WO2021011540A1 - Oral iron compositions and application for baby pigs - Google Patents

Oral iron compositions and application for baby pigs Download PDF

Info

Publication number
WO2021011540A1
WO2021011540A1 PCT/US2020/041937 US2020041937W WO2021011540A1 WO 2021011540 A1 WO2021011540 A1 WO 2021011540A1 US 2020041937 W US2020041937 W US 2020041937W WO 2021011540 A1 WO2021011540 A1 WO 2021011540A1
Authority
WO
WIPO (PCT)
Prior art keywords
iron
composition
liquid
feed
acid
Prior art date
Application number
PCT/US2020/041937
Other languages
French (fr)
Inventor
Thomas R. Hampton
Matthew J. Fischer
Kalen DUHS
Ping REN
Mercedes Vazquez-Anon
Deana L. Hancock
Matthew Sebastian BEKKER
Original Assignee
Novus International Inc.
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 Novus International Inc. filed Critical Novus International Inc.
Publication of WO2021011540A1 publication Critical patent/WO2021011540A1/en

Links

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
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/30—Oligoelements
    • 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
    • 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
    • A23K10/33—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms from molasses
    • 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
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • 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
    • A23K20/142—Amino acids; Derivatives thereof
    • A23K20/147—Polymeric derivatives, e.g. peptides or proteins
    • 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
    • A23K20/158—Fatty acids; Fats; Products containing oils or fats
    • 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
    • A23K20/163—Sugars; Polysaccharides
    • 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
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
    • 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
    • A23K20/174—Vitamins
    • 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
    • A23K20/189—Enzymes
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P60/00—Technologies relating to agriculture, livestock or agroalimentary industries
    • Y02P60/80—Food processing, e.g. use of renewable energies or variable speed drives in handling, conveying or stacking
    • Y02P60/87—Re-use of by-products of food processing for fodder production

Definitions

  • FIG. 1 illustrates the effects of iron treatments on blood hemoglobin concentrations during three different points of lactation.
  • CON represents conventional iron injection of 200 mg Fe on d 3 of lactation;
  • GLY200 represents oral gavage of 200 mg of Fe-glycinate suspension on d 3 of lactation;
  • GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of Fe-glycinate suspension on d 3 and 9 of lactation.
  • FIG. 2 shows average blood hemoglobin concentrations on d 3, 5
  • FIG. 3 presents the percentage of piglets with blood hemoglobin concentrations equal or greater than 9 g/dL within litter on d 10 and 16 of lactation.
  • INJ represents conventional iron injection of 200 mg Fe on d 3 of lactation;
  • GEL-0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe, respectively, to piglets from d 3 to 5, and from d 10 to 12 of lactation;
  • SPRAY represent applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5, and from d 10 to 12 of lactation.
  • FIG. 4 presents average blood hemoglobin concentrations on d 3
  • INJ represents conventional iron injection of 200 mg Fe on d 3 of lactation
  • GEL1 -0.44% Fe and GEL2- 0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation
  • SPRAY represent applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • FIG. 5 shows percentage of piglets with blood hemoglobin concentrations equal or greater than 9 g/dL within litter on d 10 and 16 of lactation.
  • INJ represents conventional iron injection of 200 mg Fe on d 3 of lactation;
  • GEL1 -0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation;
  • SPRAY represent applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • the present disclosure provides oral iron compositions that are formulated to prevent iron deficiency and/or anemia in nursing piglets.
  • the oral iron compositions are administered to nursing piglets during the nursing period, e.g., during the first fifteen days after birth.
  • the oral iron compositions include 1 ) a liquid iron composition and 2) an iron creep feed composition.
  • Also provided herein are methods for preventing anemia and/or iron deficiency in piglets, wherein the methods comprise administering to nursing piglets one of the oral iron compositions disclosed herein.
  • One aspect of the present disclosure provides liquid iron
  • the liquid iron composition comprises (a) an iron source; (b) a suspension medium, and (c) a viscosity modifier.
  • the liquid iron composition may further comprise a flavoring agent. It was discovered that the flavoring agent increases average daily feed in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent.
  • flavoring agent increases average daily feed intake by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, or at least about 65% in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent.
  • the iron source may comprise iron of various oxidation states.
  • the oxidation state of iron may be Fe 2_ , Fe 1_ , Fe°, Fe 1 + , Fe 2+ , Fe 3+ , Fe 5+ , or Fe 6+ .
  • the oxidation state of the iron in the iron source may be Fe 2+ (ferrous) or Fe 3+ (ferric).
  • the iron source may be an iron salt, an iron amino acid chelate or iron amino acid salt, an iron carboxylate, an iron chelate, or an iron complex.
  • iron salts include iron acetate, iron bromide, iron chloride, iron chromate, iron fluoride, iron hydroxide, iron nitrate, iron oxide, iron oxide-hydroxide, iron phosphate, iron pyrophosphate, iron sulfate, iron sulfide, and the like.
  • iron amino acid chelates/salts include iron aspartate, iron asparto glycinate, iron glycinate, iron bisglycinate, iron glycine sulfate, iron histidinate, iron methionine, iron proteinate, and iron amino acid chelate.
  • iron carboxylates examples include iron ascorbate, iron acetylacetonate, iron caprylate, iron citrate, iron ammonium citrate, iron fumarate, iron gluconate, iron ketoglutarate, iron laurate, iron malate, iron myristate, iron oxalate, iron ammonium oxalate, iron palmitate, iron stearate, iron succinate, iron tartrate, and so forth.
  • Suitable iron chelates include iron EDTA, iron DTPA, iron EDDFIA, iron FIEEDTA, and the like.
  • iron complexes examples include iron dextran, iron acetyl-hydroxamate iron polymaltose, iron hydroxide polymaltose, iron polysaccharide complex, iron trimaltose, and so forth.
  • the iron source present in the compositions disclosed herein may be an iron amino acid chelate or salt.
  • the iron source may be iron glycinate, iron proteinate, or iron trimaltose.
  • the iron source may be iron glycinate.
  • compositions may vary depending, for example, on the identity of the iron source and/or the amount of iron present in the iron source.
  • the amount of the iron source present in the iron composition may range from about 0.5% to about 40% by weight of the composition.
  • the liquid iron composition may comprise from about 0.5% to about 2.0% (w/w), from about 2% to about 5% (w/w), from about 5% to about 10% (w/w), from about 10% to about 20% (w/w), from about 20 to about 30% (w/w), or from about 30% to about 40% (w/w) of the iron source.
  • the liquid iron composition may comprise from about 10% to about 30% (w/w) of the iron source.
  • the liquid iron composition further comprises at least one suspension medium.
  • the suspension medium may be a vegetable oil (e.g., soybean oil, corn oil, canola oil, rapeseed oil, cottonseed oil, safflower oil, sunflower oil, peanut oil, etc.), long chain (> 14 carbons) fatty acids, long chain fatty acid esters, mono-, di-, or triglycerides comprising long chain fatty acids, and so forth.
  • the suspension medium may be molasses, corn syrup, high fructose corn syrup, sugar beet syrup, cane sugar syrup, raw sugar solution, sorghum syrup, dextrose, sucrose, lactose, maltose, and the like.
  • the suspension medium may be molasses, corn syrup, high fructose corn syrup, or dextrose.
  • the amount of the suspension medium present in the liquid iron composition can and will vary. In general, the amount of the suspension medium may range from about 15% to about 70% by weight of in the liquid iron composition. In certain embodiments, the liquid iron composition may comprise from about 15% to about 30% (w/w), from about 30% to about 40% (w/w), from about 40% to about 50% (w/w), from about 50%to about 60% (w/w), or from about 60% to about 70% (w/w) of the suspension medium. In specific embodiments, the liquid iron composition may comprise from about 20% to about 40% (w/w) of the suspension medium.
  • the liquid iron composition also comprises at least one viscosity modifier.
  • suitable viscosity modifiers include gums (e.g., xanthan gum, gum arabic, guar gum, gellan gum, and the like), alginates (e.g., alginic acid, alginate, sodium alginate, and so forth), pectins, gelatin, starches (e.g., corn starch, potato starch, wheat starch, rice starch, and the like), pregelatinized starch, cellulose, microcrystalline cellulose, and cellulose derivatives (e.g., methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and the like).
  • the viscosity modifier may be a gum such as xanthan gum.
  • the viscosity modifier may be included in the liquid iron composition.
  • the amount of the viscosity modifier may range from about 0.03% to about 5.0% by weight of the liquid iron composition.
  • the liquid iron composition may comprise from about 0.03% to about 0.1 % (w/w), from about 0.1 % to about 0.3% (w/w), from about 0.3% to about 1 % (w/w), from about 1 % to about 3% (w/w), or from about 3% (w/w) to about 5% (w/w) of the viscosity modifier.
  • the liquid iron composition may comprise about 0.25% (w/w) of the viscosity modifier.
  • the liquid iron composition may further comprise a flavoring agent.
  • Suitable flavoring agents include those comprising buttery, cheesy, fatty, fruity, green, meaty, musty, or sweet flavors.
  • the flavoring agent may comprise cherry flavor, apple flavor, peach flavor, pear flavor, strawberry flavor, raspberry flavor, plum flavor, pineapple flavor, apricot flavor, citrus flavor, vanilla flavor, tomato flavor, pumpkin pie flavor, cheese flavor, and the like.
  • the liquid iron composition may comprise a fruit flavor.
  • the liquid iron composition comprises cherry flavor.
  • the amount of flavoring agent may range from about 0.03% to about 3.0% by weight of the liquid iron composition.
  • the liquid iron composition may comprise from about 0.03% to about 0.1 % (w/w), from about 0.1 % to about 0.3% (w/w), or from about 0.3% to about 1 % (w/w), or from about 1 % to about 3% (w/w) of the flavoring agent.
  • the liquid iron composition may comprise about 0.3% (w/w) of the flavoring agent.
  • the liquid iron composition may further comprise a solvent.
  • suitable solvents include water, an alcohol (e.g., such as glycerin, propylene glycol, ethanol, and the like), an organic acid (e.g., formic acid, acetic acid, lactic acid, and so forth), and combinations thereof.
  • the liquid iron composition may further comprise water and glycerin.
  • the liquid iron composition may further comprise water.
  • the liquid iron composition may further comprise one or more nutrients or supplements.
  • suitable nutrients or supplements include vitamins, minerals, amino acids, antioxidants, organic acids, poly unsaturated fatty acids, essential oils, enzymes, prebiotics, probiotics, postbiotics, herbs, and pigments.
  • the liquid iron composition may further comprise one or more vitamins.
  • Suitable vitamins include vitamin A, vitamin B1
  • the form of the vitamin may include salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of a vitamin, and metabolites of a vitamin.
  • the liquid iron composition may further comprise one or more minerals.
  • suitable minerals include calcium, chromium, cobalt, copper, iodine, magnesium, manganese, molybdenum, selenium, zinc, or combinations thereof.
  • the mineral may be an inorganic mineral. Suitable inorganic minerals include, for example, metal sulfates, metal oxides, metal hydroxides, metal oxychlorides, metal carbonates, and metal halides.
  • the mineral may be an organic mineral, e.g., a metal chelate comprising a metal ion and an organic ligand.
  • the organic ligand may be an amino acid, an amino acid analog, a proteinate, a carbohydrate, or an organic acid.
  • the liquid iron composition may further comprise one or more amino acids.
  • suitable amino acids include standard amino acids (i.e., alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine), non-standard amino acids (e.g., L-DOPA, GABA, 2-aminobutyric acid, and the like), amino acid analogs, or combinations thereof.
  • Amino acid analogs include a-hydroxy analogs (e.g., methionine hydroxy analog), as well side chain protected analogs or N-derivatized amino acids.
  • the liquid iron composition may further comprise one or more antioxidants.
  • Suitable antioxidants include, but are not limited to, ascorbic acid and its salts, ascorbyl palmitate, ascorbyl stearate, anoxomer, n- acetylcysteine, benzyl isothiocyanate, m-aminobenzoic acid, o-aminobenzoic acid, p- aminobenzoic acid (PABA), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), caffeic acid, canthaxantin, alpha-carotene, beta-carotene, beta-caraotene, beta- apo-carotenoic acid, carnosol, carvacrol, catechins, cetyl gallate, chlorogenic acid, citric acid and its salts, clove extract, coffee bean extract, p-coumaric acid, 3,4- dihydroxybenzoic acid, N,
  • thiodipropionate distearyl thiodipropionate, 2,6-di-tert-butylphenol, dodecyl gallate, edetic acid, ellagic acid, erythorbic acid, sodium erythorbate, esculetin, esculin, 6- ethoxy-1 ,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin), ethyl gallate, ethyl maltol, ethylenediaminetetraacetic acid (EDTA), eucalyptus extract, eugenol, ferulic acid, flavonoids (e.g., catechin, epicatechin, epicatechin gallate, epigallocatechin (EGC), epigallocatechin gallate (EGCG), polyphenol epigallocatechin-3-gallate, flavones (e.g., apigenin, chrysin, luteolin), flavonols (e.g., dat
  • hydroxyurea rice bran extract, lactic acid and its salts, lecithin, lecithin citrate; R-alpha- lipoic acid, lutein, lycopene, malic acid, maltol, 5-methoxy tryptamine, methyl gallate, monoglyceride citrate; monoisopropyl citrate; morin, beta-naphthoflavone,
  • nordihydroguaiaretic acid NDGA
  • octyl gallate oxalic acid, palmityl citrate, phenothiazine, phosphatidylcholine, phosphoric acid, phosphates, phytic acid, phytylubichromel, pimento extract, propyl gallate, polyphosphates, quercetin, trans- resveratrol, rosemary extract, rosmarinic acid, sage extract, sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate, syringic acid, tartaric acid, thymol, tocopherols (i.e.
  • alpha-, beta-, gamma- and delta-tocopherol alpha-, beta-, gamma- and delta-tocopherol
  • tocotrienols i.e., alpha-, beta-, gamma- and delta-tocotrienols
  • tyrosol vanilic acid, 2,6-di-tert-butyl-4-hydroxymethylphenol (i.e., lonox 100), 2,4-(tris-3’,5’-bi-tert-butyl-4’-hydroxybenzyl)-mesitylene (i.e., lonox 330), 2,4,5-trihydroxybutyrophenone, ubiquinone, tertiary butyl hydroquinone (TBHQ), thiodipropionic acid, trihydroxy butyrophenone, tryptamine, tyramine, uric acid, vitamin K and derivates, vitamin Q10, wheat germ oil, zeaxanthin, or combinations thereof.
  • the liquid iron composition may further comprise one or more organic acids.
  • the organic acid may be a carboxylic acid or a substituted carboxylic acid.
  • the carboxylic acid may be a mono-, di-, or tri-carboxyl ic acid. In general, the carboxylic acid may contain from about one to about twenty-two carbon atoms.
  • Suitable organic acids include acetic acid, adipic acid, butanoic acid, benzoic acid, cinnamaldehyde, citric acid, formic acid, fumaric acid, glutaric acid, glycolic acid, lactic acid, malic acid, mandelic acid, propionic acid, sorbic acid, succinic acid, tartaric acid, or combinations thereof. Salts of organic acids comprising carboxylic acids are also suitable for certain embodiments.
  • Representative suitable salts include the ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, and zinc salts of organic acids.
  • the liquid iron composition may further comprise one or more poly unsaturated fatty acids.
  • Suitable poly unsaturated fatty acids include medium chain fatty acids having from 6 to 12 carbon atoms and long chain fatty acids having at least 12 carbon atoms having at least two carbon- carbon double bonds, generally in the cis-configuration.
  • the PUFA may be an omega fatty acid.
  • the PUFA may be an omega-3 fatty acid in which the first double bond occurs in the third carbon-carbon bond from the methyl end of the carbon chain (i.e., opposite the carboxyl acid group).
  • omega-3 fatty acids include all-cis 7, 10, 13-hexadecatrienoic acid; all-cis-9, 12,15-octadecatrienoic acid (alpha-linolenic acid, ALA); all-cis-6,9,12,15,-octadecatetraenoic acid (stearidonic acid); all-cis-8,11 ,14,17-eicosatetraenoic acid (eicosatetraenoic acid); all-cis- 5,8,11 ,14,17-eicosapentaenoic acid (eicosapentaenoic acid, EPA); all-cis- 7,10,13,16,19-docosapentaenoic acid (clupanodonic acid, DPA); all-cis-4,7, 10, 13, 16, 19- docosahexaenoic acid (docosahexaenoic acid, DHA); all-cis-4,7, 10, 13, 16, 19- docos
  • the PUFA may be an omega-6 fatty acid in which the first double bond occurs in the sixth carbon-carbon bond from the methyl end of the carbon chain.
  • omega-6 fatty acids include all-cis-9,12-octadecadienoic acid (linoleic acid); all-cis-6,9, 12-octadecatrienoic acid (gamma-linolenic acid, GLA); all-cis- 11 ,14-eicosadienoic acid (eicosadienoic acid); all-cis-8,11 ,14-eicosatrienoic acid
  • DGLA dihomo-gamma-linolenic acid
  • the PUFA may be an omega-9 fatty acid in which the first double bond occurs in the ninth carbon-carbon bond from the methyl end of the carbon chain, or a conjugated fatty acid, in which at least one pair of double bonds are separated by only one single bond.
  • omega-9 fatty acids include cis-9-octadecenoic acid (oleic acid); cis-11-eicosenoic acid (eicosenoic acid); all-cis-5,8,11 -eicosatrienoic acid (mead acid); cis-13-docosenoic acid (erucic acid), and cis-15-tetracosenoic acid (nervonic acid).
  • conjugated fatty acids examples include 9Z, 11 E-octadeca-9, 11 - dienoic acid (rumenic acid); 10E,12Z-octadeca-9,11 -dienoic acid; 8E,10E,12Z- octadecatrienoic acid (a-calendic acid); 8E,10E,12E-octadecatrienoic acid (b-Calendic acid); 8E,10Z,12E-octadecatrienoic acid (jacaric acid); 9E,11 E,13Z-octadeca-9,11 ,13- trienoic acid (a-eleostearic acid); 9E, 11 E, 13E-octadeca-9, 11 ,13-trienoic acid (b- eleostearic acid); 9Z,11Z,13E-octadeca-9,11 ,13-trienoic acid (catalpic acid), and
  • the liquid iron composition may further comprise one or more essential oils.
  • suitable essential oils include, but are not limited to, peppermint oil, cinnamon leaf oil, lemongrass oil, clove oil, castor oil, wintergreen oil, sweet orange, spearmint oil, cederwood oil, aldehyde C16, a terpineol, amyl cinnamic aldehyde, amyl salicylate, anisic aldehyde, benzyl alcohol, benzyl acetate, camphor, capsaicin, cinnamaldehyde, cinnamic alcohol, carvacrol, carveol, citral, citronellal, citronellol, p cymene, diethyl phthalate, dimethyl salicylate, dipropylene glycol, eucalyptol (cineole), eugenol, iso-eugenol, galaxolide, geraniol, gua
  • the liquid iron composition may further comprise one or more prebiotics, probiotics, and/or postbiotics.
  • Pre/pro/postbiotics include agents derived from yeast or bacteria that promote good digestive health.
  • yeast-derived pre/pro/postbiotics include yeast cell wall derived components such as b-glucans, arabinoxylan isomaltose,
  • yeast-derived agent may be b-glucans and/or mannanoligosaccharides.
  • Sources for yeast cell wall derived components include Saccharomyces bisporus,
  • Saccharomyces boulardii Saccharomyces cerevisiae, Saccharomyces capsularis, Saccharomyces delbrueckii, Saccharomyces fermentati, Saccharomyces lugwigii, Saccharomyces microellipsoides, Saccharomyces pastorianus, Saccharomyces rosei, Candida albicans, Candida cloaceae, Candida tropicalis, Candida utilis, Geotrichum candidum, Hansenula americana, Hansenula anomala, Hansenula wingei, and
  • Pre/pro/postbiotics may also include bacteria cell wall derived agents such as peptidoglycan and other components derived from gram-positive bacteria with a high content of peptidoglycan.
  • Exemplary gram-positive bacteria include Lactobacillus acidophilus, Bifedobact thermophilum, Bifedobat longhum, Streptococcus faecium, Bacillus pumilus, Bacillus subtilis, Bacillus licheniformis, Lactobacillus acidophilus, Lactobacillus casei, Enterococcus faecium, Bifidobacterium bifidium, Propionibacterium acidipropionici, Propionibacteriium freudenreichii, and
  • the liquid iron composition may further comprise one or more enzymes or enzyme variants.
  • enzymes include amylases, carbohydrases, cellulases, esterases, galactonases, galactosidases, glucanases, hemicellulases, hydrolases, lipases, oxidoreductases, pectinases, peptidases, phosphatases, phospholipases, phytases, proteases, transferases, xylanases, or combinations thereof.
  • the liquid iron composition may further comprise one or more herbals.
  • Suitable herbals and herbal derivatives refer to herbal extracts, and substances derived from plants and plant parts, such as leaves, flowers and roots, without limitation.
  • Non-limiting exemplary herbals and herbal derivatives include agrimony, alfalfa, aloe vera, amaranth, angelica, anise, barberry, basil, bayberry, bee pollen, birch, bistort, blackberry, black cohosh, black walnut, blessed thistle, blue cohosh, blue vervain, boneset, borage, buchu, buckthorn, bugleweed, burdock, capsicum, cayenne, caraway, cascara sagrada, catnip, celery, centaury, chamomile, chaparral, chickweed, chicory, chinchona, cloves, coltsfoot, comfrey, cornsilk, couch grass, cramp bark, cul
  • the liquid iron composition may further comprise one or more natural pigments.
  • Suitable pigments include, without limit, actinioerythrin, alizarin, alloxanthin, p-apo-2'-carotenal, apo-2-lycopenal, apo-6'- lycopenal, astacein, astaxanthin, azafrinaldehyde, aacterioruberin, aixin, a-carotine, b- carotine, y-carotine, b-carotenone, canthaxanthin, capsanthin, capsorubin,
  • the liquid iron composition may be formulated as a liquid solution, a liquid suspension, or a liquid emulsion.
  • the liquid iron composition may be spray dried and the spray dried particles may be agglomerated into pellets, crumbles, or capsules.
  • the liquid iron composition or spray dried particles prepared therefrom may be formed into a solid or semi-solid feeder block or lick block.
  • the feeder block or lick block may also comprise nutrients (e.g., amino acids, saccharides, fats, etc.), vitamins, minerals, and the like.
  • a further aspect of the present disclosure provides a composition comprising an iron source and a creep feed.
  • the composition may further comprise one or more flavoring agents or palatability enhancers.
  • the iron source may comprise iron of various oxidation states.
  • the oxidation state of iron may be Fe 2_ , Fe 1_ , Fe°, Fe 1 + , Fe 2+ , Fe 3+ , Fe 5+ , or Fe 6+ .
  • the oxidation state of the iron in the iron source may be Fe 2+ (ferrous) or Fe 3+ (ferric).
  • the iron source may be an iron salt, an iron amino acid chelate or iron amino acid salt, an iron carboxylate, an iron chelate, or an iron complex.
  • iron salts include iron acetate, iron bromide, iron chloride, iron chromate, iron fluoride, iron hydroxide, iron nitrate, iron oxide, iron oxide-hydroxide, iron phosphate, iron pyrophosphate, iron sulfate, iron sulfide, and the like.
  • iron amino acid chelates/salts include iron aspartate, iron asparto glycinate, iron glycinate, iron bisglycinate, iron glycine sulfate, iron histidinate, iron methionine, iron proteinate, and iron amino acid chelate.
  • iron carboxylates examples include iron ascorbate, iron acetylacetonate, iron caprylate, iron citrate, iron ammonium citrate, iron fumarate, iron gluconate, iron ketoglutarate, iron laurate, iron malate, iron myristate, iron oxalate, iron ammonium oxalate, iron palmitate, iron stearate, iron succinate, iron tartrate, and so forth.
  • Suitable iron chelates include iron EDTA, iron DTPA, iron EDDFIA, iron FIEEDTA, and the like.
  • iron complexes examples include iron dextran, iron acetyl-hydroxamate iron polymaltose, iron hydroxide polymaltose, iron polysaccharide complex, iron trimaltose, and so forth.
  • the iron source present in the compositions disclosed herein may be an iron amino acid chelate or salt.
  • the iron source may be iron glycinate, iron proteinate, or iron trimaltose.
  • the iron source may be iron glycinate.
  • the amount of the iron source present in the iron creep feed compositions may vary depending, for example, on the identity of the iron source and/or the amount of iron present in the iron source. In general, the amount of the iron source may range from about 0.1 % to about 10% by weight of the composition. In some embodiments, the iron creep feed composition may comprise from about 0.1 % to about 0.3% (w/w), from about 0.3% to about 1 % (w/w), from about 1 % to about 3% (w/w), or from about 3% to about 10% (w/w) of the iron source. In specific embodiments, the iron creep feed composition may comprise from about 0.2% to about 4% (w/w) of the iron source.
  • Creep feed is solid or semi-solid feed provided to piglets while they are suckling the sow.
  • creep feeds comprise sources of protein and carbohydrates that can be easily digested by sucking pigs.
  • a creep feed may comprise hydrated oats, cooked cereals, cereal mashes, soy bean meal, corn gluten meal, canola meal, cottonseed meal, milk by-products, milk proteins, lactose, rolled oats, rice bran, broken rice, wheat bran, milled or cracked corn, wheat, sorghum, barley, distillers residues, vegetable proteins, oilseed extracts, fatty acids, amino acids, feed phosphates, vitamins, and/or minerals.
  • the components included in the creep feed and the total amount of protein present in the creep feed can and will vary depending, for example, upon the age of the piglet.
  • the iron creep feed composition may further comprise flavoring agents or palatability enhancers.
  • suitable flavoring agents are described above in section (l)(d).
  • suitable palatability enhancers include milk by-products, dried skim milk, yeast products, spray dried porcine plasma (SDPP), sweeteners, and the like.
  • SDPP spray dried porcine plasma
  • the iron creep feed composition may further comprise optional nutrients or supplements, as described above in section (l)(f).
  • composition comprising the iron source and the creep feed may be in dry form, e.g., pelleted, dry kibble, granulates, crumbles, powders, solid or semi-solid blocks, and the like.
  • the iron creep feed may be in dry form, e.g., pelleted, dry kibble, granulates, crumbles, powders, solid or semi-solid blocks, and the like.
  • the iron creep feed may be in dry form, e.g., pelleted, dry kibble, granulates, crumbles, powders, solid or semi-solid blocks, and the like.
  • the iron creep feed may be in dry form, e.g., pelleted, dry kibble, granulates, crumbles, powders, solid or semi-solid blocks, and the like.
  • the iron creep feed may be in dry form, e.g., pelleted, dry kibble, granulates, crumbles, powders, solid or semi-solid blocks, and the like.
  • compositions may be semi-solid or liquid, e.g., gels, slurries, suspensions, extrudates, moist kibbles, gruels, and so forth.
  • Still another aspect of the present disclosure provides methods for preparing the iron compositions disclosed herein.
  • the liquid iron compositions described above in section (I) may be prepared by mixing the iron source, the suspension medium; the viscosity modifier, and an optional flavoring agent.
  • the ingredients may be mixed in any order.
  • the mixing may comprise stirring, blending, rotating, and the like.
  • the liquid composition may be spray dried and the spray dried particles may be agglomerated, pressed into pellets, pressed into block, etc.
  • the liquid composition may be extruded and dried to the desired level of moisture.
  • the iron creep feed compositions described above in section (II) may be prepared by adding the iron source with the solid or semi-solid creep feed.
  • the iron source and creep feed may be mixed by any suitable means, e.g., blending, milling, roller compacting, granulating, etc.
  • the iron creep feed composition may be pelleted, compacted, powdered, extruded, and the like to produce the final formulation.
  • the iron creep feed composition may be mixed with a liquid (e.g., water, whey, fat or oil), such that the final formulation of the iron creep feed composition may a liquid or a suspension.
  • the liquid iron creep feed composition may be spray dried and agglomerated.
  • Still another aspect of the present disclosure encompasses methods for preventing anemia and/or iron deficiency in piglets, wherein the methods comprise administering to piglets an effective amount of the oral iron composition liquid iron compositions disclosed herein, e.g., the liquid iron compositions described above in section (I) or the iron creep feed compositions described above in section (II), within the first three days after the piglet’s birth.
  • the method comprises administering to the piglets several doses of the oral iron composition within the first 15 days after the piglet’s birth.
  • the piglets may be administered a first dosage of the oral iron composition within the first three days after birth, and then may be administered a second dosage of the oral iron composition from about five days to about nine days after birth.
  • the method may comprise administering multiple or continous doses of the oral iron composition within the first 15 days, within the first 21 days, or within the first 28 days after birth.
  • the oral iron composition may be any suitable oral iron composition.
  • a lick bottle a nipple or teat bucket, a feed or lick block, feeding trough, spot feeder, timed feeder, or lick bowl, such that the piglet may ingest small amounts of the iron composition several times a day.
  • the method comprises applying the liquid iron composition onto the underline (i.e., teats and belly area) of a lactating sow, and contacting piglets with the lactating sow in a manner such that the piglets can nurse and ingest the iron composition from the underline of the sow in a quantity sufficient to prevent iron deficiency and/or anemia in the piglet.
  • the liquid iron composition may “adhere” to the underline of the sow because of the presence of the suspension medium and/or the viscosity modifier in the liquid iron composition. The adherence of the liquid iron composition to the underline of the sow permits consumption of the iron
  • the liquid iron composition may be applied to the underline of the sow by spraying, rolling, brushing, or other suitable means known in the art.
  • the liquid iron composition may be sprayed into the underline of the sow with a hand held pressure sprayer, a backpack style pressure sprayer, a garden sprayer, a tractor-mounted sprayer, or other suitable sprayer.
  • the liquid iron composition may be applied to the underline of the sow with a roller, brush, mop, wick, or oiler.
  • the liquid composition may be applied to the underline of the sow twice a day, once a day, or every other day during the nursing period.
  • the“effective amount” of the oral iron composition provides about 10 mg of iron per piglet per day.
  • a dose of the oral iron composition may vary depending, for example, upon the means for administering the oral iron composition (e.g., once per day vs. multiple times per day), and the identity and/or concentration of the iron source in the oral iron composition.
  • about 50-300 mg of iron may be provided per piglet per day.
  • nursing piglets After ingestion of the oral iron compositions as described herein, nursing piglets show no signs of iron deficiency and/or anemia. Anemia and/or iron deficiency may be monitored by blood hemoglobin concentration or other blood hematological parameters. Hemoglobin concentrations in blood may be determined using means well known in the art. Normal blood hemoglobin concentrations in sucking pigs at day three after birth range from about 7-9 g/dL. At weaning, piglets can have blood hemoglobin concentrations from about 9-12 g/dL.
  • erythrocyte count (RBC), total and differential leukocyte count, platelets, red blood cell distribution width (RDW), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular Hb concentration (MCHC), reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width (RDWr), and reticulocyte Hb distribution width (HDWr).
  • Flavored and unflavored iron glycinate (1 :1 metal:glycine ratio) formulations were prepared according to Table 1.
  • Feed preference was measured on day 8-11 (or days 1 -4 after initiation of dietary treatments) as intake of the feed with artificial flavor expressed as percentage of total feed intake in each pen.
  • the following mathematical equation was used in the calculation:
  • SAS software (SAS 9.4) was used for all data analysis. Each pen served as an experimental unit. Paired t-test was used to conduct comparisons between cherry and reference, cheese and reference, left and right feeder positions. A probability of P ⁇ 0.05 was considered significant, and 0.05 ⁇ P ⁇ 0.10 was declared a trend.
  • the 4 treatments include: 1 ) intramuscular injection of 1 ml iron dextran to supply 200 mg Fe for each piglet on d 3 of lactation (CON), 2) oral gavage of 2.7 ml of Fe-glycinate suspension (Table 4) to supply 200 mg Fe for each piglet on day 3 of lactation (GLY200), 3) oral gavage of 1.35 ml of Fe-glycinate suspension on both d 3 and 6 of lactation (GLY200D), or 4) oral gavage of 2.7 ml Fe-glycinate suspension on both d 3 and 6 of lactation (GLY400D).
  • the treatments are summarized in Table 5.
  • the microcuvette was discarded and a new microcuvette was filled from a new drop of blood. Small bubbles around the edge could be ignored. Then the filled microcuvette was placed in the cuvette holder and put in the measuring position within 10 min after filling the microcuvette. After 15 to 60 seconds, the hemoglobin value of the sample was displayed on the screen.
  • Hematological indices included erythrocyte count (RBC), total and differential leukocyte count, platelets, red blood cell distribution width (RDW), hematocrit (Hot), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular Hb concentration (MCHC).
  • Reticulocyte indices included reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width
  • RWr reticulocyte Hb distribution width
  • HDWr reticulocyte Hb distribution width
  • 1 CON represents conventional iron injection of 200 mg Fe on d 3 of lactation
  • GLY200 represents oral gavage of 200 mg of iron glycinate suspension on d 3 of lactation
  • GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of iron glycinate suspension on d 3 and 9 of lactation.
  • 1 CON represents conventional iron injection of 200 mg Fe on d 3 of lactation
  • GLY200 represents oral gavage of 200 mg of iron glycinate suspension on d 3 of lactation
  • GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of iron glycinate suspension on d 3 and 9 of lactation.
  • piglets administered GLY200D and GLY400D had significant greater (P ⁇ 0.01 ) mean cell hemoglobin concentration (MCHC) compared with piglets from CON.
  • MCHC mean cell hemoglobin concentration
  • 1 CON represents conventional iron injection of 200 mg Fe on d 3 of lactation
  • GLY200 represents oral gavage of 200 mg of iron glycinate suspension on d 3 of lactation
  • GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of iron glycinate suspension on d 3 and 9 of lactation.
  • MCV, MCH, MCHC and RDW represent mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, respectively.
  • Example 5 Comparison of Suckling Piglets Administered via Creep Feed vs. Spraying into Sow Mammary Glands - Study 1
  • the objective of the present study was to investigate the efficacy of feeding gel feed containing 0.22% Fe to piglets from d 3 to 5, and from d 10 to 12 of lactation and application of iron suspension containing 3.32% Fe on sow mammary glands from d 3 to 5, and from d 10 to 12 of lactation compared with conventional iron injection.
  • the 3 treatments include: 1 ) intramuscular injection of 1 ml iron dextran to supply 200 mg Fe for each piglet on d 3 of lactation (IN J); 2) Feeding gel feed with 1.27% iron glycinate (to achieve 0.22% Fe) to the piglets ad libitum from d 3 to 5 and from d 10 to 12 of lactation (GEL-0.22% Fe); 3) Spray iron suspension with 20% iron glycinate (Table 9) on the sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation (SPRAY). The treatments were displayed in Table 10. The study lasted 16 days.
  • the piglets in each litter were weighed individually on d 3, 9 and 15 of lactation.
  • the piglets in each litter were also be used to test their blood hemoglobin concentrations using HemoCue Hb 201 + analyzer (HemoCue, Inc., Lake Forest, CA) on d 3, 5, 9 and 15 of lactation.
  • Blood for hemoglobin analysis was obtained on d 3 of lactation either directly following tail docking or may be accomplished by ear notching on d 5, 9 and 15 of lactation. All subsequent blood collections for hemoglobin analysis were accomplished utilizing ear notching. The first 2 or 3 drops of blood were wiped away and light pressure was then re-applied until another drop of blood appeared.
  • the microcuvette When the blood drop was large enough, the microcuvette was filled in one continuous process. If there were air bubbles in the filled microcuvette, the microcuvette was discard and a new microcuvette from a new drop of blood was filled. Small bubbles around the edge could be ignored. Then the filled microcuvette was placed in the cuvette holder and put in the measuring position within 10 min after filling the
  • the cuvette was slid into the holder to the measuring position and the machine door was closed. After 15 to 60 seconds, the hemoglobin value of the sample was displayed on the screen.
  • Reticulocyte indices included reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width (RDWr), and reticulocyte Hb distribution width (HDWr).
  • CHr reticulocyte hemoglobin concentration
  • CHCMr mean reticulocyte corpuscular Hb concentration
  • MCVr reticulocyte cell volume
  • RDWr reticulocyte red cell distribution width
  • HDWr reticulocyte Hb distribution width
  • SAS 9.4 SAS Inst. Inc., Gary, NC was used for all data analysis.
  • GLIMMIX procedure was used to analyze the data. Treatments were considered as the fixed effect. Sow within treatment was considered as the random effect. If the variance component for sow within treatment was not different from zero, this component would be removed from the final model. If piglet BW and blood Hb concentration on d 3 of lactation were significant among treatments, they would be used as covariates to adjust for the analysis of growth rate and Hb concentration on d 5, 9, 10, 15 and 16 of lactation, respectively.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1 - 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1 .27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation
  • SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation
  • SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
  • 2 Hb represents blood hemoglobin.
  • piglets receiving iron injection had greater (P ⁇ 0.01 ) hematocrit (Hct) than piglets receiving GEL-0.22% Fe and SPRAY, and piglets receiving SPRAY had greater (P ⁇ 0.01 ) Hct than those from GEL-0.22% Fe (Tables 13 and 14). Additionally, piglets from iron injection had greater (P ⁇ 0.01 ) mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) on d 10 and 16 of lactation compared with those from GEL-0.22% Fe, with piglets from SPRAY
  • Lymphocyte % 44.52 36.78 39.42 3.80 0.40
  • Monocyte % 3.83 5.18 5.42 0.81 0.37 a c Within a row, means without a common superscript differ (P ⁇ 0.05).
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation;
  • GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation;
  • SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
  • Hb, Hct, MCV, MCH, MCHC, RDW, RBC and WBC represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, red blood cell count and white blood cell count, respectively.
  • Lymphocyte % 45.18 51 .28 48.75 2.20 0.20
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation
  • SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1 - 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1 .27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation
  • SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
  • 2 Hb, Hct, MCV, MCH and RDW represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red blood cell distribution width, respectively.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation
  • SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
  • the objective of the present study was to investigate the efficacy of feeding gel feed containing 0.44 or 0.88% Fe to piglets from d 3 to 15 of lactation and application of iron suspension containing 4.98% Fe on sow mammary glands from d 3 to 6 of lactation compared with conventional iron injection.
  • the 4 treatments include: 1 ) intramuscular injection of 1 ml_ iron dextran to supply 200 mg Fe for each piglet on d 3 of lactation (IN J); 2) Feeding gel feed 1 with 2.59% iron glycinate to the piglets ad libitum from d 3 to 15 of lactation (GEL1 -0.44% Fe); 3) Feeding gel feed 2 with 5.24% iron glycinate to the piglets ad libitum from d 3 to 15 of lactation (GEL2-0.88% Fe); 4) Spray iron suspension with 30% Iron glycinate (Table 17) on the sow mammary glands from d 3 to 6 of lactation (SPRAY). The treatments were displayed in Table 18. The study lasted 16 days.
  • the piglets in each litter were weighed individually on d 3, 9 and 15 of lactation.
  • the piglets in each litter were also be used to test their blood hemoglobin concentrations using HemoCue Hb 201 + analyzer (HemoCue, Inc., Lake Forest, CA) on d 3, 9 and 15 of lactation.
  • Blood for hemoglobin analysis was obtained on d 3 of lactation either directly following tail docking or may be accomplished by ear notching on d 9 and 15 of lactation. All subsequent blood collections for hemoglobin analysis were accomplished utilizing ear notching. The first 2 or 3 drops of blood were wiped away and light pressure was then re-applied until another drop of blood appeared.
  • the microcuvette When the blood drop was large enough, the microcuvette was filled in one continuous process. If there were air bubbles in the filled microcuvette, the microcuvette was discarded and a new microcuvette from a new drop of blood was filled. Small bubbles around the edge could be ignored. Then the filled microcuvette was placed in the cuvette holder and put in the measuring position within 10 min after filling the
  • the cuvette was slid into the holder to the measuring position and the machine door was closed. After 15 to 60 seconds, the hemoglobin value of the sample was displayed on the screen.
  • Reticulocyte indices included reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width (RDWr), and reticulocyte Hb distribution width (HDWr).
  • SAS 9.4 SAS Inst. Inc., Gary, NC was used for all data analysis.
  • GLIMMIX procedure was used to analyze the data. Treatments were considered as the fixed effect. Sow within treatment was considered as the random effect. If the variance component for sow within treatment was not different from zero, this component would be removed from the final model. If piglet BW and blood Hb concentration on d 3 of lactation were significant among treatments, they would be used as covariates to adjust for the analysis of growth rate and Hb concentration on d 9 and 15, respectively.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1 - 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation
  • SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1 - 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation
  • SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • Lymphocyte 10 3 /pL 5.07 4.63 5.01 4.40 0.58 0.82
  • Lymphocyte % 40.15 37.87 41.19 41.41 4.99 0.95
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation
  • SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • Hb, Hct, MCV, MCH, MCHC, RDW, RBC and WBC represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, red blood cell count and white blood cell count, respectively.
  • Lymphocyte 10 3 /pL 5.52 4.64 5.45 4.44 0.43 0.24
  • Lymphocyte % 46.44 43.94 51.20 44.81 2.94 0.37
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation
  • SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • Hb, Hct, MCV, MCH, MCHC, RDW, RBC and WBC represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, red blood cell count and white blood cell count, respectively.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation
  • SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • Hb, Hct, MCV, MCH and RDW represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red blood cell distribution width, respectively.
  • 1 1NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation
  • GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation
  • SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
  • Hb, Hct, MCV, MCH and RDW represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red blood cell distribution width, respectively.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Husbandry (AREA)
  • Zoology (AREA)
  • Food Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Birds (AREA)
  • Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Physiology (AREA)
  • Inorganic Chemistry (AREA)
  • Fodder In General (AREA)

Abstract

Oral iron compositions for preventing iron deficiency and/or anemia in nursing piglets, wherein the composition is a liquid composition comprising an iron source, a suspension medium, a viscosity modifier, and a flavoring agent, or the composition is an iron feed composition comprising an iron source and a creep feed. The oral iron compositions are administered to nursing piglets during the nursing period, e.g., within the first fifteen days after birth.

Description

ORAL IRON COMPOSITIONS AND APPLICATION FOR BABY PIGS
FIELD
[0001 ] Disclosed herein are oral iron compositions for preventing iron deficiency and/or anemia in nursing piglets.
BACKGROUND
[0002] It is well established that insufficient intake of iron in the suckling piglet results in iron deficiency and anemia due to the reduced concentration of hemoglobin (Hb) and the number and size of red blood cells (RBC). Unlike other animals, suckling piglets are susceptible to iron deficiency or anemia. One of the reasons is that newborn piglets only have approximately 50 mg of total body iron, which is mainly incorporated in hemoglobin. Secondly, the low iron concentration in sow milk, which only provides 1 mg of iron per day, exacerbates the iron deficiency in the suckling piglets. Thirdly, in the first week after birth, piglets double their weight and increase their blood volume by 30%, therefore diluting the concentration of iron. Research has shown that the daily requirement of iron for suckling piglets is approximately 8 mg, therefore, the limited body reserve, lack of iron provision from milk and fast growth rate are likely to induce iron deficiency and eventually anemia and even death in suckling piglets.
[0003] It is commonly recommended to administer a 100 to 200 mg intramuscular injection of iron dextran within the first three days after birth, which is considered as a successful strategy to combat the iron deficiency in newborn piglets. Although this iron injection practice has been successfully implemented and utilized in the swine industry for several decades, the practice of injecting baby piglets with iron dextran has come under scrutiny as animal welfare issues are more observed, particularly outside of the United States. The practice of removing and/or handling the piglets for processing (e.g., iron injections, tail docking, clip needle teeth, male castration) has become something that many producers would like to minimize. Thus, alternate iron compositions and means for providing the alternate compositions to suckling pigs would be beneficial. BRIEF DESCRIPTION OF THE DRAWINGS
[0004] FIG. 1 illustrates the effects of iron treatments on blood hemoglobin concentrations during three different points of lactation. CON represents conventional iron injection of 200 mg Fe on d 3 of lactation; GLY200 represents oral gavage of 200 mg of Fe-glycinate suspension on d 3 of lactation; GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of Fe-glycinate suspension on d 3 and 9 of lactation.
[0005] FIG. 2 shows average blood hemoglobin concentrations on d 3, 5,
9, 10, 15 and 16 of lactation for piglets receiving four iron treatments. INJ represents conventional iron injection of 200 mg Fe on d 3 of lactation; GEL-0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe,
respectively, to piglets from d 3 to 5, and from d 10 to 12 of lactation; SPRAY
represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5, and from d 10 to 12 of lactation.
[0006] FIG. 3 presents the percentage of piglets with blood hemoglobin concentrations equal or greater than 9 g/dL within litter on d 10 and 16 of lactation. INJ represents conventional iron injection of 200 mg Fe on d 3 of lactation; GEL-0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe, respectively, to piglets from d 3 to 5, and from d 10 to 12 of lactation; SPRAY represent applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5, and from d 10 to 12 of lactation.
[0007] FIG. 4 presents average blood hemoglobin concentrations on d 3,
9, 10, 15 and 16 of lactation for piglets receiving four iron treatments. INJ represents conventional iron injection of 200 mg Fe on d 3 of lactation; GEL1 -0.44% Fe and GEL2- 0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represent applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
[0008] FIG. 5 shows percentage of piglets with blood hemoglobin concentrations equal or greater than 9 g/dL within litter on d 10 and 16 of lactation. INJ represents conventional iron injection of 200 mg Fe on d 3 of lactation; GEL1 -0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represent applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
DETAILED DESCRIPTION
[0009] The present disclosure provides oral iron compositions that are formulated to prevent iron deficiency and/or anemia in nursing piglets. In general, the oral iron compositions are administered to nursing piglets during the nursing period, e.g., during the first fifteen days after birth. The oral iron compositions include 1 ) a liquid iron composition and 2) an iron creep feed composition. Also provided herein are methods for preventing anemia and/or iron deficiency in piglets, wherein the methods comprise administering to nursing piglets one of the oral iron compositions disclosed herein.
(I) Liquid Iron Compositions
[0010] One aspect of the present disclosure provides liquid iron
compositions for oral administration to piglets to prevent iron deficiency and anemia. In some embodiments, the liquid iron composition comprises (a) an iron source; (b) a suspension medium, and (c) a viscosity modifier. In other embodiments, the liquid iron composition may further comprise a flavoring agent. It was discovered that the flavoring agent increases average daily feed in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent.
[0011 ] In some embodiments, flavoring agent increases average daily feed intake by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, or at least about 65% in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent. (a) Iron source
[0012] A variety of iron sources may be included in the compositions disclosed herein. The iron source may comprise iron of various oxidation states. For example, the oxidation state of iron may be Fe2_, Fe1_, Fe°, Fe1 +, Fe2+, Fe3+, Fe5+, or Fe6+. Typically, the oxidation state of the iron in the iron source may be Fe2+ (ferrous) or Fe3+ (ferric). The iron source may be an iron salt, an iron amino acid chelate or iron amino acid salt, an iron carboxylate, an iron chelate, or an iron complex.
[0013] Examples of suitable iron salts include iron acetate, iron bromide, iron chloride, iron chromate, iron fluoride, iron hydroxide, iron nitrate, iron oxide, iron oxide-hydroxide, iron phosphate, iron pyrophosphate, iron sulfate, iron sulfide, and the like. Non-limiting examples of iron amino acid chelates/salts include iron aspartate, iron asparto glycinate, iron glycinate, iron bisglycinate, iron glycine sulfate, iron histidinate, iron methionine, iron proteinate, and iron amino acid chelate. Examples of suitable iron carboxylates include iron ascorbate, iron acetylacetonate, iron caprylate, iron citrate, iron ammonium citrate, iron fumarate, iron gluconate, iron ketoglutarate, iron laurate, iron malate, iron myristate, iron oxalate, iron ammonium oxalate, iron palmitate, iron stearate, iron succinate, iron tartrate, and so forth. Suitable iron chelates include iron EDTA, iron DTPA, iron EDDFIA, iron FIEEDTA, and the like. Examples of suitable iron complexes include iron dextran, iron acetyl-hydroxamate iron polymaltose, iron hydroxide polymaltose, iron polysaccharide complex, iron trimaltose, and so forth. In certain embodiments, the iron source present in the compositions disclosed herein may be an iron amino acid chelate or salt. In certain embodiments, the iron source may be iron glycinate, iron proteinate, or iron trimaltose. In specific embodiments, the iron source may be iron glycinate.
[0014] The amount of the iron source present in the liquid iron
compositions may vary depending, for example, on the identity of the iron source and/or the amount of iron present in the iron source. In general, the amount of the iron source present in the iron composition may range from about 0.5% to about 40% by weight of the composition. In some embodiments, the liquid iron composition may comprise from about 0.5% to about 2.0% (w/w), from about 2% to about 5% (w/w), from about 5% to about 10% (w/w), from about 10% to about 20% (w/w), from about 20 to about 30% (w/w), or from about 30% to about 40% (w/w) of the iron source. In specific embodiments, the liquid iron composition may comprise from about 10% to about 30% (w/w) of the iron source.
(b) Suspension Medium
[0015] The liquid iron composition further comprises at least one suspension medium. In some embodiments, the suspension medium may be a vegetable oil (e.g., soybean oil, corn oil, canola oil, rapeseed oil, cottonseed oil, safflower oil, sunflower oil, peanut oil, etc.), long chain (> 14 carbons) fatty acids, long chain fatty acid esters, mono-, di-, or triglycerides comprising long chain fatty acids, and so forth. In other embodiments, the suspension medium may be molasses, corn syrup, high fructose corn syrup, sugar beet syrup, cane sugar syrup, raw sugar solution, sorghum syrup, dextrose, sucrose, lactose, maltose, and the like. In particular embodiments, the suspension medium may be molasses, corn syrup, high fructose corn syrup, or dextrose.
[0016] The amount of the suspension medium present in the liquid iron composition can and will vary. In general, the amount of the suspension medium may range from about 15% to about 70% by weight of in the liquid iron composition. In certain embodiments, the liquid iron composition may comprise from about 15% to about 30% (w/w), from about 30% to about 40% (w/w), from about 40% to about 50% (w/w), from about 50%to about 60% (w/w), or from about 60% to about 70% (w/w) of the suspension medium. In specific embodiments, the liquid iron composition may comprise from about 20% to about 40% (w/w) of the suspension medium.
(c) Viscosity Modifier
[0017] The liquid iron composition also comprises at least one viscosity modifier. Non-limiting example of suitable viscosity modifiers include gums (e.g., xanthan gum, gum arabic, guar gum, gellan gum, and the like), alginates (e.g., alginic acid, alginate, sodium alginate, and so forth), pectins, gelatin, starches (e.g., corn starch, potato starch, wheat starch, rice starch, and the like), pregelatinized starch, cellulose, microcrystalline cellulose, and cellulose derivatives (e.g., methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and the like). In specific embodiments, the viscosity modifier may be a gum such as xanthan gum.
[0018] Various amounts of the viscosity modifier may be included in the liquid iron composition. In general, the amount of the viscosity modifier may range from about 0.03% to about 5.0% by weight of the liquid iron composition. In some
embodiments, the liquid iron composition may comprise from about 0.03% to about 0.1 % (w/w), from about 0.1 % to about 0.3% (w/w), from about 0.3% to about 1 % (w/w), from about 1 % to about 3% (w/w), or from about 3% (w/w) to about 5% (w/w) of the viscosity modifier. In specific embodiments, the liquid iron composition may comprise about 0.25% (w/w) of the viscosity modifier.
(d) Flavoring Agent
[0019] The liquid iron composition may further comprise a flavoring agent. Suitable flavoring agents include those comprising buttery, cheesy, fatty, fruity, green, meaty, musty, or sweet flavors. In some embodiments, the flavoring agent may comprise cherry flavor, apple flavor, peach flavor, pear flavor, strawberry flavor, raspberry flavor, plum flavor, pineapple flavor, apricot flavor, citrus flavor, vanilla flavor, tomato flavor, pumpkin pie flavor, cheese flavor, and the like. In specific embodiments, the liquid iron composition may comprise a fruit flavor. In one embodiment, the liquid iron composition comprises cherry flavor.
[0020] The amount of flavoring agent included in the liquid iron
composition may vary. In general, the amount of flavoring agent may range from about 0.03% to about 3.0% by weight of the liquid iron composition. In some embodiments, the liquid iron composition may comprise from about 0.03% to about 0.1 % (w/w), from about 0.1 % to about 0.3% (w/w), or from about 0.3% to about 1 % (w/w), or from about 1 % to about 3% (w/w) of the flavoring agent. In specific embodiments, the liquid iron composition may comprise about 0.3% (w/w) of the flavoring agent. (e) Optional Solvent
[0021 ] In certain embodiments, the liquid iron composition may further comprise a solvent. Suitable solvents include water, an alcohol (e.g., such as glycerin, propylene glycol, ethanol, and the like), an organic acid (e.g., formic acid, acetic acid, lactic acid, and so forth), and combinations thereof. In particular embodiments, the liquid iron composition may further comprise water and glycerin. In other embodiments, the liquid iron composition may further comprise water.
(f) Optional Nutrient or Supplement
[0022] In some embodiments, the liquid iron composition may further comprise one or more nutrients or supplements. Examples of suitable nutrients or supplements include vitamins, minerals, amino acids, antioxidants, organic acids, poly unsaturated fatty acids, essential oils, enzymes, prebiotics, probiotics, postbiotics, herbs, and pigments.
[0023] In some embodiments, the liquid iron composition may further comprise one or more vitamins. Suitable vitamins include vitamin A, vitamin B1
(thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 (folic acid), vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, other B-complex vitamins (e.g., choline, carnitine, adenine), or combinations thereof. The form of the vitamin may include salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of a vitamin, and metabolites of a vitamin.
[0024] In other embodiments, the liquid iron composition may further comprise one or more minerals. Examples of suitable minerals include calcium, chromium, cobalt, copper, iodine, magnesium, manganese, molybdenum, selenium, zinc, or combinations thereof. The mineral may be an inorganic mineral. Suitable inorganic minerals include, for example, metal sulfates, metal oxides, metal hydroxides, metal oxychlorides, metal carbonates, and metal halides. Alternatively, the mineral may be an organic mineral, e.g., a metal chelate comprising a metal ion and an organic ligand. The organic ligand may be an amino acid, an amino acid analog, a proteinate, a carbohydrate, or an organic acid. [0025] In further embodiments, the liquid iron composition may further comprise one or more amino acids. Non-limiting suitable amino acids include standard amino acids (i.e., alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine), non-standard amino acids (e.g., L-DOPA, GABA, 2-aminobutyric acid, and the like), amino acid analogs, or combinations thereof. Amino acid analogs include a-hydroxy analogs (e.g., methionine hydroxy analog), as well side chain protected analogs or N-derivatized amino acids.
[0026] In alternate embodiments, the liquid iron composition may further comprise one or more antioxidants. Suitable antioxidants include, but are not limited to, ascorbic acid and its salts, ascorbyl palmitate, ascorbyl stearate, anoxomer, n- acetylcysteine, benzyl isothiocyanate, m-aminobenzoic acid, o-aminobenzoic acid, p- aminobenzoic acid (PABA), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), caffeic acid, canthaxantin, alpha-carotene, beta-carotene, beta-caraotene, beta- apo-carotenoic acid, carnosol, carvacrol, catechins, cetyl gallate, chlorogenic acid, citric acid and its salts, clove extract, coffee bean extract, p-coumaric acid, 3,4- dihydroxybenzoic acid, N,N’-diphenyl-p-phenylenediamine (DPPD), dilauryl
thiodipropionate, distearyl thiodipropionate, 2,6-di-tert-butylphenol, dodecyl gallate, edetic acid, ellagic acid, erythorbic acid, sodium erythorbate, esculetin, esculin, 6- ethoxy-1 ,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin), ethyl gallate, ethyl maltol, ethylenediaminetetraacetic acid (EDTA), eucalyptus extract, eugenol, ferulic acid, flavonoids (e.g., catechin, epicatechin, epicatechin gallate, epigallocatechin (EGC), epigallocatechin gallate (EGCG), polyphenol epigallocatechin-3-gallate, flavones (e.g., apigenin, chrysin, luteolin), flavonols (e.g., datiscetin, myricetin, daemfero), flavanones, fraxetin, fumaric acid, gallic acid, gentian extract, gluconic acid, glycine, gum guaiacum, hesperetin, alpha-hydroxybenzyl phosphinic acid, hydroxycinammic acid,
hydroxyglutaric acid, hydroquinone, n-hydroxysuccinic acid, hydroxytryrosol,
hydroxyurea, rice bran extract, lactic acid and its salts, lecithin, lecithin citrate; R-alpha- lipoic acid, lutein, lycopene, malic acid, maltol, 5-methoxy tryptamine, methyl gallate, monoglyceride citrate; monoisopropyl citrate; morin, beta-naphthoflavone,
nordihydroguaiaretic acid (NDGA), octyl gallate, oxalic acid, palmityl citrate, phenothiazine, phosphatidylcholine, phosphoric acid, phosphates, phytic acid, phytylubichromel, pimento extract, propyl gallate, polyphosphates, quercetin, trans- resveratrol, rosemary extract, rosmarinic acid, sage extract, sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate, syringic acid, tartaric acid, thymol, tocopherols (i.e. , alpha-, beta-, gamma- and delta-tocopherol), tocotrienols (i.e., alpha-, beta-, gamma- and delta-tocotrienols), tyrosol, vanilic acid, 2,6-di-tert-butyl-4-hydroxymethylphenol (i.e., lonox 100), 2,4-(tris-3’,5’-bi-tert-butyl-4’-hydroxybenzyl)-mesitylene (i.e., lonox 330), 2,4,5-trihydroxybutyrophenone, ubiquinone, tertiary butyl hydroquinone (TBHQ), thiodipropionic acid, trihydroxy butyrophenone, tryptamine, tyramine, uric acid, vitamin K and derivates, vitamin Q10, wheat germ oil, zeaxanthin, or combinations thereof.
[0027] In still other embodiments, the liquid iron composition may further comprise one or more organic acids. The organic acid may be a carboxylic acid or a substituted carboxylic acid. The carboxylic acid may be a mono-, di-, or tri-carboxyl ic acid. In general, the carboxylic acid may contain from about one to about twenty-two carbon atoms. Suitable organic acids, by way of non-limiting example, include acetic acid, adipic acid, butanoic acid, benzoic acid, cinnamaldehyde, citric acid, formic acid, fumaric acid, glutaric acid, glycolic acid, lactic acid, malic acid, mandelic acid, propionic acid, sorbic acid, succinic acid, tartaric acid, or combinations thereof. Salts of organic acids comprising carboxylic acids are also suitable for certain embodiments.
Representative suitable salts include the ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, and zinc salts of organic acids.
[0028] In yet other embodiments, the liquid iron composition may further comprise one or more poly unsaturated fatty acids. Suitable poly unsaturated fatty acids (PUFAs) include medium chain fatty acids having from 6 to 12 carbon atoms and long chain fatty acids having at least 12 carbon atoms having at least two carbon- carbon double bonds, generally in the cis-configuration. In specific embodiments, the PUFA may be an omega fatty acid. The PUFA may be an omega-3 fatty acid in which the first double bond occurs in the third carbon-carbon bond from the methyl end of the carbon chain (i.e., opposite the carboxyl acid group). Suitable examples of omega-3 fatty acids include all-cis 7, 10, 13-hexadecatrienoic acid; all-cis-9, 12,15-octadecatrienoic acid (alpha-linolenic acid, ALA); all-cis-6,9,12,15,-octadecatetraenoic acid (stearidonic acid); all-cis-8,11 ,14,17-eicosatetraenoic acid (eicosatetraenoic acid); all-cis- 5,8,11 ,14,17-eicosapentaenoic acid (eicosapentaenoic acid, EPA); all-cis- 7,10,13,16,19-docosapentaenoic acid (clupanodonic acid, DPA); all-cis-4,7, 10, 13, 16, 19- docosahexaenoic acid (docosahexaenoic acid, DHA); all-cis-4,7, 10, 13, 16, 19- docosahexaenoic acid; and all-cis-6,9, 12, 15,18,21 -tetracosenoic acid (nisinic acid). In an alternative embodiment, the PUFA may be an omega-6 fatty acid in which the first double bond occurs in the sixth carbon-carbon bond from the methyl end of the carbon chain. Examples of omega-6 fatty acids include all-cis-9,12-octadecadienoic acid (linoleic acid); all-cis-6,9, 12-octadecatrienoic acid (gamma-linolenic acid, GLA); all-cis- 11 ,14-eicosadienoic acid (eicosadienoic acid); all-cis-8,11 ,14-eicosatrienoic acid
(dihomo-gamma-linolenic acid, DGLA); all-cis-5,8,11 ,14-eicosatetraenoic acid
(arachidonic acid, AA); all-cis-13,16-docosadienoic acid (docosadienoic acid); all-cis- 7,10,13,16-docosatetraenoic acid (adrenic acid); and all-cis-4,7, 10,13,16- docosapentaenoic acid (docosapentaenoic acid). In yet another alternative
embodiment, the PUFA may be an omega-9 fatty acid in which the first double bond occurs in the ninth carbon-carbon bond from the methyl end of the carbon chain, or a conjugated fatty acid, in which at least one pair of double bonds are separated by only one single bond. Suitable examples of omega-9 fatty acids include cis-9-octadecenoic acid (oleic acid); cis-11-eicosenoic acid (eicosenoic acid); all-cis-5,8,11 -eicosatrienoic acid (mead acid); cis-13-docosenoic acid (erucic acid), and cis-15-tetracosenoic acid (nervonic acid). Examples of conjugated fatty acids include 9Z, 11 E-octadeca-9, 11 - dienoic acid (rumenic acid); 10E,12Z-octadeca-9,11 -dienoic acid; 8E,10E,12Z- octadecatrienoic acid (a-calendic acid); 8E,10E,12E-octadecatrienoic acid (b-Calendic acid); 8E,10Z,12E-octadecatrienoic acid (jacaric acid); 9E,11 E,13Z-octadeca-9,11 ,13- trienoic acid (a-eleostearic acid); 9E, 11 E, 13E-octadeca-9, 11 ,13-trienoic acid (b- eleostearic acid); 9Z,11Z,13E-octadeca-9,11 ,13-trienoic acid (catalpic acid), and
9E, 11 Z, 13E-octadeca-9, 11 ,13-trienoic acid (punicic acid).
[0029] In additional embodiments, the liquid iron composition may further comprise one or more essential oils. Suitable essential oils include, but are not limited to, peppermint oil, cinnamon leaf oil, lemongrass oil, clove oil, castor oil, wintergreen oil, sweet orange, spearmint oil, cederwood oil, aldehyde C16, a terpineol, amyl cinnamic aldehyde, amyl salicylate, anisic aldehyde, benzyl alcohol, benzyl acetate, camphor, capsaicin, cinnamaldehyde, cinnamic alcohol, carvacrol, carveol, citral, citronellal, citronellol, p cymene, diethyl phthalate, dimethyl salicylate, dipropylene glycol, eucalyptol (cineole), eugenol, iso-eugenol, galaxolide, geraniol, guaiacol, ionone, listea cubea, menthol, menthyl salicylate, methyl anthranilate, methyl ionone, methyl salicylate, a phellandrene, pennyroyal oil, perillaldehyde, 1 or 2 phenyl ethyl alcohol, 1 or 2 phenyl ethyl propionate, piperonal, piperonyl acetate, piperonyl alcohol, D pulegone, terpinen 4 ol, terpinyl acetate, 4 tert butylcyclohexyl acetate, thyme oil, thymol, metabolites of trans-anethole, vanillin, ethyl vanillin, derivatives thereof, or combinations thereof.
[0030] In still other embodiments, the liquid iron composition may further comprise one or more prebiotics, probiotics, and/or postbiotics. Pre/pro/postbiotics include agents derived from yeast or bacteria that promote good digestive health. By way of non-limiting example, yeast-derived pre/pro/postbiotics include yeast cell wall derived components such as b-glucans, arabinoxylan isomaltose,
agarooligosaccharides, lactosucrose, cyclodextrins, lactose, fructooligosaccharides, laminariheptaose, lactulose, b-galactooligosaccharides, mannanoligosaccharides, raffinose, stachyose, oligofructose, glucosyl sucrose, sucrose thermal oligosaccharide, isomalturose, caramel, inulin, and xylooligosaccharides. In an exemplary embodiment, the yeast-derived agent may be b-glucans and/or mannanoligosaccharides. Sources for yeast cell wall derived components include Saccharomyces bisporus,
Saccharomyces boulardii, Saccharomyces cerevisiae, Saccharomyces capsularis, Saccharomyces delbrueckii, Saccharomyces fermentati, Saccharomyces lugwigii, Saccharomyces microellipsoides, Saccharomyces pastorianus, Saccharomyces rosei, Candida albicans, Candida cloaceae, Candida tropicalis, Candida utilis, Geotrichum candidum, Hansenula americana, Hansenula anomala, Hansenula wingei, and
Aspergillus oryzae. Pre/pro/postbiotics may also include bacteria cell wall derived agents such as peptidoglycan and other components derived from gram-positive bacteria with a high content of peptidoglycan. Exemplary gram-positive bacteria include Lactobacillus acidophilus, Bifedobact thermophilum, Bifedobat longhum, Streptococcus faecium, Bacillus pumilus, Bacillus subtilis, Bacillus licheniformis, Lactobacillus acidophilus, Lactobacillus casei, Enterococcus faecium, Bifidobacterium bifidium, Propionibacterium acidipropionici, Propionibacteriium freudenreichii, and
Bifidobacterium pseudolongum.
[0031 ] In alternate embodiments, the liquid iron composition may further comprise one or more enzymes or enzyme variants. Suitable non-limiting examples of enzymes include amylases, carbohydrases, cellulases, esterases, galactonases, galactosidases, glucanases, hemicellulases, hydrolases, lipases, oxidoreductases, pectinases, peptidases, phosphatases, phospholipases, phytases, proteases, transferases, xylanases, or combinations thereof.
[0032] In further embodiments, the liquid iron composition may further comprise one or more herbals. Suitable herbals and herbal derivatives, as used herein, refer to herbal extracts, and substances derived from plants and plant parts, such as leaves, flowers and roots, without limitation. Non-limiting exemplary herbals and herbal derivatives include agrimony, alfalfa, aloe vera, amaranth, angelica, anise, barberry, basil, bayberry, bee pollen, birch, bistort, blackberry, black cohosh, black walnut, blessed thistle, blue cohosh, blue vervain, boneset, borage, buchu, buckthorn, bugleweed, burdock, capsicum, cayenne, caraway, cascara sagrada, catnip, celery, centaury, chamomile, chaparral, chickweed, chicory, chinchona, cloves, coltsfoot, comfrey, cornsilk, couch grass, cramp bark, culver's root, cyani, cornflower, damiana, dandelion, devils claw, dong quai, echinacea, elecampane, ephedra, eucalyptus, evening primrose, eyebright, false unicorn, fennel, fenugreek, figwort, flaxseed, garlic, gentian, ginger, ginseng, golden seal, gotu kola, gum weed, hawthorn, hops,
horehound, horseradish, horsetail, hoshouwu, hydrangea, hyssop, Iceland moss, irish moss, jojoba, juniper, kelp, lady’s slipper, lemon grass, licorice, lobelia, mandrake, marigold, marjoram, marshmallow, mistletoe, mullein, mustard, myrrh, nettle, oatstraw, Oregon grape, papaya, parsley, passion flower, peach, pennyroyal, peppermint, periwinkle, plantain, pleurisy root, pokeweed, prickly ash, psyllium, quassia, queen of the meadow, red clover, red raspberry, redmond clay, rhubarb, rose hips, rosemary, rue, safflower, saffron, sage, St. John’s wort, sarsaparilla, sassafras, saw palmetto, scullcap, senega, senna, shepherd's purse, slippery elm, spearmint, spikenard, squawvine, stillingia, strawberry, taheebo, thyme, uva ursi, valerian, violet, watercress, white oak bark, white pine bark, wild cherry, wild lettuce, wild yam, willow, wintergreen, witch hazel, wood betony, wormwood, yarrow, yellow dock, yerba santa, yucca, or combinations thereof.
[0033] In still other embodiments, the liquid iron composition may further comprise one or more natural pigments. Suitable pigments include, without limit, actinioerythrin, alizarin, alloxanthin, p-apo-2'-carotenal, apo-2-lycopenal, apo-6'- lycopenal, astacein, astaxanthin, azafrinaldehyde, aacterioruberin, aixin, a-carotine, b- carotine, y-carotine, b-carotenone, canthaxanthin, capsanthin, capsorubin,
citranaxanthin, citroxanthin, crocetin, crocetinsemialdehyde, crocin, crustaxanthin, cryptocapsin, a-cryptoxanthin, b-cryptoxanthin, cryptomonaxanthin, cynthiaxanthin, decaprenoxanthin, dehydroadonirubin, diadinoxanthin, 1 ,4-diamino-2,3- dihydroanthraquinone, 1 ,4-dihydroxyanthraquinone, 2,2'-diketospirilloxanthin, eschscholtzxanthin, eschscholtzxanthone, flexixanthin, foliachrome, fucoxanthin, gazaniaxanthin, hexahydrolycopene, hopkinsiaxanthin, hydroxyspheriodenone, isofucoxanthin, loroxanthin, lutein, luteoxanthin, lycopene, lycopersene, lycoxanthin, morindone, mutatoxanthin, neochrome, neoxanthin, nonaprenoxanthin, OH- Chlorobactene, okenone, oscillaxanthin, paracentrone, pectenolone, pectenoxanthin, peridinin, phleixanthophyll, phoeniconone, phoenicopterone, phoenicoxanthin, physalien, phytofluene, pyrrhoxanthininol, quinones, rhodopin, rhodopinal, rhodopinol, rhodovibrin, rhodoxanthin, rubixanthone, saproxanthin, semi-a-carotenone, semi-b- carotenone, sintaxanthin, siphonaxanthin, siphonein, spheroidene, tangeraxanthin, torularhodin, torularhodin methyl ester, torularhodinaldehyde, torulene, 1 ,2,4- trihydroxyanthraquinone, triphasiaxanthin, trollichrome, vaucheriaxanthin, violaxanthin, wamingone, xanthin, zeaxanthin, a-zeacarotene, or combinations thereof.
(g) Formulations
[0034] The liquid iron composition may be formulated as a liquid solution, a liquid suspension, or a liquid emulsion. In other embodiments, the liquid iron composition may be spray dried and the spray dried particles may be agglomerated into pellets, crumbles, or capsules. In other embodiments, the liquid iron composition or spray dried particles prepared therefrom may be formed into a solid or semi-solid feeder block or lick block. The feeder block or lick block may also comprise nutrients (e.g., amino acids, saccharides, fats, etc.), vitamins, minerals, and the like.
(II) Composition Comprising Iron Source and Creep Feed
[0035] A further aspect of the present disclosure provides a composition comprising an iron source and a creep feed. The composition may further comprise one or more flavoring agents or palatability enhancers.
(a) Iron source
[0036] A variety of iron sources may be present in the iron creep feed compositions. The iron source may comprise iron of various oxidation states. For example, the oxidation state of iron may be Fe2_, Fe1_, Fe°, Fe1 +, Fe2+, Fe3+, Fe5+, or Fe6+. Typically, the oxidation state of the iron in the iron source may be Fe2+ (ferrous) or Fe3+ (ferric). The iron source may be an iron salt, an iron amino acid chelate or iron amino acid salt, an iron carboxylate, an iron chelate, or an iron complex.
[0037] Examples of suitable iron salts include iron acetate, iron bromide, iron chloride, iron chromate, iron fluoride, iron hydroxide, iron nitrate, iron oxide, iron oxide-hydroxide, iron phosphate, iron pyrophosphate, iron sulfate, iron sulfide, and the like. Non-limiting examples of iron amino acid chelates/salts include iron aspartate, iron asparto glycinate, iron glycinate, iron bisglycinate, iron glycine sulfate, iron histidinate, iron methionine, iron proteinate, and iron amino acid chelate. Examples of suitable iron carboxylates include iron ascorbate, iron acetylacetonate, iron caprylate, iron citrate, iron ammonium citrate, iron fumarate, iron gluconate, iron ketoglutarate, iron laurate, iron malate, iron myristate, iron oxalate, iron ammonium oxalate, iron palmitate, iron stearate, iron succinate, iron tartrate, and so forth. Suitable iron chelates include iron EDTA, iron DTPA, iron EDDFIA, iron FIEEDTA, and the like. Examples of suitable iron complexes include iron dextran, iron acetyl-hydroxamate iron polymaltose, iron hydroxide polymaltose, iron polysaccharide complex, iron trimaltose, and so forth. In certain embodiments, the iron source present in the compositions disclosed herein may be an iron amino acid chelate or salt. In certain embodiments, the iron source may be iron glycinate, iron proteinate, or iron trimaltose. In specific embodiments, the iron source may be iron glycinate.
[0038] The amount of the iron source present in the iron creep feed compositions may vary depending, for example, on the identity of the iron source and/or the amount of iron present in the iron source. In general, the amount of the iron source may range from about 0.1 % to about 10% by weight of the composition. In some embodiments, the iron creep feed composition may comprise from about 0.1 % to about 0.3% (w/w), from about 0.3% to about 1 % (w/w), from about 1 % to about 3% (w/w), or from about 3% to about 10% (w/w) of the iron source. In specific embodiments, the iron creep feed composition may comprise from about 0.2% to about 4% (w/w) of the iron source.
(b) Creep Feed
[0039] Creep feed is solid or semi-solid feed provided to piglets while they are suckling the sow. In general, creep feeds comprise sources of protein and carbohydrates that can be easily digested by sucking pigs. For example, a creep feed may comprise hydrated oats, cooked cereals, cereal mashes, soy bean meal, corn gluten meal, canola meal, cottonseed meal, milk by-products, milk proteins, lactose, rolled oats, rice bran, broken rice, wheat bran, milled or cracked corn, wheat, sorghum, barley, distillers residues, vegetable proteins, oilseed extracts, fatty acids, amino acids, feed phosphates, vitamins, and/or minerals. The components included in the creep feed and the total amount of protein present in the creep feed can and will vary depending, for example, upon the age of the piglet.
(c) Optional Flavoring Agents or Palatability Enhancers
[0040] The iron creep feed composition may further comprise flavoring agents or palatability enhancers. Examples of suitable flavoring agents are described above in section (l)(d). Suitable palatability enhancers include milk by-products, dried skim milk, yeast products, spray dried porcine plasma (SDPP), sweeteners, and the like. (d) Optional Nutrient or Supplement
[0041 ] The iron creep feed composition may further comprise optional nutrients or supplements, as described above in section (l)(f).
(e) Formulations
[0042] The composition comprising the iron source and the creep feed may be in dry form, e.g., pelleted, dry kibble, granulates, crumbles, powders, solid or semi-solid blocks, and the like. In alternate embodiments, the iron creep feed
compositions may be semi-solid or liquid, e.g., gels, slurries, suspensions, extrudates, moist kibbles, gruels, and so forth.
(Ill) Methods for Preparing the Iron Compositions
[0043] Still another aspect of the present disclosure provides methods for preparing the iron compositions disclosed herein.
[0044] The liquid iron compositions described above in section (I) may be prepared by mixing the iron source, the suspension medium; the viscosity modifier, and an optional flavoring agent. The ingredients may be mixed in any order. The mixing may comprise stirring, blending, rotating, and the like. As mentioned above, the liquid composition may be spray dried and the spray dried particles may be agglomerated, pressed into pellets, pressed into block, etc. The liquid composition may be extruded and dried to the desired level of moisture.
[0045] The iron creep feed compositions described above in section (II) may be prepared by adding the iron source with the solid or semi-solid creep feed. The iron source and creep feed may be mixed by any suitable means, e.g., blending, milling, roller compacting, granulating, etc. The iron creep feed composition may be pelleted, compacted, powdered, extruded, and the like to produce the final formulation. In other embodiments, the iron creep feed composition may be mixed with a liquid (e.g., water, whey, fat or oil), such that the final formulation of the iron creep feed composition may a liquid or a suspension. Alternatively, the liquid iron creep feed composition may be spray dried and agglomerated. (IV) Methods for Preventing Anemia and/or Iron Deficiency in Piglets
[0046] Still another aspect of the present disclosure encompasses methods for preventing anemia and/or iron deficiency in piglets, wherein the methods comprise administering to piglets an effective amount of the oral iron composition liquid iron compositions disclosed herein, e.g., the liquid iron compositions described above in section (I) or the iron creep feed compositions described above in section (II), within the first three days after the piglet’s birth.
[0047] In some embodiments, the method comprises administering to the piglets several doses of the oral iron composition within the first 15 days after the piglet’s birth. For example, the piglets may be administered a first dosage of the oral iron composition within the first three days after birth, and then may be administered a second dosage of the oral iron composition from about five days to about nine days after birth. Alternatively, the method may comprise administering multiple or continous doses of the oral iron composition within the first 15 days, within the first 21 days, or within the first 28 days after birth.
[0048] In some embodiments, the oral iron composition may be
administered to the piglet via a lick bottle, a nipple or teat bucket, a feed or lick block, feeding trough, spot feeder, timed feeder, or lick bowl, such that the piglet may ingest small amounts of the iron composition several times a day.
[0049] In one embodiment, the method comprises applying the liquid iron composition onto the underline (i.e., teats and belly area) of a lactating sow, and contacting piglets with the lactating sow in a manner such that the piglets can nurse and ingest the iron composition from the underline of the sow in a quantity sufficient to prevent iron deficiency and/or anemia in the piglet. The liquid iron composition may “adhere” to the underline of the sow because of the presence of the suspension medium and/or the viscosity modifier in the liquid iron composition. The adherence of the liquid iron composition to the underline of the sow permits consumption of the iron
composition by the piglet during nursing. The liquid iron composition that is applied to the sow may further comprise a flavoring agent to increase the palatability of the iron composition. As such, the piglet may ingest small amounts of the iron composition several times a day. [0050] The liquid iron composition may be applied to the underline of the sow by spraying, rolling, brushing, or other suitable means known in the art. For example, the liquid iron composition may be sprayed into the underline of the sow with a hand held pressure sprayer, a backpack style pressure sprayer, a garden sprayer, a tractor-mounted sprayer, or other suitable sprayer. Alternatively, the liquid iron composition may be applied to the underline of the sow with a roller, brush, mop, wick, or oiler. The liquid composition may be applied to the underline of the sow twice a day, once a day, or every other day during the nursing period.
[0051 ] In general, the“effective amount” of the oral iron composition provides about 10 mg of iron per piglet per day. The skilled person understands that a dose of the oral iron composition may vary depending, for example, upon the means for administering the oral iron composition (e.g., once per day vs. multiple times per day), and the identity and/or concentration of the iron source in the oral iron composition. In various embodiments, about 50-300 mg of iron may be provided per piglet per day.
[0052] After ingestion of the oral iron compositions as described herein, nursing piglets show no signs of iron deficiency and/or anemia. Anemia and/or iron deficiency may be monitored by blood hemoglobin concentration or other blood hematological parameters. Hemoglobin concentrations in blood may be determined using means well known in the art. Normal blood hemoglobin concentrations in sucking pigs at day three after birth range from about 7-9 g/dL. At weaning, piglets can have blood hemoglobin concentrations from about 9-12 g/dL.
[0053] Other hematological indices included erythrocyte count (RBC), total and differential leukocyte count, platelets, red blood cell distribution width (RDW), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular Hb concentration (MCHC), reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width (RDWr), and reticulocyte Hb distribution width (HDWr). DEFINITIONS
[0054] The following definitions are provided to facilitate understanding of the disclosure.
[0055] When introducing elements of the embodiments described herein, the articles "a", "an", "the" and "said" are intended to mean that there are one or more of the elements. The terms "comprising", "including" and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.
[0056] The term“about,” particularly in reference to a given quantity, is meant to encompass deviations of plus or minus five percent.
[0057] The terms“sucking” and“nursing” are used interchangeably.
EXAMPLES
[0058] The following examples illustrate various embodiments of the present disclosure.
Example 1: Preparation of Liquid Iron Formulations
[0059] Flavored and unflavored iron glycinate (1 :1 metal:glycine ratio) formulations were prepared according to Table 1.
Figure imgf000020_0001
[0060] Starting with a primary vessel, 90% of the formulation water was weighed out into the primary vessel. The primary vessel was heated to 50°C. In a secondary vessel, xanthan gum was mixed with glycerin. Using an overhead mixer, the premix from the secondary vessel was added to the primary vessel and mixed until fully dissolved. Water from the primary vessel was used to rinse the remaining premix out of the secondary vessel into the primary vessel. Iron glycinate was added to the primary vessel and mixed until fully suspended. Flavoring (e.g., cherry flavor, cheese flavor) was added to aliquots of the liquid iron formulation at 0.3%.
Example 2. Palatability Study
[0061 ] A study was designed to determine the palatability of the liquid ion formulations. Eighteen weanling piglets were randomly allotted to 1 of 3 two-way choice comparisons (i.e. , cherry flavor vs. reference, cheese flavor vs. reference, reference vs. reference). Each choice comparison (treatment) had 6 pens (replicates) with 1 pig per pen. Each pen was equipped with two side-by-side feeders.
[0062] During the first 7 days of the study, all pigs were fed the same creep feed ad libitum. The next 4 days were considered as the experimental period.
Two respective experimental diets (mixed creep feed with iron solution in 3:1 weight ratio) were placed in each feeder within each pen at 500 g/d for each diet/feeder. The daily feed was provided to each feeder once in the morning around 7:00 am. The remaining feed in each feeder was taken out and weighed on the following day and fresh feed was provided after mixing creep feed with 1 of 3 iron solutions. The same procedure was continued for day 3 and 4 until the completion of the 4-day experimental period.
[0063] Feed preference was measured on day 8-11 (or days 1 -4 after initiation of dietary treatments) as intake of the feed with artificial flavor expressed as percentage of total feed intake in each pen. The following mathematical equation was used in the calculation:
Intake of feed with flavor
%Feed preference = -—— - - - - - - x 100
Total feed intake in each pen [0064] In terms of double control comparison (reference vs. reference), a similar equation was used to calculate the preference which took into account the effect of feeder position (left vs. right). This served as the control to eliminate the effect of feeder position on feed preference.
Intake of left position
%Position preference = -—— - - - - - - x 100
Total feed intake in each pen
[0065] SAS software (SAS 9.4) was used for all data analysis. Each pen served as an experimental unit. Paired t-test was used to conduct comparisons between cherry and reference, cheese and reference, left and right feeder positions. A probability of P < 0.05 was considered significant, and 0.05 < P < 0.10 was declared a trend.
[0066] The four-day feed preference study showed that weaning pigs fed diets containing supplementation of cherry flavor in the iron solution had greater (324.96 vs. 197.38 g/d, P = 0.01 ; Table 2) average daily feed intake (ADFI) compared with pigs fed diets containing the unflavored iron solution (reference). Weaning pigs fed diets containing supplementation of cheese flavor in the iron solution tended to have lower (212.17 vs. 287.38 g/d, P = 0.11 ; Table 3) ADFI compared with pigs fed diets containing the unflavored iron solution (reference). Additionally, feeder position did not (297.17 vs. 276.00 g/d for left and right feeder, respectively, P = 0.58; Table 2) affect ADFI of piglets. The results indicate that cherry flavor is the optimal flavor for piglets, which can promote their feed intake. The preference for cherry flavored feed was about 62%, whereas the preference for cheese flavored feed was about 42%.
Figure imgf000022_0001
Figure imgf000023_0001
Example 3. Comparison of Oral Gavage of Liquid Iron Solution vs. Iron Dextran Injection on Growth Rate and Iron Status of Suckling Pigs
[0067] Four lactating sows with similar parity (around P3) and their newborn piglets were selected from a commercial sow farm located in Auxvasse, MO. within 24 h after birth, litter size was equalized to 12 for each sow. Within 24 h of birth, piglets in each litter were ear-tagged to identify each piglet. The 4 litters were randomly allotted to 1 of 4 treatments. The sows were fed the same commercial lactation diets ad libitum. The 4 treatments include: 1 ) intramuscular injection of 1 ml iron dextran to supply 200 mg Fe for each piglet on d 3 of lactation (CON), 2) oral gavage of 2.7 ml of Fe-glycinate suspension (Table 4) to supply 200 mg Fe for each piglet on day 3 of lactation (GLY200), 3) oral gavage of 1.35 ml of Fe-glycinate suspension on both d 3 and 6 of lactation (GLY200D), or 4) oral gavage of 2.7 ml Fe-glycinate suspension on both d 3 and 6 of lactation (GLY400D). The treatments are summarized in Table 5.
The study lasted 15 days.
Figure imgf000023_0002
Figure imgf000023_0003
Figure imgf000024_0001
[0068] Blood hemoglobin concentrations were determined on d 3, 9 and 15 using HemoCue Hb 201 + analyzer (HemoCue, Inc. , Lake Forest, CA). On day 3, before blood collection, the right ear of each piglet was disinfected using alcohol. Then the right ear was notched to allow for collection of blood. The first 2 or 3 drops of blood were wiped away and light pressure was re-applied towards the pinna until another drop of blood appeared. On day 9, tails were docked and blood was collected from that location. At each time point, when the blood drop was large enough, the microcuvette was filled in one continuous process. If there were air bubbles in the filled microcuvette, the microcuvette was discarded and a new microcuvette was filled from a new drop of blood. Small bubbles around the edge could be ignored. Then the filled microcuvette was placed in the cuvette holder and put in the measuring position within 10 min after filling the microcuvette. After 15 to 60 seconds, the hemoglobin value of the sample was displayed on the screen.
[0069] On day 15, approximately 3 mL of blood from each piglet was withdrawn by puncture of the anterior vena cava into a chilled K3EDTA tube. The K3EDTA tube for each weaning piglet was stored at 4 °C until analysis of hematological and reticulocyte indices within 2 days of collection. Hematological indices included erythrocyte count (RBC), total and differential leukocyte count, platelets, red blood cell distribution width (RDW), hematocrit (Hot), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular Hb concentration (MCHC).
Reticulocyte indices included reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width
(RDWr), and reticulocyte Hb distribution width (HDWr). [0070] SAS software (SAS 9.4) was used for all data analysis. Each piglet served as an experimental unit. The LSMEANS statement was used to calculate the least square means. A probability of P < 0.05 was considered significant, and 0.05 < P < 0.10 was declared a trend.
[0071 ] The GLIMMIX procedure was used to analyze the data.
Treatments were considered as the fixed effect. Birth weight was used as covariates to adjust for the analysis of BW on d 9 and 15, as well as growth rate. Hb concentration on d 3 of lactation was used as covariate to adjust for the analysis of Hb concentration on d 9 and 15.
[0072] Average birth weight of piglets assigned to GLY200 was greater (P = 0.01 ; Table 6) than those assigned to GLY200D. Therefore, the birth weight was used as covariate to adjust for analysis of body weight (BW) on d 9 and 15, as well as average daily gain during d 0 to 15. There were no differences (P > 0.10) among CON, GLY200 and GLY200D in terms of BW on d 15 and average daily gain during d 0 to d 15. However, pigs administered GLY400D had significant lower (P = 0.01 ) BW and ADG during d 0 to d 15, compared with pigs given CON or GLY200D, indicating that over supply of iron could exert toxic effect on the piglets, therefore impairing growth performance.
Figure imgf000026_0001
a cWithin a row, means without a common superscript differ (P < 0.05).
1CON represents conventional iron injection of 200 mg Fe on d 3 of lactation; GLY200 represents oral gavage of 200 mg of iron glycinate suspension on d 3 of lactation; GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of iron glycinate suspension on d 3 and 9 of lactation.
[0073] Blood hemoglobin (Hb) concentrations on d 3 of lactation (before iron treatment) were greater (P < 0.01 ; Table 7 and Figure 1 ) in piglets in the GLY200 group than piglets in the CON and GLY200D groups. Therefore, blood hemoglobin concentrations on d 3 were used as covariate to adjust the analysis of blood
hemoglobin concentrations on d 9 and 15. There were no significant differences (P > 0.10) among CON, GLY200 and GLY00D in terms of blood hemoglobin concentrations on d 9 and 15. However, piglets administered GLY400D had greater (P < 0.01 ) blood hemoglobin concentrations on d 15 of lactation than piglets given CON, GLY200, or GLY200D.
Figure imgf000027_0001
a bWithin a row, means without a common superscript differ (P < 0.05).
1CON represents conventional iron injection of 200 mg Fe on d 3 of lactation; GLY200 represents oral gavage of 200 mg of iron glycinate suspension on d 3 of lactation; GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of iron glycinate suspension on d 3 and 9 of lactation.
2Hb represents blood hemoglobin.
[0074] Piglets administered GLY200D and GLY400D had significant greater mean corpuscular volume (MCV; P = 0.01 ; Table 8), mean corpuscular hemoglobin (MCH; P < 0.01 ) and lower red blood cell distribution width (RDW; P < 0.01 ) compared with piglets receiving CON or GLY200. Similarly, piglets administered GLY200D and GLY400D had significant greater (P < 0.01 ) mean cell hemoglobin concentration (MCHC) compared with piglets from CON. The results indicated that delivering iron through oral gavage in two small amounts of 100 mg on d 3 and 9 of lactation could achieve better iron status in suckling pigs compared with conventional iron dextran injection.
Figure imgf000027_0002
Figure imgf000028_0001
a bWithin a row, means without a common superscript differ (P < 0.05).
1CON represents conventional iron injection of 200 mg Fe on d 3 of lactation; GLY200 represents oral gavage of 200 mg of iron glycinate suspension on d 3 of lactation; GLY200D and GLY400D represent oral gavage of 2 doses of 100 or 200 mg of iron glycinate suspension on d 3 and 9 of lactation.
2MCV, MCH, MCHC and RDW represent mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, respectively.
Example 4. Sow Mammary Study
[0075] An iron glycinate suspension comprising cherry flavor was applied to the underline (i.e. , teats and belly area) of a lactating sow using a pressurized garden sprayer. The piglets nursed as normal.
Example 5. Comparison of Suckling Piglets Administered via Creep Feed vs. Spraying into Sow Mammary Glands - Study 1
[0076] The objective of the present study was to investigate the efficacy of feeding gel feed containing 0.22% Fe to piglets from d 3 to 5, and from d 10 to 12 of lactation and application of iron suspension containing 3.32% Fe on sow mammary glands from d 3 to 5, and from d 10 to 12 of lactation compared with conventional iron injection.
[0077] Nine lactating sows with similar parity (P2-P4) and their newborn piglets were selected from a commercial sow farm located in Auxvasse, MO. Within 24 h after birth, litter size was equalized to 13-14 piglets for these 9 sows. The sows with their associated litters were randomly allotted to 1 of 3 dietary treatments. On d 3 of lactation, all piglets were ear-tagged to identify each piglet. The sows were fed the same commercial lactation diets ad libitum. The 3 treatments include: 1 ) intramuscular injection of 1 ml iron dextran to supply 200 mg Fe for each piglet on d 3 of lactation (IN J); 2) Feeding gel feed with 1.27% iron glycinate (to achieve 0.22% Fe) to the piglets ad libitum from d 3 to 5 and from d 10 to 12 of lactation (GEL-0.22% Fe); 3) Spray iron suspension with 20% iron glycinate (Table 9) on the sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation (SPRAY). The treatments were displayed in Table 10. The study lasted 16 days.
Figure imgf000029_0001
Figure imgf000029_0002
[0078] The piglets in each litter were weighed individually on d 3, 9 and 15 of lactation. The piglets in each litter were also be used to test their blood hemoglobin concentrations using HemoCue Hb 201 + analyzer (HemoCue, Inc., Lake Forest, CA) on d 3, 5, 9 and 15 of lactation. Blood for hemoglobin analysis was obtained on d 3 of lactation either directly following tail docking or may be accomplished by ear notching on d 5, 9 and 15 of lactation. All subsequent blood collections for hemoglobin analysis were accomplished utilizing ear notching. The first 2 or 3 drops of blood were wiped away and light pressure was then re-applied until another drop of blood appeared.
When the blood drop was large enough, the microcuvette was filled in one continuous process. If there were air bubbles in the filled microcuvette, the microcuvette was discard and a new microcuvette from a new drop of blood was filled. Small bubbles around the edge could be ignored. Then the filled microcuvette was placed in the cuvette holder and put in the measuring position within 10 min after filling the
microcuvette. The cuvette was slid into the holder to the measuring position and the machine door was closed. After 15 to 60 seconds, the hemoglobin value of the sample was displayed on the screen.
[0079] On d 10 and 16 (end of the study) of lactation, all piglets in each litter were used for blood collection. Approximately 3 ml blood from all the piglets was withdrawn by vena-puncture into a set of chilled K3EDTA tubes. Blood samples from K3EDTA tubes for each piglet were stored at 4 °C until analysis of hematological parameters within 2 days of collection. Whole blood samples were used to analyze hematological parameters, which included erythrocyte count (RBC), total and differential leukocyte count, platelets, red blood cell distribution width (RDW), hematocrit (Hot), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular Hb concentration (MCHC). Reticulocyte indices included reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width (RDWr), and reticulocyte Hb distribution width (HDWr).
[0080] SAS 9.4 (SAS Inst. Inc., Gary, NC) was used for all data analysis. GLIMMIX procedure was used to analyze the data. Treatments were considered as the fixed effect. Sow within treatment was considered as the random effect. If the variance component for sow within treatment was not different from zero, this component would be removed from the final model. If piglet BW and blood Hb concentration on d 3 of lactation were significant among treatments, they would be used as covariates to adjust for the analysis of growth rate and Hb concentration on d 5, 9, 10, 15 and 16 of lactation, respectively.
[0081 ] GEL feed disappearance. The daily average GEL feed
disappearance for each piglet was 44 g/d for GEL-0.22% Fe treatment. The estimated average iron intake for each piglet was 96 mg/d for GEL-0.22% Fe treatment.
[0082] Growth performance. There were no significance differences (P > 0.10; Table 11 ) among the three iron treatments in terms of body weight on d 3, 9 and 15 of lactation, as well as the average daily gain during d 3 to 9, during d 9 to 15, and during d 0 to 15. Even though piglets from GEL-0.22% Fe treatment consumed considerable amount of gel feed, their body weight and growth rates were similar as INJ and SPRAY treatments. The reason could be piglets from GEL-0.22% Fe treatment consumed less milk as a result of consumption of gel feed, rendering similar growth rate as the other two treatments.
Table 11. Effect of iron treatments on growth performance of suckling piglets
Iron treatments1
Items INJ GEL-0.22% Fe SPRAY SEM R value
BW on d 3, kg 1.44 1.82 1.72 0.26 0.59
BW on d 9, kg 2.52 2.99 2.85 0.42 0.73
BW on d 15, kg 4.23 4.53 4.55 0.56 0.90
ADG during d 3 to 9, g/d 177 188 188 34 0.97
ADG during d 9 to 15, g/d 290 258 285 26 0.65
ADG during d 0 to 15, g/d 231 223 235 29 0.96
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1 - 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1 .27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation; SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
[0083] Iron status. Blood hemoglobin concentrations on d 3 of lactation (before iron treatments) were not different (P = 0.81 ; Table 12) among the three iron treatments. Similarly, there was no difference (P = 0.12) among the three iron treatments in terms of blood hemoglobin concentrations on d 5 of lactation. However, piglets receiving iron injection had greater (P < 0.01 ) blood hemoglobin concentrations on d 10, 15 and 16 (FIG. 2) of lactation than pigs from GEL-0.22% Fe and SPRAY, and pigs from SPRAY had greater (P < 0.01 ) blood hemoglobin concentrations on d 10, 15 and 16 of lactation than pigs from GEL-0.22% Fe. Further analysis demonstrated that pigs received iron injection had greater (91.43, 7.90 and 55.26%, respectively; P < 0.01 ; FIG. 3) percentage of blood hemoglobin concentrations equal or greater than 9 g/dL (cutoff considered as normal iron status) within litter compared with pigs received GEL- 0.22% Fe and SPRAY on d 10 of lactation. On d 16 of lactation, 32.69 and 82.31 % of pigs received GEL-0.22% Fe and SPRAY had blood hemoglobin concentrations equal or greater than 9 g/dL within litter, whereas 100% of piglets receiving iron injection had normal blood hemoglobin concentrations. These results indicated that the iron content in the gel feed or iron suspension or the application duration may not be enough for all piglets to achieve similar and uniform iron status compared with conventional iron injection.
Table 12. Effect of iron treatments on blood hemoglobin (Hb) concentrations in suckling piglets
Iron treatments1
Items, g/dL INJ GEL-0.22% Fe SPRAY SEM R value
Hb2 on d 3 8.03 7.72 7.75 0.37 0.81
Hb on d 5 6.81 6.71 7.34 0.19 0.12
Hb on d 9 8.60a 7.15b 7.86ab 0.18 <.01
Hb on d 15 11.11 a 8.07° 9.13b 0.24 <.01 a cWithin a row, means without a common superscript differ (P < 0.05).
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation; SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
2Hb represents blood hemoglobin. [0084] On d 10 and 16 of lactation, piglets receiving iron injection had greater (P < 0.01 ) hematocrit (Hct) than piglets receiving GEL-0.22% Fe and SPRAY, and piglets receiving SPRAY had greater (P < 0.01 ) Hct than those from GEL-0.22% Fe (Tables 13 and 14). Additionally, piglets from iron injection had greater (P < 0.01 ) mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) on d 10 and 16 of lactation compared with those from GEL-0.22% Fe, with piglets from SPRAY
intermediate. These results further demonstrated that GEL and SPRAY treatments under the condition of this study were not effective to achieve similar iron status as iron injection.
Table 13. Effect of iron treatments on blood hematological parameters in suckling piglets on d 10 of lactation
Iron treatments1
Items2 INJ GEL-0.22% Fe SPRAY SEM R value
Hb d10, g/dL 9.68a 7.73° 8.96b 0.14 <.01
Hct, % 31 53a 24.89° 28.60b 0.43 <.01
MCV, fL 72.20a 57.31 b 63.17ab 2.30 0.01
MCH, pg/cell 22.17a 17.73b 19.70ab 0.62 0.01
MCHC, g/L 30.71 31 .00 31 .30 0.29 0.40
RDW, % 28.82 25.25 24.70 1 .76 0.27
RBC, 106/mI_ 4.37 4.35 4.51 0.16 0.75
WBC, 106/pL 12.77 1 1 .20 10.86 0.78 0.25
Neutrophil, 103/pL 6.68 6.52 5.91 0.70 0.72
Lymphocyte,
5.48 4.04 4.13 0.42 0.09
103/pL
Monocyte, 103/pL 0.39 0.49 0.59 0.12 0.53
Neutrophil, % 51 .63 57.52 54.28 3.34 0.50
Lymphocyte, % 44.52 36.78 39.42 3.80 0.40
Monocyte, % 3.83 5.18 5.42 0.81 0.37 a cWithin a row, means without a common superscript differ (P < 0.05). 11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation; SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
2Hb, Hct, MCV, MCH, MCHC, RDW, RBC and WBC represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, red blood cell count and white blood cell count, respectively.
Table 14. Effect of iron treatments on blood hematological parameters in suckling piglets on d 16 of lactation
Iron treatments1
Items2 INJ GEL-0.22% Fe SPRAY SEM R value
Hb_d16, g/dL 1 1 .64a 8.52° 10.23b 0.20 <.01
Hct, % 37.55a 27.92° 32.94b 0.66 <.01
MCV, fL 71 .61 a 55.09b 63.13ab 2.58 0.01
MCH, pg/cell 22.19a 16.81 b 19.54ab 0.74 0.01
MCHC, g/L 31 .12 30.50 31 .08 0.22 0.16
RDW, % 22.62 27.1 1 25.46 1 .50 0.18
RBC, 106/pL 5.27 5.06 5.20 0.16 0.65
WBC, 106/pL 9.79 9.00 10.12 0.79 0.60
Neutrophil, 103/pL 4.72 3.77 4.56 0.50 0.39
Lymphocyte,
4.43 4.63 4.85 0.34 0.71
103/pL
Monocyte, 103/pL 0.48 0.32 0.45 0.05 0.1 1 Neutrophil, % 45.31 41 .72 44.36 1 .96 0.42
Lymphocyte, % 45.18 51 .28 48.75 2.20 0.20
Monocyte, % 5.09 5.36 4.97 0.56 0.88 a cWithin a row, means without a common superscript differ (P < 0.05).
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation; SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
2Hb, Hot, MCV, MCH, MCHC, RDW, RBC and WBC represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, red blood cell count and white blood cell count, respectively.
[0085] Coefficient of variation analysis on the hematological parameters demonstrated that piglets received GEL-0.22% Fe and SPRAY had numerically greater coefficient of variation of Hb, Hot, MCV and MCH on d 10 of lactation (Table 15) compared with those from iron injection, even though no significant differences were found. Additionally, piglets from SPRAY had greater (P = 0.04) or tended (P = 0.06) to have greater coefficient of variation of Hot and red blood cell distribution width (RDW) on d 16 of lactation (Table 16), respectively, compared with those from iron injection, with piglets from GEL-0.22% Fe intermediate. These results illustrated that in the condition of this study, application of iron solutions through gel feed or spraying iron suspension on sow mammary gland could not achieve uniform iron status in the piglets within the litter. Iron concentrations or the duration of application days may be the limiting factor in the current study.
Table 15. Effect of iron treatments on coefficient of variation of blood
hematological parameters in suckling piglets within litter on d 10 of lactation
Iron treatments1
Items2 INJ GEL-0.22% Fe SPRAY SEM R value
Hb Ί 91 12.20 8.78 1.79 0.12
Hot 6.02 10.83 8.88 1.50 0.15
MCV 5.54 6.59 6.93 0.97 0.60
MCH 5.03 7.70 7.28 0.92 0.17
RDW 12.54 14.29 9.87 1.73 0.27
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1 - 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1 .27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation; SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation. 2Hb, Hct, MCV, MCH and RDW represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red blood cell distribution width, respectively.
Table 16. Effect of iron treatments on coefficient of variation of blood
hematological parameters in suckling piglets within litter on d 16 of lactation
Iron treatments1
Items2 INJ GEL-0.22% Fe SPRAY SEM R value
Hb 6.46 12.59 12.86 1.98 0.10
Hct 5.58b 12.2ab 13.33a 1.71 0.04
MCV 5.07 7.69 8.93 1.43 0.23
MCH 5.27 8.41 9.26 1.60 0.26
RDW 7.92v 12.13** 14.52x 1.54 0.06 a bWithin a row, means without a common superscript differ (P < 0.05).
x yWithin a row, means without a common superscript have statistical tendency (0.05 < P < 0.10).
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.22% Fe represents feeding gel feed supplementing iron glycinate at 1.27% to achieve 0.22% Fe to piglets from d 3 to 5 and from d 10 to 12 of lactation; SPRAY represents applying iron suspension with 20% iron glycinate on sow mammary glands from d 3 to 5 and from d 10 to 12 of lactation.
2Hb, Hot, MCV, MCH and RDW represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red blood cell distribution width, respectively.
Example 6. Comparison of Suckling Piglets Administered via Creep Feed vs. Spraying into Sow Mammary Glands - Study 2
[0086] The objective of the present study was to investigate the efficacy of feeding gel feed containing 0.44 or 0.88% Fe to piglets from d 3 to 15 of lactation and application of iron suspension containing 4.98% Fe on sow mammary glands from d 3 to 6 of lactation compared with conventional iron injection.
[0087] Twelve lactating sows with similar parity (P2-P4) and their newborn piglets were selected from a commercial sow farm located in Auxvasse, MO. Within 24 h after birth, litter size was equalized to 13-14 piglets for these 12 sows. The sows with their associated litters were randomly allotted to 1 of 4 dietary treatments. On d 2 of lactation, all piglets were ear-tagged to identify each piglet. The sows were fed the same commercial lactation diets ad libitum. The 4 treatments include: 1 ) intramuscular injection of 1 ml_ iron dextran to supply 200 mg Fe for each piglet on d 3 of lactation (IN J); 2) Feeding gel feed 1 with 2.59% iron glycinate to the piglets ad libitum from d 3 to 15 of lactation (GEL1 -0.44% Fe); 3) Feeding gel feed 2 with 5.24% iron glycinate to the piglets ad libitum from d 3 to 15 of lactation (GEL2-0.88% Fe); 4) Spray iron suspension with 30% Iron glycinate (Table 17) on the sow mammary glands from d 3 to 6 of lactation (SPRAY). The treatments were displayed in Table 18. The study lasted 16 days.
Figure imgf000037_0001
Figure imgf000037_0002
Figure imgf000038_0001
[0088] The piglets in each litter were weighed individually on d 3, 9 and 15 of lactation. The piglets in each litter were also be used to test their blood hemoglobin concentrations using HemoCue Hb 201 + analyzer (HemoCue, Inc., Lake Forest, CA) on d 3, 9 and 15 of lactation. Blood for hemoglobin analysis was obtained on d 3 of lactation either directly following tail docking or may be accomplished by ear notching on d 9 and 15 of lactation. All subsequent blood collections for hemoglobin analysis were accomplished utilizing ear notching. The first 2 or 3 drops of blood were wiped away and light pressure was then re-applied until another drop of blood appeared.
When the blood drop was large enough, the microcuvette was filled in one continuous process. If there were air bubbles in the filled microcuvette, the microcuvette was discarded and a new microcuvette from a new drop of blood was filled. Small bubbles around the edge could be ignored. Then the filled microcuvette was placed in the cuvette holder and put in the measuring position within 10 min after filling the
microcuvette. The cuvette was slid into the holder to the measuring position and the machine door was closed. After 15 to 60 seconds, the hemoglobin value of the sample was displayed on the screen.
[0089] On d 10 and 16 (end of the study) of lactation, all piglets in each litter were used for blood collection. Approximately 3 ml blood from all the piglets was withdrawn by vena-puncture into a set of chilled K3EDTA tubes. Blood samples from K3EDTA tubes for each piglet were stored at 4 °C until analysis of hematological parameters within 2 days of collection. Whole blood samples were used to analyze hematological parameters, which included erythrocyte count (RBC), total and differential leukocyte count, platelets, red blood cell distribution width (RDW), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular Hb concentration (MCHC). Reticulocyte indices included reticulocyte count (absolute and relative), reticulocyte hemoglobin concentration (CHr), mean reticulocyte corpuscular Hb concentration (CHCMr), reticulocyte cell volume (MCVr), reticulocyte red cell distribution width (RDWr), and reticulocyte Hb distribution width (HDWr). [0090] SAS 9.4 (SAS Inst. Inc., Gary, NC) was used for all data analysis. GLIMMIX procedure was used to analyze the data. Treatments were considered as the fixed effect. Sow within treatment was considered as the random effect. If the variance component for sow within treatment was not different from zero, this component would be removed from the final model. If piglet BW and blood Hb concentration on d 3 of lactation were significant among treatments, they would be used as covariates to adjust for the analysis of growth rate and Hb concentration on d 9 and 15, respectively.
[0091 ] GEL feed disappearance. The daily average GEL feed
disappearance for each piglet was 25 and 28 g/d for GEL1 -0.44% Fe and GEL2-0.88% Fe treatments, respectively. The estimated average iron intake for each piglet was 1 10 and 249 mg/d for GEL1 -0.44% Fe and GEL2-0.88% Fe treatments, respectively.
[0092] Growth performance. There were no significance differences (P > 0.10; Table 19) among the four treatments in terms of body weight on d 3, 9 and 15 of lactation, as well as the average daily gain during d 3 to 9, during d 9 to 15, and during d 0 to 15. Even though piglets from two GEL treatments consumed considerable amount of gel feed, their body weight and growth rates were similar as INJ and SPRAY treatments. The reason could be piglets from the two GEL treatments consumed less milk as a result of consumption of gel feed, rendering similar growth rate as the other two treatments.
Table 19. Effect of iron treatments on growth performance of suckling piglets
Iron treatments1
GEL1-0.44% GEL2-0.88%
Items INJ SPRAY SEM P value
Fe Fe
BW on d 3, kg 1.61 1.55 1.39 1.53 0.11 0.57
BW on d 9, kg 2.85 2.80 2.94 3.00 0.20 0.89
BW on d 15, kg 4.55 4.22 4.60 4.57 0.27 0.75
ADG during d 3 to 9, g/d 217 209 232 242 33 0.89
ADG during d 9 to 15, g/d 278 229 274 256 27 0.60
ADG during d 0 to 15, g/d 249 222 253 251 23 0.74
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1 - 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
[0093] Iron status. Blood hemoglobin concentrations on d 3 of lactation (before iron treatments) were greater (P = 0.01 ; Table 20) in piglets from GEL1 -0.44% Fe compared with piglets from INJ and GEL2-0.88% Fe treatments. Therefore, blood hemoglobin concentrations on d 3 of lactation were used as a covariate to adjust the analysis of blood hemoglobin concentrations on d 9, 10, 15 and 16. After covariate analysis, there were no significance differences (P > 0.10) among the four iron treatments in terms of blood hemoglobin concentrations on d 9 and 15 (Table 21 ).
Additionally, at the end of the study (d 16 of lactation), the average blood hemoglobin concentrations in all four iron treatments were greater than 9 g/dL (FIG. 4), which was the cutoff value for normal iron status, indicating that both GEL and SPRAY applications could serve as alternatives to replace iron injection to achieve normal iron status.
Further analysis also demonstrated that there were no differences among the four iron treatments in terms of percentage of blood hemoglobin equal or greater than 9 g/dL within litter on d 10 and 16 of lactation (FIG. 5). Specifically, all piglets within litter in two GEL and SPRAY treatments had blood hemoglobin concentrations greater than 9 g/dL on d 16 of lactation.
Table 20. Effect of iron treatments on blood hemoglobin concentrations in suckling piglets
Iron treatments1
GEL1 -0.44% GEL2-0.88% SPRA SE P
Items INJ
Fe Fe Y M value
6.63
Hb2 on d 3, g/dL 7.81 a 6.10b 6.66ab 0.28 0.01
Figure imgf000041_0001
Hb on d 9, g/dL 8.05 7.42 7.25 8.39 0.40 0.22
Hb on d 15,
9.88 10.39 10.39 10.77 0.48 0.63 g/dL
a bWithin a row, means without a common superscript differ (P < 0.05).
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1 - 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
2Hb represents blood hemoglobin.
[0094] There were no significance differences among the four iron treatments in terms of all hematological parameters on d 10 of lactation, including hematocrit (Hot; P = 0.16; Table 21 ), mean corpuscular volume (MCV; P = 0.53), mean corpuscular hemoglobin (MCH; P = 0.42) and lower red blood cell distribution width (RDW; P = 0.71 ). Similarly, there were no significance among the four iron treatments on all hematological parameters on d 16 of lactation, including Hot (P = 0.83; Table 22), MCV (P = 0.13), MCH (P = 0.20) and RDW (P = 0.57). These results further illustrated that supplementation of 2.59-5.24% Iron glycinate in gel feed and 30% iron glycinate in iron suspension when feeding to piglets from d 3 to 15 of lactation or applying on sow mammary gland from d 3 to 6 of lactation, respectively, can serve as effective strategies to replace iron injection in suckling piglets. Table 21. Effect of iron treatments on blood hematological parameters in suckling piglets on d 10 of lactation
Iron treatments1
Items2 INJ GEL 1-0.44% Fe GEL2-0.88% Fe SPRAY SEM R value
Hb, g/dL 9.94 9.10 9.57 10.24 0.34 0.17
Hct, % 32.37 28.64 30.54 32.68 1.25 0.16
MCV, fL 69.45 66.65 70.05 71.80 2.41 0.53
MCH, pg/cell 21.36 21.14 21.94 22.50 0.60 0.42
MCHC, g/L 30.82 31.76 31.29 31.28 0.34 0.34
RDW, % 26.29 24.48 26.09 24.98 1.26 0.71
RBC, 106/pL 4.58 4.33 4.37 4.56 0.21 0.77
WBC, 106/pL 13.95 12.13 12.46 10.73 1.71 0.63
Neutrophil, 103/pL 7.95 7.29 6.51 5.73 1.69 0.81
Lymphocyte, 103/pL 5.07 4.63 5.01 4.40 0.58 0.82
Monocyte, 103/pL 0.46 0.35 0.43 0.45 0.08 0.73
Neutrophil, % 54.19 57.27 52.44 52.94 5.58 0.93
Lymphocyte, % 40.15 37.87 41.19 41.41 4.99 0.95
Monocyte, % 5.00 3.18 4.52 4.51 0.89 0.54
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
2Hb, Hct, MCV, MCH, MCHC, RDW, RBC and WBC represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, red blood cell count and white blood cell count, respectively.
Table 22. Effect of iron treatments on blood hematological parameters in suckling piglets on d 16 of lactation
Iron treatments1
Items2 INJ GEL 1-0.44% Fe GEL2-0.88% Fe SPRAY SEM R value
Hb, g/dL 11.37 11.72 11.87 11.79 0.35 0.74
Hct, % 36.04 36.42 37.38 37.01 1.13 0.83
MCV, fL 67.52 68.54 71.49 67.20 1.25 0.13
MCH, pg/cell 21.29 22.06 22.56 21.42 0.43 0.20
MCHC, g/L 31.61 32.19 31.80 31.89 0.22 0.37
RDW, % 22.80 22.09 23.19 21.07 1.1 1 0.57
RBC, 106/pL 5.33 5.33 5.28 5.51 0.18 0.81
WBC, 106/pL 12.26 10.20 10.71 10.28 1.10 0.54
Neutrophil, 103/pL 5.75 4.72 4.61 4.97 0.75 0.70
Lymphocyte, 103/pL 5.52 4.64 5.45 4.44 0.43 0.24
Monocyte, 103/pL 0.57 0.61 0.35 0.54 0.08 0.18
Neutrophil, % 46.92 47.02 44.47 48.33 3.18 0.84
Lymphocyte, % 46.44 43.94 51.20 44.81 2.94 0.37
Monocyte, % 5.50 5.65 3.91 5.28 0.64 0.28
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
2Hb, Hct, MCV, MCH, MCHC, RDW, RBC and WBC represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration and red blood cell distribution width, red blood cell count and white blood cell count, respectively.
[0095] Coefficient of variation analysis on the hematological parameters demonstrated that there were no differences among the four iron treatments in terms of coefficient of variations of Hb, Hot, MCV and MCH for piglets within litter on d 10 (Table 23) and d 16 (Table 24) of lactation. The results indicated that both GEL and SPRAY could achieve uniform iron status for piglets within litter as conventional iron injection, further corroborating the effectiveness of both iron solutions. Table 23. Effect of iron treatments on coefficient of variation of blood hematological parameters in suckling piglets within litter on d 10 of lactation
Iron treatments1
Items2 INJ GEL1-0.44% Fe GEL2-0.88% Fe SPRAY SEM R value
Hb 9.08 8.19 7.56 7.69 1 .97 0.94
Hct 9.21 7.62 7.09 7.90 1 .84 0.87
MCV 5.86 4.78 7.03 5.62 0.78 0.31
MCH 4.64 4.78 6.90 4.48 0.81 0.20
RDW 8.89ab 7.62ab 9.90a 5.97b 0.68 0.02
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
2Hb, Hct, MCV, MCH and RDW represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red blood cell distribution width, respectively.
Table 24. Effect of iron treatments on coefficient of variation of blood
hematological parameters in suckling piglets within litter on d 16 of lactation
Iron treatments1
Items INJ GEL1-0.44% Fe GEL2-0.88% Fe SPRAY SEM R value
Hb 5.36 4.69 6.41 5.60 0.94 0.65
Hct 5.36 4.17 7.07 5.65 1 .04 0.34
MCV 5.64 5.21 7.34 4.15 0.81 0.12
MCH 4.66 4.79 7.04 4.05 0.89 0.17
RDW 8.72 7.58 8.49 7.51 1 .29 0.87
11NJ represents conventional iron injection of 200 mg Fe from iron dextran on d 3 of lactation; GEL1- 0.44% Fe and GEL2-0.88% Fe represent feeding gel feed supplementing iron glycinate at 2.59 and 5.24% to achieve 0.44 and 0.88% Fe, respectively, to piglets from d 3 to 15 of lactation; SPRAY represents applying iron suspension with 30% iron glycinate on sow mammary glands from d 3 to 6 of lactation.
2Hb, Hct, MCV, MCH and RDW represent hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red blood cell distribution width, respectively.

Claims

CLAIMS What is claimed is:
1. A liquid iron composition, the composition comprising:
(a) an iron source present in an amount to prevent iron deficiency and/or anemia in piglets;
(b) a suspension medium;
(c) a viscosity modifier; and
(d) a flavoring agent that increases average daily feed intake by at least about 15% in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent.
2. The liquid iron composition of claim 1 , wherein the iron source is an iron amino acid chelate, and iron amino acid salt, an iron salt, an iron carboxylate, an iron chelate, or an iron complex.
3. The liquid iron composition of claims 1 or 2, wherein the iron source is iron
glycinate, iron proteinate, or iron trimaltose.
4. The liquid iron composition of any one of claims 1 or to 3, wherein the iron source is present in the composition in an amount from about 0.5% (w/w) to about 40% (w/w).
5. The liquid iron composition of any one of claims 1 to 4, wherein the suspension medium is chosen from molasses, corn syrup, high fructose corn syrup, sugar beet syrup, cane sugar syrup, raw sugar solution, sorghum syrup, dextrose, sucrose, lactose, maltose, vegetable oil, long chain fatty acid, long chain fatty ester, long chain fatty acid mono-, di-, or triglyceride, or combination thereof.
6. The liquid iron composition of claim 5, wherein the suspension medium is
molasses, high fructose corn syrup, or dextrose.
7. The liquid iron composition of any one of claims 1 to 6, wherein the suspension media is present in the composition in an amount from about 20% (w/w) to about 70% (w/w).
8. The liquid iron composition of any one of claims 1 to 7, wherein the viscosity
modifier is chosen from xanthan gum, gum arabic, guar gum, gellan gum, alginic acid, sodium alginate, pectin, gelatin, starch, cellulose, microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose, sodium carboxymethylcellulose, or combination thereof.
9. The liquid iron composition of claim 8, wherein the viscosity modifier is xanthan gum.
10. The liquid iron composition of any one of claims 1 to 9, wherein the viscosity
modifier is present in the composition in an amount from about 0.03% (w/w) to about 5% (w/w).
11. The liquid iron composition of any one of claims 1 to 10, wherein the flavoring agent comprises a flavor chosen from cherry, apple, peach, pear, strawberry, raspberry, plum, pineapple, apricot, citrus, vanilla, tomato, pumpkin pie, cheese, or combination thereof.
12. The liquid iron composition of claim 11 , wherein the flavoring agent comprises cherry flavor.
13. The liquid iron composition of any one of claims 1 to 12, wherein the flavoring agent is present in the composition in an amount from about 0.03% (w/w) to about 3% (w/w).
14. The liquid iron composition of any one of claims 1 to 13, wherein the composition further comprises a solvent.
15. The liquid iron composition of claim 14, wherein the solvent is chosen from water, glycerin, propylene glycol, ethanol, organic acid, or combination thereof.
16. The liquid iron composition of any of claims 1 to15, wherein the flavoring agent increases average daily feed intake by at least about 20% in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent.
17. The liquid iron composition of any of claims 1 to 15, wherein the flavoring agent increases average daily feed intake by at least about 25% in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent.
18. The liquid iron composition of any of claims 1 to 15, wherein the flavoring agent increases average daily feed intake by at least about 30% in piglets fed a diet containing the iron composition with the flavoring agent compared to piglets fed a diet containing the iron composition without the flavoring agent.
19. The liquid iron composition of any one of claims 1 to 18, wherein the composition further comprises at least one additional agent chosen from vitamin, mineral, amino acid, antioxidant, organic acid, poly unsaturated fatty acid, essential oil, enzyme, prebiotic, probiotic, postbiotic, herb, pigment, or combination thereof.
20. The liquid iron composition of any of claims 1 to 19, wherein the composition is formed into a solid or semi-solid feeder block.
21 . The liquid iron composition of claim 1 , wherein the iron source is iron glycinate, the suspension medium is molasses, high fructose corn syrup, or dextrose, the viscosity modifier is xanthan gum, the flavoring agent comprises a fruit flavor, and the composition further comprises water and glycerin as solvents.
22. An oral iron feed composition comprising an iron source and a creep feed,
wherein the iron source is present in an amount from about 0.1 % to about 10% by weight of the composition.
23. The oral iron feed composition of claim 22, wherein the iron source is an iron amino acid chelate, and iron amino acid salt, an iron salt, an iron carboxylate, an iron chelate, or an iron complex.
24. The oral iron feed composition of claims 22 or 23, wherein the iron source is iron glycinate, iron proteinate, or iron trimaltose.
25. The oral iron feed composition of any one of claims 22 to 24, wherein the creep feed comprises hydrated oats, cooked cereals, cereal mashes, soy bean meal, corn gluten meal, canola meal, cottonseed meal, milk by-products, milk proteins, lactose, rolled oats, rice bran, broken rice, wheat bran, milled or cracked corn, wheat, sorghum, barley, distillers residues, vegetable proteins, oilseed extracts, fatty acids, amino acids, feed phosphates, vitamins, minerals, or combination thereof.
26. The oral iron feed composition of any one of claims 22 to 25, wherein the
composition is solid, semi-solid, or liquid.
27. A method for preventing anemia and/or iron deficiency in a piglet, the method comprising orally administering to the piglet an effective amount of the liquid iron composition of any one of claims 1 to 21 or the oral iron feed composition of any one of claims 22 to 26 within the first three days after the piglet’s birth.
28. The method of claim 27, wherein the piglet is administered several dosages of the liquid iron composition or the oral iron feed composition within the first fifteen days after the piglet’s birth.
29. The method of claim 27 or 28, wherein the piglet is administered a first dosage of the liquid iron composition or the oral iron feed composition within the first three days after the piglet’s birth and is administered a second dosage of the liquid iron composition or the oral iron feed composition from about five days to about nine days after the piglet’s birth.
30. The method of claim 27 or 28, wherein the piglet is administered a first dosage of the liquid iron composition or the oral iron feed composition within the first three days after the piglet’s birth and is administered multiple additional dosage of the liquid iron composition or the oral iron feed composition within the first fifteen days after the piglet’s birth.
31. The method of any one of claims 27 to 30, wherein the piglet is provided with about 50 to about 300 mg of iron per day.
32. The method of any one of claim 27 to 31 , wherein blood hemoglobin
concentration measurements indicate no iron deficiency or anemia in the piglet.
33. The method of any one of claim 27 to 32, wherein the liquid iron composition or the oral iron feed composition is administered using a lick bottle, a nipple or teat bucket, a feed or lick block, feeding trough, spot feeder, timed feeder, or lick bowl.
PCT/US2020/041937 2019-07-15 2020-07-14 Oral iron compositions and application for baby pigs WO2021011540A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201962874013P 2019-07-15 2019-07-15
US62/874,013 2019-07-15
US201962914717P 2019-10-14 2019-10-14
US62/914,717 2019-10-14

Publications (1)

Publication Number Publication Date
WO2021011540A1 true WO2021011540A1 (en) 2021-01-21

Family

ID=74211246

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2020/041937 WO2021011540A1 (en) 2019-07-15 2020-07-14 Oral iron compositions and application for baby pigs

Country Status (1)

Country Link
WO (1) WO2021011540A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113100343A (en) * 2021-04-21 2021-07-13 深圳市菲赛迪生物科技有限公司 Suckling pig iron supplement oral liquid and preparation method thereof
CN113383858A (en) * 2021-06-15 2021-09-14 湖南喜来高动物保健品有限公司 Water-soluble glycine iron mixed additive and preparation method and equipment thereof
WO2022198329A1 (en) * 2021-03-26 2022-09-29 Alberta Veterinary Laboratories Ltd. Water-based iron supplement formulations for dosing animal neonates

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4171379A (en) * 1978-04-05 1979-10-16 Ralston Purina Company Feed supplement for baby pigs
US6387419B1 (en) * 1998-06-02 2002-05-14 Biofiber-Damino A/S Piglet feeding method
WO2010146155A1 (en) * 2009-06-18 2010-12-23 Ceva Sante Animale Gelled iron veterinary suspension
US20130280228A1 (en) * 2009-04-24 2013-10-24 Dupont Nutrition Biosciences Aps Feed supplement
CN106615850A (en) * 2017-01-13 2017-05-10 山东贝瑞康生物科技有限公司 Piglet feed additive
WO2017147084A1 (en) * 2016-02-22 2017-08-31 Railsplitter Feed Technology, Inc. Solid form nutrient compositions
EP3020284B1 (en) * 2014-11-03 2018-09-12 Lipidos Toledo S.A. Supplementary feed for oral administration for reducing neonatal mortality of piglets
CN109699840A (en) * 2018-12-04 2019-05-03 广东省农业科学院动物科学研究所 A kind of artificial breast for alleviating weaning stress of piglet

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4171379A (en) * 1978-04-05 1979-10-16 Ralston Purina Company Feed supplement for baby pigs
US6387419B1 (en) * 1998-06-02 2002-05-14 Biofiber-Damino A/S Piglet feeding method
US20130280228A1 (en) * 2009-04-24 2013-10-24 Dupont Nutrition Biosciences Aps Feed supplement
WO2010146155A1 (en) * 2009-06-18 2010-12-23 Ceva Sante Animale Gelled iron veterinary suspension
EP3020284B1 (en) * 2014-11-03 2018-09-12 Lipidos Toledo S.A. Supplementary feed for oral administration for reducing neonatal mortality of piglets
WO2017147084A1 (en) * 2016-02-22 2017-08-31 Railsplitter Feed Technology, Inc. Solid form nutrient compositions
CN106615850A (en) * 2017-01-13 2017-05-10 山东贝瑞康生物科技有限公司 Piglet feed additive
CN109699840A (en) * 2018-12-04 2019-05-03 广东省农业科学院动物科学研究所 A kind of artificial breast for alleviating weaning stress of piglet

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022198329A1 (en) * 2021-03-26 2022-09-29 Alberta Veterinary Laboratories Ltd. Water-based iron supplement formulations for dosing animal neonates
CN113100343A (en) * 2021-04-21 2021-07-13 深圳市菲赛迪生物科技有限公司 Suckling pig iron supplement oral liquid and preparation method thereof
CN113383858A (en) * 2021-06-15 2021-09-14 湖南喜来高动物保健品有限公司 Water-soluble glycine iron mixed additive and preparation method and equipment thereof
CN113383858B (en) * 2021-06-15 2022-05-27 湖南喜来高动物保健品有限公司 Water-soluble glycine iron mixed additive and preparation method and equipment thereof

Similar Documents

Publication Publication Date Title
US20200221732A1 (en) Essential oil particles with improved stability and compositions thereof
WO2021011540A1 (en) Oral iron compositions and application for baby pigs
US11564405B2 (en) Reducing the risk of viral infection due to viral contaminated feed
US11638434B2 (en) Feed additive compositions
EP3709808A1 (en) Compositions and methods of improving dietary phosphorus and calcium utilization in animals
US20200221731A1 (en) Means for increasing methionine bioavailability
US20240024358A1 (en) Therapeutic clay compositions and methods of using
US20220354823A1 (en) Swine maternal neonatal pheromone
US11185524B2 (en) Means for protecting methionine hydroxy analog from rumen degradation
US20220142204A1 (en) Clay compositions and methods for improving animal performance
WO2023115066A1 (en) Methods of improving the nutritional status of immune stressed animals

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20840349

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20840349

Country of ref document: EP

Kind code of ref document: A1