Application of aspartic acid copper complex in preparation of animal feed additive

Abstract

The invention discloses an application of an aspartic acid copper complex in preparation of an animal feed additive. The chemical structure of the aspartic acid copper complex is [(Cu (II)) (Asp) (H2O) m]. (H2O) n, Asp is L-Asp or DL-Asp, m is any integer in the range of 0-10, and n is any value in the range of 0-10. It is found that when the copper aspartate complex with the chemical structure of [(Cu (II)) (Asp) (H2O) m]. (H2O) n is applied to bred animals, in terms of copper element, the physiological required amount of the copper aspartate complex can promote the growth of livestock and poultry in growth periods of all stages, the growth performance of the animals is normal when the copper aspartate complex is used at a high dosage, and the copper aspartate complex has no toxic or side effect. The problems of harm to animals caused by excessive use of high-dose inorganic copper in the breeding industry and the like are solved.

Description

[0001] This divisional application is patent application number: 202110372778.5, the application date is: April 7, 2021, and the name of the invention is: A divisional application for a copper aspartate complex and its application. Technical field:

[0002] The present application relates to the field of animal feed additives, and in particular to the application of a copper aspartate complex in the preparation of animal feed additives. Background technology:

[0003] Copper is one of the essential trace elements for animals. It is the key center and activity center of some enzymes in animals, the auxiliary factor of various oxidases, and the component of coagulation factor V and MT. It maintains normal hematopoietic function, the normal structure of bones, blood vessels and skin, the health of the central nervous system, protects the normal pigment and structure of hair, and protects the body's cells from the toxicity of superoxide ions. In 1984, K. Kaemmerer reported that copper deficiency can seriously delay the growth of animals, and resupply of copper can quickly restore the growth of animals. The nutritional requirement of animals for copper is 5mg / kg to 8mg / kg.

[0004] Since 1945, when a study found that high copper can significantly improve the growth performance of pigs, young piglets have been raised with 200mg / kg to 250mg / kg of high copper breeding raw materials to improve their growth performance and shorten the breeding cycle. The availability of inorganic copper is related to its solubility. Copper sulfate has the best effect among inorganic coppers, which is almost the same as organic copper and chelated copper. Therefore, inorganic copper, especially copper sulfate, has become the main source of high copper in piglet feed from the cost advantage. However, high copper has similar effects to antibiotics. It has a significant growth-promoting effect on piglets raised by conventional methods, but has no growth-promoting effect on pigs raised under sterile conditions, but has a tendency to reduce growth. The water solubility of the inorganic copper source itself or its ability to be quickly decomposed by gastric acid in the pig stomach, so that a large amount of free copper ions are quickly released and absorbed in the stomach, exceeding the physiological limit of the animal and causing toxic reactions. The copper ions released in large quantities in gastric acid are absorbed by the presence of phytic acid or fiber in the diet, so that only a small amount of copper ions can reach the middle and rear part of the small intestine to play an antimicrobial role or be absorbed by the small intestine into the body to exert its biological effect. Therefore, it is necessary to add high concentrations of copper ions in the feed to achieve the antibacterial and growth-promoting effects. Copper exceeding the physiological limit brings many side effects, such as high copper damage to the body's organs, excessive residues in organs affecting food safety, interference with the absorption of other nutrients, and unused copper polluting the environment through feces.

[0005] Copper sources for animal consumption are generally divided into two categories: the first category is inorganic copper, such as copper sulfate, copper chloride, copper oxide, copper acetate, copper carbonate and copper sulfide, etc.; the second category is chelated copper or organic-inorganic copper complexes, such as casein copper, milk protein copper, soy protein copper, methionine copper, copper stearate, and lysine copper hydrochloride. The prior art also shows that the effect of high doses of inorganic copper or organic copper on the production performance of monogastric animals or poultry tends to decrease with age.

[0006] Aspartate is not essential for mammals and can be produced from oxaloacetate by transamination.

[0007] In view of this, this application is hereby filed. Summary of the invention:

[0008] The purpose of the present application includes providing a safe copper aspartate complex which has an improving effect on the production performance of animals throughout the growth period.

[0009] The object of the present application also includes providing a feeding composition containing a safe copper aspartate complex having an improving effect on the production performance of animals throughout the growth period.

[0010] The purpose of the present application also includes providing the use of the copper aspartate complex and the feeding composition thereof in the preparation of animal feed additives.

[0011] The purpose of the present application also includes providing the use of the copper aspartate complex and the feeding composition thereof in the preparation of animal feed.

[0012] The object of the present application also includes providing a method for improving animal production performance.

[0013] In order to achieve at least one purpose of this application, the specific technical solution is as follows:

[0014] In one aspect, the present application provides a compound having a chemical structure of [(Cu(II))(Asp)(H2O) m ]·(H2O) n The invention relates to a copper aspartate complex, wherein Asp is L-Asp or DL-Asp, m is any integer between 0 and 10, and n is any value between 0 and 10.

[0015] In one technical solution, the chemical structure of the copper aspartate complex is [(Cu(II))(Asp)(H2O) m ]·(H2O) n , wherein Asp is L-Asp or DL-Asp, and n is any value between 0 and 0.62.

[0016] In some embodiments, the chemical structure of the copper aspartate complex is any one of the following:

[0017]

[0018] On the other hand, the present application also provides a feed composition, which comprises at least one copper aspartate complex provided by the present invention and at least one auxiliary material acceptable to feed, medicine or food.

[0019] In some technical solutions, the feeding composition further comprises additional animal feed additives.

[0020] The additional animal feed additives include nutritional feed additives, non-nutritional feed additives and medicinal feed additives.

[0021] In other technical solutions, the feeding composition further comprises feed raw materials.

[0022] On the other hand, the present application also provides a compound having a chemical structure of [(Cu(II))(Asp)(H2O) m ]·(H2O) n Application of copper aspartate complex and feeding composition thereof in the preparation of animal feed additives.

[0023] In some technical solutions, the animals are livestock, poultry, aquatic animals or pets at various growth stages.

[0024] On the other hand, the present application also provides a compound having a chemical structure of [(Cu(II))(Asp)(H2O) m ]·(H2O) n Application of copper aspartate complex and feeding composition thereof in preparing animal feed.

[0025] In some technical solutions, the animals are livestock, poultry, aquatic animals or pets at various growth stages.

[0026] On the other hand, the present application also provides a method for improving animal production performance, comprising: comprising a compound having a chemical structure of [(Cu(II))(Asp)(H2O) m ]·(H2O) n Feeding animals with a feed containing a copper aspartate complex and a feed composition thereof; or, feeding animals with a feed containing a copper aspartate complex and a feed composition thereof having a chemical structure of [(Cu(II))(Asp)(H2O) m ]·(H2O) n Copper aspartate complexes, or containing the chemical structure [(Cu(II))(Asp)(H2O) m ]·(H2O) nThe feeding composition or feed additive is added to the animal's diet according to the animal's growth requirement for animal feeding. The copper aspartate complex, the feeding composition or the animal feed additive is used in an amount of 5 mg / kg to 300 mg / kg, calculated based on the copper element and based on the weight of the animal's diet.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The present invention found that the chemical structure is [(Cu(II))(Asp)(H2O) m ]·(H2O) n The copper aspartate complex is used in farmed animals. Calculated in terms of copper element, the physiological requirement can promote the growth of livestock and poultry at all stages of the growth cycle, and the growth performance of animals is normal when used in high doses, overcoming the problems of harm to animals caused by excessive use of high-dose inorganic copper in the breeding industry.

[0029] Any embodiment of any aspect of the present application can be combined with other embodiments, as long as there is no contradiction between them. In addition, in any embodiment of any aspect of the present application, any technical feature can be applied to the technical feature in other embodiments, as long as there is no contradiction between them. Description of the drawings:

[0030] Figure 1 Infrared diffraction spectrum of copper aspartate complex with the chemical formula [Cu(L-Asp)(H2O)2].

[0031] Figure 2 Infrared diffraction spectrum of the raw material mixture for preparing copper aspartate complex with the chemical formula [Cu(L-Asp)(H2O)2]. Specific implementation method:

[0032] The above contents are only an overview of certain aspects of the present application, but are not limited to these aspects. The above contents and other aspects will be described in more detail and complete below.

[0033] Certain embodiments of the present application are now described in detail, examples of which are illustrated by the accompanying structural formulas and chemical formulas. The present application is intended to cover all alternatives, modifications and equivalent technical solutions, which are all included in the scope of the present application as defined in the claims. In addition, certain technical features of the present application are described separately in multiple independent embodiments for clarity, but can also be provided in a single embodiment in combination or in any suitable sub-combination.

[0034] The present invention provides a compound having a chemical structure of [(Cu(II))(Asp)(H2O) m]·(H2O) n The invention relates to a copper aspartate complex, wherein Asp is L-Asp or DL-Asp, m is any integer between 0 and 10, and n is any value between 0 and 10.

[0035] The "complex" of the present invention refers to a copper ion of a certain soluble copper salt and an aspartate ion (chemical structure: - OOC-CH2-CH(NH2)-COO - During the contact between Asp (hereinafter referred to as "Asp") and water molecules, external and internal conditions cause a stable substance to be formed by combining with covalent bonds and / or non-covalent intermolecular forces in a certain chemical molar equivalent and / or non-chemical equivalent.

[0036] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0037] Aspartic acid is also called aspartic acid, its chemical name is aminosuccinic acid, its English name is Aspartic Acid, and its chemical structure is HOOC-CH2-CH(NH2)-COOH. Aspartic acid has an asymmetric carbon atom (denoted as "-*CH(NH2)-"), which is optically active. Due to different spatial arrangement positions, it is divided into L type ( Formula I) and Form D ( Formula II), are enantiomers of each other. The racemic form of aspartic acid without optical activity is formed by equal amounts of D-type and L-type aspartic acid, which is recorded as DL type ( Formula III) may be an aspartic acid racemate mixture or racemic aspartic acid. The aspartic acid racemate mixture is a crystalline mixture of equal amounts of D-type and L-type aspartic acid, and the racemic aspartic acid is a compound formed by alternating arrangement of D-type and L-type in the crystal lattice.

[0038] The copper aspartate complex can be prepared by the following scheme:

[0039] In one preparation scheme, 1 chemical molar equivalent of aspartic acid is added to a 15% (mass percentage) aqueous solution containing 2 chemical molar equivalents of sodium hydroxide at room temperature, stirred until clear, and the reaction solution is slowly dripped into a 40% (mass percentage) aqueous solution containing 1 chemical molar equivalent of copper sulfate pentahydrate after cooling to room temperature. After dripping, stirring is continued to react to generate a blue solid. The reaction solution is filtered, and the filter cake is washed with water and then heated and dried to obtain a solid product.

[0040] In one embodiment, the sodium hydroxide may be replaced by an equimolar equivalent of potassium hydroxide.

[0041] In one embodiment, the copper sulfate pentahydrate may be replaced by an equimolar equivalent of copper chloride and its hydrate, copper bromide and its hydrate, copper nitrate and its hydrate, etc.

[0042] The complex involved in the present invention is a copper aspartate (Cu:Asp=1:1) hydrate. The inventors determined through structural identification technology that among the water contained in the complex, m water molecules, as complete components of the crystal structure, form a stable crystal structure with a copper ion and an Asp, and n water molecules are combined with the crystal structure in a non-stoichiometric manner.

[0043] Furthermore, the stirring reaction time is 0-4 hours, and the stirring is carried out at a low speed, a medium speed or a fast speed, and the solid product [(Cu(II))(Asp)(H2O) m ]·n(H2O) wherein m is any integer between 0 and 10, and n is any value between 0 and 10.

[0044] In some embodiments, m is any integer between 0-2.

[0045] In some embodiments, the heating and drying is a reduced pressure drying method, the heating temperature is 60-110° C., the drying box pressure is 0-0.1 MPa, and the solid product [(Cu(II))(Asp)(H2O) m ]·(H2O) n The copper aspartate complex is one in which n is any value selected from 0-1.

[0046] In some embodiments, the heating and drying is a reduced pressure drying method, the heating temperature is 110-150° C., the drying box pressure is 0-0.1 MPa, and the solid product [(Cu(II))(Asp)(H2O) m ]·(H2O) n It is a copper aspartate complex in which m and n are independently 0.

[0047] In some embodiments, the chemical molar equivalent of aspartic acid is L-aspartic acid, and the product is [(Cu(II))(L-Asp)(H2O) m ]·(H2O) n .

[0048] In some embodiments, the chemical molar equivalent of aspartic acid is DL-aspartic acid, and the product is [(Cu(II))(DL-Asp)(H2O) m ]·(H2O) n .

[0049] In some embodiments, the structure of the copper aspartate complex is any one of the following:

[0050]

[0051] The invention provides a feeding composition comprising at least one of the copper aspartate complexes and at least one of the auxiliary materials acceptable to feed, medicine or food.

[0052] The "composition" of the present invention refers to a compound group containing one or more compounds as active ingredients.

[0053] The term “comprising” described in the present invention is an open expression, which includes the contents explicitly mentioned in the present invention but does not exclude other contents.

[0054] The term "feed, pharmaceutical or food acceptable" as used herein means that the substance or composition must be suitable chemically or toxicologically for the feed, medicine, food or edible farmed animals it is composed of.

[0055] Optionally, the auxiliary materials include carriers, diluents, excipients, adjuvants, solvents or combinations thereof commonly used in feed, pharmaceutical or food industries.

[0056] The "carrier" of the present invention refers to a feedable material that can carry active ingredients, improve its dispersibility, and has good chemical stability and adsorption, and is divided into organic carriers and inorganic carriers. The organic carrier is generally a material containing a lot of crude fiber, including but not limited to corn flour, corn cob flour, wheat bran, rice husk powder, defatted rice bran, bran, corn stalk powder, peanut shell powder, etc. The inorganic carrier is generally a mineral, mainly divided into calcium salts and silicon oxides, used for the preparation of trace element premixes, including but not limited to calcium carbonate, silicates, vermiculite, zeolite, sepiolite, etc.

[0057] The "diluent" referred to in 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, can separate trace components from each other, reduce the mutual reaction between active components, increase the stability of active components but do not affect the physicochemical properties of related substances. The types of diluents are divided into organic diluents and inorganic diluents. Common organic diluents include but are not limited to corn flour, degermed corn flour, dextrose (glucose), sucrose, coarse wheat flour with bran, fried soybean flour, second flour, corn protein powder, etc. Commonly used inorganic diluents include but are not limited to limestone, monocalcium phosphate, shell powder, kaolin (white clay), salt and sodium sulfate.

[0058] The excipients are wetting agents that induce the inherent viscosity of the substance itself, adhesives that make the substance stick together, disintegrants that break the whole sheet of the substance into many small particles, retention agents that reduce the friction between particles or anti-sticking agents that prevent the material from sticking, including but not limited to magnesium stearate, talc, vegetable oil, magnesium lauryl sulfate, starch, starch slurry, water, inorganic salts, dextrin, powdered sugar, etc.

[0059] The auxiliary agents involved in the present invention include but are not limited to adhesives, wetting agents, disintegrants, lubricants, antioxidants, preservatives, anti-caking agents, stabilizers, emulsifiers, etc.

[0060] The "solvent" referred to in the present invention refers to the solvent required to dissolve or disperse a solid, including but not limited to water, ethanol, glycerol, etc.

[0061] In some embodiments, the feeding composition further comprises an additional animal feed additive.

[0062] The additional animal feed additive is a nutritional feed additive, a general feed additive or a medicinal feed additive.

[0063] The nutritional feed additives mentioned above refer to small or trace substances added to compound feed to balance feed nutrients, improve feed utilization, and directly exert nutritional effects on animals. They are amino acids, amino acid salts and their analogs, vitamins and vitamin-like substances, mineral elements and their complexes (chelates), microbial enzyme preparations or non-protein nitrogen.

[0064] The general feed additives mentioned above are also called non-nutritional additives, which refer to some non-nutritional substances added to feed to improve feed utilization, ensure feed quality and quality, and are beneficial to animal health or metabolism, including growth promoters, anthelmintics and health care agents, flavorings and attractants, feed conditioners, feed modulators, feed storage agents and Chinese herbal medicine additives.

[0065] Specifically, the medicinal feed additives include but are not limited to veterinary drug premixes that have the functions of preventing animal diseases and promoting animal growth and can be added to feed for a long term and mixed with carriers or diluents.

[0066] In some embodiments, the feeding composition may include feed raw materials, and the feed raw materials are selected from non-feed additives and feed materials such as animals, plants, microorganisms or minerals that can be used to process and make feed.

[0067] The animal feed raw materials are equivalent to acceptable raw materials in feed, specifically cereals and their processed products, oil seeds and their processed products, leguminous crop seeds and their processed products, tubers, roots and their processed products, other seeds, fruit products and their processed products, forage, 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, microbial fermentation products and by-products, other feed raw materials and other feeding substances.

[0068] In some embodiments, the feeding composition is an additive premix feed, a concentrated feed, a compound feed, or a concentrate supplement.

[0069] The feed additive premix refers to a uniform mixture of any two or more types of nutritious feed additives selected from mineral trace elements, vitamins, microorganisms, and amino acids, which are mainly mixed with the copper aspartate complex provided by the present invention or other feed additives, carriers and (or) diluents in a certain proportion, wherein the content of the nutritious feed additive can meet the basic nutritional requirements of the specific physiological stage of the applicable animal, and the addition amount of the copper aspartate complex in compound feed, concentrate supplement or animal drinking water is 5 mg / kg to 300 mg / kg in terms of copper element.

[0070] The concentrated feed refers to feed mainly containing protein, minerals and feed additives prepared in a certain proportion.

[0071] The compound feed refers to feed prepared by mixing a variety of feed raw materials and feed additives in a certain proportion according to the nutritional needs of farmed animals.

[0072] The concentrate supplement refers to a feed prepared by mixing a variety of feed raw materials and feed additives in a certain proportion in order to supplement the nutrition of herbivorous animals.

[0073] The invention also provides the use of the copper aspartate complex and the feeding composition thereof in the preparation of animal feed additives.

[0074] In some embodiments, the copper aspartate complex and the feed composition thereof are used in the preparation of animal feed additives, wherein the animal feed additive is a livestock feed additive, a poultry feed additive, an aquaculture animal feed additive or a pet feed additive.

[0075] The "animals" involved in the present invention refer to humans or farmed animals that cannot synthesize organic matter from inorganic matter and can only use organic matter as food to carry out life activities such as eating, digestion, absorption, breathing, circulation, excretion, sensation, movement and reproduction.

[0076] Optionally, farmed animals include poultry, livestock, aquatic animals, and other animals that are legally caught and artificially raised, including pets. Specifically, the poultry involved in the present invention is food-source animals such as chickens, ducks, geese, pigeons, quails or turkeys at various growth stages; the livestock involved in the present invention is food-source animals such as pigs, cattle, sheep, rabbits, horses at various growth stages; the aquatic animals involved in the present invention are fish, shrimps, loaches, crabs or eels at various growth stages; the pets involved in the present invention include but are not limited to cats, dogs, rabbits, etc.

[0077] Specifically, the copper aspartate complex and the feeding composition thereof are used to prepare livestock feed additives, and the livestock include but are not limited to pigs, cattle, sheep, horses, rabbits, minks, etc. at various growth stages.

[0078] Specifically, the copper aspartate complex and the feeding composition thereof are used to prepare poultry feed additives, and the poultry include but are not limited to chickens, ducks, geese, pigeons, etc. at various growth stages.

[0079] In some embodiments, the animal feed additive prepared with the copper aspartate complex and the feeding composition thereof is a premix, a composite premix, an aqueous solution or a granule.

[0080] The present invention also provides the use of the copper aspartate complex and the feed composition thereof in preparing animal feed, wherein the animal feed is livestock feed, poultry feed, aquaculture animal feed or pet feed.

[0081] Specifically, the copper aspartate complex and the feeding composition thereof are used to prepare livestock feed, and the livestock include but are not limited to pigs, cattle, sheep, horses, rabbits, minks, etc. at various growth stages.

[0082] Specifically, the copper aspartate complex and the feeding composition thereof are used to prepare poultry feed, and the poultry includes but is not limited to chickens, ducks, geese, pigeons, etc. at various growth stages.

[0083] In some embodiments, the feed prepared by comprising the copper aspartate complex and the feeding composition thereof is a single feed, a concentrated feed, a compound feed, a compound premix or a concentrate supplement.

[0084] Specifically, the compound feed is a complete compound feed.

[0085] In some embodiments, the copper aspartate complex is added to the complete feed in an amount of 5 mg / kg to 300 mg / kg in terms of copper element.

[0086] Furthermore, when the complete feed is a complete feed for livestock, the added amount of the copper aspartate complex is 5 mg / kg to 250 mg / kg in terms of copper element.

[0087] Specifically, the livestock are pigs, cattle, sheep, horses, rabbits, and minks at various growth stages, preferably pigs.

[0088] Furthermore, the complete feed is a complete feed for poultry, and the added amount of the copper aspartate complex is 8 mg / kg to 200 mg / kg in terms of copper element.

[0089] Specifically, the poultry are chickens, ducks, geese, pigeons, etc. at various growth stages, preferably chickens and ducks.

[0090] The present invention also provides a method for improving animal production performance, comprising: feeding the animal with a feed containing the copper aspartate complex; or, adding the copper aspartate complex and its feed composition or feed additive to the animal's diet according to the corresponding animal growth requirement for feeding the animal, and the usage amount of the copper aspartate complex, its feed composition or its additive is 5 mg / kg to 300 mg / kg in terms of copper element.

[0091] Professional technicians with professional feeding knowledge (referred to as "feeders") know from experience that the lack of copper in the animal's diet will delay the animal's growth and development, and timely supplementation of copper is required to restore the normal growth and development of the animal. Driven by the animal's demand for copper, the feeder can freely choose different copper sources to feed the animal, and the copper source includes the copper aspartate chelate provided by the present invention and the feeding composition, feed or feed additive containing the copper aspartate complex, and the feeder gives the animal a sufficient amount of the copper aspartate complex animal food according to the nutritional requirement of the animal for copper at each growth stage.

[0092] In some breeding schemes, the animal food includes but is not limited to animal feed, feeding composition, basal diet, etc.

[0093] In some specific breeding examples, the animals are livestock at various growth stages, preferably pigs at various growth stages. When animal food containing the copper aspartate complex containing a physiologically required amount of copper is given, the feed intake, average daily weight gain and feed conversion rate of the test pigs are improved compared with the test pigs in the copper sulfate breeding example, the aspartic acid breeding example or the control breeding example without treatment.

[0094] In other specific breeding examples, the animals are poultry at various growth stages, preferably chickens and ducks at various growth stages. When animal food containing the copper aspartate complex containing a physiologically required amount of copper is given, the feed conversion of the test chickens or ducks is improved compared with the test chickens or ducks in the copper sulfate breeding example, the aspartate breeding example or the control breeding example, and when the test dosage of the copper aspartate complex reaches 100-300 mg / kg, the test chickens do not show animal poisoning similar to the high-dose copper sulfate breeding example.

[0095] It can be seen that the copper aspartate complex provided by the present invention can not only meet the growth needs of animals but also significantly improve the production performance of animals compared with inorganic copper sources in improving the growth performance of animals.

[0096] The embodiments of the present application will be described in detail below in conjunction with the examples, but it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present application and should not be considered as limiting the scope of the present application. In the examples, if specific conditions are not specified, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0097] Example A Preparation of Copper Aspartate Complex

[0098]

[0099] Those skilled in the art will recognize that other methods for preparing the copper-L-aspartate complexes of the present application are considered to be within the scope of the present application. For example, the synthesis of the copper-L-aspartate complexes according to the present application that are not exemplified can be successfully completed by those skilled in the art through modification methods, such as by using other reagents or making some conventional modifications to the reaction conditions.

[0100] At room temperature, 50 g of L-aspartic acid was added to a reaction flask containing 30.99 g of sodium hydroxide and 200 mL of water. The mixture was stirred to dissolve and clarify. The mixture was cooled to room temperature. The prepared sodium L-aspartate aqueous solution was slowly dripped into a reaction flask containing 93.8 g of copper sulfate pentahydrate and 250 mL of water (a clear aqueous solution of copper sulfate pentahydrate). A blue solid was produced. After about 1.0 h of dripping of the sodium L-aspartate aqueous solution, the reaction was continued by stirring for 4.0 h. The mixture was filtered, the filter cake was washed with 100 mL of water, and dried at 105 ° C for 16 h to obtain 84.6 g of the product as a blue solid with a yield of 94.9%.

[0101] Elemental analysis of the product: Cu 26.40%, C 20.89%, H 4.04%, N 6.07%.

[0102] Analysis of infrared diffraction spectrum test results: Figure 1 is the infrared diffraction spectrum test result of the product, Figure 2 The infrared diffraction spectrum test result of the mixture obtained by simply mixing aspartic acid and copper sulfate pentahydrate, the raw materials required for the preparation of the product in the above preparation scheme, according to the feed ratio. Figure 1 and Figure 2 By comparison, we can see that Figure 1 The number of characteristic absorption peaks in the solution is significantly reduced, indicating that the symmetry is higher than that of aspartic acid, and Figure 1 No absorption peak Figure 2 The characteristic absorption peak of amino acids is 2083cm-1; Figure 2 There is a strong and broad absorption peak at 2500cm-1-3400cm-1, and Figure 1 There is a narrow absorption peak at 3100cm-1-3400cm-1, indicating that there is no free -OH in the product; Figure 1 The characteristic peaks of carboxyl coordination appear near 1600cm-1 and 1400cm-1, indicating that the metal is coordinated with the carboxyl group.

[0103] The product obtained by the preparation scheme shown in this example is confirmed to have the structural formula of L-Aspartate copper complex of ([(Cu(II))(L-Asp)(H2O)2], compound 1).

[0104] In addition, in some batches, the product of the above preparation scheme was dried under reduced pressure at 60-140°C, and the obtained product was confirmed by structure determination technology, elemental analysis, infrared diffraction spectroscopy and thermogravimetric analysis technology to have the structural formula ([(Cu(II))(L-Asp)(H2O)2]·(H2O) 0.34 , compound 2, a blue solid, containing non-stoichiometric water 2.74%) and ([(Cu(II))(L-Asp)(H2O)2]·(H2O) 0.62 , compound 3, blue solid, containing non-stoichiometric water 4.62%). In addition, when the product was dried under reduced pressure at 150-209°C, the structural formula of the obtained product was confirmed by structure determination technology, elemental analysis, infrared diffraction spectroscopy and thermogravimetric analysis technology. ([(Cu(II))(L-Asp)], compound 4, off-white solid).

[0105] In addition, the inventors found that when L-aspartic acid in the above preparation scheme is replaced by a racemic mixture of aspartic acid or racemic aspartic acid, the products obtained in sequence according to the preparation process of compound 1, compound 4, and compound 2 are: ([(Cu(II))(DL-Asp)(H2O)2], compound 5, blue solid), ([(Cu(II))(DL-Asp)], compound 6, off-white solid),

[0106] ([(Cu(II))(DL-Asp)(H2O)2]·(H2O) 0.16 , compound 7, a blue solid, containing non-stoichiometric water 1.23%).

[0107] Example B breeding test

[0108] Experiment on the Growth-Promoting Effect of B-1 Copper Aspartate Complex

[0109] ①Test materials

[0110] Experimental animals: 900 one-day-old Lingnan Huangkuai broiler chickens; 150 weaned piglets;

[0111] Feed: Basic feed for chickens and basic feed for pigs that does not contain any antibiotics, copper sources, or growth promoters;

[0112] Test samples: Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, (Compound 8, prepared by the method provided in Chemical World, 2005, 02, 94-96), L-aspartic acid, copper sulfate pentahydrate.

[0113] ②Test methods

[0114] A. Experiment on the growth promotion of Lingnan Huangkuai broiler chickens by copper aspartate complex

[0115] 900 one-day-old Lingnan Huangkuai large broilers were randomly divided into 18 groups, with 50 chickens in each group. The control group only added 5 mg / kg of copper sulfate in the physiologically recommended amount to the feed, and the other groups did not add any copper supplements to the feed. After adding different test samples as shown in Table 1, the chickens were allowed to eat freely. The weight gain and feed conversion of the test chickens in each test group from 1 to 21 days old were counted, and the growth-promoting effects of copper sulfate and copper aspartate complexes on broilers were compared.

[0116] Table 1 Grouping of the growth promotion test of copper aspartate complexes on broiler chickens

[0117]

[0118]

[0119] *: The dosage of different growth promoters is calculated based on the copper ions in the compound. The dosage of L-aspartic acid group is the same molar mass as the L-aspartic acid contained in the dosage of compound 1-50 group.

[0120] B. Experiment on the growth promotion of copper aspartate complex in pigs

[0121] 150 weaned piglets were grouped as shown in Table 2, with 10 pigs in each group. The control group only added 8 mg / kg of copper sulfate in the physiologically recommended amount to the feed, and the other groups did not add any copper supplement to the feed. After adding different test samples as shown in Table 2, the pigs were fed freely. The weight gain and feed conversion of the test pigs in each test group 30 days after weaning were calculated, and the growth-promoting effects of copper sulfate and copper aspartate complexes on pigs were compared.

[0122] Table 2 Grouping of the growth promotion test of copper aspartate complexes on pigs

[0123]

[0124]

[0125] *: The dosage of different growth promoters is based on the copper ion in the compound; the dosage of L-aspartic acid group is the molar mass of L-aspartic acid contained in the dosage of compound 1-50 group.

[0126] ③Test results

[0127] A. Experiment on the growth promotion of Lingnan Huangkuai broiler chickens by copper aspartate complex

[0128] During the feeding experiment of Lingnan Huang Kuai large broilers, the copper sulfate groups with 150mg / kg and 100mg / kg copper ions showed symptoms of poisoning such as ruffled feathers and dry skin in the second week of the experiment. A small number of dead chickens also appeared before the end of the experiment, indicating that long-term use of feed with a copper sulfate dosage of 100mg / kg has toxic side effects on broilers. The copper sulfate group with 50mg / kg copper ions did not show clinically visible symptoms of poisoning, but the relative weight gain rate during the trial period was 98.9%, which was close to that of the control group without medication, but the feed-to-meat ratio was 0.048 higher than that of the control group, and the feed reward was not improved. The test groups of compound 1, compound 2, compound 3, compound 4, compound 5, compound 6 and compound 7 basically showed good growth-promoting effects and the body surface characteristics of the test chickens were normal. The relative weight gain rate could be increased by 4.9%-19.6%, and the feed reward decreased by 2.95%-6.34%. Among them, the test effect of the test group with the addition amount of compound 1 of 50-100 mg / kg showed a dose effect. The relative weight gain rate of the compound 4 group increased by 7.2%, and the feed reward decreased by 3.23%. The relative weight gain rate of the L-aspartic acid group increased by 4.2%, and the feed reward decreased by 0.32%. The test results suggest that copper aspartate complexes have good safety and growth-promoting effects, but copper aspartate complexes of different structures have different effects on animal growth performance at the same addition amount (see Table 3 for details).

[0129] Table 3 Results of the growth promotion test of copper aspartate complexes on broiler chickens

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[0131]

[0132] B. Experiment on the growth promotion of copper aspartate complex in pigs

[0133] During the pig feeding experiment, the high-dose copper sulfate pentahydrate group (250 mg / kg) had a significant growth-promoting effect. The average weight gain during the experiment was 12.66% higher than that of the non-administered control group, and the feed conversion rate decreased by 7.8%. Compound 1, compound 2, compound 3, compound 4, compound 5, compound 6, compound 7 and compound 8 were used in this experiment. The first seven compounds all had the effect of promoting the growth of experimental pigs, but at the same dose, the improvement effect of compound 1, compound 2 and compound 3 on the feed conversion rate of experimental pigs was about twice that of compound 4, and at similar feed conversion rates, the dosage of compound 1, compound 2 and compound 3 was less than that of compound 4, while the production performance of experimental pigs of compound 8 at this dose was basically close to that of the control group. In addition, compound 1 showed a dose effect in improving the production performance of experimental pigs. When the dosage was 50 mg / kg, the growth-promoting effect and feed conversion rate were similar to those of the high-dose copper sulfate group (Table 4). The results suggest that 50 mg / kg of compound 1 can replace high-dose copper sulfate in pig breeding.

[0134] Table 4 Results of the growth promotion test of copper aspartate complexes on pigs

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[0136] Example C Application of copper aspartate complex in aquatic feed

[0137] (1) Test materials

[0138] Fish for the test: The fish used for the test were black carp, which were of the current year and provided by Dafeng Fish Seed Farm in Huizhou City, Guangdong Province. Healthy and lively black carp of the same size were seeded in large cages (4×2×1.5m 3 ) were used in formal breeding experiments after being raised for 4 weeks. The experimental system was a small floating cage (specifications 1.1×1.1×1.1m 3 Each small cage is equipped with an air inflator and inflated 24 hours a day. The small cages and temporary cages are placed in a 3500m 2 In the pond, the water depth was about 1.5m, and the pond water was fully aerated bottom water. During the experiment, 480 black carps that had been starved for 1 day were randomly divided into 10 groups, with 4 replicates in each group and 12 fish in each replicate. After the whole group was weighed, they were randomly placed in 28 net cages and fed with different experimental feeds.

[0139] Test feed: Test feed was prepared according to the formula in Table 5, and different copper supplements (in terms of copper ions) were added to different test groups according to Table 6. The feed raw materials were ultra-finely crushed and then made into floating puffed feed with a particle size of 3 mm by Jiangsu Muyang puffing unit, with a mold temperature of 130°C, and 3% soybean oil was sprayed on the outside through an oil spraying device, and sealed and stored in a cool place for later use.

[0140] Table 5: Formula and chemical composition of experimental black carp feed (%wt.)

[0141] Raw material composition content(%) Raw material composition content(%) Fishmeal 9.0 Soybean Oil 3.0 Casing powder 3.0 Lecithin rapeseed meal 9.0 Soybean meal 12.0 Gluten 4.0 Rapeseed meal 12.0 Blood Cell Powder 2.0 MSG Protein 3.0 Vc-Phosphate 0.1 Second powder 12.6 Calcium dihydrogen phosphate 1.8 flour 17.0 Choline chloride 0.2 Bentonite 0.70 Multidimensional 0.1 Rice bran 10.0 Micro-mineral premix 0.5

[0142] (2) Test methods

[0143] Experimental management: The experiment adopted artificial food restriction feeding, and the feeding amount was adjusted once a week. The feeding level of each group (based on the initial body weight) was exactly the same, and feeding was done twice a day (7:30 and 15:00). The experiment lasted for 8 weeks. During the experiment, the water quality was monitored regularly. The water temperature was 26.88±3.08℃ and DO>5.0mg OL -1 , pH 7.8, ammonia nitrogen <0.50mg NL -1 、Nitrite nitrogen <0.05mg NL -1 .

[0144] Parameter statistics: During the experiment, the fish in each cage were weighed after one day of feeding cessation, and their average weight gain (g) and feed-to-meat ratio were calculated. The calculation formula is as follows:

[0145] Average weight gain (g) = average final weight - average initial weight;

[0146] Feed to meat ratio = food intake / fish weight gain;

[0147] (3) Test results

[0148] The results of the growth promotion test of copper aspartate complexes on fish are shown in Table 6. The results show that the copper aspartate complexes provided by the present invention can significantly increase the daily weight gain of the test fish within the limited range of the physiological requirements of the animals, improve the feed-to-meat ratio, and have a better effect on improving the production performance of farmed fish compared with the same dose of copper sulfate.

[0149] Table 6 Application effect of copper aspartate complex in aquatic feed

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[0151]

Claims

1. A chemical structure of Application of copper aspartate complexes in the preparation of animal feed additives.

2. The use according to claim 1, characterized in that: The animal feed additive is a feed additive suitable for livestock, poultry, aquatic animals or pets at various growth stages.

3. The use according to claim 1, characterized in that: The copper aspartate complex is added to animal feed in an amount of 5 mg / kg to 300 mg / kg in terms of copper element.

4. The use according to claim 3, characterized in that: The copper aspartate complex is a copper element supplement, and its addition amount in animal feed is 5mg / kg-35mg / kg in terms of copper element.

5. The use according to claim 1, characterized in that: The copper aspartate complex is an animal growth promoter.

6. The use according to claim 5, characterized in that: The copper aspartate complex is added in an amount of 5mg / kg to 250mg / kg in terms of copper element in animal feed, and the animals are pigs, chickens or ducks at various growth stages.

7. A feeding composition, characterized in that: Contains chemical structures The invention relates to a copper aspartate complex and at least one of a pharmaceutically, food or feed acceptable carrier, excipient, diluent, solvent and adjuvant.

8. The feed composition according to claim 7, characterized in that Additional animal feed additives are also included.

9. The feed composition according to claim 7 or 8, characterized in that Also includes feed ingredients.

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