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WO2009006466A1 - Régime alimentaire permettant la prévention d'affections entéropathiques porcines - Google Patents

Régime alimentaire permettant la prévention d'affections entéropathiques porcines Download PDF

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Publication number
WO2009006466A1
WO2009006466A1 PCT/US2008/068896 US2008068896W WO2009006466A1 WO 2009006466 A1 WO2009006466 A1 WO 2009006466A1 US 2008068896 W US2008068896 W US 2008068896W WO 2009006466 A1 WO2009006466 A1 WO 2009006466A1
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WIPO (PCT)
Prior art keywords
acid
composition
weeks
combination
porcine
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Application number
PCT/US2008/068896
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English (en)
Inventor
Felipe Navarro
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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.)
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Publication date
Application filed by Novus International Inc. filed Critical Novus International Inc.
Publication of WO2009006466A1 publication Critical patent/WO2009006466A1/fr

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Classifications

    • 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
    • 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
    • A23K20/158—Fatty acids; Fats; Products containing oils or fats

Definitions

  • the present invention relates to feeding regimes comprising administering a combination of bactericidal acidifying agents to prevent enteropathic conditions in porcine.
  • Porcine proliferative enteritis is a critical problem for the swine industry. Ileitis is an intestinal disease of pigs characterized by crypt hyperplasia and by the presence of its causative agent, Lawsonia intracellularis. The clinical response of pigs affected with ileitis includes intermittent diarrhea, anorexia, marked dullness and apathy, and a wasting syndrome. Death is not uncommon with acute outbreaks, and is frequently associated with hemorrhage effect on intestines. All forms of ileitis (i.e., sub clinical, chronic, and acute) dramatically impact profitably of swine production. For example, ileitis contributes to reduced gain, diminished feed efficiency, and increased weight variation among pigs of the same age.
  • the method comprises administering to the porcine a combination comprising two bactericidal compositions.
  • the first composition of the combination comprises an acidifying agent formulated for release in the distal portion of the gastrointestinal tract, wherein the acidifying agent is embedded in a matrix.
  • the second composition of the combination comprises an acidifying agent formulated for release in the proximal portion of the gastrointestinal tract.
  • a further aspect of the invention encompasses a feeding regime to prevent the incidence of porcine proliferative enteropathy in growing to finish porcine.
  • the feeding regime comprises administering a combination of protected and unprotected acidifying agents to the porcine beginning at least 4 weeks before the onset of a critical period and continuing for at least about 3 weeks to about 5 weeks.
  • the feeding regime further comprises discontinuing administration of the combination for about 7 to about 14 days, and then administering the combination for at least 2 weeks.
  • the present invention provides bactericidal combinations of acidifying agents that are utilized in a feeding regime to prevent the onset of certain porcine enteropathic conditions, and in particular, enteropathic conditions affecting growing to finish pigs.
  • feeding regime is used in its broadest form and may include, without limitation, administering the bactericidal combination through either a feed ration or drinking source.
  • the bactericidal combination generally comprises a first composition comprising an acidifying agent formulated for intact release in the distal portion of the gastrointestinal tract, and a second composition comprising an acidifying agent formulated for release in the proximal portion of the gastrointestinal tract.
  • the first composition In order for intact release of the acidifying agent in the distal portion of the gastrointestinal tract, the first composition is generally embedded in a fatty acid matrix, such that the acidifying agent is generally resistant to degradation in the acidic stomach.
  • intestinal enzymes such as lipases and esterases, hydrolyze the composition, causing the release of intact bactericidal acidifying agents in the distal portion of the intestine.
  • the acidifying agent forming the second composition is generally not protected, and as such, the acidifying agent is subjected to degradation in the acidic environment of the stomach and duodenum, and consequently, achieves its bactericidal effects in the proximal portion of the gastrointestinal tract.
  • the combinations of the invention are formulated to deliver acidifying agents having bactericidal effects over substantially the entire gastrointestinal tract, they may be used to prevent a broad range of porcine enteropathic conditions, including without limitation, porcine proliferative enteropathy, hemorrhagic bowel syndrome, and enteritis.
  • One aspect of the invention provides a bactericidal combination generally comprising a first composition comprising an acidifying agent formulated for intact release in the distal portion of the gastrointestinal tract, and a second composition comprising an acidifying agent formulated for release in the proximal portion of the gastrointestinal tract.
  • the first composition is protected as described more thoroughly below.
  • a variety of acidifying agents are suitable for use in the invention to the extent that the agent has bactericidal effects when released in the gastrointestinal tract. Suitable acidifying agents include organic acids, fatty acids, inorganic acids, and combinations thereof.
  • the first composition and second composition generally include at least one acidifying agent that is an organic acid.
  • suitable organic acids may be utilized in the compositions of the invention. Suitable organic acids may be selected from the aliphatic, cycloaliphatic, aromatic, heterocyclic, carboxylic and sulfonic classes of organic acids.
  • the organic acid may be selected from small monocarboxylic, dicarboxylic or tricarboxylic acids, or any active derivative or salt thereof.
  • the organic acid may be a monocarboxylic acid having a straight chain or it may be branched; it may be saturated or unsaturated.
  • a variety of organic acids comprised of carboxylic acids are suitable.
  • the organic acid may contain from about two to about twenty-five carbon atoms. In another embodiment, the organic acid may have from about three to about twenty-two carbon atoms. In a further embodiment, the organic acid may contain from about three to about twelve carbon atoms. In yet another embodiment, the organic acid may contain from about eight to about twelve carbon atoms. In still another embodiment, the organic acid may contain from about two to about six carbon atoms.
  • Suitable organic acids include formic acid, acetic acid, propionic acid, butanoic acid, benzoic acid, lactic acid, malic acid, tartaric acid, mandelic acid, citric acid, fumaric acid, sorbic acid, boric acid, succinic acid, adipic acid, glycolic acid, and glutaric acid.
  • 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 organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of formic acid.
  • the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of acetic acid.
  • the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of propionic acid.
  • the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of butanoic acid. In a further embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of benzoic acid. In still another embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of lactic acid. In yet another embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of malic acid.
  • the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of tartaric acid. In a further embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of mandelic acid. In yet another embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of citric acid. In an additional embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of fumaric acid.
  • the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of sorbic acid. In another embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of boric acid. In yet another embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of succinic acid. In another embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of adipic acid.
  • the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of glycolic acid. In an additional embodiment, the organic acid is an ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, or zinc salt of glutaric acid.
  • the organic acid may be comprised of a substituted carboxylic acid.
  • a substituted carboxylic acid generally has the same features as those detailed above for carboxylic acids, but the hydrocarbyl chain has been modified such that it is branched, is part of a ring structure, or contains some other substitution.
  • the substituted carboxylic acid may contain one or more additional carboxyl groups.
  • Saturated dicarboxylic acids include malonic acid, succinic acid, glutaric acid, and adipic acid, and unsaturated dicarboxylic acids include maleic acid and fumaric acid.
  • the substituted carboxylic acid may contain one or more hydroxyl groups.
  • a substituted carboxylic acid with a hydroxyl group on the alpha carbon, i.e., the carbon adjacent to the carboxyl carbon, is generally called a ⁇ - hydroxy carboxylic acid.
  • suitable ⁇ -hydroxy carboxylic acids include glycolic acid, lactic acid, malic acid, and tartaric acid.
  • the substituted carboxylic acid may contain one or more carbonyl groups.
  • the substituted carboxylic acid may contain an amino group on the alpha carbon, i.e., is an ⁇ -amino acid.
  • the ⁇ -amino acid may be one of the twenty standard amino acids or derivatives thereof.
  • the ⁇ - amino acid may be an essential ⁇ -amino acid selected from the group consisting of arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.
  • Salts of organic acids comprising substituted 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 comprising substituted carboxylic acids.
  • the organic acid may be a compound having Formula (I):
  • n is an integer from 0 to 2;
  • R 6 is an alkyl group having from one to four carbon atoms
  • R 7 is selected from the group consisting of hydroxyl, amino, and -
  • R 8 is an organic acid derivative.
  • R 6 is methyl or ethyl
  • R 7 is hydroxyl or amino
  • n is 0 to 2.
  • Salts of compounds having Formula (I) are also suitable for certain embodiments.
  • Representative salts of the compound of Formula (I) include the ammonium, magnesium, calcium, lithium, sodium, potassium, selenium, iron, copper, and zinc salts.
  • the compound of Formula (I) is in the form of the calcium salt.
  • Representative amides include methylamide, dimethylamide, ethylmethylamide, butylamide, dibutylamide, butylmethylamide, and alkyl ester of N-acyl methionates (e.g., alkyl N-acetyl methionates).
  • esters include the methyl, ethyl, n-propyl, isopropyl, butyl esters, namely n-butyl, sec-butyl, isobutyl, t-butyl esters, pentyl esters and hexyl esters, especially n-pentyl, isopentyl, n-hexyl and isohexyl esters.
  • the compound of Formula (I) is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoe-N-(2-aminoe-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoe
  • HMTBA 2-hydroxy-4-(methylthio)butanoic acid
  • the compound of Formula (I) is HMTBA.
  • the first composition and/or second composition may include at least one acidifying agent that is a fatty acid.
  • the fatty acid may have a straight chain or it may be branched; it may be saturated or unsaturated.
  • the fatty acid may also be bound to other molecules, such as in triglycerides or phospholipids.
  • the fatty acid may be an uncombined or free fatty acid. In this context, a "free" fatty acid is not attached to another molecule.
  • the fatty acid is a saturated aliphatic compound having from four to twenty-two carbon atoms.
  • the fatty acid may be butanoic acid (C4:0), hexanoic acid (C6:0), octanoic acid (C8:0), decanoic acid (C10:0), dodecanoic acid (C12:0), tetradecanoic acid (C14:0), hexadecanoic acid (C16:0), octadecanoic acid (C18:0), eicosanoic acid (C20:0), and docosanoic acid (C22:0).
  • the fatty acid is selected from octanoic acid, decanoic acid, and dodecanoic acid.
  • the fatty acid may be an unsaturated aliphatic compound.
  • unsaturated fatty acids include a hexanoic acid with two double bonds (C6:2), myristoleic acid (i.e., a Ci 4 acid with one double bond (C14:1 )), palmitoleic acid (C16:1 ), oleic acid (C18:1 ), linoleic acid (C18:2), linolenic (C18:3), gadoleic acid (C20:1 ), arachidonic acid (C20:4), eicosapentaenoic acid (C20:5), docosahexaenoic acid (C22:6), and erucic acid (C22:1 ).
  • C6:2 hexanoic acid with two double bonds
  • myristoleic acid i.e., a Ci 4 acid with one double bond (C14:1 )
  • palmitoleic acid C16:1
  • the bactericidal combinations of the invention comprising acidifying agents generally include at least one organic acid and may optionally include one or more fatty acids.
  • the combination may comprise all organic acids.
  • the combination may comprise at least one organic acid and at least one fatty acid.
  • One aspect of the invention provides acidifying agents that are formulations of two or more organic acids detailed in (l)(a) or otherwise known in the art.
  • the mixture of organic acids is selected from the group consisting of formic acid, acetic acid, propionic acid, butanoic acid, benzoic acid, lactic acid, malic acid, tartaric acid, mandelic acid, citric acid, fumaric acid, sorbic acid, boric acid, succinic acid, adipic acid, glycolic acid, 2-hydroxy-4-methylthiobutanoic acid, and glutaric acid.
  • Suitable non-limiting examples of combinations of organic acids are shown in Table A.
  • the combinations may be protected by encapsulation or embedded in a matrix as described in (II) for intact release in the distal portion of the gastrointestinal tract.
  • the combinations may be unprotected and released substantially in the proximal portion of the gastrointestinal tract.
  • the mixture of organic acids may be protected or unprotected.
  • the mixture of organic acids forming the acidifying agent may comprise benzoic acid and formic acid.
  • the mixture of organic acids forming the acidifying agent may comprise formic acid and propionic acid.
  • the mixture of organic acids forming the acidifying agent may comprise formic acid, propionic acid, and 2-hydroxy-4- methylthiobutanoic acid.
  • the amount of formic acid is about 40% by weight
  • the amount of propionic acid is about 20% by weight
  • the amount of 2-hydroxy-4-methylthiobutanoic acid is about 40% by weight.
  • the mixture of organic acids forming the acidifying agent may comprise formic acid and sorbic acid.
  • the mixture of organic acids forming the acidifying agent may comprise formic acid, sorbic acid, and fumaric acid.
  • the mixture of organic acids forming the acidifying agent may comprise formic acid, sorbic acid, and benzoic acid.
  • the mixture of organic acids forming the acidifying agent may comprise fumaric acid and benzoic acid.
  • the mixture further comprises D,L-methionine hydroxyl analogue calcium, silicon dioxide, and mineral oil.
  • the amount of fumaric acid is about 42% by weight
  • the amount of benzoic acid is about 20% by weight
  • the amount of D,L-methionine hydroxyl analogue calcium is about 37%
  • the amount of mineral oil and silicon dioxide is less than about 2% by weight.
  • Yet another aspect of the invention provides acidifying agents that are formulations of at least one organic acids detailed in (l)(a) or otherwise known in the art in combination with at least one fatty acid detailed in (l)(b) or otherwise known in the art.
  • a composition of the invention may include from one to several organic acid(s) combined with from one to several fatty acids. Suitable examples of combinations of organic acids and fatty acids are detailed in Table B.
  • the combinations may be protected by encapsulation or embedded in a matrix as described in (II) for intact release in the distal portion of the gastrointestinal tract. Alternatively, the combinations may be unprotected and released substantially in the proximal portion of the gastrointestinal tract.
  • the organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butanoic acid, benzoic acid, lactic acid, malic acid, tartaric acid, mandelic acid, citric acid, fumaric acid, sorbic acid, boric acid, succinic acid, adipic acid, glycolic acid, and glutaric acid; and the fatty acid is selected from the group consisting of octanoic acid, decanoic acid, and dodecanoic acid.
  • the organic acid is selected from formic acid, fumaric acid, sorbic acid, benzoic acid, butanoic acid, and propionic acid; and the fatty acid is otanoic acid and/or decanoic acid.
  • the organic acid mixture comprises benzoic acid, and formic acid; and the fatty acid is octanoic acid and/or decanoic acid.
  • the organic acid is selected from fumaric acid, sorbic acid, benzoic acid, butanoic acid, and propionic acid; and the fatty acid is octanoic acid and/or decanoic acid.
  • the organic acid comprises calcium formate, sorbic acid, and benzoic acid; and the fatty acid is otanoic acid and/or decanoic acid.
  • the organic acid comprises sorbic acid, and benzoic acid; and the fatty acid is octanoic acid and/or decanoic acid.
  • compositions of the invention may have from about 0.1 % to about 99% by weight of organic acids and from about 0.1 % to about 99% by weight of fatty acids. More typically, the composition may have from about 5% by weight to about 50% by weight of organic acid and from about 5% by weight to about 50% by weight of fatty acid.
  • the matrix will comprises from about 30% to about 60% by weight of a fat source.
  • compositions of the invention may include additional ingredients without departing from the scope of the invention.
  • the composition may further optionally include one or more of a mixture of natural amino acids, analogs of natural amino acids, such as a hydroxyl analog of methionine ("HMTBA"), vitamins and derivatives thereof, supplemental protein, enzymes, animal drugs, hormones, effective microorganisms, organic acids, preservatives, flavors, and inert fats.
  • HMTBA hydroxyl analog of methionine
  • composition forming the bactericidal combination is protected such that release of an intact acidifying agent occurs in the distal portion of the gastrointestinal tract.
  • the composition may be formulated for release in the distal portion of the gastrointestinal tract by several suitable methods known in the art.
  • the composition may be encapsulated.
  • the composition is embedded in a matrix. (a) protection by matrix embedding
  • compositions comprising an acidifying agent that is embedded in a matrix.
  • the composition that is embedded may include any of the acidifying agent detailed in (l)(a) or (l)(c).
  • a variety of compounds or compositions are suitable for use as a matrix.
  • the term "matrix” is used in its broadest sense and includes any of a variety of compounds or compositions to which an acidifying agent may be embedded.
  • the matrix will comprise a lipid material from a fat source.
  • a suitable matrix is one that can be embedded with a relatively high density of composition comprising an acidifying agent.
  • the term “embedded” generally means that the acidifying agents forming the composition are disposed on the surface of or within the matrix.
  • matrix-embedded does not include encapsulated products, which are described below. Encapsulated products typically contain 100% of the active agent (e.g., acidifying agent) disposed inside of a protective coating or barrier.
  • the matrix will comprise a lipid material from a fat source.
  • the fat source may be an animal fat. Examples of animal fat include lard or butter.
  • the fat source may be a vegetable fat. Examples of vegetable fats include coconut oil, palm oil, cottonseed oil, wheat germ oil, soy oil, olive oil, corn oil, sunflower oil, safflower oil, rapeseed oil, and an essential oil.
  • the lipid is preferably hydrogenated, and can be saturated or partially saturated.
  • suitable lipid materials include, but are not limited to, monoglycehdes, diglycehdes, fatty acids, esters of fatty acids, phospholipids, salts thereof, and combinations thereof.
  • the lipid material may be a monoglyceride or diglyceride formed naturally in a biological system, as well as by partial or complete hydrolysis of triglycerides and distillation in commercial manufacturing. These methods are known to those skilled in the art.
  • Monoglycerides also known as monoacylglycerols, are molecules made up of a glycerol and a fatty acid bound as an ester.
  • Diglycerides i.e., diacylglycerols
  • diacylglycerols are molecules made up of a glycerol and two fatty acids, each fatty acid is bound to the glycerol as an ester.
  • the properties of the lipid material may vary.
  • the lipid material may be a phospholipid.
  • Phospholipids can be, for example, monoacyl and diacyl phospholipids.
  • Examples of phospholipids include, but are not limited to, phosphatidic acid, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl serine, phosphatidyl glycerol, and diphosphatidyl glycerol.
  • the lipid material may be a fatty acid having a carbon chain length of about 4 carbon atoms to about 24 carbon atoms.
  • the fatty acid will have a carbon chain length from about 6 carbon atoms to about 12 carbon atoms (i.e., a medium chain fatty acid).
  • Exemplary fatty acids include, but are not limited to, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, and combinations thereof.
  • the fatty acid may be saturated or unsaturated (e.g., partially saturated), in free form or estehfied to glycerol.
  • the lipid material may be a fatty acid ester.
  • the fatty acid esters can be mono- or diglycerol esters formed from fatty acids having from 4 to 24 carbon atoms, such as for example glyceryl distearate, glyceryl monostearate, glyceryl dipalmitate, glyceryl monopalmitate, glyceryl dilaurate, glyceryl didocosanoate, glyceryl monodocosanoate, glyceryl monocaprate, glyceryl dicaprate, glyceryl monomyristate, glyceryl dimyhstate, glyceryl monodecenoate, or glyceryl didecenoate.
  • the lipid material is preferably of food grade quality.
  • Some examples of food grade lipid materials include sorbitan monostearates, sorbitan tristearates, calcium stearoyl lactylates, and calcium stearoyl lactylates.
  • Examples of food grade fatty acid esters that are lipid materials include acetic acid esters of mono- and diglycerides, citric acid esters of mono- and di-glycehdes, lactic acid esters of mono- and di-gylcerides, polyglycerol esters of fatty acids, propylene glycol esters of fatty acids, and diacetyl tartaric acid esters of mono- and diglycerides.
  • the concentration of matrix material comprising the composition can and will vary without departing from the scope of the invention.
  • the matrix may comprise from about 1 % to about 99% by weight of the composition. More typically, the matrix will comprise about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, or about 20% by weight of the composition.
  • Another aspect of the invention encompasses processes for making a matrix-embedded composition.
  • a process of the invention includes heating the matrix comprising a lipid material, mixing the heated lipid material with the acidifying agent(s) to form an emulsion, and solidifying the emulsion to form a composition wherein the acidifying agent is embedded in a matrix.
  • the process may be initiated by heating a lipid material in a vessel for a time sufficient to thoroughly liquefy the lipid material source.
  • the fat source is heated under continuous agitation to a temperature of from about 50 0 C to about 120 0 C.
  • the vessel may be any suitable vessel that includes a heating and agitation means.
  • the liquefied lipid material may then be mixed with an acidifying agent or combination of acidifying agents to form an emulsion.
  • the process includes mixing from about 30% by weight to about 60% by weight of a lipid material with from about 0.1 % by weight to about 70% by weight of an acidifying agent.
  • the acidifying agent may be contacted with the liquefied lipid material source in a mixing vessel, thereby forming an emulsion.
  • the emulsion is then mixed and heated in the vessel until the organic acid and lipid material are thoroughly dispersed and the emulsion reaches a temperature of from about 50°C to about 100 0 C, preferably 60°C.
  • the vessel may be any suitable vessel that includes a heating and agitation means.
  • the emulsion is then fed into a solidification vessel that crystallizes or agglomerates the emulsion, thereby forming the matrix-embedded composition.
  • the solidification vessel is a spray tower.
  • a spray tower operates by atomizing the emulsion, for example with atomizers and/or nozzles, and contacting the emulsion with a gas at cool or low temperature. As the emulsion contacts the cool gas, the solution cools to a solidification temperature. Congealing then takes place at a constant temperature during release of the emulsion's heat of solidification. When no longer dispersed, the droplets further cool to give a stable solid composition embedded in a matrix.
  • the emulsion typically is introduced into the solidification vessel through the top of the vessel so that as the droplets fall onto the cool gas solidification of the emulsion starts to occur.
  • the gas used may be any gas suitable to cool and solidify, agglomerate, or crystallize the emulsion.
  • the gas is selected from air and an inert gas.
  • the gas is air.
  • the cool gas is at a temperature of from about 5 0 C to about 15°C, preferably about 10 0 C.
  • the matrix-embedded compositions may be selected so as to have the desired particle size.
  • the vessel may contain at least one screen to separate the desired sized particles.
  • the vessel may alternatively include more than one screen to separate the matrix- embedded composition into several distinctly sized particles.
  • the particles of undesired size may be recycled back into the mixing vessel to reduce waste of materials they may be discarded.
  • composition comprising an acidifying agent may be formulated for intact release in the distal portion of the gastrointestinal tract by microencapsulation or by a dry coating process. By varying the amount and type of coating and its thickness, the timing and location of release of the acidifying agent may be controlled.
  • the coating can and will vary depending upon a variety of factors, including, the particular acidifying agent, and the purpose to be achieved by its encapsulation.
  • the coating material may be a biopolymer, a semi-synthetic polymer, or a mixture thereof.
  • the microcapsule may comprise one coating layer or many coating layers, of which the layers may be of the same material or different materials.
  • the coating material may comprise a polysaccharide or a mixture of saccharides and glycoproteins extracted from a plant, fungus, or microbe.
  • Non-limiting examples include corn starch, wheat starch, potato starch, tapioca starch, cellulose, hemicellulose, dextrans, maltodextrin, cyclodextrins, inulins, pectin, mannans, gum arabic, locust bean gum, mesquite gum, guar gum, gum karaya, gum ghatti, tragacanth gum, funori, carrageenans, agar, alginates, chitosans, or gellan gum.
  • the coating material may comprise a protein. Suitable proteins include, but are not limited to, gelatin, casein, collagen, whey proteins, soy proteins, rice protein, and corn proteins.
  • the coating material may comprise a fat or oil, and in particular, a high temperature melting fat or oil.
  • the fat or oil may be hydrogenated or partially hydrogenated, and preferably is derived from a plant.
  • the fat or oil may comprise glycerides, free fatty acids, fatty acid esters, or a mixture thereof.
  • the coating material may comprise an edible wax. Edible waxes may be derived from animals, insects, or plants. Non-limiting examples include beeswax, lanolin, bayberry wax, carnauba wax, and rice bran wax.
  • the coating material may also comprise a mixture of biopolymers.
  • the coating material may comprise a mixture of a polysaccharide and a fat.
  • the coating may be an enteric coating.
  • the enteric coating generally will provide for controlled release of the acidifying agent, such that intact release can be accomplished at some generally predictable location in the lower intestinal tract below the point at which intact release would occur without the enteric coating.
  • multiple enteric coatings may be utilized. Multiple enteric coatings, in certain embodiments, may be selected to release the acidifying agent or combination of acidifying agents at various regions in the lower gastrointestinal tract and at various times.
  • the enteric coating is typically, although not necessarily, a polymeric material that is pH sensitive.
  • a variety of anionic polymers exhibiting a pH- dependent solubility profile may be suitably used as an enteric coating in the practice of the present invention to achieve delivery of the active to the lower gastrointestinal tract.
  • Suitable enteric coating materials include, but are not limited to: cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose succinate and carboxymethylcellulose sodium; acrylic acid polymers and copolymers, preferably formed from acrylic acid, methacrylic acid, methyl acrylate, ammonio methylacrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate (e.g., those copolymers sold under the trade name EUDRAGIT ® ); vinyl polymers and copolymers such as polyvinyl pyrrol idone, polyvinyl acetate, polyvinylacetate phthalate, vinylacetate crotonic acid copoly
  • the thickness of a microcapsule coating may be an important factor in some instances.
  • the "coating weight,” or relative amount of coating material per dosage form generally dictates the time interval between oral ingestion and drug release.
  • a coating utilized for time release of the acidifying agent or combination of acidifying agents into the gastrointestinal tract is typically applied to a sufficient thickness such that the entire coating does not dissolve in the gastrointestinal fluids at pH below about 5, but does dissolve at pH about 5 and above.
  • the thickness of the coating is generally optimized to achieve release of the acidifying agent at approximately the desired time and location.
  • the encapsulation or coating method can and will vary depending upon the acidifying agents used to form composition and coating, and the desired physical characteristics of the microcapsules themselves. Additionally, more than one encapsulation methods may be employed so as to create a multi-layered microcapsule, or the same encapsulation method may be employed sequentially so as to create a multi-layered microcapsule.
  • Suitable methods of microencapsulation may include spray drying, spinning disk encapsulation (also known as rotational suspension separation encapsulation), supercritical fluid encapsulation, air suspension microencapsulation, fluidized bed encapsulation, spray cooling/chilling (including matrix encapsulation), extrusion encapsulation, centrifugal extrusion, coacervation, alginate beads, liposome encapsulation, inclusion encapsulation, colloidosome encapsulation, sol-gel microencapsulation, and other methods of microencapsulation known in the art.
  • Another aspect of the invention comprises a feeding regime for porcine that is optimized to prevent the onset of at least one porcine enteropathic condition.
  • the feeding regime generally entails administering a bactericidal combination of the invention (e.g., a protected acidifying agent and an unprotected acidifying agent) to a pig at a time and in an effective amount.
  • a bactericidal combination of the invention e.g., a protected acidifying agent and an unprotected acidifying agent
  • the bactericidal combinations may be utilized to substantially reduce the number of at least one microorganism population selected from the group consisting of Lawsonia intracellula ⁇ s, Clostridium spp, Campylobacter spp, Salmonella spp, and Escherichia coli spp in the porcine gastrointestinal tract.
  • Either preventing colonization and/or reducing the rate of growth and/or division of microbes that have colonized may be utilized to reduce the number of such microorganisms. Because the combinations of the invention are formulated to deliver acidifying agents having bactericidal effects over substantially the entire gastrointestinal tract, they may be used to prevent a broad range of porcine enteropathic conditions, including without limitation, porcine proliferative enteropathy, hemorrhagic bowel syndrome, and enteritis.
  • the degree to which the bactericidal combinations inhibit gastrointestinal colonization by pathogenic microbes can and will depend in part upon the amount of acidify agent administered, the timing of administration (in relationship to gastrointestinal residence by the microbe), and the stage of the pig's lifecycle (i.e., its age, and weight).
  • the bactericidal combination is administered to the porcine before colonization of the gastrointestinal tract by a target pathogenic microbe. In some instances, depending upon the microbial target, this may mean that the bactericidal combination is continuously administered to the pig starting when it is a piglet and continuing through the growing stage and finishing stage until shortly before the pig is slaughtered.
  • the bactericidal combination may be beneficially administered periodically to the pig starting when it is a piglet and continuing through the growing stage and finishing stage until shortly before the pig is slaughtered. It is also envisioned that the bactericidal combination may be continuously or periodically administered to the breeding herd (i.e., gilts, gestating sows, lactating sows, and boars) to reduce the incidence of certain pathogenic microbes within the herd.
  • breeding herd i.e., gilts, gestating sows, lactating sows, and boars
  • the bactericidal combination is administered to pigs in the growing stage and finishing stage as a part of a feeding regime to prevent gastrointestinal colonization by microbes that cause enteropathic conditions.
  • Pigs in the growing stage are typically from about 20 to about 50 Kg in body weight, and pigs in the finishing stage are generally greater than about 50 Kg of body weight to slaughter weight (i.e., 100 to about 120 Kg of body weight).
  • the microbial target may be selected from the group consisting of Lawsonia intracellularis, Clostridium spp, Campylobacter spp, Salmonella spp, and Escherichia coli spp.
  • the feeding regime of the invention to prevent porcine proliferative enteropathy generally involves administering the bactericidal combination periodically to the pig as it progresses from a piglet through the growing and finishing stage.
  • the bactericidal combination is administered before colonization of the gastrointestinal tract by the target pathogenic microbe.
  • the feeding regime generally comprises administering the bactericidal combination for a sufficient period of time (typically at least 4 weeks) prior to a critical period and continuing for at least 2 to 3 weeks, followed by discontinuation of administration of the bactericidal combination for a sufficient period to allow an immunity to develop (typically 10 to 14 days), followed by administration of the bactericidal combination for a period of time sufficient to prevent colonization until the pig reaches slaughter weight (typically at least 2 weeks).
  • a sufficient period of time typically at least 4 weeks
  • the feeding regime generally comprises administering the bactericidal combination for a sufficient period of time (typically at least 4 weeks) prior to a critical period and continuing for at least 2 to 3 weeks, followed by discontinuation of administration of the bactericidal combination for a sufficient period to allow an immunity to develop (typically 10 to 14 days), followed by administration of the bactericidal combination for a period of time sufficient to prevent colonization until the pig reaches slaughter weight (typically at least 2 weeks).
  • the "critical period” is generally the time after which the target microbe has colonized the gastrointestinal tract of the pig in sufficient number such that sub clinical symptoms of the enteropathic condition may be present.
  • the precise onset of the "critical period” can and will vary from herd to herd. In general, a skilled artisan may predict the critical period by reviewing historical data from the herd regarding onset of the critical period, and also by utilizing diagnostic and clinical tests to determine whether an enteropathic condition is present in the herd and the time in which the critical period appears.
  • Typical diagnostic or clinical tests that may be utilized to detect pathogenic microbes include, but are not limited to, visual examination of the herd, immunochemistry, PCR, histology, serology, and postmortem examination.
  • a critical period typically may be selected from the group consisting of about 5 to about 6 weeks after the pig has been weaned from the sow, from about 8 to about 10 weeks after the pig has been weaned from the sow, from about 12 to about 14 weeks after the pig has been weaned from the sow, and from about 16 to about 18 weeks after the pig has been weaned from the sow.
  • immunogenic refers to the ability of the pig's immune system to elicit an immunogenic response to the target pathogenic microbe.
  • the degree of the immunogenic response may be determined by monitoring the serum antibody titer (i.e., antibodies produced by the pig in response to the target pathogenic microbe) in accordance with any suitable method generally known in the art.
  • the target pathogenic serum IgG may be monitored to determine the degree of "immunity.”
  • the presence of the target pathogenic microbe may be detected immunological using an antibody against the microbe.
  • the timing of administration of the bactericidal combination can and will vary in the feeding regime depending on the particular critical period, as detailed below.
  • the bactericidal combination may be utilized in a feeding regime to prevent colonization of the gastrointestinal tract by Lawsonia intracellularis (and other microbes) when the critical period is about 5 weeks to about 6 weeks after the pig has been weaned from the sow.
  • the pig is typically administered the bactericidal combination starting when it is a piglet, or from about the time of weaning and continuing until about 4 weeks after weaning.
  • Administration of the bactericidal combination is then discontinued for about 7 to about 14 days (i.e., after 5 to about 6 weeks after the pig has been weaned) to allow immunity to develop to the target microbe.
  • the bactericidal combination is then administered to the pig for a period of time sufficient to avoid infection, which is generally at least 2 weeks.
  • the period of time sufficient to prevent infection will depend upon length of the finisher cycle, but is typically the length of time in weeks it takes the pig to reach approximate slaughter weight ranging from about 100 to about 110 Kg of body weight (i.e., 220 to about 240 pounds).
  • the bactericidal combination may be utilized in a feeding regime to prevent colonization of the gastrointestinal tract by Lawsonia intracellularis (and other microbes) when the critical period is about 9 weeks to about 10 weeks after the pig has been weaned from the sow.
  • the pig is typically administered the bactericidal combination starting from about 4 weeks after weaning and continuing until about 8 weeks after weaning.
  • Administration of the bactericidal combination is then discontinued for about 7 to about 14 days (i.e., after 9 to about 10 weeks after the pig has been weaned) to allow immunity to develop to the target microbe.
  • the bactericidal combination is then administered to the pig for a period of time sufficient to avoid infection, which is generally at least 2 weeks.
  • the period of time sufficient to prevent infection will depend upon length of the finisher cycle, but is typically the length of time in weeks it takes the pig to reach approximate slaughter weight ranging from about 100 to about 110 Kg of body weight (i.e., 220 to about 240 pounds).
  • the bactericidal combination may be utilized in a feeding regime to prevent colonization of the gastrointestinal tract by Lawsonia intracellularis (and other microbes) when the critical period is about 13 weeks to about 14 weeks after the pig has been weaned from the sow.
  • the pig is typically administered the bactericidal combination starting at about 8 weeks after weaning and continuing until about 12 weeks after weaning.
  • Administration of the bactericidal combination is then discontinued for about 7 to about 14 days (i.e., after 13 to about 14 weeks after the pig has been weaned) to allow immunity to develop to the target microbe.
  • the bactericidal combination is then administered to the pig for a period of time sufficient to avoid infection, which is generally at least 2 weeks.
  • the period of time sufficient to prevent infection will depend upon length of the finisher cycle, but is typically the length of time in weeks it takes the pig to reach approximate slaughter weight ranging from about 100 to about 110 Kg of body weight (i.e., 220 to about 240 pounds), which in this case is about two to about 3 weeks.
  • the amount of protected acidifying agent and unprotected acidifying agent (i.e., forming the bactericidal combination) administered to the pig can and will vary depending upon the feeding regime, drinking water alkalinity and pH. Generally speaking, in each feeding regime detailed herein, the amount administered to the pig is an "effective amount.” In this context, an effective amount is the amount needed to either prevent colonization of the gastrointestinal tract by a target microbe all together, or to reduce the colonization to a low enough level such that no clinical or sub clinical symptoms of enteropathic conditions occur.
  • the bacterial combinations comprising a protected acidifying agent and an unprotected acidifying agent may be administered to the porcine by any method known in the art.
  • the bactericidal combination is administered to the porcine by adding one or both acidifying agents to its water source.
  • one or both acidifying agents may be added to the pig's feed ration.
  • one acidifying agent may be added to the pig's water source and the other acidifying agent may be added to the pig's feed ration.
  • the combinations may be added to a variety of types of feed formulations for swine. Suitable feed rations for swine will vary for piglets, grower pigs, finisher pigs, gilts, gestating sows, lactating sows, and boars.
  • Swine feed formulations typically comprise grains (e.g., corn, barley, grain sorghum, oats, soybeans, wheat, etc.), proteins (e.g., fish meal, gluten meal, meat meal, soybean meal, tankage, which is the residue that remains after rendering fat in a slaughterhouse, etc.), fats (e.g., fish oils, vegetable oils, animal fats, choice white grease, yellow grease, etc.), supplemental amino acids (e.g., lysine, methionine or methionine analogs, etc), vitamins, minerals, mycotoxin inhibitors, antifungal agents, and pharma/nutriceuticals.
  • grains e.g., corn, barley, grain sorghum, oats, soybeans, wheat, etc.
  • proteins e.g., fish meal, gluten meal, meat meal, soybean meal, tankage, which is the residue that remains after rendering fat in a slaughterhouse, etc.
  • fats e.g., fish oils, vegetable oils, animal fats, choice
  • the protected acidifying agent and unprotected acidifying agent forming the combination may be administered sequentially or simultaneously.
  • the protected acidifying agent may be (a) benzoic acid, formic acid, and sorbic acid, (b) formic acid, fumaric acid, and sorbic acid, or (c) formic acid and sorbic acid
  • the unprotected acidifying agent may be (a) formic acid, (b) formic acid and propionic acid; (c) formic acid, propionic acid, and 2-hydroxy-4-methylthiobutanoic acid; and (d) benzoic acid and fumaric acid.
  • Table C lists exemplary combinations of the bactericidal acidifying agents.
  • the alkyl groups described herein are preferably lower alkyl containing from one to eight carbon atoms in the principal chain and up to 20 carbon atoms. They may be straight or branched chain or cyclic and include methyl, ethyl, propyl, isopropyl, butyl, hexyl and the like.
  • the alkenyl groups described herein are preferably lower alkenyl containing from two to eight carbon atoms in the principal chain and up to 20 carbon atoms. They may be straight or branched chain or cyclic and include ethenyl, propenyl, isopropenyl, butenyl, isobutenyl, hexenyl, and the like.
  • alkynyl groups described herein are preferably lower alkynyl containing from two to eight carbon atoms in the principal chain and up to 20 carbon atoms. They may be straight or branched chain and include ethynyl, propynyl, butynyl, isobutynyl, hexynyl, and the like.
  • aryl or “ar” as used herein alone or as part of another group denote optionally substituted homocyclic aromatic groups, preferably monocyclic or bicyclic groups containing from 6 to 12 carbons in the ring portion, such as phenyl, biphenyl, naphthyl, substituted phenyl, substituted biphenyl or substituted naphthyl. Phenyl and substituted phenyl are the more preferred aryl.
  • Carboxylic acid refers to organic acids comprising hydrocarbon groups that contain a carboxyl group (COOH).
  • the hydrocarbon moiety consists exclusively of the elements carbon and hydrogen.
  • Carboxylic acids may have straight chains (aliphatic) of hydrocarbyl groups, or they may be aromatic carboxylic acids, as well as some alicyclic carboxylic acids (i.e., both aliphatic and cyclic).
  • Straight chain aliphatic carboxylic acids preferably have 3 to 24 carbons (including the terminal carboxyl carbon).
  • the hydrocarbon chain of an aliphatic carboxylic acid may be saturated (i.e., the carbon atoms have all the hydrogen atoms they can hold) and contain no double bonds between the carbons.
  • the hydrocarbon chain may be unsaturated and contain one or more double bonds between the some of the carbons.
  • Unsaturated carboxylic acids may assume cis or trans configurations, which refer to the orientation of the hydrogen atoms with respect to the double bond. Cis means “on the same side” and trans means “across” or "on the other side”.
  • distal portion of gastrointestinal tract refers to a region of the gastrointestinal area starting at about the ileum and ending at about the colon.
  • An "essential amino acid” is an amino acid that cannot be synthesized by an organism and must be supplied as part of its diet. It is generally recognized that ten amino acids are essential for humans and animals. The essential amino acids are arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.
  • heterocyclo or “heterocyclic” as used herein alone or as part of another group denote optionally substituted, fully saturated or unsaturated, monocyclic or bicyclic, aromatic or nonaromatic groups having at least one heteroatom in at least one ring, and preferably 5 or 6 atoms in each ring.
  • the heterocyclo group preferably has 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, and/or 1 to 4 nitrogen atoms in the ring, and may be bonded to the remainder of the molecule through a carbon or heteroatom.
  • heterocyclo include heteroaromatics such as furyl, thienyl, pyridyl, oxazolyl, pyrrolyl, indolyl, quinolinyl, or isoquinolinyl and the like.
  • substituents include one or more of the following groups: hydrocarbyl, substituted hydrocarbyl, keto, hydroxy, protected hydroxy, acyl, acyloxy, alkoxy, alkenoxy, alkynoxy, aryloxy, halogen, amido, amino, nitro, cyano, thiol, ketals, acetals, esters and ethers.
  • heteroaromatic as used herein alone or as part of another group denote optionally substituted aromatic groups having at least one heteroatom in at least one ring, and preferably 5 or 6 atoms in each ring.
  • the heteroaromatic group preferably has 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, and/or 1 to 4 nitrogen atoms in the ring, and may be bonded to the remainder of the molecule through a carbon or heteroatom.
  • Exemplary heteroaromatics include furyl, thienyl, pyridyl, oxazolyl, pyrrolyl, indolyl, quinolinyl, or isoquinolinyl and the like.
  • substituents include one or more of the following groups: hydrocarbyl, substituted hydrocarbyl, keto, hydroxy, protected hydroxy, acyl, acyloxy, alkoxy, alkenoxy, alkynoxy, aryloxy, halogen, amido, amino, nitro, cyano, thiol, ketals, acetals, esters and ethers.
  • HMTBA stands for 2-hydroxy-4-(methylthio)butanoic acid (sold under the trade name ALIMET ® by Novus International, Inc., St. Louis, Missouri).
  • hydrocarbon and “hydrocarbyl” as used herein describe organic compounds or radicals consisting exclusively of the elements carbon and hydrogen. These moieties include alkyl, alkenyl, alkynyl, and aryl moieties. These moieties also include alkyl, alkenyl, alkynyl, and aryl moieties substituted with other aliphatic or cyclic hydrocarbon groups, such as alkaryl, alkenaryl and alkynaryl. Unless otherwise indicated, these moieties preferably comprise 1 to 20 carbon atoms.
  • proximal portion of gastrointestinal tract refers to a region of the gastrointestinal area starting at about the stomach and ending at about the upper section of the duodenum.
  • substituted carboxylic acid refers to substitutions within the hydrocarbyl chain of a straight chain aliphatic carboxylic acid.
  • Hydrocarbyl moieties may be substituted with at least one atom, including the substitution of a carbon atom with a heteroatom such as nitrogen, oxygen, silicon, phosphorous, boron, sulfur, or a halogen atom.
  • substitutions may also include hydrocarbyl moieties, such as alkyl, alkenyl, alkynyl, and aryl moieties, with these moieties having one to 20 carbon atoms.
  • substituted moieties include hydrocarbyloxy, such as acyloxy, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, protected hydroxy, keto, acyl, acyloxy, nitro, amino, amido, cyano, thiol, ketals, acetals, heterocyclo, esters and ethers.
  • Dicarboxylic acids contain an additional carboxyl group at the other end of the molecule.
  • ⁇ -Hydroxy acids are another type of substituted carboxylic acid; ⁇ -hydroxy acids generally have a hydroxyl group on the alpha carbon atom (i.e., the carbon adjacent to the terminal carbonyl carbon).
  • ⁇ -Amino acids which have an amino group on the alpha carbon, are also substituted carboxylic acids.
  • the "substituted hydrocarbyl" moieties described herein are hydrocarbyl moieties which are substituted with at least one atom other than carbon, including moieties in which a carbon chain atom is substituted with a hetero atom such as nitrogen, oxygen, silicon, phosphorous, boron, sulfur, or a halogen atom.
  • substituents include halogen, carbocycle, aryl, heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, protected hydroxy, keto, acyl, acyloxy, nitro, amino, amido, nitro, cyano, thiol, ketals, acetals, esters and ethers.
  • Example 1 Effectiveness of a Bactericidal Combination to Control Enteritis.
  • Organic acids have antimicrobial activity in the gastrointestinal tract and may provide control of ileitis either directly or indirectly via the control of other pathogens.
  • Gastrointestinal tract environmental modifiers including protected organic acids, have been shown to improve pig performance in nursery diets, especially in low lactose diets, and improve growth performance in grower/finisher pigs with increased carcass weight compared to controls.
  • a portion of the improved growth response could be attributed to stabilization of the gastrointestinal tract microflora during times of diet phase changes, changes in dietary formulation, and changes in feed intake patterns via ontogeny changes, hot weather, and reduced animal space in conjunction with lower feeder spaces.
  • a total of about 400 pigs (Pietrain male x Duroc-Landrace female) were included in the study. They were evaluated from the time they entered the nursery (i.e., at about 4 weeks of age) until they reached market weight (i.e., at about 24 weeks of age).
  • the pigs were housed in barns of approximately 200 pigs/barn, with approximately 20 pigs per pen.
  • the pens were in thermo-controlled rooms with adequate ventilation systems and space for nursery and grower/finisher pigs. Animal care was according to standard site practices. The animals were observed daily including weekends and holidays. Ambient temperature was monitored, and feeders and waterers were observed. Any abnormal observations, mortalities, or morbidities were recorded by treatment, pen, weight, and date.
  • the animals were provided with a phase feeding program that complied with industry norms for energy, digestible amino acids, vitamins and minerals.
  • the phases were starter I (weaning to 18 Kg body weight), starter Il (18 to 25 Kg of body weight), grower (25 to 50 Kg of body weight), finish I (50 to 85 Kg of body weight), and finish Il (85 to 105 Kg of body weight). All of the diets were analyzed for nutrient and amino acid composition.
  • the bactericidal combination comprised formic acid, as provided by ACIDOMIX ® Formic 50 (Novus International) at 6 Kg per metric ton, and a blend of formic acid, fumaric acid, and sorbic acid embedded in a fat matrix, as provided by ACIDOMIX ® Protect (Novus Intl.) at 3 Kg per metric ton.
  • Feed consumption was determined at 6, 13, and 20 weeks post weaning. Feed consumption was calculated as the amount of feed offered minus the amount of feed refused. Feed offered was determined by weighing the amount of feed provided to each pen. Feed refused was determined by weighing the amount of feed left in the feeder and any remainder that had previously been recorded as feed offered.
  • Blood was collected from about 27 pigs per barn (i.e., about 27 pigs per group) at 0, 6, 13, and 20 weeks post weaning and sampled for the presence of L. intracellularis.
  • the selected pigs included normal pigs and pigs showing signs of poor performance (at about a 50:50 representation).
  • the presence of L. intracellularis in the blood was detected by ELISA using an antibody against L. intracellularis.
  • Pools of feces were also collected at 0, 6, 13, and 20 weeks post weaning and analyzed by PCR for the presence of L. intracellularis.
  • the samples comprised 4 pools representing (1 ) control healthy, (2) control poor performers, (3) treated healthy, and (4) treated poor performers.
  • Necropsy samples were collected at 6, 13, and 20 weeks post weaning from (1 ) a control healthy pig, (2) a control poor performing pig, (3) a treated healthy pig, and (4) a treated poor performing pig. The samples were analyzed by a diagnostic laboratory for incidence of ileitis and determination of Salmonella counts.
  • the pigs treated with the combination of protected and unprotected organic acids had a higher average body weight than the control pigs. At 16 weeks of age, the average body weight of the treated pigs was 76.47 Kg and the average body weight of the control pigs was 72.70 Kg.
  • Treatment will comprise a combination of a protected acidifying agent and an unprotected acidifying agent as detailed herein. Diets and care of animals will be conducted essential as described above in Example 1. Weight gain and feed intake will be monitored as detailed in Example 1. Additionally, the presence of L. intracellularis will be monitored using appropriate indicators.

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Abstract

La présente invention concerne des régimes alimentaires comprenant l'administration d'une combinaison bactéricide d'agents acidifiants pour empêcher l'apparition d'une affection entéropathique porcine. De façon particulière, la combinaison bactéricide comprend une première composition comprenant un agent acidifiant protégé et une seconde composition comprenant un agent acidifiant non protégé.
PCT/US2008/068896 2007-07-02 2008-07-01 Régime alimentaire permettant la prévention d'affections entéropathiques porcines WO2009006466A1 (fr)

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WO2014195039A1 (fr) * 2013-06-03 2014-12-11 Basf Se Compositions destinées à être utilisées dans la régulation de la microflore intestinale
BE1023491B1 (nl) * 2015-10-06 2017-04-06 Nutri-Ad International Nv Voedingsadditief voor gevogelte
CN109223750A (zh) * 2018-10-16 2019-01-18 中国水产科学研究院南海水产研究所 琥珀酸在防治对虾肠炎中的应用
US10772343B2 (en) 2014-11-19 2020-09-15 Kansas State University Research Foundation Chemical mitigants in animal feed and feed ingredients
CN111757752A (zh) * 2018-02-28 2020-10-09 勃林格殷格翰动物保健有限公司 用于减少动物中的粪臭素和/或吲哚的方法

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US20070042184A1 (en) * 2003-08-22 2007-02-22 Danisco A/S Microcapsules

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US20030060425A1 (en) * 1998-11-24 2003-03-27 Ahlem Clarence N. Immune modulation method using steroid compounds
US20040235759A1 (en) * 2000-04-27 2004-11-25 Pfizer Inc Use of azalide antibiotic compositions for treating or preventing a bacterial or protozoal infection in mammals
US20030176500A1 (en) * 2000-06-20 2003-09-18 Koen Molly Medium chain fatty acids applicable as antimicrobial agents
US20070042184A1 (en) * 2003-08-22 2007-02-22 Danisco A/S Microcapsules

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014195039A1 (fr) * 2013-06-03 2014-12-11 Basf Se Compositions destinées à être utilisées dans la régulation de la microflore intestinale
US10772343B2 (en) 2014-11-19 2020-09-15 Kansas State University Research Foundation Chemical mitigants in animal feed and feed ingredients
US10918118B2 (en) 2014-11-19 2021-02-16 Kansas State University Research Foundation Chemical mitigants in animal feed and feed ingredients
US11896035B2 (en) 2014-11-19 2024-02-13 Kansas State University Research Foundation Chemical mitigants in animal feed and feed ingredients
BE1023491B1 (nl) * 2015-10-06 2017-04-06 Nutri-Ad International Nv Voedingsadditief voor gevogelte
CN111757752A (zh) * 2018-02-28 2020-10-09 勃林格殷格翰动物保健有限公司 用于减少动物中的粪臭素和/或吲哚的方法
CN109223750A (zh) * 2018-10-16 2019-01-18 中国水产科学研究院南海水产研究所 琥珀酸在防治对虾肠炎中的应用

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