WO2017143667A1 - 一种饲用组合物及其在制备动物饲料添加剂中的应用 - Google Patents
一种饲用组合物及其在制备动物饲料添加剂中的应用 Download PDFInfo
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- 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
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- the invention belongs to the field of animal feed additives, and particularly relates to a feed composition containing a butyric acid derivative and a myristic acid derivative and the use thereof in preparing an animal feed additive.
- Animal feed is currently the essential animal-based diet to replace traditional raw produce in animal farming. It is often desirable for animals to consume the least amount of feed in a short period of time for healthy and efficient growth.
- various functional feed additives are added to the feed during the feed processing process to prepare a functional feed.
- feed antibiotics, zinc oxide or copper sulfate are commonly used feed additives in the past to improve animal performance and prevent animal diseases.
- the long-term use of high-dose inorganic zinc or inorganic copper feed additives is toxic and inhibits growth in animals; the abuse of feed antibiotics also leads to microbial resistance, drug residues and drug resistance transmission threatening human health. .
- the emergence of these problems has led to restrictions or bans on the use of traditional feed additives in animal farming. Therefore, the development of new safe and efficient feed additives is of great significance to the animal husbandry industry.
- the feed composition of the present invention comprises a butyric acid derivative and a myristic acid derivative
- the butyric acid derivative is butyrate, or the structure thereof is represented by the formula (I), or the structure thereof is as shown in the formula (II):
- M is selected from H, an alkali metal; and the alkali metal ion includes Na, K, Li, and the like.
- M is selected from the group consisting of alkaline earth metals, Zn, Fe, Mn, and Cu; and alkaline earth metal ions include Ca, Mg, Be, and the like.
- the butyrate has a structure as shown in formula (III) or formula (IV):
- R 1 is selected from C 1-4 straight or branched alkyl
- the monovalent metal ion butyrate in the above butyrate can be prepared by subjecting butyric acid to a conventional acid-base neutralization reaction with a corresponding base and drying.
- the divalent metal ion butyrate in the above butyrate is firstly subjected to a conventional neutralization reaction of butyric acid and sodium hydroxide to form sodium butyrate, and then further subjected to a metathesis reaction with a chloride of a divalent metal ion, followed by separation and drying by precipitation. preparation.
- butyrate can be prepared by rectification of butyric acid with the corresponding C 1-4 linear or branched alkanol or glycerol under esterification conditions.
- the myristic acid derivative according to the present invention is myristate, or the structure thereof is represented by the formula (V), or the structure thereof is as shown in the formula (VI):
- M is selected from H, an alkali metal; and the alkali metal ion includes Na, K, Li, and the like.
- M is selected from the group consisting of alkaline earth metals, Zn, Fe, Mn, and Cu; and alkaline earth metal ions include Ca, Mg, Be, and the like.
- the myristate has the structure as shown in formula (VII) or formula (VIII):
- R 5 is selected from C 1-4 straight or branched alkyl
- the monovalent metal ion myristate in the above myristic acid salt can be prepared by subjecting myristic acid to a conventional acid-base neutralization reaction with my corresponding base and drying.
- the divalent metal ion myristic acid salt in the above myristic acid salt is first subjected to a conventional neutralization reaction with myristic acid and sodium hydroxide to form sodium myristate, and further subjected to a metathesis reaction with a chloride of a divalent metal ion. The precipitate was isolated and dried.
- the above myristate can be prepared by rectifying the myristic acid with the corresponding C 1-4 linear or branched alkanol or glycerol under esterification conditions.
- the obtained myristate may exhibit different states of solid and liquid at different temperatures.
- Long-chain saturated fatty acid salts or long-chain saturated fatty acid esters have been used as feed supplements in excess of 2% as feed additives, especially in diets for ruminants such as cows and goats, for animals
- the intake and milk production have no effect but can change the content and composition of the ingredients in the milk. It has been reported in the literature that fatty acid esters such as glycerol myristate as an energy substance can cause high blood lipids in animals, and some animals grow slowly or even die.
- butyric acid is fat-soluble and dissociable, and can be dissociated into butyrate ions and hydrogen ions through the cell membrane to inhibit or kill certain kinds of bacteria. It has been reported that butyric acid or its derivatives The organism can be used as an intestinal regulator of animals, and some patents have reported that butyric acid derivatives can play a role in making animal feces more convergent and shaped, but they are often ineffective for more serious feed-like loose stools.
- the inventors of the present invention found for the first time in the research process that the butyric acid derivative and the myristic acid derivative are combined and applied to the rearing of the cultured animal in a certain ratio, compared with the effects of the application of the butyric acid derivative and the myristic acid derivative alone. It has a very significant effect on the control of animal diarrhea rate and the improvement of production performance, reaching the level of common doses of feed additives such as common feed antibiotics and high-dose zinc preparations or copper preparations.
- the myristic acid derivative is not sensitive to the action of Gram-negative bacteria, but has a very potent inhibitory effect on Gram-positive bacteria such as Clostridium perfringens.
- Butyric acid derivatives have shown weak effects on Gram-negative bacteria such as Escherichia coli in bacteriostatic test studies, but have shown significant control effects in the study of diarrhea control in cultured animals. The results showed that the inhibition or killing effect of butyric acid derivatives on Escherichia coli and the like was weak, but it could regulate the gastrointestinal function of animals to control the occurrence of diarrhea symptoms.
- Butyric acid derivatives and myristic acid derivatives have different degrees of effects on different bacterial groups, and inhibit or kill common infectious bacteria in two aspects, thereby maintaining the beneficial bacteria in the intestinal tract as the dominant flora. On the one hand, it controls and regulates the diarrhea caused by infected bacteria or indigestion. On the other hand, the presence of dominant bacteria promotes the digestion of animal feed nutrients, which is beneficial to alleviate the occurrence of dyspepsia and diarrhea. Absorbed through the intestinal wall.
- the invention proves that the butyric acid derivative and the myristic acid derivative can be combined into a forage composition according to a suitable mass ratio, which can effectively control various diarrhea of the cultured animal and optimize the animal production performance.
- the butyric acid derivative and the myristic acid derivative may be used in any proportion to form a feed composition, the dosage of the butyric acid derivative and the myristic acid derivative in the forage composition, in mass parts, mass
- the ratio is preferably 4 to 1:1.
- the butyric acid derivatives of the cultured animals were administered separately, and the feed intake of the test animals increased correspondingly, the incidence of diarrhea decreased, and the production performance was improved, but the production performance was not significant.
- animal-fed feed compositions containing butyric acid derivatives and myristic acid derivatives also contain other trace materials required for other animal nutrition.
- the feed composition further comprises supplementing and balancing nutrients.
- the feed composition further comprises a health care substance.
- the feed composition further comprises a physiologically modulating metabolite.
- the feed composition further comprises an appetite-promoting digestive substance.
- the feed composition further comprises a processing and preservative-like substance.
- the feed composition can be a liquid, a solid, a semi-solid, a gel, and the like.
- the present invention uses a feed composition containing a suitable mass ratio of a butyric acid derivative and a myristic acid derivative for the preparation of an animal feed additive.
- the animal feed additive further comprises, in addition to the feed composition, a pharmaceutically acceptable excipient, carrier, antioxidant, diluent, anti-caking agent, vehicle or a combination thereof.
- the feed additive can be added to the feed raw material in the feed processing industry according to the demand of the formulated feed to prepare a functional feed for the breeding of the farmed animal.
- the functional feed on the one hand maintains the health of the animal and on the other hand improves the performance of the animal.
- the present invention relates to the use of the feed composition comprising a butyric acid derivative and a myristic acid derivative for the preparation of an animal growth promoter.
- the animal growth promoter prepared by using the forage composition containing a butyric acid derivative and a myristic acid derivative has a remarkable effect in animal breeding for improving feed utilization, improving animal performance, and stimulating animal growth.
- the animal growth promoter prepared by the feed composition containing the butyric acid derivative and the myristic acid derivative can further replace the application of the antibiotic-derived animal growth promoter.
- the animal growth promoter prepared by the feed composition containing the butyric acid derivative and the myristic acid derivative may further replace the application of the high-dose zinc preparation or the copper preparation as an animal growth promoter.
- the feed compositions of the present invention comprising a butyric acid derivative and a myristic acid derivative are added to the daily ration of the animal in separate form.
- the feed composition containing the butyric acid derivative and the myristic acid derivative provided by the present invention is prepared as an additive premixed feed and concentrated in a certain ratio with feed ingredients, feed additives, carriers or diluents. Feed forms such as feed, compound feed, and concentrate feed are provided for consumption by animals.
- the feed material according to the present invention refers to a feed material derived from animals, plants, microorganisms or minerals and used for processing feeds but not belonging to feed additives.
- the feed additive according to the present invention refers to a small amount or a trace amount of substances added during the processing, production and use of feed, including nutritive feed additives and non-nutritive feed additives.
- the nutritive feed additive refers to a small amount or a trace amount of substances incorporated into the feed for supplementing the nutrients of the feed, including feed grade amino acids, vitamins, mineral trace elements, enzyme preparations, non-protein nitrogen, and the like.
- Non-nutritive feed additives are small or trace substances that are incorporated into feeds to ensure or improve feed quality and improve feed utilization.
- the carrier according to the present invention refers to a feedable substance capable of carrying an active ingredient, improving dispersibility, and having good chemical stability and adsorption.
- the diluent involved in the invention refers to a substance which uniformly distributes the additive raw material in the material and dilutes the high-concentration additive raw material into a low-concentration premix or premix, which can separate the trace components from each other and reduce the active ingredients. Mutual reaction to increase the stability of the active ingredient without affecting the physicochemical properties of the substance.
- the additive premix feed according to the present invention refers to a feed which is mainly composed of two (types) or two (types) or more nutritive feed additives, and is prepared according to a certain ratio with a carrier or a diluent, including a composite premix feed, and a trace amount. Elemental premix feed, vitamin premix feed.
- the concentrated feed according to the present invention refers to a feed mainly prepared with a certain proportion of protein, minerals and feed additives.
- the compound feed according to the present invention 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 referred to in the present invention refers to a feed which is 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 animal.
- the feed composition containing the butyric acid derivative and the myristic acid derivative provided by the present invention or the feed additive or animal growth promoter prepared therefrom comprises a livestock, a poultry and an aquaculture animal, especially The control effect of anti-diarrhea and indigestion in poultry is more significant.
- the invention provides a feed containing a butyric acid derivative and a myristic acid derivative.
- the present invention provides a feed composition containing a butyric acid derivative and a myristic acid derivative, or a feed additive or an animal growth promoter prepared therefrom, and the like, and a beef cattle and cows used in various growth stages. Feeding of livestock such as pigs, raises, horses, rabbits, dogs, cats and donkeys.
- the present invention provides a feed composition containing a butyric acid derivative and a myristic acid derivative, or a feed additive or an animal growth promoter prepared therefrom, and the like for use in various growth stages of fish and shrimp. Feeding of aquatic animals such as crickets, crabs or loach.
- the feed composition containing the butyric acid derivative and the myristic acid derivative provided by the present invention is a novel and safe animal feed additive, which replaces the feed antibiotic animal growth promoter and the high dose zinc preparation.
- the application of copper preparations to overcome the other side effects caused by the antibiotics in the animal breeding industry, such as drug resistance, drug resistance transmission and the long-term application of heavy metal preparations to animal health and human food safety, in animal breeding industry The vast market prospects.
- butyric acid derivatives and myristic acid derivatives used in the following examples of the present invention are all provided by the research and development center of Guangzhou Insex Biotechnology Co., Ltd., and the sample purity is ⁇ 99%; the virginiamycin preparation used is imported The mixture is produced by the Belgian production plant of American Huibao Co., Ltd.; the colistin sulfate used is produced by Shandong Lukang Pharmaceutical.
- the feed composition of the present invention is prepared as follows:
- the butyric acid derivative and the myristic acid derivative were uniformly mixed according to the parts by mass of each component to obtain a forage composition. It can then be added to animal feed as an animal feed additive.
- Example 1 Inhibitory activity of different butyric acid derivatives on colistin sulfate-sensitive Escherichia coli.
- Example 2 Inhibitory activity of different myristic acid derivatives on Clostridium perfringens.
- the minimum inhibitory concentration (MIC) of virginiamycin and myristic acid derivatives against Clostridium perfringens was tested by tube double dilution method. The results are shown in Table 2. As can be seen from Table 2, all the test strains were sensitive to virginiamycin, and all the myristic acid derivatives tested had similar inhibitory activities to the test strains as virginiamycin.
- Example 3 Application effect of calcium butyrate and calcium myristate in weaning pigs
- calcium butyrate can achieve the effect of 20 ppm of the antibiotic colistin sulfate when the additive amount of the calcium butyrate is 400 ppm, and the control and production performance of the animal diarrhea rate.
- the change showed a dose effect; when the amount of calcium myristate additive reached 400 ppm, the effect was obviously achieved with the effect of the use of virginiamycin at a dose of 20 ppm, and the control of diarrhea rate and the change of production performance showed a dose. Effect; however, from the overall results of the test groups, it can be seen that calcium butyrate has a significant advantage in controlling the diarrhea rate of animals, and calcium myristate is more effective in improving the performance of animals.
- Example 4 Effect of combined application of calcium butyrate and calcium myristate in weaned pigs
- Example 5 Application effect of combined application of calcium butyrate and calcium myristate in chicken feed.
- test groups 1400 1 day old fast yellow broilers were randomly divided into 7 test groups, each test group consisted of 4 parallel test groups, 50 in each parallel test group, and calcium butyrate and/or were added to each group of feeds respectively. Different doses of calcium myristate. During the test period, they were housed, fed ad libitum and freely drinking water. The test period was 28 days. The average daily gain (ADG), average meat-to-meat ratio (AFCR) and survival rate of the test chickens in each test group were counted within 28 days.
- ADG average daily gain
- AFCR average meat-to-meat ratio
- survival rate of the test chickens in each test group were counted within 28 days.
- the test results showed that the survival rate of the chickens in the blank group was higher than that of the 1200 ppm calcium butyrate; the test group fed the feed with different doses of calcium myristate while containing 1200 ppm of calcium butyrate, the test chicken The increase in survival rate was accompanied by a significant increase in production performance (Table 5).
- Example 6 Combined application effect of calcium butyrate and calcium myristate in grass carp
- the test fish used was grass carp, which was carried out by the aquatic farm of the Ince Test Site in Guangzhou.
- the healthy and lively, uniform-sized green carp species were used for formal culture trials after being kept in large cages for 4 weeks.
- the experimental system was a floating small cage. Both the small cage and the holding cage are placed in a 3500 m 2 pond at the test site. The pond water depth is ⁇ 1.5 m, and the pond water is fully aerated bottom water.
- 200 fishes that were hungry for 1 day were randomly divided into 5 groups, each group consisted of 4 replicates, and 10 fishes were placed in each replicate. After weighing, they were randomly placed in 16 cages and fed different test feeds. .
- the test feed was prepared according to the formula of Table 5. Different test groups were added with different growth promoters in the base materials. The test was fed by artificial diet, and the feeding amount was adjusted once a week. The feeding levels (by initial weight) were identical and fed twice a day (7:30 and 15:00). The trial lasted for 8 weeks.
Abstract
一种饲用组合物及其在制备动物饲料添加剂中的应用。其含有丁酸衍生物和肉豆蔻酸衍生物，丁酸衍生物选自丁酸盐或丁酸酯，肉豆蔻酸衍生物选自肉豆蔻酸盐或肉豆蔻酸酯，两者在饲用组合物中的质量比为4～1：1。该饲用组合物可作为动物生长促进剂使用，可以替代饲用抗生素或高剂量锌制剂或铜制剂，适用动物包括家畜、家禽和水产养殖动物。
Description
本发明属于动物饲料添加剂领域，具体涉及一种含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物及其在制备动物饲料添加剂中的应用。
动物饲料是目前必需的动物基础日粮替代传统的原始农产品在动物养殖中应用。人们往往希望动物在最短的时间消耗最少的饲料健康高效的成长。为了达到此目的，各种功能的饲料添加剂在饲料加工过程添加到饲料中制备成为功能性饲料。其中，饲用抗生素、氧化锌或硫酸铜等是过去常用的饲料添加剂用于提高动物的生产性能和防治动物疾病。但是高剂量无机锌或无机铜类饲料添加剂的长期使用对动物是有毒性的和抑制生长；而饲用抗生素的滥用也导致微生物耐药性产生、药物残留以及耐药性传递对人类健康造成威胁。这些问题的出现导致传统饲料添加剂在动物养殖中使用受到限制或者禁用。因此，开发新型的安全的高效的饲料添加剂对动物养殖业具有重要的意义。
发明内容：
本发明的目的是提供一种含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物及其在制备新型、安全、高效的动物饲料添加剂中的应用，用于动物养殖以维持动物健康和提高动物的生产性能。
本发明的饲用组合物，含有丁酸衍生物和肉豆蔻酸衍生物；
所述的丁酸衍生物为丁酸酯、或其结构如式(Ⅰ)所示、或其结构如式(Ⅱ)所示：
(A)
其中，M选自H、碱金属；碱金属离子包括Na、K、Li等。
(B)
其中，M选自碱土金属、Zn、Fe、Mn、Cu；碱土金属离子包括Ca、Mg、Be等。
(C)
所述的丁酸酯其结构如式(Ⅲ)或式(Ⅳ)所示：
所述的R1选自C1-4直链或支链烷基；
其中，R2、R3和R4选自H和直链C3C(＝O)，并且R2、R3和R4不全部为H；
上述丁酸盐中的一价金属离子丁酸盐可通过丁酸与相应的碱发生常规的酸碱中和反应后干燥制备。上述丁酸盐中的二价金属离子丁酸盐首先通过丁酸与氢氧化钠发生常规中和反应生成丁酸钠后，再进一步与二价金属离子的氯化物进行复分解反应后经沉淀分离干燥制备。
上述丁酸酯可经过丁酸与相应的C1-4直链或支链烷醇、甘油在酯化条件下成酯后精馏制备。
本发明涉及的肉豆蔻酸衍生物为肉豆蔻酸酯、或其结构如式(Ⅴ)所示、或其结构如式(Ⅵ)所示：
(D)
其中，M选自H、碱金属；碱金属离子包括Na、K、Li等。
(E)
其中，M选自碱土金属、Zn、Fe、Mn、Cu；碱土金属离子包括Ca、Mg、Be等。
(F)
所述的肉豆蔻酸酯其结构如式(Ⅶ)或式(Ⅷ)所示：
所述的R5选自C1-4直链或支链烷基；
其中，R6、R7和R8选自H和直链C13C(＝O)，并且R6、R7和R8不全部为H；。
上述肉豆蔻酸盐中的一价金属离子肉豆蔻酸盐可通过肉豆蔻酸与相应的碱发生常规的酸碱中和反应后干燥制备。上述肉豆蔻酸盐中的二价金属离子肉豆蔻酸盐首先通过肉豆蔻酸与氢氧化钠发生常规中和反应生成肉豆蔻酸钠后，进一步与二价金属离子的氯化物进行复分解反应后经沉淀分离干燥制备。
上述肉豆蔻酸酯可经过肉豆蔻酸与相应的C1-4直链或支链烷醇、甘油在酯化条件下成酯后精馏制备。所得肉豆蔻酸酯在不同温度下可呈现为固液不同状态。
长链饱和脂肪酸盐或长链饱和脂肪酸酯以高于2％的添加量作为饲料添加剂一直仅作为能量补充剂应用，尤其是应用在反刍动物如奶牛和山羊等的日粮中，对动物的采食量、产奶量没有影响却可改变奶中的成分含量和组成。有文献报道，脂肪酸酯如甘油三肉豆蔻酸酯作为能量物质可引起动物的血脂偏高，有些动物出现生长缓慢甚至死亡。
而关于丁酸的报道是丁酸具有脂溶性和解离性，可通过细胞膜后解离为丁酸根离子和氢离子，对某些种类的细菌具有抑制或杀灭作用。有报道说丁酸或其衍
生物可作为动物肠道调节剂，而也有专利报道说丁酸衍生物虽然可以起到使动物粪便更为收敛和成型的作用，但对更为严重的饲料样稀便往往无效。
综上所述，肉豆蔻酸衍生物或丁酸衍生物在动物养殖中单独使用的过程有相应的用途的同时也存在不同的问题。
本发明的发明人在研究过程中首次发现将丁酸衍生物和肉豆蔻酸衍生物按一定比例联合应用于养殖动物的饲养，与丁酸衍生物和肉豆蔻酸衍生物单独应用的效果相比，对动物腹泻率的控制和生产性能的改进具有非常显著的作用，达到常用饲用抗生素和高剂量锌制剂或铜制剂等饲料添加剂常用剂量的水平。
在抑菌试验研究中，肉豆蔻酸衍生物对革兰氏阴性菌的作用不敏感，但却对革兰氏阳性菌如产气荚膜梭菌等具有非常强效的抑制作用。
丁酸衍生物在抑菌试验研究中显示对大肠杆菌等革兰氏阴性菌很弱的作用，然而却在养殖动物腹泻控制研究中表现了出了显著的控制效果。结果表明，丁酸衍生物对大肠杆菌等的抑制或杀灭作用很弱却能调节动物的肠胃功能控制腹泻症状的出现。
丁酸衍生物和肉豆蔻酸衍生物分别对不同菌群产生不同程度的作用，从两个方面对动物常见感染病菌进行抑制或杀灭，从而维持肠道内有益菌群成为优势菌群。一方面对动物因感染病菌或消化不良导致的腹泻起到控制和调节作用，另一方面优势菌群的存在促进动物饲料营养物质的消化，有利于缓解消化不良性腹泻的发生更有利于营养物质通过肠壁吸收。
本发明通过试验证明可将丁酸衍生物和肉豆蔻酸衍生物，按合适的质量比联合组成饲用组合物，既可以有效的控制养殖动物的各种腹泻又可以达到动物生产性能最优化。
丁酸衍生物和肉豆蔻酸衍生物可按任一比例组成饲用组合物，所述的饲用组合物中丁酸衍生物和肉豆蔻酸衍生物的使用剂量，按质量份数计，质量比优选为4～1：1。
在一动物养殖方案中，单独给与养殖动物丁酸衍生物，随着给药剂量的上升试验动物的采食量相应增加、动物腹泻发生率下降、生产性能有改善却不显著。
在另一动物养殖方案中，单独给与养殖动物肉豆蔻酸衍生物，动物的生产性能改善效果很显著但动物采食量没有显著的提高，腹泻率与另一养殖方案的同等
剂量的丁酸钙比效果不显著。
在另一动物养殖方案中，应用动物养殖的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物还含有其他动物营养所需的其他微量物质。
在另一实施方案中，该饲用组合物还进一步包含补充和平衡营养类物质。
在另一实施方案中，该饲用组合物还进一步包含保健类物质。
在另一实施方案中，该饲用组合物还进一步包含生理调节代谢类物质。
在另一实施方案中，该饲用组合物还进一步包含增食欲助消化类物质。
在另一实施方案中，该饲用组合物还进一步包含加工和保存剂类物质。
在另一实施方案中，该饲用组合物可以是液体、固体、半固体、凝胶等。
本发明所述的“含有”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。
进一步的，本发明将含有合适质量比的丁酸衍生物和肉豆蔻酸衍生物的饲用组合物用于制备动物用饲料添加剂。
所述的动物用饲料添加剂除了所述的饲用组合物还含有药学上可接受的赋形剂、载体、抗氧化剂、稀释剂、抗结块剂、溶媒或它们的组合。
所述的饲料添加剂可根据配方饲料需求在饲料加工业中添加到饲料原料中制备成功能性饲料应用于养殖动物的饲养。
所述的功能性饲料一方面可维持动物的健康另一方面改善动物的生产性能。
另外，本发明还涉及本发明提供含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物在制备动物生长促进剂的用途。
所述的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物制备的动物生长促进剂应用于动物养殖在改善饲料利用率、提高动物的生产性能、刺激动物生长方面具有显著的效果。
所述的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物制备的动物生长促进剂可进一步替代饲用抗生素类动物生长促进剂的应用。
所述的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物制备的动物生长促进剂还可进一步替代高剂量锌制剂或铜制剂作为动物生长促进剂的应用。
在一实施方案中，本发明提供的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物以单独形式添加到动物的每日口粮中使用。
在另一实施方案中，本发明提供的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物与饲料原料、饲料添加剂、载体或稀释剂等按照一定比例制备成添加剂预混合饲料、浓缩饲料、配合饲料、精料补充饲料等饲料形式供动物食用。
本发明涉及的饲料原料是指来源于动物、植物、微生物或矿物质，用于加工制作饲料但不属于饲料添加剂的饲用物质。
本发明涉及的饲料添加剂是指在饲料加工、制作、使用过程添加的少量或者微量物质，包括营养性饲料添加剂和非营养性饲料添加剂。营养性饲料添加剂是指为补充饲料营养成分而掺入饲料中的少量或者微量物质，包括饲料级氨基酸、维生素、矿物质微量元素、酶制剂、非蛋白氮等。非营养性饲料添加剂是指为保证或改善饲料品质、提高饲料利用率等作用而掺入饲料中的少量或者微量物质。
本发明涉及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。
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。
本发明涉及的添加剂预混合饲料是指由两种(类)或两种(类)以上的营养性饲料添加剂为主，与载体或者稀释剂按照一定比例配制的饲料，包括复合预混合饲料、微量元素预混合饲料、维生素预混合饲料。
本发明涉及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。
本发明涉及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。
本发明涉及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。
另外，本发明提供的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物或由其制备的饲用添加剂或动物生长促进剂适用的养殖动物包括家畜、家禽和水产养殖动物等，尤其在家禽的抗腹泻和消化不良等的控制效果更为显著。
在另一实施方案中，本发明提供的含有丁酸衍生物和肉豆蔻酸衍生物的饲用
组合物或由其制备的饲用添加剂或动物生长促进剂等用于各个生长阶段的肉鸡、蛋鸡、母鸡、肉鸭、蛋鸭、鹅、火鸡、珍珠鸡、鸽、鹌鹑及其他可人工饲养的鸟类的饲养。
在另一实施方案中，本发明提供的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物或由其制备的饲用添加剂或动物生长促进剂等用于各个生长阶段的肉牛、奶牛、猪、养、马、兔、狗、猫和驴等家畜的饲养。
在另一实施方案中，本发明提供的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物或由其制备的饲用添加剂或动物生长促进剂等用于各个生长阶段的鱼、虾、鳝、蟹或泥鳅等水产动物的饲养。
综上所述，本发明提供的含有丁酸衍生物和肉豆蔻酸衍生物的饲用组合物是一种新型、安全的动物饲料添加剂，替代饲用抗生素类动物生长促进剂和高剂量锌制剂或铜制剂的应用，克服饲用抗生素在动物养殖业中造成的耐药、耐药性传递等其它毒副作用和重金属制剂长期应用对动物健康以及人类食品安全造成的影响，在动物养殖业中具有广大的市场前景。
为了描述本发明，以下列出了实施例。但需要理解，本发明不限于这些实施例，只是提供实践本发明的方法。
本发明以下实施例所使用的丁酸衍生物和肉豆蔻酸衍生物均由广州英赛特生物技术有限公司的研发中心提供，样品纯度≥99％；所用维吉尼亚霉素制剂是进口预混剂，由美国辉宝有限公司比利时生产厂生产；所用硫酸粘杆菌素由山东鲁抗药业生产。
本发明的饲用组合物，其制备方法如下：
按照各组份的质量份数，将丁酸衍生物和肉豆蔻酸衍生物混合均匀后得到饲用组合物。然后可以作为动物饲料添加剂添加到动物饲料中使用。
实施例1：不同丁酸衍生物对硫酸粘杆菌素敏感大肠杆菌的抑制活性研究。
利用试管二倍稀释法测试不同丁酸衍生物对硫酸粘杆菌素敏感大肠杆菌的体外最小抑制浓度(MIC)，结果如表1所示。从表1可以看出，所有试验菌株对硫酸粘杆菌素敏感而所有试验用的丁酸衍生物对试验菌株的抑制活性很弱(表
1)。
表1 丁酸衍生物对硫酸粘杆菌素敏感大肠杆菌的体外最小抑制浓度(MIC，ppm)
| 大肠杆菌3Y-9 | 大肠杆菌2S-19 | 大肠杆菌5W-7 | |
| 硫酸粘杆菌素 | 2.0 | 2.0 | 1.0 |
| 丁酸钠 | 2000 | 4000 | 2000 |
| 丁酸钙 | 2000 | 1000 | 1000 |
| 丁酸锌 | 1000 | 1000 | 4000 |
| 丁酸铜 | 1000 | 1000 | 1000 |
| 丁酸乙酯 | 1000 | 4000 | 4000 |
| 甘油三丁酸酯 | 1000 | 4000 | 1000 |
实施例2：不同肉豆蔻酸衍生物对产气荚膜梭菌的抑制活性研究。
利用试管二倍稀释法测试维吉尼亚霉素和肉豆蔻酸衍生物对产气荚膜梭菌的体外最小抑制浓度(MIC)，结果如表2所示。从表2可以看出，所有试验菌株对维吉尼亚霉素敏感，所有试验用的肉豆蔻酸衍生物对试验菌株有与维吉尼亚霉素相似的抑制活性。
表2 肉豆蔻酸衍生物对产气荚膜梭菌的体外最小抑制浓度(MIC，ppm)
实施例3：丁酸钙和肉豆蔻酸钙在断奶猪料中的应用效果
180头28日龄平均体重7.61kg的断奶猪、体重相近的杜长大三元杂瘦肉型小猪如表3分9组，每组20头。各组在常规教槽料(不含任何药物饲料添加剂、氧化锌及高铜制剂)中添加不同测试添加物后，自由采食和饮水，统计10天内各试验组试验猪的平均日采食量(ADF)、平均日增重(ADG)、饲料报酬及腹
泻率。结果如表3所示，从表3可以看出，丁酸钙在饲料中的添加剂量400ppm时就可以达到饲用抗生素硫酸粘杆菌素20ppm的作用效果，并且对动物腹泻率的控制和生产性能的改变呈现剂量效应；肉豆蔻酸钙的添加剂量达到400ppm时作用效果明显达到了与维吉尼亚霉素的允许使用剂量20ppm的作用效用效果，对腹泻率的控制和生产性能的改变呈现剂量效应；但是，从各试验组的整体结果对比可见在控制动物腹泻率方面丁酸钙具有明显的优势而肉豆蔻酸钙在对动物生产性能的改善上相对效果更显著。
表3 丁酸钙和肉豆蔻酸钙对断奶猪的生长性能的影响和保健作用研究
实施例4：丁酸钙和肉豆蔻酸钙的联合应用在断奶猪料中的作用效果
140头28日龄体重相近的杜长大三元杂瘦肉型断奶仔猪分成7组，每组20头。各组在不含任何饲料添加剂的教槽料中添加肉豆蔻酸钙和/或不同剂量的丁酸钙，试验期间自由采食和饮水，统计10天内各试验组试验猪的平均日增重(ADG)、饲料报酬和腹泻率。结果显示(表4)，丁酸钙与肉豆蔻酸钙联合应用对试验猪的腹泻率的控制效果显著的同时，试验猪的生产性能具有显著的改善效果。
表4 丁酸钙和肉豆蔻酸钙在断奶仔猪料中的联合应用效果
实施例5：丁酸钙和肉豆蔻酸钙的联合应用在鸡料中的应用效果。
1400羽1日龄快大黄羽肉鸡随机分成7个试验组，每个试验组包含4个平行试验组，每个平行试验组为50羽，并分别在每组饲料中添加丁酸钙和/或不同剂量的肉豆蔻酸钙。试验期笼养，自由采食和自由饮水，试验期共28天，统计28天内各试验组试验鸡的平均日增重(ADG)、平均料肉比(AFCR)和存活率。试验结果显示，与1200ppm的丁酸钙相比，对空白组试验鸡的存活率更高；在含有1200ppm丁酸钙的同时给与不同剂量的肉豆蔻酸钙的饲料喂养的测试组，试验鸡的存活率升高的同时生产性能提升效果显著(表5)。
表5 丁酸钙和肉豆蔻酸钙在肉鸡料中的联合应用效果
实施例6：丁酸钙和肉豆蔻酸钙在草鱼料中的联合应用效果
所用试验鱼为草鱼，由广州英赛特试验场水产场进行。健康活泼、规格一致的青鱼种在大网箱中饲养4周后才用于正式养殖试验，实验体系为浮性小网箱。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～1.5m，池塘水为充分曝气底下水。试验时，将饥饿1d的草鱼200尾随机分成5组，每组设4个重复，每个重复放10尾鱼，整体称重后随机放入16个网箱中，分别饲喂不同的试验饲料。试验用饲料按表5配方自行配制，不同试验组按在基础料中分别加入不同的生长促进剂。试验采用人工限食投喂，投食量每周调整一次，两组投喂水平(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。
丁酸钙或丁酸钙与肉豆蔻酸钙联合应用对鱼的促生长试验结果见表6。结果显示添加丁酸钙或丁酸钙与肉豆蔻酸钙联合的试验组在增重、饲料系数及存活率方面均优于对照组，具有明显的促生长效应。
表6 丁酸钙和肉豆蔻酸钙在草鱼料中的联合应用试验分组及结果
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施
例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化等均应为等效的置换方式，都包含在本发明的保护范围之内。
Claims (8)
- 一种饲用组合物，其特征在于，含有丁酸衍生物和肉豆蔻酸衍生物；所述的丁酸衍生物为丁酸酯、或其结构如式(Ⅰ)所示、或其结构如式(Ⅱ)所示：
其中，M选自H、碱金属；
其中，M选自碱土金属、Zn、Fe、Mn、Cu；(C)所述的丁酸酯其结构如式(Ⅲ)或式(Ⅳ)所示：
所述的R1选自C1-4直链或支链烷基；
其中，R2、R3和R4选自H和直链C3C(＝O)，并且R2、R3和R4不全部为H；所述的肉豆蔻酸衍生物为肉豆蔻酸酯、或其结构如式(Ⅴ)所示、或其结构如式(Ⅵ)所示：
其中，M选自H、碱金属；
其中，M选自碱土金属、Zn、Fe、Mn、Cu；(F)所述的肉豆蔻酸酯其结构如式(Ⅶ)或式(Ⅷ)所示：
所述的R5选自C1-4直链或支链烷基；
其中，R6、R7和R8选自H和直链C13C(＝O)，并且R6、R7和R8不全部为H。 - 根据权利要求1所述的饲用组合物，其特征在于，按质量份数计，含有丁酸衍生物1～4份和肉豆蔻酸衍生物1份。
- 权利要求1或2所述的饲用组合物在制备动物饲料添加剂中的应用。
- 根据权利要求3所述的应用，其特征在于，所述的动物饲料添加剂是动物用生长促进剂。
- 根据权利要求3所述的应用，其特征在于，所述的动物为家畜、家禽或水产动物。
- 根据权利要求5所述的应用，其特征在于，所述的家畜为各个生长阶段的猪、牛、羊、马、兔、狗、猫或驴。
- 根据权利要求5所述的应用，其特征在于，所述的家禽为各个生长阶段的鸡、火鸡、珍珠鸡、鸭、鹅、鸽或鹌鹑。
- 根据权利要求5所述的应用，其特征在于，所述的水产动物为各个生长 阶段的鱼、虾或蟹。
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| CN101601439A (zh) * | 2009-06-19 | 2009-12-16 | 新奥（厦门）农牧发展有限公司 | 含丁酸钾的丁酸盐混合物及其制法和在饲料添加剂中的应用 |
| CN102138639B (zh) * | 2011-01-26 | 2014-11-12 | 龙岩新奥生物科技有限公司 | 助消化复合物及其制法和在饲料添加剂中的应用 |
| CN105076726A (zh) * | 2015-09-06 | 2015-11-25 | 新奥（厦门）农牧发展有限公司 | 丁酸盐及其衍生物与苯甲酸复合配方及制备方法及其做为饲料添加剂的应用 |
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| CN101647516A (zh) * | 2009-06-17 | 2010-02-17 | 新奥（厦门）农牧发展有限公司 | 丁酸盐或丁酸甘油脂与膳食纤维的复合物及其制法和在饲料添加剂中的应用 |
| CN101905025A (zh) * | 2010-07-20 | 2010-12-08 | 浙江大学 | 一种肠黏膜屏障保护剂的制备方法 |
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| CN104171313A (zh) * | 2014-07-21 | 2014-12-03 | 镇江天和生物技术有限公司 | 一种猪保育期专用饲料添加剂及其制备方法 |
| CN105053563A (zh) * | 2015-08-07 | 2015-11-18 | 浙江万方生物科技有限公司 | 丁酸盐精油复合饲料添加剂的制备方法 |
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| BE1025170B1 (nl) * | 2017-10-17 | 2018-11-21 | Vds Nv | Voedersupplement voor een voeder voor schaaldieren |
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