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WO2024097601A1 - Procédé de réduction de la boiterie et d'amélioration de la minéralisation osseuse chez le porc - Google Patents

Procédé de réduction de la boiterie et d'amélioration de la minéralisation osseuse chez le porc Download PDF

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Publication number
WO2024097601A1
WO2024097601A1 PCT/US2023/077994 US2023077994W WO2024097601A1 WO 2024097601 A1 WO2024097601 A1 WO 2024097601A1 US 2023077994 W US2023077994 W US 2023077994W WO 2024097601 A1 WO2024097601 A1 WO 2024097601A1
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Prior art keywords
swine
feed
nitrate
fed
combinations
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Inventor
Marc Guillaume Ionam David DECOUX
Richard Joel FARIS
Kaat Fransie Gusta GORIS
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CAN Technologies Inc
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CAN Technologies Inc
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Priority to EP23813222.9A priority Critical patent/EP4611554A1/fr
Priority to KR1020257014269A priority patent/KR20250099142A/ko
Publication of WO2024097601A1 publication Critical patent/WO2024097601A1/fr
Priority to MX2025005052A priority patent/MX2025005052A/es
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • 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
    • 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
    • A23K20/111—Aromatic compounds
    • 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
    • A23K20/116—Heterocyclic compounds
    • A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • 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
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/24—Compounds of alkaline earth metals, e.g. magnesium
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/15—Inorganic Compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A23V2250/2132—Other phenolic compounds, polyphenols

Definitions

  • This application relates to methods for reducing lameness in swine that includes feeding to the swine a feed that includes a nitrate compound.
  • Feeding calcium nitrate and other ingredients to livestock is one way to mitigate methane production.
  • U.S. Patent No. 8,771,723 titled “Compositions For Reducing Gastro-Intestinal Methanogenesis In Ruminants” issued to Hindrik Bene Perdok et al. discloses one such method.
  • Van Den Bosch et al. International Patent Application Publication No. WO 2016/090366, published June 9, 2016
  • Ascensao et al. International Patent Application Publication No. WO 2018/237233 describes methods of improving meat quality (such as meat color and carcass yield (%)) in an animal by feeding an effective amount of nitrate to the animal.
  • nitrate in humans, dietary nitrate, as presented in beetroot juice, has been shown to reduce blood pressure and the risk of adverse cardiovascular events in healthy individuals after single dose of 500 ml of beetroot juice. It is hypothesized that nitrate might represent a source of vasoprotective nitric oxide (NO) via bioactivation (Webb et al. 2008). A non-enzymatic pathway for the generation of NO has been proposed (nitrate-nitrite-NO pathway) for humans. Dietary inorganic nitrate molecules may be reduced by facultative anaerobic bacteria on the dorsal surface of the tongue to nitrite which can be chemically and enzymatically be further reduced to NO (Lundberg et al.
  • the endothelial isoform of the NO synthase uses arginine and molecular oxygen as precursors to tonically release NO in the endothelium, which is important for the control of vascular tone, smooth muscle growth, platelet aggregation and inflammation (Umans and Levi, 1995; Bruckdorfer 2005). This induces vasodilation and increased blood flow (Siervo et al. 2011; Keim 1999).
  • Pig farm efficiency can be defined in different ways. For reproducers, one indicator is longevity, measured with respect to the culling age for a sow. Longevity is reduced when sows are culled for lameness. Lameness is the second cause for culling in modem sow farms (Supakorn et al., 2022; Phuym et al., 2013) in modern genetic breed. Leg pain is one contributor to lameness, which is a result of heavy weight in swine. Gilts and primiparous sows are highly sensitive to this problem due to the fast growth rate of modern genetics.
  • the present invention is directed to methods of feeding pigs at key moments in their life cycle a specific dose of a swine feed or feed supplement that includes nitrate compounds with or without polyphenols. As a result, bones development is stimulated, which supports higher sow longevity.
  • the present technology provides a method for method of feeding swine, the method includes: feeding swine a swine feed that includes about 0.01 weight percent (wt%) to about 0.5 wt% per day of a nitrate compound, hydrates thereof, salts thereof, or combinations thereof, and optionally an antioxidant that includes polyphenols; wherein swine fed the swine feed exhibit a reduced occurrence of joint lesions compared to a control swine not fed the swine feed.
  • reference to weight percent (wt%) per day is based on total weight of swine fed as part of the swine’s daily feed intake.
  • the present technology provides a method for improving bone development in swine, the method comprising: feeding swine a swine feed, wherein the swine feed comprises: a nitrate compound, hydrates thereof, salts thereof, or combinations thereof; and optionally an antioxidant comprising polyphenols; wherein: the swine is fed a daily feed intake comprising an amount of nitrate in a range of about 0.01% by weight to less than about 0.5% by weight based on total weight of the swine feed; the method improves bone mineral deposition in swine fed the swine feed compared to a control swine not fed the swine feed.
  • the present technology provides the use of a swine feed as described herein in any aspect for increasing bone mineral deposition and/or reducing the occurrence of joint lesions in swine compared to a control swine not fed the swine feed, wherein the swine feed comprises a nitrate compound, hydrates thereof, salts thereof, or combinations thereof, and optionally an antioxidant that include polyphenols, and wherein the daily feed intake amount of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof is about 0.01% by weight to less than about 0.5% by weight based on total weight of the swine feed.
  • values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited.
  • a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range.
  • the terms "for example,” “for instance,” “such as,” or “including” are meant to introduce examples that further clarify more general subject matter. Unless otherwise specified, these examples are provided only as an aid for understanding the applications illustrated in the present disclosure, and are not meant to be limiting in any fashion. [0014] In the methods described herein, the acts can be carried out in a specific order as recited herein. Alternatively, in any aspect(s) disclosed herein, specific acts may be carried out in any order without departing from the principles of the disclosure, except when a temporal or operational sequence is explicitly recited. Furthermore, specified acts can be carried out concurrently unless explicit claim language recites that they be carried out separately or the plain meaning of the claims would require it. For example, a claimed act of doing X and a claimed act of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process.
  • substantially refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%.
  • mammals as used in this disclosure includes monogastric and ruminant animals.
  • the term “monogastric” means any organism having a simple single-chambered stomach. Such monogastric animals include, but are not limited to, porcine, equine, avian animals, seafood (aquaculture) animals.
  • Porcine monogastric animals refers to domesticated swine (or pigs) and wild boars.
  • Swine include, but are not limited to, feeder pigs and breeder pigs, including piglets, sows, gilts, barrows, and boars.
  • Gilts refers to female pigs intended for slaughter or breeding purposes that have not yet farrowed a litter.
  • Arrows refers to castrated male pigs intended for slaughter, whereas “boars” as used herein refers to intact, sexually mature, male pigs intended for breeding purposes.
  • Swine production can be logically separated into a number of phases.
  • the stages include, breeding and gestation, farrowing, weaning, growing or growth, and finishing or finisher phases.
  • the stages described herein may vary across geographies as understood by persons skilled in the art, and the definitions provided herein provide exemplary descriptions, that include but are not limited to, weights, ages, and development stages in swine production.
  • breeding and Gestation The sow is bred during her estrous period. In the phase between weaning the sow and breeding, a special breeding feed can be fed to the sow. After breeding, the sow “gestates” her litter for 113 to 116 days before the piglets are born or “farrowed.” As used herein, the term “gestation” or gestation phase means the 113 to 116 day period when the sow is pregnant from breeding until farrowing.
  • Farrowing The process of giving birth is called farrowing. Typically, sows are moved to a farrowing room a few days prior to farrowing and farrow about eight to fourteen piglets (as a group called a “litter”). The piglets are born weighing about 1.5 kg at birth.
  • the term “farrowing” means birth
  • the term “farrowing phase” means the period from birth to weaning. The period of time called the transition period is typically seven days prefarrowing until one to five days post farrowing.
  • the piglets stay with the lactating sow for about 19-35 days after farrowing, during which time the piglets drink milk produced by the lactating sow.
  • weaning means the process of separating the piglets from the sow. During a weaning or nursery phase, the piglets remain in the nursery — for example, until about four to eight weeks after farrowing (or in other instances, up to about 18 kg to about 30 kg).
  • Postweaning as used herein means the period following the weaning or nursery phase — typically at about six to ten weeks of age where the pig is fed a transitioning diet and before being fed a suitable grower/finishing phase diet based on the pigs age and weight.
  • Pigs are normally placed in a grow-fini shing building until they reach market weight, following the weaning (or nursery) phase.
  • “Growing phase” or “growth phase” as used herein refers to the stage where pigs starting from about 35 pounds to 60 pounds (-16-27 kg) are fed to a body weight of about 120 to about 165 pounds (-54-75 kg).
  • “Finishing phase” or “finisher phase” as used herein refers to the stage where pigs are fed from about 120 to 150 pounds (-54-68 kg) are fed to a market body weight — typically about 200 to about 309 pounds (-91-140 kg), and preferably about 243 pounds to about 309 pounds (—110- 140 kg).
  • nitrate compound refers to any material including one or more nitrate-containing compounds suitable for use in swine feed.
  • nitrate compounds as described in any aspect herein may be any suitable nitrate-containing compound.
  • a suitable nitrate-containing compound may be defined as any physiologically acceptable or tolerated nitrate compound.
  • the nitrate compound may be well-soluble in water, z.e., the compound has sufficient solubility for bioavailability after administration to the swine.
  • the nitrate compound may be an ionic nitrate compound, preferably an inorganic nitrate salt.
  • the ionic nitrate salts may include, but are not limited to, sodium nitrate, potassium nitrate, calcium nitrate, magnesium nitrate, ammonium nitrate, or mixtures thereof, all of which are readily soluble in water at standard temperature (e.g., 0°C (32°F)) and pressure (e.g., 1 bar).
  • the ionic nitrate salt may be calcium nitrate.
  • the ionic nitrate salts may include different hydrated forms.
  • the ionic nitrate salts may also include double salts (e.g., calcium nitrate and ammonium nitrate). In any aspect described herein, a mixture of two or more different ionic nitrate salts or salt forms may be used in the method.
  • nitrate is a source for the biological messenger nitric oxide (NO) according to a non-enzymatic pathway for the generation of NO (nitrate-nitrite-NO pathway).
  • NO biological messenger nitric oxide
  • nitrate-nitrite-NO pathway Unlike arginine conversion to nitric oxide, nitrate conversion to nitric oxide via the nitrate-nitrite-NO pathway is not dependent upon oxygen levels. It is believed that the release of NO in the animal is important for the control of vascular tone, smooth muscle growth, platelet aggregation and inflammation. The release of NO in the animal is believed to induce vasodilation and increased blood flow and exchange of oxygen.
  • vasodilation is one biological pathway affected by nitrate supplementation
  • vasodilation does not account for all improvements observed following nitrate supplementation and can vary based on a number of factors (e.g., species, age, feed, etc.).
  • nitric oxide has also been shown increase bone formation and bone mineral density (van’t Hof and Ralston, 2001). Accordingly, outcomes can vary across species (or within a species) fed a feed containing nitrates.
  • the nitrate compound may be provided as calcium nitrate having the formula Ca(NCh)2.
  • Calcium nitrate is also referred to as calcium dinitrate, Kalksalpeter, nitrocalcite, Norwegian saltpeter, and lime nitrate.
  • Calcium nitrate may be produced by treating limestone with nitric acid, according to the reaction: CaCCh + 2HNCh Ca(NCh)2 + CO2 + H2O.
  • the one or more nitrates may be provided as an inorganic salt of magnesium nitrate hexahydrate having the formula (Mg(NO3)2*6H2O). This product contains 10.8% N from nitrate and 9.5% Mg.
  • a variety of related complex inorganic salts of calcium nitrate include calcium ammonium nitrate decahydrate and calcium potassium nitrate decahydrate.
  • Calcium ammonium nitrate is a double salt (calcium nitrate and ammonium nitrate) having the formula 5Ca(NO3)2*NH4NO3*10H2O.
  • the calcium ammonium nitrate may be pentacalcium ammonium nitrate decahydrate commercially available from Bri-Chem Supply Limited with the following specification: Ammonium-N (NH4-N): 1.1%; Nitrate-N (NO3-N): 14.4%; Total N: 15.5%; Calcium (Ca): 18.8%.
  • the calcium nitrate may be BOLIFOR CNF calcium nitrate feed grade having the formula SCafNChC’NILNCh’ I OFhO commercially available from Yara Phosphates Oy of Helsingborg Sweden.
  • the calcium nitrate may have the following specification: Calcium (Ca): 18.9%; Nitrogen (N) 15.5%; pH (10% solution): 6; bulk density (kg/m 3 ): 1050; appearance: prilled; size: ⁇ 1.0 mm: 2%; 1.0-2.0 mm: 78%; >2 mm: 20%.
  • Exemplary formulations of calcium nitrate lacking ammonia include Ca(NO3)2*4H2O.
  • An exemplary anhydrous air-stable derivative of calcium nitrate may include urea complex Ca(NO3)2*4[OC(NH2)2].
  • Antioxidants when included in swine diets, are known to protect cells from damage caused by free radicals and peroxides.
  • antioxidants available for feeding swine, including natural dietary antioxidants.
  • natural antioxidants may include, but are not limited to, vitamins, minerals, carotenoids, and polyphenols.
  • the antioxidant preferably includes polyphenols.
  • Suitable polyphenol sources may include, but are not limited to, fruits (such as apples, apricots, currants, blackberries, blueberries, cherries, chokeberries, cranberries, dates, elderberries, gooseberries, grapes, kiwis, lemons, lingonberries, limes, mangoes, marionberries, nectarines, olives, oranges, peaches, pears, plums, pomegranates, quinces, raspberries, rhubarb, strawberries, tomatoes, or mixtures thereof), vegetables (such as artichokes, broccoli, celery, corn, eggplant, fennel, garlic, greens, kohlrabi, leeks, lovage, onions, parsnips, peppers, spinach, red cabbage, rutabagas, scallions, shallots, sweet potatoes, watercress, or mixtures thereof), legumes (such as chick peas, beans, lentils, snap beans, English peas, green
  • a polyphenol source suitable for use in any aspect of the present technology may include commercially available sources.
  • a polyphenol source is commercially available under the trade name PROVIOX 50, available from Cargill, Incorporated, Wayzata, MN, USA.
  • the formulation of PROVIOX 50 includes a blend of polyphenol grape seed and skin extracts, onion extracts, and rosemary extracts.
  • PROVIOX 50 is a standardized product for its total polyphenol content.
  • PROVIOX 50 contains sources of polyphenols with antioxidant properties.
  • the antioxidant that includes polyphenols is PROVIOX 50.
  • swine feed refers to a feed ration produced for consumption by swine.
  • compound feed refers to a swine feed blended to include two or more ingredients which assist in meeting certain daily nutritional requirements of swine, preferably swine in one or more of a postweaning, growth, or finishing phase.
  • the swine feed may be a complete swine feed according to any aspect described herein.
  • the term “complete feed” as used in any aspect described herein refers to a swine feed having a nutritionally balanced blend of ingredients designed as the sole ration to provide all the daily nutritional requirements of a swine to maintain life and promote production without any additional substances being consumed except for water.
  • the swine feed may also be a concentrate swine feed according to any aspect described herein.
  • concentrate feed or “concentrate swine feed” as used herein in any aspect described herein refers to a swine feed that typically includes a protein source blended with supplements or additives or vitamins, trace minerals, other micro ingredients, macro minerals, etc. to provide a part of the ration for the swine.
  • the concentrate feed may be fed along with other ingredients.
  • the swine feed may include a premix according to any aspect described herein.
  • premix refers to a blend of primarily vitamins and/or minerals along with appropriate carriers.
  • the swine feed may also include a base mix according to any aspect described herein.
  • base mix refers to a blend containing vitamins, trace minerals and/or other micro ingredients plus macro minerals such as calcium, phosphorus, sodium, magnesium, and potassium, vitamins, or combinations thereof.
  • the swine feed may be a feed “supplement.”
  • feed supplement or “swine feed supplement” refers to a concentrated additive premix that includes the active ingredients, which premix or supplement may be added to a swine’s feed or ration to form a supplemented feed in accordance with the present technology.
  • additive or “feed additive” refers to an ingredient such as a protein source, salt, mineral, additive, or buffer that is added to a swine feed.
  • an additive may include, but is not limited to, calcium, zinc, manganese, copper, iodine, cobalt, selenium, other trace ingredients, or mixtures thereof.
  • nitrate in the daily feed intake of swine significantly improved bone development (i.e., bone mineralization measured as metacarpals bone ash content(published method according to Adeola et al., 2015)) of the swine compared to swine fed a conventional feed that does not include exogenous nitrate.
  • the inventors surprisingly discovered the occurrence of joint lesions is significantly reduced in swine fed a daily amount of nitrate compared to swine fed a conventional feed.
  • joint lesions refers to swelling and puffiness around the joints of the pigs.
  • the present technology provides a method for method of feeding swine, the method includes: feeding swine a swine feed that includes about 0.01 weight percent (wt%) to about 0.5 wt% per day of a nitrate compound, hydrates thereof, salts thereof, or combinations thereof, and optionally an antioxidant that includes polyphenols; wherein swine fed the swine feed exhibit a reduced occurrence of joint lesions compared to a control swine not fed the swine feed.
  • reference to weight percent (wt%) per day is based on total weight of swine fed as part of the swine’s daily feed intake.
  • swine may be in one or more of a post- weaning, growth, or finishing phase encompasses gilts, barrows, boars, or combinations thereof.
  • gilts may be housed separately from barrows and/or boars during post-weaning, growth, and/or finishing phases.
  • the swine may include gilts, barrows, boars, or combinations thereof.
  • the swine may be gilts.
  • the swine may be barrows.
  • the swine may be boars.
  • the swine may be a reproducing swine.
  • the reproducing swine may be a sow (such as nullparous sow, primiparous sow, or multiparous sow).
  • the swine may be fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof during a growth phase, finishing phase, or combination thereof. In any aspect, the swine may be fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof during a growth phase. In any aspect, the swine may be fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof during a finishing phase. [0040] In any aspect, the swine may be fed a daily swine feed intake that includes an amount of nitrate in a range of about 0.01% by weight to about 0.50% by weight based on total weight of a swine feed.
  • the daily feed intake amount of nitrate fed to the swine may be in a range of about 0.02% by weight to about 0.35% by weight based on total weight of the swine feed. In any aspect, the daily feed intake amount of nitrate fed to the swine may be about 0.03% by weight to about 0.25% by weight based on total weight of the swine feed. In any aspect, the daily feed intake amount of nitrate fed to the swine may be about 0.05% by weight to about 0.2% by weight based on total weight of the swine feed.
  • the daily feed intake amount of nitrate fed to the swine may be about 0.07% by weight to about 0.15% by weight based on total weight of the swine feed.
  • suitable amounts of nitrate compound present in the swine’s daily feed intake may be about 0.01wt%, about 0.015 wt%, about 0.02 wt%, about 0.025 wt%, about 0.03 wt%, about 0.035 wt%, about 0.04 wt%, about 0.045 wt%, about 0.05 wt%, about 0.055 wt%, about 0.06 wt%, about 0.065 wt%, about 0.07 wt%, about 0.075 wt%, about 0.08 wt%, about 0.085 wt%, about 0.09 wt%, about 0.1 wt%, about 0.15 wt%, about 0.2 wt%, about 0.25 wt%, about 0.3 wt
  • the nitrate compound may include an ionic nitrate salt as described herein.
  • the nitrate compound may include an ionic nitrate salt selected from sodium nitrate, potassium nitrate, calcium nitrate, magnesium nitrate ammonium nitrate, or mixtures thereof.
  • the nitrate compound may be calcium nitrate, complex inorganic salts of calcium nitrate, hydrates thereof (e.g., calcium nitrate dihydrate, calcium nitrate tetrahydrate, calcium nitrate decahydrate), or mixtures thereof.
  • the nitrate compound may be calcium ammonium nitrates, or hydrates thereof (e.g. 4 5Ca(NO3)2*NH4NO3*10H2O).
  • the nitrate compound may also be provided by a variety of plant ingredients according to alternative aspects.
  • plant ingredients may include, but are not limited to, leafy greens such as spinach, arugula, beetroot, or mixtures thereof.
  • the plant ingredient is beetroot.
  • Beetroot has an inorganic nitrate content typically ranging from 110 to 3670 mg nitrate/kg.
  • the method reduces the occurrence of joint lesions in swine fed the swine feed by up to about 65% compared to a control swine not fed the swine feed. In any aspect, the method reduces the occurrence of joint lesions in swine fed the swine feed by at least about 1% to about 65% compared to a control swine not fed the swine feed. In any aspect, the method reduces the occurrence of joint lesions in swine fed the swine feed by about 5% to about 50% compared to a control swine not fed the swine feed.
  • the method reduces the occurrence of joint lesions in swine fed the swine feed by about 40% to about 60% compared to a control swine not fed the swine feed.
  • the method may reduce the occurrence of joint lesions in swine fed the swine feed by at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, or 40% and up to about 65%, 64%, 63%, 62%, 61%, 60%, 59%, 58%, 57%, 56%, 55%, 54%, 53%, 52%, 51%, 50%, 49%, 48%, 47%,
  • the method may reduce the occurrence of lameness in swine.
  • the method may further include feeding the swine antioxidants that include polyphenols (e.g., quercetin).
  • the swine feed may further include antioxidants that include the polyphenols.
  • Polyphenols are known to those of skill in the art for their free radical scavenging function. Without being bound by any particular theory, it is believed that dietary polyphenols at gastric pH may enhance the formation of nitric oxide. (Rocha et al., Food Funct., 2014, 5: 1646-1652).
  • Suitable sources of polyphenols may include polyphenols extracted from fruits, vegetables, legumes, nuts, seeds, tea, herbs, spices, tree barks, or mixtures thereof.
  • the polyphenols may be from polyphenol sources including onion extract, grape seed extract, grape skin extract, rosemary extract, or mixtures thereof.
  • the polyphenols may be PROVIOX 50 (Cargill, Incorporated).
  • the polyphenols as described herein may be fed to the swine in an amount of about 1 ppm to about 500 ppm per day. Suitable amounts of the polyphenols may include about 1 ppm to about 500 ppm, about 5 ppm to about 500 ppm, about 10 ppm to about 500 ppm, about 50 ppm to about 300 ppm, about 75 ppm to about 250 ppm, about 90 ppm to about 150 ppm, or any range including and/or in between any two of the preceding values.
  • the antioxidants may further include natural antioxidants, other than polyphenols.
  • the antioxidants may include vitamins, minerals, carotenoids, or mixtures thereof.
  • Vitamins may include, but are not limited to, vitamin A (including vitamin A sources such as vitamin A supplement, vitamin A oil, etc.) vitamin Bl, vitamin B2, vitamin B3, vitamin B4, vitamin B5, vitamin B6, vitamin B7, vitamin B8, vitamin B9, vitamin B 12, vitamin C, Vitamin D, (including vitamin D sources such as vitamin D supplement, etc.), vitamin E (including vitamin E sources such as Vitamin E supplement), vitamin K, and other vitamin product ingredients (including riboflavin, vitamin D3 supplement, niacin, betaine, choline chloride, tocopherol, inositol, etc.).
  • the vitamins may preferably be vitamins E, vitamins C, or combinations thereof.
  • Minerals may include, for example and without limitation, calcium, chlorine (as chloride ions), magnesium, phosphorus, potassium, sodium, sulfur, cobalt, copper, chromium, iodine, manganese, molybdenum, nickel, selenium vanadium, zinc, or mixtures thereof.
  • the minerals may preferably be selenium, zinc, manganese, copper, or mixtures thereof.
  • the present technology provides a method for improving bone development in swine, the method comprising: feeding swine a swine feed, wherein the swine feed comprises: a nitrate compound, hydrates thereof, salts thereof, or combinations thereof; and optionally an antioxidant comprising polyphenols; wherein: the swine is fed a daily feed intake comprising an amount of nitrate in a range of about 0.01% by weight to less than about 0.5% by weight based on total weight of the swine feed; the method improves bone mineral deposition in swine fed the swine feed compared to a control swine not fed the swine feed.
  • the swine may be fed a daily swine feed intake that includes an amount of nitrate in a range of about 0.01% by weight to about 0.50% by weight based on total weight of a swine feed.
  • the daily feed intake amount of nitrate fed to the swine may be in a range of about 0.02% by weight to about 0.35% by weight based on total weight of the swine feed.
  • the daily feed intake amount of nitrate fed to the swine may be about 0.03% by weight to about 0.25% by weight based on total weight of the swine feed.
  • the daily feed intake amount of nitrate fed to the swine may be about 0.05% by weight to about 0.2% by weight based on total weight of the swine feed. In any aspect, the daily feed intake amount of nitrate fed to the swine may be about 0.07% by weight to about 0.15% by weight based on total weight of the swine feed.
  • suitable amounts of nitrate compound present in the swine’s daily feed intake may be about 0.01wt%, about 0.015 wt%, about 0.02 wt%, about 0.025 wt%, about 0.03 wt%, about 0.035 wt%, about 0.04 wt%, about 0.045 wt%, about 0.05 wt%, about 0.055 wt%, about 0.06 wt%, about 0.065 wt%, about 0.07 wt%, about 0.075 wt%, about 0.08 wt%, about 0.085 wt%, about 0.09 wt%, about 0.1 wt%, about 0.15 wt%, about 0.2 wt%, about 0.25 wt%, about 0.3 wt%, about 0.35 wt%, about 0.4 wt%, about 0.45 wt%, about 0.5 wt%, or any range including and/or in between any two of the preceding
  • the nitrate compound may include an ionic nitrate salt as described herein.
  • the nitrate compound may include an ionic nitrate salt selected from sodium nitrate, potassium nitrate, calcium nitrate, magnesium nitrate ammonium nitrate, or mixtures thereof.
  • the nitrate compound may be calcium nitrate, complex inorganic salts of calcium nitrate, hydrates thereof (e.g., calcium nitrate dihydrate, calcium nitrate tetrahydrate, calcium nitrate decahydrate), or mixtures thereof.
  • the nitrate compound may be calcium ammonium nitrates, or hydrates thereof (e.g. 4 5Ca(NO3)2*NH4NO3*10H2O).
  • the nitrate compound may also be provided by a variety of plant ingredients according to alternative aspects.
  • plant ingredients may include, but are not limited to, leafy greens such as spinach, arugula, beetroot, or mixtures thereof.
  • the plant ingredient is beetroot.
  • Beetroot has an inorganic nitrate content typically ranging from 110 to 3670 mg nitrate/kg.
  • the method of the present technology may increase bone mineral deposition in swine fed the swine feed, as described herein in any aspect, compared to a control swine not fed the swine feed.
  • bone mineral deposition may be measured as metacarpals bone ash content.
  • bone mineral deposition may be measured as metacarpals bone ash content after slaughter.
  • the method increases bone mineral deposition in swine fed the swine feed by at least about 0.5% compared to a control swine not fed the swine feed. In any aspect, the method may increase bone mineral deposition in swine fed the swine feed by at least about 0.5% to about 10% compared to a control swine not fed the swine feed. In any aspect, the method may increase bone mineral deposition in swine fed the swine feed by about 1% to about 8% compared to a control swine not fed the swine feed.
  • the method may increase bone mineral deposition in swine fed the swine feed by about 4% to about 7% compared to a control swine not fed the swine feed.
  • the method may increase bone mineral deposition in swine fed the swine feed by at least about 0.05%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or up to about 10%, or any range including and/or in between any two of the preceding values.
  • the method may further reduce the occurrence of or prevent lameness in swine fed the swine feed compared to a control swine not fed the swine feed.
  • the swine feed may be a premix, a feed additive, a feed supplement, a compound feed, or a complete feed as described herein.
  • the swine feed may be a composition that includes an amount of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof fed to the swine before, during, or after providing the swine a feed that does not include nitrate.
  • the swine feed comprising the nitrate compound, hydrates thereof, salts thereof, or combinations thereof may be provided in a supplement separately from the feed or is provided in a supplement that is mixed with the feed.
  • the amount of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof would typically be different from the final swine feed, z.e., the supplement may include a higher concentration of the nitrate compound compared to the final swine feed itself such that the daily feed intake of the swine fed the final swine feed is from about 0.01% by weight to about 0.5% by weight based on total weight of the swine feed.
  • the method may further include feeding the swine antioxidants that include polyphenols (e.g., quercetin).
  • polyphenols e.g., quercetin
  • Polyphenols are known to those of skill in the art for their free radical scavenging function.
  • Suitable sources of polyphenols, as described herein, may include polyphenols extracted from fruits, vegetables, legumes, nuts, seeds, tea, herbs, spices, tree barks, or mixtures thereof.
  • the polyphenols may be from polyphenol sources including onion extract, grape seed extract, grape skin extract, rosemary extract, or mixtures thereof.
  • the polyphenols may be PROVIOX 50 (Cargill, Incorporated).
  • the polyphenols as described herein may be fed to the swine as part of the swine feed in an amount of about 1 ppm to about 500 ppm per day. Suitable amounts of the polyphenols may include about 1 ppm to about 500 ppm, about 5 ppm to about 500 ppm, about 10 ppm to about 500 ppm, about 50 ppm to about 300 ppm, about 75 ppm to about 250 ppm, about 90 ppm to about 150 ppm, or any range including and/or in between any two of the preceding values.
  • the antioxidants may further include natural antioxidants, other than polyphenols.
  • the antioxidants may include vitamins, minerals, carotenoids, or mixtures thereof.
  • Vitamins may include, but are not limited to, vitamin A (including vitamin A sources such as vitamin A supplement, vitamin A oil, etc.) vitamin Bl, vitamin B2, vitamin B3, vitamin B4, vitamin B5, vitamin B6, vitamin B7, vitamin B8, vitamin B9, vitamin B 12, vitamin C, Vitamin D, (including vitamin D sources such as vitamin D supplement, etc.), vitamin E (including vitamin E sources such as Vitamin E supplement), vitamin K, and other vitamin product ingredients (including riboflavin, vitamin D3 supplement, niacin, betaine, choline chloride, tocopherol, inositol, etc.).
  • the vitamins may preferably be vitamins E, vitamins C, or combinations thereof.
  • Minerals may include, for example and without limitation, calcium, chlorine (as chloride ions), magnesium, phosphorus, potassium, sodium, sulfur, cobalt, copper, chromium, iodine, manganese, molybdenum, nickel, selenium vanadium, zinc, or mixtures thereof.
  • the minerals may preferably be selenium, zinc, manganese, copper, or mixtures thereof.
  • the swine may include gilts, barrows, boars, or combinations thereof.
  • the swine may be gilts.
  • the swine may be barrows.
  • the swine may be boars.
  • the swine may be a reproducing swine.
  • the reproducing swine may be a sow (such as nullparous sow, primiparous sow, or multiparous sow).
  • the swine may be fed the swine feed during a growth phase, finishing phase, or combination thereof. In any aspect, the swine may be fed the feed during a growth phase. In any aspect, the swine may be fed the feed during a finishing phase.
  • the present technology provides the use of a swine feed as described herein in any aspect for increasing bone mineral deposition and/or reducing the occurrence of joint lesions in swine compared to a control swine not fed the swine feed, wherein the swine feed comprises a nitrate compound, hydrates thereof, salts thereof, or combinations thereof, and optionally an antioxidant that include polyphenols, and wherein the daily feed intake amount of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof is about 0.01% by weight to less than about 0.5% by weight based on total weight of the swine feed.
  • a method of feeding swine comprising: feeding swine a swine feed comprising about 0.01 weight percent (wt%) to about 0.5 wt% per day of a nitrate compound, hydrates thereof, salts thereof, or combinations thereof, and optionally an antioxidant comprising polyphenols; wherein swine fed the swine feed exhibit a reduced occurrence of joint lesions compared to a control swine not fed the swine feed.
  • Para. B The method of Para. A, wherein the swine is in one or more of a postweaning phase, growth phase, or finishing phase.
  • Para. C The method of Para. A or B, wherein the swine comprises gilts, barrows, boars, or combinations thereof.
  • Para. D The method of Para. A or B, wherein the swine comprises gilts.
  • Para. E The method of Para. A or B, wherein the swine comprises barrows or boars.
  • Para. F The method of any one of Paras. A-E, wherein the swine is in a growth phase or a finishing phase.
  • Para. G The method of Para. A or B, wherein the swine comprises reproducing swine.
  • Para. H The method of Para. G, wherein the reproducing swine is a sow.
  • Para. I The method of any one of Paras. A-H, wherein the daily feed diet comprises about 0.05 wt% to about 0.2 wt% per day of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. J The method of any one of Paras. A-I, comprising feeding the swine about 0.07 wt% to about 0.15 wt% per day of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. K The method of any one of Paras. A- J, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises ionic nitrate salts.
  • Para. L The method of any one of Paras. A-K, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises sodium nitrate, potassium nitrate, calcium nitrate, magnesium nitrate, ammonium nitrate, or mixtures thereof.
  • Para. M The method of any one of Paras. A-L, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises calcium nitrate, complex inorganic salts of calcium nitrate, or mixtures thereof.
  • Para. N The method of any one of Paras. A-M, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises calcium ammonium nitrate, pentacalcium ammonium nitrate decahydrate, or combinations thereof.
  • Para. O The method of any one of Paras. A-N, wherein the method reduces joint lesions in swine by up to about 65% compared to a control swine not fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. P The method of any one of Paras. A-O, wherein the method reduces joint lesions in swine by about 1% to up to about 30% compared to a control swine not fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. Q The method of any one of Paras. A-O, wherein the method reduces joint lesions in swine by about 5% to about 25% compared to a control swine not fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. R The method of any one of Paras. A-O, wherein the method reduces joint lesions in swine by about 15% to about 25% compared to a control swine not fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. S The method of any one of Paras. A-R further comprising feeding the swine about 1 ppm to about 500 ppm per day of an antioxidant comprising polyphenols based on total weight of the swine feed.
  • Para. T The method of Para. S, wherein the polyphenols comprise polyphenols sources selected from the group consisting of onion extract, grape seed extract, grape skin extract, rosemary extract, and mixtures thereof.
  • a method for improving bone development in swine comprising: feeding swine a swine feed, wherein the swine feed comprises: a nitrate compound, hydrates thereof, salts thereof, or combinations thereof; and optionally an antioxidant comprising polyphenols as part of the feed; wherein: the swine is fed a daily feed intake comprising an amount of nitrate is in a range of about 0.01% by weight to less than about 0.50% by weight based on total weight of the swine feed; the method increases bone mineral deposition in swine fed the swine feed compared to a control swine not fed the swine feed.
  • Para. V The method of Para. U, wherein the daily feed intake amount of nitrate is in a range of about 0.05% by weight to about 0.25% by weight of based on total weight of a swine feed.
  • Para. W The method of Para. U or V, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises ionic nitrate salts.
  • Para. X The method of any one of Paras. U-W, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises sodium nitrate, potassium nitrate, calcium nitrate, magnesium nitrate, ammonium nitrate, or mixtures thereof.
  • Para. Y The method of any one of Paras. U-X, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises calcium nitrate, complex inorganic salts of calcium nitrate, or mixtures thereof.
  • Para. Z The method of any one of Paras. U-Y, wherein the nitrate compound, hydrates thereof, salts thereof, or combinations thereof comprises calcium ammonium nitrate, pentacalcium ammonium nitrate decahydrate, or combinations thereof.
  • Para. AA The method of any one of Paras. U-Z, wherein the method increases bone mineralization in the swine by at least about 0.5% compared to a control swine not fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. AB The method of any one of Paras. U-AA, wherein the method improves the feed to gain ratio of the swine by about 0.5% to about 10% compared to a control swine not fed the nitrate compound, hydrates thereof, salts thereof, or combinations thereof.
  • Para. AC The method of any one of Paras. U-AB, wherein bone mineralization in swine is measured as total amount of metacarpals bone ash content present after slaughter.
  • Para. AD The method of any one of Paras. U-AC further comprising feeding the swine about 1 ppm to about 500 ppm per day of an antioxidant comprising polyphenols based on total weigh of the swine feed.
  • Para. AE The method of Para. AD, wherein the polyphenols comprise polyphenols sources selected from the group consisting of onion extract, grape seed extract, grape skin extract, rosemary extract, and mixtures thereof.
  • Para. AF The method of any one of Paras. U-AE, wherein the swine is in a growth phase or a finishing phase.
  • Para. AG The method of any one of Paras. U-AF, wherein the swine comprises gilts, barrows, boars, or combinations thereof.
  • Para. AH The method of any one of Paras. U-AF, wherein the swine feed is a premix, a feed additive, a feed supplement, a compound feed, or a complete feed.
  • Para. Al The method of any one of Paras. A-T or U-AH, wherein the method reduces the occurrence of or prevents lameness in swine fed the swine feed compared to a control swine not fed the swine feed.
  • AJ Use of a swine feed for increasing bone mineral deposition in swine fed the swine feed compared to a control swine not fed the swine feed, wherein the swine feed comprises a nitrate compound, hydrates thereof, salts thereof, or combinations thereof, and optionally an antioxidant comprising polyphenols, and wherein the daily feed intake amount of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof is about 0.01% by weight to less than about 0.5% by weight based on total weight of the swine feed.
  • AK Use of a swine feed for reducing joint lesions in swine fed the swine feed compared to a control swine not fed the swine feed, wherein the swine feed comprises a nitrate compound, hydrates thereof, salts thereof, or combinations thereof, and optionally an antioxidant comprising polyphenols, and wherein the daily feed intake amount of the nitrate compound, hydrates thereof, salts thereof, or combinations thereof is about 0.01% by weight to less than about 0.5% by weight based on total weight of the swine feed.
  • vitamin A 5,000 IU; vitamin D3, 800 IU; vitamin E, 50 IU; vitamin B12, 17.5 pg; menadione, 1.75 mg; folic acid, 0.55 mg; niacin, 25 mg, pantothenic acid, 30 mg; pyroxidine, 1 mg; riboflavin, 4 mg; thiamine, 0.75 mg; copper, 12.6 mg; iron, 77 mg; iodine, 0.49 mg; manganese, 35 mg; zinc, 77 mg; selenium 0.21 mg; phytase, 391 FTU.
  • Experimental diets were made by inclusion of calcium nitrate (CAS # 10124-37- 5; ADOB, Ponzan, PL) at the expense of com and provided as pellets (4 mm). Calcium nitrate was included at 0%, 0.08%, 0.16% and 0.32% of the diet which is equivalent to 0 wt%, 0.05 wt%, 0.10 wt% and 0.20 wt% (0 ppm, 500 ppm, 1000 ppm, and 2000 ppm) supplemental dietary nitrate inclusion, respectively. Experimental diets were fed ad libitum for 28 days. Bodyweights were measured at dO and d28.
  • Bone ash was measured at the University of Wisconsin (Madison, WI) according to the method of Adeola et al. (2015). Briefly, the hooves were thawed, and the 3rd metacarpal was dissected out and cleaned. Bones were dried, defatted with petroleum ether, and dried again. Thereafter, bones were ashed in a muffle furnace. Ash weight was recorded as percent of dry fat free bone.
  • Example 2 Evaluation of Dietary Nitrate Effect on Bone Mineralization and Joint Lesion Occurrence.
  • phase feeding program 40-100 kg with 16% crude protein, 1.02% total lysine, and 1983 kcal/kg net energy; 100 kg -Slaughter with 14.5% crude protein, 0.90% total lysine, and 1945 kcal/kg (gilts) or 1856 kcal/kg (boars) net energy.
  • Joint Lesion Results Reductions in joint inflammation symptoms were measured as probability of observing joint lesions (observed joint lesions/total pigs) total occurrence of joint lesions at 40, 100, and 130 kg BW, gilts and boars. Inclusion of 0.12 wt% nitrate reduced the probability of observing joint lesions for the entirety of the trial, including a 24% reduction at 100 kg-
  • Example 2 demonstrates nitrate increases ash content of bones to a larger extent than Example 1 when fed to pigs at 0.12% dietary nitrate for 100 days (-40 - 132 kg). Pigs were fed during 28 days in the trial described in Example 1.
  • the difference between Example 1 and Example 2 is believed to be due to a difference in the length of feeding or feeding age, and/or a synergistic effect of the dietary polyphenols contained in PROVIOX that were added to the nitrate source in Example 2.
  • Example 2 demonstrates nitrate increases ash content of bones to a larger extent than Example 1 when fed to pigs at 0.12% dietary nitrate for 100 days (-40 - 132 kg). Pigs were fed during 28 days in the trial described in Example 1.
  • the difference between Example 1 and Example 2 is believed to be due to a difference in the length of feeding or feeding age, and/or a synergistic effect of the dietary polyphenols contained in PROVIOX that were added to the nitrate source in Example 2.
  • the proposed trial design will include six treatments, plus a negative control with 12 replicates per treatment and 13 pigs per replicate — a total of 936 pigs will receive a swine feed that includes calcium nitrate.
  • the study will evaluate three levels of calcium nitrate supplementation, beginning at either weaning or the end of the nursery phase of production. Pigs will be allotted to treatment based on weight and sex at weaning. Supplemental dietary nitrate levels being considered are 400 ppm, 600 ppm, and 1200 ppm. Animals will be harvested at typical commercial weights. Diets will be formulated to meet or exceed nutrient requirements determined by the Cargill Nutrition System as appropriate for the growth phase. Experimental diets will be made by inclusion of Calcium Nitrate (CAS # 10124-37-5; ADOB, Ponzan, PL) at the expense of corn and provided as meal.

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Abstract

La présente technologie concerne un procédé d'alimentation de porc, le procédé comprenant : l'alimentation de porc avec un aliment pour porc qui comprend un composé de nitrate, ses hydrates, ses sels, ou leurs combinaisons, et éventuellement un antioxydant qui comprend des polyphénols ; le procédé augmentant le dépôt de minéraux osseux et/ou réduisant l'apparition de lésions articulaires chez le porc alimenté avec l'aliment pour porc par rapport à un porc témoin non alimenté avec les composés de nitrate, leurs hydrates et leurs sels.
PCT/US2023/077994 2022-10-31 2023-10-27 Procédé de réduction de la boiterie et d'amélioration de la minéralisation osseuse chez le porc Ceased WO2024097601A1 (fr)

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