANG extruder unit to produce floating extruded feed with a particle diameter of 3 mm. The die temperature was 130 °C, 3% soybean oil was sprayed by an oil spraying facility, and it was sealed and stored in a cool place for later use.

Table 6

Table 7

[0181] (2) Experimental method Experimental management: The experiment adopted artificial restricted feeding, and the feeding amount was adjusted once a week. The feeding level (initial weight) of each group was exactly the same. Feeding was carried out twice a day (7:30 and 15:00), and the total feeding amount was 580 g / replicate experimental group. The experimental period was 8 weeks. During the experimental period, the water quality was monitored regularly. The water temperature throughout the aquaculture process was 26.88 ± 3.08 °C, DO > 55.0 mg / L -1 、pH 7.8, ammonia nitrogen < 0.50 mg / L -1 、nitrite nitrogen < 0.05 mg / L -1 It was.

[0182] Parameter statistics: During the experiment, feeding of the fish in each cage was stopped for one day and the weight was measured as a whole, and its weight gain rate (WG, %) and feed conversion ratio (FCR) were calculated. Calculated by the following formula: Weight gain rate (WG, %) = 100 × (average final weight - average initial weight) / average initial weight, Feed conversion ratio (FCR) = feed intake / weight gain of fish.

[0183] (3) Experimental results As can be seen from the experimental results shown in Table 8, when aspartic acid derivatives are used in aquatic feeds, it has an improving effect on the production capacity of carp, which is reflected in the increase in the weight gain rate and the feed conversion rate. The weight gain rate of each experimental group was improved. Among them, the weight gain rate of the experimental groups given N-glycyl-DL-aspartic acid and N-carbamoyl-DL-aspartic acid diethyl ester had a significant increasing effect compared with the control group. For each experimental group regarding feed conversion, the feed coefficient was significantly reduced compared with the control group, and the utilization rate of the feed was improved.

Table 8

[0184] The above examples only show some embodiments of the present invention, and the present invention can also be implemented by other methods. Similarly, the examples of the present invention are described by way of example, and should not be construed as limiting the scope of the patent of the present invention. Modifications made within the scope of the present invention within the same inventive concept, or equivalent content added to the claims, may also be acceptable.

Claims

1. Use of N-carbamoyl-DL-aspartic acid, or a feed acceptable salt thereof, in the preparation of an animal feed additive.

2. The use according to claim 1, characterized in that the feed acceptable salt of said N-carbamoyl-DL-aspartic acid is a metal ion salt.

3. The use according to claim 2, characterized in that the metal ion salt is a sodium ion salt, a zinc ion salt, a copper ion salt, an iron ion salt or a calcium ion salt.

4. A feed composition comprising at least one of N-carbamoyl-DL-aspartic acid according to any one of claims 1 to 3, or a feed acceptable salt thereof, and a feed adjuvant.

5. The feed composition according to claim 4, characterized in that the composition further comprises an additional animal feed additive, and the additional animal feed additive is selected from a nutritional feed additive, a non-nutritional feed additive or a pharmaceutical feed additive.

6. The feed composition according to claim 4 or 5, characterized in that it further comprises an animal feed raw material.

7. Use of the feed composition according to any one of claims 4 to 6 in the preparation of an animal feed.

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