CN110799197A - 钙粘结剂用于防止死产的用途 - Google Patents
钙粘结剂用于防止死产的用途 Download PDFInfo
- Publication number
- CN110799197A CN110799197A CN201880027495.3A CN201880027495A CN110799197A CN 110799197 A CN110799197 A CN 110799197A CN 201880027495 A CN201880027495 A CN 201880027495A CN 110799197 A CN110799197 A CN 110799197A
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- Prior art keywords
- calcium
- animal
- binder
- calcium binder
- stillbirth
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- 239000011575 calcium Substances 0.000 title claims abstract description 52
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 229910052791 calcium Inorganic materials 0.000 title claims abstract description 51
- 239000011230 binding agent Substances 0.000 title claims abstract description 39
- 208000002254 stillbirth Diseases 0.000 title claims abstract description 14
- 231100000537 stillbirth Toxicity 0.000 title claims abstract description 14
- 241001465754 Metazoa Species 0.000 claims abstract description 36
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- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 8
- 229910001424 calcium ion Inorganic materials 0.000 claims description 8
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- 102000005701 Calcium-Binding Proteins Human genes 0.000 claims description 3
- 108010045403 Calcium-Binding Proteins Proteins 0.000 claims description 3
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- 206010021143 Hypoxia Diseases 0.000 description 3
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- 230000000694 effects Effects 0.000 description 3
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 2
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- 235000002949 phytic acid Nutrition 0.000 description 2
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- 208000010444 Acidosis Diseases 0.000 description 1
- GNJBBCHFWCTEBP-UHFFFAOYSA-M C=C.C=C.C(C)(=O)[O-].[Na+] Chemical compound C=C.C=C.C(C)(=O)[O-].[Na+] GNJBBCHFWCTEBP-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
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- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 1
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- LQPLDXQVILYOOL-UHFFFAOYSA-I pentasodium;2-[bis[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC(=O)[O-])CCN(CC([O-])=O)CC([O-])=O LQPLDXQVILYOOL-UHFFFAOYSA-I 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
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- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
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- 239000012266 salt solution Substances 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical class [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
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- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 description 1
- WHNXAQZPEBNFBC-UHFFFAOYSA-K trisodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(2-hydroxyethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].OCCN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O WHNXAQZPEBNFBC-UHFFFAOYSA-K 0.000 description 1
- HERBOKBJKVUALN-UHFFFAOYSA-K trisodium;2-[bis(carboxylatomethyl)amino]acetate;hydrate Chemical compound O.[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CC([O-])=O HERBOKBJKVUALN-UHFFFAOYSA-K 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及钙粘结剂在提高母猪的后代的围产期存活和减少或防止小猪的死产中的用途。本发明还涉及用于所述用途的组合物，该组合物包括钙粘结剂，特别地与氯化物盐组合的钙粘结剂，以补充动物，特别是怀孕的动物的膳食。
Description
技术领域
本发明大体上涉及使动物，特别地哺乳动物，进一步特别地猪，的生殖性能最大化的领域。本发明特别地涉及通过调节动物的营养使它们和它们的后代的性能最大化。
背景技术
使怀孕的动物和它们的后代的性能最大化长期以来是营养学家的主要目标。其中饲料加工技术、氨基酸补充和增加的膳食能量密度已经用于解决使该性能最大化的目标。
使生殖性能最大化的一个重要的方面是优化怀孕的动物和分娩期间其(未出生的)后代的健康。特别地，认为这可减少后代的围产期死亡率，比如死产(分娩期死亡率)和初生死亡率。特别地，小猪的死产主要由胎盘的血液灌注减少的重复发作导致的氧不足造成，其由子宫收缩压缩胎盘造成，并且由胎仔经过子宫和产道时，脐带的拉伸和有时破裂导致。氧不足导致胎仔中血液乳酸水平增加、血液pH下降以及细胞外液碱剩余的减少——称为酸中毒的情况。当该情况加重时，这可导致小猪死亡。短期氧不足是可逆的；但是，长时间的氧不足可导致不可逆的影响并且最终导致死亡，因此可理解死产主要出现在出生顺序结束时出生的小猪中。出于相同的原因，在产仔耗时长的母猪中死产率更高，并且所以，在长时间分娩的母猪中加重了出生顺序的影响。通常认为长时间分娩的一个主要原因是母体循环中减少的游离可用的钙(离子钙，或iCa)的浓度。钙参与调节子宫收缩的力量和协调性，并且血液中不足的iCa导致差的肌肉功能，并且因此，导致长时间分娩。出于该原因，通常提出对怀孕动物的膳食的钙补充作为减少围产期死亡率的措施。
但是，还未确定地探究营养物对使性能，特别地生殖性能最大化的影响。
发明目的
本发明的目的是增加怀孕的动物的生殖性能，特别地减少后代的围产期死亡率，减少死产的数量，从而提高围产期存活。
发明内容
与教导用额外的钙补充膳食是有利的现有技术完全相反，发现将钙粘结剂添加至膳食对于围产期死亡率，特别地对于减少死产具有积极作用。不受理论限制，认为通过有效降低动物膳食中可用的钙的量，可能刺激动物从其矿物质储备(特别地从骨头)释放钙的天然能力。
因此，已经令人吃惊地发现，使用口服施用的钙粘结剂(比如磷酸)以提高母猪的围产期存活和防止死产是有利的。特别地，已经发现，可用这种方式减少怀孕的动物的死产后代的数量和/或具有一个或多个死产后代的动物的百分数。
定义
动物的膳食是动物的习惯性营养品，包括饲料(固体和液体饲料)和饮用水。
钙粘结剂是防止钙离子以大于10mM，特别地大于1mM的浓度溶于水的化合物。
如果盐的水溶液在室温下每升水包含小于1mmol的盐，则盐是不溶于水的。
膳食补充剂是意图用于摄入的产品，其包含意图向膳食添加营养价值的膳食成分。例如，产品可添加至动物的固体饲料(在该情况下，补充剂通常称为撒饲饲料(top-dress))或添加至饮用水(在该情况下，补充剂通常称为饮用水添加剂)。
围产期死亡率是死产和初生死亡的总数。
死产是其中后代是死胎，但是仅在分娩前很短时间(特别地至多24-48小时)内死亡或在分娩期间死亡的现象。
初生死亡是其中后代在出生之后很快死亡，通常在出生后10天内死亡的现象。
具体实施方式
本公开提供了钙粘结剂，比如磷酸，以提高动物的后代中的围产期存活。
动物优选为怀孕的动物，更优选为怀孕的家畜，甚至更优选为怀孕的单胃家畜，并且最优选为怀孕的母猪。这样，后代优选为小猪。
在实施方式中，钙粘结剂，比如磷酸，被添加至动物的膳食中(其也包含通过提取其他组分，使膳食富集某些组分)。发现这是提供口服施用的方便的方式。钙粘结剂，比如磷酸，可添加至动物的饮用水或饲料中。例如，钙粘结剂可包含在组合物中，该组合物为预混合料、液体、粉末、颗粒、小球、糖衣丸、片剂、丸剂或胶囊的形式。
特别地，钙粘结剂，比如磷酸，可添加至动物的饮用水中。其优势在于怀孕的动物，即使在分娩之前，通常显示出正常的或甚至增加的饮用行为，而它们可能减少或甚至停止固体饲料的进食。因此，特别地在当接近分娩的时间点时(其是母猪中的iCa在其最高的时候，并且钙粘结剂最有效的时候)，可以继续消耗钙粘结剂，比如磷酸。
在又另一实施方式中，在分娩之前的0至5天的时间段，特别地至少在分娩之前的1至5天的时间段施用钙粘结剂，比如磷酸(其不排除还在更早或更晚，例如分娩期间，施用钙粘结剂)。
在特定的实施方式中，钙粘结剂为在水溶液中与钙离子形成水不溶性盐的阴离子。这种离子可例如为共轭碱离子。
适当的钙粘结剂包括但不限于能够结合反刍动物胃肠道中的游离钙，由此该游离钙不能被动物吸收的任何化合物。因此，触发了动物的天然钙调节防御机制。这种化合物包括但不限于：磷酸、草酸、草酸钠、肌醇六磷酸、肌醇六磷酸盐、包括沸石的粘土矿物、二乙烯乙酸钠、乙二胺四乙酸(EDTA)、EDTA的钠盐Na2EDTA和Na4EDTA、次氮基三乙酸三钠一水化物、硝基三乙酸三钠、二乙烯三胺五乙酸五钠、N-羟乙基乙二胺三乙酸三钠、柠檬酸、柠檬酸盐、多磷酸盐、三聚磷酸盐、磷酸盐、纤维素磷酸盐、谷氨酸N,N-二乙酸(GLDA)、GLDA的钠盐、GLDA的钾盐、甲基甘氨酸-N,N-二乙酸(MGDA)、MGDA的钠盐、MGDA的钾盐、N,N’-乙二胺二琥珀酸(EDDS)、EDDS的钠盐、EDDS的钾盐、亚氨基二琥珀酸(IDS)、IDS的钠盐或IDS的钾盐，或任何这样的化合物的不含钙的衍生物。
钙粘结剂可有利地为磷酸或磷酸盐，特别地当钙粘结剂被添加至饮用水时。磷酸具有有趣的性质，其在低pH下不与钙离子形成水不溶性盐(即，即使当与比如氯化钙的钙盐一起配制时，在向动物施用之前当在溶液中时，其保持可溶的形式)，但是在生理学pH下(即，在动物的胃肠道中)，其与钙离子一起沉淀。钙粘结剂优选为在生理学小肠pH(例如，范围为6-7.5，优选6.5-7.5的pH)下与钙离子形成水不溶性盐，但是在酸性pH(例如，低于6，优选低于5.5的pH)下不与钙离子形成水不溶性盐的阴离子。
可通过任何适当的封装材料封装钙粘结剂。适于钙粘结剂的封装的化合物为选自由下述组成的组中的化合物：脂肪、脂肪的非钙衍生物(比如肥皂和硬脂酸酯)、蛋白质、多糖、纤维素和任何这种化合物的衍生物、树胶、乙二醇和明胶。
当与氯化物盐，特别是氯化钙的施用组合时，将钙粘结剂添加至动物的膳食中是特别地有利的。
现将使用下述非限制性实施例进一步解释本发明。
实施例
实施例1
以0.01mol/升的浓度(相当于1g/L的磷酸)添加钙粘结剂(磷酸，PhA)。饲喂给母猪的膳食是相同的。研究的结果在这里指示在下面表1中。
表1：磷酸对死产的影响
| PhA* | 对照 | |
| 母猪的数量 | 25 | 24 |
| 死产小猪，# | 1.1 | 1.6 |
*PhA＝磷酸
在该实验中，每窝的死产从1.6减少至1.1头小猪。认为分娩之前内脏中膳食钙的结合以及减少动物可用的钙的量的内在影响产生的结果是刺激动物从其自身的骨头中的矿物质储备调动钙。所以，当如在分娩的情况下，对于钙的需求增加时，动物面对该需求做出了更好的准备，并且更有能力维持血液Ca水平。在上述实施例中，通过提供的处理的确增加了血液钙水平(数据未显示)。
Claims (10)
1.钙粘结剂在提高动物的后代中的围产期存活中的用途。
2.钙粘结剂在减少或防止新生动物的死产中的用途。
3.根据权利要求1或2中的任一项所述的钙粘结剂的用途，其中所述钙粘结剂被添加至怀孕的动物的膳食。
4.根据权利要求3所述的钙粘结剂的用途，其中所述钙粘结剂被添加至所述怀孕的动物的饮用水或饲料中。
5.根据前述权利要求中的任一项所述的钙粘结剂的用途，其中在分娩之前的0至5天的时间段，特别地至少在分娩之前的1至5天的时间段施用所述钙粘结剂。
6.根据前述权利要求中的任一项所述的钙粘结剂的用途，其中所述钙粘结剂为在范围为6-7.5的pH下与钙离子形成水不溶性盐，但是在低于6的pH下不与钙离子形成水不溶性盐的阴离子。
7.根据前述权利要求中的任一项所述的钙粘结剂的用途，所述钙粘结剂为磷酸。
8.根据前述权利要求中的任一项所述的钙粘结剂的用途，在所述怀孕的动物的所述饮用水中施用所述钙粘结剂。
9.根据权利要求7-8中的任一项所述的钙粘结剂的用途，所述钙粘结剂与氯化物盐组合使用。
10.根据前述权利要求中的任一项所述的钙粘结剂的用途，其中所述动物为母猪。
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| KR20200012855A (ko) | 2020-02-05 |
| WO2018199748A1 (en) | 2018-11-01 |
| CA3060994A1 (en) | 2018-11-01 |
| PL3615042T3 (pl) | 2023-02-06 |
| RU2019137635A3 (zh) | 2021-08-05 |
| EP3615041A1 (en) | 2020-03-04 |
| BR112019022215A2 (pt) | 2020-05-12 |
| EP3615042A1 (en) | 2020-03-04 |
| EP3615041B1 (en) | 2022-02-23 |
| PH12019502353A1 (en) | 2020-12-07 |
| PL3615042T4 (pl) | 2023-02-06 |
| DK3615041T3 (da) | 2022-04-04 |
| ES2916248T3 (es) | 2022-06-29 |
| KR20200010268A (ko) | 2020-01-30 |
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