combination, use thereof, method for producing said combination and formulated composition for admin

专利摘要:
COMBINATION, COMPOSITION, AND METHOD FOR ADMINISTERING THE COMBINATION OR COMPOSITION TO ANIMALS. Embodiments of a combination and/or composition for administration to animals are described herein. In some embodiments, the combination and/or composition can be administered to treat and/or prevent a disease in animals. In some embodiments, the combination and/or composition can be administered to promote health in animals. In some embodiments, the combination comprises a composition comprising Yucca schidigera, Quillaja saponária, and combinations thereof, and a composition comprising an antimicrobial, an antibiotic, an anticoccidial, a vaccine, or combinations thereof. The combinations or compositions described herein can also improve feed conversion rates in animals.
公开号:BR112016027335B1
申请号:R112016027335-4
申请日:2015-05-22
公开日:2021-06-08
发明作者:Kenneth W. Bafundo；Bruce A. Johnson；David Calabotta；Wendell Knehans
申请人:Phibro-Animal Health Corporation；Desert King International Llc；
IPC主号:

专利说明:

CROSS REFERENCE ON RELATED REQUEST
[001] This application claims priority over U.S. Provisional Application 62/002,527, filed May 23, 2014, the entirety of which is incorporated herein by reference. FIELD
[002] This disclosure relates to modalities of a combination and/or composition for administration to animals, as well as methods for producing the combination and/or composition and administering the same to animals. BACKGROUND
[003] Feed conversion rates (or ratios) provide livestock producers with a method to monitor the effectiveness of animal husbandry. Estimating the amount of feed required per unit of body gain for animals provides livestock producers with the ability to effectively budget the costs associated with raising animals. Feed conversion rates can also be used to reduce risks associated with animal husbandry, such as lack or wasted feed, and can make it easier to determine profit margins.
[004] Coccidiosis is a parasitic disease of the intestinal tract of animals caused by coccidian protozoa of the genus Eimeria. The disease can spread among animals through contact with infected feces through an infectious form called an oocyst. Coccidiosis is a significant disease of certain animals, such as cattle or poultry, as it can affect animals at a very young age. It can be fatal or compromise the animal's health, thus harming the animals' feed conversion rate. Thus, animal production, reproductive efficacy and health are adversely affected by coccidiosis. Diseases such as coccidiosis cause significant economic losses in certain animal industries. Such diseases can also negatively affect the health of domestic animals. SUMMARY
[005] Embodiments of a combination comprising a first combination comprising yucca, quillaja or both are disclosed herein; and a second composition comprising an antibiotic, an antimicrobial, an anticoccidial agent or a combination thereof. In some embodiments, the combination comprises 200 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria, Yucca schidigera, or a combination thereof and a second composition comprising an antimicrobial, an antibiotic, an anticoccidial agent, or combinations thereof . The second composition may comprise 10 ppm to 30 ppm Virginiamycin and/or 50 ppm to 70 ppm Salinomycin. In some embodiments, the first composition may comprise a mixture of Quillaja saponaria and Yucca schidigera in a ratio in the range of 70:30 Quillaja saponaria:Yucca schidigera to 90:10 Quillaja saponaria:Yucca schidigera.
The combination modalities may also include a third composition comprising a vaccine, and in some embodiments the vaccine is a composition comprising oocysts derived from Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria tenella, Eimeria mitis , Eimeria necatrix, Eimeria praecox, Eimeria brunetti, Eimeria hagani or combinations thereof.
[007] In some embodiments, the first and second compositions, and optionally the third composition, are addition mixed to form an addition mixed composition. Compositions can be mixed simultaneously or sequentially. The addition-mixed composition may further be add-mixed with a feed to form a feed-addition mixture.
[008] The combination can be formulated for administration to a bird. In some embodiments, the combination is formulated for administration to chickens and turkeys. In some other embodiments, the combination is formulated for administration to animals other than chickens or turkeys.
[009] The components of the addition-mixed composition, the addition-mixed composition, or both, may be sized, concentrated or diluted to facilitate addition-mixing, facilitate administration to an animal or combinations thereof. The combination may further comprise a vitamin, a trace mineral, a bulking agent, a vehicle, a colorant, a flavor enhancer, or any combination thereof, and in some embodiments, the combination further comprises corn, corn flour. soybean, wheat, barley, rye, canola, corn oil, limestone, salt, soluble distillers dry grains (DDGS), dicalcium phosphate, sodium sesquicarbonate, methionine source, lysine source, L-threonine, choline or any combination of them.
[0010] A method comprising administering the composition and/or combinations described herein is also disclosed herein. In some embodiments, the method further comprises administering a third composition comprising a coccidiosis vaccine comprising oocysts derived from Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria tenella, Eimeria mitis, Eimeria necatrix, Eimeria praecox, Eimeria brunetti , Eimeria hagani or combinations thereof. The first and second compositions, and the third composition and/or feed if present, may be administered substantially simultaneously, or they may be administered sequentially, in any order.
[0011] There is further disclosed a method for producing a combination which comprises providing a first composition comprising Quillaja saponaria, Yucca schidigera, or both; providing a second composition comprising an antimicrobial agent, an antibiotic, an anticoccidial agent or a combination thereof; and mixing the first composition and the second composition. The method may further comprise admixing the blend with a feed to form an addition mixed feed. In some embodiments, the method further comprises formulating the first and/or second compositions for mixing with the feed to provide a substantially homogeneous addition mixed feed.
In certain embodiments, the method further comprises combining the first composition, the second composition, or both, with a third composition comprising a vaccine.
[0013] The above or other purposes, features and advantages of the present disclosure will become more apparent from the following detailed description proceeding with reference to the accompanying figures. BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Figure 1 is a graph of the average weight (kg) and adjusted feed conversion of birds fed for 28 days with bird feed (Treatment Group 1), and the bird feed comprising 125 ppm of one modality of one composition according to the present disclosure (composition modality (Treatment Group 2), 250 ppm of the same composition modality (Treatment Group 3), 500 ppm of the same composition modality (Treatment Group 4) and 2,500 ppm of the same type of composition (Treatment Group 5).
[0015] Figure 2 is a graph of the mean weight (kg) and adjusted feed conversion obtained from birds fed for 28 to 42 days with bird food (Treatment Group 1), and the bird feed comprising 125 ppm of a compounding modality (Treatment Group 2), 250 ppm of a compounding modality (Treatment Group 3), 500 ppm of a compounding modality (Treatment Group 4) and 2,500 ppm of a compounding modality (Treatment Group Treatment 5).
[0016] Figure 3 is a graph of mean weight (kg) and adjusted feed conversion obtained from birds fed for 42 days on bird feed (Treatment Group 1), and bird feed comprising 125 ppm of a compounding modality (Treatment Group 2), 250 ppm of a compounding modality (Treatment Group 3), 500 ppm of a compounding modality (Treatment Group 4) and 2,500 ppm of a compounding modality (Treatment Group 5 ).
[0017] Figure 4 is a graph of bird weight gain (kg) illustrating the results obtained from feeding birds with several different treatments of a composition modality (0ppm, 150ppm, 200ppm and 250ppm ) and Virginiamycin (0 ppm and 22 ppm), with the graph giving the results obtained after 18 days of feeding.
[0018] Figure 5 is a graph of bird weight gain (kg) illustrating the results obtained from feeding birds with several different treatments of a composition modality (0ppm, 150ppm, 200ppm and 250ppm ) and Virginiamycin (0 ppm and 22 ppm), with the graph providing the results obtained after 18 to 32 days of feeding.
[0019] Figure 6 is a graph of bird weight gain (kg) illustrating the results obtained from feeding birds with several different treatments of a composition modality (0ppm, 150ppm, 200ppm and 250ppm ) and Virginiamycin (0 ppm and 22 ppm), with the graph providing the results obtained after 0 to 32 days of feeding.
[0020] Figure 7 is a graph of bird weight gain (kg) illustrating the results obtained from feeding birds with several different treatments of a composition modality (0ppm, 150ppm, 200ppm and 250ppm ) and Virginiamycin (0 ppm and 22 ppm), with the graph providing the results obtained after 32 days of feeding.
[0021] Figure 8 is a graph of bird weight gain (kg) illustrating the results obtained from feeding birds with several different treatments of a composition modality (0ppm, 150ppm, 200ppm and 250ppm ) and Virginiamycin (0 ppm and 22 ppm), with the graph providing the results obtained after 32 to 42 days of feeding.
[0022] Figure 9 is a graph of bird weight gain (kg) illustrating the results obtained from feeding birds with several different treatments of a composition modality (0 ppm, 150 ppm, 200 ppm and 250 ppm ) and Virginiamycin (0 ppm and 22 ppm), with the graph giving the results obtained after 0 to 42 days of feeding.
[0023] Figure 10 is a graph of bird weight gain (kg) illustrating the results obtained from feeding birds with several different treatments of a composition modality (0 ppm, 150 ppm, 200 ppm and 250 ppm ) and Virginiamycin (0 ppm and 22 ppm), with the graph giving the results obtained after 42 days of feeding.
[0024] Figure 11 is a graph of feed conversion rates illustrating the results obtained 18 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0025] Figure 12 is a graph of feed conversion rates illustrating the results obtained 28 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0026] Figure 13 is a graph of feed conversion rates illustrating the results obtained 42 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0027] Figure 14 is a graph of body weight gain illustrating the results obtained 18 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0028] Figure 15 is a graph of body weight gain illustrating the results obtained 28 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0029] Figure 16 is a graph of body weight gain illustrating the results obtained 42 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0030] Figure 17 is a graph of oocysts per gram of feces illustrating the results obtained 21 days after feeding birds vaccinated with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0031] Figure 18 is a graph of post-challenge lesion scores illustrating results obtained 21 to 28 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a modality of composition and/or 0 ppm or 22 ppm Virginiamycin.
[0032] Figure 19 is a graph of post-challenge lesion scores illustrating the results obtained 28 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin, where the results were grouped by Virginiamycin levels.
[0033] Figure 20 is a graph of the adjusted feed conversion illustrating the results obtained 18 days after feeding birds with different combinations comprising a composition modality (0 ppm and 250 ppm) and/or Salinomycin (0 ppm and 66 ppm).
[0034] Figure 21 is a graph of the adjusted feed conversion illustrating the results obtained 28 days after feeding birds with different combinations comprising a composition modality (0 ppm and 250 ppm) and/or Salinomycin (0 ppm and 66 ppm).
[0035] Figure 22 is a graph of the adjusted feed conversion illustrating the results obtained 42 days after feeding birds with different combinations comprising a composition modality (0 ppm and 250 ppm) and/or Salinomycin (0 ppm and 66 ppm).
[0036] Figure 23 is a graph of body weight gain illustrating the results obtained 18 days after feeding birds with different combinations comprising a composition modality (0 ppm and 250 ppm) and/or Salinomycin (0 ppm and 66 ppm).
[0037] Figure 24 is a graph of body weight gain illustrating the results obtained 28 days after feeding birds with different combinations comprising a composition modality (0 ppm and 250 ppm) and/or Salinomycin (0 ppm and 66 ppm).
[0038] Figure 25 is a graph of body weight gain illustrating the results obtained 42 days after feeding birds with different combinations comprising a composition modality (0 ppm and 250 ppm) and/or Salinomycin (0 ppm and 66 ppm).
[0039] Figure 26 is a graph of oocysts per gram of feces illustrating the results obtained 28 days after feeding vaccinated birds with different feed combinations comprising a composition modality (0 ppm and 250 ppm) and/or Salinomycin (0ppm and 66ppm).
[0040] Figure 27 is a graph of post-challenge lesion scores illustrating the results obtained 28 days after feeding vaccinated birds with different feed combinations comprising 0 ppm, 200 ppm or 250 ppm of a composition modality and/or 0 ppm or 22 ppm Virginiamycin.
[0041] Figure 28 is a graph of oocysts per gram of faeces illustrating the results at day 18 for birds fed (a) salinomycin and 250 mg of a composition modality or (b) salinomycin alone.
[0042] Figure 29 is a graph of oocysts per gram of faeces illustrating the results at day 28 for birds fed salinomycin and 250 mg of a compounding modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0043] Figure 30 is a graph of the adjusted feed conversion illustrating the results at day 18 for birds fed salinomycin and 250 mg of a composition modality on days 0 to 42, days 0 to 28, days 29 to 42, and days 19 to 42.
[0044] Figure 31 is a graph of the adjusted feed conversion illustrating the results at day 28 for birds fed salinomycin and 250 mg of a composition modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0045] Figure 32 is a graph of the adjusted feed conversion illustrating the results at day 42 for birds fed salinomycin and 250 mg of a composition modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0046] Figure 33 is a graph of the adjusted feed conversion illustrating the results on days 29 to 42 for birds fed salinomycin and 250 mg of a composition modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0047] Figure 34 is a graph of body weight gain (kg) illustrating the results on day 18 for birds fed salinomycin and 250 mg of a compounding modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0048] Figure 35 is a graph of body weight gain (kg) illustrating the results on day 28 for birds fed salinomycin and 250 mg of a compounding modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0049] Figure 36 is a graph of body weight gain (kg) illustrating the results on day 42 for birds fed salinomycin and 250 mg of a compounding modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0050] Figure 37 is a graph of body weight gain (kg) illustrating the results on days 29 to 42 for birds fed salinomycin and 250 mg of a compounding modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0051] Figure 38 is a graph of the adjusted feed conversion illustrating the effects of a compounding modality in birds vaccinated with a coccidiosis vaccine at birth where the results illustrated are for birds that were not fed the compounding modality (left bar) and for birds that have been fed the composition for different periods of time (right bar); results were measured on day 18.
[0052] Figure 39 is a graph of the adjusted feed conversion illustrating the effects of a compounding modality on birds vaccinated with a coccidiosis vaccine at birth where the results illustrated are for birds that were not fed with the modality. composition (left bar) and for birds that were fed the composition for different periods of time (right bar); results were measured on day 28.
[0053] Figure 40 is a graph of the adjusted feed conversion illustrating the results on day 42 for birds that received a coccidiosis vaccine and were fed 0 mg or 250 mg of a composition modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0054] Figure 41 is a graph of body weight gain illustrating the effects of a compounding modality on birds vaccinated with a coccidiosis vaccine at birth where the results illustrated are for birds that were not fed the compounding modality (left bar) and for birds that have been fed the composition for different periods of time (right bar); results were measured on day 18.
[0055] Figure 42 is a graph of body weight gain illustrating the effects of a compounding modality on birds vaccinated with a coccidiosis vaccine at birth where the results illustrated are for birds that were not fed the compounding modality (left bar) and for birds that have been fed the composition for different periods of time (right bar); results were measured on day 28.
[0056] Figure 43 is a graph of body weight gain illustrating the results on day 42 for birds that received a coccidiosis vaccine and were fed 0 mg or 250 mg of a composition modality on days 0 to 42, days 0 to 28, days 29 to 42 and days 19 to 42.
[0057] Figure 44 is a graph of oocysts per gram of faeces illustrating the results on day 18 for birds that received a coccidiosis vaccine and were fed 0 mg or 250 mg of a compounding modality on days 0 to 42. days 0 to 28, days 29 to 42 and days 19 to 42.
[0058] Figure 45 is a graph of oocysts per gram of faeces illustrating the results on day 28 for birds that received a coccidiosis vaccine and were fed 0 mg or 250 mg of a compounding modality on days 0 to 42. days 0 to 28, days 29 to 42 and days 19 to 42. DETAILED DESCRIPTION
[0059] This disclosure relates to modalities of a combination comprising quillaja (eg Quillaja saponaria), yucca (eg Yucca schidigera), an antimicrobial, an antibiotic, an anticoccidial agent and/or a vaccine, such as a coccidiosis vaccine. Methods for administering the composition and/or combination modalities disclosed herein are described, as they are methods of treating and/or preventing certain diseases, such as coccidiosis, in animals using the disclosed combination modalities and /or composition modes. I. TERMS AND DEFINITIONS
[0060] The following explanations of terms and abbreviations are provided to further describe the present disclosure and guide those of ordinary skill in the art in practicing the present disclosure. As used herein, "comprises" means "which includes", and the singular forms "a" or "an" or "the" include plural referents unless the context clearly dictates otherwise. The term "or" refers to a single element of certain alternative elements or a combination of two or more elements, unless the context clearly indicates otherwise.
[0061] Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art to which this disclosure belongs. While 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 are not intended to be limiting. Other features of the disclosure are apparent from the following detailed description and claims.
[0062] Unless otherwise indicated, all numbers expressing amounts of components, molecular weights, percentages, temperatures, times and so on, as used in the specification or claims, shall be understood to be modified by the term "about". Consequently, unless otherwise stated, implicitly or explicitly, the stated numerical parameters are approximations which may depend on the required desired properties and/or detection limits under standard test methods/conditions. In directly and explicitly distinguishing modalities from the discussed prior art, modality numbers are not approximations unless the term "about" is cited. Furthermore, not all alternatives cited in this document are equivalent.
[0063] To facilitate the analysis of the various modalities of disclosure, the following explanations of specific terms are provided:
[0064] Administer: Provide a combination, composition or component disclosed herein by any means suitable for an animal. In some embodiments disclosed herein, administration may refer to oral administration.
[0065] Animal: This term includes, but is not limited to, humans, mammals, aquaculture species and avian species. In some embodiments, this term may refer to mammals, aquaculture species, and avian species that are bred for consumption by humans or that are domestic animals. Such exemplary animal species are provided herein.
[0066] Aquaculture Species: An animal that lives in salt or fresh water. Exemplary aquaculture species are disclosed in this document.
[0067] Binding agent or binder: A material or substance that is used to retain or join other materials to form a cohesive unit. Examples include, but are not limited to, acacia, alginic acid, carboxymethylcellulose, sodium compressible sugar, ethylcellulose gelatin, liquid glucose, methylcellulose, povidone or pregelatinized starch.
[0068] Co-administration: Administering two or more combinations, compositions or components simultaneously or sequentially in any order to an individual to provide overlapping periods of time in which the individual is experiencing the beneficial and/or harmful effects of each component. One or more of the components can be a therapeutic agent. The components can be combined into a single composition or dosage form, or they can be administered as separate components or simultaneously or sequentially in any order. When administered sequentially, the two or more components are administered within a time period effective to provide overlapping time periods in which the individual experiences the effects of each component.
[0069] Combination: A combination comprises two or more compositions or components that are administered so that the effective time period of the first composition or component overlaps the effective time period of the second and subsequent compositions or components. A combination can be a composition comprising the components, or it can be two or more individual components administered substantially simultaneously or sequentially in any order.
[0070] Excipient or vehicle: A physiologically inert substance that is used as an additive in (or with) a combination, composition or component as disclosed herein. As used herein, an excipient or carrier can be incorporated into the particles of a combination, composition or component, or it can be physically mixed with the particles of a combination, composition or component. An excipient or vehicle can be used, for example, to dilute an active agent and/or modify the properties of a combination or composition. Examples of excipients and vehicles include, but are not limited to, calcium carbonate, polyvinylpyrrolidone (PVP), tocopheryl polyethylene glycol 1000 succinate (also known as vitamin E TPGS or TPGS), dipalmitoyl phosphatidyl choline (DPPC), trehalose, bicarbonate sodium, glycine, sodium citrate and lactose.
[0071] Feed conversion rate: A measure of the effectiveness of an animal in converting feed mass into increased body mass; also known in the art as feed conversion ratio (which is expressed herein as a dimensionless number).
[0072] Ration: Anything that can be consumed by an animal. The term "feed" includes, but is not limited to, solid and liquid animal feed (eg, a serving of food), supplements (eg, a mineral supplement), water, and feed additive vehicles (eg, molasses).
[0073] Saponin: A class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in specific abundance in various plant species. More specifically, they are amphipathic glycosides grouped, in terms of structure, by their composition. In certain embodiments, the saponin comprises one or more hydrophilic glycoside moieties combined with a lipophilic triterpene derivative.
[0074] Therapeutically Effective Amount or Effective Amount: An amount or concentration of a specified compound or composition sufficient to achieve the desired effect in an animal being treated for a disease. The therapeutically effective amount can 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 AND COMBINATIONS
Disclosed herein are embodiments of a combination of yucca or quillaja, more typically both, with an antimicrobial, an antibiotic, an anticoccidial agent and/or a vaccine, such as a vaccine against coccidiosis. In some embodiments, the disclosed combination modalities can be administered prophylactically or therapeutically to an animal to reduce the animal's risk of developing specific diseases, such as coccidiosis, and/or to treat an animal suffering from a disease, such as coccidiosis. In some embodiments, the disclosed combinations can also improve the feed conversion rate of certain animals that are bred for consumption by humans, such as poultry and livestock. In still further embodiments, the combinations and compositions can be used to improve overall animal health.
[0076] In some embodiments, the compositions and combinations disclosed herein can be used to significantly reduce the costs associated with animal production. In specific embodiments, the compositions and combinations can significantly reduce the costs associated with poultry production (e.g., poultry) as the compositions and combinations provide improvements in animal health and growth. Just as an example, a reduction of just one point in the feed conversion ratio per 1 million broilers per week can translate into a cost/feed savings of almost $750,000 per year. Some modalities of the combinations disclosed in this document may provide 5 or more point reductions in feed conversion, thus illustrating their utility and superior activity.
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 filamentous, Yucca filifera, Yucca flaccida, Yucca gigantean, Yucca glauca, Yucca gloriosa, Yucca harrimaniae, , Yucca intermedia, Yucca jaliscensis, Yucca lacandonica, Yucca linearifolia, Yucca luminous, Yucca madrensis, Yucca mixtecana, Yucca necopina, Yucca neo-Mexicana, Yucca pallida, Yucca periculosa, Yucca potosina, Yucca queretaroensis, Yucca reverchonii, Yucca rostrata, , Yucca schidigera, Yucca schottii, Yucca sterilis, Yucca tenuistyla, Yucca thompsoniana, Yucca treculeana, Yucca utahensis, or Yucca valida. In certain revealed modalities, the yucca component is Yucca schidigera.
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 Quilla- already smegmadermos. In specific revealed modalities, the quillaja is Quillaja saponaria.
[0079] 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 , flowers, flower stems or seeds or a combination thereof. These plant parts can be used fresh or dried and can be whole, pulverized, crushed, shredded or crushed. 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 skilled in the art or disclosed hereinafter. Plant extracts can include compounds that are saponins, triterpenoids, polyphenols, antioxidants, resveratrol or combinations thereof.
[0080] A composition comprising yucca and/or quillaja can be used to produce the modalities of the disclosed combination. Such compositions may also include carriers and binding agents suitable for formulating the yucca and/or quillaja for administration to animals. In some embodiments, the compositions are formulated for administration to mammals, birds or aquaculture species. In certain independent embodiments, the composition may be a commercially available product, such as a composition comprising Yucca schidigera and Quillaja saponaria, which is sold under the tradename NUTRAFITO PLUS by Desert King International and/or MAGNI-PHI by Phibro Animal Health Corporation . Such compositional modalities may comprise 85% Quillaja saponaria and 15% Yucca schidigera or 90% Quillaja saponaria and 10% Yucca schidigera.
[0081] In some embodiments, the combination also comprises an antimicrobial, an antibiotic, an anticoccidial agent, a vaccine and/or combinations of such components. Combination components can be managed in any order. In some embodiments, an antimicrobial, an antibiotic, an anticoccidial agent, and a vaccine can be administered to the animal prior to administration of yucca, quillaja, or a composition thereof. Alternatively, a vaccine can be administered to an animal, followed by administration of yucca, quillaja, or a composition thereof. In such embodiments, an antimicrobial, an antibiotic and/or an anticoccidial agent can be administered simultaneously with yucca, quillaja or composition thereof; or an antimicrobial, an antibiotic and/or an anticoccidial agent may be administered before or after each of yucca and/or quillaja. In an independent modality, an antimicrobial, an antibiotic and/or an anticoccidial agent need not be administered. In yet another independent modality, a vaccine does not need to be administered.
Suitable antimicrobials and/or antibiotics include, but are not limited to Virginiamycin, Bacitracin MD, Zinc Bacitracin, Tylosin, Lincomycin, Flavomycin, Terramycin, Neo-Terramycin or combinations thereof. In still additional modalities, the antimicrobial or antibiotic can be selected from penicillin, tetracycline, ceftiofur, florfenicol, tilmicosin, enrofloxacin and tulathromycin, procaine penicillin, benzathine penicillin, ampicillin, amoxicillin, spectinomycin, dihydrostreptomycin, chlortetracycline, trimethomycin, gentamicin , oxytetracycline, erythromycin, norfloxacin and combinations thereof.
[0083] Suitable anticoccidial agents include, but are not limited to, ionophores and chemical anticoccidials. Ionophores can include, but are not limited to, Monensin, Salinomycin, Lasalocida, Narasin, Maduramycin, Semduramycin, Laidlomycin, or combinations thereof.
The anticoccidial chemicals may include, but are not limited to, Nicarbazine, Maxiban, Diclazuril, Toltrazuril, Robenidine, Stenorol, Clopidol, Decoquinate, DOT (zoalene), Amprolium or combinations thereof.
[0085] Suitable vaccines can be selected from live coccidiosis vaccines such as COCCIVAC (eg 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 to 500 live sporulated oocysts from each attenuated strain of Eimeria acervulina, E. maxima and E. tenella in a 1% aqueous solution in 1% w/v 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 AND imeria 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.
[0086] In still further embodiments, other vaccines can be used. For example, any vaccine suitable for use in any of the animals described herein can be used in the disclosed combinations and methods. In some embodiments, the vaccine can be selected based on the specific animal receiving the combination. In some embodiments, the vaccine can be selected based on the specific diseases to which a specific animal is susceptible. By way of example only, a vaccine administered to a ruminant can be selected from any vaccine suitable to prevent or treat sudden death (eg clostridial diseases, anthrax and the like), respiratory diseases (eg infectious bovine rhinotracheitis, parainfluenza-3 , bovine viral diarrhea, bovine respiratory syncytial virus, pasteurella, haemophilus somnus and the like), reproductive diseases (IBR, BVD, brucellosis, vibriosis, lepto, trichomoniasis and the like), dysentery (rota and coronaviruses, E. coli and the like) , conjunctivitis, hepatitis E virus, porcine endogenous retrovirus, swine flu virus, porcine parvovirus, and the like. In some modalities, vaccines can be selected from B ALPHA, BAR-GUARD-99, BAR-VAC, BIOMICIN 200, BO-BAC-2X, BOVIKALC, CALIBER, CITADEL, CYDECTIN INJECTABLE, CYDECTIN POUR-ON, ANTITOXIN C and D , DIAQUE, DRY-CLOX, ENTERVENE-D, EXPRESS, EXPRESS FP, HETACIN-K, LYSIGIN, OCU-GUARD MB-1, POLYFLEX, PRESPONSE, PRISM 5, PYRAMID, PYRAMID, PRESPONSE SQ, QUATRACON-2X, SYNANTHIC, TODAY , TOMORROW, TRIANGLE, TRIVIB 5L, TRICHGUARD and similar. In still additional modalities, the vaccine can be selected from CIRCUMVENT PCV G2, CIRCUMVENT PCV-M G2, MAGESTIC 7, MAXIVAC, EXCELL 5.0, PROSYSTEM RCE, PROSYSTEM ROTA, TGE/ROTA, PROSYSTEM TREC and the like.
[0087] The amount of antimicrobial or antibiotic used is within the amounts set forth below, but may depend on the specific antimicrobial or antibiotic used as will be understood by a person of ordinary skill in the art. In a standalone embodiment, the amount of antibiotic or antimicrobial that is used can be a therapeutically effective amount that is at an approved or authorized dosage level for a specific antibiotic. In some embodiments, the amount of antibiotic or antimicrobial used may be in the range of more 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 2000ppm or 1ppm to 1500ppm or 5ppm to 1000ppm or 10ppm to 500ppm or 25ppm to 300ppm. In still further embodiments, the amount of antibiotic or antimicrobial used can range from more than 0 mg/kg body weight to 100,000 mg/kg body weight, such as 0.5 mg/kg to 2,500 mg/kg or 1 mg/kg to 1500 mg/kg or 5 mg/kg to 1000 mg/kg or 10 mg/kg to 500 mg/kg or 25 mg/kg to 300 mg/kg or 10 to 20 mg/kg.
[0088] In some embodiments, the amount of antimicrobial or antibiotic that is included in the composition may be in the range of at least 1 g/t food to 230 g/t food (or at least 1.1 ppm to 256 ppm) , such as at least 1 g/t feed to 220 g/t feed (or at least 1.1 ppm to 243 ppm), at least 1 g/t feed to 100 g/t feed (or at least 1.1 ppm to 110 ppm), at least 1 g/t feed to 50 g/t feed (or at least 1.1 ppm to 55 ppm) or at least 1 g/t feed to 10 g/t of food (or at least 1.1 ppm to 11 ppm). The specific antimicrobials or antibiotics that may be used and the dosage amounts of such antimicrobials and antibiotics include, but are not limited to, the following: Virginiamycin in an amount in the range of 5 g/t of feed to 25 g/t of food (or 5 ppm to 27 ppm, such as 22 ppm); Bacitracin MD in an amount in the range of 40 g/t feed to 220 g/t feed (or 44 ppm to 242 ppm, or 50 ppm to 250 ppm in some other modalities); Zinc Bacitracin in an amount in the range of 40 g/t feed to 220 g/t feed (or 44 ppm to 242 ppm); Tylosin in an amount ranging from 1 g/t feed to 1,000 g/t feed (or 1 ppm to 1,100 ppm); Lincomycin in an amount ranging from 1 g/t feed to 5 g/t feed (or 1 ppm to 6 ppm); Flavomycin in an amount ranging from 1 g/t feed to 5 g/t feed (or 1 ppm to 6 ppm); or combinations thereof.
[0089] The amount of anticoccidial agent, as will be understood by a person of ordinary skill in the art (eg, a veterinarian), may be selected depending on the specific anticoccidial agent used. In some embodiments, the amount of anticoccidial agent used can be a therapeutically effective amount for a specific animal species. In some embodiments, the amount of anticoccidial agent used may be in the range of more 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 1ppm to 1500ppm or 5ppm to 1000ppm or 10ppm to 500ppm or 25ppm to 300ppm. In still further embodiments, the amount of antibiotic or microbial used may range from more than 0 mg/kg body weight to 100,000 mg/kg body weight, such as 0.5 mg/kg to 2,500 mg/kg or 1 mg/kg to 1500 mg/kg or 5 mg/kg to 1000 mg/kg or 10 mg/kg to 500 mg/kg or 25 mg/kg to 300 mg/kg or 10 to 20 mg/kg.
[0090] In some embodiments, the amount of anticoccidial agent that is included in the composition may be in the range of at least 1 g/t of food to 250 g/t of food (or at least 1 ppm to 275 ppm), such as at least 1 g/t feed to 200 g/t feed (or at least 1 ppm to 242 ppm) or at least 1 g/t feed to 150 g/t feed (or at least 1 ppm to feed 165 ppm), at least 1 g/t feed at 100 g/t feed (or at least 1 ppm at 110 ppm) or at least 1 g/t feed at 50 g/t feed (or at least 1 ppm to 55 ppm). The specific 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 in the range of 35 g/t feed to 110 g/t feed (or 38ppm to 121ppm); Salinomycin in an amount in the range of 25 g/t feed to 90 g/t feed (or 27 ppm to 99 ppm); Lasalocid in an amount in the range of 35 g/t feed to 113 g/t feed (or 38 ppm to 125 ppm); Narasin in an amount in the range of 35 g/t feed to 72 g/t feed (or 38 ppm to 79 ppm); Maduramicin in an amount in the range of 2 g/t feed to 7 g/t feed (or 2 ppm to 8 ppm); Semduramycin in an amount in the range of 12 g/t feed to 23 g/t feed (or 13 ppm to 25 ppm); Nicarbazine in an amount in the range of 60 g/t feed to 113 g/t feed (or 66 ppm to 125 ppm); Maxiban in an amount in the range of 40 g/t feed to 90 g/t feed (or 44 ppm to 99 ppm); Diclazuril in an amount in the range of 0.5 g/t feed to 10 g/t feed (or 0.6 ppm to 11 ppm); Toltrazuril in an amount in the range of 1 g/t feed to 10 g/t feed (or 1 ppm to 11 ppm); Robenidine in an amount in the range of 20 g/t feed to 60 g/t feed (or 22 ppm to 66 ppm); Estenorol in an amount in the range of 1.5 g/t feed to 15 g/t feed (or 1.5 ppm to 17 ppm); Clopidol in an amount ranging from 90 g/t feed to 227 g/t feed (or 99 ppm to 250 ppm); Decoquinate in an amount in the range of 18 g/t feed to 27 g/t feed (or 19 ppm to 29 ppm); Zoalene in an amount in the range of 25 g/t feed to 113 g/t feed (or 28 ppm to 125 ppm); Amprolium in an amount in the range of 20 g/t feed to 227 g/t feed (or 22 ppm to 250 ppm).
[0091] The amount of vaccine administered to the animal in combination with any of the components described herein may depend on the type of animal to which the vaccine is administered. In some embodiments, the amount of vaccine used is a therapeutically effective amount in the range of more than 0 ml/animal to 1000 ml/animal or 0.25 ml/animal to 500 ml/animal or 0.5 ml/animal to 150 ml/animal or 1 ml/animal at 100 ml/animal or 2 ml/animal at 50 ml/animal or 3 ml/animal at 25 ml/animal or 5 ml/animal at 15 ml/animal.
[0092] In some embodiments the composition and/or combination further comprises a vitamin, a trace mineral, a bulking agent, a vehicle, a colorant, a flavor enhancer or any combination thereof. In other embodiments, the combination further comprises corn, soy flour, wheat, barley, rye, canola, corn oil, limestone, salt, soluble distillers dry grains (DDGS), dicalcium phosphate, sodium sesquicarbonate, source of methionine, source of lysine, L-threonine, choline or any combination thereof.
[0093] In some embodiments, the combination can be mixed by addition with a ration. The blend can be formulated to form a homogeneous mixture with the feed, such as by crushing, crumbling, grinding or otherwise sizing the blend. Alternatively, the combination can be formulated as a solution, suspension or slurry with the feed or separately and then added to the feed. In embodiments where the combination comprises two or more compositions, the compositions may be formulated separately or substantially together. Any of the compositions disclosed herein can also be mixed by addition with the feed. In some embodiments, a composition and feed can be mixed by addition sequentially, in any order, or substantially simultaneously.
[0094] In some embodiments, the amount of yucca administered to an animal can range from 0 to more than 0.283 kg (10 ounces) per ton of feed, typically more than 0 ounces to at least 0.283 kg (10 ounces) ) per ton of feed, such as 0.028 kg to 0.255 kg (1 ounce to 9 ounces) or 0.028 kg to 0.227 kg (1 ounce to 8 ounces) or 0.028 kg to 0.198 kg (1 ounce to 7 ounces). The amount of quillaja administered to an animal can range from 0 to more than 0.283 kg (10 ounces) per ton of feed, typically more than 0 ounces to at least 0.283 kg (10 ounces) per ton of feed, such such as 0.028 kg to 0.255 kg (1 ounce to 9 ounces) or 0.028 kg to 0.227 kg (1 ounce to 8 ounces) or 0.028 kg to 0.198 kg (1 ounce to 7 ounces). In certain modalities, both yucca and quillaja are administered, and the combined amount administered is from more than 0 ounces to more than 0.283 kg (10 ounces) per ton of feed, such as from 10.028 kg to 0.255 kg (1 ounce to 9 ounces) or 0.028 kg to 0.227 kg (1 ounce to 8 ounces) or 0.057 kg to 0.198 kg (2 ounces to 7 ounces). In an independent modality, Yucca schidigera and Quillaja saponaria can be fed together in an amount ranging from 0.057 kg to 0.227 kg (2 ounces to 8 ounces) per ton of feed.
[0095] In some embodiments, the amount of compositions comprising yucca, quillaja, or a combination thereof that is administered to animals may be an amount sufficient to promote animal health, reduce susceptibility to disease, and/or improve animal health. feed conversion performance in animals. The amount of the composition comprising yucca, quillaja or a combination thereof that can be administered to animals can be measured based on the concentration of the composition per unit of feed, such as in ppm of feed. In such embodiments, the amount of the composition comprising yucca, quillaja, or a combination thereof, may range from more than 0 ppm to 100,000 ppm, such as more than 0 ppm to 5,000 ppm, such as 50 ppm to 3,000 or 100ppm at 2,500ppm or 200ppm at 2,500ppm or 250ppm at 600ppm or 150ppm at 600ppm or 200ppm at 400ppm or 250ppm at 300ppm.
In some embodiments, the amount of the composition comprising yucca, quillaja, or a combination thereof that can be administered to animals can be measured based on the amount of the composition per unit body weight of an animal, such as mg /kg BW/day and/or g/kg BW/day, where "BW" refers to body weight. In some embodiments, the amount of the composition comprising yucca, quillaja, or a combination thereof that is administered may be in the range of more than 0 mg/kg of BW/day to 1,000 mg/kg of BW/day, such as such as 10 mg/kg of BW/day to 500 mg/kg of BW/day or 20 mg/kg of BW/day to 250 mg/kg of BW/day or 30 mg/kg of BW/day at 200 mg/kg of BW/day or 40 mg/kg of BW/day to 100 mg/kg of BW/day. In still further embodiments, the amount of the composition comprising yucca, quillaja, or a combination thereof that can be administered to an animal can be measured based on the amount of composition per animal per day, such as mg/head/day and /or g/head/day. In some embodiments, the amount of the composition comprising yucca, quillaja, or a combination thereof that is administered may be in the range of more than 0 mg/head/day to 100 g/head/day, such as 0.25 mg/head/day at 100 g/head/day or 1 mg/head/day at 75 g/head/day or 10 mg/head/day at 50 g/head/day or 50 mg/head/day at 25 g /head/day.
[0097] In an independent embodiment, a composition comprising Yucca schidigera and Quillaja saponaria can be administered using at least 200 ppm to 5,000 ppm, such as 200 ppm to 2,500 ppm, 200 ppm to 500 ppm, 200 ppm to 300 ppm, 225 ppm to 275 ppm or 230 ppm to 260 ppm. An exemplary embodiment of the disclosed combination comprises 200 ppm, 250 ppm or 300 ppm of a composition comprising Yucca schidigera and Quillaja saponaria.
[0098] In some sports, the ratio between Quillaja saponaria and Yucca schidigera can be in the range of 70:30 (Quillaja saponaria: Yucca schidigera) to 90:10 (Quillaja saponaria: Yucca schidigera). In an independent modality, the ratio between Quillaja saponaria and Yucca schidigera can be 85:15. III. METHODS OF USE
Embodiments of a method for using the compositions and combinations disclosed herein are disclosed herein. Certain embodiments of the method may refer to administering the disclosed compositions and/or combinations to an animal to treat and/or prevent certain diseases, such as coccidiosis. In some disclosed modalities, the administration of the composition and/or combination results in the reduction of negative effects associated with diseases, such as coccidiosis, in animals, such as, but without limitation, unsatisfactory body weights, feed conversion rates, production of oocysts and/or injury scores. In some embodiments, the animal can be an animal raised for consumption by humans or a domestic animal. Examples of animals that can receive the compositions and combinations disclosed herein include, but are not limited to, mammals, such as cattle (e.g., dairy or feed cattle) or pigs; poultry such as domestic poultry (e.g. laying hens, chicken, turkey, goose, duck, Cornish hens, quail, partridge, pheasant, guinea fowl, ostrich, rhea, swan or pigeon); aquaculture species, such as fish (for example, salmon, trout, cod, halibut, snapper, herring, catfish and the like), crustaceans (for example, lobster, shrimp, prawns, crab, krill, crayfish, crayfish, copepods and the like) or molluscs (eg abalone, snails, snails, whelks, clams, oysters, mussels, cockles and the like). In other embodiments, the animal can be a domestic animal, such as a dog, cat, fish or rabbit. In some other embodiments, the animal may be a ruminant species, such as a sheep, goat, cow, deer, bison, buffalo or llama. In still other embodiments, the animal can be an ungulate, such as a horse, donkey or pig.
[00100] In some embodiments, the method comprises administering a combination comprising a first composition and a second composition. The first composition may comprise yucca, quillaja or a combination thereof. In some modalities, the first composition comprises Yucca schidigera, Quillaja saponaria or a combination thereof. In some embodiments, the method may comprise administering an amount of a composition comprising yucca, quillaja or a combination thereof to an animal in amounts ranging from more than 0 ppm to 100,000 ppm, such as 0 ppm to 5,000 ppm or 10 ppm to 3,000 ppm or 25 ppm to 4,000 ppm or 50 ppm to 3,000 or 100 ppm to 2,500 ppm or 200 ppm to 2,500 ppm or 250 ppm to 600 ppm or 250 ppm to 300 ppm.
In some embodiments, the method may comprise administering an amount of a composition comprising yucca, quillaja or a combination thereof in the range of more than 0 mg/head/day to 100 g/head/day, such as 0 .25 mg/head/day to 100 g/head/day or 1 mg/head/day to 75 g/head/day or 10 mg/head/day to 50 g/head/day or 50 mg/head/day to 25 g/head/day.
[00102] In some exemplary embodiments of the disclosed methods, the first composition comprises Yucca schidigera, Quillaja saponaria, and the composition is administered to birds. In such embodiments, the amount of the first composition can range from more than 150 ppm to 5,000 ppm, such as at least 200 ppm to 5,000 ppm, such as at least 200 ppm to 500 ppm or 250 ppm to 300 ppm of a composition comprising Yucca schidigera, Quillaja saponaria or a combination thereof.
[00103] In some embodiments, the methods may comprise administering the compositions disclosed herein to animals other than chickens and turkeys. In some embodiments relating to the administration of a first composition comprising Yucca schidigera and Quillaja saponaria to animals other than chickens or turkeys, the amount of the first composition that is administered may be in the range of more than 0 ppm to 100,000 ppm, such as more than 0ppm to 5,000ppm or 50ppm to 3,000ppm or 100ppm to 2,500ppm or 200ppm to 2,500ppm or 250ppm to 600ppm or 250ppm to 300ppm.
[00104] In some embodiments, the method may comprise administering the compositions or combinations to ruminants or ungulates. Such embodiments may comprise administering a disclosed composition or combination embodiment to a livestock animal in an amount suitable to improve the animal's health or increase milk production. In some embodiments, a composition comprising yucca, quillaja or a combination thereof may be administered to a ruminant or ungulate in an amount ranging from more than 0 ppm to 100,000 ppm, such as more than 0 ppm to 5,000 ppm, such as 50ppm to 3000 or 100ppm to 2,500ppm or 200ppm to 2,500ppm or 250ppm to 600ppm or 150ppm to 600ppm or 200ppm to 400ppm or 250ppm to 300ppm. In exemplary embodiments, the amount of the composition comprising yucca, quillaja or a combination thereof that is administered to certain ruminants, such as swine, is in the range of 50 ppm to 600 ppm. In still further embodiments, a composition comprising yucca, quillaja or a combination thereof may be administered to a ruminant or ungulate in an amount ranging from more than 0 mg/head/day to 100 g/head/day, such as 0.25 mg/head/day to 100 g/head/day or 1 mg/head/day to 75 g/head/day or 10 mg/head/day to 50 g/head/day or 50 mg/head/day at 25 g/head/day.
In still further embodiments, the composition comprising yucca, quillaja or a combination thereof can be administered to aquaculture species. In such embodiments, the methods may comprise providing the aquaculture species with an amount of the composition that is in the range of more than 0 ppm to 100,000 ppm, such as 100 ppm to 50,000 ppm or 200 ppm to 25,000 ppm or 300 ppm to 15,000 ppm or 400 ppm to 5,000 ppm or 500 ppm to 1,000 ppm. In some exemplary embodiments, the amount is in the range of 300ppm to 2000ppm, such as 300ppm to 500ppm.
[00106] In an independent embodiment, the method may comprise administering a composition comprising yucca, quillaja or a combination thereof, wherein the amount of the composition that is administered is in the range of at least 200 ppm to 5,000 ppm, such such as 200ppm to 2,500ppm, 200ppm to 500ppm, 200ppm to 300ppm, 225ppm to 275ppm or 230ppm to 260ppm. An exemplary embodiment of the disclosed combination comprises 200 ppm or 250 ppm of a composition comprising Yucca schidigera and Quillaja saponaria.
[00107] In certain embodiments of the method, the second composition may comprise an antimicrobial, an antibiotic, an anticoccidial agent, a vaccine, or a combination thereof. In some embodiments, the second composition comprises Virginiamycin, Salinomycin or a combination thereof. The amount of antibiotic, antimicrobial, anticoccidial agent or vaccine in the second composition can be in the range of amounts disclosed for such components provided herein. In some embodiments, the amount of antibiotic, antimicrobial, anticoccidial agent or vaccine may range from more than 0 ppm to 500 ppm, such as 10 ppm to 100 ppm or 10 ppm to 70 ppm. In some embodiments, the amount is in the range of at least 10 ppm to 30 ppm Virginiamycin and/or at least 25 ppm to 90 ppm Salinomycin, such as 20 ppm to 80 ppm, 20 ppm to 70 ppm, 20 ppm at 60 ppm or 20 ppm at 50 ppm. Exemplary amounts in certain working embodiments include, but are not limited to, 22 ppm Virginiamycin and/or 50 ppm to 70 ppm, such as 66 ppm Salinomycin.
[00108] The embodiments of the method disclosed herein may also comprise administering the combination comprising the first composition and the second composition in combination with a feed. For example, the combination of the first composition and the second composition can be administered in combination with a suitable amount of feed to obtain an animal having a suitable weight for that specific species. By way of example only, some embodiments may comprise administering the first composition and the second composition in combination with 3.18 kg to 4.54 kg (7 pounds to 10 pounds) of a feed to a chicken. Any suitable dosage of the combination comprising the first composition, the second composition and the feed can be used. In some embodiments, the amount of feed that is fed to the animal can be varied according to its food intake needs as growth occurs.
In some embodiments, the combination may comprise a first composition comprising Yucca schidigera and Quillaja saponaria, a second composition comprising an antimicrobial agent and/or an antibiotic, and a third composition comprising a vaccine. A ration can also be administered in such modalities. The combination of the first, second and/or third composition that is administered may be mixed by addition with a feed prior to administration to the animal, or the feed may be administered before or after the combination of the first, second and/or the third compositions. These modalities are not intended to limit the order of administration, as any suitable order of administration can be selected.
[00110] The combination and/or composition modalities disclosed herein may be administered using any suitable technique. In some embodiments, the combination and/or composition is orally administered by actively introducing the combination into the animal's mouth or orally administered by allowing the bird to ingest the combination and/or composition on its own. The combination and/or composition can be administered to the animal during any stage of its life cycle where it consumes food. In some embodiments, the animal is a bird, such as a domestic slaughter bird, and the combination or composition disclosed herein is administered after hatching (or "day of life"), or at any later stage, such as the day of life to 42 days after birth or 18 days after birth to 35 days after birth. In some embodiments, the combination or composition can be fed to 18 day old broilers and thereafter until mowing, typically at 8 weeks. In some embodiments, the combination or composition can be fed to an animal that is bred for consumption by humans from the day of life to the day of death or from the day of life to a period of time before death.
[00111] The method modalities disclosed in this document improve the feed conversion rate of an animal, such as reducing the feed conversion rate value of the animal, relative to animals that are fed a standard diet ( for example, a ration). In a stand-alone embodiment, the method described herein can be used to improve the feed conversion rate of an animal relative to animals that are just fed a ration in combination with amounts of a composition comprising Yucca schidigera and Quillaja saponaria in the range of 100 ppm to 150 ppm. In some embodiments, the animal is an animal bred for consumption by humans, such as a domestic slaughter bird and/or cattle. A feed conversion ratio (feed conversion ratio) is a measure of an animal's effectiveness in converting feed mass to increased body mass. In embodiments where the combination or composition is administered to a bird, such as a domesticated bird, a bird (e.g., a domesticated bird) that exhibits a low feed conversion rate (e.g., at least one to less than 2, such as more than 1 to 1.8, 1.7, 1.6, 1.5, 1.4 or less) is considered effective as it requires less feeding to achieve a desired weight. In some embodiments, a low feed conversion ratio for pigs can be 1 to 3, such as 1 to 3 or 2 to 3. In some embodiments, a low feed conversion rate to cattle can be 5 to 8, such as 6 to 8 or 7 to 8. In some embodiments, the feed conversion rate of a bird, such as a domestic slaughter bird, can be improved by 0.5% to more than 20%, such as 2% to 10% and, in certain independent modalities, in 3% to 5%. The exemplary embodiments disclosed in this document provide a feed conversion rate improvement for beef-type broilers from 4 to 5%.
[00112] Some modalities of the method disclosed in this document also comprise reducing the concentration of oocysts in the feces of animals, thus reducing the incidence of coccidiosis in such animals, administering a modality of combination and/or composition. In some embodiments, the method may comprise administering a combination or composition disclosed herein to an animal and then evaluating the number of oocysts produced by the animal compared to an animal that did not receive the combination and/or composition. In some modalities, the number of oocysts can be reduced by a factor of 2, 3, 4, 5 or 6 or by about 20% to 80%, such as 20% to 70%, 20% to 60% or 20% to 50%. In certain vaccinated animals, such as domestic poultry, the number of oocysts can be in the range of 10,000 to 20,000 oocysts per gram of faeces which can be reduced by a factor of four or 25%. IV. WORK EXAMPLES
[00113] The subject matter disclosed herein is further understood by reference to the following examples which are intended to be only examples of certain working embodiments of the present disclosure. The present disclosure is not limited in scope by the exemplified embodiments which are only intended to be illustrations of unique aspects of the claimed invention. Any methods that are functionally equivalent fall within the scope of the claimed invention. Various modifications of the presently disclosed matter, in addition to those described herein, will become apparent to those of ordinary skill in the art from the foregoing description and accompanying figures. Such modifications fall within the scope of the appended claims. EXAMPLE 1
[00114] In this example, the revealed combination was administered to broilers to determine doses at which the revealed combination can be administered without negatively affecting feed intake and at what level of administration the toxicity occurs.
[00115] Approximately 50 broilers were kept in pens (8 pens in total, with 50 birds per pen) and fed a composition comprising Yucca schidigera and Quillaja saponaria (referred to in Examples 1 to 5 herein as " the composition" or the "composition of Yucca schidigera and Quillaja saponaria") in different doses. The doses used in that specific example included feed with 0 ppm of the composition, 125 ppm of the composition, 250 ppm of the composition, 500 ppm of the composition and 2,500 ppm of the composition. No disease stimulus was administered to the enclosure. Performance measurements were conducted, food intake was assessed, and the incidence of death measured. The results obtained from this specific modality are graphically illustrated in Figures 1 to 3.
[00116] As illustrated in Figure 1, performance (in the form of average weight and adjusted feed conversion) was first measured after 28 days, with doses of 250 ppm and 500 ppm providing better feed conversion than doses of 0 ppm and /or 125 ppm. Figure 2 illustrates the results obtained from days 28 to 42 of the study, and these results again indicate lower feed conversion numbers for doses of 250 ppm and 500 ppm than those achieved from feeding birds with food only and/or food including 125 ppm of the composition. Figure 3 illustrates the results obtained on the final day of the study (day 42); similar results were obtained. Consequently, this specific modality states that there is no adverse effect on feed intake, feed conversion or body weight in birds that have ingested up to 2,500 ppm. The results also indicate that higher doses of the composition (for example, about 200 ppm to about 500 ppm) than that amount typically suggested in the art (i.e., 125 or 150 ppm) can be administered to the animal without adverse effects. EXAMPLE 2
[00117] In this example, the live performance of male broilers during a standard diet program with and without a disclosed combination modality was determined. In this modality, the combination comprised Virginiamycin and different levels of the composition, particularly 0 ppm, 150 ppm, 200 ppm and 250 ppm and also comprising Avatec 90. A disease stimulus was presented in each pen, adding contaminated debris with coccidiosis to the enclosure.
[00118] The results of this modality are provided in Figures 4 to 10. Body weight gain was measured on day 18 (Figure 4), on days 18 to 32 (Figure 5), on day 32 (Figure 6), on days 32 to 42 (Figure 7) and on day 42 (Figure 8) of feeding. Figures 9 and 10 illustrate the results from days 0 to 32 and days 0 to 42, respectively. Virginiamycin was administered at two different dosage levels, 0 ppm and 22 ppm. As indicated in Figures 4 to 10, Virginiamycin improved feed conversion rates throughout the test. In the modalities where only the composition was administered, there was no significant improvement in the gain/adjusted feed, but it significantly affected the weight gain of birds throughout the tests. The results also establish that Virginiamycin and the composition provide an additive effect when used in combination. As illustrated in Figure 9, the composition improved bird weight gain when administered at 150 ppm and 200 ppm, and the overall bird weight gain response (illustrated in Figure 10) corroborated that good responses were obtained using these two amounts of the composition. Table 1, below, provides the body weight gain (in grams) representing the growth response per dose (using only the composition and no Virginiamycin) and feeding phase for each dose versus the control modality for each modality . TABLE 1
EXAMPLE 3
[00119] In this modality, the effects of a modality of the combination revealed in broiler chickens vaccinated against coccidiosis were determined. In that example, the combination comprised the composition of Yucca schidigera and Quillaja saponaria, an antibiotic composition and/or a vaccine composition. Also, the ability of the Yucca schidigera and Quillaja saponaria composition to enhance the activity of the antibiotic composition (in this example Virginiamycin) and/or the vaccine composition in birds vaccinated against coccidiosis was determined. In this modality, all birds were vaccinated against coccidiosis with CocciVac. The composition of Yucca schidigera and Quillaja saponaria was administered in doses of 0 ppm, 200 ppm and 250 ppm. Virginiamycin was also administered to broilers at doses of 0 ppm and 22 ppm. Feed conversion performance, number of oocysts per gram of feces and lesions after coccidial stimulation were measured.
[00120] The results of this modality are illustrated in Figures 11 to 19. As illustrated in Figures 11 to 13, the broilers that received only the vaccine did not show the low feed conversion rates that the broilers that received the composition from Yucca schidigera and Quillaja saponaria and/or Virginiamycina. Figures 11 to 13 also illustrate that broilers that received a combination of the vaccine, the composition of Yucca schidigera and Quillaja saponaria and Virginiamycin exhibited the lowest feed conversion rates. Without being limited to a specific theory of operation, it is currently believed that higher levels of the composition of Yucca schidigera and Quillaja saponaria (eg, at least 200ppm to 500ppm) promote the vaccine's effect whereas Virginiamycin controls the bacterial proliferation, thus providing an additive effect that results in an overall improvement in feed conversion efficiency.
[00121] The effect of a combination of the vaccine, the composition of Yucca schidigera and Quillaja saponaria and Virginiamycin on weight gain was determined. Figures 14 to 16 illustrate these results. Additionally, the ability of coccidian organisms to reproduce in broiler chickens that received a combination of the vaccine, the composition of Yucca schidigera and Quillaja saponaria and Virginiamycin was also tested. As indicated in Figure 17, the number of oocysts (which results from the reproduction of coccidian organisms) was substantially reduced in broilers that received the vaccine, the composition of Yucca schidigera and Quillaja saponaria and Virginiamycin. Figure 17 also illustrates that the combinations of the vaccine and the composition of Yucca schidigera and Quillaja saponaria also resulted in diminished oocysts.
[00122] In this modality, a stimulus study was also conducted to determine immune potentiation. On day 21 of this modality, five birds from each pen were removed and stimulated with a coccidial stimulus of 3 species. The birds were then placed in battery cages for seven days. On the 28th, the birds were killed, and the injury scored. It was hypothesized that if immune potentiation had occurred, then lesion scores after the stimulus study would be lower in birds that received the Yucca schidigera and Quillaja saponaria composition than in birds that did not receive the Yucca schidigera composition. and Quillaja saponaria and/or Virginiamycin. Surprisingly, however, lesion scores lower than those obtained with control birds (eg, vaccine only) were not observed in birds that received the composition of Yucca schidigera and Quillaja saponaria in amounts ranging from about 200 ppm to 500 ppm, alone or in combination, as illustrated in Figures 18 and 19. Without being limited to a specific theory of operation, it is currently believed that higher lesion scores were obtained in birds that received the composition of Yucca schidigera and Quillaja saponaria and/or Virginiamycin than control birds because birds that received the composition of Yucca schidigera and Quillaja saponaria and/or Virginiamycin experienced lower levels of exposure to coccidia prior to extraction from the pens. That is, birds that received the composition of Yucca schidigera and Quillaja saponaria in amounts of about 200 ppm to about 500 ppm and/or Virginiamycin exhibited better anticoccidial capabilities than birds that did not receive the composition of Yucca schidigera and Quillaja saponaria and/or Virginiamycin. Non-control birds therefore did not develop as much immunity to coccidia while in the pen as control birds that did not receive the combination and therefore were more susceptible to coccidia and had a better ability to develop more immunity while in the pen. surrounded. Control birds therefore exhibited lower injury scores once extracted from pens as they had already developed immunity to the coccidial stimulus. The anticoccidial effects of the composition of Yucca schidigera and Quillaja saponaria in amounts ranging from about 200 ppm to about 500 ppm, alone or in combination with Virginiamycin, are therefore corroborated with the data illustrated in Figures 18 and 19, in the measure where higher lesion scores are indicative of better coccidiosis control (ie, less immunity). The results of these injury scoring examples are provided in Figures 18 and 19.
Based on this example, it has been determined that the composition of Yucca schidigera and Quillaja saponaria, particularly in amounts from about 200 ppm to about 500 ppm, exerts clearly anticoccidial effects in vaccinated broilers. There was an approximate 4- to 5-fold reduction in faecal oocyst counts during the first 28 days in birds that received a combination of a vaccine and the composition of Yucca schidigera and Quillaja saponaria. Also, the anticoccidial effects of the composition of Yucca schidigera and Quillaja saponaria were supported by the stimulus study revealed above which clearly showed an increased susceptibility to coccidian stimuli in birds that did not receive the composition of Yucca schidigera and Quillaja saponaria. EXAMPLE 4
[00124] In this specific modality, the compatibility of the composition of Yucca schidigera and Quillaja saponaria with Salinomycin was evaluated. Treatments included modalities where no feed additive was provided (eg no part of the composition added), where 250 ppm of the composition was provided, where 66 ppm of Salinomycin was provided, and modalities where 250 ppm of the composition and 66 ppm Salinomycin was provided in combination. The anticoccidial effects and immune potentiation of each test modality were evaluated, and the results are graphically provided in Figures 20 to 26.
[00125] As illustrated in Figures 20 to 23, the adjusted feed conversions of birds were determined after 18 days, 28 days and 42 days, respectively. The results show an improvement in the feed conversion rate in birds that received the composition of Yucca schidigera and Quillaja saponaria and Salinomycin in combination. A significant point difference in feed conversion rate was seen after each time period, as illustrated in Figures 20 to 23. Without adhering to a single theory of operation, it is currently believed that administering the composition in combination with Salinomycin increases the effectiveness of Salinomycin in reducing the negative effects of coccidiosis (eg, poorer feed conversion rates). The results also illustrated an additive effect between the composition and Salinomycin. Body weight gain also increased in birds that received a combination of the composition and Salinomycin compared to birds that did not receive the combination (eg, birds that received only food, birds that received only the composition, and birds that received only Salinomycin). These results are clearly illustrated in Figures 24 to 26.
[00126] The combination of the composition and Salinomycin also reduced the number of oocysts per gram of feces in broiler chickens, as indicated in Figure 27. A stimulus study was also conducted to assess the potential for immune boosting. Similar to the challenge study described in Example 3, 5 birds were removed from each pen after 21 days. These birds were stimulated with a coccidial stimulus from three species and then placed in battery cages for seven days. On the 28th, the birds were killed, and the injury scored. This stimulus study indicated anticoccidial effects independent of composition and salinomycin, as both increased the broilers' susceptibility to coccidial stimulation between days 21 and 28. EXAMPLE 5
[00127] In this specific modality, the effects of composition and Salinomycin were independently evaluated. Smaller amounts of the composition were tested, including the amount that is typically used by those skilled in the art (i.e., 125 ppm). Salinomycin treatments used either 44 ppm or 66 ppm Salinomycin. Uninfected birds that received no medication were used as a control (entry 1 of Table 2, below). Also, some birds received 66 ppm Salinomycin but were not infected (entry 7 in Table 2, below). The remaining birds were infected with 200,000 isolated field oocysts of E. acervulina, which is an Eimeria species that causes coccidiosis in birds, particularly older birds, and subjected to the treatments described below in entries 2 to 6 of Table 2 As indicated by the data provided in Table 2, no significant difference in body weights and/or adjusted feed conversion was observed at the lower levels of the composition of Yucca schidigera and Quillaja saponaria (abbreviated as "YQ composition" in Table 2) used in these modalities tested. TABLE 2

[00128] Similar protocols have been used to determine the effects of smaller amounts of NFP (eg, 100 ppm, 125 ppm and 150 ppm) in birds infected with E. maxima, a common form of Eimeria found in commercial broilers. Infected birds were infected with 37,500 isolated field oocysts of E. maxima. Infected birds were subjected to the treatments described below in entries 2 to 6 of Table 3. As indicated by the data provided in Table 3, no significant differences in body weights and/or adjusted feed conversion were observed at lower levels of Yucca schidigera composition. and Quillaja saponaria (abbreviated as "YQ composition" in Table 3) used in these tested modalities. TABLE 3

[00129] In another modality of testing, the effects of smaller amounts of NFP (eg, 100 ppm, 125 ppm and 150 ppm) in birds infected with E. tenella, an Eimeria species that causes hemorrhagic cecal coccidiosis in birds, particularly young birds. Infected birds were infected with 100,000 isolated field oocysts of E. tenella. Infected birds were subjected to the treatments described below in entries 2 to 6 of Table 4. As indicated by the data provided in Table 4, no significant differences in body weights and/or adjusted feed conversion were observed at lower levels of Yucca schidigera composition. and Quillaja saponaria (abbreviated as "YQ composition" in Table 4) used in these tested modalities. Table 4

[00130] Consequently, the results provided in this example establish that amounts of the composition of Yucca schidigera and Quillaja saponaria in the range of 100 ppm to 150 ppm are not as effective in improving feed conversion rates as are amounts. of the composition of Yucca schidigera and Quillaja saponaria which is in the range of about 200 ppm to about 500 ppm. The results also reflect that the composition amounts of Yucca schidigera and Quillaja saponaria in the range of 100ppm to 150ppm do not have the same anticoccidial activity as those modalities where about 200ppm to about 500ppm of the composition of Yucca schidigera and Quillaja saponarias are used. GENERAL PROCEDURES FOR EXAMPLES 6 TO 8
[00131] In the embodiments described below in Examples 6 to 8, the following conditions and methods were used. The test housing was divided into equal-sized pens arranged along a central corridor. Excluding equipment, the initial bird density was ~0.078 square meter (0.84 square foot)/bird. Each enclosure had sidewalls 1.52 meters (5 feet) high with the 0.46 meter (1.5 foot) bottom being made of solid wood to prevent bird migration. The entire floor of each enclosure had approximately 10.16 centimeters (4 inches) of accumulated debris. The temperature of the building was monitored. The environmental conditions during the test (temperature) were appropriate (ideal) for the age of the animals. Lighting was provided by fluorescent bulbs placed above the fences. The lighting scheme was 24 hours of light a day.
[00132] The diets were fed freely in a tube-type feeder per enclosure. From day 1 to day 7, food will also be provided on a tray placed directly in the debris of each pen.
[00133] Standard floor enclosure management practices were used throughout the experiment. Animals and housing facilities were inspected twice a day, observing and recording general health status, constant food and water supply as well as temperature, removing all dead birds and recognizing unexpected events.
[00134] All foods were supplied as crumbs/pellets. The quantities of all test articles and basal feed used to prepare the treatment lots were documented. Each batch of food was mixed and bagged separately. Each bag was identified with the study number, date of mixing, type of food and the correct treatment number. Complete records of food mix and test article inventories were maintained. Samples from the beginning, middle and end of each treatment feed were mixed to form a composite sample. This sample from each treatment was retained until the end of the study. All food was weighed by enclosure. The starter food was given from Day 0 to 18. On Day 18, the unconsumed starter food was weighed and discarded. The fattening food was issued and given until day 28. On Day 28, the unconsumed fattening food was weighed and discarded. The finisher food was issued and given until day 42. On day 42, the finisher food not consumed was weighed and discarded.
[00135] On the day of hatching, male pups were obtained from the Cobb-Vantress brooder, Cleveland, GA. The strain was Cobb 500. The breeding flock was registered. 1,760 chicks were allocated to the study. In the brooder, the birds received routine vaccinations. The birds had their sex determined in the brooder. In Example 7, all chicks were spray vaccinated with standard doses of Coccivac-B. Only healthy looking chicks were used in the study. In Examples 6 and 7, fifty-five males were allocated to each block treatment pen. In example 8, fifty-two males were allocated to each block treatment pen. No birds were replaced during the course of the study. The number and disposition of all birds not used for the allocation were documented. Bird weights (kg) per pen were recorded at baseline, day 18, 28, and end (day 42).
[00136] On days 18, 28 and 35, three birds per pen were sacrificed and scored by coccidial lesion for degree of infection by E. acervulina, E. maxima and E. tenella (Examples 6 and 7). Johnson and Reid's (1970) system where 0 is normal and 1, 2, 3 or 4 indicate increasing severity of infection was used for the injury score. In Example 8, three birds per pen were sacrificed on day 28 and scored for coccidial injury for degree of infection by E. acervulina, E. maxima, and E. tenella. Johnson and Reid's (1970) system where 0 is normal and 1, 2, 3 or 4 indicate increasing severity of infection was used for the injury score.
[00137] On Days 18 and 28, fresh faecal samples were collected from each pen (Examples 6 and 7). On Days 18 and 28, fresh faecal samples were collected from each pen (Example 8). These representative samples were tested to determine the degree of dissemination/cycling of oocysts. Oocysts per gram were determined for each sample. EXAMPLE 6
[00138] In this specific example, the compositions were administered for different time periods during the lifetime of the birds to determine preferred administration time periods for improved performance. The control of field strains less sensitive to ionophore medication and the performance of compounding modalities alone or in combination with Salinomycin fed to broiler chickens were also studied.
The birds received a diet comprising 250 mg of a composition modality comprising 90% Quillaja saponaria and 10% Yucca schidigera in combination with 66 ppm Salinomycin for different periods of time. In some embodiments, the compounding mode was fed to birds for the entire period between birth and death (typically days 0 through 42, referred to as a "complete program") or for intermediate periods of time during the lifetime of the birds. , such as from days 0 to 28 (referred to as a "start/fattener program"), from days 29 to 42 (referred to as a "finish program") or from days 19 to 42 (referred to as a " fattening/finishing program"). Birds were exposed to a coccidian stimulus from day of life (eg, day 0). Numerical results are provided by Tables 5 to 7 and are also graphically presented by Figures 28 to 37.





[00140] The data provided by Tables 5 to 8 indicate that the compositions and combinations disclosed in this document have the ability to provide significant and beneficial reductions in adjusted feed conversion rates, thus illustrating the benefits that compositions and combinations ( for example, compositions and antibiotics, antimicrobials and/or anticoccidials) may have on the animal's health and fertility. In some embodiments, a significant difference (eg, a reduction of 2% or more) in feed conversion rates for birds that received the composition during a full program was observed (see Figures 30 to 33). In some embodiments, the use of a complete one composition/combination program (eg, a composition and Salinomycin) resulted in a 5-point difference in feed conversion. See, for example, Figures 31 and 32. Referring to Figure 31, a comparison of the results represented by bar 3100 (which represents modalities where no composition was administered at the time of measurement) with bar 3102 (which represents a complete program) and/or bar 3104 (which represents a start/fattener program) corroborates that feed conversion rates can be significantly improved by using the composition in combination with a component with the ability to reduce adverse effects of coccidial infection (eg, a component that has activity against coccidia, such as Salinomycin). Referring to Figure 32, improved feed conversion rates are even more pronounced on day 42 as can be seen by comparing bus 3200 (days 0 to 42) and bus 3202 (days 0 to 28). The data provided by this example illustrates that compositional modalities can enhance the activity of Salinomycin and, therefore, can be effective with other antimicrobials, antibiotics, and/or anticoccidial agents.
[00141] The data also indicate that significant reductions in oocyst production were observed when birds were fed the composition compared to birds that did not receive any of the compositions (see Figure 28). Furthermore, birds receiving a complete composition program exhibited significant decreases in oocyst production as indicated by Figure 29 and Table 7. Additionally, the composition also did not exhibit any detrimental effects on bird body weight gain as evidenced by Figures 34 to 37. EXAMPLE 7
[00142] In this modality, the effects of a composition modality on different feeds and as a complete program were evaluated in combination with the use of a coccidiosis vaccine. The coccidiosis vaccine was administered to birds at hatch in this example; however, the vaccine can be given at other times during a bird's life cycle and even in combination with the composition. Birds in this modality were bred for a growth period of 42 days. A control group of birds was used, in which birds were vaccinated but not fed the composition. Other groups included groups of birds fed 250 mg of a composition modality from day 0 to day 28 (starter/fattening program), from day 29 to day 42 (finish program) and from day 0 to day 42 (full program) . The data for the modalities described in this example are provided below in Tables 9 to 11 and are also graphically illustrated in Figures 38 to 45.



EXAMPLE 8
[00143] In this example, the ability of the exemplary compositions to improve bird performance under stimulus conditions was determined. In some embodiments, an exemplary composition was administered alone, and in other embodiments, it was administered in combination with Salinomycin. In some embodiments, birds were not fed any additives (ie, neither composition nor Salinomycin) and in other embodiments birds were fed only Salinomycin. The birds used in this example were exposed to ionophore-tolerant coccidia in the debris of all pens starting from the day of life. On day 18, only Salinomycin did not improve performance. Both treatments with the composition (composition alone and the composition and Salinomycin), however, exhibited statistically significant improvements in adjusted feed conversion rates, thus indicating that the composition, alone or in combination with Salinomycin, can control coccidia and improve the performance. In still some embodiments, the combination of the composition and Salinomycin exhibited performance improvements at later stages (eg, after 28 days, even up to 42 days), indicating a synergistic relationship between the composition and the antibiotic. The oocyst data obtained from this example further supports the effectiveness of the composition and combination of the composition and Salinomycin, as statistically significant reductions in oocyst production were observed. The results of this example further illustrate that the disclosed compositions and combinations are effective to better control coccidia that are partially resistant to ionophores.




[00144] The information provided in Tables 12 to 14 indicates, in some embodiments, that the disclosed compositions can be used in combination with an antibiotic, antimicrobial and/or anticoccidial agent to improve performance even in animals that have developed ionophore resistance. OVERVIEW OF THE VARIOUS MODALITIES
In some embodiments disclosed herein, the combination may comprise 200 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria, Yucca schi-digera or a combination thereof; and a second composition comprising an antimicrobial agent, an antibiotic, an anticoccidial agent or combinations thereof; wherein the combination is formulated for administration to a chicken or turkey; or more than 0 ppm to 5,000 ppm of the first composition comprising Quillaja saponaria, Yucca schidigera or a combination thereof; and the second composition; where the combination is formulated for administration to an animal other than a chicken or turkey.
[00146] In some embodiments, the combination is formulated for birds other than chicken or turkey, cattle, aquaculture species, domesticated animals, ruminants or ungulates. In some modalities, the chicken is a broiler.
In some embodiments, the first composition is formulated for administration to an animal other than a chicken or turkey, and the amount of the first composition is in the range of 50 ppm to 5,000 ppm. In some embodiments, the first composition is formulated for administration to an animal other than a chicken or turkey, and the amount of the first composition is in the range of 50 ppm to 2,500 ppm.
[00148] In any or all of the above modalities, the first composition comprises a mixture of Quillaja saponaria and Yucca schidigera in a ratio in the range of 70:30 Quillaja saponaria:Yucca schidigera to 90:10 Quillaja saponaria: Yucca schidigera.
[00149] In any or all of the above embodiments, the second composition comprises 10 ppm to 30 ppm Virginiamycin.
In any or all of the above embodiments, the second composition comprises 25 ppm to 90 ppm Salinomycin.
In any or all of the above embodiments, the combination may comprise a third composition comprising a vaccine. In some embodiments, the vaccine is a coccidiosis vaccine comprising oocysts derived from Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria tenella, Eimeria necatrix, Eimeria mitis, Eimeria praecox, Eimeria brunetti, Eimeria hagani, or combinations thereof.
[00152] In any or all of the above embodiments, Quillaja saponaria is a plant extract of Quillaja saponaria, Yucca schidigera is a plant extract of Yucca schidigera, or both. In some embodiments, the Quillaja saponaria plant extract comprises at least a saponin, a polyphenol, an antioxidant, a resveratrol, or any combination thereof. In some embodiments, the plant extract of Yucca schidigera comprises at least a saponin, a polyphenol, an antioxidant, a resveratrol or any combination thereof.
[00153] In any or all of the above embodiments, the first and second compositions are addition mixed to form an addition mixed composition.
[00154] In any or all of the above embodiments, the first composition, the second composition, and the third composition are add-mixed to form an add-mixed composition. In some embodiments, the addition-mixed composition is further addition-mixed with a feed to form a feed-addition mixture. In some embodiments, the components of the add-mix composition, the feed add mix, or both, are sized, concentrated, or diluted to facilitate addition-mixing, ease of administration to an animal, or combinations thereof.
[00155] In any or all of the above embodiments, the combination may comprise a vitamin, a trace mineral, a bulking agent, a vehicle, a colorant, a flavor enhancer or any combination thereof.
[00156] In any or all of the above modalities, the combination may further comprise corn, soy flour, wheat, barley, rye, canola, corn oil, limestone, salt, dry grains from distillers with solubles (DDGS ), dicalcium phosphate, sodium sesquicarbonate, methionine source, lysine source, L-threonine, choline or any combination thereof.
[00157] In any or all of the above modalities, the combination is administered to an animal that has been or is at risk of being exposed to coccidia. In some modalities, coccidia are ionophore-resistant coccidia.
In some embodiments, the combination comprises 200 ppm to 300 ppm of a first composition comprising Quillaja saponaria, Yucca schidigera, or a combination thereof; and 10 ppm to 70 ppm of an antibiotic, an antimicrobial, anticoccidial or a combination thereof; and wherein the combination is formulated for administration to a poultry for domestic use.
[00159] Also disclosed herein are modalities of methods comprising administering a combination as disclosed herein to an animal at least once daily from day of life and for a period of time sufficient to promote a beneficial effect on the health. In some embodiments, the combination comprises 200 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria, Yucca schidigera, or a combination thereof; and a second composition which comprises an antimicrobial agent, an antibiotic, an anticoccidial agent, or a combination thereof and wherein the combination is administered to a chicken or turkey. In some embodiments, the combination comprises greater than 0 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria, Yucca schidigera, or a combination thereof; and a second composition which comprises an antimicrobial agent, an antibiotic, an anticoccidial agent, or combinations thereof and wherein the combination is administered to an animal other than a chicken or turkey.
[00160] In any or all of the above modalities, the first composition comprises a mixture of Quillaja saponaria and Yucca schidigera in a ratio in the range of 70:30 Quillaja saponaria:Yucca schidigera to 90:10 Quillaja saponaria: Yucca schidigera.
In any or all of the above embodiments, the first and second compositions are administered substantially simultaneously.
[00162] In any or all of the above embodiments, the first and second compositions are administered sequentially in any order.
[00163] In any or all of the above embodiments, the method may further comprise administering the first composition and the second composition in combination with a feed.
[00164] In some embodiments, the combination is given to a chicken or turkey, and the feed is provided in an amount ranging from at least 3.18 kg to 4.54 kg (7 pounds to 10 pounds) of one feed per chicken or turkey. In some embodiments, the first composition, second composition and feed are administered substantially simultaneously. In some embodiments, the first composition, second composition and feed are administered sequentially in any order.
In any or all of the above embodiments, the method comprises administering a third composition comprising a vaccine against coccidiosis comprising oocysts derived from Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria tenella, Eimeria necatrix, Eimeria mitis, Eimeria praecox, Eimeria bruntetti, Eimeria hagani or combinations thereof. In some embodiments, the first composition, second composition, third composition and feed are administered substantially simultaneously. In some embodiments, the first composition, second composition, third composition, and feed are administered sequentially in any order.
[00166] In any or all of the above embodiments, the animal other than a chicken or turkey is a bird other than a chicken or turkey, a mammal, a ruminant, an ungulate or an aquaculture species. In some modalities, the chicken is a broiler type chicken.
[00167] In any or all of the above embodiments, the animal has a lower feed conversion rate relative to an animal that did not receive the combination. In some embodiments, the feed conversion rate is improved by at least 0.5% to at least 5%.
[00168] In any or all of the above embodiments, administration of the combination to the animal has a beneficial effect on the animal's health relative to an animal that did not receive the combination. In some modalities, the beneficial effect on the animal's health is a beneficial effect on the animal's digestive system. In some embodiments, the method comprises improving the feed conversion rate of an animal in a commercial feeding operation by administering, at least once a day, a mixture comprising a feed, an antimicrobial, an antibiotic, an anticoccidial agent or a combination thereof, and 200 ppm to 5,000 ppm of Quillaja saponaria, Yucca schidigera, or both, where the mixture improves the feed conversion rate of the animal by more than 0.5% to at least 5% relative to an animal that has not received the mixture. In some modalities, the first composition comprises a mixture of Quillaja saponaria and Yucca schidigera in a ratio ranging from 70:30 Quillaja saponaria:Yucca schidigera to 90:10 Quillaja saponaria:Yucca schidigera.
Also disclosed herein are embodiments of a method for producing a combination comprising providing a first composition comprising Quillaja saponaria, Yucca schidigera, or both; providing a second composition comprising an antimicrobial agent, an antibiotic, an anticoccidial agent or a combination thereof; and combine the first and second compositions. In some embodiments, the amount of the first composition is in the range of greater than 0 ppm to 5,000 ppm. In some embodiments, the amount of the first composition is in the range of 50 ppm to 5,000 ppm.
[00170] In any or all of the above embodiments, Quillaja saponaria is a plant extract of Quillaja saponaria, Yucca schidigera is a plant extract of Yucca schidigera, or both. In some embodiments, the Quillaja saponaria plant extract comprises at least one saponin, the Yucca schidigera plant extract comprises at least one saponin, or both.
[00171] In any or all of the above modalities, the first composition comprises a mixture of Quillaja saponaria and Yucca schidigera in a ratio in the range of 70:30 Quillaja saponaria:Yucca schidigera to 90:10 Quillaja saponaria: Yucca schidigera.
[00172] In any or all of the above embodiments, the method further comprises admixing the combination with a feed to form an addition mixed feed. In some embodiments, the method further comprises formulating the first and/or second compositions for mixing with the feed to provide a substantially homogeneous addition mixed feed.
In any or all of the above embodiments, the method further comprises combining the first composition, the second composition, or both, with a third composition comprising a vaccine. In some embodiments, the first composition, second composition, and third composition are mixed by addition simultaneously or sequentially.
In view of the many possible embodiments to which the principles of the present disclosure may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the disclosure and should not be taken as limiting the scope of the claimed invention. Claimed as an invention is everything that falls within the scope and spirit of the following claims.

权利要求:
Claims (27)
[0001]
1. Combination, characterized in that it comprises: 200 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria and Yucca schidigera; and a second composition comprising an antimicrobial agent, an antibiotic, an anticoccidial agent or combinations thereof; wherein the combination is formulated for administration to a chicken or turkey; or more than 0 ppm to 5,000 ppm of the first composition comprising Quillaja saponáriae Yucca schidigera; and the second composition; wherein the combination is formulated for administration to an animal other than a chicken or turkey.
[0002]
2. Use of a combination, characterized in that it is for the manufacture of a medicine to promote a beneficial effect on health, wherein the combination comprises: (a) 200 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria and Yucca schidigera; and a second composition comprising an antimicrobial agent, an antibiotic, an anticoccidial agent or combinations thereof; or (b) more than 0 ppm to 5,000 ppm of the first composition comprising Quillaja saponaria and Yucca schidigera; and the second composition.
[0003]
3. Use according to claim 2, characterized in that the combination comprises 200 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria and Yucca schidigera; and a second composition which comprises an antimicrobial agent, an antibiotic, an anticoccidial agent or a combination thereof, and wherein the medicament is formulated for use with a chicken or turkey.
[0004]
4. Use according to claim 2, characterized in that the combination comprises more than 0 ppm to 5,000 ppm of a first composition comprising Quillaja saponaria, Yucca schidigera or a combination thereof; and a second composition which comprises an antimicrobial agent, an antibiotic, an anticoccidial agent or combinations thereof, and wherein the medicament is formulated for use with an animal other than a chicken or turkey.
[0005]
5. Use according to any one of claims 1 to 4, characterized in that the first composition comprises a mixture of Quillaja saponaria and Yucca schidigera in a ratio in the range of 70:30 of Quillaja saponaria:Yucca schidigera to 90: 10 of Quillaja saponaria: Yucca schidigera.
[0006]
6. Use according to any one of claims 1 to 5, characterized in that the drug further comprises a third composition comprising a vaccine against coccidiosis comprising oocysts derived from Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria tenella, Eimeria necatrix, Eimeria mitis, Eimeria praecox, Eimeria brunetti, Eimeria hagani or combinations thereof.
[0007]
7. Use according to any one of claims 1 to 6, characterized in that the animal other than a chicken or turkey is a bird other than a chicken or turkey, a mammal or an aquaculture species.
[0008]
8. Use according to claim 4, characterized by the fact that the chicken is a chicken of the meat type.
[0009]
9. Use according to any one of claims 1 to 8, characterized in that the beneficial effect on health is a beneficial effect on the animal's digestive system and providing a beneficial effect on health comprises decreasing conversion rates of feeding in the animal.
[0010]
10. Use according to claim 9, characterized in that the feed conversion rate is improved by at least 0.5% to at least 5%.
[0011]
11. Use according to claim 2, characterized in that the first composition comprises a mixture of Quillaja saponaria and Yucca schidigera in a ratio ranging from 70:30 of Quillaja saponaria: Yucca schidigera to 90:10 of Quillaja saponaria : Yucca schidigera.
[0012]
12. Method for producing a combination, characterized in that it comprises: providing a first composition comprising Quillaja saponaria and Yucca schidigera; providing a second composition comprising an antimicrobial agent, an antibiotic, an anticoccidial agent or a combination thereof; and combine the first and second compositions.
[0013]
13. Method according to claim 12, characterized in that it further comprises mixing by addition the combination with a feed to form a mixed feed by addition and/or formulating the first and/or second compositions for mixing with the feed to provide a substantially homogeneous mixed feed by addition.
[0014]
14. Method according to claim 12 or 13, characterized in that it further comprises combining the first composition, the second composition, or both, with a third composition comprising a vaccine.
[0015]
15. Method according to claim 14, characterized in that the first composition, the second composition and the third composition are mixed by addition simultaneously or sequentially.
[0016]
16. Composition, characterized by the fact that it comprises: (i) 200 ppm to 5,000 ppm of Quillaja saponaria and Yucca schidigera; and an antimicrobial agent, an antibiotic, an anticoccidial agent or combinations thereof; wherein the composition is formulated for administration to a chicken or turkey; or (ii) more than 0 ppm to 5,000 ppm Quillaja saponaria and Yucca schidigera; and an antimicrobial agent, an antibiotic, an anticoccidial agent or combinations thereof; wherein the composition is formulated for administration to an animal other than a chicken or turkey.
[0017]
17. Composition according to claim 16, characterized in that it is formulated for domestic poultry selected from laying hens, goose, duck, Cornish hen, quail, partridge, pheasant, guinea fowl, ostrich, rhea, swan, pigeon, cattle, aquaculture species, domesticated animals, ruminants or ungulates.
[0018]
18. Composition according to claim 16, characterized in that Quillaja saponaria and Yucca schidigera is present in an amount ranging from 50 ppm to 2,500 ppm.
[0019]
19. Composition according to any one of claims 16 to 18, characterized in that Quillaja saponaria and Yucca schidigera is present in a ratio in the range of 70:30 from Quillaja saponaria: Yucca schidigera to 90:10 from Quillaja saponaria: Yucca schidigera.
[0020]
20. Composition according to any one of claims 16 to 19, characterized in that the composition comprises 10 ppm to 30 ppm of Virginiamycin or 25 ppm to 90 ppm of Salinomycin.
[0021]
21. Composition according to any one of claims 16 to 20, characterized in that it further comprises a vaccine comprising oocysts derived from Eimeria acervulina, Eimeria mivati, Eimeria maxima, Eimeria tenella, Eimeria necatrix, Eimeria mitis, Eimeria praecox, Eimeria brunetti, Eimeria hagani or combinations thereof.
[0022]
22. Composition according to any one of claims 16 to 21, characterized in that the composition is further mixed by addition with a feed to form a mixture by adding feed.
[0023]
23. Composition according to claim 16, characterized in that the chicken is a broiler.
[0024]
24. Composition according to any one of claims 16 to 23, characterized in that it further comprises a vitamin, a trace mineral, a bulking agent, a vehicle, a dye, a flavor enhancer, corn, soy flour , wheat, barley, rye, canola, corn oil, limestone, salt, soluble distillers dry grains (DDGS), dicalcium phosphate, sodium sesquicarbonate, methionine source, lysine source, L-threonine, choline or any combination of the same.
[0025]
25. Composition according to claim 16, characterized in that it comprises 200 ppm to 300 ppm of Quillaja saponaria, Yucca schidigera, or their combination: and 10 ppm to 70 ppm of antibiotic, antimicrobial, anticoccidial or your combination; and wherein the composition is formulated for administration to a poultry for domestic use.
[0026]
26. Combination according to claim 1, characterized in that Quillaja saponaria is processed Quillaja plant material and Yucca schidigera is processed Yucca plant material.
[0027]
27. Composition according to claim 16, characterized in that Quillaja saponaria is processed Quillaja plant material and Yucca schidigera is processed Yucca plant material.

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法律状态:
2019-10-08| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |

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2019-12-10| B07B| Technical examination (opinion): publication cancelled [chapter 7.2 patent gazette]|Free format text: ANULADA A PUBLICACAO CODIGO 7.4 NA RPI NO 2544 DE 08/10/2019 POR TER SIDO INDEVIDA. |

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2020-04-28| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-12-08| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|

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2021-03-30| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2021-06-08| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 22/05/2015, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US201462002527P| true| 2014-05-23|2014-05-23|

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