Unique blend of plant-derived components in drinking water to support piglets
The addition of a phytogenic composition containing eugenol and carvacrol to the drinking water of post-weaning piglets addresses the challenge of post-weaning diarrhea, reducing mortality and improving welfare while offering an antibiotic-free solution.
Patent Information
- Application Number
- PCT/US2024/049178
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-04-15
- Filing Date
- 2024-09-30
- Publication Date
- 2025-04-10
AI Technical Summary
Post-weaning diarrhea (PWD) is a significant challenge in swine production, causing diarrhea, dehydration, mortality, and growth retardation in piglets, and traditional antimicrobial growth promoters are being phased out due to resistance concerns and consumer pressure for natural solutions.
A unique blend of plant-derived components, specifically a phytogenic composition comprising an essential oil core with eugenol and carvacrol, is added to the drinking water of post-weaning piglets to support their health and reduce pathogenicity.
The use of this phytogenic composition in drinking water significantly reduces mortality rates, improves animal welfare, and provides an antibiotic-free management approach for piglet health during the critical post-weaning period.
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Figure US2024049178_10042025_PF_FP_ABST
Abstract
Description
PT-2055-WO-PCT UNIQUE BLEND OF PLANT-DERIVED COMPONENTS IN DRINKING WATER TO SUPPORT PIGLETS CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 634,090, filed April 15, 2024, and U.S. Provisional Application No. 63 / 587,597, filed October 3, 2023, each of which is incorporated by reference herein in its entirety. FIELD
[0002] This disclosure relates to feeding piglets and more particularly relates to plant-derived compositions provided in drinking water to post-weaning piglets. BACKGROUND
[0003] Post-weaning diarrhea (PWD) is a problem swine producers face worldwide, and it is characterized by diarrhea, dehydration, mortality, and growth retardation in surviving pigs. The impact ranges from mild reductions in the growth performance to severe weight loss and mortality. An etiological agent commonly associated with PWD are pathogenic strains of enterotoxin producing Escherichia coli.
[0004] Many factors, including husbandry, environment, nutrition, and genetic susceptibility, play a critical role in the severity of this syndrome. Therefore, the control of PWD usually has to be approached at different levels: husbandry practices at the sow farms and nursery sites with proper sanitation and vaccination programs; minimize the stress after weaning by providing a fresh and easily accessible feed and water and an adequate environment (temperature and humidity) and space to the newly weaned pigs.
[0005] Management of nutritional programs is also an essential aspect of controlling PWD. Conventional swine production systems rely on the in-feed application of antibiotics, pharmacological levels of zinc, fiber, high digestible protein, spray-dried plasma, dietary acidification, functional feed additives, and others to help the newly weaned pigs to overcome post-weaning challenges. Antibiotics and other in-feed antimicrobial growth promoters such as zinc oxide are phased out more and more globally due to rising concerns regarding the development of bacterial resistances to clinically important antibiotic and accumulation in manure and the environment. Therefore, regulatory provisions, combined with an increasing pressure ofPT-2055-WO-PCT consumers demanding more “natural” solutions, necessitates the search for alternatives to traditional antimicrobial growth promoters (AGPs) to maintain efficient farming in the future. Especially, promising in this regard are plant-derived bio-active compounds (hereinafter referred to as phytogenics). SUMMARY
[0006] PWD is a syndrome affecting piglets with a major impact on welfare, growth performance and cost efficacy of swine production. The present description relates to a unique blend of plant-derived components provided in drinking water to support post-weaning (PW) piglets. Without being bound by theory, it is thought that the plant-derived components can interact specifically with the intestinal tract and its microbiome, targeting microorganisms to reduce pathogenicity and increasing intestinal barrier integrity. Bacteria such as pathogenic E. coli, an etiological agent most commonly associated with PWD, are influenced in their ability to express virulence factors or invade intestinal epithelia. Successful prevention of pathogenicity supports reduced mortality, improved animal welfare and may provide antibiotic free management of livestock production.
[0007] The present description relates to modern livestock production methods to support piglets during the critical PW period. The methods and compositions described herein therefore are part of modern health and nutrition management strategies to support piglets during the critical weaning period.
[0008] In one aspect, the present disclosure provides a method of production of livestock animals in a nursery The method includes providing a phytogenic composition in drinking water to post-weaning piglets, wherein the phytogenic composition comprises an essential oil core, and one or more additives, e.g., dextrose. The essential oil core comprises essential oils, wherein the essential oils comprise eugenol and carvacrol. The PW piglets provided the phytogenic composition in the drinking water have improved nursery performance relative to PW piglets provided the drinking water without the phytogenic composition. The improved performance comprises a reduced mortality rate during the post-weaning period of the PW piglet lifecycle.
[0009] In another aspect, the present disclosure provides a phytogenic drinking water composition comprising drinking water and a phytogenic composition, wherein the phytogenic composition comprises essential oils. The essential oils include eugenol and carvacrol. The PWPT-2055-WO-PCT piglets in a nursery provided drinking water with the phytogenic composition have a reduced mortality rate relative to PW piglets provided drinking water without the phytogenic composition.
[0010] In yet another aspect, the present disclosure provides a phytogenic composition comprising an essential oil core and one or more additives, wherein the essential oil core comprises essential oils, wherein the essential oils comprise eugenol between about 2% by weight and about 8% by weight of the phytogenic composition and carvacrol between about 2% by weight and about 8% by weight of the phytogenic composition. Preferably, the phytogenic composition further comprises one or more additives. The one or more additives may comprise dextrose. Preferably, the essential oils are microencapsulated with an encapsulation matrix. BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The drawings illustrate generally, by way of example, but not by way of limitation, various aspects discussed herein.
[0012] Figure 1 is a schematic diagram of one exemplary formulation of an essential oil composition. Percentages without brackets refer to inclusion in the whole product. Percentages in brackets refer to inclusion in the next level.
[0013] Figure 2 is a plot of the average influence of tested substances on biofilm formation in E. coli O88 and E. coli O143.
[0014] Figure 3 is a plot of the influence of tested substances on violacein production in Chromobacterium violaceum. DETAILED DESCRIPTION
[0015] Reference will now be made in detail to certain aspects of the disclosed subject matter, examples of which are illustrated in part in the accompanying drawings. While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the exemplified subject matter is not intended to limit the claims to the disclosed subject matter.
[0016] The present disclosure relates to a method of production of livestock animals. The method improves the performance of piglets in a nursery during the PW period. The method includes providing a phytogenic composition in drinking water. The drinking water can be supplemented with the phytogenic composition at the disclosed inclusion rates. The PW piglets are provided the phytogenic composition in the drinking water during the post-weaning period toPT-2055-WO-PCT improve performance. The method can improve performance by a reduction of the mortality rate in the nursery. The method may also improve performance by reducing the morbidity rate, by reducing disease during the PW phase, e.g., post-weaning diarrhea (PWD), enhancing the growth, enhancing the health of the PW piglets or combinations thereof.
[0017] In the methods described herein, the PW piglets may have reduced severity of PWD symptoms, i.e., diarrhea, dehydration, mortality, and growth retardation in surviving pigs. Improved performance, animal welfare and reduced need for medication may be the direct effects when providing the phytogenic drinking water described herein to piglets during the post-weaning period. Without being bound by any theory, the phytogenic compositions provided in the drinking water may improve the welfare of the animals by supporting the development of a normal and functional gut, supporting their resilience against stress factors.
[0018] In one aspect, the phytogenic composition comprises an essential oil core, preferably a microencapsulated essential oil core. The essential oil core includes an essential oil, preferably a mixture of essential oils. Preferably, the essential oils include at least two essential oils at the disclosed percentages and / or ratios. In one aspect, the mixture of essential oils comprises eugenol and carvacrol. One or more of the essential oils may be microencapsulated. Microencapsulation may be performed prior to combining the essential oils or after combining the essential oils. The phytogenic composition may further comprise one or more additives, for example, dextrose.
[0019] The term “post-weaning piglets” or “PW piglets” as used herein relates to the period from weaning of piglets until the start of the fattening stage. The PW piglet is at least 10 days old, preferably at least 15 days old, preferably at least 17 days old, preferably at least 21 days old, preferably at least 23 days old, more preferably between 21 days and 25 days old at the initiation of the method described herein. The feeding method may also be initiated when the PW piglets are older than 25 days old. It will be understood that the exact day of weaning can vary and post- weaning refers to any day of life after the piglet weaning is initiated and continues until the start of the fattening phase. The terms “PW phase”, “PW stage” and “PW period” are used interchangeably.
[0020] The PW phase comprises 3 phases. The term “phase 1” as used herein relates to the period from initiation of post-weaning (day 1) to about day 10 of post-weaning.
[0021] The term “phase 2” as used herein relates to the period from about day 11 to about day 22 of post-weaning. The end of Phase 2 can vary and is generally the end of the critical period of weaning of the PW piglets.PT-2055-WO-PCT
[0022] The term “phase 3” as used herein relates to the period from end of Phase 2, e.g., about day 23 to until the start of the fattening phase (about day 35 of post-weaning).
[0023] The term “critical period” relates to the period after weaning when the piglets are most susceptible to disease and mortality. The critical period is generally about 14-20 days post- weaning.
[0024] The term “phytogenic” as used herein relates to plant-derived products, e.g., herbs, spices, extracts and the like, and / or bioactive compounds found in plants. Phytogenic includes natural products directly derived from plants. Phytogenic also includes synthetic and / or nature- identical components / compositions that can be made artificially but the molecules are identical in their chemical composition to molecules found in plants. Phytogenic extracts include, e.g., essential oils.
[0025] The term “phytogenic composition” as used herein relates to a composition comprising a phytogenic core and may also include additives. Additives can include an encapsulation matrix, carriers, e.g., dextrose and the like, and may be of organic and / or inorganic origin. The phytogenic composition includes natural, nature identical and / or synthetic phytogenics. The phytogenic composition can include synthetic and / or nature-identical phytogenics that are formed by combining or formulating individual phytogenics, e.g., natural, and / or synthetic phytogenics, to form a composition that is found in nature. Phytogenic composition also includes compositions based on phytogenics that are not found in nature, but the individual components are natural, nature-identical and / or synthetic phytogenics that can be found in nature. The present phytogenic composition will be described with synthetic and / or nature-identical components, but it will be understood that natural phytogenics may also be included in the phytogenic composition. The phytogenic composition is combined or included in the drinking water of the PW piglets.
[0026] The term “plants” and plant derivatives” as used herein relates to any portion of a growing plant, including the roots, stems, stalks, leaves, branches, seeds, flowers, fruits, and the like.
[0027] The term “essential oil mixture” or “essential oils” as used herein relates to an essential oil or a combination of essential oils or essential oil components in an essential oil core. The essential oil core of the phytogenic composition preferably includes at least 2 essential oils or essential oil components. Essential oils and essential oil mixture will be used interchangeably. “Essential oils” as used herein relates to aromatic, volatile liquids extracted from plant material whereas “essential oil components” refers to specific chemical molecules found in essential oils.PT-2055-WO-PCT Essential oils are often concentrated hydrophobic liquids containing volatile aroma compounds. Essential oil chemical constituents can fall within a wide range of chemical classes such as terpenes, terpenoids, phenols, aldehydes, ketones and phenylpropanoids. Essential oils can be natural (i.e., derived from plants), synthetic or a combination to achieve a nature identical essential oil.
[0028] The term “essential oil core” as used herein relates to an essential oil or a mixture of essential oils that are included and further includes additives such as encapsulation matrix, carriers, e.g., dextrose and the like. One or more of the essential oils may be microencapsulated with an encapsulation matrix and / or combined with a carrier to form the essential oil core. The essential oils may comprise, for example, eugenol and carvacrol.
[0029] The term “eugenol” as used herein relates to 2-methoxy-4-prop-2-enylphenol which can be derived from plants, synthetically produced or a combination to achieve a natural or nature identical eugenol. Eugenol can be derived from, for example, clove (Syzygium aromaticum), nutmeg (Myristica fragrans), cinnamon (Cinnamomum verum), basil (Ocimum basilicum), and / or bay leaf (Laurus nobilis). Eugenol derived from other plants can also be used and is also within the scope of this disclosure.
[0030] The term “carvacrol” as used herein relates to 2-methyl-5-propan-2-ylphenol which can be derived from plants, synthetically produced or a combination to achieve a natural or nature identical carvacrol. Carvacrol can be derived from, for example, oregano (Origanum vulgare), and / or thyme (Thymus vulgaris). Carvacrol derived from other plants can also be used and is also within the scope of this disclosure.
[0031] The term “basal feed” as used herein relates to feed that is fed to the PW piglets during the post-weaning period. It includes the ingredients and nutrients needed for the PW piglets. Basal feed does not include the phytogenic compositions.
[0032] The term “PW piglet drinking water” or “piglet drinking water” or “phytogenic drinking water” as used herein relates to drinking water comprising a phytogenic composition.
[0033] In one aspect, the present description comprises a method of production of livestock animals, e.g., PW piglets, in a nursery. The method improves the performance of the livestock animals. The method includes providing drinking water supplemented with a phytogenic composition to the animals at the initiation of weaning. The animal is preferably a piglet, more preferably a PW piglet. The PW piglet is at least 10 days old, at least 15 days old, at least 17 days old, at least 19 days old, preferably at least 21 days old, or more preferably at least 23 days old,PT-2055-WO-PCT or more preferably between 21 days and 25 days old at the initiation of the method described herein of providing phytogenic drinking water. The method of providing the phytogenic drinking water may also be initiated when the PW piglets are older than 25 days old.
[0034] In one aspect, the present description comprises a phytogenic composition for inclusion in the drinking water of PW piglets in a nursery. The phytogenic compositions included in the drinking water comprise an essential oil core. The phytogenic composition further comprises one or more additives, e.g., dextrose. The essential oil core may include an essential oil or a mixture of essential oils, e.g., a combination of preferably at least two essential oils. The phytogenic composition can include additives such as encapsulation materials, carriers and the like.
[0035] The essential oil core preferably includes a mixture of at least two essential oils. The essential oil core may include more than two essential oils. A variety of combinations of essential oils can be used in the essential oil core. The essential oil mixtures may comprise, for example, carvacrol, cinnamaldehyde, eugenol, trans-anethole, terpinene-4-ol, Ȗ-terpinene, diallyl disulfide, diallyl trisulfide, D-limonene, and combinations thereof. In one aspect, essential oils included in the essential oil core comprise eugenol and carvacrol.
[0036] In one aspect, the essential oil core in the phytogenic composition comprises eugenol and carvacrol. In one aspect, the phytogenic composition consists essentially of eugenol and carvacrol as the essential oils. By consists essentially of, it is meant that the phytogenic composition may not include any other essential oils except eugenol and carvacrol. In one aspect, the phytogenic composition does not include other essential oils except eugenol and carvacrol.
[0037] The phytogenic composition comprises microencapsulated essential oils wherein the eugenol and the carvacrol are microencapsulated with an encapsulation matrix and combined with a carrier, e.g. dextrose, to form a phytogenic composition as shown in FIG. 1. Alternatively, eugenol and / or carvacrol may be combined prior to microencapsulation.
[0038] The amount of eugenol is between 20% by weight and 80% by weight of the total essential oils in the composition, preferably between 20% by weight and 60% by weight, preferably between 30% by weight and 70% by weight, more preferably between 30% by weight and 60% by weight, more preferably between 40% by weight and 60% by weight, more preferably between 45% by weight and 55% by weight, more preferably between 48% by weight and 52% by weight, more preferably between 49% by weight and 51% by weight, more preferably about 50% by weight of the total essential oils in the composition.PT-2055-WO-PCT
[0039] The amount of carvacrol is between 20% by weight and 80% by weight of the total essential oils in the composition, preferably between 20% by weight and 60% by weight, preferably between 30% by weight and 70% by weight, more preferably between 30% by weight and 60% by weight, more preferably between 40% by weight and 60% by weight, more preferably between 45% by weight and 55% by weight, more preferably between 48% by weight and 52% by weight, more preferably between 49% by weight and 51% by weight, more preferably about 50% by weight of the total essential oils in the composition.
[0040] The ratio of the eugenol to carvacrol in the phytogenic composition is between 5:1 and 1:5, preferably between 4:1 and 1:4, more preferably between 3:1 and 1:3, more preferably between 2:1 and 1:2, more preferably about 1:1.
[0041] The percentage of essential oils in the phytogenic composition, e.g., eugenol and carvacrol, is between about 2% by weight and about 40% by weight of the phytogenic composition, preferably between about 5% by weight and about 30% by weight, preferably between about 5% by weight and about 25% by weight, more preferably between about 5% by weight and about 20% by weight, more preferably between about 6% by weight and about 30% by weight, more preferably between about 6% by weight and about 20% by weight, more preferably between about 6% by weight and about 10% by weight, more preferably between about 7% by weight and about 10% by weight, more preferably between about 7% by weight and about 8% by weight, more preferably about 7.5% by weight of the phytogenic composition.
[0042] The amount of eugenol in the phytogenic composition is between about 2% by weight and about 20% by weight, preferably between about 3% by weight and about 20% by weight, more preferably between about 3% by weight and about 10% by weight, more preferably between about 3% by weight and about 8% by weight, more preferably between about 3% by weight and about 5% by weight, more preferably between about 3% by weight and about 4% by weight, more preferably about 3.75% by weight of the phytogenic composition.
[0043] The amount of carvacrol in the phytogenic composition is between about 2% by weight and about 20% by weight, preferably between about 3% by weight and about 20% by weight, more preferably between about 3% by weight and about 10% by weight, more preferably between about 3% by weight and about 8% by weight, more preferably between about 3% by weight and about 5% by weight, more preferably between about 3% by weight and about 4% by weight, more preferably about 3.75% by weight of the phytogenic composition.PT-2055-WO-PCT
[0044] The essential oil core of the phytogenic composition can comprise a mixture of essential oils, preferably one or more of the essential oils in the essential oil core are microencapsulated. The phytogenic composition may comprise an essential core wherein all of the essential oils are microencapsulated. The essential oils may be microencapsulated individually and then combined to form the essential oil core. Alternatively, the essential oils may be combined prior to microencapsulation. The essential oil core may comprise one microencapsulated essential oil and one essential oil that has not been microencapsulated. Microencapsulation of essential oils is known in the art and can be performed, for example, as described in EP patent 1419811A1, incorporated herein by reference. Other methods of encapsulation may also be used and are within the scope of this description.
[0045] The phytogenic compositions described herein may further comprise one or more additives. The additives can be soluble in water and / or enhance the solubility and / or stabililty of the essential oils in water. The additives may be a liquid or a powder. Preferably, the one or more additives are soluble and / or dispersible in water. The one or more additives may comprise carriers. Carrier(s) can be combined with the essential oil core and / or the essential oils to form the phytogenic composition. Carriers included in the phytogenic composition may include, for example, starch hydrolysates, such as dextrins, dextrose, starches, modified starches, gum arabic alginates, natural resins, such as shellac, wood rosin, cellulose derivatives, such as hydroxypropyl cellulose sodium carboxylcellulose, methylcellulose, ethylcellulose, animal and / or vegetable proteins or their hydrolysates, such as gelatin, collagen, egg protein, wheat protein, caseinates, milk protein, soy protein, pea protein, soluble fibers (pectins) and / or mixtures thereof may be used. In one aspect, the phytogenic composition comprises dextrose combined with the essential oil core.
[0046] Additives can also comprise components present in an encapsulation matrix. Essential oil core can include essential oils combined in an encapsulation matrix. The essential oils can be combined with the encapsulation matrix during a microencapsulation process. A variety of the additives may be used in the encapsulation matrix during the microencapsulation process, during the formation of the essential oil core and / or during the formation of the phytogenic composition. Encapsulation matrix may also include natural polymers such as starch, dextrose, glucose-fructose syrup, proteins such as wheat and yeast protein, citric acid, and the like.
[0047] The phytogenic composition comprises a microencapsulated essential oil core in an amount of at least about 10% by weight, or preferably at least about 15% by weight, or preferablyPT-2055-WO-PCT at least about 20% by weight, or preferably at least about 25% by weight of the composition. The phytogenic composition comprises a microencapsulated essential oil core of at an amount between about 10% by weight and about 70% by weight, preferably between about 15% by weight and about 60% by weight, preferably between about 20% by weight and about 50% by weight, preferably between about 20% by weight and about 40% by weight, preferably between about 20% by weight and about 30% by weight, preferably about 25% by weight of the composition.
[0048] The amount of one or more additives in the phytogenic composition can vary. In one aspect, the phytogenic composition may comprise dextrose as an additive. The amount of additive can be in an amount of at least about 20% by weight, or preferably at least about 30% by weight, or preferably at least about 40% by weight, or preferably at least about 45% by weight, or preferably at least about 50%, or preferably at least about 60% by weight, or preferably at least about 70% by weight, or preferably at least about 70% by weight of the composition. The phytogenic composition may comprise an additive at an amount between about 20% by weight and about 90% by weight, preferably between about 20% by weight and about 80% by weight, preferably between about 30% by weight and about 80% by weight, preferably between about 40% by weight and about 80% by weight, preferably between about 50% by weight and about 80% by weight, preferably between about 60% by weight and about 80% by weight, preferably between about 70% by weight and about 80% by weight, preferably about 75% by weight of the composition.
[0049] The essential oil core may include essential oils or essential oil mixtures that are microencapsulated. The matrix for encapsulation may comprise modified starch and dextrose. The essential oils may be microencapsulated as indicated above. The amount of the encapsulation matrix in the microencapsulated essential oils can vary. The microencapsulated essential oil core may comprise encapsulation matrix of at least about 30% by weight, preferably at least about 40% by weight, preferably at least about 50% by weight, preferably at least about 60% by weight, preferably at least about 70% by weight of the microencapsulated essential oil core. The microencapsulated essential oil core may comprise essential oils in an amount of at least about 10% by weight, preferably at least about 20% by weight, preferably at least about 25% by weight, preferably at least about 30% by weight, by weight of the microencapsulated essential oil core.
[0050] In one aspect, the present description includes a powder phytogenic composition that can form a stable dispersion in liquids, e.g., in water. “Dispersion” as used herein relates to composition comprising dissolved components and dispersed components. The dispersedPT-2055-WO-PCT components can include dispersed liquid components and dispersed solid components and emulsions. Emulsions comprise a liquid / liquid dispersion. In other words, the powdered phytogenic composition that is combined with water to form the stock phytogenic composition and / or the phytogenic drinking water comprises a portion of the phytogenic composition that is soluble in the water, a portion that is particles suspended in the water, and a portion that is an emulsion in the water.
[0051] The phytogenic composition may be added to water or other liquid to form a stock phytogenic liquid. The stock phytogenic composition and the drinking water with the added stock phytogenic composition comprise a mixture of dispersed and dissolved components. The phytogenic composition is preferably dispersed in water but dispersion in other liquids is also within the scope of this description. Stock phytogenic liquid as used herein relates to the phytogenic composition dispersed in a liquid, preferably water, at a concentrated dose and will be referred to herein as the stock phytogenic composition. The stock phytogenic composition can be diluted to the desired concentration / dose by addition of the stock phytogenic composition with the drinking water to generate phytogenic drinking water. The phytogenic drinking water comprises the desired dose of the phytogenic composition. The phytogenic drinking water in a PW piglet nursery is further described below.
[0052] In one aspect, the phytogenic composition comprises a powder, a blended powder and / or other particulate composition. The phytogenic composition can be added to the liquid and mixed to disperse the composition into the water. Many mixing mechanisms are known in the art and any may be used to disperse the phytogenic composition in the drinking water. Any type of mixing mechanism may be used, e.g., a mixer, an agitator, a powered paint stirrer and the like. The phytogenic composition is dispersed in the water. The water with the phytogenic composition may result in a thin film at the bottom of the vessel without further mixing after about 3 hours, preferably after about 6 hours, preferably after about 10 hours, preferably after about 15 hours, preferably after about 20 hours.
[0053] The phytogenic composition may remain dispersed in the water for at least about 1 day, preferably at least about 2 days, preferably at least about 3 days, preferably at least about 4 days, preferably at least about 5 days, preferably at least about 6 days without stirring. It will be understood that minimal sedimentation may occur after about 4 days and stirring or mixing the composition can redisperse the phytogenic composition in the water.PT-2055-WO-PCT
[0054] The amount of the phytogenic composition in the stock phytogenic composition can vary and can be, for example, at least about 20 grams(g) / gallon (gal), or preferably at least about 30 g / gal, or preferably at least about 50 g / gal, or preferably at least about 70g / gal, or preferably at least about 90 g / gal. The amount of the phytogenic composition in the stock phytogenic composition can be between about 20g / gal and about 200g / gal, preferably between about 50g / gal and about 150 g / gal, preferably between about 70 g / gal and about 120 g / gal, preferably between about 90 g / gal and about 105 g / gal, preferably between about 95g / gal and about 100 g / gal, more preferably 98 g / gal. Stock phytogenic composition outside of this range may also be made and are within the scope of this description.
[0055] In one aspect, the present description includes drinking water with the phytogenic composition. The phytogenic composition is added to the water in the nursery to generate the desired concentration or dose of the phytogenic composition in the drinking water. A stock solution of the phytogenic composition can be added to the water to generate the desired concentration or dose of the phytogenic composition in the drinking water. Alternatively, the phytogenic composition may be added directly to the water. In one aspect, the stock phytogenic composition is combined with the drinking water at a dilution rate that can generate the desired concentration of the essential oils in the drinking water.
[0056] The dilution rate of the stock phytogenic composition into the water can vary. The stock phytogenic composition may be diluted at a ratio of 1:25 or more, preferably diluted at a ratio of 1:50 or more, preferably diluted 1:75 or more, preferably diluted 1:100 or more, preferably diluted 1:110 or more, preferably diluted 1:120 or more, preferably diluted at a ratio of 1:128 or more, preferably diluted at a ratio of 1:256 or more, preferably diluted at a ratio of 1:512 or more. Dilutions greater than 1:512 or also within the scope of this description.
[0057] The amount of phytogenic composition in the drinking water can be at a concentration between about 0.001wt% and 0.1wt% of the drinking water, preferably between about 0.005wt% and about 0.05wt%, preferably between about 0.0075wt% and about 0.04wt%, preferably between about 0.01wt% and about 0.03wt%, preferably between about 0.015wt% and about 0.025wt%, preferably about 0.02wt% of the drinking water.
[0058] The amount of phytogenic composition included in the phytogenic drinking water can be between about 10 ppm and about 1000 ppm, preferably between about 50 ppm and about 750 ppm, more preferably between about 65 ppm and about 500 ppm, more preferably between aboutPT-2055-WO-PCT 100 ppm and about 300 ppm, more preferably between about 150 ppm and about 250 ppm, and more preferably about 200 ppm.
[0059] The amount of eugenol included in the phytogenic drinking water can be an amount between about 1 ppm and about 30 ppm, preferably between about 3 ppm and about 20 ppm, more preferably between about 5 ppm and about 13 ppm, more preferably between about 7 ppm and about 9 ppm, and more preferably 7.5 ppm.
[0060] The amount of carvacrol included in the phytogenic drinking water can be at an amount between about 1 ppm and about 30 ppm, preferably between about 3 ppm and about 20 ppm, more preferably between about 5 ppm and about 13 ppm, more preferably between about 7 ppm and about 9 ppm, and more preferably 7.5 ppm.
[0061] In one aspect, the present description includes a method for improving the performance of animals in a nursery, preferably PW piglets. The method includes providing drinking water supplemented with the phytogenic composition as described herein. The method can reduce the mortality rate of the PW piglets in a nursery relative to PW piglets that are not provided the phytogenic composition. The method may reduce the morbidity rate of PW piglets in a nursery relative to PW piglets that are not provided the phytogenic composition.
[0062] The method includes providing the phytogenic drinking water in a nursery with PW piglets. The PW piglets in the nursery are generally provided the phytogenic drinking water at the initiation of the PW period. At the initiation of the PW period, the PW piglets are at least 10 days old, preferably at least 15 days old, preferably at least 17 days old, preferably at least 19 days old, preferably at least 21 days old, or more preferably at least 23 days old, or more preferably between about 21 days and about 25 days old at the initiation of the method described herein with the phytogenic composition. The method of providing phytogenic drinking water may also be initiated when the PW piglets are older than 25 days old.
[0063] The weight of the PW piglets at the initiation of the PW period can vary. The PW piglets are at least 6 lbs, or preferably at least 8 lbs, or preferably at least 9 lbs, or preferably at least 10 lbs at the initiation of the method providing the phytogenic drinking water. The weight of the PW piglets at the initiation of the PW period can be between 6 lbs and about 22 lbs, or preferably between about 10 lbs and about 18 lbs.
[0064] The method of providing the phytogenic drinking is initiated and / or provided to the PW piglets anytime during the PW period. The method described herein is provided to PW piglets between about day 10 and about day 75 of life. The method of providing phytogenic drinkingPT-2055-WO-PCT water is preferably for at least the critical period, e.g., until 14 days PW, preferably at least until 22 days PW, preferably at least until 33 days PW. It will be understood that weaning times differ depending on the region and swine production systems, but the method described herein can be initiated as soon as piglets are weaned.
[0065] The method described herein is provided to PW piglets between about day 10 and about day 75 of life, preferably between days 15 and 70, preferably between days 18 and 70, preferably between days 18 and 60, preferably between days 18 and 50, preferably between days 18 and 45, preferably between days 21 and 70, more preferably between days 21 and 66, more preferably between days 21 and 60, more preferably between days 21 and 56, more preferably between days 21 and 50, more preferably between days 21 and 45, more preferably between days 23 and 75, more preferably between days 23 and 70, more preferably between days 23 and 66, more preferably between days 23 and 60, more preferably between days 23 and 50, more preferably between days 23 and 45, more preferably between days 25 and 75, more preferably between days 25 and 70, more preferably between days 25 and 66, more preferably between days 25 and 60, more preferably between days 27 and 70, more preferably between days 27 and 66, more preferably between days 27 and 60. The phytogenic drinking water is provided to PW piglets until at least day 31, preferably at least until day 42 of the PW piglets life.
[0066] The method comprises provided the phytogenic drinking water to PW piglets in a nursery for at least phase 1 and / or phase 2. In one aspect, the phytogenic water is provided in phase 1. In one aspect, the phytogenic water is provided in phase 2. Preferably, the phytogenic drinking water is provided in phase 1 and phase 2, or preferably in phase 1, phase 2 and phase 3. The phytogenic composition is preferably provided in the drinking water after weaning (transition from milk feeding to cereal-based diets) and provided preferably for at least until about 10 days PW (throughout phase 1), preferably for at least until about 14 days PW (through the critical period), preferably for at least until about 22 days PW (throughout phase 1 and phase 2). The phytogenic composition may be provided after about 22 days PW (through all or part of phase 3). The phytogenic composition may be provided for any range between day 1 of PW and day 35 of PW (end of phase 3). The phytogenic composition may be provided for at least 3 days PW, or for at least 5 days PW, or for at least 10 days PW, or for at least 14 days PW, or for at least 21 days PW, or for at least 28 days PW, or for at least 35 days PW. The phytogenic composition is provided for at most 10 days, or preferably at most 14 days, or preferably at most 25 days, or preferably atPT-2055-WO-PCT most 35 days. It will be understood that weaning times differ depending on the region and swine production systems, but the method described herein can be initiated as soon as piglets are weaned.
[0067] The method comprises providing the drinking water with the phytogenic composition. The method can include combining the phytogenic composition with the water in the nursery to generate the desired concentration. A stock phytogenic composition can be combined with the water and diluted to generate a desired concentration of the phytogenic composition, e.g., about 0.02wt%, in the drinking water. Preferably, the stock phytogenic composition is prepared daily for use in dilution, preferably within 24 hours of initiation of dilution into the drinking water, preferably within 12 hours of dilution, preferably within 6 hours of dilution, preferably within 4 hours of initiation of dilution. Alternatively, the phytogenic composition may be added directly to the water.
[0068] The phytogenic composition is combined with water at a rate that improves the performance of the PW piglets in the nursery. The inclusion amount of the phytogenic composition in the drinking water can be between about 0.001wt% and 0.1wt% of the drinking water, preferably between about 0.005wt% and about 0.05wt%, preferably between about 0.0075wt% and about 0.04wt%, preferably between about 0.01wt% and about 0.03wt%, preferably between about 0.015wt% and about 0.025wt%, preferably about 0.02wt% of the drinking water.
[0069] The method may optionally include mixing or agitating the phytogenic drinking water to ensure that the phytogenic composition continues to be dispersed in the drinking water and to avoid settling of the phytogenic composition, preferably mixing or agitation is performed if the phytogenic composition has been added to the drinking water for about a day or longer. Mixing or agitation may not be necessary if the phytogenic composition has been combined in the drinking water for less than a day. In one aspect, the mixing or agitating may be performed to redisperse the phytogenic composition that has settled in the drinking water by a variety of mechanisms known in the art.
[0070] The method may include providing drinking water in a delivery method appropriate for the PW piglets such as a delivery device with a nipple for PW piglet suckling. Other delivery methods may be used and are within the scope of this description. The method may include combining water and a stock phytogenic composition, preferably with mixing, to maintain the desired levels of the phytogenic composition in the water delivery device. The stock phytogenic composition can be used to dose the appropriate amount into the drinking water in a PW piglet nursery.PT-2055-WO-PCT
[0071] The method includes providing eugenol and carvacrol in the drinking water. The amount of eugenol provided in the drinking water can be an amount between about 1 ppm and about 30 ppm, preferably between about 3 ppm and about 20 ppm, more preferably between about 5 ppm and about 13 ppm, more preferably between about 7 ppm and about 9 ppm, and more preferably 7.5 ppm. The carvacrol is included at an amount between about 1 ppm and about 30 ppm, preferably between about 3 ppm and about 20 ppm, more preferably between about 5 ppm and about 13 ppm, more preferably between about 7 ppm and about 9 ppm, and more preferably 7.5 ppm.
[0072] The method includes providing a basal feed to the PW piglets while the PW piglets are provided the phytogenic drinking water. The basal feed can vary and can be a commercially available feed appropriate for the age / phase of the piglets. A variety of basal feeds are known in the art and appropriate for PW piglets. Basal feeds for PW piglets are formulated, for example, by Cargill, Inc. Other age-appropriate and / or phase appropriate basal feeds for PW piglets are within the scope of this disclosure. The basal feed may be supplemented with the phytogenic drinking water with phytogenic compositions described herein at the inclusion rates and doses disclosed.
[0073] The method may include providing the PW piglets ad libitum access to the feed. The method may include providing the PW piglets defined amounts of feed, e.g., not ad libitum access. Preferably, the method includes providing the PW piglets ad libitum access to the feed in a mash feed and / or pellet feed. Preferably, the method includes providing PW piglets feed in a mash feed. More preferably, the method includes providing the PW piglets ad libitum access to the feed in a pellet form.
[0074] The method of production of PW piglets in a nursery as described herein may, optionally, include separating PW piglets. The PW piglets of a smaller size may be separated from piglets that are average size or greater at the initiation of the PW period. PW piglets that develop a disease may be separated / removed from the PW piglets that are healthy and placed in a separate pen upon displaying symptoms of a disease. “Average pigs” referred to herein or PW piglets that are average in size, as known in the art, at the initiation of Phase 1 of the PW period and without symptoms of disease. In one aspect, the method may, optionally, include separating PW piglets that are less than about 10lbs at day 1 of phase 1 from the average size PW piglets of about 10lbs or greater. Other cutoffs for separation of average size piglets from small piglets may be used, for example, separating PW piglets less than about 9 lbs from piglets greater than or equal to 9 lbs, separating PW piglets less than about 11 lbs from piglets greater than or equal to 11 lbs and thePT-2055-WO-PCT like. The size / weight of the PW piglets that are separated can vary and all are within the scope of this description.
[0075] The separation of smaller piglets and / or piglets displaying disease symptoms enables more directed care in pens. PW piglets that are less than about 10 lbs will be referred to herein as “small PW piglets”, but it will be understood that the weight of the “small PW piglets” may vary and can be between, for example, between about 5lbs and 12 lbs, or between 6lbs and 11 lbs, or between 7lbs and 11 lbs, or between 8lbs and 11lbs, or between 9lbs and 11lbs. PW piglets that display disease symptoms during the PW phase will be separated from the average PW piglets and / or the small PW piglets and placed in separate pens. The PW piglets that are removed because of disease will be referred to as “removals”. Removal pigs from the various treatments were moved to removal pens and were kept in the same water treatment.
[0076] The number of pigs / pen may vary and all are within the scope of this description. The method may comprise about at least 6 pigs / pen, or preferably at least 10 pigs / pen, preferably at least about 15 pigs / pen, preferably at least about 20 pigs / pen, preferably at least about 25pigs / pen. The method may comprise greater than 25 pigs / pen as long as sufficient drinking water and feed are provided for the number of pigs in the pen.
[0077] The PW piglets have ad libitum access to the phytogenic drinking water in the pens. The amount of water consumed per pig can vary and generally increases with the increase of age and body weight. The amount of phytogenic drinking water consumed per pig can be between about 0.02 gal / pig / day and about 1 gal / pig / day, preferably between about 0.03 gal / pig / day and about 0.8gal / pig / day. It will be understood that the amount of water consumed per pig will change as the piglets mature and increase as the body weight of the piglet increases. The amount of water provided can be increased as the weight of the piglets increases. Consumption of the phytogenic water outside of this range is also within the scope of this description.
[0078] The method described herein can improve the performance of the PW piglets. Improved performance characteristics of the PW piglets includes, for example, reduced mortality rate, reduced morbidity rate, enhanced growth, enhanced health and the like. The performance of the PW piglets can be improved by a reduction of the mortality rate in the nursery. The performance of the PW piglets can also improve a combination of the performance characteristics.
[0079] The method of the present description can reduce the closeout mortality rate of the PW piglets in a nursery. “Closeout mortality rate” as used herein is the mortality rate of the PW piglets at the end of the PW period (end of phase 3 (about day 35 of trial)). The closeout mortality rate ofPT-2055-WO-PCT the combined PW piglets (of average size, small piglets and removal piglets) in the pens provided the phytogenic drinking water can be reduced by at least about 25%, preferably be at least about 30%, preferably at least about 35%, preferably at least about 40%, preferably at least about 45% by the end of the PW period relative to the mortality rate of PW piglets that were not provided the phytogenic drinking water. The mortality rate of the combined PW piglets (average size piglets, small PW piglets and removal piglets) in the pens provided the phytogenic drinking water is reduced to between about 10% and about 50%, preferably between about 20% and about 40%, preferably between about 25% and about 35% and about 30% at the end of the PW period relative to the mortality rate of PW piglets that were not provided the phytogenic drinking water.
[0080] The method of the present description can reduce the closeout mortality rate of the average size PW piglets (without the small PW piglets) in a nursery relative to the control without the phytogenic drinking water. The closeout mortality rate of the average size PW piglets in the pens provided the phytogenic drinking water is reduced by at least about 5%, preferably by at least about 10%, preferably by at least about 15% relative to the mortality rate of the average size PW piglets that were not provided the phytogenic drinking water. The closeout mortality rate of the average size PW piglets provided the phytogenic drinking water is reduced by about 5% to about 40%, preferably by about 10% to about 35%, preferably by about 15% to about 30%, preferably by about 25% relative to the mortality rate of average PW piglets that were not provided the phytogenic drinking water.
[0081] The method of the present description can reduce the closeout mortality rate of the small PW piglets (separated from the average size PW piglets) in a nursery relative to the control without the phytogenic drinking water. The closeout mortality rate of the small PW piglets in the pens provided the phytogenic drinking water is reduced by at least 10%, preferably by at least 20% relative to the mortality rate of PW piglets that were not provided the phytogenic drinking water. The closeout mortality rate of the small PW piglets provided the phytogenic drinking water is reduced by about 10% to about 50%, preferably by about 20% to about 45%, preferably by about 30% to about 40%, preferably by about 35% relative to the mortality rate of PW piglets that were not provided the phytogenic drinking water.
[0082] The method of the present description can reduce the mortality rate of the combined PW piglets (average size piglets, small PW piglets and removal piglets) in a nursery by the end of phase 2 relative to the control without the phytogenic drinking water. The mortality rate of the combined PW piglets (average piglets and small piglets) at the end of phase 2 in the pens providedPT-2055-WO-PCT the phytogenic drinking water is reduced by at least about 10%, or preferably by at least about 20%, or preferably by at least about 25%, at the end of phase 2 of PW period relative to the mortality rate of PW piglets at the end of phase 2 that were not provided the phytogenic drinking water. The mortality rate of the PW piglets (average size piglets, small PW piglets and removal piglets) at the end of phase 2 in the pens provided the phytogenic drinking water is reduced by between about 10% and about 50%, or preferably by about 10% to about 40%, or preferably between about 20% and 40%, or preferably between about 25% and about 35% , or preferably about 30% at the end of phase 2 of the PW period relative to the mortality rate of PW piglets at the end of phase 2 that were not provided the phytogenic drinking water.
[0083] The method of the present description can reduce the mortality rate of the average size PW piglets (without small pigs) in a nursery after phase 2 relative to the control without the phytogenic drinking water. The mortality rate of the average PW piglets (without small pigs) at the end of phase 2 in the pens provided the phytogenic drinking water is reduced by at least about 25%, preferably by at least about 30% at the end of phase 2 of PW period relative to the mortality rate of PW piglets that were not provided the phytogenic drinking water. The mortality rate of the average size PW piglets (without small pigs) at the end of phase 2 in the pens provided the phytogenic drinking water is reduced by about 10% to about 50%, preferably by about 10% to about 40%, preferably by about 20% to about 40%, preferably by about 25% to about 35%, or preferably about 30% at the end of phase 2 of the PW period relative to the mortality rate of PW piglets at the end of phase 2 that were not provided the phytogenic drinking water.
[0084] The method of the present description can enhance the health of the PW piglets. The method of the present description can reduce the morbidity of the PW piglets in a nursery. The method can reduce the number of removals of the PW piglets from the PW piglet pens provided the phytogenic drinking water compared to average PW piglet pens that were not provided phytogenic drinking water. The reduction in the number of removals can be at least one pig, or at least two pigs, or at least 3 pigs relative to the control.
[0085] The method of the present description can enhance the growth of the PW piglets. The method can contribute to increasing the average daily weight gain, final weight of the PW piglets.
[0086] Representative features of the present invention are set out in the following clauses, which stand alone or may be combined, in any combination, with one or more features disclosed in the text of the Specification.
[0087] The present invention is as set out in the following clauses:PT-2055-WO-PCT
[0088] Clause 1: A method of production of livestock animals in a nursery comprising: providing drinking water supplemented with a phytogenic composition to post-weaning piglets, wherein the phytogenic composition comprises essential oils, wherein the PW piglets have improved performance, the improved performance comprising a reduction in mortality rate in the nursery relative to PW piglets provided drinking water without the phytogenic composition.
[0089] Clause 2: The method of clause 1, wherein the essential oils comprise eugenol and carvacrol.
[0090] Clause 3: The method of any one of the preceding clauses, wherein the phytogenic composition comprises between about 5% by weight and about 40% by weight of the essential oils, preferably about 7.5% by weight of the essential oils.
[0091] Clause 4: The method of any one of the preceding clauses, wherein the drinking water comprises the phytogenic composition at an amount between about 10ppm and 1000ppm, preferably between 100ppm and 300ppm.
[0092] Clause 5: The method of any one of the preceding clauses, wherein the phytogenic composition comprises between about 1% by weight and about 20% by weight of the eugenol and between about 1% by weight and about 20% by weight of the carvacrol, preferably the phytogenic composition comprises about 3.75% by weight of the eugenol and about 3.75% by weight of the carvacrol.
[0093] Clause 6: The method of any one of the preceding clauses, wherein the drinking water comprises eugenol at an amount between 1ppm and 30ppm and carvacrol at an amount between 1ppm and 30ppm.
[0094] Clause 7: The method of any one of the preceding clauses, wherein the drinking water comprises the phytogenic composition at a concentration between about 0.005% to 0.1% by weight.
[0095] Clause 8: The method of any one of the preceding clauses, wherein the drinking water comprises the phytogenic composition at a concentration of about 0.02% by weight.
[0096] Clause 9: The method of any one of the preceding clauses, wherein the phytogenic composition further comprises an additive.
[0097] Clause 10: The method of any one of the preceding clauses, wherein the phytogenic composition comprises an additive and the additive comprises dextrose.PT-2055-WO-PCT
[0098] Clause 11: The method of any one of the preceding clauses, wherein the essential oils are microencapsulated in an encapsulation matrix.
[0099] Clause 12: The method of any one of the preceding clauses, wherein the drinking water comprising the phytogenic composition is provided for at least 10 days post weaning.
[0100] Clause 13: The method of any one of the preceding clauses, wherein the drinking water comprising the phytogenic composition is provided for at least 14 days post weaning.
[0101] Clause 14: The method of any one of the preceding clauses, wherein the PW piglets have a mortality rate reduced by at least 10% relative to PW piglets in a nursery without the phytogenic composition in the drinking water.
[0102] Clause 15: The method of any one of the preceding clauses, wherein the PW piglets have a mortality rate reduced by at least 25% relative to PW piglets in a nursery without the phytogenic composition in the drinking water.
[0103] Clause 16: The method of any one of the preceding clauses, wherein the PW piglets comprise average size PW piglets, small PW piglets, or a combination thereof.
[0104] Clause 17: The method of any one of the preceding clauses, wherein the method further comprises separating PW piglets, wherein separating PW piglets comprises separating the small PW piglets from the average size PW piglets at the initiation of the PW period, separating PW piglets that display symptoms of disease during the PW period from healthy piglets or a combination thereof.
[0105] Clause 18: The method of any one of the preceding clauses, wherein the improved performance further comprises reduced morbidity, enhanced growth, enhanced health or combinations thereof of the PW piglets in the nursery.
[0106] Clause 19: A phytogenic drinking water composition comprising: drinking water; and a phytogenic composition, wherein the phytogenic composition comprises essential oils, wherein PW piglets in a nursery provided drinking water with the phytogenic composition have a reduced mortality rate relative to PW piglets provided drinking water without the phytogenic composition.
[0107] Clause 20: The composition of clause 19, wherein the essential oils comprise eugenol and carvacrol.
[0108] Clause 21: The composition of clauses 19-20, wherein the phytogenic composition further comprises one or more additives.PT-2055-WO-PCT
[0109] Clause 22: The composition of clauses 19-21, wherein the phytogenic composition comprises between 5% by weight and 40% by weight of the essential oils, preferably the phytogenic composition comprises about 7.5% by weight of the essential oils.
[0110] Clause 23: The composition of clauses 19-22, wherein the drinking water composition comprises the phytogenic composition at an amount between about 10ppm and 1000ppm, preferably between 100ppm and 300ppm.
[0111] Clause 24: The composition of clauses 19-23, wherein the phytogenic composition comprises between 1% by weight and 20% by weight of the eugenol, preferably the phytogenic composition comprises about 3.75% by weight of the eugenol.
[0112] Clause 25: The composition of clauses 19-24, wherein drinking water comprises eugenol at an amount between 1ppm and 30ppm.
[0113] Clause 26: The composition of clauses 19-25, wherein the phytogenic composition comprises between 1% by weight and 20% by weight of the carvacrol, preferably the phytogenic composition comprises about 3.75% by weight of the carvacrol.
[0114] Clause 27: The composition of clauses 19-26, wherein the drinking water comprises carvacrol at an amount between 1ppm and 30ppm.
[0115] Clause 28: The composition of clauses 19-27, wherein the drinking water comprises the phytogenic composition at a concentration between about 0.005% to 0.1% by weight.
[0116] Clause 29: The composition of clauses 19-28, wherein the drinking water comprises the phytogenic composition at a concentration of 0.02% by weight.
[0117] Clause 30: The composition of clauses 19-29, wherein the one or more additives comprises dextrose.
[0118] Clause 31: The composition of clauses 19-30, wherein the essential oils are microencapsulated in an encapsulation matrix.
[0119] Clause 32: The composition of clauses 19-31, wherein the drinking water comprising the phytogenic composition is provided to the piglets for at least 14 days post weaning.
[0120] Clause 33: The composition of clauses 19-32, wherein the drinking water comprising the phytogenic composition is provided to the piglets for at least 21 days post weaning.
[0121] Clause 34: The composition of clauses 19-33, wherein the PW piglets have a mortality rate reduced by at least 10% relative to PW piglets in a nursery without the phytogenic composition in the drinking water.PT-2055-WO-PCT
[0122] Clause 35: The composition of clauses 19-34, wherein the PW piglets have a mortality rate reduced by at least 25% relative to PW piglets in a nursery without the phytogenic composition in the drinking water.
[0123] Clause 36: The composition of clauses 19-35, wherein the PW piglets have a mortality reduced by at least 40% relative to the PW piglets in a nursery without the phytogenic composition in the drinking water by about 42 days post-weaning.
[0124] Clause 37: A phytogenic composition comprising an essential oil core and one or more additives, wherein the essential oil core comprises essential oils, wherein the essential oils comprise eugenol between about 1% by weight and about 15% by weight of the phytogenic composition and carvacrol between about 1% by weight and about 15%% by weight of the phytogenic composition.
[0125] Clause 38: The composition of clause 37, wherein the phytogenic composition comprises eugenol at 3.75% by weight.
[0126] Clause 39: The composition of clauses 37-38, wherein the phytogenic composition comprises carvacrol at 3.75% by weight.
[0127] Clause 40: The composition of clauses 37-39, wherein the composition is included in water at a concentration between about 0.005% to 0.1% by weight.
[0128] Clause 41: The composition of clauses 37-40, wherein the composition is included in the water at a concentration of about 0.02% by weight.
[0129] Clause 42: The composition of clauses 37-41, wherein the one or more additives comprise dextrose.
[0130] Clause 43: The composition of clauses 37-42, wherein the composition comprises the polymer between about 25% by weight and about 90% by weight.
[0131] Clause 44: The composition of any one of clauses 37-43, wherein the eugenol and the carvacrol are microencapsulated.
[0132] The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.PT-2055-WO-PCTExample 1-Determination of Minimum Inhibitory Concentrations
[0133] The minimum inhibitory concentration (MIC) in each assay was optically determined as the lowest concentration of the test compound that completely inhibits visible growth (no obvious cell pellet or turbidity) after the incubation period (18 h at 30°C for C. violaceum, 18 h at 37°C for E. coli O88:H8 and O143:H4). The median value of all replicates was defined as the MIC value of the respective test compound.
[0134] Individual components (Carvacrol and Eugenol), a 1:1 mix of eugenol and carvacrol, and a phytogenic prototype composition were tested. The phytogenic prototype composition is as shown in Fig. 1 with eugenol (3.75%) and carvacrol (3.75%). Phytogenic prototype composition includes 75% dextrose as the carrier. Quorum sensing inhibition assayviolaceum violacein production)
[0135] The influence of the phytogenic test compounds on C. violaceum DSM 30191 was assessed in concentrations ranging from 10000 ppm to 5 ppm. Violacein production was quantified based on the protocol of Skogman et al. (2016). Serial dilutions ranging from 20000 ppm to 10 ppm were prepared from stock solutions (200000 ppm) of the phytogenic test compounds in ^^^^^^^HWKDQRO^^9:5^,QWHUQDWLRQDO^*PE+^ Vienna, Austria). Four technical replicates of each concentration (50 μl in each well) were arranged vertically in Nunc® polystyrene 96-well microtiter plates (Thermo Scientific, Waltham, USA). An overnight culture of C. violaceum in 10 ml tryptic soy broth (TSB) was diluted to approximately 1-2 × 106&)8ÂPO-1in fresh TSB and aliquots of 50 μl were added to each test well and four wells containing only medium, serving as positive growth control without test compounds. An additional four wells containing only TSB were used as negative (sterility) controls. The starting bacterial concentration was verified using the colony count method. The microtiter plates as well as the colony count plates were incubated for 18 h at 30 °C. After the incubation period, MIC values were determined before the cells and violacein pigment were pelleted by centrifugation at 3000 rpm for 10 min. The supernatant was removed from the wells by pipetting and 200 μl ^^^^^^ ethanol (VWR International GmbH) were added to each well. The plates were sealed with Microseal ‘B’ PCR Plate Sealing Film (Bio-Rad, Hercules, USA) and incubated overnight in the dark to allow the pelleted violacein pigment to dissolve. The next day, the plates were centrifuged at 3000 rpm for 10 min to sediment the decolored cells. Subsequently, 100 μl of the violacein-stained supernatant were transferred to aPT-2055-WO-PCT new microtiter plate and the absorbance was measured at 570 nm using a PHOmo microplate reader (Anthos Mikrosysteme GmbH, Friesoythe, Germany). Biofilm inhibition assay
[0136] The effect of the phytogenic test compounds on biofilm formation of E. coli field isolates O88:H8 and O143:H4 was assessed in a broth micro-dilution assay followed by crystal violet staining according to Axmann et al. (2021) with minor modifications. Briefly, phytogenic test compounds were serially diluted in TSB+and arranged vertically in 96-well microtiter plates as described in section Quorum sensing inhibition assay (Chromobacterium violaceum violacein production). The outer columns of the microtiter plates were filled with sterile TSB+to prevent evaporation from the central wells. Overnight cultures of the respective E. coli in TSB+were adjusted to approximately 2 × 106&)8ÂPO-1in fresh TSB+and 50 μl of this dilution were placed in each test well. Four wells containing either only bacterial culture without phytogenic test compounds or sterile TSB+medium served as positive or negative control, respectively. The plates were incubated under aerobic conditions for 18 h at 37°C.
[0137] The antimicrobial activity of the phytogenic test compounds was evaluated as described in section Determination of Minimum Inhibitory Concentrations. After removal of theculture medium, the microtiterplates were washed twice with deionized H2O (diH2O) to removethe unattached cells and mediacomponents and air-dried for 30 min. The attached biomass wasstained with 130 μl of a 0.1% (w / v) crystalviolet solution (Alfa Aesar by Thermo Fisher GmbH,Kandel, Germany) in diH2O for 20 min at room temperature. Afterwards, the microtiter plateswere washed 3 times with diH2O and left to air-drycompletely. The adherent dye was solubilizedwith 130 μl 30% (v / v) acetic acid (Merck KgaA, Darmstadt, Germany) and transferred to a new microtiter plate. Absorbance was measured at 570 nm with a PHOmo microplate reader (Anthos Mikrosysteme GmbH). The mean of the four replicates was calculated followed by subtraction of the negative control measurements and the results were expressed as a percentage biofilm relative to the positive control. Each test compound was assayed three to four times. In this study, the entirety of adherent cell mass which was stained by the crystal violet solution is referred to as biofilm without distinction of the maturation stage.
[0138] Results:
[0139] Minimum inhibitory concentrations for the individual substances, a 1:1 combination and the phytogenic prototype are shown in Table 1.PT-2055-WO-PCT Table 1
[0140] Table 1 shows the minimum inhibitory concentration of carvacrol, eugenol, their 1:1 mixture as well as the complete prototype with its carrier matrix against E. coli strains O88:H8 and O143:H4 and C. violaceum. The MIC of the 1:1 mix compares very well to the single components showing they contribute equally to the effect of the mixture. The phytogenic prototype has the highest MIC values with a concentration of 7.5% active compounds in its formulation. Considering the difference to pure compounds and their mixture, the MIC value is around 8.3 times higher, compared to 13.3 times lower amounts of actives.
[0141] similar ranking can be seen with both an E. coli biofilm assay (Figure 2) and a C. violaceum quorum sensing assay (Figure 3). The control without test compounds is set to 100% in these results. Carvacrol is the most potent substance in these assays, with a >50% reduction of biofilm formation or violacein production at 150 ppm and 40 ppm, respectively . The prototype shows a similar difference as in the MIC ranking, being 8.3 times less effective than carvacrol alone while its composition consists of 13.3 times less active compounds. A difference in these ranking comparisons is also seen in the C. violaceum quorum sensing assay. The phytogenic prototype requires about 15 times higher concentration (600 ppm vs 40 ppm) compared to carvacrol or the 1:1 mix of carvacrol and eugenol. Considering the dilution steps used this would most likely reflect the 13.3 times difference in active compounds.
[0142] These results show a good correlation between active substances and their effect in these assays. Encapsulating the active compounds can stabilize the components and also improve biological efficacy.
[0143] PROPHETIC EXAMPLE-Evaluation of water supplementation
[0144] Materials and Methods: The study will include, for example, about 1,100 weaned pigs / treatment with about 22pigs / pen. The pigs can be randomly placed into pens not accounting for sex. The production period can be 12-40lbs. Treatments can be applied to pigs between 12- 26lbs.
[0145] There can be two treatment groups:PT-2055-WO-PCT
[0146] Treatment A: Plain water and a basal diet (Control)
[0147] Treatment B: Water supplemented with 0.02% of the phytogenic prototype and a basal diet. 1. The phytogenic prototype will include 3.75% of eugenol and 3.75% of carvacrol. Eugenol and carvacrol are microencapsulated according to the process described in as described in EP patent 1419811A1. The additive dextrose will be included as a carrier in the phytogenic prototype.
[0148] The amount of the phytogenic prototype is described below.
[0149] Animals can be placed as follows:
[0150] General population: n = 37 pens per treatment; Pigs / pen = 22-23;
[0151] Initial BW = can be about 14.5 lb;
[0152] Mixed sex and weight pens; Pigs randomly allotted to pens
[0153] Small Pens: n = 5 pens per treatment; Pigs / pen = 21-23;
[0154] Initial BW = can be about 10.1 lb;
[0155] Mixed sex and weight pens; Pigs randomly allotted to pens
[0156] Table 2 shows the characteristics of each of the phases. Table 2
[0157] Treatments (40 reps / TRT):
[0158] Treatment A: Plain water and a basal commercially available diet (Control)
[0159] Treatment B: Water will be supplemented with phytogenic prototype (0.02wt% in water “intake” / pig / day) and a basal commercially available diet.
[0160] Diets: All water treatments will be fed same commercial diets during phase 1 and 2, and fed common commercial phase 3 diets during phase 3.
[0161] Duration: Water supplements will be given from d 0 – 10 postweaning.
[0162] Water Medications: Will be administrated along the treatments when intervention is necessary.PT-2055-WO-PCT
[0163] Performance variables that will be measured are (average body weight, average daily gain (ADG), average daily feed intake (ADFI), and gain:feed ratio (G:F).
[0164] Count data (health variables – mortality and removals) can be analyzed.
[0165] Contrasts can test the effect of water treatments: plain water vs. water with Phytogenic prototype.
[0166] Water disappearance and stock solution will be monitored daily.
[0167] Phase 1 Objective: The primary purpose of phase 1 will be to determine the effects of water supplementation on performance and health of nursery pigs. Pen weight and feed consumption will be recorded after assigned days on test. Scour scores will be taken on day 3, 6, 12, 17, and 23 post-weaning. The feeding schedule for Treatments A-B will be about 1.81kg / pig.
[0168] Phase 2 Objective: The primary purpose of phase 2 will be to evaluate carry over responses on performance of nursery pigs and health of nursery pigs.
[0169] Pigs will be fed the same dietary sequence as the previous phase. Pen weight and feed consumption can be recorded after assigned days on test. The feeding schedule for Treatments A-B can be about 5.44 kg / pig.
[0170] Phase 3 Objective: The primary purpose of phase 3 will be to evaluate carry over responses on performance of nursery pigs and health of nursery pigs. Pigs can be fed a common diet. Phase three diet can be fed until pigs were shipped to finishers. Pen weight and feed consumption can be measured at the end of the trial.
[0171] Closeout mortalities will be monitored and include the pigs that died during the trial with addition of the pigs that were removed during the trial that end up dead. Removals will be the pigs that were removed from the original pen due to health issues and were placed in another pen for extra care and monitoring.
[0172] In this document, the terms “a,” “an,” or “the” are used to include one or more than one unless the context clearly dictates otherwise. The term “or” is used to refer to a nonexclusive “or” unless otherwise indicated. All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls.PT-2055-WO-PCT
[0173] Values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range were explicitly recited. For example, a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement “about X to Y” has the same meaning as “about X to about Y,” unless indicated otherwise. Likewise, the statement “about X, Y, or about Z” has the same meaning as “about X, about Y, or about Z,” unless indicated otherwise.
[0174] Unless expressly stated, ppm (parts per million), percentage, and ratios are on a by weight basis. Percentage on a by weight basis is also referred to as wt% or % (wt) below.
Claims
PT-2055-WO-PCT CLAIMS What is claimed is:
1. A method of production of livestock animals in a nursery comprising: providing drinking water comprising a phytogenic composition to post-weaning (PW) piglets, wherein the phytogenic composition comprises essential oils, wherein the PW piglets have improved performance, the improved performance comprising a reduction in mortality rate in the nursery relative to PW piglets provided drinking water without the phytogenic composition.
2. The method of claim 1, wherein the essential oils comprise eugenol and carvacrol.
3. The method of any one of the preceding claims, wherein the phytogenic composition comprises between about 5% by weight and about 40% by weight of the essential oils, preferably about 7.5% by weight of the essential oils.
4. The method of any one of the preceding claims, wherein the drinking water comprises the phytogenic composition at an amount between about 10ppm and 1000ppm, preferably between 100ppm and 300ppm.
5. The method of any one of the preceding claims, wherein the phytogenic composition comprises between about 1% by weight and about 20% by weight of the eugenol and between about 1% by weight and about 20% by weight of the carvacrol, preferably the phytogenic composition comprises about 3.75% by weight of the eugenol and about 3.75% by weight of the carvacrol.
6. The method of any one of the preceding claims, wherein the drinking water comprises eugenol at an amount between 1ppm and 30ppm and carvacrol at an amount between 1ppm and 30ppm.
7. The method of any one of the preceding claims, wherein the drinking water comprises the phytogenic composition at a concentration between about 0.005% to 0.1% by weight.PT-2055-WO-PCT 8. The method of any one of the preceding claims, wherein the drinking water comprises the phytogenic composition at a concentration of about 0.02% by weight.
9. The method of any one of the preceding claims, wherein the phytogenic composition further comprises an additive.
10. The method of any one of the preceding claims, wherein the phytogenic composition comprises an additive, wherein the additive comprises dextrose.
11. The method of any one of the preceding claims, wherein the essential oils are microencapsulated in an encapsulation matrix.
12. The method of any one of the preceding claims, wherein the drinking water comprising the phytogenic composition is provided for at least 10 days post weaning.
13. The method of any one of the preceding claims, wherein the drinking water comprising the phytogenic composition is provided for at least 14 days post weaning.
14. The method of any one of the preceding claims, wherein the PW piglets have a mortality rate reduced by at least 10% relative to PW piglets in a nursery without the phytogenic composition in the drinking water.
15. The method of any one of the preceding claims, wherein the PW piglets have a mortality rate reduced by at least 25% relative to the PW piglets in a nursery without the phytogenic composition in the drinking water.
16. The method of any one of the preceding claims, wherein the PW piglets comprise average size PW piglets, small PW piglets, or a combination thereof.
17. The method of any one of the preceding claims, wherein the method further comprises separating PW piglets, wherein separating PW piglets comprises separating the small PW piglets from the average size PW piglets at the initiation of the PW period, separating PWPT-2055-WO-PCT piglets that display symptoms of disease during the PW period from healthy piglets or a combination thereof.
18. The method of any one of the preceding claims, wherein the improved performance further comprises reduced morbidity, enhanced growth, enhanced health or combinations thereof of the PW piglets in the nursery.
19. A phytogenic drinking water composition comprising: drinking water; and a phytogenic composition, wherein the phytogenic composition comprises essential oils, wherein PW piglets in a nursery provided the drinking water comprising the phytogenic composition have a reduced mortality rate relative to PW piglets provided drinking water without the phytogenic composition.
20. The composition of claim 19, wherein the essential oils comprise eugenol and carvacrol.
21. The composition of claims 19-20, wherein the phytogenic composition further comprises one or more additives.
22. The composition of claims 19-21, wherein the phytogenic composition comprises between 5% by weight and 40% by weight of the essential oils, preferably the phytogenic composition comprises about 7.5% by weight of the essential oils.
23. The composition of claims 19-22, wherein the drinking water composition comprises the phytogenic composition at an amount between about 10ppm and 1000ppm, preferably between 100ppm and 300ppm.
24. The composition of claims 19-23, wherein the phytogenic composition comprises between 1% by weight and 20% by weight of the eugenol, preferably the phytogenic composition comprises about 3.75% by weight of the eugenol.PT-2055-WO-PCT 25. The composition of claims 19-24, wherein the drinking water comprises eugenol at an amount between 1ppm and 30ppm.
26. The composition of claims 19-25, wherein the phytogenic composition comprises between 1% by weight and 20% by weight of the carvacrol, preferably the phytogenic composition comprises about 3.75% by weight of the carvacrol.
27. The composition of claims 19-26, wherein the drinking water comprises carvacrol at an amount between 1ppm and 30ppm.
28. The composition of claims 19-27, wherein the drinking water comprises the phytogenic composition at a concentration between about 0.005% to 0.1% by weight.
29. The composition of claims 19-28, wherein the water comprises the phytogenic composition at a concentration of 0.02% by weight.
30. The composition of claims 19-29, wherein the one or more additives comprises dextrose.
31. The composition of claims 19-30, wherein the essential oils are microencapsulated in an encapsulation matrix.
32. The composition of claims 19-31, wherein the drinking water comprising the phytogenic composition is provided to the piglets for at least 14 days post weaning.
33. The composition of claims 19-32, wherein the drinking water comprising the phytogenic composition is provided to the piglets for at least 21 days post weaning.
34. The composition of claims 19-33, wherein the PW piglets have a mortality rate reduced by at least 10% relative to PW piglets in a nursery without the phytogenic composition in the drinking water.PT-2055-WO-PCT 35. The composition of claims 19-34, wherein the PW piglets have a mortality rate reduced by at least 25% relative to PW piglets in a nursery without the phytogenic composition in the drinking water.
36. The composition of claims 19-35, wherein the PW piglets have a mortality reduced by at least 40% relative to the PW piglets in a nursery without the phytogenic composition in the drinking water by about 42 days post-weaning.
37. A phytogenic composition comprising an essential oil core and one or more additives, wherein the essential oil core comprises essential oils, wherein the essential oils comprise eugenol between about 1% by weight and about 15% by weight of the phytogenic composition and carvacrol between about 1% by weight and about 15%% by weight of the phytogenic composition.
38. The composition of claim 37, wherein the phytogenic composition comprises eugenol at about 3.75% by weight.
39. The composition of any one of claims 37-38, wherein the phytogenic composition comprises carvacrol at about 3.75% by weight.
40. The composition of any one of claims 37-39, wherein the composition is included in water at a concentration between about 0.005% to 0.1% by weight.
41. The composition of any one of claims 37-40, wherein the composition is included in the water at a concentration of about 0.02% by weight.
42. The composition of any one of claims 37-41, wherein the one or more additives comprises dextrose.
43. The composition of any one of claims 37-42, wherein the composition comprises the polymer between about 25% by weight and about 90% by weight.PT-2055-WO-PCT 44. The composition of any one of claims 37-43, wherein the eugenol and the carvacrol are microencapsulated.
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