WO2021099507A1 - Procédé d'alimentation d'un animal gravide - Google Patents

Procédé d'alimentation d'un animal gravide Download PDF

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Publication number
WO2021099507A1
WO2021099507A1 PCT/EP2020/082755 EP2020082755W WO2021099507A1 WO 2021099507 A1 WO2021099507 A1 WO 2021099507A1 EP 2020082755 W EP2020082755 W EP 2020082755W WO 2021099507 A1 WO2021099507 A1 WO 2021099507A1
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WO
WIPO (PCT)
Prior art keywords
ursolic acid
ester
salt
composition
pregnant
Prior art date
Application number
PCT/EP2020/082755
Other languages
English (en)
Inventor
Pieter LANGENDIJK
Theodorus Antonius Theresia Gerardus VAN KEMPEN
Original Assignee
Nutreco Ip Assets B.V.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Nutreco Ip Assets B.V. filed Critical Nutreco Ip Assets B.V.
Publication of WO2021099507A1 publication Critical patent/WO2021099507A1/fr

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Classifications

    • 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
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines

Definitions

  • the present invention pertains to the field of maximizing performance of animals, particularly of pregnant mammals and their offspring, particularly of pregnant sows and their offspring.
  • the present invention is in the field of increasing the colostrum production, increasing average daily gain of the offspring, improving neonatal survival of the offspring and/or increasing numbers of weaned offspring.
  • the present invention relates to a method of feeding a pregnant mammal, comprising administering ursolic acid or an ester or salt thereof in an immediate release form to the pregnant mammal.
  • the ursolic acid or an ester or salt thereof in an immediate release form is administered in the form of a top dress formulation, an animal feed, a premix or supplement or animal drinking water.
  • the present invention relates to a method of producing a composition for feeding a pregnant mammal, comprising mixing ursolic acid or an ester or salt thereof in immediate release form with one or more feed components or one or more feed additives or water, to produce the composition, wherein the amount of ursolic acid or an ester or salt thereof in the composition is intended to provide a dosage in a range of 0.01 - 100 grams per day.
  • the mammal is a monogastric mammal.
  • the monogastric mammal is a sow.
  • the composition is selected from a group consisting of a top dress formulation, an animal feed, a premix or supplement and an animal drinking water.
  • the ursolic acid or an ester or salt thereof in an immediate release form is administered to the pregnant animal in a period from about 45 days prior to parturition until parturition.
  • the ursolic acid or an ester or salt thereof in an immediate release form is administered to the pregnant animal in a period from about 40 days prior to parturition until parturition.
  • the ursolic acid or an ester or salt thereof in an immediate release form is administered to the pregnant animal in a period from about 35 days prior to parturition until parturition.
  • the present invention relates to the use of a composition comprising ursolic acid or an ester or salt thereof in an immediate release form, in a diet for a pregnant mammal, wherein the dosage of ursolic acid or an ester or salt thereof is in a range of 0.01 - 100 grams per day.
  • the present invention relates to the use of a composition comprising ursolic acid or an ester or salt thereof, for increasing colostrum production.
  • the present invention relates to the use of a composition comprising ursolic acid or an ester or salt thereof, for increasing average daily gain of offspring of a pregnant mammal.
  • the present invention relates to a composition comprising ursolic acid or an ester or salt thereof, for use in improving neonatal survival of offspring of a pregnant mammal.
  • the present invention relates to a composition comprising ursolic acid or an ester or salt thereof, for use in increasing numbers of weaned offspring of a pregnant mammal.
  • the composition is selected from a group consisting of a top dress formulation, an animal feed, a premix, a supplement, and an animal drinking water.
  • pregnant or ‘pregnancy’, also known as ‘gestation’, as used herein refers to the period of time between conception and parturition, wherein the embryo or fetus is developing in the uterus.
  • the duration of the gestation strongly varies from species to species. Smaller animals usually have shorter periods of gestation than larger animals. In pigs the gestation normally lasts for about 115 days, but there can be some variability from case to case. Gestation can be divided into different phases like fertilization at the very beginning, placental formation, fetal development and major fetal growth at the end, before parturition.
  • mammary gland development Another important development during gestation is mammary gland development, which in pigs typically takes place between around day 80 (around 35 days before parturition) and parturition. During that period of time the mammary gland will develop and get ready for the energy demanding lactation phase.
  • parturition also known as ‘farrowing’, as used herein refers to the process of giving birth. In pigs this process typically ranges from three to eight hours and piglets are usually delivered every 10 to 20 minutes but there is a wide variation. Between the first and second piglet there can be a gap of up to an hour. The process of parturition is activated by the piglets when they reach the final stage of maturity and signal the uterus to produce prostaglandins which are circulated to the ovary and cause luteolysis. This finally results in termination of the pregnancy and activation of parturition.
  • iatal survival’ refers to the survival of newborn animals within ten days after birth. It is the opposite of neonatal mortality or neonatal death, which is the phenomenon where offspring dies shortly after birth, typically within ten days after birth.
  • pre-wean survival refers to the survival of newborn animals until weaning, which is within about 3 to 4 weeks after birth. It is the opposite of pre-wean mortality or pre-wean death or mortality before weaning, which is the phenomenon where offspring dies after birth, typically within 3 to 4 weeks after birth. Pre-wean survival means that the animal survives the first 3 weeks after birth, preferably the animal survives the first 4 weeks after birth.
  • colonstrum refers to the milk secreted between parturition and 24 hours thereafter.
  • Colostrum uptake by the offspring which typically corresponds to the colostrum production of the pregnant animals, can be calculated based on the increase in body weight of the offspring between birth and 24 hours thereafter, based on the algorithm developed by Theil et al. (Mechanistic model to predict colostrum intake based on deuterium oxide dilution technique data and impact of gestation and prefarrowing diets on piglet intake and sow yield of colostrum. J. Anim. Sci. 2014, 92:5507-5519).
  • average daily gain refers to a value that shows the average weight gain of an animal per day. It is obtained by dividing how much an animal has grown (weight increase) by the number of days needed to accomplish it.
  • ursolic acid refers to a pentacyclic triterpenoid identified in the epicuticular waxes of apples as early as 1920 and widely found in the peels of fruits, as well as in herbs and spices like rosemary and thyme. It has the following molecular structure:
  • ursolic acid is extracted from rosemary, from which it can be obtained in purity levels of about 90% or more.
  • ursolic acid or an ester or salt thereof refers to any ester form or salt form of ursolic acid.
  • Non-limiting examples of ursolic acid esters are cis- and trans-3-O-p- hydroxycinnamoyl esters of ursolic acid or ursolic acid alkyl esters like methyl ursolate.
  • Non limiting examples of ursolic acid salts are sodium ursolate or calcium ursolate.
  • immediate release also known as ‘fast release’, as used herein refers to a form wherein a particular compound is directly, or in a fast way, physiologically available for the animal after ingestion of the said compound; in contrary to forms like controlled release, yed release, where a compound is released at a later point in time after ingestion of the compound.
  • Such controlled-, slow- or delayed release can be achieved for example by addition of controlled release agents or a coating or matrix around such a compound, delaying the availability of the said compound for the animal.
  • Immediate release means immediate or fast availability of the compound, for example by contact with the aqueous environment of the gastro-intestinal tract after ingestion of the compound.
  • in immediate release form is meant that no measures have been taken to control release of the ursolic acid, salt or ester thereof in the animal body.
  • said ursolic acid, salt or ester thereof may not be surrounded by a coating controlling its release, and is preferably essentially free or free of an enteric coating.
  • the animal feed, ingredient, supplement or premix is essentially free or free of a coating such as an enteric coating, or any other coating or measures controlling its release.
  • diet refers to the habitual nourishment of the animal, including feed (solid and liquid feed) and drinking water.
  • the term ‘supplement’ also known as ‘additive’, as used herein refers to a product intended for ingestion, which contains one or more ingredients intended to add nutritional value to the diet.
  • the supplement may be added to a feed composition, and includes, without limitation, animal feeds, top dresses or premixes. It may also be added to the drinking water (in which case the supplement is often referred to as a drinking water additive).
  • top dress refers to an animal feed which is added on the normal diet of the animal.
  • a top dress can be used as a way to add one or more supplements to the diet.
  • a top dress typically contains materials like barley, wheat, corn, wheat bran, molasses, vegetable oil, and/or sugar.
  • premix refers to a complex mixture of compounds like vitamins, minerals, trace elements, supplements and/or other nutritional additives, for incorporation into feed.
  • the premix is typically incorporated at a level of between 0.2 and 2 % (micro premix) or between 2 to 8 % (macro premix) into the feed. It is usually mixed with feed in an early stage in the manufacturing and distribution process.
  • to improve or ‘improving’ as used herein refer to the ability to bring in a more desirable state or condition. Someone or something might for example become better or might get better properties or quality. The ability to make things better is also covered in a sense of the ability to ameliorate, like improving a bad situation or quality, or repairing bad or not working properties.
  • a e may be increased or decreased when it is at least 5%, such as 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% higher or lower, respectively, than the corresponding level in a control sample or reference sample.
  • 'about' indicates a range of normal tolerance in the art, for example within 2 standard deviations of the mean.
  • the term "about” can be understood as encompassing values that deviate at most 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1 %, 0.5%, 0.1 %, 0.05%, or 0.01 % of the indicated value.
  • the present inventor surprisingly found that use of a composition comprising ursolic acid or an ester or salt thereof in an immediate release form, in a diet for a pregnant mammal, preferably a pregnant monogastric mammal, preferably a pregnant sow, increased colostrum production, increased average daily gain of the offspring, improved neonatal survival of the offspring and increased numbers of weaned offspring.
  • the present invention relates to a method of feeding a pregnant mammal, comprising administering ursolic acid or an ester or salt thereof in an immediate release form.
  • the dosage of ursolic acid or an ester or salt thereof is in a range of 0.01 - 100 grams per day.
  • the dosage of ursolic acid or an ester or salt thereof is in a range of 0.01 - 50 grams per day, more preferably in a range of 0.02 - 20 grams per day, more preferably in a range of 0.02 - 10 grams per day, more preferably in a range of 0.03 - 5 grams per day, even more preferably in a range of 0.04 - 3 grams per day.
  • the pregnant mammal is preferably a pregnant monogastric mammal, even more preferably a pregnant sow. It is not relevant in which form the ursolic acid or an ester or salt thereof is added to the diet as long as the animal receives the necessary daily dose of ursolic acid or an ester or salt thereof.
  • Pregnant sows for example eat about 2.5 to 3.5 kg feed a day and drink about 7 liters of drinking water a day. This means that the amount of ursolic acid or an ester or salt thereof to be added either to the feed, or to the drinking water, and drinking water, can easily be determined in order to result in the necessary daily dose of the invention.
  • the ursolic acid or an ester or salt thereof is added to an animal feed, wherein the dosage is in a range of 0.01 - 100 grams per kilogram animal feed.
  • the dosage of ursolic acid or an ester or salt thereof is in a range of 0.01 - 50 grams per kg animal feed, more preferably in a range of 0.01 - 20 grams per kg animal feed, more preferably in a range of 0.01 - 10 grams per kg animal feed, more preferably in a range of 0.01 - 5 grams per kg animal feed, even more preferably in a range of 0.01 - 3 grams per kg animal feed.
  • animal feed can be formulated in many different ways, which means supplements can be added to the feed in different ways.
  • ursolic acid or an ester or salt thereof is added to an animal feed as a top dress formulation.
  • Top dresses are typically added to the feed in a certain amount per kilogram feed.
  • a non-limiting example is the addition of 100 grams of top dress to 1 kg of feed. In that case, for a dosage of 0.2 gram ursolic acid per kg of feed, 100 grams of top dress should contain 2 grams of ursolic acid in order to formulate the necessary dose per kilogram feed.
  • feed is formulated containing 0.4 grams of ursolic acid per kilogram feed, by the use of 50 grams of a top dress formulation per kilogram of feed, the top dress formulation should contain 8 grams of ursolic acid in 50 grams of top dress.
  • the top dress may comprise one or more additional components in addition to the composition as taught herein. These one or more additional components may serve as a carrier material for the composition as taught herein. Non-limiting examples of the one or more additional components are barley, wheat, corn, wheat bran, molasses, vegetable oil, sugar, chalk and the like. In an embodiment, the top dress comprises the composition as taught herein without one or more additional components.
  • the top dress comprises the composition as taught herein, wherein the dosage of the composition is 0.1 - 100%, based on the total weight of the said top dress, preferably the dosage of the composition is 0.2 - 75%, based on the total weight of the said top dress, more preferably the dosage of the composition is 0.3 - 50%, based on the total weight of the said top dress, more preferably the dosage of the composition is 0.4 - 30%, based on the total weight of the said top dress, even more preferably the dosage of the composition is 0.5 - 20%, based on the total weight of the said top dress, most preferably the dosage of the composition is 0.6 - 10%, based on the total weight of the said top dress.
  • ursolic acid or an ester or salt thereof may be added to an animal feed by direct addition of the composition in the feed formulation process, or by the use of a supplement or premix.
  • a premix which is a complex mixture of compounds, may be incorporated in feed in certain percentages during the feed formulation process. The poration can vary from one feed to the other.
  • a non-limiting example is a feed comprising 1 gram ursolic acid per kg feed, formulated by addition of 1 % of premix into the animal feed.
  • the premix should contain 100 grams of ursolic acid for 1 kilogram of premix, in order to end up with a dosage of 1 gram of ursolic acid per kilogram feed.
  • the supplement or premix may comprise one or more additional components in addition to the composition as taught herein. These one or more additional components may serve as a carrier material for the composition as taught herein.
  • additional components are vitamins, minerals, trace elements, supplements, other nutritional additives, chalk and the like.
  • the supplement or premix comprises the composition as taught herein without one or more additional components.
  • the supplement or premix comprises the composition as taught herein, wherein the dosage of the composition is 5 - 100%, based on the total weight of the said supplement or premix, preferably the dosage of the composition is 3 - 90%, based on the total weight of the said supplement or premix, more preferably the dosage of the composition is 6 - 80%, based on the total weight of the said supplement or premix, more preferably the dosage of the composition is 9 - 70%, based on the total weight of the said supplement or premix, even more preferably the dosage of the composition is 15 - 60%, based on the total weight of the said supplement or premix, most preferably the dosage of the composition is 20 - 45%, based on the total weight of the said supplement or premix.
  • the ursolic acid or an ester or salt thereof is added to an animal drinking water wherein the dosage is in a range of 0.01 - 100 grams per liter of animal drinking water.
  • the dosage of ursolic acid or an ester or salt thereof is in a range of 0.01 - 50 grams per liter animal drinking water, more preferably in a range of 0.01 - 20 grams per liter animal drinking water, more preferably in a range of 0.01 - 10 grams per liter animal drinking water, more preferably in a range of 0.01 - 5 grams per liter animal drinking water, even more preferably in a range of 0.01 - 3 grams per liter animal drinking water.
  • composition as taught herein may be added to the diet of animals by adding part of the daily dose to the animal feed and the other part of the daily dose to the drinking water.
  • no measures have been taken to control release of the ursolic acid, salt or ester thereof in the animal body.
  • said animal feed, ingredient, supplement or premix is essentially free or free from a coating such as an enteric coating, or any other coating or measures controlling its release.
  • the invention relates to a method of producing a composition for feeding a pregnant mammal, said method comprising mixing ursolic acid or an ester or salt thereof in immediate release form, with one or more feed components or one or more feed D produce the animal feed or drinking water taught herein, wherein the amount of ursolic acid or an ester or salt thereof is intended to provide a dosage in a range of 0.01 - 100 grams per day.
  • the invention relates to a method of feeding a pregnant mammal, preferably a pregnant monogastric mammal, more preferably a pregnant sow, or a method to produce a composition as taught herein for a pregnant mammal, preferably a monogastric mammal, more preferably a sow, wherein the composition is selected from a group consisting of a top dress formulation, an animal feed, a premix, a supplement, and an animal drinking water.
  • the composition as taught herein is administered to the pregnant mammal in a period from about 45 days prior to parturition until parturition. In an embodiment, the composition as taught herein is administered to the pregnant mammal in a period from about 40 days prior to parturition until parturition. In an embodiment, the composition as taught herein is administered to the pregnant mammal in a period from about 35 days prior to parturition until parturition.
  • the invention relates to the use of a composition as taught herein in a diet for a pregnant mammal, preferably a pregnant monogastric mammal, preferably a pregnant sow, wherein the dosage of ursolic acid or an ester or salt thereof is in a range of 0.01 - 100 grams per day.
  • a composition as taught herein can be used for non-medical as well as medical purposes.
  • the invention relates to use of a composition as taught herein, for increasing the colostrum production. It is known to the person skilled in the art that the offspring consumes more colostrum if more colostrum is available to the newborn animals. A higher colostrum uptake by the litter therefore means that more colostrum was produced by the pregnant animal.
  • the invention relates to use of a composition as taught herein, for increasing average daily gain of offspring of a pregnant mammal, preferably a pregnant monogastric mammal, more preferably a pregnant sow.
  • the invention relates to a composition as taught herein, for use in improving neonatal survival of offspring of a pregnant mammal, preferably a pregnant monogastric mammal, more preferably a pregnant sow.
  • the invention relates to a composition as taught herein, for use in increasing numbers of weaned offspring of a pregnant mammal, preferably a pregnant monogastric mammal, more preferably a pregnant sow.
  • the composition taught herein may be administered to the animal for enhancing mammary gland development.
  • composition taught herein may be administered to the animal for increasing mammary gland tissue mass.
  • the composition taught herein is administered to the animal only during gestation, preferably in a period from about 45 days prior to parturition up to parturition, more preferably in a period from about 40 days prior to parturition until parturition, more preferably in a period from about 35 days prior to parturition until parturition.
  • the composition taught herein is selected from a group consisting of a top dress formulation, an animal feed, a premix, a supplement, and an animal drinking water.
  • Sows of different parities were equally distributed across treatments (control, ursolic acid).
  • the normal diet was fed at approximately 3 kg/day.
  • the top dress was formulated from barley, wheat, corn, wheat bran, molasses, vegetable oil, and sugar.
  • piglets were weighed immediately as they were born, and again at 24 h after birth, to estimate colostrum intake based on the algorithm developed by Theil et al. (Mechanistic model to predict colostrum intake based on deuterium oxide dilution technique data and impact of gestation and prefarrowing diets on piglet intake and sow yield of colostrum. J. Anim. Sci. 2014, 92:5507-5519).
  • piglets were weighed again and the number in each litter was assessed. At weaning, number of piglets per litter was assessed. r litter was increased for sows that were fed ursolic acid in gestation. The neonatal mortality and the total mortality before weaning was reduced for sows that were fed ursolic acid during gestation. As a result, the number of piglets weaned per litter was increased for sows in the ursolic acid treatment (Table 1). The average daily gain per litter was increased as well.

Abstract

La présente invention concerne le domaine de la maximisation des performances d'animaux, en particulier de mammifères gravides et de leur descendance, en particulier de truies gravides et de leur descendance. En particulier, la présente invention concerne le domaine de l'augmentation de la production de colostrum, l'augmentation du gain quotidien moyen de la progéniture, l'amélioration de la survie néonatale de la progéniture et/ou l'augmentation du nombre de descendance sevrée.
PCT/EP2020/082755 2019-11-19 2020-11-19 Procédé d'alimentation d'un animal gravide WO2021099507A1 (fr)

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EP19210162.4 2019-11-19

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Citations (2)

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CN102578387A (zh) * 2012-02-03 2012-07-18 北京大北农科技集团股份有限公司 一种用于畜禽饲料的缓释复合酸化剂及其制备方法与饲料
CN106036122A (zh) * 2016-08-03 2016-10-26 董标 一种母猪产前营养饲料

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102578387A (zh) * 2012-02-03 2012-07-18 北京大北农科技集团股份有限公司 一种用于畜禽饲料的缓释复合酸化剂及其制备方法与饲料
CN106036122A (zh) * 2016-08-03 2016-10-26 董标 一种母猪产前营养饲料

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