WO2022047840A1 - 一种动物用复方氨基酸溶液及其制备方法和应用 - Google Patents

一种动物用复方氨基酸溶液及其制备方法和应用 Download PDF

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WO2022047840A1
WO2022047840A1 PCT/CN2020/116378 CN2020116378W WO2022047840A1 WO 2022047840 A1 WO2022047840 A1 WO 2022047840A1 CN 2020116378 W CN2020116378 W CN 2020116378W WO 2022047840 A1 WO2022047840 A1 WO 2022047840A1
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amino acid
parts
acid solution
animals
compound amino
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French (fr)
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李凤英
陈淑芳
裴有志
郭艳玉
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河北科星药业有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
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    • A61K31/33—Heterocyclic compounds
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • 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
    • A61K47/02—Inorganic compounds
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    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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    • A61K9/08—Solutions
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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    • A61P39/06—Free radical scavengers or antioxidants

Definitions

  • the invention belongs to the technical field of animal husbandry and veterinary medicine, and relates to a compound amino acid solution and a preparation method thereof, in particular to a compound amino acid solution for animals and a preparation method and application thereof.
  • the supplementary solutions used to enhance the physical energy of animals mainly use glucose solution, sodium chloride solution and glucose sodium chloride solution, which can adjust the balance of electrolytes in the body, but cannot improve the nutritional deficiency of animals, nor can they supplement the body of animals.
  • required amino acids and vitamins are very important nutrients in animals and have a profound impact on the growth and development of animals. If the animal lacks amino acids and vitamins, it will show symptoms such as stunted growth, slow metabolism, soft bones, frailty, and growth retardation, which will further affect the absorption of nutrients, and even cause kidney damage and stop growth in severe cases. During the period of illness, animals will be weak and their own anabolic capacity will be weakened. If sufficient amino acids and vitamins are not supplemented in time, a series of diseases may also be caused, such as loss of appetite, weight loss, vomiting, severe diarrhea, etc.
  • the purpose of the present invention is to provide a compound amino acid solution for animals to solve the problem of animal body nutrition deficiency
  • Another object of the present invention is to provide a preparation method of the above-mentioned compound amino acid solution for animals;
  • Another object of the present invention is to provide the application of the above-mentioned compound amino acid solution for animals.
  • a compound amino acid solution for animals prepared as raw materials of active ingredients per 1000 parts by volume of the compound amino acid solution for animals, including in parts by weight:
  • the ratio of parts by weight to parts by volume is 1kg:1L.
  • the antioxidant is sodium bisulfite, thiourea or sodium metabisulfite.
  • the complexing agent is disodium EDTA, tartaric acid or citric acid.
  • the preservative is sodium benzoate, sodium ethylparaben or sodium propylparaben.
  • the present invention also provides a method for preparing the above-mentioned compound amino acid solution for animals, comprising the following steps performed in sequence:
  • step 2) the pH value is adjusted to 4.2-6.8.
  • the filtration is divided into coarse filtration and fine filtration
  • Purified water is prepared by boiling for 30-40min.
  • the fine filtration uses a microporous membrane to filter and sterilize the bacteria.
  • the present invention also provides the application of the above-mentioned compound amino acid solution for animals, which is used for improving the nutritional deficiency of animals.
  • the compound amino acid solution for animals is added to drinking water for feeding animals.
  • the present invention obtains a compound amino acid solution for animals with suitable proportions applied to animals through a large number of experiments.
  • the functions of amino acids and vitamins in the animal body are complementary to each other.
  • the present invention utilizes vitamins to promote better absorption of amino acids, and at the same time utilizes amino acids to promote greater medicinal value of vitamins, thereby better supplementing animals
  • Body nutrition improve animal metabolism, accelerate blood flow, promote body recovery, and improve animal production performance.
  • the compound amino acid solution for animals of the present invention can also improve the feed utilization rate, improve the feed-to-meat ratio, promote the synthesis of protein, improve the immunity and antioxidant capacity of the body, and reduce the mortality rate.
  • the compound amino acid solution for animals of the present invention can also improve the liver ability, protect the liver and protect the liver, and reduce the toxic effect of the toxic metabolites produced by the body in the metabolic process on the tissue;
  • Valine, leucine and isoleucine are branched-chain amino acids, which can correct the imbalance of branched-chain amino acids and aromatic amino acids in plasma when entering animals, and can regulate energy substrates, gluconeogenesis substrates and muscle proteins. ; Valine, leucine and isoleucine can also be oxidized to energy in the periphery, which can improve energy intake without increasing the burden on the liver; valine, leucine and isoleucine can also It can be used as a substrate for gluconeogenesis. There is a cyclic metabolic mechanism between oxidation and alanine synthesis in the body, which generates more heat.
  • Each gram molecule of valine, leucine and isoleucine produces 32 , 42, 43 moles of ATP, can provide a lot of energy for the body.
  • Arginine hydrochloride participates in the ornithine cycle in animals, promotes the formation of urea, and makes the ammonia produced in the animal body turn into non-toxic urea through the ornithine cycle, which is excreted with the urine, thereby reducing the blood ammonia concentration.
  • Each amino acid can also enter tissue cells, participate in protein synthesis and metabolism, obtain positive nitrogen balance, and generate enzymes, hormones, antibodies, structural proteins, promote tissue healing, and restore normal physiological functions.
  • Vitamin B1 one of the B vitamins, is an important cofactor in sugar metabolism, plays a role as a coenzyme in the active transport of aldehyde groups and sugar groups, and plays an auxiliary role in nerve conduction and neuronal conduction.
  • Vitamin B 2 riboflavin
  • Vitamin B 2 acts as a coenzyme during metabolism in animals, helping to maintain animal health.
  • Vitamin B2 is deficient , substances such as carbohydrates, fats and proteins in animals cannot be converted into energy to maintain normal body functions.
  • Vitamin B 3 (nicotinamide) has a variety of photoprotective effects in animals. It can enhance DNA repair in animals, reduce the effect of ultraviolet radiation on the immune response of animal skin, regulate the skin barrier function produced by inflammatory cells, and restore the skin caused by ultraviolet radiation.
  • B 6 is a component of some coenzymes in animals and participates in various metabolic reactions, especially closely related to amino acid metabolism.
  • B vitamins are essential nutrients for all animal tissues. They are coenzymes that participate in the metabolism of protein, sugar and fat in the body, and are the key to the release of energy from food.
  • the functions of various B vitamins complement each other. After taking a certain B vitamin alone, due to the increase in cell activity, the demand for other B vitamins increases, which is the so-called "cask principle", which is also called the fusion of vitamin B. It has the function of increasing appetite, maintaining nerve function, and promoting growth and development. Therefore, it is very important to properly match the components of B vitamins.
  • Amino acids are the main source of protein synthesis, which is directly related to the physical fitness and health of animals, and B vitamins directly affect the absorption and utilization of amino acids. Therefore, a reasonable ratio of amino acids and B vitamins directly affects the animal body. The absorption and utilization of B vitamins and B vitamins will affect the physical fitness and health of animals. At the same time, supplementing amino acids and B vitamins is of great significance in the process of animal breeding.
  • the invention adjusts the pH value to 4.2-6.8, thereby ensuring the stability of amino acids and vitamins, and further ensuring the reasonable ratio of amino acids and vitamins; filtering and sterilizing by microporous membrane, while ensuring the stability of amino acids and vitamins, removing The microorganisms in the solution ensure the quality of an animal compound amino acid solution;
  • the preparation method of the invention is simple, and the prepared compound amino acid solution for animals is safe and controllable;
  • the compound amino acid solution for animals of the present invention can save production, packaging and transportation costs during production and use, and is convenient for veterinarians to use;
  • the invention has wide raw material sources and low cost, and can bring good economic benefits to breeding enterprises.
  • the compound amino acid solution for animals of the present invention is suitable for adding to water and feeding animals, so as to improve the nutritional deficiency of animals.
  • Embodiment 1 A kind of preparation method of compound amino acid solution for animals
  • the present embodiment prepares 1000L of a compound amino acid solution for animals, including the following steps in sequence:
  • thiourea is used as an antioxidant, which is added before each amino acid and vitamin is added, which can effectively prevent amino acids and vitamins from occurring during the dissolution process. oxidation reaction;
  • Disodium EDTA can chelate with the metal ions introduced in the raw materials, and it is added before adding amino acids and vitamins to effectively avoid the catalytic oxidation of metal ions to amino acids and vitamins.
  • the dissolution time of amino acids and vitamins shortened with the increase of temperature. When the temperature was above 80 °C, the dissolution speed was the fastest. When the temperature was higher than 80 °C, the solubility and dissolution speed of most amino acids and vitamins did not change significantly. Considering factors such as content and dissolution time, group A amino acids and B vitamins were added step by step between 80 and 100°C for dissolution.
  • a compound amino acid solution for animals is filled, and after the filling is completed, the lamp inspection is qualified, and an independently packaged compound amino acid solution for animals (marked as N1) is prepared.
  • tryptophan Since the stability of tryptophan is not very high, the content of tryptophan will decrease greatly with the increase of temperature. It has been verified by experiments that the content of tryptophan in the solution is relatively high at 60-70 °C. The tryptophan is controlled to dissolve at 60 ⁇ 70°C, which can effectively reduce the oxidation of tryptophan in the process of dissolving tryptophan.
  • the pH value is controlled at 4.2-6.8, which can maintain the stability of amino acid and vitamin content in the solution.
  • the 0.2 ⁇ m or 0.22 ⁇ m microporous membrane can sterilize the bacteria, ensure that the microbial limit in the obtained solution meets the requirements, and increase the stability of the solution quality.
  • the obtained compound amino acid solution for animals is suitable for adding to drinking water and feeding animals to improve the nutritional deficiency of animals.
  • Embodiment 2 ⁇ 6 A kind of preparation method of compound amino acid solution for animals
  • Embodiments 2 to 6 are respectively a preparation method of compound amino acid solution for animals, and their steps are basically the same as those of embodiment 1, and the difference is only the difference in the amount of raw materials and process parameters, as shown in Table 1 for details:
  • Embodiment 7 A kind of content determination result of compound amino acid solution for animals
  • the corresponding labeled amount of amino acids and vitamins should be controlled at 90.0-110.0%, and the labeled amount is calculated based on the content of raw materials in the obtained solution/corresponding raw materials amount, calculated.
  • the appearance and content of the compound amino acid solutions N1-N6 for animals prepared in Examples 1-6 were measured, and the specific results are shown in Table 2:
  • Embodiment 8 A kind of stability detection of compound amino acid solution for animals
  • the accelerated test is placed under the conditions of temperature 40 ⁇ 2°C and relative humidity 75 ⁇ 5% for 6 months, and samples are taken at the end of the 0th, 1st, 2nd, 3rd and 6th months of the test period respectively.
  • "State Food and Drug Administration Drug Standards" WS1 ⁇ (X ⁇ 324) ⁇ 2003Z quality standards for testing, the corresponding labeled amount of amino acids and vitamins should be controlled at 90.0 ⁇ 110.0%, the labeled amount is calculated based on the raw materials in the obtained solution. The content/corresponding raw material dosage is calculated, and the specific test results are shown in Tables 3-8:
  • Embodiment 9 A kind of application of compound amino acid solution for animals
  • Necropsy of the dead chickens showed extensive skin edema; obvious hypertrophy of the adrenal glands, gastrointestinal inflammation, and duodenal ulcers; the right side of the heart often dilated, the atrium was more obvious than the ventricle; the reproductive organs were atrophied, especially the testicles of the rooster.
  • control group was given a premixed 0.5 ⁇ liquid Vitamin drinking water
  • JA1-JA6 groups were given drinking water pre-mixed with 0.5 ⁇ of an animal compound amino acid injection N1-N6, unlimited supply throughout the day, continuous test for 20 days, and given normal feeding.
  • the experiment was carried out in three-layer three-dimensional cages, fed with corresponding feed, and had free access to food and water. According to the routine immunization program of Hyland gray laying hens, the immunization and feeding management are carried out daily, and the chicken house is disinfected every day to ensure the hygiene of the chicken house. During the test period, the weight gain and egg production of laying hens were observed every day, and statistics were made. The specific results are shown in the following table:
  • Table 9 a list of application effects of compound amino acid solution for animals on B deficiency in laying hens
  • the weight ratio of the control group increased by more than 3g/piece, the feed-to-egg ratio of the JA1-JA6 groups was reduced by more than 0.1% compared with the control group, and the egg breaking rate of the JA1-JA6 groups was reduced by more than 0.9% compared with the control group.
  • the above experimental results prove that the compound amino acid solution for animals prepared by the present invention has a good improvement effect on B vitamin deficiency in laying hens.
  • Table 10 A list of application effects of compound amino acid solution for animal use on dairy cow amino acid deficiency

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Abstract

涉及畜牧兽医技术领域，公开了一种动物用复方氨基酸溶液及其制备方法和应用，是取辅料、9种氨基酸和B族维生素在水中溶解后，再加入色氨酸溶解，然后通过调pH值、定容、过滤等步骤制得；所得溶液用于改善动物机体营养缺失，适合添加至水中，饲喂动物。通过添加合适比例的氨基酸和维生素，利用维生素促进氨基酸更好吸收，同时利用氨基酸促进维生素发挥更大的药用价值，从而更好的补充动物机体营养，提高动物代谢水平，加速血流运转，促进身体恢复，提高动物的生产性能，解决动物机体营养缺失的问题。

Description

一种动物用复方氨基酸溶液及其制备方法和应用 技术领域
本发明属于畜牧兽医技术领域，涉及一种复方氨基酸溶液及其制备方法，具体地说是一种动物用复方氨基酸溶液及其制备方法和应用。
背景技术
目前用于增强动物体能的补充液主要使用葡萄糖溶液、氯化钠溶液和葡萄糖氯化钠溶液，能够调节机体内电解质的平衡，但无法改善动物机体营养缺失的状况，也无法补充动物机体内所需的氨基酸和维生素。氨基酸和维生素作为动物体内非常重要营养素，对动物体生长发育有着深远影响。若动物体内缺乏氨基酸和维生素，会表现出发育不良、代谢缓慢、骨骼松软、体弱多病、生长迟缓等症状，还会进一步影响营养物质的吸收，严重时还会造成肾脏受损、停止生长。动物在生病期间会出现体质虚弱、自身合成代谢能力减弱，若不及时补充足够的氨基酸和维生素，也可能引发一系列疾病，如食欲减退、体重减少、呕吐、严重腹泻等。
发明内容
本发明的目的，是要提供一种动物用复方氨基酸溶液，以解决动物机体营养缺失的问题；
本发明的另一个目的，是要提供上述一种动物用复方氨基酸溶液的制备方法；
本发明还有一个目的，是要提供上述一种动物用复方氨基酸溶液的应用。
为了实现上述目的，本发明采用的技术方案是：
一种动物用复方氨基酸溶液，制成每1000体积份所述动物用复方氨基酸溶液的有效成分的原料，以重量份数计包括：
①由盐酸精氨酸0.80～10.00份、盐酸组氨酸0.60～6.50份、亮氨酸2.00～16.00 份、异亮氨酸0.40～14.00份、赖氨酸0.90～13.00份、苯丙氨酸1.00～16.50份、苏氨酸0.60～6.80份、缬氨酸0.40～12.90份和甘氨酸0.90～20.00份组成的组合氨基酸；
②色氨酸0.18～4.80份；
③由维生素B 1 1.00～4.00份、维生素B 2 2.00～8.00份、维生素B 3 10.00～30.00份和维生素B 6 2.00～10.00份组成的B族维生素；
④由抗氧剂0.50～1.00份、络合剂0.10～0.30份和防腐剂2.00～10.00份组成的辅料；
⑤余量为水；
其中，重量份数与体积份数的比例关系为1kg：1L。
作为一种限定，所述抗氧剂为亚硫酸氢钠、硫脲或焦亚硫酸钠。
作为另一种限定，所述络合剂为乙二胺四乙酸二钠、酒石酸或柠檬酸。
作为第三种限定，所述防腐剂为苯甲酸钠、尼泊金乙酯钠或尼泊金丙酯钠。
本发明还提供了上述一种动物用复方氨基酸溶液的制备方法，包括依次进行的以下步骤：
1)取辅料加至足够量的纯化水(一般为所得所述动物用复方氨基酸溶液总体积的60～80％)中，80～100℃充分溶解后，再加入组合氨基酸和B族维生素，80～100℃充分溶解，得溶液X；
2)溶液X降温至70℃以下(以60～70℃为佳)，加入色氨酸，维持在70℃以下(以60～70℃为佳)充分溶解后，降温至30℃以下，调节pH值，用纯化水定容，过滤，即得所述一种动物用复方氨基酸溶液。
作为一种限定，步骤2)中，调节pH值至4.2～6.8。
作为第二种限定，所述过滤分为粗滤和精滤；
纯化水是煮沸30～40min制得。
作为第三种限定，所述精滤是利用微孔滤膜进行过滤除菌。
本发明也提供了上述一种动物用复方氨基酸溶液的应用，所述一种动物用复方氨基酸溶液用于改善动物机体营养缺失。
作为一种限定，所述一种动物用复方氨基酸溶液添加至饮水中，用于饲喂动物。
由于采用了上述技术方案，本发明与现有技术相比，所取得的技术进步在于：
本发明通过大量实验得到了应用于动物的合适配比的一种动物用复方氨基酸溶液。动物机体内氨基酸与维生素的作用是相辅相成的，本发明通过添加合适比例的氨基酸和维生素，利用维生素促进氨基酸更好吸收，同时利用氨基酸促进维生素发挥更大的药用价值，从而更好的补充动物机体营养，提高动物代谢水平，加速血流运转，促进身体恢复，提高动物的生产性能。本发明的一种动物用复方氨基酸溶液还能够提高饲料利用率，改善料肉比，促进蛋白质的合成，提高机体免疫力和抗氧化能力，降低死亡率。本发明的一种动物用复方氨基酸溶液也可以提高肝脏能力，保肝护肝，减轻机体在代谢过程中产生的毒性代谢产物对组织的毒性作用；
缬氨酸、亮氨酸及异亮氨酸均为支链氨基酸，进入动物体内能够纠正血浆中支链氨基酸和芳香氨基酸失衡，具有调节能量底物、糖元异生底物和肌蛋白的作用；缬氨酸、亮氨酸及异亮氨酸还能在外周被氧化为能源，在不增加肝脏负担的情况下，提高能量的摄入；缬氨酸、亮氨酸及异亮氨酸还可以作为糖元异生的底物，在体内氧化与丙氨酸合成间有一个循环代谢机制，产生较多的热量，每克分子的缬氨酸、亮氨酸、异亮氨酸分别产生32、42、43克分子的ATP，能够为机体提供大量的能量。盐酸精氨酸在动物体内参与鸟氨酸循环，促进尿素的形成，使动物体内产生的氨，经鸟氨酸循环变成无毒的尿素，随尿液排出， 从而降低血氨浓度。各氨基酸还可以进入组织细胞，参与蛋白质的合成代谢，获得正氮平衡，并生成酶类、激素、抗体、结构蛋白，促进组织愈合，恢复正常生理功能。
维生素B 1是B族维生素之一，是糖代谢的重要辅助因子，在醛基和糖基的主动运输中起辅酶作用，在神经传导和神经元传导中起辅助作用。维生素B 2(核黄素)在动物体内代谢过程中起辅酶的作用，有助于维持动物的健康。当缺乏维生素B 2时，动物体内的碳水化合物、脂肪和蛋白质等物质就不能被转化成能量来维持身体正常功能。维生素B 3(烟酰胺)在动物体内有多种光保护作用，它能增强动物体的DNA修复，减少紫外线辐射对动物体皮肤免疫反应的作用，调节炎症细胞产生的皮肤屏障功能，恢复因紫外线照射后的细胞损伤。B 6是动物体内某些辅酶的组成成分，参与多种代谢反应，尤其是和氨基酸代谢有密切关系。B族维生素是所有动物体组织必不可少的营养素，均是辅酶，参与体内蛋白质、糖和脂肪的代谢，是食物释放能量的关键。各种维生素B的作用相辅相成，单独摄入某种维生素B后，由于细胞活动增加，从而对其它B族维生素的需求跟着增加，即所谓的“木桶原理”，这也称为维生素B的融合作用，具有增加食欲、维持神经功能、促进生长发育，因此合理配比B族维生素中的各组分至关重要。而氨基酸是蛋白质合成的主要来源，直接关系到动物体能以及健康情况，而B族维生素直接影响氨基酸的吸收利用率，因此，合理配比氨基酸和B族维生素中各组分直接影响动物体对氨基酸和B族维生素的吸收利用，进而影响动物体能及健康状况，同时补充氨基酸和B族维生素在动物体养殖过程中具有重要意义。
本发明将pH值调节至4.2～6.8，从而保证氨基酸和维生素的稳定性，进一步保障氨基酸和维生素的合理配比；采用微孔滤膜过滤除菌，在保障氨基酸和维生素稳定性的同时，去除溶液中的微生物，保障一种动物用复方氨基酸溶液 的质量；
本发明的制备方法简单，制备的一种动物用复方氨基酸溶液安全可控；
进一步地，本发明的一种动物用复方氨基酸溶液在生产、使用过程中，能够节约生产、包装、运输成本，方便兽医使用；
本发明原料来源广、成本低廉，能够给养殖企业带来良好的经济效益。
本发明的一种动物用复方氨基酸溶液适合添加至水中，饲喂动物，以改善动物机体营养缺失。
具体实施方式
下面通过具体实施例对本发明做进一步详细说明，应当理解所描述的实施例仅用于解释本发明，并不限定本发明。
实施例1一种动物用复方氨基酸溶液的制备方法
本实施例制备1000L一种动物用复方氨基酸溶液，包括依次进行的以下步骤：
1)称取0.8kg盐酸精氨酸、0.65kg盐酸组氨酸、3.49kg亮氨酸、0.52kg异亮氨酸、1.55kg赖氨酸、1.96kg苯丙氨酸、0.80kg苏氨酸、2.56kg缬氨酸和3.48kg甘氨酸，作为A组氨基酸备用；
称取2.31kg维生素B 1、4.52kg维生素B 2、25kg维生素B 3和6.84kg维生素B 6，作为B族维生素备用；
纯化水经煮沸30min，备用；
取800L(一般取600～800L，本实施例取800L)纯化水加入配制容器中，维持80℃，加入0.1kg乙二胺四乙酸二钠、0.5kg硫脲和5.0kg尼泊金乙酯钠，维持80℃搅拌至充分溶解后，再加入38.67kg的B族维生素，维持80℃搅拌至充分溶解，然后加入14.81kg的A组氨基酸，维持80℃搅拌至充分溶解，得溶液X 1。
亚硫酸氢钠、硫脲和焦亚硫酸钠均具有防止氨基酸和维生素氧化的作用，本实施例使用硫脲作为抗氧化剂，在加入各氨基酸和维生素之前加入，能够有效防止氨基酸和维生素在溶解过程中发生氧化反应；
乙二胺四乙酸二钠能够与原料中所带入的金属离子发生螯合作用，在加入氨基酸和维生素之前加入，有效避免金属离子对氨基酸和维生素的催化氧化作用。
氨基酸和维生素的溶解时间随温度的升高而缩短，温度在80℃以上时，溶解速度最快，而高于80℃时，大部分氨基酸及维生素的溶解度和溶解速度均不再发生明显变化。综合考虑含量与溶解时间等因素，在80～100℃之间分步加入A组氨基酸和B族维生素进行溶解。
2)溶液X 1降温至70℃，加入0.48kg色氨酸，维持70℃搅拌至充分溶解后，降温至30℃，使用1mol/L氢氧化钠溶液调节pH值至4.5，然后再加入煮沸后的纯化水定容至1000L，经1μm的滤芯进行粗滤、0.2μm的微孔滤膜进行精滤除去杂质及微生物，即得一种动物用复方氨基酸溶液。
一种动物用复方氨基酸溶液进行灌装，灌装完成后经灯检合格，制得独立包装的一种动物用复方氨基酸溶液(标记为N1)。
由于色氨酸稳定性不太高，随着温度升高，含量反而会大幅度下降，经实验验证，色氨酸在60～70℃时溶液内的含量较高。将色氨酸控制在60～70℃溶解，有效减少色氨酸溶解过程中的氧化作用。
在制备一种动物用复方氨基酸溶液过程中，将pH值控制在4.2～6.8，能够保持溶液中的氨基酸和维生素含量的稳定性。
0.2μm或0.22μm的微孔滤膜可以起到除菌的作用，保证所得溶液中的微生物限度符合要求，增加溶液质量的稳定性。
所得的一种动物用复方氨基酸溶液适合添加至饮水中，饲喂动物，以改善 动物机体营养缺失。
实施例2～6一种动物用复方氨基酸溶液的制备方法
实施例2～6分别为一种动物用复方氨基酸溶液的制备方法，它们的步骤与实施例1基本相同，不同之处仅在于原料用量及工艺参数的不同，具体详见表1：
表1实施例2～6中各项工艺参数一览表
Figure PCTCN2020116378-appb-000001
Figure PCTCN2020116378-appb-000002
实施例2～6其它部分的内容，与实施例1相同。
实施例7一种动物用复方氨基酸溶液的含量测定结果
根据国家食品药品监督管理总局质量标准WS1-(X-077)-2006Z，氨基酸和维生素相应的标示量应控制在90.0～110.0％，标示量计算是根据所得溶液中原料的含有量/相应的原料用量，计算得到的。对实施例1～6制备的一种动物用复方氨基酸溶液N1～N6的外观和含量进行测定，具体结果见表2：
表2实施例1～6中制得的一种动物用复方氨基酸溶液质量检测结果一览表
Figure PCTCN2020116378-appb-000003
Figure PCTCN2020116378-appb-000004
由表2可知，实施例1～6制备的一种动物用复方氨基酸溶液N1～N6颜色呈无色澄清，氨基酸与维生素的含量均符合标准，且其他检查相关项均已全部合格。
实施例8一种动物用复方氨基酸溶液的稳定性检测
对实施例1～6制备的一种动物用复方氨基酸溶液N1～N6进行质量检测，具体检测方法如下：
加速试验在温度40±2℃、相对湿度75±5％的条件下放置6个月，在试验期间第0个月、1个月、2个月、3个月、6个月末分别取样，按《国家食品药品监督管理局药品标准》WS1～(X～324)～2003Z的质量标准进行检测，氨基酸和维生素相应的标示量应控制在90.0～110.0％，标示量计算是根据所得溶液中原料的含有量/相应的原料用量，计算得到的，具体检测结果见表3～8：
表3一种动物用复方氨基酸溶液N1质量检测结果
Figure PCTCN2020116378-appb-000005
表4一种动物用复方氨基酸溶液N2质量检测结果
Figure PCTCN2020116378-appb-000006
表5一种动物用复方氨基酸溶液N3质量检测结果
Figure PCTCN2020116378-appb-000007
Figure PCTCN2020116378-appb-000008
表6一种动物用复方氨基酸溶液N4质量检测结果
Figure PCTCN2020116378-appb-000009
表7一种动物用复方氨基酸溶液N5质量检测结果
Figure PCTCN2020116378-appb-000010
Figure PCTCN2020116378-appb-000011
表8一种动物用复方氨基酸溶液N6质量检测结果
Figure PCTCN2020116378-appb-000012
Figure PCTCN2020116378-appb-000013
由表3～8可知，实施例1～6制备的一种动物用复方氨基酸溶液N1～N6经过加速试验，各指标均无明显变化，质量稳定性良好，因此，本发明的制备的一种动物用复方氨基酸溶液具有很好的稳定性。
实施例9一种动物用复方氨基酸溶液的应用
一)一种动物用复方氨基酸溶液对蛋鸡的B族维生素缺乏症的改善效果实验
鸡的氨基酸和B族维生素缺乏症常突然发生，表现为厌食、消瘦、贫血、体温降低、腿软无力，有的甚至出现腹泻，继而引发多发性神经炎，腿、翅、颈出现伸肌痉挛，病鸡以飞节和尾部着地，仿佛坐于地面，头向后仰，呈特征性的“观星”姿势，有时倒地侧卧，头仍向后仰，严重时衰竭死亡。成年鸡发病较慢，除精神、食欲失常外，还表现出鸡冠呈蓝紫色、步态不稳、进行性瘫痪等症状。
剖检病死鸡，可见皮肤广泛水肿；肾上腺明显肥大，胃肠有炎症，十二指肠溃疡；心脏右侧常出现扩张，心房较心室明显；生殖器官萎缩，尤其是公鸡的睾丸较为明显。
本次试验在出现B族维生素缺乏症的石家庄某大型鸡场进行，鸡群出现食欲不振、消瘦、跛行、体重减少等症状，结合临床症状与维生素检测，经当地兽医确诊，患有B族维生素缺乏症。选取700只300日龄具有B族维生素缺乏症的海兰灰蛋鸡，随机分成7组，每组100只，分别为对照组和JA1～JA6组，其中，对照组给予预混了0.5‰液态维生素的饮水，JA1～JA6组一一对应给予预混了0.5‰一种动物用复方氨基酸注射液N1～N6的饮水，全天不限量供应，连续试验20天，并给予正常饲喂。
试验采用三层立体笼养，饲喂对应饲料，自由采食与饮水。按照海兰灰蛋鸡常规免疫程序免疫和饲养管理，每日进行鸡舍消毒，保证鸡舍卫生。试验期间每天观察蛋鸡的增重和产蛋情况，并进行统计，具体结果见下表：
表9一种动物用复方氨基酸溶液对蛋鸡B族缺乏症的应用效果一览表
Figure PCTCN2020116378-appb-000014
由表9可知，JA1～JA6组和对照组鸡群体重减少症状消失，产蛋率和平均蛋重均有所提高，料蛋比和破蛋率均有所降低，但JA1～JA6组的体重的平均增长值比对照组提高0.008kg以上，JA1～JA6组的死亡率比对照组降低9％以上，JA1～JA6组的产蛋率比对照组提高13％以上，JA1～JA6组的平均蛋重比对照组增加3g/个以上，JA1～JA6组的料蛋比比对照组降低0.1％以上，JA1～JA6组的破蛋率比对照组降低0.9％以上。以上实验结果证明本发明制备的一种动物用复方氨基酸溶液对于蛋鸡的B族维生素缺乏症具有很好的改善作用。
二)一种动物用复方氨基酸溶液促进病奶牛生长发育的效果实验
本次试验在某大型奶牛养殖场进行，奶牛出现厌食、消瘦、全身无力、产奶量减少等症状，结合临床症状，经当地兽医确诊，患有氨基酸缺乏症。选取28只中国荷斯坦奶牛，随机分成7组，每组4只，分别为对照组和NA1～NA6 组，其中，对照组给予预混了1‰口服葡萄糖溶液的饮水，NA1～NA6组一一对应给予预混了1‰一种动物用复方氨基酸注射液N1～N6的饮水，全天不限量供应，连续试验7天，并给予正常饲喂。试验期间每天观察奶牛的增重和产奶情况，并进行统计，具体结果见下表：
表10一种动物用复方氨基酸溶液对奶牛氨基酸缺乏症的应用效果一览表
组别 对照组 NA1组 NA2组 NA3组 NA4组 NA5组 NA6组
奶牛数(头) 4 4 4 4 4 4 4
20天后体重的平均增长值(kg) 0.30 1.56 1.32 1.20 1.15 1.26 1.37
开始时平均采食量(kg/d) 18.5 18.0 18.3 18.2 18.6 18.4 18.6
20天后平均采食量(kg/d) 18.6 21.2 20.7 20.9 21.1 21.0 20.8
开始时平均产奶量(kg/d) 16.8 16.7 16.9 16.5 16.5 16.6 16.8
20天后平均产奶量(kg/d) 16.7 22.1 21.2 21.5 21.6 21.9 21.3
开始时牛奶中乳脂含量(％) 3.0 2.9 3.1 3.0 2.8 3.2 3.1
20天后牛奶中乳脂含量(％) 3.1 3.68 3.55 3.62 3.58 3.64 3.63
开始时牛奶中乳蛋白含量(％) 3.0 2.9 3.0 3.1 2.9 3.0 2.9
20天后牛奶中乳蛋白含量(％) 2.9 3.2 3.3 3.3 3.4 3.4 3.3
开始时牛奶中乳糖含量(％) 3.92 3.93 3.92 3.95 3.91 3.94 3.92
20天后牛奶中乳糖含量(％) 3.95 4.76 4.56 4.70 4.67 4.63 4.59
由表10可知，NA1～NA6组的体重的平均增长值比对照组提高0.85kg以上，NA1～NA6组的平均采食量比对照组提高2.3kg/d以上，NA1～NA6组的产奶量比对照组提高4.4kg/d以上，NA1～NA6组的牛奶中乳脂含量比对照组提高0.43％以上，NA1～NA6组的牛奶中乳蛋白含量比对照组提高0.3％以上，NA1～NA6组的牛奶中乳糖含量比对照组提高0.61％以上。以上实验结果证明本发明制备的一种动物用复方氨基酸溶液对于奶牛的氨基酸缺乏症具有很好的改善作用。

Claims (10)

  1. 一种动物用复方氨基酸溶液，其特征在于，制成每1000体积份所述动物用复方氨基酸溶液的有效成分的原料，以重量份数计包括：
    ①由盐酸精氨酸0.80～10.00份、盐酸组氨酸0.60～6.50份、亮氨酸2.00～16.00份、异亮氨酸0.40～14.00份、赖氨酸0.90～13.00份、苯丙氨酸1.00～16.50份、苏氨酸0.60～6.80份、缬氨酸0.40～12.90份和甘氨酸0.90～20.00份组成的组合氨基酸；
    ②色氨酸0.18～4.80份；
    ③由维生素B 11.00～4.00份、维生素B 22.00～8.00份、维生素B 310.00～30.00份和维生素B 62.00～10.00份组成的B族维生素；
    ④由抗氧剂0.50～1.00份、络合剂0.10～0.30份和防腐剂2.00～10.00份组成的辅料；
    ⑤余量为水；
    其中，重量份数与体积份数的比例关系为1kg：1L。
  2. 根据权利要求1所述的一种动物用复方氨基酸溶液，其特征在于，所述抗氧剂为亚硫酸氢钠、硫脲或焦亚硫酸钠。
  3. 根据权利要求1或2所述的一种动物用复方氨基酸溶液，其特征在于，所述络合剂为乙二胺四乙酸二钠、酒石酸或柠檬酸。
  4. 根据权利要求1或2所述的一种动物用复方氨基酸溶液，其特征在于，所述防腐剂为苯甲酸钠、尼泊金乙酯钠或尼泊金丙酯钠。
  5. 权利要求1-4中任一项所述的一种动物用复方氨基酸溶液的制备方法，其特征在于，该制备方法包括依次进行的以下步骤：
    1)取辅料加至足够量的水中，80～100℃充分溶解后，再加入组合氨基酸和B族维生素，80～100℃充分溶解，得溶液X；
    2)溶液X中加入色氨酸，在70℃以下充分溶解后，调节pH值，用水定容，过滤，即得所述一种动物用复方氨基酸溶液。
  6. 根据权利要求5所述的一种动物用复方氨基酸溶液的制备方法，其特征在于，步骤2)中，调节pH值至4.2～6.8。
  7. 根据权利要求5或6所述的一种动物用复方氨基酸溶液的制备方法，其特征在于，所述过滤分为粗滤和精滤。
  8. 根据权利要求7所述的一种动物用复方氨基酸溶液的制备方法，其特征在于， 所述精滤是利用微孔滤膜进行过滤除菌。
  9. 权利要求1-4中任一项所述的一种动物用复方氨基酸溶液的应用，其特征在于，所述一种动物用复方氨基酸溶液用于改善动物机体营养缺失。
  10. 根据权利要求9所述的一种动物用复方氨基酸溶液的应用，其特征在于，所述一种动物用复方氨基酸溶液添加至饮水中，用于饲喂动物。
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