CN104114034A - 酸稳定的蛋白酶在动物饲料中的用途,优选地是增加球虫疫苗接种的肉鸡的生产性能 - Google Patents
酸稳定的蛋白酶在动物饲料中的用途,优选地是增加球虫疫苗接种的肉鸡的生产性能 Download PDFInfo
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Abstract
本发明涉及与禽的抗球虫疫苗接种相结合的至少一种酸稳定的蛋白酶的用途,用于增加疫苗接种的动物的生产性能。出乎意料的是,已经发现将根据本发明的至少一种酸稳定的蛋白酶添加至“球虫”疫苗接种的禽食物中显著地改进了动物的生产性能。诸位发明人发现,尤其是使用丝氨酸蛋白酶改进了疫苗接种的肉鸡的生产性能,特别是使用丝氨酸蛋白酶增加了体重增加并且改进了球虫疫苗接种的禽的饲料转化率(FCR)。
Description
技术领域
本发明涉及动物饲料中酸稳定的蛋白酶与抗球虫剂相结合的用途,尤其涉及此类蛋白酶用于增加接种动物的生产性能的用途。
动物饲料中蛋白酶的用途从以下文件中获悉:
W095/28850披露了一种动物饲料添加剂,它包括植酸酶和蛋白水解酶。各类蛋白水解酶在第7页中具体指明。
W096/05739披露了一种酶饲料添加剂,它包括木聚糖酶和蛋白酶。适宜的蛋白酶在第25页中列出。W095/02044披露了衍生自棘孢曲霉的蛋白酶,以及它在动物饲料中的用途。
US3966971披露了通过用一种酸性植酸酶以及可任选地蛋白水解酶,从一种蔬菜蛋白质来源获取蛋白质的步骤。适宜的蛋白酶在栏2中具体指明。
技术背景
球虫亚纲是一种单细胞原生动物有机体的通用名称,它们是感染脊椎动物和无脊椎动物的肠道寄生虫。这些有机体引起球虫病,并且通常停留在小肠,例如结肠中。对于农场动物而言,感染球虫亚纲不仅严重地降低生长,还可能会危及生命。球虫感染的症状包括上皮细胞损失,肠粘膜剥落以及腹泻(通常会伴有血液损失)。对于某些农场动物如家禽而言,球虫感染会是致命的,即使不是这样也严重损害动物的健康。
家禽尤其易患球虫病,原因如下:(1)6至8天的寄生周期会在第2周至第4周的关键阶段袭击家禽,此时家禽通常会表现出最大化的生长。因为寄生虫基本上损坏了整个小肠上皮,所以营养物质的吸收剧烈减少,这就导致了生长的明显抑制。在第5或6周被屠宰之前,没有足够的时间来恢复。(2)能感染家禽的艾美球虫属物种有7种,比其他任何动物种类都多,并且其中它们中至少有4种在商业运行中是常见的。因此,当一个感染周期结束时,另一个周期可能出于初始阶段,这样球虫病就变成慢性的。(3)在家禽体内观察到最具致病性的物种(柔嫩艾美球虫、毒害艾美球虫),它们诱发严重的出血,并且在某些情况下所造成的死亡率能高达50%。这种紧急球虫病事件能很容易摧毁一个家禽饲养场主。(4)家禽在厚褥草上密集饲养(一个家禽舍十万只小鸡或更多),促使家禽经由食粪接近粪便中球虫亚纲的传染阶段,并因此使得该疾病通过整群家禽快速传播。如果消毒条件并不严格,则该疾病还将传播至同一饲养场的其他家禽舍,并且持续存在数年。
为了对抗球虫病,动物饲料经常补充一种球虫抑制剂和/或动物会接种一种药物,例如先灵葆雅动物健康公司(Shering-Plough AnimalHealth Corporation)的一种抗球虫疫苗。经EEC认证用于家禽(鸡、火鸡、嫩鸡和蛋鸡)的球虫抑制剂包括磺胺类药、氨丙嘧吡啶、地可喹酯以及离子载体。
球虫疫苗接种导致肉鸡的生产性能下降,这一点是熟知的。尤其是,球虫疫苗接种导致饲料摄取和饲料效率的下降。目前,美国所产的所有肉鸡中有20%已接种对抗球虫病。预期,到2020年球虫疫苗接种在美国肉鸡生产中的使用将增加至50%。因此,球虫疫苗接种的使用对肉鸡生产者具有巨大的经济影响。
发明概述
出乎意料的是,已发现将如以下定义的至少一种酸稳定的蛋白酶添加至经球虫疫苗接种的禽的食物中,导致动物生产性能的显著改进。诸位发明人发现,尤其是丝氨酸蛋白酶与球虫疫苗接种结合使用改进了肉鸡的生产性能。尤其是,使用丝氨酸蛋白酶增加了体重增加并且改进了经球虫疫苗接种的鸟类的饲料转化率(FCR)。因此,使用此类蛋白酶可以克服有通过使用这种球虫疫苗接种所造成的问题。
术语“鸟类”包括家禽,例如火鸡、鸭和鸡(包括但不限于肉鸡、蛋鸡)。
本发明的详细说明
蛋白酶根据其催化机制分为以下几类:丝氨酸蛋白酶(S)、半胱氨酸蛋白酶(C)、天冬氨酸蛋白酶(A)、金属蛋白酶(M)以及未知或还未分类的蛋白酶(U),参见《催化酶手册》,A.J.Barrett,N.D.Rawlings,J.F.Woessner(编),学术出版社(1998),尤其是总体介绍部分。
根据本发明所使用的蛋白酶是酸稳定的蛋白酶。根据本发明的优选的蛋白酶是酸稳定的丝氨酸蛋白酶。术语丝氨酸蛋白质是指丝氨酸肽酶以及如以上手册中定义的它们的宗族(clan)。在该手册的1998年版本中,丝氨酸肽酶和它们的宗族在第1章至175章中进行了讨论。丝氨酸蛋白酶可以被定义成以下蛋白酶,其中其催化机制取决于丝氨酸残基的羟基基团,它充当袭击肽键的亲核体。根据本发明所使用的丝氨酸蛋白酶的实例是宗族SA的蛋白酶,例如家族S2(链霉菌蛋白酶(Streptogrisin)),例如亚家族S2A(α-裂解蛋白酶),正如以上手册所定义。
蛋白酶活性可以通过以下任何测定测量,该测定中使用了一种底物,它含有与所讨论的蛋白酶的特异性相关的肽键。PH测定和温度测定同样应用于所讨论的蛋白酶。PH值测定的实例是pH5、6、7、8、9、10或11。温度测定的实例是30℃、35℃、37℃、40℃、45℃、50℃、55℃、60℃、65℃或70℃。
蛋白酶底物的实例是酪蛋白、以及pNA底物,例如Suc-AAPF-NA(可以从例如Sigma S7388获得)。该pNA-底物中的大写字母是指单字母氨基酸密码。另一个实例是Protazyme AK(天青精所染的交联酪蛋白,由Megazyme公司制备成片剂T-PRAK)。对于pH活性和pH稳定性的研究,该pNA-底物是优选的,其中对于温度活性研究,Protazyme AK底物是优选的。
根据本发明所使用的酸稳定的丝氨酸蛋白酶的起源没有限制。因此,术语蛋白酶不仅包括自然或野生型的蛋白酶,还包括它们的展示出蛋白酶活性的任一突变体、变体、片段等等,以及合成的蛋白酶,例如改组蛋白酶以及共有蛋白酶。此类基因工程处理的蛋白酶可以按照本领域通常所知的方法制备,例如通过定点突变、通过PCR(使用含有所希望突变的一个PCR片段作为PCR反应的引物之一),或通过随机突变。共有蛋白质的制备在例如EP0897985中说明。
根据本发明所使用的酸稳定的蛋白酶的实例是
a)从拟诺卡氏菌属NRRL18262以及无色拟诺卡氏菌衍生的蛋白酶;
b)与以下(i)的任一蛋白酶具有至少60%、65%、70%、75%、80%、85%、90%或至少95%氨基酸同一性的蛋白酶;
c)与以下任一序列具有至少60%、65%、70%、75%、80%、85%、90%或至少95%同一性的蛋白酶:SEQ ID NO:1,和/或SEQ ID NO:2。
为了计算百分数同一性,可以使用本领域已知的任何计算机程序。此类计算机程序的实例是Clustal V算法(Higgins,D.G.,和Sharp,P.M.(1989),基因(阿姆斯特丹(Amsterdam))73,237-244;以及GAP程序,由GCG第8版程序包提供(威斯康辛数据包的程序操作(Program Manual for theWisconsin Package),第8版,遗传计算机基团(Genetics Computer Group),575科学驱动(Science Drive),麦迪逊(Madison),威斯康辛州(Wisconsin),美国53711)(Needleman,S.B.和Wunsch,C.D.,(1970),分子生物学杂志(ournal of Molecular Biology,)48,443-453。
在一个特定的实施例中,根据本发明所使用的蛋白酶是一种微生物蛋白酶,该术语微生物是指该蛋白酶衍生自或源自一种微生物,或是衍生自一种微生物的类似物、片段、变体或合成的蛋白质。它可以在该原始野生型微生物菌株、在另一种微生物菌株或一种植物中产生或表达,即该术语涵盖了野生型、自然发生的蛋白质的表达,以及任一重组、基因工程处理或合成蛋白质在宿主中的表达。
微生物的实例是细菌,例如放线菌门的细菌,例如纲I的:放线菌纲,例如亚纲V的:放线菌亚纲,例如目I的:放线菌目,例如亚目XII的:链孢囊菌亚目,例如科II的:拟诺卡氏菌科,例如属I的:拟诺卡氏菌属,例如拟诺卡氏菌属物种NRRL18262和无色拟诺卡氏菌,例如芽胞杆菌属物种,或它们的展示出蛋白酶活性的突变体或变体。这种分类法的根据是伯杰氏细菌系统分类学手册(Berge's Manual of Systematic Bacteriology),第二版,2000,斯普林格(Springer)(预印本:伯杰氏路线图(Road Map to Bergey's))。
微生物的其他实例是真菌,例如酵母或丝状真菌。
在根据本发明的用途中,该蛋白酶可以在经球虫疫苗接种的鸟类食物之前、之后或同时喂给动物。后者是优选的。
在本文中,术语酸稳定的是指该纯蛋白酶的蛋白酶活性,以相当于A280=1.0的稀释,并且随后在以下缓冲液中在37C孵育2小时:
·100mM琥珀酸、100mM HEPES、100mM CHES、
·100mM CABS、1mM CaCl2、150mM KCl、0.01%X-100、pH3.5,
是参比活性的至少40%,如使用在此实例1中所说明的测定所测量(底物:Suc-AAPF-pNA,pH9.0,25℃)。
在以上酸稳定性定义的特定实施例中,该蛋白酶活性是该参比活性的至少45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%或至少97%。
术语参比活性是指相同蛋白酶,按照对应于A280=1.0的稀释、以纯化形式在5C下在以下缓冲液中孵育2小时后的蛋白酶活性:100mM琥珀酸、100mM HEPES、100mM CHES、100mM CABS、1mM CaCl2、150mM KCl、0.01%X-100、pH9.0,其中该活性如以上说明确定。
换言之,确定酸稳定性的方法包括以下步骤:
a)有待测试的蛋白酶样本(处于纯化形式,A280=1.0)被分成两等份(I和II);
b)等份I在37℃和pH3.5下孵育2小时;
c)测量等份I的残余活性(pH9.0和25℃);
d)等份II在5℃和pH9.0下孵育2小时;
e)测量等份II的剩余活性(pH9.0和25℃);
f)计算等份I的残余活性相对于等份II的残余活性的百分数。
可替代地,在酸稳定性的以上定义中,步骤b)缓冲液pH值可以是1.0、1.5、2.0、2.5、3.0、3.1、3.2、3.3或3.4。
在与以上可替代的步骤b)缓冲液pH值相关的以上酸稳定性定义的其他可替代的实施例中,该残余蛋白酶活性与参比值相比,是至少5%、10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%或至少97%。
在可替代的实施例中,pH值6.0、6.5、7.0、7.5、8.0或8.5可以应用至步骤d)缓冲液。
在以上酸稳定性的定义中,术语A280=1.0是指所述纯蛋白酶的此类浓度(稀释),它在280nm下在1cm路径长度的比色皿中相对于一种缓冲液空白产生1.0的吸收。
并且在以上酸稳定性的定义中,术语纯蛋白酶是指一个样本,它的A280/A260比率大于或等于1.70。
在另一个特定的实施例中,根据本发明所使用的蛋白酶除了酸稳定之外,还是热稳定的。
术语热稳定的是指以下情况中的一种或多种:该温度最适宜是至少50℃、52℃、54℃、56℃、58℃、60℃、62℃、64℃、66℃、68℃、或至少70℃。
当然,该蛋白酶应当以一个有效的量值来应用,即以一个量值,它足以用于改进用一种抗球虫疫苗来接种的禽的饲料转化率。
在一个优选的实例中,该蛋白酶的预期剂量是每千克最终饲料0.01-200mg蛋白酶。
术语饲料转化率是根据一个生长试验确定的,该试验包括一个第一处理,其中根据本发明的组合物按照每千克饲料适宜的浓度添加至动物饲料中,以及一个第二处理(对照),没有将该组合物添加至动物饲料中。
如通常所知,改进的FCR比对照FCR低。在特定的实施例中,与对照相比,FCR被改进(即减少)至少1.0%或5%。
对于根据本发明的用途,该蛋白酶不需要那么纯;它可以是例如包括其他酶类,甚至其他酸稳定的蛋白酶,其中它可以被命名为一种酶或蛋白酶制品。然而,一种很好定义的酶/蛋白酶制品是具有优势的。例如,它更容易将一种蛋白酶剂量正确地加入到饲料中,该蛋白酶基本上不会干扰或污染其他蛋白酶。术语剂量正确地加入尤其是指获得一致且恒定结果的目的,以及根据所希望的效果优化剂量的能力。
在家禽饲养概念的一个优选实施例中,该蛋白酶以一种饲料添加剂的形式使用。
将如以上在此示例的饲料添加剂的组合物合并到家禽饲料中在实际情况下是使用一种浓缩剂或一种预混料进行的。预混料是指一种或多种微小成分与稀释剂和/或载体的一种优选地均匀的混合物。预混料用于促进微小成分在较大混合物中均匀分散。根据本发明的一种预混料可以作为固体(例如作为水溶性粉末)或液体添加到饲料成分或饮用水中。
本发明的酸稳定的蛋白酶的一部分,本发明的动物饲料添加剂含有至少一种-脂溶性维生素、和/或至少一种水溶性维生素、和/或至少一种痕量矿物质、和/或至少一种巨量矿物质。
此外,任选的饲料添加剂成分是着色剂,例如类胡萝卜素像β-胡萝卜素、虾青素、角黄素、阿卜酯以及叶黄素;芳香化合物;稳定剂;抗微生物肽类;多不饱和脂肪酸(PUFAs);产生活性氧的物质;和/或至少一种选自下组的酶:植酸酶(EC3.1.3.8或3.1.3.26);木聚糖酶(EC3.2.1.8);半乳聚糖酶(EC3.2.1.89);α-半乳糖苷酶(EC3.2.1.22);蛋白酶(EC3.4.,磷脂酶A1(EC3.1.1.32);磷脂酶A2(EC3.1.1.4);溶血磷脂酶(EC3.1.1.5);磷脂酶C(EC3.1.4.3);磷脂酶D(EC3.1.4.4);淀粉酶例如像α-淀粉酶(EC3.2.1.1);和/或β-葡聚糖酶(EC3.2.1.4或EC3.2.1.6)。
抗微生物肽类(AMP)的实例是CAP18、林可霉素A(Leucocin A)、Protegrin-1、Thanatin、死亡素(Defensin)、Lactoferrin、牛乳铁蛋白抗菌肽(Lactoferricin)、以及Ovispirin例如Novispirin(Robert Lehrer,2000)、Plectasins、以及他汀类。
多不饱和脂肪酸的实例是C18、C20和C22多不饱和脂肪酸,例如花生四烯酸、二十二碳六烯酸、二十碳五烯酸以及γ-亚油酸。
产生活性氧的物质的实例是化学物质例如过硼酸盐、过硫酸盐、或过碳酸盐;以及酶类例如氧化酶、加氧酶或合成酶。
通常,脂溶-和水溶-性维生素、以及痕量矿物质形成了一种所谓的旨在添加到饲料中的预混料的一部分,其中巨量矿物质通常被分开地添加到饲料中。
以下是这些组分的实例的非排外性列表:
-脂溶性-维生素的实例是维生素A、维生素D3、维生素E和维生素K,例如维生素K3。
-水溶性-维生素的实例是维生素B12,生物素和胆碱、维生素B1、维生素B2、维生素B6、烟酸、叶酸和泛酸盐,例如Ca-D-泛酸盐。
-痕量矿物质的实例是锰、锌、铁、铜、碘、硒和钴。
-巨量矿物质的实例是钙、磷和钠。
预混料(每吨家禽饲料)可以包含,例如50至200g这些活性化合物的混合物的丙二醇溶液,20至1000g的一种乳化剂,50至900g谷物和副产品,20至100g的一种蛋白质支持物(奶粉、酪蛋白等)以及50至300g的一种矿物质组分(多空硅胶(expanded silica)、饲料质量石灰、二钙磷酸盐等)。
如以上说明的一种饲料添加剂或预混料最终被添加到动物饲料组合物。该组合物如此制备并添加,使得该蛋白酶的量值对应于每千克饲料预期添加0.01-200mg蛋白酶蛋白质。
动物饲料组合物或食物具有较高含量的蛋白质。根据以上所提及的美国国家研究委员会(NRC)的公开文件,家禽和猪食物可以如WO01/58276的表B所指描述。根据本发明的动物饲料组合物的粗蛋白含量是50-800g/kg,并且进一步含有如在此主张的至少一种蛋白酶。
此外,或可替代(以上指出的粗蛋白含量),本发明的动物饲料组合物的可代谢能量的含量是10-30MJ/kg;和/或钙含量是0.1-200g/kg;和/或可获得的磷的含量是0.1-200g/kg;和/或甲硫氨酸的含量是0.1-100g/kg;和/或甲硫氨酸加半胱氨酸的含量是0.1-150g/kg;和/或赖氨酸的含量是0.5-50g/kg。
在特定的实施例中,可代谢能量、粗蛋白质、钙、磷、甲硫氨酸、甲硫氨酸加半胱氨酸、和/或赖氨酸的含量在如WO01/58276的表B所披露的2、3、4或5范围中的任何一个。
为了确定每千克饲料的蛋白酶蛋白质的mg,该蛋白酶从该饲料组合物纯化,并且使用一种相对测定来确定该纯化的蛋白酶的特异活性(参见蛋白酶活性、底物和测定部分)。此类饲料组合物的蛋白酶活性还使用同一测定来确定,并且根据这两个确定结果,计算每kg饲料的蛋白酶mg的剂量。
相同的原理用于确定饲料添加剂中的蛋白酶蛋白质mg。
根据本发明的拟诺卡氏菌属NRRL18262的蛋白酶可以使用常规方法准备,如通常在WO01/58276中说明。一种含有拟诺卡氏菌属NRRL18262的蛋白酶的饲料添加剂也是可商购的(例如像ProAct,由帝斯曼营养品公司(DSM Nutritional Products),凯泽劳斯特(Kaiseraugst),瑞士提供)或可以很容易由技术人员使用本领域所熟知的步骤和方法制备。
在此说明并主张的本发明并非局限于在此披露的特定的实施例的范围之内,因为这些实施例旨在阐述本发明的某些方面。任何等价的实施例旨在处于本发明的范围之内。实际上,除了在此显示并说明的那些之外,本发明的各种修改将在之前的说明书对本领域的普通技术人员而言应当是显而易见的。此类修改还旨在处于所附权利要求的范围之内。
以下实例进一步阐明了本发明。
实例
实例1pH稳定性测定
Suc-AAPF-pNA(Sigma S-7388)用来获取pH稳定性特征。
测定缓冲液:100mM琥珀酸、100mM HEPES、100mM CHES、100mMCABS、1mM CaCl2、150mM KCl、0.01%X-100,使用HCl或NaOH将pH值调整至2.0、2.5、3.0、3.5、4.0、4.5、5.0、60、7.0、8.0、9.0、10.0或11.0。
每个蛋白酶样品(在1mM琥珀酸、2mM CaCl2、100mM NaCl中、pH6.0并且A280吸收>10)在每个pH值下用该测定缓冲液稀释至A280=1.0。经稀释的蛋白酶样品在37℃孵育2小时。
孵育后,蛋白酶样品在100mM琥珀酸、100mM HEPES、100mM CHES、100mM CABS、1mM CaCl2、150mM KCl、0.01%X-100,pH9.0稀释,所有样品的pH变成pH9.0。
在以下活性测量过程中,温度为25℃。
300μl经稀释的蛋白酶样品与1.5ml pH9.0的测定缓冲液混合,并且该活性反应通过加入1.5ml pNA底物(50mg溶解在1.0ml DMSO中,并进一步用0.01%X-100稀释45x)起始,并且,混合后,通过分光光度计监测A405的增加,作为该(残余)蛋白酶活性的测量值。
37C孵育在不同pH值条件下进行,并且活性测量值按照残余活性对比pH作图。将残余活性用平行孵育(对比)的活性归一化,其中该蛋白酶在该测定缓冲液中在pH9.0被稀释至A280=1.0,并且在活性测量前在5℃孵育2小时,正如其他孵育。在活性测量前将蛋白酶样品稀释,以确保所有活性测量值处于该测定的剂量-反应曲线的线性部分内。
实例2-用酸稳定的蛋白酶饲养疫苗接种的禽
使用日龄雄性禽Ross708进行地面围栏试验。该试验中使用了共计27栏,每栏在1日龄放置禽10只。围栏在三次处理中随机分配,9重复/处理。这些禽饲以基于玉米/大豆食物的营养足够的基本食物,并且通过从第1至21天饲以一种起始食物,并且从第22至42天饲一种生长饲料来调整禽龄。
处理1:基本食物
在1日龄+食谱(球虫抑制剂)80ppm。所有禽在1日龄在禽舍中经鼻饲给药接受
处理2:
在1日龄,没有
处理3:
如处理2加400ppm酶混合物(由帝斯曼营养品公司,凯泽劳斯特,瑞士提供提供)
饲以Monteban,以便抑制Cocci Vac的效果。Cocci Vac通过造成低水平的疾病来诱导对球虫病的免疫。
该酶混合物包括:
-200ppmProAct(酸稳定的蛋白酶)以及
-100ppm RONOZYME WX+50ppm RONOZYME A+50ppmROXAZYME G2(=酶混合物,包括木聚糖酶、淀粉酶、纤维素、β-葡聚糖酶以及其他)
在该试验末,在第42天,确定平均鸟重量以及平均饲料消耗,并且通过饲料摄入除以每一处理的体重增加来计算饲料转化配给(FCR)。
这些结果总结在下表中,其中表1列举了第42天的体重,表2列举了第42天FCR。
表1平均42天体重
平均体重g | |
处理1 | 2832a |
处理2 | 2546c |
处理3 | 2710b |
abcP<0.05
表2第42天饲料转化配给
FCR | |
处理1 | 1.544b |
处理2 | 1.656a |
处理3 | 1.559b |
abcP<0.05
这些结果清楚地显示,球虫疫苗接种(处理2)降低了体重并且负面影响了FCR,而球虫抑制剂(处理1)消除了这些效应。与处理2相比,添加这种酶混合物导致体重增加显著更高以及FCR改进。将该酶混合物添加到经历过球虫病的禽,使得这些禽的生产性能接近饲以球虫抑制剂的禽。
实例3-用酸稳定的蛋白酶饲养疫苗接种的禽
使用日龄雄性禽Cobb X Cobb雏鸡进行地面围栏试验。共计有2160只鸡被分配到该研究中。该实验包括48栏,每栏45只肉鸡。处理在八(8)块区域中重复,每块随机进行六个(6)处理。这些鸟类被饲以基于玉米/大豆饮食的营养足够的基本食物,并且通过从第1至16天饲以一种起始食物、并且从第17至32天饲以一种生长食物、并且从第33至42天饲以一种终止食物来调整禽龄。六个处理如下:
处理
在处理过程中,使用了由帝斯曼营养品公司,凯泽劳斯特,瑞士提供的酶产品。
AX=80%WX+20%
ProAct=纯蛋白酶产物。
所有禽在1日龄时在禽舍中鼻饲给药接受阳性对照禽除外,这些禽在整个研究过程中被给予每吨饲料60g标准剂量的球虫抑制剂盐霉素(Salinomcyin)
盐霉素是最常用的球虫抑制剂,它抑制了常见死亡球虫病的发展。
通过造成低水平的球虫病来诱导对该病的免疫。
在试验末在第42天,平均禽体重(平均体重增加)和平均饲料消耗(饲料消耗)被确定,并且通过饲料摄入除以每一处理的体重增加来计算饲料转化配给(FCR)
与给予盐霉素处理的PC相比,Cocci Vac(处理2)降低了体重,并且负面影响了FCR。
在之外添加蛋白酶RONOZYME ProAct,导致与Cocci Vac(处理2)相比FCR显著改进。任何该酶与RONOZYME PROACT产物一起的混合物的添加导致对经历过球虫病的禽的甚至进一步的改进,使这些禽的生产性能接近饲以球虫抑制剂的鸟类。
Claims (8)
1.与禽的抗球虫疫苗接种相结合的至少一种酸稳定的蛋白酶的用途,用于增加体重增加和/或改进该动物的饲料转化率(FCR),其中该蛋白酶与以下各项具有至少70%的同一性(i)SEQ ID NO:1,和/或(ii)SEQ ID NO:2。
2.根据权利要求1的用途,其中该蛋白酶用于在针对禽的饲料中使用,包括家禽例如火鸡、鸭和鸡。
3.如权利要求2所述的用途,其中该蛋白酶的预期剂量是每千克饲料0.01-200mg蛋白酶蛋白质。
4.一种针对疫苗接种的禽的动物饲料添加剂,包括(a)至少一种酸稳定的蛋白酶以及(b)至少一种脂溶性维生素,和/或(c)至少一种水溶性维生素,和/或(d)至少一种痕量矿物质,和/或(e)至少一种巨量矿物质;其中该蛋白酶与以下各项具有至少70%的同一性(i)SEQ ID NO:1,和/或(ii)SEQID NO:2。
5.如权利要求4所述的动物饲料添加剂,其中该蛋白酶的量值对应于每千克饲料预期添加0.01-200mg蛋白酶蛋白质。
6.如权利要求4或5所述的动物饲料添加剂,进一步包括植酸酶、木聚糖酶、半乳聚糖酶、β-葡聚糖酶、淀粉酶和/或纤维素。
7.一种针对疫苗接种的禽的动物饲料组合物,其具有50-800g/kg的粗蛋白质含量并且包括至少一种酸稳定的蛋白酶,其中该蛋白酶与以下各项具有至少70%的同一性(i)SEQ ID NO:1,和/或(ii)SEQ ID NO:2。
8.如权利要求7所述的动物饲料组合物,其中该蛋白酶的量值是每千克饲料0.01-200mg蛋白酶蛋白质。
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- 2012-11-19 IN IN4408CHN2014 patent/IN2014CN04408A/en unknown
- 2012-11-19 CN CN201280056288.3A patent/CN104114034A/zh active Pending
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CN107404907A (zh) * | 2015-02-10 | 2017-11-28 | 帝斯曼知识产权资产管理有限公司 | 用于改进饲料消化率和生长性能的方法 |
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WO2013072521A2 (en) | 2013-05-23 |
BR112014011508A2 (pt) | 2017-05-09 |
US20160271232A1 (en) | 2016-09-22 |
AU2012338741A1 (en) | 2014-05-22 |
MX358174B (es) | 2018-08-08 |
MX2014005856A (es) | 2015-04-01 |
US20190160156A1 (en) | 2019-05-30 |
US20140314910A1 (en) | 2014-10-23 |
ES2700738T3 (es) | 2019-02-19 |
EP2782458B1 (en) | 2018-09-12 |
WO2013072521A3 (en) | 2014-04-24 |
EP2782458A2 (en) | 2014-10-01 |
BR112014011508B1 (pt) | 2020-12-01 |
IN2014CN04408A (zh) | 2015-09-04 |
AU2012338741B2 (en) | 2015-12-03 |
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