WO2023163884A1 - Liquid formulation comprising yucca and quillaja for administration to animals - Google Patents

Liquid formulation comprising yucca and quillaja for administration to animals Download PDF

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Publication number
WO2023163884A1
WO2023163884A1 PCT/US2023/013136 US2023013136W WO2023163884A1 WO 2023163884 A1 WO2023163884 A1 WO 2023163884A1 US 2023013136 W US2023013136 W US 2023013136W WO 2023163884 A1 WO2023163884 A1 WO 2023163884A1
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composition
ppm
animal
solids obtained
decreases
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PCT/US2023/013136
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French (fr)
Inventor
A. Bruce Johnson
Rodrigo OTERO
Kenneth W. Bafundo
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Phibro Animal Health Corporation
Desert King International Llc
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Application filed by Phibro Animal Health Corporation, Desert King International Llc filed Critical Phibro Animal Health Corporation
Publication of WO2023163884A1 publication Critical patent/WO2023163884A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/73Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present disclosure concerns a liquid formulation comprising yucca and quillaja for administration to an animal.
  • an aqueous composition comprises from 12 wt% to 36 wt% solids obtained from Quillaja saponaria, and from 3 wt% to 25 wt% solids obtained from Yucca schidigera.
  • the Quillaja saponaria solids are provided by an aqueous Quillaja saponaria extract comprising 25 wt% to 50 wt% dissolved solids; or (ii) the Yucca schidigera solids are provided by an aqueous Yucca schidigera extract comprising 30 wt% to 60 wt% dissolved solids; or (iii) both (i) and (ii).
  • the aqueous composition may have a Quillaja saponaria:Yucca schidigera solids ratio on a w/w basis of from 1.3 to 4.5.
  • the aqueous composition may further include a defoaming agent.
  • the aqueous composition includes from 25 ppm to 15,000 ppm of the defoaming agent.
  • the aqueous composition may further include citric acid.
  • the aqueous composition includes from 1 ppm to 10,000 ppm of the citric acid.
  • Embodiments of a method for using the aqueous composition include combining the disclosed aqueous composition with water in an amount of from greater than 0 ppm to 500 ppm to provide a diluted composition, and administering the diluted composition to an animal.
  • the aqueous composition does not comprise a defoaming agent, and the method further includes combining a defoaming agent with the aqueous composition and the water to provide the diluted composition.
  • the diluted composition may be administered to the animal in place of drinking water.
  • the diluted composition may be administered daily to the animal.
  • the animal is an avian, such as a chicken, a turkey, a goose, a duck, a Cornish game hen, a quail, a pheasant, a partridge, a guinea fowl, a peafowl, a pigeon, an ostrich, an emu, or a swan.
  • the diluted composition may be administered to the avian beginning on day of hatching.
  • an effective amount of the diluted composition is administered daily to the animal for a period of time sufficient to promote a beneficial health effect.
  • administering the diluted composition to the animal may increase body weight, decrease feed conversion ratio, decrease mortality rate, decrease Clostridium incidence, decrease Salmonella incidence, increase villus height:crypt depth ratio, or any combination thereof compared to (i) an animal that did not receive the diluted composition, (ii) an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera, and/or (iii) an animal that received a diluted composition comprising water and solids obtained from only one of Quillaja saponaria or Yucca schidigera.
  • the method may further include administering a therapeutic agent to the animal.
  • the therapeutic agent is an antimicrobial, an antibiotic, an antifungal, an anticoccidial agent, a vaccine, a direct-fed microbial, yeast, a polyphenol, or any combination thereof.
  • the therapeutic agent may be administered to the animal prior to, concurrently with, or following administration of the diluted composition.
  • FIG. 1 is a graph of bird weight (g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Quillaja saponaria (Q) liquid extract, 100% Yucca schidigera (Y) liquid extract, 25/75 Quillaja saponaria / Yucca schidigera (QY) liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm Magni-Phi® (MP) powder, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
  • FIG. 2 is a graph of feed conversion ratio (FCR, g:g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
  • FCR feed conversion ratio
  • FIG. 3 is a graph illustrating Clostridium enumeration results (logio) obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 21 days of feeding.
  • FIG. 4 is a graph of Salmonella incidence (%) illustrating results obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
  • FIG. 5 is a graph of villus height:crypt depth ratio illustrating results obtained from feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 21 days of feeding.
  • FIG. 6 is a graph of bird weight (g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Quillaja saponaria (Q) liquid extract, 100% Yucca schidigera (Y) liquid extract, 25/75 Quillaja saponaria / Yucca schidigera (QY) liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm Magni-Phi® (MP) powder, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
  • FIG. 7 is a graph of feed conversion ratio (FCR, g:g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
  • FCR feed conversion ratio
  • FIG. 8 is a graph illustrating Clostridium enumeration results (loglO) obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 21 days of feeding.
  • FIG. 9 is a graph of Salmonella incidence (%) illustrating results obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
  • This disclosure concerns embodiments of a liquid composition comprising quillaja and yucca, and a method for administering the composition to animals.
  • the liquid composition comprises extracts of Quillaja saponaria and Yucca schidigera.
  • the animals are avians.
  • Administering Providing a combination, composition, or component disclosed herein by any suitable route to an animal.
  • administration can refer to oral administration.
  • Animal This term includes, but is not limited to, humans, mammals, aquaculture species, and avian species. In some embodiments, this term can refer to mammals, aquaculture species (animals that live in salt or fresh water), and avian species that are raised for human consumption or that are domesticated animals. Exemplary such animal species are provided herein.
  • a combination includes two or more components that are administered such that the effective time period of at least one component overlaps with the effective time period of at least one other component.
  • a combination, or a component thereof may be a composition.
  • effective time periods of all components administered overlap with each other.
  • the effective time period of the first component administered may overlap with the effective time periods of the second and third components, but the effective time periods of the second and third components independently may or may not overlap with one another.
  • a combination may be a composition comprising the components, a composition comprising one or more components and another separate component (or components) or composition(s) comprising the remaining component(s), or the combination may be two or more individual components.
  • the two or more components may comprise the same component administered at two or more different times, two or more different components administered substantially simultaneously or sequentially in any order, or a combination thereof.
  • Direct fed microbial A composition that contains live and/or viable microorganisms, typically bacteria and/or yeast, that provides a beneficial effect on an animal.
  • Feed conversion rate/ratio A measure of the efficiency of an animal, such as an avian, to convert feed mass into increased body mass.
  • Poultry domesticated birds raised for meat and/or eggs, e.g., chickens, turkeys, geese, ducks, Cornish game hens, quail, pheasants, partridges, guinea fowl, peafowl, pigeons, ostriches, emus, and swans.
  • meat and/or eggs e.g., chickens, turkeys, geese, ducks, Cornish game hens, quail, pheasants, partridges, guinea fowl, peafowl, pigeons, ostriches, emus, and swans.
  • Saponin A class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in particular abundance in various plant species. More specifically, they are amphipathic glycosides grouped, in terms of structure, by their composition.
  • saponin comprises one or more hydrophilic glycoside moieties combined with a lipophilic triterpene derivative.
  • a steroidal saponin has a steroid base (e.g., spirostanol or furostanol) in place of the triterpene moiety.
  • Yucca saponins are steroidal saponins.
  • Quillaja saponins are triterpenoid saponins.
  • Therapeutic agent An agent that is capable of providing a therapeutic effect, e.g., preventing a disorder, inhibiting a disorder, such as by arresting the development of the disorder or its clinical symptoms, or relieving a disorder by causing regression of the disorder or its clinical symptoms.
  • Therapeutically Effective Amount or Effective Amount A quantity or concentration of a specified compound or composition sufficient to achieve a desired effect in an animal being treated for a disorder.
  • the therapeutically effective amount may depend at least in part on the species of animal being treated, the size of the animal, and/or the severity of the disorder.
  • a liquid composition comprising water, solids obtained from quillaja and solids obtained from yucca.
  • the liquid composition is an aqueous composition comprising solids obtained from Quillaja saponaria and solids obtained from Yucca schidigera.
  • an aqueous composition is a composition in which the solvent is water.
  • liquid composition and aqueous composition may be used interchangeably, whereby it is understood that the composition is a liquid composition in which the solvent is water.
  • the liquid composition consists of, or consists essentially of, water, dissolved solids obtained from Quillaja saponaria and dissolved solids obtained from Yucca schidigera.
  • Consists of means that the composition does not include any other component except for impurities ordinarily associated with the recited components.
  • Consists essentially of means that the composition does not include other components that may provide a health benefit to an animal receiving the liquid composition.
  • the term “consists essentially of’ precludes therapeutic agents as discussed infra, vitamins, minerals, amino acids, or the like, in amounts effective to provide any health benefit.
  • the term “consists essentially of’ does not preclude small amounts (e.g., less than 2 wt%) of additives that do not provide a health benefit to the animal, e.g., a defoaming agent, a colorant, a taste enhancer, a preservative, or the like. “Consists essentially of’ also does not preclude administering separate compositions to an animal that do include therapeutic agents.
  • quillaja examples include, but are not limited to, Quillaja brasiliensis, Quillaja lanceolata, Quillaja lancifolia, Quillaja molinae, Quillaja petiolaris, Quillaja poeppigii, Quillaja saponaria, Quillaja sellowiana, or Quillaja smegmadermos.
  • the quillaja is Quillaja saponaria.
  • Examples of yucca that can be used in the disclosed combination include, but are not limited to, Yucca aloifolia, Yucca angustissima, Yucca arkansana, Yucca baccata, Yucca baileyi, Yucca brevifolia, Yucca campestris, Yucca capensis, Yucca carnerosana, Yucca cernua, Yucca coaeriensis, Yucca constricta, Yucca decipiens, Yucca declinata, Yucca de-smetiana, Yucca elata, YuccaIFFiana, Yucca faxoniana, Yucca filamentosa, Yucca filifera, Yucca flaccida, Yucca gigantean, Yucca glauca, Yucca gloriosa, Yucca grandiflora, Yucca harrimaniae, Yucca intermedia, Yucca jaliscensis, Yucca lacandonica, Yucca linearifolia, Yucca luminosa, Yucca madrensis, Yucca
  • a plant name may refer to the plant as a whole, or to any part of the plant, such as the roots, stem or trunk, bark, leaves, flower, flower stems, or seeds or a combination thereof.
  • the name may also refer to extracts from any part or parts of the plant, such as chemical extracts, or extracts obtained by pressing, or any other methods of concentrating or extracting oils or other extracts known to those in the art or that are hereafter discovered.
  • Plant extracts may include compounds that are saponins, triterpenoids, polyphenols, antioxidants, resveratrol, or combinations thereof.
  • the liquid composition may comprise a Quillaja saponaria extract and a Yucca schidigera extract.
  • the Quillaja saponaria plant extract comprises at least one saponin, polyphenol, antioxidant, resveratrol or any combination thereof.
  • the Yucca schidigera plant extract comprises at least one saponin, polyphenol, antioxidant, resveratrol or any combination thereof.
  • the aqueous composition comprises, consists essentially of, or consists of from 12 wt% to 36 wt% solids obtained from Quillaja saponaria, and from 3 wt% to 25 wt% solids obtained from Yucca schidigera.
  • the aqueous composition comprises 15 wt% to 35 wt% solids obtained from Quillaja saponaria and 4 wt% to 20 wt% solids obtained from Yucca schidigera, or 20 wt% to 35 wt% solids obtained from Quillaja saponaria and 8 wt% to 15 wt% solids obtained from Yucca schidigera, or 20 wt% to 30 wt% solids obtained from Quillaja saponaria and 10 wt% to 12 wt% solids obtained from Yucca schidigera.
  • the aqueous composition comprises, consists essentially of, or consists of from 22 wt% to 30 wt% solids obtained from Quillaja saponaria and 11 wt% to 12 wt% solids obtained from Yucca schidigera.
  • the solids may be dissolved solids.
  • the aqueous composition may have a Quillaja saponaria : Yucca schidigera solids ratio (Q:Y ratio) on a w/w basis of from 0.5 to 12, such as a Q:Y ratio of from 0.75 to 9, from 1.3 to 4.5, or 1.7 to 3.
  • the aqueous composition has a Q:Y solids ratio of from 2 to 2.7.
  • the aqueous composition may be prepared from a Quillaja saponaria extract and a Yucca schidigera extract, in amounts to provide a Quillaja saponaria : Yucca schidigera extract volume ratio of from 50:50 to 90:10, i.e., 50 vol% to 90 vol% Quillaja saponaria extract and 10 vol% to 50 vol% Yucca schidigera extract.
  • the aqueous composition has a Quillaja saponaria : Yucca schidigera extract volume ratio of from 75:25 to 90:10, i.e., 75-90 vol% Quillaja saponaria extract and 10-25 vol% Yucca schidigera extract.
  • the Quillaja saponaria extract may have a solids content of from 25 wt% to 50 wt% dissolved solids, such as from 30 wt% to 40 wt% dissolved solids.
  • the Yucca schidigera extract may have a solids content of from 30 wt% to 60 wt% dissolved solids, such as from 45 wt% to 50 wt% dissolved solids.
  • the aqueous composition consists essentially of, or consists of, the two extracts.
  • the aqueous composition may further comprise a defoaming agent.
  • defoaming agents include, but are not limited to, wax-, oil- and/or silica-based defoamers.
  • Exemplary commercially available defoaming agents include Magrabar® Organic 3000 defoamer (Magrabar, Morton Grove, IL), which includes natural waxes, vegetable oil, emulsifiers, and silicon dioxide, and Magrabar® Organic 3200 defoamer, which includes vegetable oil, silicon dioxide, and vegetable-derived mixed tocopherols.
  • the composition comprises up to 15,000 ppm (1.5 wt%), such as up to 10,000 ppm (1 wt%) of a defoaming agent.
  • the composition may comprise a defoaming agent in an amount of from greater than 0 ppm to 15,000 ppm, 10 ppm to 10,000 ppm, 15 ppm to 5,000 ppm, 20 ppm to 2,500 ppm, 25 ppm to 1000 ppm, 25 ppm to 500 ppm, 25 ppm to 250 ppm, or a defoaming agent in any range having endpoints selected from greater than 0 ppm, 1 ppm, 5 ppm, 10 ppm, 15 ppm, 20 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 250 ppm, 500 ppm 750 ppm, 1,000 ppm, 2,500 ppm, 5,000 ppm, 7,500 ppm, 10,000 ppm, 12,500 ppm, or 15,000 ppm, wherein the range is inclusive of the endpoints.
  • the composition comprises 25 ppm to 250 ppm (0.0025 ppm (0.00
  • the aqueous composition may further comprise a flavoring agent, a preservative, or a flavoring agent and preservative.
  • the aqueous composition further comprises up to 10,000 ppm citric acid.
  • the composition may comprise citric acid in an amount of greater than 0 ppm to 10,000 ppm, 10 ppm to 10,000 ppm, 15 ppm to 5,000 ppm, 20 ppm to 2,500 ppm, 25 ppm to 1000 ppm, 25 ppm to 500 ppm, 25 ppm to 250 ppm, or citric acid in any range having endpoints selected from greater than 0 ppm, 1 ppm, 5 ppm, 10 ppm, 15 ppm, 20 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 250 ppm, 500 ppm 750 ppm, 1,000 ppm, 2,500 ppm, 5,000 ppm, 7,500 ppm, or 10,000 ppm, wherein the range is inclusive of the endpoints.
  • the liquid aqueous composition comprises not less than 73.75 wt% Qiiillaja saponaria extract and not more than 23.75 wt% Yucca schidigera extract.
  • the liquid composition further comprises up to 1.5 wt% defoaming agent and/or up to 1 wt% citric acid.
  • the liquid composition may have a pH of 3.5 to 4.5, such as a pH of 3.9+0.2.
  • the liquid composition may have a shelf life of at least two years when stored at ambient temperature in a dry place.
  • some embodiments of the disclosed liquid composition when mixed with water to provide a diluted composition and administered to animals as described below, provide superior results on several indicators of animal health compared to results achieved with an equivalent amount of quillaja and yucca solids provided by existing powdered formulations of Quillaja saponaria and/or Yucca schidigera. Additionally, certain embodiments of the disclosed liquid composition provide statistically equivalent or better results than those achieved with a 2X amount of quillaja and yucca solids provided by existing powdered formulations of Quillaja saponaria and/or Yucca schidigera. Moreover, the liquid composition provides handling and administration advantages over the powdered formulations.
  • Embodiments of the disclosed aqueous compositions are readily mixed homogeneously with drinking water for administration to the animals.
  • the aqueous composition may be referred to a “concentrated composition” to differentiate it from a diluted composition formed when the aqueous composition is mixed with water.
  • compositions comprising quillaja and yucca in water are administered to animals in an amount sufficient to promote animal health, reduce susceptibility to disease, and/or improve feed conversion performance in the animals.
  • the disclosed aqueous compositions comprise, consist essentially of, or consist of water, solids obtained from Quillaja saponaria, and solids obtained from Yucca schidigera. The solids may be dissolved solids.
  • Embodiments of the disclosed aqueous composition may be administered prophylactic ally or therapeutically to animals to increase body weight and/or improve the feed conversion rate of animals that are raised for human consumption.
  • the aqueous compositions can be used to improve animal health generally and/or reduce the incidence of disease-causing organisms, e.g., Clostridium species, Salmonella species, and the like.
  • gut health is an indicator of general health, and administering the aqueous composition to the animals increases the villus height:crypt depth ratio compared to animals that do not receive the aqueous composition.
  • the animals may be avians.
  • Suitable avians include, but are not limited to, chickens, turkeys, geese, ducks, Cornish game hens, quail, pheasant, partridges, guinea fowl, peafowl, pigeons, ostriches, emus, and swans.
  • the avians are poultry.
  • the poultry are chickens or turkeys.
  • the chickens may be broiler chickens.
  • the aqueous compositions disclosed herein can be used to significantly reduce the costs associated with animal production.
  • the aqueous compositions and combinations can significantly reduce the costs associated with animal production as the aqueous compositions and combinations provide improvements in animal health and growth. Solely by way of example, a reduction of just one point in feed conversion ratio for one million chickens per week can translate into a cost/feed savings of nearly $750,000 per year.
  • Embodiments of the disclosed aqueous compositions are liquids and can be administered to animals via drinking water. The amount of the aqueous composition administered to the animals can be measured based on the concentration of the aqueous composition in the drinking water provided to the animals.
  • a method of using the disclosed aqueous compositions includes combining the aqueous composition with water to provide a diluted composition, and administering the diluted composition to an animal.
  • the aqueous composition may be referred to a “concentrated composition” to differentiate it from the diluted composition produced by combining the concentrated composition with water.
  • the amount of the concentrated composition combined with water to provide the diluted composition may range from greater than 0 g of the concentrated composition per m 3 of diluted composition to 1 ,000 g of the concentrated composition per m 3 of diluted composition, or from greater than 0 ppm to 1,000 ppm of the concentrated composition in water.
  • the amount of the concentrated composition combined with water to provide the diluted composition ranges from greater than 0 ppm to 750 ppm, greater than 0 ppm to 500 ppm, 1 ppm to 1,000 ppm, 1 ppm to 500 ppm, 10 ppm to 250 ppm, 25 ppm to 125 ppm, 40 ppm to 100 ppm, 50 ppm to 75 ppm, 55 ppm to 70 ppm, or 60 ppm to 65 ppm, or any range having endpoints selected from 1 ppm, 10 ppm, 25 ppm, 40 ppm, 50 ppm, 55 ppm, 60 ppm, 65 ppm, 70 ppm, 75 ppm, 100 ppm, 125 ppm, 250 ppm, or 500 ppm, wherein the range is inclusive of the endpoints.
  • the diluted composition includes 62 g of the concentrated composition per m 3 of diluted composition, or 62 ppm of the concentrated composition.
  • 240 mL (8 fluid ounces) of the concentration composition is combined with 7.5 L (248 fluid ounces) of water with minimal stirring to avoid foaming. This creates 7.75 L (2 gallons) of a stock solution that can be mixed with 970 L (0.97 m 3 , 256 gallons) of water and administered to animals, such as avians.
  • the aqueous composition may be administered in water throughout the production cycle of an animal.
  • the animal is an avian, such as a poultry avian, and the concentrated composition is combined with water to provide 50 ppm to 70 ppm of the concentrated composition in the water.
  • the animal is a mammal, such as a pig, and the concentrated composition is combined with water to provide 400 ppm to 500 ppm of the concentrated composition in the water.
  • 0.5 mL/pig/day of the concentrated composition may be administered to rearing pigs (weaned) as a prevention dose for six to ten consecutive days, such as for eight consecutive days.
  • a concentrated composition as disclosed herein is combined with water in an amount sufficient to provide a diluted composition having a solids (e.g., dissolved solids) content of from greater than 0 ppm to 250 ppm, such as from greater than 0 ppm to 120 ppm, and the diluted composition is administered to animals, such as avians.
  • the concentrated composition is mixed with drinking water and administered to the animals.
  • an amount of the composition is combined with water to provide a diluted composition having a dissolved solids content of from 6 ppm to 60 ppm, such as from 9 ppm to 45 ppm, 11 ppm to 35 ppm, 13 ppm to 32 ppm, or 14 ppm to 30 ppm.
  • the diluted composition includes 21 ppm to 23 ppm dissolved solids.
  • the diluted composition may have a quillaja:yucca (Q:Y) solids (e.g., dissolved solids) ratio on a w/w basis of from 1.3 to 10, such as a Q:Y ratio of from 1.6 to 7.5, from 1.7 to 3.3, or 1.9 to 2.5.
  • the diluted composition has a Q:Y solids ratio of from 2 to 2.3.
  • the method may further include combining a defoaming agent with the composition as disclosed herein and water to provide the diluted composition.
  • the defoaming agent is added to the dilute composition in an amount of from greater than 0 ppm to 100 ppm, such as greater than 0 ppm to 50 ppm, greater than 0 ppm to 25 ppm, greater than 0 ppm to 10 ppm, greater than 0 ppm to 1 ppm, greater than 0 ppm to 0.1 ppm, 0.01 ppm-100 ppm, 0.01 ppm to 50 ppm, or 0.01 ppm to 25 ppm.
  • Suitable defoaming agents include, but are not limited to, wax-, oil- and/or silica-based defoamers, as previously described.
  • administration of an effective amount of the diluted composition comprising quillaja and yucca, such as Quillaja saponaria and Yucca schidigera provides a health benefit to an animal compared to an animal that is not administered the composition.
  • the health benefit may occur at any time during the time period during which the diluted composition is administered, or within a period of time when administered compositions still have a beneficial effect for the animal.
  • the effective amount of the diluted composition is administered daily to the animal.
  • the animal may be an avian.
  • the effective amount of the diluted composition is administered to the avian on a daily basis beginning on the day of hatching, such as from the day of hatching to day of harvest, and the health benefit may occur at any time from the day of hatching.
  • the diluted composition may be administered alone, or in combination with, a therapeutic agent, such as an antimicrobial (e.g., an antibiotic, an antifungal, an antiparasitic (including anticoccidial agents), an antiviral) a vaccine, a direct-fed microbial, or a combination thereof, as disclosed herein.
  • the diluted composition is administered in the amounts disclosed herein.
  • an adult chicken consumes from 0.2-1 L of water per day or from 1.5 to 2X as much water as feed (on a weight basis), and an effective amount of the diluted composition for an adult chicken therefore is from 0.2-1 L of water per day.
  • an adult turkey consumes from 0.6- 1.2 L of water per day, and an effective amount of the diluted composition for an adult turkey therefore is from 0.2-1 L of water per day.
  • average water consumption generally increases with increasing body weight and/or increasing environmental temperature.
  • administering the effective amount of the diluted composition to an adult chicken administered provides from greater than 0 mg to 250 mg of the composition on a daily basis, correlating to from greater than 0 mg to 75 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 38 mg solids obtained from Yucca schidigera.
  • the solids may be dissolved solids.
  • the adult chicken is administered from 5 mg to 125 mg, such as from 8 mg to 100 mg, 10 mg to 75 mg, 11 mg to 70 mg, or 12 mg to 65 mg of the composition daily, correlating to (a) from 1 mg to 38 mg, 1.6 mg to 30 mg, 2 mg to 23 mg, 2.2 mg to 21 mg, or 2.4 mg to 20 mg solids obtained from Quillaja saponaria, and (b) from 0.15 mg to 19 mg, 0.24 mg to 15 mg, 0.30 mg to 11.2 mg, 0.33 mg to 10.5 mg, or 0.36 mg to 9.8 mg solids obtained from Yucca schidigera.
  • 5 mg to 125 mg such as from 8 mg to 100 mg, 10 mg to 75 mg, 11 mg to 70 mg, or 12 mg to 65 mg of the composition daily, correlating to (a) from 1 mg to 38 mg, 1.6 mg to 30 mg, 2 mg to 23 mg, 2.2 mg to 21 mg, or 2.4 mg to 20 mg solids obtained from Quillaja saponaria, and (b) from 0.15 mg to 19
  • administering the effective amount of the diluted composition to an adult turkey provides from greater than 0 mg to 300 mg of the composition on a daily basis, correlating to from greater than 0 mg to 90 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 45 mg solids obtained from Yucca schidigera.
  • the adult turkey is administered from 15 mg to 150 mg, such as from 24 mg to 120 mg, 30 mg to 90 mg, 33 mg to 84 mg, or 36 mg to 78 mg of the composition daily, correlating to (a) from 3 mg to 45 mg, 5 mg to 36 mg, 6 mg to 27 mg, 6.5 mg to 25 mg, or 7 mg to 24 mg solids obtained from Quillaja saponaria, and (b) from 0.4 mg to 23 mg, 0.7 mg to 18 mg, 0.9 mg to 14 mg, 1.0 mg to 13 mg, or 1.1 mg to 12 mg solids obtained from Yucca schidigera.
  • administering the diluted composition to animals may provide a health benefit compared to animals that do not receive the diluted composition.
  • the health benefit is increased body weight, decreased feed conversion ratio, decreased mortality rate, decreased Clostridium incidence, decreased Salmonella incidence, increased villus height:crypt depth ratio, or any combination thereof, compared to (i) an animal that did not receive the diluted composition, (ii) an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera, and/or (iii) an animal that received a diluted composition comprising water and solids (e.g., dissolved solids) obtained from only one of Quillaja saponaria or Yucca schidigera.
  • the animal also may be administered a therapeutic agent, wherein the therapeutic agent is an antimicrobial, an antibiotic, an anticoccidial agent, a vaccine, a direct-fed microbial (DFM), a yeast, a polyphenol, or any combination thereof.
  • the therapeutic agent may be administered to the animal prior to, concurrently with, or following administration of the diluted composition.
  • the diluted composition is administered daily to the animal as the animal’s sole or primary source of drinking water, and one or more doses of the therapeutic agent are concurrently administered to the animal.
  • the therapeutic agent is added to the diluted composition.
  • the therapeutic agent is mixed with the animal’s feed.
  • the therapeutic agent is administered as a supplement.
  • the therapeutic agent is a vaccine and may be administered by any suitable route, such as by injection, intranasal administration, or oral administration.
  • the animal may be an avian.
  • Suitable antibiotics include, but are not limited to, virginiamycin, bacitracin MD, zinc bacitracin, tylosin, lincomycin, flavomycin, bambermycin, terramycin, neo-terramycin, penicillin, tetracycline, ceftiofur, florfenicol, tilmicosin, enrofloxacin, tulathromycin, procaine penicillin, benzathine penicillin, ampicillin, amoxicillin, spectinomycin, dihydrostreptomycin, chlortetracycline, gentamicin, sulphadimidine, trimethoprim, oxytetracycline, erythromycin, norfloxacin, oxolinic acid, bronopol (2-bromo-2-nitro-l,3-propanediol, Pyceze®), sulfadimethozine, ormetroprim, sulf
  • Exemplary antiparasitics may be selected from anticoccidial agents, copper sulfate, fenbendazole, formalin, formalin-F, hyposalinity, hadaclean A, praziquantel, emamectin benzoate (SLICE®), or any combination thereof.
  • Suitable anticoccidial agents include, but are not limited to, ionophores and chemical anticoccidial products. Ionophores can include, but are not limited to, monensin, salinomycin, lasalocid, narasin, maduramicin, semduramicin, laidlomycin, or any combination thereof.
  • Chemical anticoccidial products can include, but are not limited to, nicarbazin, Maxiban® combination of narasin and nicrabazin, diclazuril, toltrazuril, robenidine, Stenorol® feed additive (halofuginone), clopidol, decoquinate, DOT (dinitolmid, zoalene), amprolium, or any combination thereof.
  • the amount of antimicrobial administered can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm.
  • the amount of antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg.
  • the antimicrobial is administered in the animal’s feed in an amount ranging from at least 1 g/ton of feed to 230 g/ton of feed (or at least 1.1 ppm to 256 ppm), such as at least 1 g/ton of feed to 220 g/ton of feed (or at least 1.1 ppm to 243 ppm), at least 1 g/ton of feed to 100 g/ton of feed (or at least 1.1 ppm to 110 ppm), at least 1 g/ton of feed to 50 g/ton of feed (or at least 1.1 ppm to 55 ppm), or at least 1 g/ton of feed to 10 g/ton of feed (or at least 1.1 ppm to 11 ppm).
  • an anticoccidial agent as will be understood by a person of ordinary skill in the art (e.g., a veterinarian), can be selected depending on the particular anticoccidial agent used.
  • the amount of anticoccidial agent administered may be a therapeutically effective amount for a particular animal species.
  • the amount of anticoccidial agent used can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm.
  • the amount of antibiotic or antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg.
  • Suitable vaccines can be selected from live coccidiosis vaccines, such as COCCIVAC (e.g., a composition comprising live oocysts of Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria mitis, Eimeria tenella, Eimeria necatrix, Eimeria praecox, Eimeria brunetti, Eimeria hagani, or combinations thereof), LivaCox (a composition comprising 300 - 500 live sporulated oocysts of each attenuated line of Eimeria acervulina, E. maxima and E.
  • COCCIVAC live coccidiosis vaccines
  • ParaCox a composition comprising live sporulated oocysts derived from E. acervulina HP, E. brunetti HP, E. maxima CP, E. maxima MFP, E mitis HP, E. necatrix HP, E. praecox HP, E.
  • Hatch Pack Cocci III a composition comprising oocysts derived from Eimeria acervulina, Eimeria maxima, Eimeria tenella, or combinations thereof
  • INOVOCOX a composition comprising oocysts derived from Eimeria acervulina, Eimeria maxima, Eimeria tenella, and a sodium chloride solution
  • IMMUCOX a composition comprising live oocysts derived from Eimeria acervulina, Eimeria maxima, Eimeria necatrix, Eimeria tenella, and combinations thereof
  • the amount of antimicrobial or antibiotic used may be within the amounts stated below but may depend on the particular antimicrobial or antibiotic used as will be understood by a person of ordinary skill in the art.
  • the amount of the antibiotic or antimicrobial that is used can be a therapeutically effective amount that is at an approved or authorized dosage level for a particular antibiotic.
  • the amount of antibiotic or antimicrobial used can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm.
  • the amount of antibiotic or antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg.
  • the antimicrobial or antibiotic is administered to the animals in feed, and the amount can range from at least 1 g/ton of feed to 230 g/ton of feed (or at least 1.1 ppm to 256 ppm), such as at least 1 g/ton of feed to 220 g/ton of feed (or at least 1.1 ppm to 243 ppm), at least 1 g/ton of feed to 100 g/ton of feed (or at least 1.1 ppm to 110 ppm), at least 1 g/ton of feed to 50 g/ton of feed (or at least 1.1 ppm to 55 ppm), or at least 1 g/ton of feed to 10 g/ton of feed (or at least 1.1 ppm to 11 ppm).
  • antimicrobials or antibiotics that can be used, and dosage amounts of such antimicrobials and antibiotics include, but are not limited to, the following: virginiamycin in an amount ranging from 5 g/ton of feed to 25 g/ton of feed (or 5 ppm to 27 ppm, such as 22 ppm); bacitracin MD in an amount ranging from 40 g/ton of feed to 220 g/ton of feed (or 44 ppm to 242 ppm, or 50 ppm to 250 ppm in some other embodiments); zinc bacitracin in an amount ranging from 40 g/ton of feed to 220 g/ton of feed (or 44 ppm to 242 ppm); ty Iosin in an amount ranging from 1 g/ton of feed to 1000 g/ton of feed (or 1 ppm to 1100 ppm); lincomycin in an amount ranging from 1 g/ton of feed to 5 g/ton of feed
  • the amount of anticoccidial agent can be selected depending on the particular anticoccidial agent used. In some embodiments, the amount of anticoccidial agent used can be a therapeutically effective amount for a particular animal species.
  • the amount of anticoccidial agent used can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm.
  • the amount of antibiotic or antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg.
  • the anticoccidial agent is included in the animals’ feed in an amount that can range from at least 1 g/ton of feed to 250 g/ton of feed (or at least 1 ppm to 275 ppm), such as at least 1 g/ton of feed to 200 g/ton of feed (or at least 1 ppm to 242 ppm), or at least 1 g/ton of feed to 150 g/ton of feed (or at least 1 ppm to 165 ppm), at least 1 g/ton of feed to 100 g/ton of feed (or at least 1 ppm to 110 ppm), or at least 1 g/ton of feed to 50 g/ton of feed (or at least 1 ppm to 55 ppm).
  • anticoccidial agents that can be used, and dosage amounts of such anticoccidial agents include, but are not limited to, the following: monensin in an amount ranging from 35 g/ton of feed to 110 g/ton of feed (or 38 ppm to 121 ppm); salinomycin in an amount ranging from 25 g/ton of feed to 90 g/ton of feed (or 27 ppm to 99 ppm); lasalocid in an amount ranging from 35 g/ton of feed to 113 g/ton of feed (or 38 ppm to 125 ppm); narasin in an amount ranging from 35 g/ton of feed to 72 g/ton of feed (or 38 ppm to 79 ppm); maduramicin in amount ranging from 2 g/ton of feed to 7 g/ton of feed (or 2 ppm to 8 ppm); semduramicin in an amount ranging from 12 g/ton of feed to 23 g
  • the amount of vaccine administered to the animal can depend on the animal species to which the vaccine is administered.
  • the amount of vaccine used is a therapeutically effective amount ranging from greater than 0 mL/animal to 1,000 mL/animal, or 0.25 mL/animal to 500 mL/animal, or 0.5 mL/animal to 150 mL/animal, or 1 mL/animal to 100 mL/animal, or 1 mL/animal to 50 mL/animal, or 1 mL/animal to 25 mL/animal, or 1 mL/animal to 15 mL/animal.
  • the direct-fed microbial may be any DFM suitable for administration to the particular animal.
  • DFMs include, but are not limited to, a Bacillus species or a Bacilli combination.
  • the Bacilli combination is a probiotic combination or a composition comprising plural bacilli.
  • the composition and/or combination comprises three or four DFMs selected from Bacillus coagulans, Bacillus subtilis, Bacillus licheniformis and Bacillus amyloliquefaciens.
  • the terms “Bacillus amyloliquefaciens,” “Bacillus coagulans '' “Bacillus subtilis” and “Bacillus licheniformis” independently may refer to a single strain of the respective Bacillus species, or to multiple strains, such as 2, 3, 4, 5, 6, 7, 8, 9, 10 or more strains, of each respective Bacillus species.
  • the DFM comprises Bacillus amyloliquefaciens, Bacillus subtilis and Bacillus licheniformis.
  • the DFM comprises Bacillus coagulans, Bacillus subtilis and Bacillus licheniformis.
  • the DFM comprises Bacillus amyloliquefaciens, Bacillus subtilis, Bacillus licheniformis and Bacillus coagulans.
  • a Bacilli combination may provide a substantial additional benefit with respect to one or more of feed conversion rate, average body weight, average body weight gain, body weight coefficient of variation, bird mortality, lesion scores, Salmonella/E. Coli/Clostridium perfingens (CP) incidence, and/or oocysts in fecal matter relative to poultry fed none, one, or two of these bacilli in any combination.
  • DFMs may include, by way of example and without limitation, an additional Bacillus species, Lactobacillus, Enterococcus, Bifidobacterium, Propionibacterium, Streptococcus, Pediococcus, or any combination thereof.
  • Exemplary other DFMs include, but are not limited to, Bacillus alcalophilus, Bacillus alvei, Bacillus aminovorans, Bacillus aneurinolyticus, Bacillus anthracis, Bacillus aquaemaris, Bacillus atrophaeus, Bacillus boroniphilus, Bacillus brevis, Bacillus caldolyticus, Bacillus centrosporus, Bacillus cereus, Bacillus circulans, Bacillus firmus, Bacillus flavothermus, Bacillus fusiformis, Bacillus galliciensis, Bacillus globigii, Bacillus infernus, Bacillus larvae, Bacillus laterosporus, Bacillus lentus, Bacillus megaterium, Bacillus mesentericus, Bacillus mucilaginosus, Bacillus mycoides, Bacillus nato, Bacillus pantothenticus, Bacillus polymyxa, Bacillus pseudoanthracis, Bacill
  • the yeast may be a yeast culture, a live yeast, a dead yeast, yeast extract, or a combination thereof.
  • the yeast may be a baker’ s yeast, a brewer’ s yeast, a distiller’ s yeast, a probiotic yeast or a combination thereof.
  • Exemplary yeasts include, but are not limited to, Saccharomyces cerevisiae, Saccharomyces boulardii, Saccharomyces pastorianus, Brettanomyces bruxellensis, Brettanomyces anomalus, Brettanomyces custersianus , Brettanomyces naardenensis , and Brettanomyces nanus, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii, or Zygosaccharomyces bailii.
  • a polyphenol may be useful for the prevention and inhibition of inflammatory processes, thereby improving animal gut health which, in turn, improves both animal health and performance.
  • the polyphenol may be provided by a plant extract from a polyphenol-containing plant material.
  • the plant material also may include non-polyphenol compounds, including polyphenol degradation products, such as gallic acid and trans-caftaric acid. Degradation can occur, for example, through oxidative and/or biological processes. Both the polyphenols and the non-polyphenol compounds may have biological activity.
  • the plant extract may be prepared from a single plant material or from a combination of plant materials.
  • Suitable plant materials from which a plant extract can be obtained include, but are not limited to, apples, blackberries, black chokeberries, black currants, black elderberries, blueberries, cherries, cranberries, grapes, green tea, hops, onions, quillaja, plums, pomegranates, raspberries, strawberries, and yucca.
  • the plant extract is prepared from a pressed plant material, such as grape pomace, a dried plant material, such as tea, or a combination thereof.
  • Pomace may be obtained substantially immediately post-pressing or as an ensiled product, i.e., pomace collected and stored for up to several months post-pressing.
  • Suitable plants have a plurality of polyphenols and/or other non-polyphenolic compounds including, but not limited to, non-polyphenolic organic acids (such as gallic acid and/or trans- caftaric acid), flavanols, gallate esters, flavanodiols, phloroglucinol, pyrogallol, and catechol.
  • non-polyphenolic organic acids such as gallic acid and/or trans- caftaric acid
  • flavanols such as gallic acid and/or trans- caftaric acid
  • flavanols such as gallic acid and/or trans- caftaric acid
  • flavanols such as gallate esters
  • flavanodiols such as phloroglucinol
  • pyrogallol pyrogallol
  • Embodiments of the disclosed aqueous compositions are made by combining an aqueous quillaja extract and an aqueous yucca extract.
  • the quillaja extract is a Quillaja saponaria extract
  • the yucca extract is a Yucca schidigera extract.
  • the composition further includes additional water.
  • a Quillaja saponaria extract is prepared by grinding pieces, such as chips, of the Quillaja saponaria tree.
  • the Quillaja saponaria pieces may be obtained from branches of the Quillaja saponaria tree.
  • the ground pieces are immersed in water for a period of time to produce an aqueous crude extract.
  • the water may be heated to facilitate the extraction.
  • a solids content of the crude extract may be determined.
  • Water and dissolved solids in the crude extract are separated from undissolved solids by filtration.
  • the crude extract is contacted with a clay, such as bentonite, prior to filtration. The clay may facilitate separation of undissolved solids from the crude extract.
  • the initial filtered extract includes ⁇ 5 wt% dissolved solids and is concentrated (e.g., by evaporation) to provide a solids content of from 25 wt% to 50 wt% dissolved solids, such as from 30 wt% to 40 wt% dissolved solids.
  • the pH may be reduced, e.g., to a pH of from 3 to 5.5.
  • the concentrated extract is pasteurized and/or further filtered (e.g., through a 1 pm filter) to provide the Quillaja saponaria extract.
  • a Yucca schidigera extract is prepared by shredding Yucca schidigera plant material to provide a pulp.
  • the Yucca schidigera plant material may be stems of the Yucca schidigera plant.
  • the pulp is pressed to squeeze crude juice from the pump to provide a crude extract.
  • water is added to the pressed pulp, and pressing is performed again with the resulting liquid added to the crude extract.
  • a solids content of the crude extract may be determined.
  • the liquid extract optionally is filtered and/or concentrated to a desired dissolved solids content.
  • an initial concentration is performed, such as by evaporation, to provide a semi-concentrate, and the semi-concentrate is then filtered.
  • the pH Prior to filtration, the pH may be reduced, e.g., to a pH of from 3 to 5.5.
  • the filtered semi-concentrate is evaporated to a desired solids content.
  • the solids content is of from 30 wt% to 60 wt% dissolved solids, such as from 40 wt% to 50 wt% dissolved solids.
  • the concentrated extract is pasteurized and/or filtered again (e.g., through a 10 pm filter, followed by a 1 pm filter) to provide the Yucca schidigera extract.
  • a Quillaja saponaria extract and a Yucca schidigera extract may be combined to form a liquid composition as disclosed herein.
  • the liquid composition comprises not less than 73.75 wt% Quillaja saponaria extract and not more than 23.75 wt% Yucca schidigera extract.
  • up to 1.5 wt% defoaming agent and/or up to 1 wt% citric acid is added to the liquid composition.
  • An aqueous composition comprising: from 12 wt% to 36 wt% solids obtained from Quillaja saponaria', and from 3 wt% to 25 wt% solids obtained from Yucca schidigera.
  • composition of claim 9, wherein the composition comprises from 25 ppm to 250 ppm of the defoaming agent.
  • a method comprising: combining an aqueous composition according to any one of clauses 1-18 with water in an amount of from greater than 0 ppm to 1,000 ppm of the aqueous composition to provide a diluted composition; and administering the diluted composition to an animal.
  • the therapeutic agent is an antimicrobial, an antibiotic, an antifungal, an anticoccidial agent, a vaccine, a direct-fed microbial, yeast, a polyphenol, or any combination thereof.
  • a composition for use in a method of administration to an animal wherein an aqueous composition according to any one of clauses 1-18 is combined with water in an amount of from greater than 0 ppm to 1,000 ppm of the aqueous composition to provide a diluted composition for administration to the animal.
  • composition for use of clause 53 wherein: the animal is an adult chicken, and the effective amount of the diluted composition provides from greater than 0 mg to 75 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 38 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition provides from greater than 0 mg to 90 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 45 mg solids obtained from Yucca schidigera.
  • composition for use of any one of clauses 42-57 wherein administration of diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera.
  • composition for use of any one of clauses 42-57 wherein administration of the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a diluted composition comprising water and dissolved solids obtained from only one of Quillaja saponaria or Yucca schidigera.
  • Magni-Phi® powder is a proprietary blend of triterpenoid saponins (Phibro Animal Health Corporation, Teaneck, NJ)
  • Gut health variables were measured at 21 and 42 days. Assessed parameters included body weight (FIG. 1), feed conversion ratio (g:g) (FIG. 2), Clostridium enumeration (FIG. 3), Salmonella incidence percentage (FIG. 4), and villus height:crypt depth ratio (FIG. 5). Letters shown on the bars are indicative of statistically significant or insignificant results. For example, with respect to FIG. 1, 100% Y and 50/50 QY both are designated “d,” indicating that the results are not statistically different from one another. Similarly, 100% Q is designated as “de,” indicating that the result is not statistically different from results of trials labeled with “d” (100% Y, 50/50 QY) or “e” (MP250).
  • the 75/25 QY result is designated “a.” Because no other result is designated with “a,” the 75/25 QY result is statistically different from all of the other trials.
  • Each graph also displays a numerical result from Micro Aid Liquid (MA).
  • the MA concentrate includes 50 wt% yucca dissolved solids.
  • the MA concentrate is used at a ratio of 2 fluid oz. to 126 fluid oz. of H2O, which is then diluted 1:128 to use, providing ⁇ 61 ppm yucca solids.
  • MP powder produced linear responses (0-500 ppm) in all variables measured, with 500 ppm MP powder providing consistently better performance than 250 ppm MP powder.
  • the QY liquid provided many of the same effects as MP powder with most responses falling within the range of the results obtained from 250-500 ppm MP powder.
  • the 75/25 QY liquid produced responses that were largely equivalent to 500 ppm MP powder. While other QY liquids also were effective, superior results were obtained with the 75/25 QY liquid. Notably, the 75/25 QY liquid provided statistically significant improvements in each gut health variable compared to either Quillaja alone or Yucca alone.
  • Four of the five variables also were statistically better than MP powder administered at 125 ppm or 250 ppm, and three of the five variables were statistically better than MA.
  • Magni-Phi® powder is a proprietary blend of triterpenoid saponins (Phibro Animal Health Corporation, Teaneck, NJ)
  • Gut health variables were measured at 21 and 42 days. Assessed parameters included body weight (FIG. 6), feed conversion ratio (g:g) (FIG. 7), Clostridium enumeration (FIG. 8), and Salmonella incidence percentage (FIG. 9). Fetters shown on the bars are indicative of statistically significant or insignificant results. For example, with respect to FIG. 6, 100% Y, 25/75 QY, and 50/50 QY are designated “c,” indicating that the results are not statistically different from one another. In contrast, the MP 500 trial is the only result designated “a,” indicating that the results are statistically different from all of the other trials.
  • MP powder produced linear responses (0-500 ppm) in all variables measured, with 500 ppm MP powder providing consistently better performance than 250 ppm MP powder.
  • MP 500 ppm was the best performer of all treatments evaluated.
  • Several QY liquid ratios effectively improved performance.
  • Most liquid responses were as good as or better than 250 ppm MP powder. Differences among various liquid ratios tended to be small.
  • the highest quillaja levels produced the best responses.
  • the liquid formulation results did not exceed the results obtained with 500 ppm MP powder.
  • the 75/25 QY liquid did not provide uniquely outstanding results as in Example l,but was effective.
  • the results indicate that liquid QY formulations may be a reasonable alternative to powder formulations. Some foaming occurred with higher concentrations of liquid quillaja, and an antifoaming agent may be beneficial.

Abstract

A liquid composition comprising water, solids obtained from quillaja, and solids obtained from yucca is disclosed. The liquid composition may include from 20 wt% to 30 wt% solids obtained from Quillaja saponaria and from 3 wt% to 15 wt% solids obtained from Yucca schidigera. A method of using the liquid composition includes combining the composition with water to provide a diluted composition, and administering the diluted composition to an animal.

Description

LIQUID FORMULATION COMPRISING YUCCA AND QUILLAJA FOR ADMINISTRATION TO ANIMALS
CROSS REFERENCE TO RELATED APPLICATIONS
[001] This application claims the benefit of the earlier filing date of U.S. Provisional Application No. 63/312,430, filed February 22, 2022, which is incorporated by reference in its entirety here.
FIELD
[002] The present disclosure concerns a liquid formulation comprising yucca and quillaja for administration to an animal.
SUMMARY
[003] Embodiments of a liquid formulation comprising yucca and quillaja are disclosed. In some embodiments, an aqueous composition comprises from 12 wt% to 36 wt% solids obtained from Quillaja saponaria, and from 3 wt% to 25 wt% solids obtained from Yucca schidigera. In certain embodiments, (i) the Quillaja saponaria solids are provided by an aqueous Quillaja saponaria extract comprising 25 wt% to 50 wt% dissolved solids; or (ii) the Yucca schidigera solids are provided by an aqueous Yucca schidigera extract comprising 30 wt% to 60 wt% dissolved solids; or (iii) both (i) and (ii). In any of the foregoing or following embodiments, the aqueous composition may have a Quillaja saponaria:Yucca schidigera solids ratio on a w/w basis of from 1.3 to 4.5.
[004] In any of the foregoing or following embodiments, the aqueous composition may further include a defoaming agent. In some embodiments, the aqueous composition includes from 25 ppm to 15,000 ppm of the defoaming agent.
[005] In any of the foregoing or following embodiments, the aqueous composition may further include citric acid. In some embodiments, the aqueous composition includes from 1 ppm to 10,000 ppm of the citric acid.
[006] Embodiments of a method for using the aqueous composition include combining the disclosed aqueous composition with water in an amount of from greater than 0 ppm to 500 ppm to provide a diluted composition, and administering the diluted composition to an animal. In some embodiments, the aqueous composition does not comprise a defoaming agent, and the method further includes combining a defoaming agent with the aqueous composition and the water to provide the diluted composition. In any of the foregoing or following embodiments, the diluted composition may be administered to the animal in place of drinking water. [007] In any of the foregoing or following embodiments, the diluted composition may be administered daily to the animal. In some embodiments, the animal is an avian, such as a chicken, a turkey, a goose, a duck, a Cornish game hen, a quail, a pheasant, a partridge, a guinea fowl, a peafowl, a pigeon, an ostrich, an emu, or a swan. In any of the foregoing or following embodiments, the diluted composition may be administered to the avian beginning on day of hatching. In some embodiments, an effective amount of the diluted composition is administered daily to the animal for a period of time sufficient to promote a beneficial health effect.
[008] In any of the foregoing or following embodiments, administering the diluted composition to the animal may increase body weight, decrease feed conversion ratio, decrease mortality rate, decrease Clostridium incidence, decrease Salmonella incidence, increase villus height:crypt depth ratio, or any combination thereof compared to (i) an animal that did not receive the diluted composition, (ii) an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera, and/or (iii) an animal that received a diluted composition comprising water and solids obtained from only one of Quillaja saponaria or Yucca schidigera.
[009] In any of the foregoing or following embodiments, the method may further include administering a therapeutic agent to the animal. In some embodiments, the therapeutic agent is an antimicrobial, an antibiotic, an antifungal, an anticoccidial agent, a vaccine, a direct-fed microbial, yeast, a polyphenol, or any combination thereof. The therapeutic agent may be administered to the animal prior to, concurrently with, or following administration of the diluted composition.
[010] The foregoing and other objects, features, and advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[Oil] FIG. 1 is a graph of bird weight (g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Quillaja saponaria (Q) liquid extract, 100% Yucca schidigera (Y) liquid extract, 25/75 Quillaja saponaria / Yucca schidigera (QY) liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm Magni-Phi® (MP) powder, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
[012] FIG. 2 is a graph of feed conversion ratio (FCR, g:g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding. [013] FIG. 3 is a graph illustrating Clostridium enumeration results (logio) obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 21 days of feeding.
[014] FIG. 4 is a graph of Salmonella incidence (%) illustrating results obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
[015] FIG. 5 is a graph of villus height:crypt depth ratio illustrating results obtained from feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 125 ppm MP, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 21 days of feeding.
[016] FIG. 6 is a graph of bird weight (g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Quillaja saponaria (Q) liquid extract, 100% Yucca schidigera (Y) liquid extract, 25/75 Quillaja saponaria / Yucca schidigera (QY) liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm Magni-Phi® (MP) powder, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
[017] FIG. 7 is a graph of feed conversion ratio (FCR, g:g) illustrating results obtained from feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
[018] FIG. 8 is a graph illustrating Clostridium enumeration results (loglO) obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 21 days of feeding.
[019] FIG. 9 is a graph of Salmonella incidence (%) illustrating results obtained after feeding birds various different treatments (negative control, 100% Q liquid extract, 100% Y liquid extract, 25/75 QY liquid extract, 50/50 QY, 75/25 QY, 90/10 QY, 250 ppm MP, or 500 ppm MP) with the graph providing results obtained after 42 days of feeding.
DETAILED DESCRIPTION
[020] This disclosure concerns embodiments of a liquid composition comprising quillaja and yucca, and a method for administering the composition to animals. In some embodiments, the liquid composition comprises extracts of Quillaja saponaria and Yucca schidigera. In certain embodiments, the animals are avians.
I. Terms and Definitions
[021] The following explanations of terms and abbreviations are provided to better describe the present disclosure and to guide those of ordinary skill in the art in the practice of the present disclosure. As used herein, “comprising” means “including” and the singular forms “a” or “an” or “the” include plural references unless the context clearly dictates otherwise. The term “or” refers to a single element of stated alternative elements or a combination of two or more elements, unless the context clearly indicates otherwise.
[022] Unless explained otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting. Other features of the disclosure are apparent from the following detailed description and the claims.
[023] Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, percentages, temperatures, times, and so forth, as used in the specification or claims are to be understood as being modified by the term “about.” Accordingly, unless otherwise indicated, implicitly or explicitly, the numerical parameters set forth are approximations that may depend on the desired properties sought and/or limits of detection under standard test conditions/methods. When directly and explicitly distinguishing embodiments from discussed prior art, the embodiment numbers are not approximates unless the word “about” is recited. Furthermore, not all alternatives recited herein are equivalents.
[024] To facilitate review of the various embodiments of the disclosure, the following explanations of specific terms are provided:
[025] Administering: Providing a combination, composition, or component disclosed herein by any suitable route to an animal. In some embodiments disclosed herein, administration can refer to oral administration.
[026] Animal: This term includes, but is not limited to, humans, mammals, aquaculture species, and avian species. In some embodiments, this term can refer to mammals, aquaculture species (animals that live in salt or fresh water), and avian species that are raised for human consumption or that are domesticated animals. Exemplary such animal species are provided herein.
[027] Broiler chicken: A chicken raised for meat. [028] Combination: A combination includes two or more components that are administered such that the effective time period of at least one component overlaps with the effective time period of at least one other component. A combination, or a component thereof, may be a composition. In some embodiments, effective time periods of all components administered overlap with each other. In an exemplary embodiment of a combination comprising three components, the effective time period of the first component administered may overlap with the effective time periods of the second and third components, but the effective time periods of the second and third components independently may or may not overlap with one another. In another exemplary embodiment of a combination comprising three components, the effective time period of the first component administered overlaps with the effective time period of the second component, but not that of the third component; and the effective time period of the second component overlaps with those of the first and third components. A combination may be a composition comprising the components, a composition comprising one or more components and another separate component (or components) or composition(s) comprising the remaining component(s), or the combination may be two or more individual components. In some embodiments, the two or more components may comprise the same component administered at two or more different times, two or more different components administered substantially simultaneously or sequentially in any order, or a combination thereof. [029] Direct fed microbial: A composition that contains live and/or viable microorganisms, typically bacteria and/or yeast, that provides a beneficial effect on an animal.
[030] Feed conversion rate/ratio (FCR): A measure of the efficiency of an animal, such as an avian, to convert feed mass into increased body mass.
[031] Poultry: Domesticated birds raised for meat and/or eggs, e.g., chickens, turkeys, geese, ducks, Cornish game hens, quail, pheasants, partridges, guinea fowl, peafowl, pigeons, ostriches, emus, and swans.
[032] Saponin: A class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in particular abundance in various plant species. More specifically, they are amphipathic glycosides grouped, in terms of structure, by their composition. In certain embodiments, saponin comprises one or more hydrophilic glycoside moieties combined with a lipophilic triterpene derivative. A steroidal saponin has a steroid base (e.g., spirostanol or furostanol) in place of the triterpene moiety. Yucca saponins are steroidal saponins. Quillaja saponins are triterpenoid saponins.
[033] Therapeutic agent: An agent that is capable of providing a therapeutic effect, e.g., preventing a disorder, inhibiting a disorder, such as by arresting the development of the disorder or its clinical symptoms, or relieving a disorder by causing regression of the disorder or its clinical symptoms.
[034] Therapeutically Effective Amount or Effective Amount: A quantity or concentration of a specified compound or composition sufficient to achieve a desired effect in an animal being treated for a disorder. The therapeutically effective amount may depend at least in part on the species of animal being treated, the size of the animal, and/or the severity of the disorder.
II. Compositions
[035] Disclosed herein are embodiments of a liquid composition comprising water, solids obtained from quillaja and solids obtained from yucca. In some embodiments, the liquid composition is an aqueous composition comprising solids obtained from Quillaja saponaria and solids obtained from Yucca schidigera. As will be readily understood, an aqueous composition is a composition in which the solvent is water. As used hereinafter, the terms “liquid composition” and “aqueous composition” may be used interchangeably, whereby it is understood that the composition is a liquid composition in which the solvent is water. In certain embodiments, the liquid composition consists of, or consists essentially of, water, dissolved solids obtained from Quillaja saponaria and dissolved solids obtained from Yucca schidigera. “Consists of’ means that the composition does not include any other component except for impurities ordinarily associated with the recited components. “Consists essentially of’ means that the composition does not include other components that may provide a health benefit to an animal receiving the liquid composition. For example, the term “consists essentially of’ precludes therapeutic agents as discussed infra, vitamins, minerals, amino acids, or the like, in amounts effective to provide any health benefit.
However, the term “consists essentially of’ does not preclude small amounts (e.g., less than 2 wt%) of additives that do not provide a health benefit to the animal, e.g., a defoaming agent, a colorant, a taste enhancer, a preservative, or the like. “Consists essentially of’ also does not preclude administering separate compositions to an animal that do include therapeutic agents.
[036] Examples of quillaja that can be used in the disclosed combination include, but are not limited to, Quillaja brasiliensis, Quillaja lanceolata, Quillaja lancifolia, Quillaja molinae, Quillaja petiolaris, Quillaja poeppigii, Quillaja saponaria, Quillaja sellowiana, or Quillaja smegmadermos. In particular disclosed embodiments, the quillaja is Quillaja saponaria.
[037] Examples of yucca that can be used in the disclosed combination include, but are not limited to, Yucca aloifolia, Yucca angustissima, Yucca arkansana, Yucca baccata, Yucca baileyi, Yucca brevifolia, Yucca campestris, Yucca capensis, Yucca carnerosana, Yucca cernua, Yucca coahuilensis, Yucca constricta, Yucca decipiens, Yucca declinata, Yucca de-smetiana, Yucca elata, Yucca endlichiana, Yucca faxoniana, Yucca filamentosa, Yucca filifera, Yucca flaccida, Yucca gigantean, Yucca glauca, Yucca gloriosa, Yucca grandiflora, Yucca harrimaniae, Yucca intermedia, Yucca jaliscensis, Yucca lacandonica, Yucca linearifolia, Yucca luminosa, Yucca madrensis, Yucca mixtecana, Yucca necopina, Yucca neomexicana, Yucca pallida, Yucca periculosa, Yucca potosina, Yucca queretaroensis, Yucca reverchonii, Yucca rostrata, Yucca rupicola, Yucca schidigera, Yucca schottii, Yucca sterilis, Yucca tenuistyla, Yucca thompsoniana, Yucca treculeana, Yucca utahensis, or Yucca valida. In certain disclosed embodiments, the yucca component is Yucca schidigera.
[038] A person of ordinary skill in the art will appreciate that, as used herein, a plant name may refer to the plant as a whole, or to any part of the plant, such as the roots, stem or trunk, bark, leaves, flower, flower stems, or seeds or a combination thereof. The name may also refer to extracts from any part or parts of the plant, such as chemical extracts, or extracts obtained by pressing, or any other methods of concentrating or extracting oils or other extracts known to those in the art or that are hereafter discovered. Plant extracts may include compounds that are saponins, triterpenoids, polyphenols, antioxidants, resveratrol, or combinations thereof.
[039] In any of the foregoing or following embodiments, the liquid composition may comprise a Quillaja saponaria extract and a Yucca schidigera extract. In some embodiments, the Quillaja saponaria plant extract comprises at least one saponin, polyphenol, antioxidant, resveratrol or any combination thereof. In some embodiments, the Yucca schidigera plant extract comprises at least one saponin, polyphenol, antioxidant, resveratrol or any combination thereof.
[040] In some embodiments, the aqueous composition comprises, consists essentially of, or consists of from 12 wt% to 36 wt% solids obtained from Quillaja saponaria, and from 3 wt% to 25 wt% solids obtained from Yucca schidigera. In certain embodiments, the aqueous composition comprises 15 wt% to 35 wt% solids obtained from Quillaja saponaria and 4 wt% to 20 wt% solids obtained from Yucca schidigera, or 20 wt% to 35 wt% solids obtained from Quillaja saponaria and 8 wt% to 15 wt% solids obtained from Yucca schidigera, or 20 wt% to 30 wt% solids obtained from Quillaja saponaria and 10 wt% to 12 wt% solids obtained from Yucca schidigera. In particular embodiments, the aqueous composition comprises, consists essentially of, or consists of from 22 wt% to 30 wt% solids obtained from Quillaja saponaria and 11 wt% to 12 wt% solids obtained from Yucca schidigera. In any of the foregoing or following aspects, the solids may be dissolved solids.
[041] In any of the foregoing or following embodiments, the aqueous composition may have a Quillaja saponaria : Yucca schidigera solids ratio (Q:Y ratio) on a w/w basis of from 0.5 to 12, such as a Q:Y ratio of from 0.75 to 9, from 1.3 to 4.5, or 1.7 to 3. In particular embodiments, the aqueous composition has a Q:Y solids ratio of from 2 to 2.7.
[042] In any of the foregoing or following embodiments, the aqueous composition may be prepared from a Quillaja saponaria extract and a Yucca schidigera extract, in amounts to provide a Quillaja saponaria : Yucca schidigera extract volume ratio of from 50:50 to 90:10, i.e., 50 vol% to 90 vol% Quillaja saponaria extract and 10 vol% to 50 vol% Yucca schidigera extract. In some embodiments, the aqueous composition has a Quillaja saponaria : Yucca schidigera extract volume ratio of from 75:25 to 90:10, i.e., 75-90 vol% Quillaja saponaria extract and 10-25 vol% Yucca schidigera extract. In any of the foregoing or following embodiments, the Quillaja saponaria extract may have a solids content of from 25 wt% to 50 wt% dissolved solids, such as from 30 wt% to 40 wt% dissolved solids. In any of the foregoing or following embodiments, the Yucca schidigera extract may have a solids content of from 30 wt% to 60 wt% dissolved solids, such as from 45 wt% to 50 wt% dissolved solids. In certain embodiments, the aqueous composition consists essentially of, or consists of, the two extracts.
[043] In any of the foregoing or following embodiments, the aqueous composition may further comprise a defoaming agent. Exemplary defoaming agents include, but are not limited to, wax-, oil- and/or silica-based defoamers. Exemplary commercially available defoaming agents include Magrabar® Organic 3000 defoamer (Magrabar, Morton Grove, IL), which includes natural waxes, vegetable oil, emulsifiers, and silicon dioxide, and Magrabar® Organic 3200 defoamer, which includes vegetable oil, silicon dioxide, and vegetable-derived mixed tocopherols. Another suitable defoaming agent is Gil Defoam FGE defoamer (Gilmer Industries, Inc., Harrisonburg, VA). In some embodiments, the composition comprises up to 15,000 ppm (1.5 wt%), such as up to 10,000 ppm (1 wt%) of a defoaming agent. For example, the composition may comprise a defoaming agent in an amount of from greater than 0 ppm to 15,000 ppm, 10 ppm to 10,000 ppm, 15 ppm to 5,000 ppm, 20 ppm to 2,500 ppm, 25 ppm to 1000 ppm, 25 ppm to 500 ppm, 25 ppm to 250 ppm, or a defoaming agent in any range having endpoints selected from greater than 0 ppm, 1 ppm, 5 ppm, 10 ppm, 15 ppm, 20 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 250 ppm, 500 ppm 750 ppm, 1,000 ppm, 2,500 ppm, 5,000 ppm, 7,500 ppm, 10,000 ppm, 12,500 ppm, or 15,000 ppm, wherein the range is inclusive of the endpoints. In some implementation, the composition comprises 25 ppm to 250 ppm (0.0025 wt% to 0.025 wt%) of a defoaming agent.
[044] In any of the foregoing or following embodiments, the aqueous composition may further comprise a flavoring agent, a preservative, or a flavoring agent and preservative. In some embodiments, the aqueous composition further comprises up to 10,000 ppm citric acid. For example, the composition may comprise citric acid in an amount of greater than 0 ppm to 10,000 ppm, 10 ppm to 10,000 ppm, 15 ppm to 5,000 ppm, 20 ppm to 2,500 ppm, 25 ppm to 1000 ppm, 25 ppm to 500 ppm, 25 ppm to 250 ppm, or citric acid in any range having endpoints selected from greater than 0 ppm, 1 ppm, 5 ppm, 10 ppm, 15 ppm, 20 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 250 ppm, 500 ppm 750 ppm, 1,000 ppm, 2,500 ppm, 5,000 ppm, 7,500 ppm, or 10,000 ppm, wherein the range is inclusive of the endpoints.
[045] In some embodiments, the liquid aqueous composition comprises not less than 73.75 wt% Qiiillaja saponaria extract and not more than 23.75 wt% Yucca schidigera extract. In some implementations, the liquid composition further comprises up to 1.5 wt% defoaming agent and/or up to 1 wt% citric acid. The liquid composition may have a pH of 3.5 to 4.5, such as a pH of 3.9+0.2. In any of the foregoing embodiments, the liquid composition may have a shelf life of at least two years when stored at ambient temperature in a dry place.
[046] Advantageously, some embodiments of the disclosed liquid composition, when mixed with water to provide a diluted composition and administered to animals as described below, provide superior results on several indicators of animal health compared to results achieved with an equivalent amount of quillaja and yucca solids provided by existing powdered formulations of Quillaja saponaria and/or Yucca schidigera. Additionally, certain embodiments of the disclosed liquid composition provide statistically equivalent or better results than those achieved with a 2X amount of quillaja and yucca solids provided by existing powdered formulations of Quillaja saponaria and/or Yucca schidigera. Moreover, the liquid composition provides handling and administration advantages over the powdered formulations. Embodiments of the disclosed aqueous compositions are readily mixed homogeneously with drinking water for administration to the animals. Hereinafter, the aqueous composition may be referred to a “concentrated composition” to differentiate it from a diluted composition formed when the aqueous composition is mixed with water.
III. Methods of Use
[047] This disclosure further concerns embodiments of a method for using the disclosed aqueous compositions. For certain disclosed embodiments, disclosed aqueous compositions comprising quillaja and yucca in water are administered to animals in an amount sufficient to promote animal health, reduce susceptibility to disease, and/or improve feed conversion performance in the animals. In certain embodiments, the disclosed aqueous compositions comprise, consist essentially of, or consist of water, solids obtained from Quillaja saponaria, and solids obtained from Yucca schidigera. The solids may be dissolved solids. Embodiments of the disclosed aqueous composition may be administered prophylactic ally or therapeutically to animals to increase body weight and/or improve the feed conversion rate of animals that are raised for human consumption. In additional embodiments, the aqueous compositions can be used to improve animal health generally and/or reduce the incidence of disease-causing organisms, e.g., Clostridium species, Salmonella species, and the like. In some embodiments, gut health is an indicator of general health, and administering the aqueous composition to the animals increases the villus height:crypt depth ratio compared to animals that do not receive the aqueous composition.
[048] In any of the foregoing or following embodiments, the animals may be avians. Suitable avians include, but are not limited to, chickens, turkeys, geese, ducks, Cornish game hens, quail, pheasant, partridges, guinea fowl, peafowl, pigeons, ostriches, emus, and swans. In some embodiments, the avians are poultry. In certain embodiments, the poultry are chickens or turkeys. The chickens may be broiler chickens.
[049] In some embodiments, the aqueous compositions disclosed herein can be used to significantly reduce the costs associated with animal production. In particular embodiments, the aqueous compositions and combinations can significantly reduce the costs associated with animal production as the aqueous compositions and combinations provide improvements in animal health and growth. Solely by way of example, a reduction of just one point in feed conversion ratio for one million chickens per week can translate into a cost/feed savings of nearly $750,000 per year. [050] Embodiments of the disclosed aqueous compositions are liquids and can be administered to animals via drinking water. The amount of the aqueous composition administered to the animals can be measured based on the concentration of the aqueous composition in the drinking water provided to the animals.
[051] In some embodiments, a method of using the disclosed aqueous compositions includes combining the aqueous composition with water to provide a diluted composition, and administering the diluted composition to an animal. Hereinafter, the aqueous composition may be referred to a “concentrated composition” to differentiate it from the diluted composition produced by combining the concentrated composition with water. The amount of the concentrated composition combined with water to provide the diluted composition may range from greater than 0 g of the concentrated composition per m3 of diluted composition to 1 ,000 g of the concentrated composition per m3 of diluted composition, or from greater than 0 ppm to 1,000 ppm of the concentrated composition in water. In some embodiments, the amount of the concentrated composition combined with water to provide the diluted composition ranges from greater than 0 ppm to 750 ppm, greater than 0 ppm to 500 ppm, 1 ppm to 1,000 ppm, 1 ppm to 500 ppm, 10 ppm to 250 ppm, 25 ppm to 125 ppm, 40 ppm to 100 ppm, 50 ppm to 75 ppm, 55 ppm to 70 ppm, or 60 ppm to 65 ppm, or any range having endpoints selected from 1 ppm, 10 ppm, 25 ppm, 40 ppm, 50 ppm, 55 ppm, 60 ppm, 65 ppm, 70 ppm, 75 ppm, 100 ppm, 125 ppm, 250 ppm, or 500 ppm, wherein the range is inclusive of the endpoints. In some embodiments, the diluted composition includes 62 g of the concentrated composition per m3 of diluted composition, or 62 ppm of the concentrated composition. In certain embodiments, 240 mL (8 fluid ounces) of the concentration composition is combined with 7.5 L (248 fluid ounces) of water with minimal stirring to avoid foaming. This creates 7.75 L (2 gallons) of a stock solution that can be mixed with 970 L (0.97 m3, 256 gallons) of water and administered to animals, such as avians.
[052] For nutritional purposes, the aqueous composition may be administered in water throughout the production cycle of an animal. In some implementations, the animal is an avian, such as a poultry avian, and the concentrated composition is combined with water to provide 50 ppm to 70 ppm of the concentrated composition in the water. In some implementations, the animal is a mammal, such as a pig, and the concentrated composition is combined with water to provide 400 ppm to 500 ppm of the concentrated composition in the water. In certain aspects, 0.5 mL/pig/day of the concentrated composition may be administered to rearing pigs (weaned) as a prevention dose for six to ten consecutive days, such as for eight consecutive days.
[053] In some embodiments, a concentrated composition as disclosed herein is combined with water in an amount sufficient to provide a diluted composition having a solids (e.g., dissolved solids) content of from greater than 0 ppm to 250 ppm, such as from greater than 0 ppm to 120 ppm, and the diluted composition is administered to animals, such as avians. For example, the concentrated composition is mixed with drinking water and administered to the animals. In certain embodiments, an amount of the composition is combined with water to provide a diluted composition having a dissolved solids content of from 6 ppm to 60 ppm, such as from 9 ppm to 45 ppm, 11 ppm to 35 ppm, 13 ppm to 32 ppm, or 14 ppm to 30 ppm. In some examples, the diluted composition includes 21 ppm to 23 ppm dissolved solids.
[054] The diluted composition may have a quillaja:yucca (Q:Y) solids (e.g., dissolved solids) ratio on a w/w basis of from 1.3 to 10, such as a Q:Y ratio of from 1.6 to 7.5, from 1.7 to 3.3, or 1.9 to 2.5. In particular embodiments, the diluted composition has a Q:Y solids ratio of from 2 to 2.3.
[055] In any of the foregoing or following embodiments, the method may further include combining a defoaming agent with the composition as disclosed herein and water to provide the diluted composition. In some embodiments, the defoaming agent is added to the dilute composition in an amount of from greater than 0 ppm to 100 ppm, such as greater than 0 ppm to 50 ppm, greater than 0 ppm to 25 ppm, greater than 0 ppm to 10 ppm, greater than 0 ppm to 1 ppm, greater than 0 ppm to 0.1 ppm, 0.01 ppm-100 ppm, 0.01 ppm to 50 ppm, or 0.01 ppm to 25 ppm. Suitable defoaming agents include, but are not limited to, wax-, oil- and/or silica-based defoamers, as previously described.
[056] In any of the foregoing or following embodiments, administration of an effective amount of the diluted composition comprising quillaja and yucca, such as Quillaja saponaria and Yucca schidigera, provides a health benefit to an animal compared to an animal that is not administered the composition. The health benefit may occur at any time during the time period during which the diluted composition is administered, or within a period of time when administered compositions still have a beneficial effect for the animal. In some embodiments, the effective amount of the diluted composition is administered daily to the animal.
[057] In any of the foregoing or following embodiments, the animal may be an avian. In some embodiments, the effective amount of the diluted composition is administered to the avian on a daily basis beginning on the day of hatching, such as from the day of hatching to day of harvest, and the health benefit may occur at any time from the day of hatching. The diluted composition may be administered alone, or in combination with, a therapeutic agent, such as an antimicrobial (e.g., an antibiotic, an antifungal, an antiparasitic (including anticoccidial agents), an antiviral) a vaccine, a direct-fed microbial, or a combination thereof, as disclosed herein. In some embodiments, the diluted composition is administered in the amounts disclosed herein.
[058] In some embodiments, an adult chicken consumes from 0.2-1 L of water per day or from 1.5 to 2X as much water as feed (on a weight basis), and an effective amount of the diluted composition for an adult chicken therefore is from 0.2-1 L of water per day. In some embodiments, an adult turkey consumes from 0.6- 1.2 L of water per day, and an effective amount of the diluted composition for an adult turkey therefore is from 0.2-1 L of water per day. A person of ordinary skill in the art will understand that average water consumption generally increases with increasing body weight and/or increasing environmental temperature. Accordingly, in some embodiments, administering the effective amount of the diluted composition to an adult chicken administered provides from greater than 0 mg to 250 mg of the composition on a daily basis, correlating to from greater than 0 mg to 75 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 38 mg solids obtained from Yucca schidigera. The solids may be dissolved solids. In certain embodiments, the adult chicken is administered from 5 mg to 125 mg, such as from 8 mg to 100 mg, 10 mg to 75 mg, 11 mg to 70 mg, or 12 mg to 65 mg of the composition daily, correlating to (a) from 1 mg to 38 mg, 1.6 mg to 30 mg, 2 mg to 23 mg, 2.2 mg to 21 mg, or 2.4 mg to 20 mg solids obtained from Quillaja saponaria, and (b) from 0.15 mg to 19 mg, 0.24 mg to 15 mg, 0.30 mg to 11.2 mg, 0.33 mg to 10.5 mg, or 0.36 mg to 9.8 mg solids obtained from Yucca schidigera. In some embodiments, administering the effective amount of the diluted composition to an adult turkey provides from greater than 0 mg to 300 mg of the composition on a daily basis, correlating to from greater than 0 mg to 90 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 45 mg solids obtained from Yucca schidigera. In certain embodiments, the adult turkey is administered from 15 mg to 150 mg, such as from 24 mg to 120 mg, 30 mg to 90 mg, 33 mg to 84 mg, or 36 mg to 78 mg of the composition daily, correlating to (a) from 3 mg to 45 mg, 5 mg to 36 mg, 6 mg to 27 mg, 6.5 mg to 25 mg, or 7 mg to 24 mg solids obtained from Quillaja saponaria, and (b) from 0.4 mg to 23 mg, 0.7 mg to 18 mg, 0.9 mg to 14 mg, 1.0 mg to 13 mg, or 1.1 mg to 12 mg solids obtained from Yucca schidigera.
[059] In any of the foregoing embodiments, administering the diluted composition to animals may provide a health benefit compared to animals that do not receive the diluted composition. In some embodiments, the health benefit is increased body weight, decreased feed conversion ratio, decreased mortality rate, decreased Clostridium incidence, decreased Salmonella incidence, increased villus height:crypt depth ratio, or any combination thereof, compared to (i) an animal that did not receive the diluted composition, (ii) an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera, and/or (iii) an animal that received a diluted composition comprising water and solids (e.g., dissolved solids) obtained from only one of Quillaja saponaria or Yucca schidigera.
[060] In any of the foregoing embodiments, the animal also may be administered a therapeutic agent, wherein the therapeutic agent is an antimicrobial, an antibiotic, an anticoccidial agent, a vaccine, a direct-fed microbial (DFM), a yeast, a polyphenol, or any combination thereof. The therapeutic agent may be administered to the animal prior to, concurrently with, or following administration of the diluted composition. In some embodiments, the diluted composition is administered daily to the animal as the animal’s sole or primary source of drinking water, and one or more doses of the therapeutic agent are concurrently administered to the animal. In one embodiment, the therapeutic agent is added to the diluted composition. In an independent embodiment, the therapeutic agent is mixed with the animal’s feed. In another independent embodiment, the therapeutic agent is administered as a supplement. In still another independent embodiment, the therapeutic agent is a vaccine and may be administered by any suitable route, such as by injection, intranasal administration, or oral administration. In any of the foregoing or following embodiments, the animal may be an avian.
[061] Suitable antibiotics include, but are not limited to, virginiamycin, bacitracin MD, zinc bacitracin, tylosin, lincomycin, flavomycin, bambermycin, terramycin, neo-terramycin, penicillin, tetracycline, ceftiofur, florfenicol, tilmicosin, enrofloxacin, tulathromycin, procaine penicillin, benzathine penicillin, ampicillin, amoxicillin, spectinomycin, dihydrostreptomycin, chlortetracycline, gentamicin, sulphadimidine, trimethoprim, oxytetracycline, erythromycin, norfloxacin, oxolinic acid, bronopol (2-bromo-2-nitro-l,3-propanediol, Pyceze®), sulfadimethozine, ormetroprim, sulfadiazine, trimethoprim, or any combination thereof. An antifungal may be selected from, by way of example, formalin, formalin-F, bronopol, or any combination thereof.
[062] Exemplary antiparasitics may be selected from anticoccidial agents, copper sulfate, fenbendazole, formalin, formalin-F, hyposalinity, hadaclean A, praziquantel, emamectin benzoate (SLICE®), or any combination thereof. Suitable anticoccidial agents include, but are not limited to, ionophores and chemical anticoccidial products. Ionophores can include, but are not limited to, monensin, salinomycin, lasalocid, narasin, maduramicin, semduramicin, laidlomycin, or any combination thereof. Chemical anticoccidial products can include, but are not limited to, nicarbazin, Maxiban® combination of narasin and nicrabazin, diclazuril, toltrazuril, robenidine, Stenorol® feed additive (halofuginone), clopidol, decoquinate, DOT (dinitolmid, zoalene), amprolium, or any combination thereof.
[063] In some embodiments, the amount of antimicrobial administered can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm. In yet additional embodiments, the amount of antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg. In some embodiments, the antimicrobial is administered in the animal’s feed in an amount ranging from at least 1 g/ton of feed to 230 g/ton of feed (or at least 1.1 ppm to 256 ppm), such as at least 1 g/ton of feed to 220 g/ton of feed (or at least 1.1 ppm to 243 ppm), at least 1 g/ton of feed to 100 g/ton of feed (or at least 1.1 ppm to 110 ppm), at least 1 g/ton of feed to 50 g/ton of feed (or at least 1.1 ppm to 55 ppm), or at least 1 g/ton of feed to 10 g/ton of feed (or at least 1.1 ppm to 11 ppm). The amount of an anticoccidial agent, as will be understood by a person of ordinary skill in the art (e.g., a veterinarian), can be selected depending on the particular anticoccidial agent used. In some embodiments, the amount of anticoccidial agent administered may be a therapeutically effective amount for a particular animal species. In some embodiments, the amount of anticoccidial agent used can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm. In yet additional embodiments, the amount of antibiotic or antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg.
[064] Suitable vaccines can be selected from live coccidiosis vaccines, such as COCCIVAC (e.g., a composition comprising live oocysts of Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria mitis, Eimeria tenella, Eimeria necatrix, Eimeria praecox, Eimeria brunetti, Eimeria hagani, or combinations thereof), LivaCox (a composition comprising 300 - 500 live sporulated oocysts of each attenuated line of Eimeria acervulina, E. maxima and E. tenella in a 1% w/v aqueous solution of Chloramine B), ParaCox (a composition comprising live sporulated oocysts derived from E. acervulina HP, E. brunetti HP, E. maxima CP, E. maxima MFP, E mitis HP, E. necatrix HP, E. praecox HP, E. tenella HP, and combinations thereof), Hatch Pack Cocci III (a composition comprising oocysts derived from Eimeria acervulina, Eimeria maxima, Eimeria tenella, or combinations thereof), INOVOCOX (a composition comprising oocysts derived from Eimeria acervulina, Eimeria maxima, Eimeria tenella, and a sodium chloride solution), IMMUCOX (a composition comprising live oocysts derived from Eimeria acervulina, Eimeria maxima, Eimeria necatrix, Eimeria tenella, and combinations thereof), Advent, or combinations thereof.
[065] The amount of antimicrobial or antibiotic used may be within the amounts stated below but may depend on the particular antimicrobial or antibiotic used as will be understood by a person of ordinary skill in the art. In an independent embodiment, the amount of the antibiotic or antimicrobial that is used can be a therapeutically effective amount that is at an approved or authorized dosage level for a particular antibiotic. In some embodiments, the amount of antibiotic or antimicrobial used can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm. In yet additional embodiments, the amount of antibiotic or antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg. [066] In some embodiments, the antimicrobial or antibiotic is administered to the animals in feed, and the amount can range from at least 1 g/ton of feed to 230 g/ton of feed (or at least 1.1 ppm to 256 ppm), such as at least 1 g/ton of feed to 220 g/ton of feed (or at least 1.1 ppm to 243 ppm), at least 1 g/ton of feed to 100 g/ton of feed (or at least 1.1 ppm to 110 ppm), at least 1 g/ton of feed to 50 g/ton of feed (or at least 1.1 ppm to 55 ppm), or at least 1 g/ton of feed to 10 g/ton of feed (or at least 1.1 ppm to 11 ppm). Particular antimicrobials or antibiotics that can be used, and dosage amounts of such antimicrobials and antibiotics include, but are not limited to, the following: virginiamycin in an amount ranging from 5 g/ton of feed to 25 g/ton of feed (or 5 ppm to 27 ppm, such as 22 ppm); bacitracin MD in an amount ranging from 40 g/ton of feed to 220 g/ton of feed (or 44 ppm to 242 ppm, or 50 ppm to 250 ppm in some other embodiments); zinc bacitracin in an amount ranging from 40 g/ton of feed to 220 g/ton of feed (or 44 ppm to 242 ppm); ty Iosin in an amount ranging from 1 g/ton of feed to 1000 g/ton of feed (or 1 ppm to 1100 ppm); lincomycin in an amount ranging from 1 g/ton of feed to 5 g/ton of feed (or 1 ppm to 6 ppm); flavomycin in an amount ranging from 1 g/ton of feed to 5 g/ton of feed (or 1 ppm to 6 ppm); or combinations thereof.
[067] The amount of anticoccidial agent, as will be understood by a person of ordinary skill in the art (e.g., a veterinarian), can be selected depending on the particular anticoccidial agent used. In some embodiments, the amount of anticoccidial agent used can be a therapeutically effective amount for a particular animal species. In some embodiments, the amount of anticoccidial agent used can range from greater than 0 ppm to 100,000 ppm, such as 0.25 ppm to 5,000 ppm, or 0.5 ppm to 2,500 ppm, or 0.75 ppm to 2,000 ppm, or 1 ppm to 1,500 ppm, or 5 ppm to 1,000 ppm, or 10 ppm to 500 ppm, or 25 ppm to 300 ppm. In yet additional embodiments, the amount of antibiotic or antimicrobial used can range from greater than 0 mg/kg of body weight to 100,000 mg/kg of body weight, such as 0.5 mg/kg to 2,500 mg/kg, or 1 mg/kg to 1,500 mg/kg, or 5 mg/kg to 1,000 mg/kg, or 10 mg/kg to 500 mg/kg m, or 25 mg/kg to 300 mg/kg, or 10-20 mg/kg. [068] In some embodiments, the anticoccidial agent is included in the animals’ feed in an amount that can range from at least 1 g/ton of feed to 250 g/ton of feed (or at least 1 ppm to 275 ppm), such as at least 1 g/ton of feed to 200 g/ton of feed (or at least 1 ppm to 242 ppm), or at least 1 g/ton of feed to 150 g/ton of feed (or at least 1 ppm to 165 ppm), at least 1 g/ton of feed to 100 g/ton of feed (or at least 1 ppm to 110 ppm), or at least 1 g/ton of feed to 50 g/ton of feed (or at least 1 ppm to 55 ppm). Particular anticoccidial agents that can be used, and dosage amounts of such anticoccidial agents include, but are not limited to, the following: monensin in an amount ranging from 35 g/ton of feed to 110 g/ton of feed (or 38 ppm to 121 ppm); salinomycin in an amount ranging from 25 g/ton of feed to 90 g/ton of feed (or 27 ppm to 99 ppm); lasalocid in an amount ranging from 35 g/ton of feed to 113 g/ton of feed (or 38 ppm to 125 ppm); narasin in an amount ranging from 35 g/ton of feed to 72 g/ton of feed (or 38 ppm to 79 ppm); maduramicin in amount ranging from 2 g/ton of feed to 7 g/ton of feed (or 2 ppm to 8 ppm); semduramicin in an amount ranging from 12 g/ton of feed to 23 g/ton of feed (or 13 ppm to 25 ppm); Nicarbazin in an amount ranging from 60 g/ton of feed to 113 g/ton of feed (or 66 ppm to 125 ppm); Maxiban® agent in an amount ranging from 40 g/ton of feed to 90 g/ton of feed (or 44 ppm to 99 ppm); diclazuril in an amount ranging from 0.5 g/ton of feed to 10 g/ton of feed (or 0.6 ppm to 11 ppm); toltrazuril in an amount ranging from 1 g/ton of feed to 10 g/ton of feed (or 1 ppm to 11 ppm); robenidine in an amount ranging from 20 g/ton of feed to 60 g/ton of feed (or 22 ppm to 66 ppm); Stenorol® agent in an amount ranging from 1.5 g/ton of feed to 15 g/ton of feed (or 1.5 ppm to 17 ppm); clopidol in an amount ranging from 90 g/ton of feed to 227 g/ton of feed (or 99 ppm to 250 ppm); decoquinate in an amount ranging from 18 g/ton of feed to 27 g/ton of feed (or 19 ppm to 29 ppm); zoalene in an amount ranging from 25 g/ton of feed to 113 g/ton of feed (or 28 ppm to 125 ppm); amprolium in an amount ranging from 20 g/ton of feed to 227 g/ton of feed (or 22 ppm to 250 ppm).
[069] The amount of vaccine administered to the animal can depend on the animal species to which the vaccine is administered. In some embodiments, the amount of vaccine used is a therapeutically effective amount ranging from greater than 0 mL/animal to 1,000 mL/animal, or 0.25 mL/animal to 500 mL/animal, or 0.5 mL/animal to 150 mL/animal, or 1 mL/animal to 100 mL/animal, or 1 mL/animal to 50 mL/animal, or 1 mL/animal to 25 mL/animal, or 1 mL/animal to 15 mL/animal.
[070] The direct-fed microbial (DFM) may be any DFM suitable for administration to the particular animal. Exemplary DFMs include, but are not limited to, a Bacillus species or a Bacilli combination. In one example, the Bacilli combination is a probiotic combination or a composition comprising plural bacilli. In certain particular embodiments, the composition and/or combination comprises three or four DFMs selected from Bacillus coagulans, Bacillus subtilis, Bacillus licheniformis and Bacillus amyloliquefaciens. As used herein the terms “Bacillus amyloliquefaciens,” “Bacillus coagulans '' “Bacillus subtilis” and “Bacillus licheniformis” independently may refer to a single strain of the respective Bacillus species, or to multiple strains, such as 2, 3, 4, 5, 6, 7, 8, 9, 10 or more strains, of each respective Bacillus species. In one embodiment, the DFM comprises Bacillus amyloliquefaciens, Bacillus subtilis and Bacillus licheniformis. In an independent embodiment, the DFM comprises Bacillus coagulans, Bacillus subtilis and Bacillus licheniformis. In another independent embodiment, the DFM comprises Bacillus amyloliquefaciens, Bacillus subtilis, Bacillus licheniformis and Bacillus coagulans. With particular reference to poultry, a Bacilli combination may provide a substantial additional benefit with respect to one or more of feed conversion rate, average body weight, average body weight gain, body weight coefficient of variation, bird mortality, lesion scores, Salmonella/E. Coli/Clostridium perfingens (CP) incidence, and/or oocysts in fecal matter relative to poultry fed none, one, or two of these bacilli in any combination. Other suitable DFMs may include, by way of example and without limitation, an additional Bacillus species, Lactobacillus, Enterococcus, Bifidobacterium, Propionibacterium, Streptococcus, Pediococcus, or any combination thereof. Exemplary other DFMs include, but are not limited to, Bacillus alcalophilus, Bacillus alvei, Bacillus aminovorans, Bacillus aneurinolyticus, Bacillus anthracis, Bacillus aquaemaris, Bacillus atrophaeus, Bacillus boroniphilus, Bacillus brevis, Bacillus caldolyticus, Bacillus centrosporus, Bacillus cereus, Bacillus circulans, Bacillus firmus, Bacillus flavothermus, Bacillus fusiformis, Bacillus galliciensis, Bacillus globigii, Bacillus infernus, Bacillus larvae, Bacillus laterosporus, Bacillus lentus, Bacillus megaterium, Bacillus mesentericus, Bacillus mucilaginosus, Bacillus mycoides, Bacillus nato, Bacillus pantothenticus, Bacillus polymyxa, Bacillus pseudoanthracis, Bacillus pumilus, Bacillus schlegelii, Bacillus sphaericus, Bacillus sporothermodurans, Bacillus stearothermophilus, Bacillus thermo gluco sidasius, Bacillus thuringiensis, Bacillus vulgatis, Bacillus weihenstephanensis, Lactobacillus acidophilis, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus gallinarum, Lactobacillus lactis, Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus bulgaricus, Bifidobacterium pseudoIongum, Bifidobacterium thermophilium, Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium inf antis, Streptococcus bovis, Streptococcus f aecium, Enterococcus faecium, Enterococcus faecalis, Enterococcus diacety lactis, Aspergillus oryzae, Aspergillus niger, Selenomonas ruminantium, Megasphaera elsdenii, Propionibacteriumfreudenreichii, Propionibacterium shermanii, Propionibacterium acidipropionici, Propionibacterium fensenii, Prevotella bryantii, Pediococcus acidilactici, Pediococcus cerevisiae, or any combination thereof. In certain embodiments, Bacillus pumilus may be administered in combination with an aforementioned Bacilli combination. In any of the foregoing embodiments, the DFM may be administered in an amount sufficient to provide a desired amount of the DFM, to the animal.
[071] The yeast may be a yeast culture, a live yeast, a dead yeast, yeast extract, or a combination thereof. The yeast may be a baker’ s yeast, a brewer’ s yeast, a distiller’ s yeast, a probiotic yeast or a combination thereof. Exemplary yeasts include, but are not limited to, Saccharomyces cerevisiae, Saccharomyces boulardii, Saccharomyces pastorianus, Brettanomyces bruxellensis, Brettanomyces anomalus, Brettanomyces custersianus , Brettanomyces naardenensis , and Brettanomyces nanus, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii, or Zygosaccharomyces bailii.
[072] A polyphenol may be useful for the prevention and inhibition of inflammatory processes, thereby improving animal gut health which, in turn, improves both animal health and performance. The polyphenol may be provided by a plant extract from a polyphenol-containing plant material. The plant material also may include non-polyphenol compounds, including polyphenol degradation products, such as gallic acid and trans-caftaric acid. Degradation can occur, for example, through oxidative and/or biological processes. Both the polyphenols and the non-polyphenol compounds may have biological activity. The plant extract may be prepared from a single plant material or from a combination of plant materials. Suitable plant materials from which a plant extract can be obtained include, but are not limited to, apples, blackberries, black chokeberries, black currants, black elderberries, blueberries, cherries, cranberries, grapes, green tea, hops, onions, quillaja, plums, pomegranates, raspberries, strawberries, and yucca. In some embodiments, the plant extract is prepared from a pressed plant material, such as grape pomace, a dried plant material, such as tea, or a combination thereof. Pomace may be obtained substantially immediately post-pressing or as an ensiled product, i.e., pomace collected and stored for up to several months post-pressing. Suitable plants have a plurality of polyphenols and/or other non-polyphenolic compounds including, but not limited to, non-polyphenolic organic acids (such as gallic acid and/or trans- caftaric acid), flavanols, gallate esters, flavanodiols, phloroglucinol, pyrogallol, and catechol.
IV. Method of Making the Composition
[073] Embodiments of the disclosed aqueous compositions are made by combining an aqueous quillaja extract and an aqueous yucca extract. In some embodiments, the quillaja extract is a Quillaja saponaria extract, and/or the yucca extract is a Yucca schidigera extract. In certain embodiments, the composition further includes additional water.
[074] In some embodiments, a Quillaja saponaria extract is prepared by grinding pieces, such as chips, of the Quillaja saponaria tree. The Quillaja saponaria pieces may be obtained from branches of the Quillaja saponaria tree. The ground pieces are immersed in water for a period of time to produce an aqueous crude extract. The water may be heated to facilitate the extraction. A solids content of the crude extract may be determined. Water and dissolved solids in the crude extract are separated from undissolved solids by filtration. In some embodiments, the crude extract is contacted with a clay, such as bentonite, prior to filtration. The clay may facilitate separation of undissolved solids from the crude extract. In certain embodiments, the initial filtered extract includes ~5 wt% dissolved solids and is concentrated (e.g., by evaporation) to provide a solids content of from 25 wt% to 50 wt% dissolved solids, such as from 30 wt% to 40 wt% dissolved solids. The pH may be reduced, e.g., to a pH of from 3 to 5.5. In some embodiments, the concentrated extract is pasteurized and/or further filtered (e.g., through a 1 pm filter) to provide the Quillaja saponaria extract.
[075] In some embodiments, a Yucca schidigera extract is prepared by shredding Yucca schidigera plant material to provide a pulp. The Yucca schidigera plant material may be stems of the Yucca schidigera plant. The pulp is pressed to squeeze crude juice from the pump to provide a crude extract. In some embodiments, water is added to the pressed pulp, and pressing is performed again with the resulting liquid added to the crude extract. A solids content of the crude extract may be determined. The liquid extract optionally is filtered and/or concentrated to a desired dissolved solids content. In some embodiments, an initial concentration is performed, such as by evaporation, to provide a semi-concentrate, and the semi-concentrate is then filtered. Prior to filtration, the pH may be reduced, e.g., to a pH of from 3 to 5.5. The filtered semi-concentrate is evaporated to a desired solids content. In some embodiments, the solids content is of from 30 wt% to 60 wt% dissolved solids, such as from 40 wt% to 50 wt% dissolved solids. In certain embodiments, the concentrated extract is pasteurized and/or filtered again (e.g., through a 10 pm filter, followed by a 1 pm filter) to provide the Yucca schidigera extract.
[076] In any of the foregoing embodiments, a Quillaja saponaria extract and a Yucca schidigera extract may be combined to form a liquid composition as disclosed herein. In some embodiments, the liquid composition comprises not less than 73.75 wt% Quillaja saponaria extract and not more than 23.75 wt% Yucca schidigera extract. In some implementations, up to 1.5 wt% defoaming agent and/or up to 1 wt% citric acid is added to the liquid composition.
V. Representative Aspects
[077] Certain representative aspects are described in the following numbered clauses.
[078] 1. An aqueous composition, comprising: from 12 wt% to 36 wt% solids obtained from Quillaja saponaria', and from 3 wt% to 25 wt% solids obtained from Yucca schidigera.
[079] 2. The aqueous composition of clause 1, comprising: from 20 wt% to 35 wt% solids obtained from Quillaja saponaria; and from 8 wt% to 15 wt% solids obtained from Yucca schidigera.
[080] 3. The aqueous composition of clause 1, comprising: from 20 wt% to 30 wt% solids obtained from Quillaja saponaria; and from 10 wt% to 12 wt% solids obtained from Yucca schidigera.
[081] 4. The aqueous composition of any one of clauses 1-3, wherein: (i) the Quillaja saponaria solids are provided by an aqueous Quillaja saponaria extract comprising 25 wt% to 50 wt% dissolved solids; or (ii) the Yucca schidigera solids are provided by an aqueous Yucca schidigera extract comprising 30 wt% to 60 wt% dissolved solids; or (iii) both (i) and (ii).
[082] 5. The aqueous composition of clause 1, having a Quillaja saponaria'.Yucca schidigera solids ratio on a w/w basis of from 1.3 to 4.5.
[083] 6. The aqueous composition of clause 5, wherein the Quillaja saponaria : Yucca schidigera solids ratio is of from 1.7 to 3.
[084] 7. The aqueous composition of any one of clauses 1-6, consisting essentially of the water, the solids obtained from Quillaja saponaria, and the solids obtained from Yucca schidigera. [085] 8. The aqueous composition of any one of clauses 1-6, consisting of the water, the solids obtained from Quillaja saponaria, and the dissolved solids obtained from Yucca schidigera.
[086] 9. The aqueous composition of any one of clauses 1-8, further comprising a defoaming agent.
[087] 10. The aqueous composition of clause 9, wherein the composition comprises from 25 ppm to 15,000 ppm of the defoaming agent.
[088] 11. The aqueous composition of claim 9, wherein the composition comprises from 25 ppm to 250 ppm of the defoaming agent.
[089] 12. The aqueous composition of any one of clauses 9-11, consisting essentially of the water, the solids obtained from Quillaja saponaria, the solids obtained from Yucca schidigera, and the defoaming agent.
[090] 13. The aqueous composition of any one of clauses 9-11, consisting of the water, the solids obtained from Quillaja saponaria, the solids obtained from Yucca schidigera, and the defoaming agent.
[091] 14. The aqueous composition of any one of clauses 1-12, further comprising citric acid.
[092] 15. The aqueous composition of clause 14, wherein the composition comprises from 1 ppm to 10,000 ppm of the citric acid.
[093] 16. The aqueous composition of clause 14 or clause 15 consisting essentially of the water, the solids obtained from Quillaja saponaria, the solids obtained from Yucca schidigera, the defoaming agent, and the citric acid.
[094] 17. The aqueous composition of clause 14 or clause 15 consisting of the water, the solids obtained from Quillaja saponaria, the solids obtained from Yucca schidigera, the defoaming agent, and the citric acid.
[095] 18. The aqueous composition of any one of clauses 1-17, wherein (i) the solids obtained from Quillaja saponaria are dissolved solids, or (ii) the solids obtained from Yucca schidigera are dissolved solids, or (iii) both (i) and (ii).
[096] 19. A method, comprising: combining an aqueous composition according to any one of clauses 1-18 with water in an amount of from greater than 0 ppm to 1,000 ppm of the aqueous composition to provide a diluted composition; and administering the diluted composition to an animal.
[097] 20. The method of clause 19, wherein the aqueous composition is combined with water in an amount of from 25 ppm to 500 ppm of the aqueous composition.
[098] 21. The method of clause 19, wherein the aqueous composition is combined with water in an amount of from 40 ppm to 100 ppm of the aqueous composition. [099] 22. The method of clause 19, wherein the aqueous composition is combined with water in an amount of from 50 ppm to 75 ppm of the aqueous composition.
[0100] 23. The method of clause 19, wherein the aqueous composition does not comprise a defoaming agent, the method further comprising combining a defoaming agent with the aqueous composition and the water to provide the diluted composition.
[0101] 24. The method of clause 23, wherein the defoaming agent is added in an amount of from greater than 0 ppm to 100 ppm of the defoaming agent.
[0102] 25. The method of any of clauses 19-24, wherein the diluted composition is administered daily to the animal.
[0103] 26. The method of any one of clauses 19-25, wherein the animal is an avian.
[0104] 27. The method of clause 26, wherein the avian is a chicken, a turkey, a goose, a duck, a Cornish game hen, a quail, a pheasant, a partridge, a guinea fowl, a peafowl, a pigeon, an ostrich, an emu, or a swan.
[0105] 28. The method of clause 26, wherein the avian is a chicken or a turkey.
[0106] 29. The method of any one of clauses 26-28, wherein the diluted composition is administered to the avian beginning on day of hatching.
[0107] 30. The method of any one of clauses 19-29, wherein an effective amount of the diluted composition is administered daily to the animal for a period of time sufficient to promote a beneficial health effect.
[0108] 31. The method of clause 30, wherein: the animal is an adult chicken, and the effective amount of the diluted composition is from 0.2 L to 1 L per day; or the animal is an adult turkey, and the effective amount of the diluted composition is from 0.6 L to 1.2 L per day.
[0109] 32. The method of clause 30, wherein: the animal is an adult chicken, and the effective amount of the diluted composition provides from greater than 0 mg to 75 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 38 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition provides from greater than 0 mg to 90 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 45 mg solids obtained from Yucca schidigera.
[0110] 33. The method of clause 30, wherein: the animal is an adult chicken, and the effective amount of the diluted composition provides from 1 mg to 38 mg solids obtained from Quillaja saponaria and from 0.15 mg to 19 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition provides from 3 mg to 45 mg solids obtained from Quillaja saponaria and from 0.4 mg to 23 mg solids obtained from Yucca schidigera. [0111] 34. The method of clause 32 or clause 33, wherein (i) the solids obtained from Quillaja saponaria are dissolved solids, or (ii) the solids obtained from Yucca schidigera are dissolved solids, or (iii) both (i) and (ii).
[0112] 35. The method of any one of clauses 19-34, wherein administering the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that did not receive the diluted composition.
[0113] 36. The method of any one of clauses 19-34, wherein administering the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera. [0114] 37. The method of any one of clauses 19-34, wherein administering the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a diluted composition comprising water and dissolved solids obtained from only one of Quillaja saponaria or Yucca schidigera.
[0115] 38. The method of any one of clauses 19-37, wherein the diluted composition is administered to the animal in place of drinking water.
[0116] 39. The method of any one of clauses 19-38, further comprising administering a therapeutic agent to the animal.
[0117] 40. The method of clause 39, wherein the therapeutic agent is an antimicrobial, an antibiotic, an antifungal, an anticoccidial agent, a vaccine, a direct-fed microbial, yeast, a polyphenol, or any combination thereof.
[0118] 41. The method of clause 39 or clause 40, wherein the therapeutic agent is administered to the animal prior to, concurrently with, or following administration of the diluted composition.
[0119] 42. A composition for use in a method of administration to an animal, wherein an aqueous composition according to any one of clauses 1-18 is combined with water in an amount of from greater than 0 ppm to 1,000 ppm of the aqueous composition to provide a diluted composition for administration to the animal.
[0120] 43. The composition for use of clause 42, wherein the aqueous composition is combined with water in an amount of from 25 ppm to 500 ppm of the aqueous composition. [0121] 44. The composition for use of clause 42, wherein the aqueous composition is combined with water in an amount of from 25 ppm to 500 ppm of the aqueous composition.
[0122] 45. The composition for use of clause 42, wherein the aqueous composition is combined with water in an amount of from 40 ppm to 100 ppm of the aqueous composition.
[0123] 46. The composition for use of clause 42, wherein the aqueous composition is combined with water in an amount of from 50 ppm to 75 ppm of the aqueous composition.
[0124] 47. The composition for use of any one of clauses 42-46, wherein the aqueous composition does not comprise a defoaming agent, and a defoaming agent is combined with the diluted composition prior to the administration to the animal.
[0125] 48. The composition for use of clause 47, wherein the defoaming agent is combined with the diluted composition in an amount of from greater than 0 ppm to 100 ppm of the defoaming agent.
[0126] 49. The composition for use of any one of clauses 42-48, wherein the animal is an avian. [0127] 50. The composition for use of clause 49, wherein the avian is a chicken, a turkey, a goose, a duck, a Cornish game hen, a quail, a pheasant, a partridge, a guinea fowl, a peafowl, a pigeon, an ostrich, an emu, or a swan.
[0128] 51. The composition for use of clause 49, wherein the avian is a chicken or a turkey.
[0129] 52. The composition for use of any one of clauses 49-51, wherein the diluted composition is administered to the avian beginning on day of hatching.
[0130] 53. The composition for use of any one of clauses 42-52, wherein an effective amount of the diluted composition is administered daily to the animal for a period of time sufficient to promote a beneficial health effect.
[0131] 54. The composition for use of clause 53, wherein: the animal is an adult chicken, and the effective amount of the diluted composition is from 0.2 L to 1 L per day; or the animal is an adult turkey, and the effective amount of the diluted composition is from 0.6 L to 1.2 L per day.
[0132] 55. The composition for use of clause 53, wherein: the animal is an adult chicken, and the effective amount of the diluted composition provides from greater than 0 mg to 75 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 38 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition provides from greater than 0 mg to 90 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 45 mg solids obtained from Yucca schidigera.
[0133] 56. The composition for use of clause 53, wherein: the animal is an adult chicken, and the effective amount of the diluted composition provides from 1 mg to 38 mg solids obtained from Quillaja saponaria and from 0.15 mg to 19 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition provides from 3 mg to 45 mg solids obtained from Quillaja saponaria and from 0.4 mg to 23 mg solids obtained from Yucca schidigera.
[0134] 57. The composition for use of clause 55 or clause 56, wherein (i) the solids obtained from Quillaja saponaria are dissolved solids, or (ii) the solids obtained from Yucca schidigera are dissolved solids, or (iii) both (i) and (ii).
[0135] 58. The composition for use of any one of clauses 42-57, wherein administration of the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that did not receive the diluted composition.
[0136] 59. The composition for use of any one of clauses 42-57, wherein administration of diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera.
[0137] 60. The composition for use of any one of clauses 42-57, wherein administration of the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a diluted composition comprising water and dissolved solids obtained from only one of Quillaja saponaria or Yucca schidigera.
[0138] 61. The composition for use of any one of clauses 42-60, wherein the diluted composition is administered to the animal in place of drinking water.
VI. Examples
[0139] Example 1
[0140] The efficacy of liquid compositions comprising extracts of Quillaja saponaria and Yucca schidigera was studied. Ten treatments, 12 replicates each, were performed with 55 Ross 708 broilers per pen. A disease challenge was performed with coccidia, Clostridium, and Salmonella from an Eastern Shore commercial litter with control mortality of 5%. All birds were vaccinated for coccidiosis with Coccivac®-B52 vaccine (Merck Animal Health, USA). Gut health variables were measured at 21 and 42 days. [0141] In some evaluations, Micro-Aid® Liquid 50 (50% dissolved solids derived from Yucca schidigera, Distributors Processing, Inc., USA) was used as a comparison. The Micro-Aid® Liquid 50 was used as instructed, i.e., 2 oz. mixed into 126 oz. of water, and then 1 oz. dispensed per one gallon of drinking water.
[0142] Treatments:
1. Control (MP 0 - no Quillaja or Yucca in any form)
2. 100% Quillaja saponaria extract (32.5 wt% solids) (100% Q)
3. 100% Yucca schidigera extract (45.3 wt% solids) (100% Y)
4. 25/75 QY liquid, 62 g/m3 in water (25/75 QY)
5. 50/50 QY liquid, 62 g/m3 in water (50/50 QY)
6. 75/25 QY liquid, 62 g/m3 in water (75/25 QY)
7. 90/10 QY liquid, 62 g/m3 in water (90/10 QY; approximately equal in content to
Magni-Phi® powder*)
8. Magni-Phi® (MP) powder, 125 ppm as powder (MP125)
9. Magni-Phi® powder, 250 ppm as powder (MP250)
10. Magni-Phi® powder, 500 ppm as powder (MP500)
* Magni-Phi® powder is a proprietary blend of triterpenoid saponins (Phibro Animal Health Corporation, Teaneck, NJ)
[0143] Gut health variables were measured at 21 and 42 days. Assessed parameters included body weight (FIG. 1), feed conversion ratio (g:g) (FIG. 2), Clostridium enumeration (FIG. 3), Salmonella incidence percentage (FIG. 4), and villus height:crypt depth ratio (FIG. 5). Letters shown on the bars are indicative of statistically significant or insignificant results. For example, with respect to FIG. 1, 100% Y and 50/50 QY both are designated “d,” indicating that the results are not statistically different from one another. Similarly, 100% Q is designated as “de,” indicating that the result is not statistically different from results of trials labeled with “d” (100% Y, 50/50 QY) or “e” (MP250). The 75/25 QY result is designated “a.” Because no other result is designated with “a,” the 75/25 QY result is statistically different from all of the other trials. Each graph also displays a numerical result from Micro Aid Liquid (MA). The MA concentrate includes 50 wt% yucca dissolved solids. The MA concentrate is used at a ratio of 2 fluid oz. to 126 fluid oz. of H2O, which is then diluted 1:128 to use, providing ~61 ppm yucca solids.
[0144] In general, MP powder produced linear responses (0-500 ppm) in all variables measured, with 500 ppm MP powder providing consistently better performance than 250 ppm MP powder. The QY liquid provided many of the same effects as MP powder with most responses falling within the range of the results obtained from 250-500 ppm MP powder. The 75/25 QY liquid produced responses that were largely equivalent to 500 ppm MP powder. While other QY liquids also were effective, superior results were obtained with the 75/25 QY liquid. Notably, the 75/25 QY liquid provided statistically significant improvements in each gut health variable compared to either Quillaja alone or Yucca alone. Four of the five variables also were statistically better than MP powder administered at 125 ppm or 250 ppm, and three of the five variables were statistically better than MA.
[0145] These results establish that the 75/25 QY liquid at a concentration of 250 ppm in water provides results at least equivalent to 500 ppm MP powder. Moreover, a liquid concentrate has the advantage of being easier to use since it can be readily mixed homogeneously with the avians’ drinking water.
[0146] Example 2
[0147] The efficacy of liquid compositions comprising extracts of Quillaja saponaria and Yucca schidigera was studied. Nine treatments, 12 replicates each, were performed with 55 Ross 708 broilers per pen. A disease challenge was performed with coccidia, Clostridium, and Salmonella from an Eastern Shore commercial litter with control mortality of 7.3%. All birds were vaccinated for coccidiosis with Coccivac®-B52 vaccine (Merck Animal Health, USA). Gut health variables were measured at 21 and 42 days.
[0148] Treatments:
1. Control (MP 0 - no Quillaja or Yucca in any form)
2. 100% Quillaja saponaria extract (32.5 wt% solids) (100% Q)
3. 100% Yucca schidigera extract (45.3 wt% solids) (100% Y)
4. 25/75 QY liquid, 62 g/m3 in water (25/75 QY)
5. 50/50 QY liquid, 62 g/m3 in water (50/50 QY)
6. 75/25 QY liquid, 62 g/m3 in water (75/25 QY)
7. 90/10 QY liquid, 62 g/m3 in water (90/10 QY; approximately equal in content to Magni-Phi® powder*)
8. Magni-Phi® powder, 250 ppm as powder (MP250)
9. Magni-Phi® powder, 500 ppm as powder (MP500)
* Magni-Phi® powder is a proprietary blend of triterpenoid saponins (Phibro Animal Health Corporation, Teaneck, NJ)
[0149] Gut health variables were measured at 21 and 42 days. Assessed parameters included body weight (FIG. 6), feed conversion ratio (g:g) (FIG. 7), Clostridium enumeration (FIG. 8), and Salmonella incidence percentage (FIG. 9). Fetters shown on the bars are indicative of statistically significant or insignificant results. For example, with respect to FIG. 6, 100% Y, 25/75 QY, and 50/50 QY are designated “c,” indicating that the results are not statistically different from one another. In contrast, the MP 500 trial is the only result designated “a,” indicating that the results are statistically different from all of the other trials.
[0150] In general, MP powder produced linear responses (0-500 ppm) in all variables measured, with 500 ppm MP powder providing consistently better performance than 250 ppm MP powder. MP 500 ppm was the best performer of all treatments evaluated. Several QY liquid ratios effectively improved performance. Most liquid responses were as good as or better than 250 ppm MP powder. Differences among various liquid ratios tended to be small. The highest quillaja levels produced the best responses. The liquid formulation results did not exceed the results obtained with 500 ppm MP powder. The 75/25 QY liquid did not provide uniquely outstanding results as in Example l,but was effective. The results indicate that liquid QY formulations may be a reasonable alternative to powder formulations. Some foaming occurred with higher concentrations of liquid quillaja, and an antifoaming agent may be beneficial.
[0151] In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as limiting the scope of the invention. Rather, the scope of the invention is defined by the following claims. We therefore claim as our invention all that comes within the scope and spirit of these claims.

Claims

We claim:
1. An aqueous composition, comprising: from 12 wt% to 36 wt% solids obtained from Quillaja saponaria; and from 3 wt% to 25 wt% solids obtained from Yucca schidigera.
2. The aqueous composition of claim 1 , wherein:
(i) the Quillaja saponaria solids are provided by an aqueous Quillaja saponaria extract comprising 25 wt% to 50 wt% dissolved solids; or
(ii) the Yucca schidigera solids are provided by an aqueous Yucca schidigera extract comprising 30 wt% to 60 wt% dissolved solids; or
(iii) both (i) and (ii).
3. The aqueous composition of claim 1, having a Quillaja saponaria'.Yucca schidigera solids ratio on a w/w basis of from 1.3 to 4.5.
4. The aqueous composition of any one of claims 1-3, consisting of the water, the solids obtained from Quillaja saponaria, and the solids obtained from Yucca schidigera.
5. The aqueous composition of any one of claims 1-4, further comprising a defoaming agent.
6. The aqueous composition of claim 5, wherein the composition comprises from 25 ppm to 15,000 ppm of the defoaming agent.
7. The aqueous composition of claim 6, consisting of the water, the solids obtained from Quillaja saponaria, the solids obtained from Yucca schidigera, and the defoaming agent.
8. The aqueous composition of any one of claims 1-7, further comprising citric acid.
9. The aqueous composition of claim 7, wherein the composition comprises from
1 ppm to 10,000 ppm of the citric acid.
10. The aqueous composition of claim 8 or claim 9 consisting of the water, the solids obtained from Quillaja saponaria, the solids obtained from Yucca schidigera, the defoaming agent, and the citric acid.
11. The composition of any one of claims 1-10, wherein:
(i) the solids obtained from Quillaja saponaria are dissolved solids; or
(ii) the solids obtained from Yucca schidigera are dissolved solids; or
(iii) both (i) and (ii).
12. A method, comprising: combining an aqueous composition according to any one of claims 1-11 with water in an amount of from greater than 0 ppm to 1,000 ppm of the aqueous composition to provide a diluted composition; and administering the diluted composition to an animal.
13. The method of claim 12, wherein the aqueous composition does not comprise a defoaming agent, the method further comprising combining a defoaming agent with the aqueous composition and the water to provide the diluted composition.
14. The method of claim 13, wherein the defoaming agent is added in an amount of from greater than 0 ppm to 100 ppm of the defoaming agent.
15. The method of any of claims 12-14, wherein the diluted composition is administered daily to the animal.
16. The method of any one of claims 12-15, wherein the animal is an avian.
17. The method of claim 16, wherein the diluted composition is administered to the avian beginning on day of hatching.
18. The method of any one of claims 12-17, wherein an effective amount of the diluted composition is administered daily to the animal for a period of time sufficient to promote a beneficial health effect.
19. The method of claim 18, wherein: the animal is an adult chicken, and the effective amount of the diluted composition is from 0.2 L to 1 L per day; or the animal is an adult chicken, and the effective amount of the diluted composition provides from greater than 0 mg to 75 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 38 mg solids obtained from Yucca schidigera; or the animal is an adult chicken, and the effective amount of the diluted composition provides from 1 mg to 38 mg solids obtained from Quillaja saponaria and from 0.15 mg to 19 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition is from 0.6 L to 1.2 L per day; or the animal is an adult turkey, and the effective amount of the diluted composition provides from greater than 0 mg to 90 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 45 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition provides from 3 mg to 45 mg solids obtained from Quillaja saponaria and from 0.4 mg to 23 mg solids obtained from Yucca schidigera.
20. The method of any one of claims 12-19, wherein: administering the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that did not receive the diluted composition; or administering the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera; or administering the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a diluted composition comprising water and dissolved solids obtained from only one of Quillaja saponaria or Yucca schidigera.
21. The method of any one of claims 12-20, wherein the diluted composition is administered to the animal in place of drinking water.
22. The method of any one of claims 12-21, further comprising administering a therapeutic agent to the animal.
23. The method of claim 22, wherein the therapeutic agent is an antimicrobial, an antibiotic, an antifungal, an anticoccidial agent, a vaccine, a direct-fed microbial, yeast, a polyphenol, or any combination thereof.
24. A composition for use in a method of administration to an animal, wherein an aqueous composition according to any one of claims 1-11 is combined with water in an amount of from greater than 0 ppm to 1 ,000 ppm of the composition to provide a diluted composition for administration to the animal.
25. The composition for use of claim 24, wherein the composition does not comprise a defoaming agent, and a defoaming agent is combined with the diluted composition prior to the administration to the animal.
26. The composition for use of claim 25, wherein the defoaming agent is combined with the diluted composition in an amount of from greater than 0 ppm to 100 ppm of the defoaming agent.
27. The composition for use of any one of claims 24-26, wherein the animal is an avian.
28. The composition for use of claim 27, wherein the diluted composition is administered to the avian beginning on day of hatching.
29. The composition for use of any one of claims 24-28, wherein an effective amount of the diluted composition is administered daily to the animal for a period of time sufficient to promote a beneficial health effect.
30. The composition for use of claim 29, wherein: the animal is an adult chicken, and the effective amount of the diluted composition is from 0.2 L to 1 L per day; or the animal is an adult chicken, and the effective amount of the diluted composition provides from greater than 0 mg to 75 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 38 mg solids obtained from Yucca schidigera; or the animal is an adult chicken, and the effective amount of the diluted composition provides from 1 mg to 38 mg solids obtained from Quillaja saponaria and from 0.15 mg to 19 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition is from 0.6 L to 1.2 L per day; or the animal is an adult turkey, and the effective amount of the diluted composition provides from greater than 0 mg to 90 mg solids obtained from Quillaja saponaria and from greater than 0 mg to 45 mg solids obtained from Yucca schidigera; or the animal is an adult turkey, and the effective amount of the diluted composition provides from 3 mg to 45 mg solids obtained from Quillaja saponaria and from 0.4 mg to 23 mg solids obtained from Yucca schidigera
31. The composition for use of any one of claims 24-30, wherein: administration of the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that did not receive the diluted composition; or administration of diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a solid composition comprising equivalent amounts of solids obtained from Quillaja saponaria and Yucca schidigera; or administration of the diluted composition to the animal increases body weight, decreases feed conversion ratio, decreases mortality rate, decreases Clostridium incidence, decreases Salmonella incidence, increases villus height:crypt depth ratio, or any combination thereof compared to an animal that received a diluted composition comprising water and dissolved solids obtained from only one of Quillaja saponaria or Yucca schidigera.
32. The composition for use of any one of claims 24-31 wherein the diluted composition is administered to the animal in place of drinking water.
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