WO2019080155A1 - N,n-二甲基甘氨酸有机酸共轭酸盐及其组合物和应用 - Google Patents

N,n-二甲基甘氨酸有机酸共轭酸盐及其组合物和应用

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Publication number
WO2019080155A1
WO2019080155A1 PCT/CN2017/109143 CN2017109143W WO2019080155A1 WO 2019080155 A1 WO2019080155 A1 WO 2019080155A1 CN 2017109143 W CN2017109143 W CN 2017109143W WO 2019080155 A1 WO2019080155 A1 WO 2019080155A1
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Prior art keywords
acid
dimethylglycine
organic acid
feed
salt
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PCT/CN2017/109143
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English (en)
French (fr)
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彭险峰
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广州英赛特生物技术有限公司
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Application filed by 广州英赛特生物技术有限公司 filed Critical 广州英赛特生物技术有限公司
Priority to EP17929682.7A priority Critical patent/EP3674286B1/en
Priority to ES17929682T priority patent/ES2896260T3/es
Priority to BR112020006576-5A priority patent/BR112020006576B1/pt
Priority to US16/755,152 priority patent/US10912749B2/en
Priority to DK17929682.7T priority patent/DK3674286T3/da
Publication of WO2019080155A1 publication Critical patent/WO2019080155A1/zh

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    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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    • C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
    • C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/105—Aliphatic or alicyclic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
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    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/22—Compounds of alkali metals
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/24—Compounds of alkaline earth metals, e.g. magnesium
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/30—Oligoelements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
    • A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/80—Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/32—Manganese; Compounds thereof
    • A—HUMAN NECESSITIES
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    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
    • C07C229/12—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/126—Acids containing more than four carbon atoms
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/13—Dicarboxylic acids
    • C07C57/15—Fumaric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
    • C07C63/04—Monocyclic monocarboxylic acids
    • C07C63/06—Benzoic acid
    • C07C63/08—Salts thereof
    • C—CHEMISTRY; METALLURGY
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
    • C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages

Definitions

  • the present invention relates to the field of animal feed additives, and more particularly to an N,N-dimethylglycine organic acid conjugate acid salt and compositions and uses thereof.
  • “Feed additive” refers to small or trace substances added during the processing, production and use of feed (Regulations on the Administration of Feed and Feed Additives, State Council Order No. 609), which are divided into nutritive feed additives and general feed additives. Also called non-nutritive feed additives.
  • Nutritional feed additives refer to small or trace substances added to compound feeds, balanced feed nutrients, improved feed utilization, and direct nutritional effects on animals, including vitamins, trace elements, amino acids and small peptides and non-protein nitrogen.
  • General feed additives also called non-nutritive additives, are non-nutritive substances added to feeds to improve feed utilization, ensure feed quality and quality, and contribute to animal health or metabolism, including growth promoters and deworming care.
  • DMG Dimethylglycine
  • dimethylglycine As a nutritional antioxidant additive, dimethylglycine also shows important physiological and biochemical functions in human and animal health. A large number of animal experiments have found that dimethylglycolic acid is a very safe food-based nutritional supplement.
  • N,N-dimethylglycine is a highly hygroscopic solid that is inconvenient to store and use. Often The N,N-dimethylglycine hydrochloride, sodium N,N-dimethylglycine, and potassium N,N-dimethylglycine are also very strong in moisture absorption, and are easy to absorb moisture and deliquescent during storage. In the processing of products, the requirements for production equipment and plant facilities are high. Otherwise, the products will be agglomerated due to moisture absorption during the production process, which will not meet the application requirements of the feed processing industry. In addition, packaging containing DMG or DMG hydrochloride or alkali metal salt must be tightly sealed. Once the sealing is insufficient, the product will be mildewed due to moisture absorption during storage.
  • an object of the present invention is to provide a N,N-dimethylglycine metal organic acid conjugate salt or a solvate thereof which is not easily hygroscopic.
  • N,N-dimethylglycine metal organic acid conjugated salt having the following structural formula:
  • the organic acid is selected from the group consisting of polybasic organic acids, C 2 -C 18 linear fatty acids or aromatic acids.
  • the organic acid is a polybasic organic acid selected from the group consisting of fumaric acid, maleic acid, tartaric acid, succinic acid, fumaric acid, malonic acid, malic acid, dihydroxypropionic acid, pyruvic acid, and ethanol. Acid, gluconic acid, galactonic acid, aspartic acid, glutamic acid, citric acid or oxalic acid.
  • the polybasic organic acid is preferably fumaric acid.
  • the C 2 -C 18 linear fatty acid is a C 2 -C 18 linear fatty monoacid selected from the group consisting of acetic acid, propionic acid, butyric acid, citric acid, palmitic acid, lauric acid, or stearic acid. acid.
  • the aromatic acid is selected from the group consisting of benzoic acid, p-toluic acid, naphthoic acid, mandelic acid, p-chlorobenzoic acid, p-bromobenzoic acid, p-aminobenzoic acid, cinnamic acid, salicylic acid, Acetylsalicylic acid, p-toluenesulfonic acid or benzenesulfonic acid.
  • the aromatic acid is benzoic acid or p-toluic acid.
  • the divalent metal ion is selected from the group consisting of Ca(II), Mg(II), Cu(II), Zn(II), Fe(II), Mn(II), Co(II). Or Ni(II).
  • the N,N-dimethylglycine metal organic acid conjugate salt is one of the following salts: [(CH 3 ) 2 NCH 2 COO] 2 Ca ⁇ [benzoic acid], [( CH 3 ) 2 NCH 2 COO] 2 Ca ⁇ [fumaric acid], [(CH 3 ) 2 NCH 2 COO] 2 Cu ⁇ [benzoic acid], [(CH 3 ) 2 NCH 2 COO] 2 Cu ⁇ [rich Horse acid], [(CH 3 ) 2 NCH 2 COO] 2 Zn ⁇ [benzoic acid], [(CH 3 ) 2 NCH 2 COO] 2 Zn ⁇ [fumaric acid].
  • the N,N-dimethylglycine metal organic acid conjugate salt is a solvate, preferably a hydrate or an ethanolate.
  • Another object of the present invention is to provide the use of the above N,N-dimethylglycine metal organic acid conjugate salt.
  • the N,N-dimethylglycine metal organic acid conjugate salt is used in the preparation of an animal feed additive.
  • the N,N-dimethylglycine metal organic acid conjugate salt is used in the preparation of an animal feed.
  • the animal is selected from the group consisting of poultry, livestock, aquatic animals, or pets.
  • the poultry is selected from the group consisting of a chicken, a duck, a goose, or a pigeon;
  • the livestock is selected from the group consisting of a pig, a cow, a sheep, or a horse;
  • the aquatic animal is selected from the group consisting of shrimp, fish, loach, cricket, or crab.
  • N,N-dimethylglycine metal organic acid conjugated salt is used for feeding poultry of chickens, ducks, geese, pigeons and the like at different stages, and N,N-dimethylglycine or N,N-dimethylglycine Compared with sodium N,N-dimethylglycine, the production performance of poultry has a more significant improvement effect, which is reflected in the average daily gain and feed-to-meat ratio.
  • N,N-dimethylglycine metal organic acid conjugated salt is used for the breeding of livestock such as pigs, cattle, sheep, horses or donkeys, and can significantly improve the production performance of the animals, which is expressed in the average daily gain, average daily intake. Quantity and feed compensation.
  • N,N-dimethylglycine metal organic acid conjugated salt is used for feeding aquatic animals such as shrimp, fish, loach, scorpion, crab, scorpion, etc., which can significantly improve the growth rate of aquatic animals and also improve the resistance of aquatic animals. Hypoxia ability, alleviate the hypoxia hazard of aquatic animals and improve survival rate.
  • Another object of the invention is to provide a feed composition.
  • a feed composition comprising the above N,N-dimethylglycine metal organic acid conjugate salt and a pharmaceutically, food or feed acceptable carrier.
  • the carrier includes an excipient, a diluent, an adjuvant, a vehicle, or a combination thereof, and is prepared into a feed additive dosage form such as a tablet, a pill, an emulsion, a capsule, a premix, or the like by a formulation process.
  • nutritional feed additives and/or non-nutritive feed additives are also included.
  • the nutritive feed additive is selected from the group consisting of vitamins, proteins, fats, amino acids, cellulose, mineral trace elements, and the like.
  • the non-nutritive feed additive is selected from the group consisting of a growth promoter, an insect repellent, a feed conditioner, a feed preparation, a feed storage agent, and a Chinese herbal medicine additive.
  • the forage composition further comprises a feed material.
  • the present invention provides the use of a feed composition comprising the above N,N-dimethylglycine metal organic acid conjugate salt.
  • the use of the forage composition in the preparation of an animal feed additive in some embodiments, the use of the forage composition in the preparation of an animal feed additive.
  • the use of the feed composition in the preparation of an animal feed in some embodiments, uses of the feed composition in the preparation of an animal feed.
  • the animal is a farm animal selected from the group consisting of livestock, poultry, aquaculture animals or pets.
  • the invention also provides a method of improving the performance of a farmed animal.
  • the method comprises administering to the farmed animal a N,N-dimethylglycine metal organic acid conjugate salt provided by the present invention in a manner admixed with the feed.
  • the method comprises administering to a cultured animal a feed composition comprising a N,N-dimethylglycine metal organic acid conjugate salt provided herein.
  • N,N-dimethylglycine metal organic acid conjugated salt is formed by introducing another organic acid having a hydrophobic group to form a conjugated acid salt based on the salt of N,N-dimethylglycine with a metal ion. Decreasing the affinity of the salt with water molecules in the air or reducing the affinity of the surface of the molecular aggregate formed by the crystal form to the water molecules in the air or the adsorption force to improve N, N-II Methyl glycine absorbs moisture.
  • the production of the feed or feed additive can be reduced due to the decrease in the moisture absorption resistance of the production equipment of the feed or feed additive. cost.
  • the moisture absorption of the product reduces the sealing requirements of the product packaging, and the cost is reduced, and the risk of short-term moisture deterioration of the product due to the damage of the packaging due to accidents during transportation or storage can be avoided.
  • the N,N-dimethylglycine metal organic acid conjugate salt provided by the invention has the effect of improving the production performance of poultry and livestock in the culture test, and is equivalent to the N,N-dimethylglycine sodium salt, and some salts even show a little Better improvement.
  • Figure 1 is a flow chart showing the production process of the mixed pellet feed additive.
  • the invention provides a N,N-dimethylglycine metal organic acid conjugated salt, and the structural formula is as follows:
  • the invention relates to M representing a metal ion.
  • the divalent metal ion to which the present invention relates includes an alkaline earth metal ion or other divalent metal ion.
  • the alkali metal ion according to the present invention refers to a +1 valent cation in which a group IA element sodium, potassium, rubidium, cesium, cesium or the like in the periodic table of the elements loses electrons in a chemical reaction.
  • the alkaline earth metal ion referred to in the present invention refers to a +2 valent cation formed by a group IIA element lanthanum, magnesium, calcium, strontium, barium, radium, etc., which loses electrons in a chemical reaction, respectively, and is Ca(II), Mg ( II), Ba(II) or Sr(II).
  • divalent metal ions to which the present invention relates include transition metal divalent ions, which may be selected from Cu(II), Zn(II), Fe(II), Cd(II), Co(II) or Ni(II).
  • C 2 -C 18 linear fatty acid represents a linear fatty acid having 2 to 18 carbon atoms
  • C 2 -C 18 linear fatty monobasic acid means 2 to 18 A carbon atom, a fatty acid having only one carboxyl group.
  • conjugated acid salt means that the organic acid provides a proton-forming anion and the N,N-dimethylglycine metal salt forms a salt formed by a proton-forming cation provided by the organic acid.
  • the method for preparing, separating and purifying the above N,N-dimethylglycine metal organic acid conjugate salt comprises the following steps:
  • the water soluble solvent is selected from the group consisting of anhydrous ethanol, methanol, isopropanol, n-butanol or tetrahydrofuran, and the like.
  • the alkali metal hydroxide may be selected from the group consisting of sodium hydroxide, potassium hydroxide, and the like.
  • the divalent metal hydroxide is an alkaline earth metal hydroxide.
  • the alkaline earth metal hydroxide is calcium hydroxide (Ca(OH) 2 ), magnesium hydroxide (Mg(OH) 2 ), barium hydroxide (Ba(OH) 2 ) or barium hydroxide (Sr) (OH) 2 ), the corresponding product [(CH 3 ) 2 NCH 2 COO] n M ⁇ [organic acid] metal ion M is a divalent alkaline earth metal ion, which may be selected from Ca(II), Mg(II) , Ba(II) or Sr(II).
  • the divalent metal hydroxide is a basic transition metal hydroxide.
  • the basic transition metal hydroxide is copper hydroxide (Cu(OH) 2 ), zinc hydroxide (Zn(OH) 2 ), ferrous hydroxide (Fe(OH) 2 ), and hydroxide.
  • the metal ion M is a transition metal divalent ion and may be selected from Cu (II), Zn (II), Fe (II), Cd (II), Co (II) or Ni (II).
  • the suspension involved in the step (2) is stirred under a basic condition by adding a divalent metal halide, wherein the alkaline condition is to add sufficient sodium hydroxide to the reaction system to adjust the pH of the reaction system. It is 7-8.
  • the polyvalent metal chloride is specifically copper chloride (CuCl 2 ), zinc chloride (ZnCl 2 ), manganese chloride (MnCl 2 ), ferrous chloride (FeCl 2 ), chromous chloride (CrCl 2 ) ), cadmium chloride (CdCl 2 ), cobalt chloride (CoCl 2 ) or nickel chloride (NiCl 2 ).
  • the polyvalent metal bromide in particular copper bromide (CuBr 2), zinc bromide (ZnBr 2), manganese bromide (MnBr 2), iron bromide (FeBr 2), chromic bromide (CrBr 2) , cadmium bromide (CdBr 2 ), cobalt bromide (CoBr 2 ) or nickel bromide (NiBr 2 ).
  • the polyvalent metal iodide is specifically copper bromide (CuI 2 ), zinc iodide (ZnI 2 ), manganese iodide (MnI 2 ), iron iodide (FeI 2 ), chromium cyanide (CrI 2 ). , cadmium iodide (CdI 2 ), cobalt iodide (CoI 2 ) or nickel iodide (NiI 2 ).
  • the corresponding product [(CH 3 ) 2 NCH 2 COO] n M ⁇ [organic acid] produced by the above process contains metal ions of Cu(II), Zn(II), Fe(II), Mn(II), Cr. (II), Cd (II), Co (II) or Ni (II).
  • the organic acid in which the above chemical reaction step (3) is dissolved in a water-soluble solvent may be selected from a polybasic organic acid, a linear aliphatic monobasic acid or an aromatic organic acid.
  • the polybasic organic acid may be selected from the group consisting of fumaric acid, maleic acid, tartaric acid, succinic acid, fumaric acid, malonic acid, malic acid, dihydroxypropionic acid, pyruvic acid, glycolic acid, glucuronic acid, galacturonic acid.
  • Aspartic acid, glutamic acid, citric acid or oxalic acid is preferably fumaric acid.
  • the linear fatty monobasic acid may be selected from a C 4 - C 18 linear fatty monobasic acid, preferably tetradecanoic acid.
  • the aromatic organic acid may be selected from the group consisting of benzoic acid, p-toluic acid, p-chlorobenzoic acid, p-bromobenzoic acid, p-aminobenzoic acid, mandelic acid, cinnamic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthoic acid, water.
  • Salicylic acid or acetylsalicylic acid is preferably benzoic acid, p-toluic acid or p-toluenesulfonic acid.
  • the crude product in order to obtain a N,N-dimethylglycine metal organic acid conjugate salt having higher chemical purity and lower impurity content, is used in an alcohol solvent, an alcohol-water mixed solvent or the like for recrystallization of the product.
  • the N,N-dimethylglycine metal organic acid conjugated salt having a certain crystal form is recrystallized and separated in an organic solvent under conditions of suitable temperature, light, and mechanical vibration.
  • the N,N-dimethylglycine metal organic acid conjugated salt having a certain crystal form may be a solvate thereof.
  • solvate means that in the process of contacting the complex salt of the present invention with a solvent molecule, external conditions and internal conditions cause a combination of chemically equivalent or non-stoichiometric solvent molecules by non-covalent intermolecular forces. A eutectic association formed. Solvents that form solvates include, but are not limited to, water, acetone, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, isopropanol, and the like. "Hydrate” means a solvent or molecule that is an association or crystal formed by water, that is, a compound that combines a chemical equivalent or a non-stoichiometric amount of water by a non-covalent intermolecular force.
  • the solvate of the N,N-dimethylglycine metal organic acid conjugate salt is A hydrate or an ethanolate selected from the group consisting of N,N-dimethylglycine metal organic acid conjugated salts.
  • the N,N-dimethylglycine metal organic acid conjugate salt is [(CH 3 ) 2 NCH 2 COO] 2 Ca ⁇ [benzoic acid].
  • the N,N-dimethylglycine metal organic acid conjugate salt is [(CH 3 ) 2 NCH 2 COO] 2 Ca ⁇ [fumaric acid].
  • the N,N-dimethylglycine metal organic acid conjugate salt is [(CH 3 ) 2 NCH 2 COO] 2 Cu ⁇ [benzoic acid].
  • the N,N-dimethylglycine metal organic acid conjugate salt is [(CH 3 ) 2 NCH 2 COO] 2 Cu ⁇ [fumaric acid].
  • the N,N-dimethylglycine metal organic acid conjugate salt is [(CH 3 ) 2 NCH 2 COO] 2 Zn ⁇ [benzoic acid].
  • the N,N-dimethylglycine metal organic acid conjugate salt [(CH 3 ) 2 NCH 2 COO] 2 Zn ⁇ [fumaric acid].
  • the present invention provides high-humidity stability studies of the above N,N-dimethylglycine metal organic acid conjugated salt.
  • the N,N-dimethylglycine metal organic acid conjugate salt was placed at a RH95% condition of 25 ° C until the 10th day of moisture absorption. The weight is less than 5%, which meets the humidity requirements of the feed additive.
  • the present invention relates to the use of the above N,N-dimethylglycine metal organic acid conjugate salt for the preparation of animal feed additives or animal feed.
  • animal refers to a person who cannot synthesize inorganic substances into organic matter, and can only use organic matter as a food material for feeding, digesting, absorbing, breathing, circulating, excreting, feeling, exercising, and breeding as a living activity or breeding. animal.
  • farmed animals include poultry, livestock, aquatic animals, and other animals legally caught by captivity, including pets.
  • the poultry according to the present invention is a food-eating animal such as a chicken, a duck, a goose, a pigeon, a donkey or a turkey in each growth stage;
  • the livestock according to the present invention are pigs, cattle, sheep, rabbits at various growth stages, Food-eating animals such as horses;
  • the aquaculture animals involved in the present invention are fish of various growth stages,shrimp, loach, crab or cockroach, etc.;
  • the pets involved in the present invention include, but are not limited to, cats, dogs, rabbits and the like.
  • the addition of the N,N-dimethylglycine metal organic acid conjugate salt provided by the present invention to the basic diet of poultry such as chicken, duck, goose or pigeon can significantly reduce the feed ratio coefficient. Improve the utilization rate of feed for poultry and achieve the equivalent effect with N,N-dimethylglycine sodium.
  • the N,N-dimethylglycine metal organic acid conjugate salt provided by the present invention is added to the basic diet of livestock such as pig, cow, sheep, etc., such as monogastric or ruminant, to produce livestock performance. It has a significant improvement effect, which is reflected in the average daily gain and the average feed-to-meat ratio.
  • the addition of the N,N-dimethylglycine metal organic acid conjugated salt provided by the present invention to the basal diet of aquaculture animals such as fish and shrimp can significantly improve aquaculture animals, especially fish.
  • the ability to resist hypoxia increases survival.
  • N,N-dimethylglycine metal organic acid conjugated salt can be used in combination with cat food, dog food and other pet rations to achieve the regulation of gastrointestinal function of cats, dogs and other pets, effectively alleviating pets. Symptoms of diarrhea caused by indigestion.
  • the N,N-dimethylglycine metal organic acid conjugated salt which is not easy to absorb moisture meets the requirements of high feed stability of the new feed additive and has similar or better improved culture with sodium N,N-dimethylglycine.
  • the effect of animal performance can be applied to the preparation of animal feed additives or animal feed.
  • the present invention provides a feed composition comprising at least one of N,N-dimethylglycine metal organic acid conjugate salt provided by the present invention and a feedable adjuvant.
  • composition refers to a collective of compounds comprising one or more compounds which constitute an active ingredient.
  • the feedable auxiliary material comprises a feed additive or a carrier commonly used for the feed, a binder, an anti-caking agent, a stabilizer, an emulsifier, a diluent, a solvent or a combination thereof.
  • the “carrier” of the present invention means a feedable substance capable of supporting an active ingredient, improving dispersibility, and having good chemical stability and adsorption, and is classified into an organic vehicle and an inorganic carrier.
  • the organic carrier is generally a material containing a large amount of crude fiber, including but not limited to corn flour, corn cob powder, wheat bran, rice husk powder, defatted rice bran, taro, corn stalk powder, peanut shell powder and the like.
  • the inorganic carrier is generally mineral, the main points It is a calcium salt and silicon oxide used in the preparation of trace element premixes, including but not limited to calcium carbonate, silicate, vermiculite, zeolite, sepiolite, and the like.
  • the "diluent” referred to in the present invention refers to a substance in which the additive raw material is uniformly distributed in the material, and the high-concentration additive raw material is diluted into a low-concentration premix or premix, and the trace components can be separated from each other to reduce the active ingredient. The interaction between them increases the stability of the active ingredient without affecting the physicochemical properties of the substance.
  • the types of diluents are classified into organic diluents and inorganic diluents. Common organic diluents include, but are not limited to, corn flour, deblasted corn flour, dextrose (glucose), sucrose, semolina with bran, and fried soybeans. Powders, secondary powders, corn gluten meal, etc., commonly used inorganic diluents include, but are not limited to, limestone, calcium dihydrogen phosphate, shell powder, kaolin (white clay), salt and sodium sulfate.
  • Adjuvants to which the present invention relates include, but are not limited to, binders, wetting agents, disintegrants, lubricants, antioxidants, preservatives.
  • vehicle refers to a solvent required to dissolve or disperse a solid, including but not limited to water, ethanol, glycerol, and the like.
  • the forage composition comprises an additional animal feed additive, the additional animal feed addition being selected from the group consisting of a nutritive feed additive, a general feed additive or a pharmaceutical feed additive.
  • the nutritive feed additive includes, but is not limited to, an amino acid, an amino acid salt and the like, a vitamin and a vitamin, a mineral element and a chelating compound thereof, a microbial enzyme preparation or a non-protein nitrogen;
  • General feed additives include, but are not limited to, growth promoters, insect repellents, flavoring and attractants, feed conditioners, feed conditioners, feed stocks, and herbal additives;
  • the pharmaceutical feed additives include, but are not limited to, A veterinary drug premix which is used to prevent animal diseases, promote animal growth, and can be incorporated into a feed for a long period of time and incorporated into a carrier or a diluent.
  • the feed composition may comprise a feed material selected from the group consisting of non-feed additives, feed materials for animals, plants, microorganisms or minerals that can be used to process feed.
  • the feed composition is an additive premix feed, concentrate feed, compound feed, or concentrate supplement.
  • the feed additive premix feed refers to a nutritive feed additive of any two or more types of mineral trace elements, vitamins, microorganisms, and amino acids, and the butyrylglutamic acid derivative provided by the present invention. Or other feed additives, carriers and/or diluents formulated in a certain ratio a homogeneous mixture, wherein the content of the nutritive feed additive can meet the basic nutrient requirement of the specific physiological stage of the applicable animal, and the addition amount in the compound feed, the concentrate supplement or the animal drinking water is not less than 0.1% and not more than 10%. .
  • the concentrated feed refers to a feed mainly prepared with a certain proportion of protein, minerals and feed additives.
  • the compound feed refers to a feed prepared by a plurality of feed raw materials and feed additives according to a certain proportion according to the nutritional needs of the farmed animals.
  • the concentrate supplement refers to a feed prepared by supplementing a plurality of feed materials and feed additives according to a certain ratio in order to supplement the nutrition of the herbivore.
  • the invention also relates to a process for the preparation of the forage composition comprising the steps of weighing the raw materials and excipients, mixing the mixing unit, granulating, quality testing and packaging.
  • Sample 1 N,N-dimethylglycine hydrochloride, BEHRINGER TECHNOLOGY CO., LTD.;
  • Sample 2 sodium N,N-dimethylglycine, Shandong West Asia Chemical Industry Co., Ltd.;
  • Sample 8 N,N-dimethylglycine copper benzoic acid conjugate acid salt, prepared in Example 4.
  • a saturated solution of KNO3 (25 ° C, RH 90%) was placed in the lower part of the constant temperature and humidity sealed container.
  • Three test samples were set in parallel for the test sample, and placed at 25 ° C, RH 95% ⁇ 1% for 10 days, on the 5th and 10th. The average weight of the test article is measured in days.
  • N,N-dimethylglycine metal organic acid conjugated salt is kept at a constant temperature and humidity of 25 ° C, RH95% ⁇ 1% for 10 days, and the moisture absorption weight is less than 5%, and has relative stability. Meet the humidity requirements of feed additives.
  • N,N-dimethylglycine metal organic acid conjugated salts of Examples 1 to 7 were respectively mixed with corresponding auxiliary materials to prepare corresponding mixed granular feed additives.
  • Carrier corn starch
  • Binder 1.3% aqueous solution of hydroxypropylmethylcellulose.
  • Raw material supply R&D center of Guangzhou Instech Biotechnology Co., Ltd., which has passed the inspection by the Quality Control Department as a qualified product with a purity of ⁇ 99%.
  • Excipient purchase Purchasing excipients from qualified suppliers, and sampling after excipients to the factory. After passing the inspection, they can be put into storage and stored for standby. This process is a key control point, and the quality of excipients must be strictly controlled.
  • Production picking and weighing According to the proportion of the product formula, the raw materials and auxiliary materials are weighed and reviewed in turn, and the waste (packaging bags) produced are stored and treated uniformly.
  • Mixing Mix the raw materials and auxiliary materials into the mixing unit. This step is the key control point. The mixing time must be strictly controlled, and the mixing uniformity should be verified periodically.
  • the mixer is equipped with a pulse dust collector to reduce dust.
  • Granulation The product obtained by mixing the raw materials and auxiliary materials and the 1.3% aqueous solution of hydroxypropylmethylcellulose are put into the granulator according to the mass ratio of 100:35, and the mixing and cutting operation are started for 3-5 min. After the material is granulated, the granulation is carried out. It was dried in a fluidized bed and passed through a 16 mesh screen after 30 minutes.
  • Packing and inspection Weigh and package according to the packaging specifications, store in the finished product warehouse, identify the production batch and inspection status, etc. Each production batch is sampled at least two samples and sent to the laboratory for factory inspection and sample retention. After passing the inspection, it can be shipped. Thus, each mixed type pellet feed additive was obtained.
  • Production equipment cleaning After each batch of products is finished, the production area must be cleaned. When the production variety is replaced, the production equipment must be transported to remove impurities and prevent cross-contamination.
  • a single factor randomized design was used to select 1080 brood chickens of 22 days old, with an average body weight of 153 g and similar body weight. They were randomly divided into 9 treatment groups, with 6 replicates in each group, half male and half female, and 20 replicates each. Three yellow feather broilers. Sterilize the house and utensils before the test. The trial period is carried out under the same feeding and management conditions in the same chicken house. The basal diet is dominated by corn-soybean meal, and no additional antioxidants or growth promoters are added throughout the feeding process. Each test group was a blank group, a control group, and a test group 1-7.
  • the blank group was given only the basal diet, the control group and the trial groups 1 to 7 respectively added 5000 ppm of the mixed pellet feed additive product provided by the present invention to the basal diet (see the section "Preparation method of feed composition").
  • the test chickens were given free access to water and food, and fed twice a day. Weighed at 42 days of age (12h, no water stop) in each repeat, the experimental chicken consumption was counted, and the average daily feed intake (ADFI) and average daily gain of each group of test chickens were calculated. ADG) and feed to meat ratio (FCR).
  • the experimental data were statistically analyzed using SPSS18 software. The data were analyzed by one-way analysis of variance (ANOVA).
  • test results are expressed as "mean ⁇ standard error", and the test results are shown in Table 4. From the results, it was found that the control group and each test group had no significant effect on the feed intake of the experimental chickens compared with the blank group, but both significantly increased the average daily gain of the test chickens and significantly reduced the feed-to-meat ratio; Compared with the control group, the average daily weight gain of the test group was not significant. The meat content of the test group 1-3 was not significantly lower than that of the control group. The feed ratio of the test group 4-7 was compared with that of the control group. The decline is significant.
  • N,N-dimethylglycine calcium benzoic acid conjugate acid salt, N,N-dimethylglycine calcium fumaric acid conjugate acid provided by the present invention in the improvement of feed conversion efficiency in broiler breeding experiments
  • the salt and the N,N-dimethylglycine calcium myristate conjugate acid salt have an aquaculture effect equivalent to the N,N-dimethylglycine sodium salt, and the N,N-dimethylglycine copper provided by the present invention
  • the carboxylic acid conjugate acid salt has a better culture effect than the N,N-dimethylglycine sodium salt, and the meat-to-meat ratio is reduced by about 10% to 11.5% compared with the experimental group which does not give any feed additive.
  • test groups 240 pairs of 65-day-old Du Changda ternary miscellaneous meat pigs with similar body weight were randomly divided into 8 treatment groups, 3 replicates in each group, and half male and female, each with 10 heads.
  • the pigsty and utensils were sterilized before the test.
  • the test period is housed in the same breeding and management conditions under the same pig pen.
  • the test pigs were fed ad libitum and water, and fed twice a day.
  • Each test group was a control group and a test group 1-7. Among them, the control group was given only the basal diet, and the test groups 1 to 7 were respectively added with 1150 ppm of the mixed pellet feed additive products 1 to 7 provided by the present invention in the basal diet.
  • test period was 28 days, and the performance of the test pigs was counted in units of each replicate, which were average daily feed intake (ADFI), average daily gain (ADG), and feed to meat ratio (FCR).
  • ADFI average daily feed intake
  • ADG average daily gain
  • FCR feed to meat ratio
  • the test data was statistically analyzed using SPSS18 software, and the data was first analyzed by one-way analysis of variance (ANOVA). If the differences between treatments were significant, multiple comparisons were performed using Duncan's method with a significance level of 0.05. The test results are expressed as "mean ⁇ standard error", and the test results are shown in Table 5.
  • Test fish The test fish used was grass carp, and the fish species of the year were from the Dafeng fish farm in Huizhou City, Guangdong province. The healthy and lively, uniform-sized grass carp species were used for formal culture experiments after being kept in large cages (4 ⁇ 2 ⁇ 1.5m 3 ) for 4 weeks.
  • the experimental system was a floating small cage (size 1.1 ⁇ 1.1 ⁇ 1.1m 3 ). Each small cage is equipped with an inflatable head that inflates 24 hours a day. Both the small cage and the holding cage are placed in a 3500 m 2 pond at the test site. The pond has a water depth of about 1.5 m and the pond water is fully aerated.
  • Test feed The test feed was prepared according to the formula of Table 6. Different test groups were added with the same dose of different N,N-dimethylglycine metal organic acid conjugate salt according to Table 7.
  • the feed material used was finely pulverized and then made into a floating bulking feed with a particle size of 3 mm through a Jiangsu shepherd expansion unit.
  • the mold temperature was 130 ° C. Spray 3% soybean oil on the outside of the fuel injection equipment, and keep it in a cool place for storage.
  • Raw material composition content(%) Raw material composition content(%) Fish meal 9.0 Soybean oil 3.0 Casing powder 3.0 Phospholipid 9.0 Cardamom 12.0 Gluten 4.0 Dish 12.0 Blood cell powder 2.0 Monosodium glutamate 3.0 Vc-phosphate 0.1 Secondary 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
  • Trial management The test was fed by artificial food restriction. The feeding amount was adjusted once a week. The feeding level of each group (according to the initial weight) was completely consistent and fed twice a day (7:30 and 15:00). The trial lasted for 8 weeks. The water quality was monitored regularly during the test. The whole process water temperature was 26.88 ⁇ 3.08°C, DO>5.0mg O L -1 , pH7.8, ammonia nitrogen ⁇ 0.50mg N L -1 , nitrite nitrogen ⁇ 0.05mg N L -1 .
  • Weight gain rate 100 ⁇ (average final weight - average initial weight) / average initial weight;
  • Feed coefficient (FCR) food intake / fish weight gain
  • Survival rate (SR, %) 100 ⁇ number of fish at the end of the test / number of fish at the start of the test.

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Abstract

本发明涉及一种N，N-二甲基甘氨酸金属有机酸共轭盐及其制备方法和应用，N，N-二甲基甘氨酸金属有机酸共轭盐结构式如下：[(CH3)2NCH2COO]nM·[有机酸]，其中，n为1或2；M选自碱金属离子或二价金属离子；有机酸选自多元有机酸、C2-C18直链脂肪酸或芳香酸。上述N，N-二甲基甘氨酸金属有机酸共轭盐是在N,N-二甲基甘氨酸与金属离子成盐的基础上引入另一种带有疏水基团的有机酸形成共轭酸盐，使所述盐与空气中的水分子的亲和力下降或使所述盐通过晶型行为形成的分子聚集体表面对空气中的水分子的亲和力下降或吸附力下降从而达到改善N,N-二甲基甘氨酸吸潮性。

Description

N,N-二甲基甘氨酸有机酸共轭酸盐及其组合物和应用 技术领域
本发明涉及动物饲料添加剂领域，特别是涉及一种N,N-二甲基甘氨酸有机酸共轭酸盐及其组合物和应用。
背景技术
“饲料添加剂”是指在饲料加工、制作、使用过程中添加的少量或者微量物质(《饲料和饲料添加剂管理条例》中华人民共和国国务院令第609号)，分为营养性饲料添加剂和一般饲料添加剂也叫非营养性饲料添加剂。营养性饲料添加剂是指添加到配合饲料中，平衡饲料养分，提高饲料利用率，直接对动物发挥营养作用的少量或微量物质，包括维生素、微量元素、氨基酸与小肽和非蛋白氮。一般饲料添加剂也叫非营养性添加剂，是指加入到饲料中用于改善饲料利用率、保证饲料质量和品质、有利于动物健康或代谢的一些非营养性物质，包括生长促进剂、驱虫保健剂、饲料调质剂、饲料调制剂、饲料贮藏剂和中草药添加剂。其中，抗生素作为常用的动物生长促进剂型的饲料添加剂在现代饲料加工业中广为使用甚至造成滥用。无论是养殖领域还是医药领域抗生素的滥用导致病原菌对抗生素的耐药性不断出现并形成非常严峻的形势，目前欧盟、日本、美国等一些发达国家已陆续颁发部分抗生素在动物养殖业禁用的决定，在我国相似的工作已提上日程，因此，开发新型、安全、稳定及有效的动物饲料添加剂提高养殖业经济效益的关键。二甲基甘氨酸(Dimethylglycine，简称DMG)，分子式为(CH3)2NCH2COOH，外观白色结晶，溶于水和乙醇，是一种天然存在于食物、谷物豆类及肝脏中具有生理活性的营养物质，是动植物代谢途径的天然物质。二甲基甘氨酸作为一种营养抗氧化添加剂，在人和动物的健康上也显示出重要的生理生化功能。大量的动物试验发现二甲基甘酸是一种非常安全的食品类营养添加剂。
但是，N,N-二甲基甘氨酸是一种强吸湿性的固体，不方便储存和使用。常 用的N,N-二甲基甘氨酸盐酸盐、N,N-二甲基甘氨酸钠、N,N-二甲基甘氨酸钾等的吸潮性也非常强，在储存中容易吸潮潮解，在产品加工中对生产设备和厂房设施要求高，否则将会导致生产过程中因吸潮而导致产品结块，达不到饲料加工业的应用要求。另外，含有DMG或DMG盐酸盐或碱金属盐的产品包装打包必须严格密封，一旦密封性不够产品在储存过程会因吸潮而导致产品霉变变质。
发明内容
基于此，本发明的目的是提供一种不易吸潮的N,N-二甲基甘氨酸金属有机酸共轭盐或其溶剂合物。
具体的技术方案如下：
一种N,N-二甲基甘氨酸金属有机酸共轭盐，结构式如下：
[(CH3)2NCH2COO]nM·[有机酸]
其中，n为1或2；M选自碱金属离子或二价金属离子；
有机酸选自多元有机酸、C2-C18直链脂肪酸或芳香酸。
在其中一些实施例中，所述的有机酸为多元有机酸，选自富马酸、马来酸、酒石酸、琥珀酸、延胡索酸、丙二酸、苹果酸、二羟基丙酸、丙酮酸、乙醇酸、葡萄糖酸、半乳糖酸、天冬氨酸、谷氨酸、柠檬酸或草酸。
在其中一些实施例中，所述的多元有机酸优选为富马酸。
在其中一些实施例中，所述C2-C18直链脂肪酸为C2-C18直链脂肪一元酸，选自乙酸、丙酸、丁酸、癸酸、棕榈酸、月桂酸或硬脂酸。
在其中一些实施例中，所述芳香酸选自苯甲酸、对甲基苯甲酸、萘甲酸、扁桃酸、对氯苯甲酸、对溴苯甲酸、对氨基苯甲酸、肉桂酸、水杨酸、乙酰水杨酸、对甲苯磺酸或苯磺酸。
在其中一些实施例中，所述芳香酸为苯甲酸或对甲苯甲酸。
在其中一些实施例中，所述的二价金属离子选自Ca(II)、Mg(II)、Cu(II)、Zn(II)、Fe(II)、Mn(II)、Co(II)或Ni(II)。
在其中一些实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐是如下盐之一：[(CH3)2NCH2COO]2Ca·[苯甲酸]、[(CH3)2NCH2COO]2Ca·[富马酸]、 [(CH3)2NCH2COO]2Cu·[苯甲酸]、[(CH3)2NCH2COO]2Cu·[富马酸]、[(CH3)2NCH2COO]2Zn·[苯甲酸]、[(CH3)2NCH2COO]2Zn·[富马酸]。在其中一些实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐是溶剂合物，优选为水合物或乙醇合物。
本发明的另一目的是提供上述N,N-二甲基甘氨酸金属有机酸共轭盐的应用。
在一些实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐在制备动物饲料添加剂中应用。
在一些实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐在制备动物饲料中应用。
在其中一些实施例中，所述动物选自家禽、家畜、水产动物或宠物。
在其中一些实施例中，所述家禽选自鸡、鸭、鹅或鸽子；所述家畜选自猪、牛、羊或马；所述水产动物选自虾、鱼、泥鳅、鳝或蟹。
上述N,N-二甲基甘氨酸金属有机酸共轭盐用于不同阶段的鸡、鸭、鹅、鸽子等家禽的饲养，与N,N-二甲基甘氨酸或N,N-二甲基甘氨酸盐酸盐或N,N-二甲基甘氨酸钠相比，对家禽的生产性能具有更显著的改善效果，体现在平均日增重和料肉比上。
上述N,N-二甲基甘氨酸金属有机酸共轭盐用于猪、牛、羊、马或驴等家畜的养殖可显著提高饲养动物的生产性能，表现在平均日增重、平均日采食量和饲料报酬方面。
上述N,N-二甲基甘氨酸金属有机酸共轭盐用于虾、鱼、泥鳅、鳝、蟹、鲫等水产动物的饲养可明显提高水产动物的生长速率的同时还可提高水产动物的抗缺氧能力，缓解水产动物的缺氧危害提高存活率。
本发明的另一目的是提供一种饲用组合物。
一种饲用组合物，包括上述N,N-二甲基甘氨酸金属有机酸共轭盐以及药学、食品或饲料可接受的载体。
所述载体包括赋形剂、稀释剂、辅剂、媒介物或它们的组合经制剂工艺制备为片剂、丸剂、乳剂、胶囊剂、预混剂等饲料添加剂剂型。
在其中一些实施例中，还包括营养性饲料添加剂和/或非营养性饲料添加剂。
所述营养性饲料添加剂选自维生素、蛋白质、脂肪、氨基酸、纤维素、矿物质微量元素等。
所述非营养性饲料添加剂选自生长促进剂、驱虫保健剂、饲料调质剂、饲料调制剂、饲料贮藏剂和中草药添加剂。
在其中一些实施例中，所述饲用组合物还包括饲料原料。
本发明提供了包含上述N,N-二甲基甘氨酸金属有机酸共轭盐的饲用组合物的应用。
在一些实施方案中，所述的饲用组合物在制备动物饲料添加剂中的应用。
在一些实施方案中，所述的饲用组合物在制备动物饲料中的应用。
所述的动物为养殖动物，选自家畜、家禽、水产养殖动物或宠物。
另一方面，本发明还提供了一种改善养殖动物生产性能的方法。
在一些实施方案中，所述的方法包括与饲料伴服的方式给予养殖动物本发明提供的N,N-二甲基甘氨酸金属有机酸共轭盐。
在一些实施方案中，所述的方法包括给予养殖动物本发明提供的包含本发明提供的N,N-二甲基甘氨酸金属有机酸共轭盐的饲用组合物。
上述N,N-二甲基甘氨酸金属有机酸共轭盐是在N,N-二甲基甘氨酸与金属离子成盐的基础上引入另一种带有疏水基团的有机酸形成共轭酸盐，使所述盐与空气中的水分子的亲和力下降或使所述盐通过晶型行为形成的分子聚集体表面对空气中的水分子的亲和力下降或吸附力下降从而达到改善N,N-二甲基甘氨酸吸潮性。当所述N,N-二甲基甘氨酸金属有机酸共轭盐应用在制备动物饲料添加剂或饲料中，由于吸潮性的降低饲料或饲料添加剂的生产设备在防潮功能的要求下降，可降低生产成本。另外，产品的吸潮性降低对产品包装的密封性要求下降，成本降低的同时也可避免由于运输或存放过程的意外导致包装破损而带来的产品短期受潮变质的风险。
本发明提供的N,N-二甲基甘氨酸金属有机酸共轭盐在养殖试验中，对家禽和家畜生产性能的改善效果与N,N-二甲基甘氨酸钠盐相当，部分盐甚至显示稍微更优的改善效果。
附图说明
图1混合型颗粒饲料添加剂的生产工艺流程图。
具体实施方式
为了便于理解本发明，下面将对本发明进行更全面的描述。但是，本发明可以以许多不同的形式来实现，并不限于本文所描述的实施例。相反地，提供这些实施例的目的是使对本发明的公开内容的理解更加透彻全面。
除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。
本发明提供一种N,N-二甲基甘氨酸金属有机酸共轭盐，结构式如下：
[(CH3)2NCH2COO]nM·[有机酸]
其中，n为1或2；M选自碱金属离子或二价金属离子；有机酸选自多元有机酸、C2-C18直链脂肪酸或芳香酸。
本发明涉及的M代表金属离子。
本发明涉及的二价金属离子包括碱土金属离子或其它二价金属离子。
本发明涉及的碱金属离子是指元素周期表中IA族元素钠、钾、铷、铯、钫等在化学反应中失去电子形成的+1价阳离子。
本发明涉及的碱土金属离子指元素周期表中IIA族元素铍、镁、钙、锶、钡、镭等在化学反应中分别失去电子形成的+2价阳离子，分别为Ca(II)、Mg(II)、Ba(II)或Sr(II)。
本发明涉及的其它二价金属离子包括过渡金属二价离子，可选自Cu(II)、Zn(II)、Fe(II)、Cd(II)、Co(II)或Ni(II)。
本发明所涉及的一些化合物表达：“C2-C18直链脂肪酸”代表含有2-18个碳原子的直链脂肪酸；“C2-C18直链脂肪一元酸”代表含有2-18个碳原子、只有一个羧基的脂肪酸。
本发明的“共轭酸盐”是指有机酸提供一个质子形成阴离子与N,N-二甲基甘氨酸金属盐接受有机酸提供的一个质子形成阳离子所形成的盐。
上述N,N-二甲基甘氨酸金属有机酸共轭盐的制备、分离和纯化的方法包括如下步骤：
(1)于反应器中依次加入N,N-二甲基甘氨酸盐酸盐和水溶性溶剂，室温下剧烈搅拌形成混悬液；
(2)于混悬液中加入碱金属氢氧化物或二价金属氢氧化物或在碱性条件下加入二价金属卤化物，室温搅拌；
(3)将有机酸溶于水溶性溶剂中，投入步骤(2)得到的反应液中，搅拌反应30～60min；
(4)将步骤(3)得到的反应物减压抽滤，滤渣于100-110℃减压干燥，即得所述N，N-二甲基甘氨酸金属有机酸共轭盐。
在其中一些实施例中，所述水溶性溶剂选自无水乙醇、甲醇、异丙醇、正丁醇或四氢呋喃等。
在一些实施例中，所述的碱金属氢氧化物可选自氢氧化钠、氢氧化钾等。
在一些实施例中，所述的二价金属氢氧化物为碱土金属氢氧化物。具体的，所述的碱土金属氢氧化物为氢氧化钙(Ca(OH)2)、氢氧化镁(Mg(OH)2)、氢氧化钡(Ba(OH)2)或氢氧化锶(Sr(OH)2)，相应的产物[(CH3)2NCH2COO]nM·[有机酸]的金属离子M为二价的碱土金属离子，可选自Ca(II)、Mg(II)、Ba(II)或Sr(II)。
在一些实施例中，所述的二价金属氢氧化物为碱性过渡金属氢氧化物。具体的，所述的碱性过渡金属氢氧化物为氢氧化铜(Cu(OH)2)、氢氧化锌(Zn(OH)2)、氢氧化亚铁(Fe(OH)2)、氢氧化镉(Cd(OH)2)、氢氧化钴(Co(OH)2)或氢氧化镍(Ni(OH)2)，相应的产物[(CH3)2NCH2COO]nM·[有机酸]的金属离子M为过渡金属二价离子，可选自Cu(II)、Zn(II)、Fe(II)、Cd(II)、Co(II)或Ni(II)。
在一些实施例中，步骤(2)涉及的混悬液在碱性条件下加入二价金属卤化物搅拌反应，所述的碱性条件为在反应体系中加入足够的氢氧化钠使反应体系pH为7～8。
所述的多价金属氯化物具体为氯化铜(CuCl2)、氯化锌(ZnCl2)、氯化锰(MnCl2)、氯化亚铁(FeCl2)、氯化亚铬(CrCl2)、氯化镉(CdCl2)、氯化钴(CoCl2)或氯化镍(NiCl2)。
所述的多价金属溴化物具体为溴化铜(CuBr2)、溴化锌(ZnBr2)、溴化锰(MnBr2)、溴化亚铁(FeBr2)、溴化铬(CrBr2)、溴化镉(CdBr2)、溴化钴(CoBr2)或溴化镍(NiBr2)。
所述的多价金属碘化物具体为溴化铜(CuI2)、碘化锌(ZnI2)、碘化锰(MnI2)、碘化亚铁(FeI2)、碘化铬(CrI2)、碘化镉(CdI2)、碘化钴(CoI2)或碘化镍(NiI2)。
上述过程生成的相应的产物[(CH3)2NCH2COO]nM·[有机酸]包含的金属离子为Cu(II)、Zn(II)、Fe(II)、Mn(II)、Cr(II)、Cd(II)、Co(II)或Ni(II)。
在一些实施例中，上述化学反应步骤(3)溶于水溶性溶剂中的有机酸可选自多元有机酸、直链脂肪一元酸或芳香有机酸。
所述的多元有机酸可选自富马酸、马来酸、酒石酸、琥珀酸、延胡索酸、丙二酸、苹果酸、二羟基丙酸、丙酮酸、乙醇酸、葡萄糖醛酸、半乳糖醛酸、天冬氨酸、谷氨酸、柠檬酸或草酸，优选为富马酸。
所述的直链脂肪一元酸可选自C4-C18直链脂肪一元酸，优选为十四碳酸。
所述的芳香有机酸可选自苯甲酸、对甲苯甲酸、对氯苯甲酸、对溴苯甲酸、对氨基苯甲酸、扁桃酸、肉桂酸、苯磺酸、对甲苯磺酸、萘甲酸、水杨酸或乙酰水杨酸，优选为苯甲酸、对甲苯甲酸或对甲苯磺酸。
在一些实施例中，为了获得化学纯度更高、杂质含量更低的N,N-二甲基甘氨酸金属有机酸共轭盐，粗品经醇溶剂、醇水混合溶剂或其他可用于产品重结晶的有机溶剂中在合适的温度、光照以及机械振动等条件下重结晶和分离得到具有一定晶型状态的N,N-二甲基甘氨酸金属有机酸共轭盐。所述具有一定晶型状态的N,N-二甲基甘氨酸金属有机酸共轭盐可以是其溶剂合物。
本发明涉及的“溶剂合物”是指本发明的复合盐与溶剂分子接触的过程中，外部条件与内部条件因素造成通过非共价分子间力而结合化学当量或非化学当量的溶剂分子而形成的共晶缔合物。形成溶剂合物的溶剂包括但是不限于水、丙酮、乙醇、甲醇、二甲亚砜、乙酸乙酯、乙酸、异丙醇等溶剂。“水合物”是指溶剂分子是水所形成的缔合物或结晶体，也就是通过非共价分子间力而结合化学当量或非化学当量的水的化合物。
在一些实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐的溶剂合物可 选自N,N-二甲基甘氨酸金属有机酸共轭盐的水合物或乙醇合物。
在一具体的实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐为[(CH3)2NCH2COO]2Ca·[苯甲酸]。
在一具体的实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐为[(CH3)2NCH2COO]2Ca·[富马酸]。
在一具体的实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐为[(CH3)2NCH2COO]2Cu·[苯甲酸]。
在一具体的实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐为[(CH3)2NCH2COO]2Cu·[富马酸]。
在一具体的实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐为[(CH3)2NCH2COO]2Zn·[苯甲酸]。
在一具体的实施例中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐[(CH3)2NCH2COO]2Zn·[富马酸]。
本发明提供了上述N,N-二甲基甘氨酸金属有机酸共轭盐的高湿稳定性研究。在新饲料添加剂稳定性试验规范要求的高湿稳定性试验研究中，所述的N,N-二甲基甘氨酸金属有机酸共轭盐在25℃的RH95％条件下放置到第10天吸湿增重量均低于5％，符合饲料添加剂的对湿度的要求。
本文所使用的术语“和/或”包括一个或多个相关的所列项目的任意的和所有的组合。
本发明涉及上述N,N-二甲基甘氨酸金属有机酸共轭盐在制备动物饲料添加剂或动物饲料中的应用。
本发明涉及的“动物”是指不能将无机物合成有机物，只能以有机物作为食料，以进行摄食、消化、吸收、呼吸、循环、排泄、感觉、运动和繁殖等为生命活动的人或养殖动物。
可选的，养殖动物包括家禽、家畜、水产动物以及人工饲养合法捕获的其他动物包括宠物。具体的，本发明涉及的家禽为各个生长阶段的鸡、鸭、鹅、鸽、鹌鹑或火鸡等食源性动物；本发明涉及的家畜为各个生长阶段的猪、牛、羊、家兔、马等食源性动物；本发明涉及的水产养殖动物为各个生长阶段的鱼、 虾、泥鳅、蟹或鳝等；本发明涉及的宠物包括但不限于猫、狗、兔等。
在一些养殖方案中，在鸡、鸭、鹅或鸽等家禽的基础日粮中添加本发明提供的N,N-二甲基甘氨酸金属有机酸共轭盐，可显著的降低料肉比系数，提高家禽对饲料的利用率，达到与N,N-二甲基甘氨酸钠的等效的作用效果。
在一些养殖方案中，在猪、牛、羊等单胃的或反刍等家畜的基础日粮中添加本发明提供的N,N-二甲基甘氨酸金属有机酸共轭盐，对家畜的生产性能具有显著的改善作用，表现在平均日增重和平均料肉比的下降。
在一些养殖方案中，在鱼、虾等水产养殖动物的基础日粮中添加本发明提供的N,N-二甲基甘氨酸金属有机酸共轭盐，可显著的改善水产养殖动物尤其是鱼类的抗缺氧能力提高存活率。
在一些养殖方案中，N,N-二甲基甘氨酸金属有机酸共轭盐可与猫粮、狗粮等宠物口粮联合使用，达到调节猫、狗等宠物的肠胃功能的功效，有效缓解宠物因消化不良导致的拉稀症状。
因此，不易吸潮的N,N-二甲基甘氨酸金属有机酸共轭盐满足新饲料添加剂对高湿稳定性的要求还具有与N,N-二甲基甘氨酸钠相似或更优的改善养殖动物生产性能的效果，可应用在制备动物饲料添加剂或动物饲料中。
本发明提供一种饲用组合物，包含本发明提供的N,N-二甲基甘氨酸金属有机酸共轭盐的至少一种和可饲用辅料。
本发明涉及的“组合物”是指包含一种或一种以上的化合物组成有效成分的化合物集体。
本发明所述的“包含”为开放式表达，既包括本发明所明指的内容，但并不排除其他方面的内容。
可选的，所述可饲用辅料包括饲料添加剂或饲料常用的载体、粘结剂、抗结块剂、稳定剂、乳化剂、稀释剂、溶媒或它们的组合。
本发明的“载体”是指能够承载活性成分，改善其分散性，并有良好的化学稳定性和吸附性的可饲用物质，分为有机载体和无机载体。所述的有机载体般是含粗纤维多的物料，包括但不限于玉米粉、玉米芯粉、麦麸、稻壳粉、脱脂米糠、统糠、玉米秸秆粉、花生壳粉等。所述的无机载体一般是矿物质，主要分 为钙盐类和硅的氧化物类，用于微量元素预混料的制作，包括但不限于碳酸钙、硅酸盐、蛭石、沸石、海泡石等。
本发明涉及的“稀释剂”是指将添加剂原料均匀分布于物料中，将高浓度的添加剂原料稀释为低浓度的预混剂或预混料的物质，可将微量成分彼此分开，减少活性成分之间的相互反应，以增加活性成分的稳定性但不影响有关物质的物化性质。稀释剂的种类分为有机稀释剂和无机稀释剂，常见的有机稀释剂包括但不限于玉米粉、去胚玉米粉、右旋糖(葡萄糖)、蔗糖、带有麸皮的粗小麦粉、炒大豆粉、次粉、玉米蛋白粉等，常用的无机稀释剂包括但不限于石灰石、磷酸二氢钙、贝壳粉、高岭土(白陶土)、食盐和硫酸钠。
本发明涉及的辅剂包括但不限于指粘合剂、润湿剂、崩解剂、润滑剂、抗氧化剂、防腐剂。
本发明涉及的“媒介物”是指溶解或分散固体所需的溶剂，包括但不限于水、乙醇、甘油等。
进一步的，所述的饲用组合物包含附加的动物饲料添加剂，所述的附加的动物饲料添加选自营养性饲料添加剂、一般性饲料添加剂或药物饲料添加剂。
具体的，所述的营养性饲料添加剂包括但不限于氨基酸、氨基酸盐及其类似物、维生素及类维生素、矿物元素及其络(螯)合物、微生物酶制剂或非蛋白氮；所述的一般性饲料添加剂包括但不限于生长促进剂、驱虫保健剂、调味和诱食剂、饲料调质剂、饲料调制剂、饲料贮藏剂和中草药添加剂；所述的药物饲料添加剂包括但不限于具有预防动物疾病、促进动物生长作用并可在饲料中长期添加使用而掺入载体或稀释剂的兽药预混合物质。
进一步的，所述的饲用组合物可包含饲料原料，所述的饲料原料选自非饲料添加剂的可用于加工制作饲料的动物、植物、微生物或矿物等饲用物质。
在一些实施方案中，所述饲用组合物为添加剂预混合饲料、浓缩饲料、配合饲料或精料补充料。
所述的饲料添加剂预混合饲料，是指以矿物质微量元素、维生素、微生物、氨基酸中任何两类或两类以上的营养性饲料添加剂为主，与本发明提供的丁酰谷氨酸衍生物或其他饲料添加剂、载体和(或)稀释剂按照一定比例配制的均 匀混合物，其中营养性饲料添加剂的含量能够满足其适用动物特定生理阶段的基本营养需求，在配合饲料、精料补充料或动物饮用水中的添加量不低于0.1％且不高于10％。
所述的浓缩饲料是指主要有蛋白质、矿物质和饲料添加剂按照一定比例配制的饲料。
所述的配合饲料是指根据养殖动物营养需要，将多种饲料原料和饲料添加剂按照一定比例配制的饲料。
所述的精料补充料是指为补充草食动物的营养，将多种饲料原料和饲料添加剂按照一定比例配制的饲料。
本发明还涉及所述饲用组合物的制备过程，包括称重原料和辅料、混合机组混合、制粒、质检和包装的过程。
一、N,N-二甲基甘氨酸金属有机酸共轭盐的制备
实施例1 N,N-二甲基甘氨酸钙苯甲酸共轭酸盐
化学式为[(CH3)2NCH2COO-]2Ca2+(PhCOOH)2，结构式如下：
Figure PCTCN2017109143-appb-000001
制备步骤：
步骤1：N,N-二甲基甘氨酸盐酸盐的制备
三口反应烧瓶中加入三甲胺水溶液275mL(40％，2.44mol，4.6eq)，低温反应槽中机械搅拌，恒压滴液漏斗缓慢滴加氯乙酸水溶液50mL(50.0g/50ml，0.53mol，1.0eq)，控制氯乙酸水溶液流速使反应体系温度不超50.0℃，滴毕，室温反应11h，减压浓缩除去未反应的二甲胺和水得50mL N,N-二甲基甘氨酸粗品水溶液。N,N-二甲基甘氨酸粗品水溶液在低温反应槽中0℃冷却搅拌，缓慢滴加浓盐酸至反应体系pH值为1～2，搅拌10min反应体系析出大量白色絮状固体，往反应体系加入无水乙醇40mL，0℃搅拌20min，趁冷过滤，滤渣移至50℃烘箱内减压干燥过夜得N,N-二甲基甘氨酸盐酸盐为白色粉末状晶体(52.3g， 70.7％)。
步骤2：N,N-二甲基甘氨酸钙苯甲酸共轭酸盐的制备
1L三口反应烧瓶中依次加入N,N-二甲基甘氨酸盐酸盐20.0g(143.3mmol，1.00eq)，无水乙醇250mL，室温下剧烈搅拌形成均匀混悬液；反应体系中分批加入固体氢氧化钠6.0g(1g×6，150.0mmol，1.05eq)，放热，室温搅拌反应0.5h；反应体系加入粉末状固体氢氧化钙5.31g(771.64mmol，0.50eq)，室温剧烈搅拌反应2.0h，得黏稠状反应液；苯甲酸17.50g(143.3mmol，0.50eq)溶于60ml无水乙醇中，投入反应体系搅拌反应3.0h得白色混悬液，减压抽滤，滤渣在105℃烘箱减压干燥过夜得产物为灰白色粉末状固体(19.77g，56.6％)。
实施例2 N,N-二甲基甘氨酸钙富马酸共轭酸盐
化学式为[(CH3)2NCH2COO-]2Ca2+(COOHCHCHCOOH)，结构式如下：
Figure PCTCN2017109143-appb-000002
1L三口反应烧瓶中依次加入N,N-二甲基甘氨酸盐酸盐20.0g(143.3mmol，1.00eq)，无水乙醇250mL，室温下剧烈搅拌形成均匀混悬液；反应体系中分批加入固体氢氧化钠5.80g(1g×6，145.0mmol，1.00eq)，放热，室温搅拌反应0.5h；反应体系加入粉末状固体氢氧化钙5.35g(72.35mmol，0.50eq)，室温剧烈搅拌反应2.0h，得黏稠状反应液；富马酸8.35g(71.94mmol，0.50eq)溶于60ml无水乙醇中，投入反应体系搅拌反应3.0h得白色混悬液，减压抽滤，滤渣在105℃烘箱减压干燥过夜得产物为灰白色粉末状固体(16.03g，62.10％)。
实施例3 N,N-二甲基甘氨酸钙十四酸共轭酸盐
化学式为[(CH3)2NCH2COO-]2Ca2+(CH3(CH2)12COOH)2，结构式如下：
Figure PCTCN2017109143-appb-000003
1L三口反应烧瓶中依次加入N,N-二甲基甘氨酸盐酸盐20.0g(143.3mmol，1.00eq)，无水乙醇250mL，室温下剧烈搅拌形成均匀混悬液；反应体系中分批加入固体氢氧化钠6.0g(1g×6，150.0mmol，1.05eq)，放热，室温搅拌反应0.5h； 反应体系加入粉末状固体氢氧化钙5.30g(71.64mmol，0.50eq)，室温剧烈搅拌反应2.0h，得黏稠状反应液；十四酸16.36g(71.64mmol，0.50eq)溶于75ml无水乙醇中，投入反应体系搅拌反应3.0h得白色混悬液，减压抽滤，滤渣在105℃烘箱减压干燥过夜得产物为白色粉末状固体(23.05g，45.90％)。
实施例4 N,N-二甲基甘氨酸铜苯甲酸共轭酸盐
化学式为[(CH3)2NCH2COO-]2Cu2+(PhCOOH)2，结构式如下：
Figure PCTCN2017109143-appb-000004
1L三口反应烧瓶中依次加入N,N-二甲基甘氨酸盐酸盐20.0g(143.3mmol，1.00eq)，无水乙醇250mL，室温下剧烈搅拌形成均匀混悬液；反应体系中分批加入固体氢氧化钠5.73g(1g×6，143.3mmol，1.00eq)，放热，室温搅拌反应0.5h；反应体系加入粉末状氢氧化铜7.00g(75.6mmol，0.53eq)，室温剧烈搅拌反应2.0h，得黏稠状反应液；苯甲酸17.50g(143.3mmol，0.50eq)溶于60ml无水乙醇中，投入反应体系搅拌反应3.0h得白色混悬液，减压抽滤，滤渣在105℃烘箱减压干燥过夜得产物为灰白色粉末状固体(18.93g，51.70％)。
实施例5 N,N-二甲基甘氨酸铜富马酸共轭酸盐
化学式为[(CH3)2NCH2COO-]2Cu2+(COOHCHCHCOOH)，结构式如下：
Figure PCTCN2017109143-appb-000005
1L三口反应烧瓶中依次加入N,N-二甲基甘氨酸盐酸盐20.0g(143.3mmol，1.00eq)，无水乙醇250mL，室温下剧烈搅拌形成均匀混悬液；反应体系中分批加入固体氢氧化钠5.75g(1g×6，143.8mmol，1.00eq)，放热，室温搅拌反应0.5h；反应体系加入粉末状固体氢氧化铜7.00g(71.65mmol，0.50eq)，室温剧烈搅拌反应2.0h，得黏稠状反应液；富马酸8.32g(71.64mmol，0.50eq)溶于60ml无水乙醇中，投入反应体系搅拌反应3.0h得白色混悬液，减压抽滤，滤渣在110℃烘箱减压干燥过夜得产物为灰白色粉末状固体(12.90g，46.9％)。
实施例6 N,N-二甲基甘氨酸锌苯甲酸共轭酸盐
化学式为[(CH3)2NCH2COO-]2Zn2+(PhCOOH)2，结构式如下：
Figure PCTCN2017109143-appb-000006
1L三口反应烧瓶中依次加入N,N-二甲基甘氨酸盐酸盐20.0g(143.3mmol，1.00eq)，无水乙醇250mL，室温下剧烈搅拌形成均匀混悬液；反应体系中分批加入固体氢氧化钠6.0g(1g×6，150.0mmol，1.05eq)，放热，室温搅拌反应0.5h；反应体系加入粉末状固体氢氧化锌7.20g(72.44mmol，0.50eq)，室温剧烈搅拌反应2.0h，得黏稠状反应液；苯甲酸17.50g(143.30mmol，0.50eq)溶于60ml无水乙醇中，投入反应体系搅拌反应3.0h得白色混悬液，减压抽滤，滤渣在105℃烘箱减压干燥过夜得产物为灰白色粉末状固体(15.36g，41.8％)。
实施例7 N,N-二甲基甘氨酸锌富马酸共轭酸盐
化学式为[(CH3)2NCH2COO-]2Zn2+(COOHCHCHCOOH)，结构式如下：
Figure PCTCN2017109143-appb-000007
1L三口反应烧瓶中依次加入N,N-二甲基甘氨酸盐酸盐20.0g(143.3mmol，1.00eq)，无水乙醇250mL，室温下剧烈搅拌形成均匀混悬液；反应体系中分批加入固体氢氧化钠5.75g(1g×6，143.76mmol，1.00eq)，放热，室温搅拌反应0.5h；反应体系加入粉末状固体氢氧化锌7.12g(71.64mmol，0.50eq)，室温剧烈搅拌反应2.0h，得黏稠状反应液；富马酸8.30g(71.51mmol，0.50eq)溶于60ml无水乙醇中，投入反应体系搅拌反应3.0h得白色混悬液，减压抽滤，滤渣在105℃烘箱减压干燥过夜得产物为灰白色粉末状固体(12.49g，45.2％)。
二、N,N-二甲基甘氨酸金属有机酸共轭盐的相关性质
供试品及供应商：
样品1：N,N-二甲基甘氨酸盐酸盐，百灵威科技有限公司；
样品2：N,N-二甲基甘氨酸钠，山东西亚化学工业有限公司；
样品3：N,N-二甲基甘氨酸钙，广州英赛特生物技术有限公司研发中心；
样品4：苯甲酸钙，广州英赛特生物技术有限公司研发中心；
样品5：N,N-二甲基甘氨酸钙苯甲酸共轭酸盐，实施例1制备；
样品6：N,N-二甲基甘氨酸钙富马酸共轭酸盐，实施例2制备；
样品7：N,N-二甲基甘氨酸钙十四酸共轭酸盐，实施例3制备；
样品8：N,N-二甲基甘氨酸铜苯甲酸共轭酸盐，实施例4制备；
样品9：N,N-二甲基甘氨酸铜富马酸共轭酸盐，实施例5制备；
样品10：N,N-二甲基甘氨酸锌苯甲酸共轭酸盐，实施例6制备；
样品11：N,N-二甲基甘氨酸锌富马酸共轭酸盐，实施例7制备。
1、性状及熔点测定
表1 N,N-二甲基甘氨酸金属有机酸共轭盐的性状及熔点测定
供试品 性状 熔点/℃
N,N-二甲基甘氨酸盐酸盐 白色结晶状颗粒 189-193
N,N-二甲基甘氨酸钠 白色粉末 217℃
N,N-二甲基甘氨酸钙 白色粉末 220℃，未溶解，分解
苯甲酸钙 白色粉末 ﹥260℃，未溶解，未分解
样品5 白色粉末 ﹥245℃，未溶解，分解
2、高湿稳定性试验
方法：
恒温恒湿密闭容器下部放置KNO3饱和溶液(25℃，RH90％)，供试品平行设置三个检测样品，于25℃、RH95％±1％条件下放置10天，于第5天和第10天检测供试品的平均增重量。
结果：试验数据采用SPSS18软件进行统计分析，试验结果以“平均值±标准误”表示如表2所示。在25℃下的RH95％条件下，样品1、样品2和样品3分别为DMG的盐酸盐、钠盐和钙盐，吸潮性非常严重，实验进行到第5天供试品的 吸水量达到使样品成为水样状。样品5-11分别属于N,N-二甲基甘氨酸有机酸钙、N,N-二甲基甘氨酸有机酸铜或N,N-二甲基甘氨酸有机酸锌，在试验进行到第5天时吸湿增重量不超过3.7％，并且第5天与第10天的吸潮增重量没有显著的改变。
结论：N,N-二甲基甘氨酸金属有机酸共轭盐在恒温恒湿的25℃、RH95％±1％条件下放置10天吸潮增重量均低于5％，并具有相对稳定性，符合饲料添加剂对湿度的要求。
表2 N,N-二甲基甘氨酸金属有机酸共轭盐的高湿稳定性研究
化合物 第5天(％) 第10天(％)
样品1 79.86±0.94 80.69±0.59
样品2 49.09±1.14 52.44±0.48
样品3 38.40±0.22 41.83±0.35
样品5 3.67±0.41 3.69±0.28
样品6 3.11±0.23 3.21±0.07
样品7 2.41±0.04 3.06±0.29
样品8 2.51±0.07 2.90±0.09
样品9 2.74±0.10 2.90±0.05
样品10 3.02±0.15 3.65±0.08
样品11 2.39±0.12 2.88±0.22
三、饲用组合物制备方法
实施例1～7的N,N-二甲基甘氨酸金属有机酸共轭盐分别与相应的辅料混合制备相应的混合型颗粒饲料添加剂。
1.材料
原料：实施例1～7的N,N-二甲基甘氨酸金属有机酸共轭盐、N,N-二甲基甘氨酸钠；
载体：玉米淀粉；
粘合剂：1.3％羟丙基甲基纤维素水溶液。
2.产品配方
表3 N,N-二甲基甘氨酸金属有机酸共轭盐的混合型颗粒饲料添加剂的配方
Figure PCTCN2017109143-appb-000008
3.生产工艺
本发明涉及的混合型颗粒饲料添加剂的生产工艺以下结合图1进行说明。
原料供应：广州英赛特生物技术有限公司研发中心，经品控部检验为合格产品，纯度≥99％。
辅料采购：从合格供应商处采购辅料，辅料到厂后抽样，经检验合格方能入库，存放备用，此过程为关键控制点，必须严格把控辅料质量。
生产领料、称量：根据产品配方的比例，对原料和辅料依次称重和复核，对产生的废弃物(包装袋)统一存放、处理。
混合：将原料和辅料投入混合机组混合均匀，此步骤为关键控制点，必须严格控制混合时间，定期对混合均匀度进行验证。混合机配有脉冲除尘器减少粉尘。
制粒：将原料和辅料混合后的产品与1.3％羟丙基甲基纤维素水溶液按照100:35的质量比例投入制粒机内，启动混合及切刀运行3-5min，物料制粒好以后进入流化床进行干燥，30min后过16目筛网。
包装和检验：根据包装规格进行称重打包，存入成品仓，标识生产批次和检验状态等信息，每一生产批次至少抽检两份样品送化验室进行出厂检验和留样。检验合格后方能出厂。由此得到各混合型颗粒饲料添加剂。
生产设备清洗：每一批产品生产完毕，必须对生产区域进行清洁。当更换生产品种时，必须对生产设备进行载体运转除杂，防止交叉污染。
三、动物饲养试验
实验例A N,N-二甲基甘氨酸金属有机酸共轭盐在肉鸡料中的应用效果
试验采用单因子随机设计，选择22日龄、平均体重153g、体重相近的三黄羽肉鸡1080只，随机分为9个处理组，每组6个重复，公母各半，每个重复20只三黄羽肉鸡。试验前对鸡舍及器具进行消毒。试验期在同一鸡舍同一饲养管理条件下进行进行笼养。基础日粮以玉米-豆粕为主，整个饲养过程不额外添加其它抗氧化成分及促生长剂。各试验组分别为空白组、对照组、试验1～7组。其中空白组仅给与基础日粮，对照组和试验1～7组分别在基础日粮中添加5000ppm的本发明提供的混合型颗粒饲料添加剂产品(参见“饲用组合物的制备方法”部分)。试验期共20天，试验鸡自由饮水和采食，日喂料2次。以每个重复为单位，于42日龄称重(停料12h、不停水)，统计试验鸡耗料量，计算各组试验鸡的平均日采食量(ADFI)、平均日增重(ADG)和料肉比(FCR)。试验数据采用SPSS18软件进行统计分析，先对数据作单因素方差分析(ANOVA)，若处理间差异显著，再用Duncan's法进行多重比较，显著性水平为0.05。试验结果以“平均值±标准误”表示，试验结果如表4所示。从结果可知，与空白组相比对照组和各试验组对实验鸡的采食量的影响不显著，但是均显著提高了试验鸡的平均日增重和显著的降低了料肉比；其中，试验组与对照组相比，试验鸡的平均日增重改变不显著，试验组1-3的料肉比相比对照组下降不显著，试验组4-7的料肉比相比于对照组下降显著。
结论：在肉鸡的养殖实验中提高饲料的转化效率方面，本发明提供的N,N-二甲基甘氨酸钙苯甲酸共轭酸盐、N,N-二甲基甘氨酸钙富马酸共轭酸盐和N,N-二甲基甘氨酸钙十四酸共轭酸盐具有与N,N-二甲基甘氨酸钠盐等效的养殖效果，而本发明提供的N,N-二甲基甘氨酸铜苯甲酸共轭酸盐、N,N-二甲基甘氨酸锌苯甲酸共轭酸盐、N,N-二甲基甘氨酸铜富马酸共轭酸盐和N,N-二甲基甘氨酸锌富马酸共轭酸盐比N,N-二甲基甘氨酸钠盐具有更优的养殖效果，与不给予任何饲料添加剂的实验组相比料肉比下降了约10％～11.5％。
表4 N,N-二甲基甘氨酸金属有机酸共轭盐对肉鸡生产性能影响结果
Figure PCTCN2017109143-appb-000009
实施例B N,N-二甲基甘氨酸金属有机酸共轭盐在猪料中的应用研究
体重相近的65日龄杜长大三元杂瘦肉型小猪240头，随机分成8个处理组，每组3个重复，公母各半，每组10头。试验前对猪圈及器具进行消毒。试验期在同一猪圈同一饲养管理条件下分栏圈养。试验期间，以试验猪自由采食和饮水，日喂料2次。各试验组分别为对照组和试验1～7组。其中，对照组仅给与基础日粮，试验1～7组分别给予分别在基础日粮中添加1150ppm的本发明提供的混合型颗粒饲料添加剂产品1～7。整个饲养过程各试验组不额外添加其它抗氧化成分及促生长剂。试验周期28天，以每个重复为单位，统计试验猪的生产性能，分别为平均日采食量(ADFI)、平均日增重(ADG)和料肉比(FCR)。试验数据采用SPSS18软件进行统计分析，先对数据作单因素方差分析(ANOVA)， 若处理间差异显著，再用Duncan's法进行多重比较，显著性水平为0.05。试验结果以“平均值±标准误”表示，试验结果如表5所示。从结果可知，给与含有N,N-二甲基甘氨酸金属有机酸共轭盐的试验组与对照组相比，试验猪的采食量没有受到显著影响，但是平均日增重显著的提高的同时料肉比下降了6.8％～12.2％。另外，N,N-二甲基甘氨酸铜有机酸共轭盐和N,N-二甲基甘氨酸锌有机酸共轭盐对试验猪的生产性能的改善效果相比于N,N-二甲基甘氨酸钙有机酸共轭盐的效果更为显著。
表5 N,N-二甲基甘氨酸金属有机酸共轭盐对小猪的生产性能影响
  供试品 试验数量 ADFI(kg) ADG(kg) FCR
对照组 - 10*3 11.87±0.32 4.51±0.08a 2.63±0.02a
试验1组 产品1 10*3 12.73±0.33 5.24±0.10b 2.43±0.02b
试验2组 产品2 10*3 12.40±0.26 5.11±0.07b 2.43±0.02b
试验3组 产品3 10*3 12.77±0.20 5.20±0.10b 2.45±0.01b
试验4组 产品4 10*3 12.53±0.27 5.42±0.12b 2.31±0.01c
试验5组 产品5 10*3 12.70±0.26 5.47±0.13b 2.32±0.01cd
试验6组 产品6 10*3 12.43±0.43 5.24±0.21b 2.38±0.01e
试验7组 产品7 10*3 12.50±0.38 5.28±0.18b 2.37±0.01de
实施例C N,N-二甲基甘氨酸金属有机酸共轭盐在水产料中的应用
(1)试验材料
试验用鱼：所用试验鱼为草鱼，当年鱼种，由广东省惠州市大丰鱼种场。健康活泼、规格一致的草鱼种在大网箱中(4×2×1.5m3)饲养4周后才用于正式养殖试验，实验体系为浮性小网箱(规格1.1×1.1×1.1m3)，每个小网箱均置有一个充气头，每天24h充气。小网箱与暂养网箱均置于试验场一个3500m2的池塘中，池塘水深约1.5m，池塘水为充分曝气底下水。试验时，将体重相近、饥饿1天的草鱼384尾随机分成8组，每组设4个重复，每个重复放12尾鱼，以每个重复为单位称重后放入36个网箱中，分别饲喂不同的试验饲料。
试验饲料：试验用饲料按表6配方自行配制，不同试验组按表7分别加入相同剂量的不同的N,N-二甲基甘氨酸金属有机酸共轭盐。所用饲料原料经超微粉碎后通过江苏牧羊膨化机组制成粒径3mm浮性膨化饲料，出模温度130℃，通 过喷油设备外喷3％豆油，阴凉处密封保存备用。
表6 试验用草鱼饲料配方及化学成分(％wt.)
原料组成 含量(％) 原料组成 含量(％)
鱼粉 9.0 豆油 3.0
肠衣粉 3.0 磷脂菜粕 9.0
豆粕 12.0 谷朊粉 4.0
菜粕 12.0 血球粉 2.0
味精蛋白 3.0 Vc-磷酸酯 0.1
次粉 12.6 磷酸二氢钙 1.8
面粉 17.0 氯化胆碱 0.2
膨润土 0.70 多维 0.1
米糠 10.0 微矿预混剂 0.5
表7 N,N-二甲基甘氨酸金属有机酸共轭盐的促生长试验分组
Figure PCTCN2017109143-appb-000010
(2)试验方法
试验管理：试验采用人工限食投喂，投食量每周调整一次，每组投喂水平(按初始体重)完全一致，每天投喂两次(7:30及15:00)。试验为期8周。试验期间定时对水质进行监控，养殖全程水温26.88±3.08℃、DO>5.0mg O L-1、pH7.8、氨氮<0.50mg N L-1、亚硝酸盐氮<0.05mg N L-1。
参数统计：试验时，停喂1d后对各网箱鱼进行整体称重，计算其增重率 (WG,％)、饲料系数(FCR)和存活率(SR,％)。计算公式如下：
增重率(WG，％)＝100×(平均末重－平均初重)/平均初重；
饲料系数(FCR)＝摄食量/鱼体增重；
存活率(SR，％)＝100×试验结束时鱼数量/试验开始时鱼数量。
(3)试验结果
N,N-二甲基甘氨酸金属有机酸共轭盐对草鱼的生产性能的影响结果见表8。结果显示添加了N,N-二甲基甘氨酸金属有机酸共轭盐的试验组在增重和饲料系数方面均优于空白对照组，具有明显的促生长效应，另外，还可显著提高草鱼的存活率，具有明显的改善草鱼的抗缺氧能力。
表8 N,N-二甲基甘氨酸金属有机酸共轭盐在鱼料中的应用试验结果
  初重(g) 末重(g) 增重率(％) (FCR) SR(％)
空白对照组 251.25±2.68 574.64±11.04 133.15±4.54 1.56±0.04 55.31±2.57a
试验1组 249.81±4.09 586.87±10.44 134.96±2.82 1.48±0.03 83.10±3.65b
试验2组 246.56±3.54 589.33±12.75 138.98±3.02 1.48±0.03 83.90±5.30b
试验3组 249.62±2.51 585.22±11.23 134.40±2.90 1.46±0.04 73.00±3.63b
试验4组 246.81±7.18 598.68±9.66 143.40±10.09 1.41±0.03 80.04±3.80b
试验5组 250.31±6.28 598.12±9.27 139.12±2.34 1.43±0.03 83.96±5.68b
试验6组 256.75±6.69 597.66±9.69 133.08±4.70 1.45±0.03 78.04±4.21b
试验7组 250.31±7.05 600.00±9.30 139.98±3.58 1.44±0.02 84.94±4.26b
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。

Claims (10)

  1. 一种N,N-二甲基甘氨酸金属有机酸共轭盐，其特征在于，结构式如下：
    [(CH3)2NCH2COO]nM·[有机酸]
    其中，n为1或2；M选自碱金属离子或二价金属离子；
    有机酸选自多元有机酸、C2-C18直链脂肪酸或芳香酸。
  2. 根据权利要求1所述的N,N-二甲基甘氨酸金属有机酸共轭盐，其特征在于，所述多元有机酸选自富马酸、马来酸、酒石酸、琥珀酸、延胡索酸、丙二酸、苹果酸、二羟基丙酸、丙酮酸、乙醇酸、葡萄糖酸、半乳糖酸、天冬氨酸、谷氨酸、柠檬酸或草酸；所述C2-C18直链脂肪酸选自乙酸、丙酸、丁酸、癸酸、棕榈酸、月桂酸或硬脂酸；所述芳香酸选自苯甲酸、对甲基苯甲酸、萘甲酸、扁桃酸、对氯苯甲酸、对溴苯甲酸、对氨基苯甲酸、肉桂酸、水杨酸、乙酰水杨酸、对甲苯磺酸或苯磺酸。
  3. 根据权利要求1所述的N,N-二甲基甘氨酸金属有机酸共轭盐，其特征在于，所述有机酸为苯甲酸、对甲苯甲酸或富马酸。
  4. 权利要求1所述的N，N-二甲基甘氨酸金属有机酸共轭盐，其特征在于，所述的二价金属离子选自Ca(II)、Mg(II)、Cu(II)、Zn(II)、Fe(II)、Mn(II)、Co(II)或Ni(II)。
  5. 根据权利要求1-4任一项所述的N,N-二甲基甘氨酸金属有机酸共轭盐，其特征在于，选自：[(CH3)2NCH2COO]2Ca·[苯甲酸]、[(CH3)2NCH2COO]2Ca·[富马酸]、[(CH3)2NCH2COO]2Cu·[苯甲酸]、[(CH3)2NCH2COO]2Cu·[富马酸]、[(CH3)2NCH2COO]2Zn·[苯甲酸]或[(CH3)2NCH2COO]2Zn·[富马酸]。
  6. 权利要求1-5任一项所述的N,N-二甲基甘氨酸金属有机酸共轭盐在制备动物饲料添加剂中的应用。
  7. 权利要求1-5任一项所述的N,N-二甲基甘氨酸金属有机酸共轭盐在制备动物饲料中的应用。
  8. 一种饲用组合物，其特征在于，包括权利要求1-5任一项所述的N,N-二甲基甘氨酸金属有机酸共轭盐的至少一种以及药学、食品或饲料可接受的载 体。
  9. 根据权利要求8所述的饲用组合物，其特征在于，还包括营养性饲料添加剂和/或非营养性饲料添加剂。
  10. 根据权利要求8或权利要求9所述的饲用组合物，其特征在于，还包括饲料原料。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115260068A (zh) * 2022-07-20 2022-11-01 天宝动物营养科技股份有限公司 以羟基蛋氨酸为片基的二价金属共盐化合物及其制备方法与应用

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3670493T3 (da) * 2017-10-25 2022-03-07 Guangzhou Insighter Biotechnology Co Ltd Salt af en organisk n,n-dimethylglycinsyreforbindelse og sammensætning og anvendelse deraf
CN111727932B (zh) * 2020-06-30 2022-07-22 湖南恒智农业综合开发有限公司 有机黑猪的养殖方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1091430A (zh) * 1993-02-16 1994-08-31 北京市潮白河新技术研究所 复配氨基酸螯合物的制备方法
US6197815B1 (en) * 1998-03-18 2001-03-06 J.H. Biotech, Inc. Amino acid chelates to reduce still births and increase birth weight in non-human animals
CN1887887A (zh) * 2005-06-29 2007-01-03 曾雄飞 有机金属络合物、其制备方法、组合物和用途
CN101209975A (zh) * 2006-12-29 2008-07-02 沈阳东宇精细化工有限公司 左旋肉碱富马酸钙及其制备方法与用途
CN101304670A (zh) * 2005-11-11 2008-11-12 埃德瓦多·沃特·埃特林 用氨基酸和/或铵盐稳定的矿质营养素的盐，含有这种盐的产品和食品补充剂及这种盐的获得方法
CN101827530A (zh) * 2007-09-12 2010-09-08 塔明克公司 降低饲料转化率或提高生长速率的猪的处理
CN102911067A (zh) * 2011-08-04 2013-02-06 广州市奥海生物科技有限公司 左旋肉碱丙酮酸盐及其制备方法与用途
CN105777534A (zh) * 2014-12-24 2016-07-20 辽宁科硕营养科技有限公司 柠檬酸钙盐及其制备方法与用途
CN105884637A (zh) * 2016-04-12 2016-08-24 广州先至饲料添加剂有限公司 γ-氨基丁酸富马酸盐及其在制备动物用饲料添加剂中的应用

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI111796B (fi) * 1997-05-28 2003-09-30 Finnfeeds Finland Oy Kiinteä betaiinituote, menetelmä sen valmistamiseksi, ja sen käyttö
BRPI0621518B1 (pt) * 2006-03-21 2022-05-10 Taminco Método para o tratamento não terapêutico das aves domésticas, ração para aves domésticas, e, uso de um composto de glicina e/ou de um sal do mesmo
CN101121672B (zh) * 2006-08-09 2010-11-24 上海祥韦思化学品有限公司 甜菜碱磷酸盐及其生产方法与应用
CN101580476A (zh) * 2009-06-11 2009-11-18 北京贝丽莱斯生物化学有限公司 N,n-二甲基甘氨酸月桂酯的盐
CA2855787C (en) * 2011-11-15 2020-01-14 Tiense Suikerraffinaderij N.V. Process for the recovery of betaine from molasses
CN103387518B (zh) * 2013-07-24 2016-06-08 重庆紫光化工股份有限公司 一种n,n-二甲基甘氨酸的制备方法
CN105494951A (zh) * 2015-12-02 2016-04-20 山东祥维斯生物科技股份有限公司 一种生产650甜菜碱的方法

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1091430A (zh) * 1993-02-16 1994-08-31 北京市潮白河新技术研究所 复配氨基酸螯合物的制备方法
US6197815B1 (en) * 1998-03-18 2001-03-06 J.H. Biotech, Inc. Amino acid chelates to reduce still births and increase birth weight in non-human animals
CN1887887A (zh) * 2005-06-29 2007-01-03 曾雄飞 有机金属络合物、其制备方法、组合物和用途
CN101304670A (zh) * 2005-11-11 2008-11-12 埃德瓦多·沃特·埃特林 用氨基酸和/或铵盐稳定的矿质营养素的盐，含有这种盐的产品和食品补充剂及这种盐的获得方法
CN101209975A (zh) * 2006-12-29 2008-07-02 沈阳东宇精细化工有限公司 左旋肉碱富马酸钙及其制备方法与用途
CN101827530A (zh) * 2007-09-12 2010-09-08 塔明克公司 降低饲料转化率或提高生长速率的猪的处理
CN102911067A (zh) * 2011-08-04 2013-02-06 广州市奥海生物科技有限公司 左旋肉碱丙酮酸盐及其制备方法与用途
CN105777534A (zh) * 2014-12-24 2016-07-20 辽宁科硕营养科技有限公司 柠檬酸钙盐及其制备方法与用途
CN105884637A (zh) * 2016-04-12 2016-08-24 广州先至饲料添加剂有限公司 γ-氨基丁酸富马酸盐及其在制备动物用饲料添加剂中的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3674286A4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115260068A (zh) * 2022-07-20 2022-11-01 天宝动物营养科技股份有限公司 以羟基蛋氨酸为片基的二价金属共盐化合物及其制备方法与应用

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