Compositions containing narasin and methods of their use
Patent Information
- Authority / Receiving Office
- RU · RU
- Patent Type
- Applications
- Current Assignee / Owner
- ELANCO US INC
- Filing Date
- 2024-12-02
- Publication Date
- 2026-07-10
Abstract
Description
COMPOSITIONS COMPRISING NARASIN AND METHODS OF USING THE SAMETECHNICAL FIELD10001 ] The disclosure relates to compositions comprising narasin, as well as various methods utilizing the compositions.BACKGROUND
[0002] Ionophores are compounds capable of forming complexes with ions leading to potential transport of the ions across cell membranes. Ionophores are generally known to increase feed efficiency in non-human animals, for instance, by altering the fermentation process of feed in the animal. For example, ionophores can be used in bovines such as cattle to improve weight gain and to create greater feed efficiency by increasing production of propionate in the rumen. Narasin is an exemplary ionophore that can be individually administered to non-human animals.
[0003] Furthermore, an emerging goal in animal nutrition activities is to achieve reduction in methane production from animals. For instance, cattle are known to produce methane via their natural food consumption, and the resultant methane may contribute to an undesirable increase of greenhouse gases. Therefore, there exists a need in identifying new methods that may reduce animal production of methane, thus reducing potentially harmful effects of the gas on climate change.BRIEF DESCRIPTION OF THE DRAWINGS
[0004] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, with a detailed description of the embodiments given below, serve to explain the principles of the invention. The components in the figures are not necessarily to scale. Moreover, in the figures, like-referenced numerals designate corresponding parts throughout the different views.
[0005] Fig. 1 is a graph showing the average grams of methane produced per animal each day over the course of 26 weeks, discussed further in Example 4.
[0006] Fig. 2 is a graph showing the average grams of methane produced per kg of dry matter intake (“DMI”) each day over the course of 26 weeks, discussed further in Example 4.SUMMARY OF THE INVENTION
[0007] In a first aspect of the present invention, an animal nutrient composition including narasin is provided. Narasin may be present in the animal nutrient composition at between 5- 150 g / ton, alternatively 13-150 g / ton, alternatively 50-150 g / ton, alternatively between 50-130g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15- 25 g / ton, or alternatively 5-13 g / ton. The animal nutrient composition may be or comprise a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, or a combination thereof. In one embodiment, the animal nutrient composition comprises a diet composition. In one embodiment, the animal nutrient composition comprises a supplement composition. In one embodiment, the animal nutrient composition comprises a mineral composition. Optionally, a plurality of ionophores may be provided, wherein the plurality of ionophores includes narasin and at least one secondary ionophore, wherein the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly non-toxic ionophores, or some combination thereof. In a further embodiment thereof, the secondary ionophore may be present in the animal nutrient composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton. In one such embodiment, the secondary ionophore is monensin.
[0008] In a second aspect of the present invention, an animal feed composition including an animal nutrient composition and a feed is provided, wherein the animal nutrient composition includes narasin. The animal nutrient composition may be or comprise a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, or a combination thereof. In one embodiment, the animal nutrient composition comprises a diet composition. In one embodiment, the animal nutrient composition comprises a supplement composition. In one embodiment, the animal nutrient composition comprises a mineral composition. The feed may include a Type A feed, a Type B feed, a Type C feed, or some combination thereof. In one such embodiment, the feed includes a Type A feed. In an alternate embodiment, the feed includes a Type B feed. In an alternate embodiment, the feed includes a Type C feed. The feed may include a material selected from the list consisting of com, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, or some combination thereof. In an alternate embodiment, the feed includes com. In an alternate embodiment, the feed includes cotton seed. In an alternate embodiment, the feed includes soybean. In an alternate embodiment, the feed includes soybean meal. In an alternate embodiment, the feed includes soybean oil. In an alternate embodiment, the feed includes rapeseed. In an alternate embodiment, the feed includes rapeseed oil. In an alternate embodiment, the feed includes a mineral mix.
[0009] With further respect to the second aspect of the invention, the feed may include a total mixed ration (TMR) forage ingredient. In one such embodiment, the feed includes a TMRforage ingredient selected from the group consisting of corn silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and any combination thereof. In an alternate embodiment, the TMR forage ingredient includes corn silage. In an alternate embodiment, the TMR forage ingredient includes grass silage. In an alternate embodiment, the TMR forage ingredient includes oat silage. In an alternate embodiment, the TMR forage ingredient includes alfalfa silage. In an alternate embodiment, the TMR forage ingredient includes wheat silage. In an alternate embodiment, the TMR forage ingredient includes straw. In an alternate embodiment, the TMR forage ingredient includes grass. In an alternate embodiment, the TMR forage ingredient includes fresh grass. In an alternate embodiment, the TMR forage ingredient includes alfalfa. In an alternate embodiment, the TMR forage ingredient includes hay. In an alternate embodiment, the TMR forage ingredient includes hay from grass. In an alternate embodiment, the TMR forage ingredient includes hay from alfalfa. The TMR forage ingredient may account for at least 10% (w / w) of the feed, alternatively at least 15% (w / w) of the feed, alternatively at least 20% (w / w) of the feed, alternatively at least 25% (w / w) of the feed, alternatively at least 30% (w / w) of the feed, alternatively at least 50% (w / w) of the feed, alternatively at least 70% (w / w) of the feed, alternatively at least 90% (w / w) of the feed, or alternatively at least 98% (w / w) of the feed.
[0010] With further respect to the second aspect of the invention, narasin may be present in the animal nutrient composition at between 5-150 g / ton, alternatively 13-150 g / ton, alternatively 50-150 g / ton, alternatively between 50-130 g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15-25 g / ton, or alternatively 5-13 g / ton. Optionally, a plurality of ionophores may be provided, wherein the plurality of ionophores includes narasin and at least one secondary ionophore, wherein the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly non-toxic ionophores, or some combination thereof. In a further embodiment thereof, the secondary ionophore may be present in the animal nutrient composition at between 5-1200 g / ton, alternatively between 5- 500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton. In one such embodiment, the secondary ionophore is monensin. In an alternate embodiment including a secondary ionophore, the secondary ionophore may be present in the animal feed composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton.
[0011] In a third aspect of the present invention, a method for increasing performance of an animal is provided, the method comprising administering an animal nutrient composition oran animal feed composition comprising narasin to the animal, wherein the administration of the animal nutrient composition or the animal feed composition increases performance of the animal. The increase in performance may comprise one or more item selected from the list consisting of an increase in feed efficiency in the animal, an increase in average daily gain in the animal, an increase in hot carcass weight of the animal, an optimization of rumen flora of the animal, optimization of volatile fatty acid production in the animal, optimization of propionic acid production in the animal, or some combination thereof. In one such embodiment, the increase in performance comprises optimization of propionic acid production in the animal. The animal nutrient composition or the animal feed composition may be administered for at least 14 days, alternatively at least a month, alternatively at least 3 months, or alternatively at least 6 months. Narasin may be present in the animal nutrient composition or the animal feed composition at between 5-150 g / ton, alternatively 13-150 g / ton, alternatively 50-150 g / ton, alternatively between 50-130 g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15-25 g / ton, or alternatively 5-13 g / ton. In embodiments including the step for administering an animal nutrient composition, the animal nutrient composition may be or comprise a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, or a combination thereof. In one embodiment, the animal nutrient composition comprises a diet composition. In one embodiment, the animal nutrient composition comprises a supplement composition. In one embodiment, the animal nutrient composition comprises a mineral composition.
[0012] Optionally, a plurality of ionophores may be provided, wherein the plurality of ionophores includes narasin and at least one secondary ionophore, wherein the administration of the combination of narasin and the secondary ionophore synergistically increases the performance of the animal. In one such embodiment, the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly non-toxic ionophores, or some combination thereof. In a further embodiment thereof, the secondary ionophore may be present in the animal nutrient composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton. In one such embodiment, the secondary ionophore is monensin. In an alternate embodiment including a secondary ionophore, the secondary ionophore may be present in the animal feed composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton. In one such embodiment, the secondary ionophore is monensin.
[0013] With further respect to the third aspect of the invention, the animal is a ruminant. In one such embodiment, the ruminant is selected from a list consisting of a bovine, an ovine, and a caprine. In a further embodiment wherein the ruminant is a bovine, the bovine is selected from a list consisting of cattle, bison, African buffalo, water buffalo, and antelope. In a further embodiment where the animal is cattle, the cattle may be selected from the list consisting of a heifer, a steer, a bull, and a cow.
[0014] With further respect to the third aspect of the invention, in embodiments administering the animal feed composition comprising narasin to the animal, the animal feed composition further comprises a feed. In one embodiment, the feed comprises a feed selected from the list consisting of a Type A feed, a Type B feed, a Type C feed, or some combination thereof. The feed may include a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, or some combination thereof. The feed may comprise a total mixed ration (TMR) forage ingredient. In one embodiment, the feed comprises a TMR forage ingredient selected from the list consisting of com silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and any combination thereof. In one embodiment, the TMR forage ingredient comprises at least 10% (w / w) of the feed, alternatively at least 15% (w / w) of the feed, alternatively at least 20% (w / w) of the feed, alternatively at least 25% (w / w) of the feed, alternatively at least 30% (w / w) of the feed, alternatively at least 50% (w / w) of the feed, alternatively at least 70% (w / w) of the feed, alternatively at least 90% (w / w) of the feed, or alternatively at least 98% (w / w) of the feed.
[0015] In a fourth aspect of the present invention, a method for decreasing methane production of an animal is provided, the method comprising administering an animal nutrient composition or an animal feed composition comprising narasin to the animal, wherein the administration decreases methane production from the animal. In one such embodiment, the decrease in methane production comprises an absolute decrease in methane. Alternatively, the decrease in methane production may be relative to the animal’s body weight (“BW”) (e.g., methane / kg of BW). Alternatively, the decrease in methane production may be relative to dry matter (“DM”) intake (e.g., methane / kg of DM intake). In one such embodiment, the decrease in methane production comprises an indirect decrease in methane. In one such embodiment, the decrease in methane production is associated with a decrease in methanogenesis in the animal. In one embodiment, the decrease in methane production may be associated with an improvement in the ratio of volatile fatty acids (VFAs). In one such embodiment, the production of propionate is improved relative to other VFAs.
[0016] With further respect to the fourth aspect of the invention, the animal nutrient composition or the animal feed composition may be applied for at least 14 days, alternatively at least one month, alternatively at least three months, alternatively at least 6 months. Narasin may be present in the animal nutrient composition or in the animal feed composition at between 5-150 g / ton, alternatively 13-150 g / ton, alternatively 50-150 g / ton, alternatively between 50- 130 g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15-25 g / ton, or alternatively 5-13 g / ton. In embodiments including the step for administering an animal nutrient composition, the animal nutrient composition may be or comprise a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, or a combination thereof. In one embodiment, the animal nutrient composition comprises a diet composition. In one embodiment, the animal nutrient composition comprises a supplement composition. In one embodiment, the animal nutrient composition comprises a mineral composition.
[0017] Optionally, a plurality of ionophores may be provided, wherein the plurality of ionophores includes narasin and at least one secondary ionophore, wherein the administration of the combination of narasin and the secondary ionophore synergistically provides the decrease in methane production in the animal. In one such embodiment, the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly non-toxic ionophores, or some combination thereof. In a further embodiment thereof, the secondary ionophore may be present in the animal nutrient composition at between 5-1200 g / ton, alternatively between 5- 500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton. In one such embodiment, the secondary ionophore is monensin. In an alternate embodiment including a secondary ionophore, the secondary ionophore may be present in the animal feed composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton. In one such embodiment, the secondary ionophore is monensin.
[0018] With further respect to the fourth aspect of the invention, in one embodiment, the animal is selected from the group consisting of a ruminant, an ovine, and a caprine. In one embodiment wherein the ruminant is a bovine, the bovine is selected from the list consisting of cattle, bison, African buffalo, water buffalo, and antelope. In one embodiment wherein the bovine is cattle, the cattle is selected from the list consisting of a heifer, a steer, a bull, and a cow.
[0019] With further respect to the fourth aspect of the invention, in embodiments wherein an animal feed composition is administered to the animal, the animal feed composition includes a feed. In one such embodiment, the feed is selected from a group consisting of a Type A feed, a Type B feed, a Type C feed, and combinations thereof. In one such embodiment, the feed may include a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, or some combination thereof. In one such embodiment, the feed may comprise a total mixed ration (TMR) forage ingredient. In one embodiment, the feed comprises a TMR forage ingredient selected from the list consisting of com silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and any combination thereof. In one embodiment, the TMR forage ingredient comprises at least 10% (w / w) of the feed, alternatively at least 15% (w / w) of the feed, alternatively at least 20% (w / w) of the feed, alternatively at least 25% (w / w) of the feed, alternatively at least 30% (w / w) of the feed, alternatively at least 50% (w / w) of the feed, alternatively at least 70% (w / w) of the feed, alternatively at least 90% (w / w) of the feed, or alternatively at least 98% (w / w) of the feed.
[0020] In a fifth aspect of the present invention, a kit comprising narasin is provided. The kit may be configured to be administered to an animal as an animal nutrient composition or as an animal feed composition. In embodiments where the kit is administered to an animal as an animal nutrient composition, the animal nutrient composition may be or comprise a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, or a combination thereof. In one embodiment, the animal nutrient composition comprises a diet composition. In one embodiment, the animal nutrient composition comprises a supplement composition. In one embodiment, the animal nutrient composition comprises a mineral composition. Narasin may be present in the animal nutrient composition, the animal feed composition, or the kit at between 5-150 g / ton, alternatively 13- 150 g / ton, alternatively 50-150 g / ton, alternatively between 50- 130 g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15-25 g / ton, or alternatively 5-13 g / ton. Optionally, a plurality of ionophores may be provided, wherein the plurality of ionophores includes narasin and at least one secondary ionophore. In one such embodiment, the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly non-toxic ionophores, or some combination thereof. In an alternate embodiment including a secondary ionophore, the secondary ionophore may be present in the animal nutrient composition, the animal feed composition, or the kit at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between50-250 g / ton, or alternatively between 100-200 g / ton. In one such embodiment, the secondary ionophore is monensin.
[0021] With further respect to the fifth embodiment of the present invention, the kit may be configured to be administered to an animal as an animal feed composition, wherein the animal feed composition comprises the animal nutrient composition and a feed. In one such embodiment, the feed is selected from the list consisting of a Type A feed, a Type B feed, a Type C feed, or some combination thereof. In one such embodiment, the feed may include a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, or some combination thereof. In one such embodiment, the feed may comprise a total mixed ration (TMR) forage ingredient. In one embodiment, the feed comprises a TMR forage ingredient selected from the list consisting of com silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and any combination thereof. In one embodiment, the TMR forage ingredient comprises at least 10% (w / w) of the feed, alternatively at least 15% (w / w) of the feed, alternatively at least 20% (w / w) of the feed, alternatively at least 25% (w / w) of the feed, alternatively at least 30% (w / w) of the feed, alternatively at least 50% (w / w) of the feed, alternatively at least 70% (w / w) of the feed, alternatively at least 90% (w / w) of the feed, or alternatively at least 98% (w / w) of the feed.DETAILED DESCRIPTION
[0022] In some aspects, the present disclosure provides compositions including narasin as well as methods for administering the compositions to animals. As described herein, the compositions and methods exhibit desirable properties and provide benefits for increasing performance of animals as well as reducing methane production by animals. In particular, the compositions and methods can result in fewer resources (e.g., feed inputs) that are needed in order to achieve desired outputs such as improved animal performance parameters and / or reduced methane production. Without being bound by theory, the compositions and methods may result in improvements in feed efficiency.
[0023] In a first aspect of the invention, an animal nutrient composition is provided, wherein the animal nutrient composition includes narasin. In a second aspect of the invention, an animal feed composition including narasin is provided, wherein the animal feed composition includes a feed and an animal nutrient composition including narasin, such as the animal nutrient composition of the first aspect of the invention. In a third aspect of the invention, a method for increasing performance of an animal is provided, the method comprising administering at least one of an animal nutrient composition including narasin, such as theanimal nutrient composition of the first aspect of the invention, or an animal feed composition including narasin, such as the animal feed composition of the second aspect of the invention, to the animal, wherein the administration of the animal nutrient composition increases performance of the animal. In a fourth aspect of the invention, a method for decreasing methane production of an animal is provided, the method comprising administering at least one of an animal nutrient composition including narasin, such as the animal nutrient composition of the first aspect of the invention, or an animal feed composition including narasin, such as the animal feed composition of the second aspect of the invention, to an animal, wherein said administration decreases methane production from the animal. In a fifth aspect of the invention, a kit including narasin is provided.
[0024] With respect to the animal nutrient composition, narasin may be present in the animal nutrient composition at between 5-150 g / ton, alternatively 13-150 g / ton, alternatively 50-150 g / ton, alternatively between 50-130 g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15-25 g / ton, or alternatively 5-13 g / ton. The animal nutrient composition may be or comprise a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, or a combination thereof. In one embodiment, the animal nutrient composition comprises a diet composition. In one embodiment, the animal nutrient composition comprises a supplement composition. In one embodiment, the animal nutrient composition comprises a mineral composition.
[0025] With further respect to the animal nutrient composition, a plurality of ionophores, including narasin and at least one secondary ionophore, may be provided. In one embodiment, the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly non-toxic ionophores, or some combination thereof. Further, by utilizing a plurality of ionophores in the described compositions, ionophore toxicity may be avoided or reduced since a reduced quantity of narasin and / or the secondary ionophore can be administered to the animal but still achieve desirable results, such as increased production or decreased methane production. In one embodiment, the secondary ionophore may be present in the animal nutrient composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton.
[0026] With respect to the animal feed composition, the animal feed composition includes narasin and a feed. Optionally, the narasin included in the animal feed composition may be incorporated into an animal nutrient composition, such as the animal nutrient compositions described above. In such embodiments, the animal nutrient composition may beor comprise a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, or a combination thereof. In one embodiment, the animal nutrient composition comprises a diet composition. In one embodiment, the animal nutrient composition comprises a supplement composition. In one embodiment, the animal nutrient composition comprises a mineral composition. It is believed that administration of the animal feed compositions of the present disclosure can improve feed efficiency, thus leading to a reduction in resource requirements necessary to achieve a similar production output.
[0027] Narasin may be present in the animal nutrient composition within the animal feed composition at between 5-150 g / ton, alternatively 13-150 g / ton, alternatively 50-150 g / ton, alternatively between 50-130 g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15-25 g / ton, or alternatively 5-13 g / ton. Alternatively, narasin may be present in the animal feed composition at between 5-150 g / ton, alternatively 13-150 g / ton, alternatively 50-150 g / ton, alternatively between 50-130 g / ton, alternatively between 50-100 g / ton, alternatively between 50-80 g / ton, alternatively 15-25 g / ton, or alternatively 5-13 g / ton.
[0028] A plurality of ionophores, including narasin and at least one secondary ionophore, may be present in the animal nutrient composition. In one embodiment, the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly nontoxic ionophores, or some combination thereof. Further, by utilizing a plurality of ionophores in the described compositions, ionophore toxicity may be avoided or reduced since a reduced quantity of narasin and / or the secondary ionophore can be administered to the animal but still achieve desirable results, such as increased production or decreased methane production. In one embodiment, the secondary ionophore may be present in the animal nutrient composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton. In an alternate embodiment, the secondary ionophore may be present in the animal feed composition at between 5-1200 g / ton, alternatively between 5-500 g / ton, alternatively between 25-400 g / ton, alternatively between 50-250 g / ton, or alternatively between 100-200 g / ton.
[0029] The feed may include a Type A feed, a Type B feed, a Type C feed, or some combination thereof. In one such embodiment, the feed includes a Type A feed. In an alternate embodiment, the feed includes a Type B feed. In an alternate embodiment, the feed includes a Type C feed.
[0030] The feed may include a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, or some combination thereof. In an alternate embodiment, the feed includes corn. In an alternateembodiment, the feed includes cotton seed. In an alternate embodiment, the feed includes soybean. In an alternate embodiment, the feed includes soybean meal. In an alternate embodiment, the feed includes soybean oil. In an alternate embodiment, the feed includes rapeseed. In an alternate embodiment, the feed includes rapeseed oil. In an alternate embodiment, the feed includes a mineral mix.
[0031] The feed may include a total mixed ration (TMR) forage ingredient. In one such embodiment, the feed includes a TMR forage ingredient selected from the group consisting of com silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and any combination thereof. In an alternate embodiment, the TMR forage ingredient includes corn silage. In an alternate embodiment, the TMR forage ingredient includes grass silage. In an alternate embodiment, the TMR forage ingredient includes oat silage. In an alternate embodiment, the TMR forage ingredient includes alfalfa silage. In an alternate embodiment, the TMR forage ingredient includes wheat silage. In an alternate embodiment, the TMR forage ingredient includes straw. In an alternate embodiment, the TMR forage ingredient includes grass. In an alternate embodiment, the TMR forage ingredient includes fresh grass. In an alternate embodiment, the TMR forage ingredient includes alfalfa. In an alternate embodiment, the TMR forage ingredient includes hay. In an alternate embodiment, the TMR forage ingredient includes hay from grass. In an alternate embodiment, the TMR forage ingredient includes hay from alfalfa.
[0032] With further respect to the TMR forage ingredient, the TMR forage ingredient may account for at least 10% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 15% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 20% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 25% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 30% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 50% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 70% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 90% (w / w) of the feed. Alternatively, the TMR forage ingredient may account for at least 98% (w / w) of the feed.
[0033] With reference to the third aspect of the invention, methods of increasing performance of an animal are provided. The method comprises the step of administering an animal nutrient composition including narasin or an animal feed composition including narasin to the animal, wherein the administration increases the performance of the animal. Without being bound by any theory, it is believed that animal performance may exemplary be increasedvia modulation of rumen microflora and / or optimization of volatile fatty acid production (e.g., propionic acid) in the rumen.
[0034] In one embodiment, the increase in performance comprises one or more item selected from the list consisting of an increase in feed efficiency in the animal, an increase in average daily gain in the animal, an increase in hot carcass weight of the animal, an optimization of rumen flora of the animal, optimization of volatile fatty acid production in the animal, or some combination thereof. In an alternate embodiment, the increase in performance comprises an increase in feed efficiency in the animal. In an alternate embodiment, the increase in performance comprises an increase in average daily gain in the animal. In an alternate embodiment, the increase in performance comprises an increase in hot carcass weight of the animal. In an alternate embodiment, the increase in performance comprises an optimization of rumen flora of the animal. In an alternate embodiment, the increase in performance comprises optimization of volatile fatty acid production in the animal. In an alternate embodiment, the increase in performance comprises optimization of propionic acid production in the animal.
[0035] In one embodiment, the method comprises administering an animal nutrient composition comprising narasin to the animal, such as the animal nutrient compositions described above. Administering an animal nutrient composition to the animal may comprise administering the animal nutrient composition according to the first aspect of the invention. In one embodiment, the animal nutrient composition is administered to the animal for at least 14 days. In an alternate embodiment, the animal nutrient composition is administered to the animal for at least a month. In an alternate embodiment, the animal nutrient composition is administered to the animal for at least 3 months. In an alternate embodiment, the animal nutrient composition is administered to the animal for at least 6 months.
[0036] In an alternate embodiment, the method comprises administering an animal feed composition to the animal, such as the animal feed compositions described above. Administering the animal feed composition to the animal comprises administering the animal feed composition according to the second aspect of the invention. In one embodiment, the animal feed composition is administered to the animal for at least 14 days. In an alternate embodiment, the animal feed composition is administered to the animal for at least a month. In an alternate embodiment, the animal feed composition is administered to the animal for at least 3 months. In an alternate embodiment, the animal feed composition is administered to the animal for at least 6 months.
[0037] With reference to the fourth aspect of the invention, a method of decreasing methane production of an animal is provided. In one such embodiment, the decrease in methane production comprises an absolute decrease in methane. Alternatively, the decrease inmethane production may be relative to the animal’s body weight (“BW”) (e.g., methane / kg of BW). Alternatively, the decrease in methane production may be relative to dry matter (“DM”) intake (e.g., methane / kg of DM intake). In one such embodiment, the decrease in methane production comprises an indirect decrease in methane. In one such embodiment, the decrease in methane production is associated with a decrease in methanogenesis in the animal. In one embodiment, the decrease in methane production may be associated with an improvement in the ratio of volatile fatty acids (VFA). In one such embodiment, the production of propionate is improved relative to other VFAs.
[0038] In one embodiment, the method comprises the step of administering an animal nutrient composition comprising narasin to the animal, such as the animal nutrient compositions described above, wherein the administration decreases methane production from the animal. Administering an animal nutrient composition to the animal may comprise administering the animal nutrient composition according to the first aspect of the invention. In one embodiment, the animal nutrient composition is administered to the animal for at least 14 days. In an alternate embodiment, the animal nutrient composition is administered to the animal for at least a month. In an alternate embodiment, the animal nutrient composition is administered to the animal for at least 3 months. In an alternate embodiment, the animal nutrient composition is administered to the animal for at least 6 months.
[0039] In an alternate embodiment, the method comprises administering an animal feed composition to the animal, such as the animal feed compositions described above.Administering the animal feed composition to the animal comprises administering the animal feed composition according to the second aspect of the invention. In one embodiment, the animal feed composition is administered to the animal for at least 14 days. In an alternate embodiment, the animal feed composition is administered to the animal for at least a month. In an alternate embodiment, the animal feed composition is administered to the animal for at least 3 months. In an alternate embodiment, the animal feed composition is administered to the animal for at least 6 months.
[0040] In another embodiment, the method comprises the step of administering an animal feed composition comprising narasin to the animal, such as the animal feed compositions described above, wherein the administration decreases methane production from the animal. Without being bound by any theory, it is believed that methane production may exemplary be reduced via a reduction of methanogenesis in the animal. Further, without being bound by any theory, it is believed that a decrease in methane production according to the present disclosure is capable of reducing absolute and indirect methane production per unit of production, thus reducing the effect of methane on greenhouse gas emissions.
[0041] With further respect to the method for increasing performance of an animal and the method of decreasing methane production of an animal, the animal may be a ruminant. The ruminant may be selected from the list consisting of a ruminant, an ovine, and a caprine. In embodiments wherein the animal is a bovine, the bovine may be selected from the list consisting of cattle, bison, African buffalo, water buffalo, and antelope. In embodiments wherein the animal is cattle, the cattle may be selected from the list consisting of a heifer, a steer, a bull, and a cow.
[0042] With reference to the kit, a kit comprising narasin is provided. The kit may be or include an animal nutrient composition, such as the animal nutrient compositions discussed above, or an animal feed composition, such as the animal feed compositions discussed above. In one such embodiment, the kit is or includes an animal nutrient composition according to the first aspect of the invention. In another such embodiment, the kit is or includes an animal feed composition according to the second aspect of the invention. Optionally, a plurality of ionophores may be provided in either the animal nutrient composition or the animal feed composition. The kit may be configured to be administered to an animal as an animal nutrient composition or as an animal feed composition.
[0043] EXAMPLE 1
[0044] Method
[0045] The instant example describes an analysis of compositions comprising narasin.The compositions in the instant example are administered to cattle. In the analyses below, a control group, wherein a mineral supplement not including narasin was administered to the cattle, was compared to an experimental group, wherein narasin was administered to the cattle in a mineral supplement (i.e., an animal nutrient composition). Exemplary evaluations of the administration of the compositions to cattle can include clinical observations in the live animals as well as histopathological and biochemical evaluations of tissues as well as rumen content collected during necropsy of the animals. For instance, tissues can be collected for residue analysis. Furthermore, sample collection can include body weight of animals at treatment initiation and at completion.
[0046] In total, 160 cattle were tested across the control and experimental groups, with the cattle having an initial average weight of 177 kg. All cattle were pastured in paddocks comprising primarily brachiaria brizantha during a rain season and were further provided with a mineral supplement. Upon information and belief, the pasture had a Total Digestible Nutrient (TDN) amount of approximately 55% and a Crude Protein (CP) amount of approximately 10%. The control group contained 80 cattle, with 8 cattle in each of 10 different paddocks. The experimental group also consisted of 80 cattle, with 8 cattle in 10 different paddocks. In thepresent example, 1,200 mg of narasin per kg of mineral was administered to each animal in the experimental group. Accordingly, the experimental group corresponds with a total diet narasin dosage of 13 ppm for the experimental group, and approximately corresponds with a narasin dosage of 75 mg / (cattle*day). The groups were tested for 84 days before results were compared.
[0047] Results
[0048] With respect to mineral intake, which measures the average mineral intake per cattle per day, the control group had an average mineral intake of 64 g / (cattle*day). The experimental group had an average mineral intake of approximately 61 g / (cattle*day). Accordingly, since these measured mineral intakes are approximately equal to each other, measured differences between experimental and control groups may be attributed to narasin intake.
[0049] With respect to average daily gain, which measures average weight gain per cattle per day, the control group had an average daily gain of 493 g / (cattle*day). The experimental group had an average daily gain of 575 g / (cattle*day). Accordingly, the inclusion of narasin in the mineral supplement of the control group resulted in an increase in average daily gain of 82 g / (cattle*day), or a 17% increase.
[0050] EXAMPLE 2
[0051] Method
[0052] The instant example describes an analysis of compositions comprising narasin.The compositions in the instant example are administered to cattle. In the analyses below, a control group, wherein a mineral supplement not including narasin was administered to the cattle, was compared to an experimental group, wherein narasin was administered to the cattle in a mineral supplement (i.e., an animal nutrient composition). Exemplary evaluations of the administration of the compositions to cattle can include clinical observations in the live animals as well as histopathological and biochemical evaluations of tissues as well as rumen content collected during necropsy of the animals. For instance, tissues can be collected for residue analysis. Furthermore, sample collection can include body weight of animals at treatment initiation and at completion.
[0053] In total, 240 cattle were tested across the control and experimental groups, with the cattle having an initial average weight of 193 kg. All cattle were pastured in paddocks comprising primarily brachiaria brizantha during a rain season and were further provided with a mineral supplement. Upon information and belief, the pasture had a TDN amount of approximately 55% and a CP amount of approximately 10%. The control group contained 120 cattle divided among 16 different paddocks. The experimental group also consisted of 120cattle divided among 16 different paddocks. In the present example, 1,200 mg of narasin per kg of mineral was administered to each animal in the experimental group. Accordingly, the experimental group corresponds with a total diet narasin dosage of 13 ppm for the experimental group, and approximately corresponds with a narasin dosage of 78 mg / (cattle*day). The groups were tested for 112 days before results were compared.
[0054] Results
[0055] With respect to mineral intake, which measures the average mineral intake per cattle per day, the control group had an average mineral intake of 64.1 g / (cattle*day). The experimental group had an average mineral intake of approximately 64.9 g / (cattle*day). Accordingly, since these measured mineral intakes are approximately equal to each other, measured differences between experimental and control groups may be attributed to narasin intake.
[0056] With respect to average daily gain, which measures average weight gain per cattle per day, the control group had an average daily gain of 555 g / (cattle*day). The experimental group had an average daily gain of 639 g / (cattle*day). Accordingly, the inclusion of narasin in the mineral supplement of the control group resulted in an increase in average daily gain of 84 g / (cattle*day), or a 15% increase.
[0057] EXAMPLE 3
[0058] Method
[0059] The instant example describes an analysis of compositions comprising narasin.The compositions in the instant example are administered to cattle. In the analyses below, a control group, wherein a protein supplement not including narasin was administered to the cattle, was compared to an experimental group, wherein narasin was administered to the cattle in a protein supplement (i.e., the animal nutrient composition). Exemplary evaluations of the administration of the compositions to cattle can include clinical observations in the live animals as well as histopathological and biochemical evaluations of tissues as well as rumen content collected during necropsy of the animals. For instance, tissues can be collected for residue analysis. Furthermore, sample collection can include body weight of animals at treatment initiation and at completion.
[0060] In total, 150 cattle were tested across the control and experimental groups, with the cattle having an initial average weight of 331 kg. All cattle were pastured in paddocks comprising primarily brachiaria brizantha during a drought season and were further provided with a protein supplement. Upon information and belief, the pasture had a TDN amount of approximately 50% and a CP amount of approximately 7%. The control group contained 120 cattle divided among 16 different paddocks. The experimental group also consisted of 120cattle divided among 16 different paddocks. In the present example, 1,200 mg of narasin per kg of protein was administered to each animal in the experimental group. Accordingly, the experimental group corresponds with a total diet narasin dosage of 13 ppm for the experimental group, and approximately corresponds with a narasin dosage of 78 mg / (cattle*day). The groups were tested for 112 days before results were compared.
[0061] Results
[0062] With respect to proteinated intake, which measures the average protein intake per cattle per day, the control group had an average proteinated intake of 435 g / (cattle*day). The experimental group had an average mineral intake of approximately 431 g / (cattle*day). Accordingly, since these measured proteinated intakes are approximately equal to each other, measured differences between experimental and control groups may be attributed to narasin intake.
[0063] With respect to average daily gain, which measures average weight gain per cattle per day, the control group had an average daily gain of 240 g / (cattle*day). The experimental group had an average daily gain of 284 g / (cattle*day). Accordingly, the inclusion of narasin in the mineral supplement of the control group resulted in an increase in average daily gain of 44 g / (cattle*day), or an 18% increase.
[0064] EXAMPLE 4
[0065] Method
[0066] The instant example describes an analysis of compositions comprising narasin.The compositions in the instant example are administered to cattle. In the analyses below, a control group, wherein a mineral supplement not including narasin was administered to the cattle was compared to an experimental group wherein narasin was administered to the cattle in a mineral supplement (i.e., an animal nutrient composition). Exemplary evaluations of the administration of the compositions to cattle can include clinical observations in the live animals as well as histopathological and biochemical evaluations of tissues as well as rumen content collected during necropsy of the animals. For instance, tissues can be collected for residue analysis. Furthermore, sample collection can include body weight of animals at treatment initiation and at completion.
[0067] In total, 44 Nelore cattle having an average initial body weight of 350 kg / cattle were tested across the control and experimental groups. All cattle were pastured in dry lot pens and were given a feed consisting of 90% grass silage (comprising primarily brachiaria brizantha) and 10% of a Type B proteic supplement. The control group contained 22 cattle divided among 2 different dry lots. The experimental group also consisted of 22 cattle divided among 2 different dry lots. The proteic supplement for the experimental group had a narasindosage of 130 ppm, such that the total diet had a narasin dosage of 13 ppm for the experimental group. Methane production was measured for each cattle 3-5 times each day using a greenfeed to determine the effects of narasin compared to the control group.|00068| The groups were tested for 197 days before results were compared. Day 0 was a fasting day. The next 14 days (days 1-14) were an acclimation period wherein the cattles’ previous diet was slowly shifted to the control and experimental diets. Day 15 was a fasting day. The remaining 182 days (days 15-197) constituted a treatment period where the control and experimental diets were given to the cattle for comparison. Day 197 was a fasting day. Body weight measurements were taken on a daily basis.
[0069] Results
[0070] With respect to absolute methane production, which measures the average total methane production per cattle per day, the control group had an average absolute methane production of 199.94 g / (cattle*day). The experimental group had an average absolute methane production of 177.75 g / (cattle*day). Accordingly, the inclusion of narasin in the diet of the experimental group resulted in a decrease in absolute methane production of 22. 19 g / (cattle*day), or a 11% decrease.
[0071] Referring now to Fig. 1, the average absolute methane production for the control group and the experimental group is shown over the course of the 2 weeks. For entries showing an asterisk above the data point, the P value was greater than 0.05. In general, both the control group and the experimental group exhibited lower than average absolute methane production from week 1 to week 10. The control group also exhibited lower than average methane production from week 18 to week 20.
[0072] With respect to methane production per kilogram body weight (g / kg), the experimental group exhibited a lower average methane production per kilogram of body weight than the control group. The control group had an average methane production per kilogram of bodyweight of 0.47 g / kg. The experimental group had an average methane production per kilogram of bodyweight of 0.42 g / kg.
[0073] Referring now to Fig. 2, the average methane production per kg of DMI is shown over the course of the 26 weeks. For entries showing an asterisk above the data point, the P value was greater than 0.05. In general, the experimental group treated with narasin exhibited lower methane production relative to DMI than the control group. There were only a few weeks (1, 14, 26) where the control group exhibited a lower methane production per kilogram of DMI and a few weeks (15, 20) where the methane production per kilogram of DMI was roughly equal for both groups.
[0074] EXAMPLE 5
[0075] Method
[0076] Six fistulated cattle receiving a standard diet (70% roughages and 30% concentrate) were used as inoculum donors. The animals were kept in a collective pen and were given food (a total and water daily ad libitum. Ruminal fluid was collected from each animal. Solid phase rumen fluid was collected manually. Liquid phase rumen fluid was collected using a vacuum pump. The ruminal fluids were stored at elevated temperature (approximately 39°C). For each ruminal fluid, half of the solid phase and half of the liquid phase were homogenized in a blender for 10 seconds and subsequently filtered using three layers of cotton tissue. Then, three inoculums were prepared by creating three pairs of the six homogenized and filtered ruminal fluids.
[0077] An in vitro analysis was designed using a 2x7 factorial design for each of the three inoculums obtained above. Each of the three inoculums were split in half into two treatment groups, a high roughage substrate treatment group and a high grain substrate treatment group. Each of those treatment groups were then split into seven sub-groups: a negative control sub-group (no ionophore), a positive control sub-group (25 ppm monensin), and 5 experimental sub-groups (5 ppm narasin, 10 ppm narasin, 15 ppm narasin, 20 ppm narasin, and 25 ppm narasin). Accordingly, each of the three inoculums were subjected to 14 different test conditions as shown below in Table 1.Table 1: Table 1 demonstrates the 14 different test conditions analyzed in this example.
[0078] For each of the above test conditions, a methanogenesis bioassay was carried out over a 24-hour incubation period for each of the three inoculums. In the methanogenesis bioassay, approximately 500mg of ground substrate was sifted through a 1 mm sieve and placed in each of three 160 mL fermentation flasks (one for each inoculum). Then, 25 mL of inoculum was diluted in 50 mL of buffered mineral solution, mixed with the treatment corresponding tothe test condition, and added to each fermentation flask. An additional flask for each inoculum was prepared as a blank (i.e., not including a substrate) to subtract background noise. All flasks were subsequently sealed and kept in a forced air oven at 39°C for the incubation period.|00079| For each of the above test conditions, a fermentative kinetics bioassay was also carried out over a 96-hour incubation period for each of the three inoculums. In the fermentative kinetics bioassay, approximately 1000 mg of ground substrate was sifted through a 1 mm sieve and placed in a 160 mL fermentation flask. Then, 10 mL of inoculum was diluted in 90 mL of buffered mineral solution, mixed with the treatment corresponding to the test condition, and added to the fermentation flask. An additional flask for each inoculum was prepared as a blank (i.e., not including a substrate) to subtract background noise. All flasks were subsequently sealed and kept in a forced air oven at 39°C for the incubation period.
[0080] During the incubation period for the methanogenesis bioassay, a PressData 800 pressure transducer was used to measure internal pressure of each flask at 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, and 24 hours. During the incubation period for the fermentative kinetics bioassay, a PressData 800 pressure transducer was used to measure internal pressure of each flask at 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 31 hours, 38 hours, 48 hours, 60 hours, and 72 hours. These internal pressure measurements were used to estimate gas volumes produced during incubation.
[0081] After the incubation period, samples of gases from each flask were collected and pooled in Vacutainer tubes for methane concentration analysis. Collected samples were analyzed using gas chromatography with a micropacked Schincarbon column and a calibration curve was generated using 50% purity methane as standard.
[0082] After the methane concentration analysis, the gas was released and a 2 mL sample of the liquid phase were sampled from each flask with a micro syringe and frozen for qualitative and quantitative analyses of short chain fatty acids (SCFAs). Samples were subjected to gas chromatography with a Stabilwax column to analyze acetic, propionic, isobutyric, iso-valeric, valeric, and total fatty acids.
[0083] An additional 2 mL sample of the liquid phase from each flask was collected using a micro syringe and stored in a freezer at -80°C for methanogenesis and PCR analyses. Samples were sent to the Molecular Biology Laboratory of USP-FZEA for metagenomic and PCR analyses.
[0084] An additional 2 mL sample of the liquid phase from each flask was collected using a micro syringe, subsequently acidified, and analyzed to determine ammonia concentration.
[0085] ResultsTable 2: Table 2 demonstrates averages for methane production taken from both the methanogenesis and fermentative kinetics bioassays. Values modified by an asterisk have means that differ from the Negative Control by P < 0.1.
[0086] With respect to methane production, experimental group 3 (15 ppm narasin), experimental group 5 (25 ppm narasin), and positive control group (25 ppm monensin) were effective (P < 0.01) to decrease the in vitro dry matter digestibility (IVDMD) CH4 adjusted (mL / g IVDMD) when compared to the negative control. Specifically, the treatments resulted in reductions of 27% (15 ppm narasin), 34% (25 ppm narasin), and 38% (25 ppm monensin) of the adjusted methane production per gram of the IVDMD when compared to the negative control. These outcomes demonstrate that at least the above treatments increase positive parameters when compared to the negative control because reduced methane production is associated with lower environmental impact and a decrease in energy loss for the animals (methane production represents a significant loss of dietary energy in ruminants). When comparing the highroughage diet to the high concentrate diet, CH4 content was higher (approximately 11%) and CH4 adjusted was higher (approximately twice as high).Table 3: Table 3 demonstrates, for the methanogenesis bioassay, the averages for amounts of various short chain fatty acids (SCFA) per gram of digestible dry matter — including acetic acid, propionic acid, butyric acid, iso-butyric acid, valeric acid, and iso-valeric acid — amount of ammoniacal nitrogen per gram of dry matter, in vitro dry matter digestibility (IVDMD), in vitro neutral detergent fiber digestibility (IVNDFD), and the partition factor for both tested substrates. Entries marked with an “a” differ from the Negative Control (P < 0.01).
[0087] With respect to the SCFAs measured in the methanogenesis bioassay, percentages of the total SCFA content can be obtained by dividing the amount of any individualSCFA by the total amount for that control or experimental group. In the high roughage diet, a linear effect was observed (P < 0.1) for the valeric and iso-valeric acid concentrations as well as the butyric acid percentage. While the valeric and iso- valeric concentrations increased with increasing the narasin doses, the percentage of butyric acid decreased with increasing the narasin doses. In the high concentrate diet, the butyric acid percentage decreased (P = 0.003) with increasing doses of narasin. However, a quadratic effect (P = 0.07) was observed for the valeric acid percentage, where the percentage increased with the narasin doses of 10 ppm and 15 ppm and decreased with the doses of 20 ppm and 25 ppm. Digestibility parameters were higher in high concentrate diet compared to high roughage diet and the proportion of propionic acid was also higher for high concentrate diet than high roughage diet. These results are in agreement with in vivo observations.Table 4: Table 4 demonstrates, for the fermentative kinetics bioassay, the gas adjusted for the grams of dry matter, the averages for amounts of various short chain fatty acids (SCFA) per gram of digestible dry matter — including acetic acid, propionic acid, butyric acid, iso-butyric acid, valeric acid, and iso-valeric acid — in vitro dry matter digestibility (IVDMD), in vitro neutral detergent fiber digestibility (IVNDFD), and the partition factor for both tested substrates. Entries marked with an “a” differ from the Negative Control (P < 0.1). Entries marked with a “b” differ from the Positive Control (P < 0.1).
[0088] With respect to the SCFAs measured in the fermentative kinetics bioassay, percentages of the total SCFA content can be obtained by dividing the amount of any individual SCFA by the total amount for that control or experimental group. In the high roughage diet, a linear effect was observed (P < 0.1) for the gas adjusted, butyric acid, iso-butyric acid, and isovaleric acid concentrations as well as the butyric acid percentage, IVDMD, IVNDFD and partition factor. Specifically, as narasin dosage increased, each of the forgoing decreased linearly except for the partition factor, which increased linearly with narasin dosage. A quadratic effect was observed (P < 0.06) for gas adjusted, acetic acid, butyric acid, iso-butyric acid, and iso-valeric acid concentrations as well as for the partition factor. In the high concentrate diet, the IVNDFD decreased (P = 0.09) and the partition factor increased (P = 0.05) with increasing in narasin dose. A quadratic effect was detected (P = 0.09) for IVNDFD, sinceExperimental Group 4 (narasin 20 ppm) had a higher IVNDFD value compared to the other treatment doses.
[0089] In general, both high roughage and high concentrate diets demonstrated that treatment improved the percentage of propionic acid and increased the proportion of propionic acid relative to the total amount of SCFAs produced, which is in line with expectations. With respect to the gas adjusted values in both diets, the usage of narasin and monensin correlates with a reduction gas production and digestibility without impacting SCFA concentration. This is unexpected and not reflective of the literature surrounding ionophores and rumen fermentation. Moreover, these results are different than the outcomes observed in the methanogenesis bioassay study above. Without being bound by theory, one possible explanation is that the increased incubation length for the fermentative kinetics bioassay may be responsible, at least in part, for this difference.
[0090] With respect to both the methanogenesis bioassay and the fermentative kinetics bioassay, it is clear that increased inclusion rate of narasin resulted in decreased methane concentrations in high roughage diets. Both the positive control (25 ppm monensin) and Experimental Group 5 (25 ppm narasin) decreased total, net, content, and adjusted methane parameters in the high roughage diet. In particular, Experimental Group 3 (15 ppm narasin) and 5 (25 ppm narasin) were effective to decrease methane production per gram of IVDMD by 27 % and 34% respectively when compared to the negative control group not treated with ionophores.
[0091] EXAMPLE 6
[0092] Method
[0093] The instant example describes an analysis of compositions comprising monensin and narasin. The compositions in the instant example are administered to cattle.
[0094] Exemplary evaluations of the administration of the compositions to cattle can include clinical observations in the live animals as well as histopathological and biochemical evaluations of tissues as well as rumen content collected during necropsy of the animals.For instance, tissues can be collected for residue analysis. Furthermore, sample collection can include i) body weight of animals at treatment initiation and at completion, ii) whole blood collected at treatment initiation and at completion for complete blood count (CBC) analysis, iii) whole blood collected in serum separating tube (SST) at treatment initiation and at completion for serum chemistry analysis, and / or iv) feed samples for nutrient analysis and Investigational Veterinary Product (IVP) concentration, here monensin and narasin.
[0095] In the instant example, cattle can be administered the compositions of the present disclosure for approximately 14 days. Administration of the compositions can be achieved bycombining the compositions comprising monensin and narasin with a Type C feed and having the animals eat the combination.Table 5: Table 5 demonstrates the control group (1) and the 3 experimental groups (2-4) analyzed in Example 6.|00096| With respect to the groups above, Experimental Groups 2 and 3 had a monensin to narasin ratio of approximately 3 to 1. With respect to Experimental Group 4, a monensin to narasin ratio of approximately 4 to 3 was used instead. These experimental groups were compared to a negative control administered neither narasin nor monensin.
[0097] Experimental Groups 2-4 were first subjected to an acclimatization period wherein their diet was gradually substituted for the experimental diets used. Specifically, this involved a gradual introduction of a non-medicated grain-based diet to the standard roughage and lucerne pellets diet, followed by the gradual introduction of the medicated version of the diet including monensin and narasin for the experimental groups. During this acclimatization period and the test period, the cattle were allowed to feed only on the study food ad libitum. Cattle were subjected to a veterinary health examination on day -1 and on day 14, wherein the veterinary examination included weighing the cattle, collecting blood, general health observations, and otherwise assessing the health of the cattle. General health observations were also conducted on a twice daily basis. After day 14, the cattle were euthanized and tissue samples were preserved for further analysis including histopathology and residue analysis for monensin and narasin. Specifically, tissue from the muscle, liver, kidneys, and fat were taken to determine ionophore concentration.
[0098] Blood samples were collected in a sodium citrate tube to analyze coagulation variables, serum tubes to analyze clinical chemistry variables, and EDTA tubes for hematology variables. Blood specimens collected into citrate tubes were centrifuged at approximately 2400 x g for 15 minutes in a centrifuge and the plasma separated and retained. Blood specimenscollected into serum tubes were allowed to stand for at least 30 minutes before centrifuging at approximately 1800-2000 x g for 10-15 minutes in a centrifuge ensuring that the gel had moved between, and was separating, serum from blood cells. Blood specimens collected into EDTA tubes were mixed well and the whole blood was used to assess the hematology variables.
[0099] Results[000100] Several non-serious adverse effects were observed during the study, including diarrhea, minor ocular discharge, corneal oedema / lesions / scarring, lump under chin, cuts / grazes on legs, alopecia and crust / infection. Some of these changes can likely be attributed to the change in diet (e.g., diarrhea). However, all of these changes were unlikely to be attributable to the IVP tested herein.Table 6: Table 6 demonstrates average daily weight gain (ADWG) and average daily feed intake (ADFI) for the control group and each experimental group.[000101] With respect to Table 6, it is clear that all animals exhibited a positive average daily weight gain. Feed intake was measured using a scale in the feed trough. Average daily weight gain was measured using calibrated scales at the point of feeding. Of note, the ratio between average daily weight gain to average daily feed intake was greater for all experimental groups than for the negative control group. Experimental Group 3 exhibited the greatest ADWG: ADFI ratio (0.21 ), followed by Experimental Group 2 (0. 151 ), followed by Experimental Group 4 (0.145), and followed by the Negative Control Group 1 (0.132).Table 7: Table 7 demonstrates the micrograms of each IVP (monensin and narasin) found per kg of the respective tissue, specifically kidney tissue, liver tissue, muscle tissue, and fat tissue.[000102] No amounts of monensin or narasin were detected in the negative control Experimental Group 1. Accordingly, none of the experimental groups exhibited an adverse reaction to administration of narasin and monensin as shown in the micrograms of IVP per kilogram of tissue.[000103] The in- feed administration of monensin and narasin in combination, at all dose rates examined in this study, was not associated with any adverse effect. The test rations were well tolerated and not associated with clinical pathology abnormalities, gross pathological or histological findings. Tissue residues of monensin and narasin were successfully determined. ASPECTS OF THE INVENTION[000104] The following numbered embodiments are contemplated and are non-limiting.[000105] 1. An animal nutrient composition comprising narasin.[000106] 2. The animal nutrient composition of clause 1, wherein narasin is present in an amount between 5- 150 g / ton.[000107] 3. The animal nutrient composition of clause 1, wherein narasin is present in an amount between 13-150 g / ton.[000108] 4. The animal nutrient composition of clause 1, wherein narasin is present in an amount between 50-150 g / ton.[000109] 5. The animal nutrient composition of clause 1, wherein narasin is present in an amount between 50-130 g / ton.[000110] 6. The animal nutrient composition of clause 1, wherein narasin is present in an amount between 50-100 g / ton.[000111] 7. The animal nutrient composition of clause 1 , wherein narasin is present in an amount between 50-80 g / ton.[000112] 8. The animal nutrient composition of clause 1, wherein narasin is present in an amount between 15-25 g / ton.[000113] 9. The animal nutrient composition of clause 1, wherein narasin is present in an amount between 5-13 g / ton.[000114] 10. The animal nutrient composition of any of clauses 1 through 10, wherein the animal nutrient composition comprises a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, and a combination thereof. [000115] 11. The animal nutrient composition of clause 10, wherein the animal nutrient composition comprises a diet composition.[000116] 12. The animal nutrient composition of clause 10, wherein the animal nutrient composition comprises a supplement composition.[000117] 13. The animal nutrient composition of clause 10, wherein the animal nutrient composition comprises a mineral composition.[000118] 14. The animal nutrient composition of any of clauses 1 through 13, wherein the animal nutrient composition comprises a plurality of ionophores, and wherein the plurality of ionophores comprises narasin and at least one secondary ionophore.[000119] 15. The animal nutrient composition of clause 14, wherein the secondary ionophore is selected from a list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, and a combination thereof.[000120] 16. The animal nutrient composition of clause 14, wherein the secondary ionophore is monensin.[000121] 17. The animal nutrient composition of any of clauses 14 through 16, wherein the secondary ionophore is present in the animal nutrient composition at between 5- 1200 g / ton.[000122] 18. The animal nutrient composition of any of clauses 14 through 16, wherein the secondary ionophore is present in the animal nutrient composition at between 5-500 g / ton.[000123] 19. The animal nutrient composition of any of clauses 14 through 16, wherein the secondary ionophore is present in the animal nutrient composition at between 25- 400 g / ton.[000124] 20. The animal nutrient composition of any of clauses 14 through 16, wherein the secondary ionophore is present in the animal nutrient composition at between 50- 250 g / ton.[000125] 21. The animal nutrient composition of any of clauses 14 through 16, wherein the secondary ionophore is present in the animal nutrient composition at between 100- 200 g / ton.[000126] 22. An animal feed composition comprising: a feed; and an animal nutrient composition, wherein the animal nutrient composition comprises narasin.[000127] 23. The animal feed composition of clause 22, wherein the animal nutrient composition comprises a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, and a combination thereof.[000128] 24. The animal feed composition of clause 22, wherein the animal nutrient composition comprises a diet composition.[000129] 25. The animal feed composition of clause 22, wherein the animal nutrient composition comprises a supplement composition.[000130] 26. The animal feed composition of clause 22, wherein the animal nutrient composition comprises a mineral composition.[000131] 27. The animal feed composition of any of clauses 22 through 26, wherein the feed comprises a Type A feed, a Type B feed, a Type C feed, and a combination thereof.[000132] 28. The animal feed composition of any of clauses 22 through 26, wherein the feed comprises a Type A feed.[000133] 29. The animal feed composition of any of clauses 22 through 26, wherein the feed comprises a Type B feed.[000134] 30. The animal feed composition of any of clauses 22 through 26, wherein the feed comprises a Type C feed.[000135] 31. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, and a combination thereof.[000136] 32. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises corn.[000137] 33. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises cotton seed.[000138] 34. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises soybean.[000139] 35. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises a soybean meal.[000140] 36. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises soybean oil.[000141] 37. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises rapeseed.[000142] 38. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises a rapeseed oil.[000143] 39. The animal feed composition of any of clauses 22 through 30, wherein the feed comprises a mineral mix.[000144] 40. The animal feed composition of any of clauses 22 through 39, wherein the feed comprises a total mixed ration (TMR) forage ingredient.[000145] 41. The animal feed composition of clause 40, wherein the TMR forage ingredient is selected from the group consisting of com silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and a combination thereof.[000146] 42. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises corn silage.[000147] 43. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises grass silage.[000148] 44. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises oat silage.[000149] 45. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises alfalfa silage.[000150] 46. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises wheat silage.[000151] 47. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises straw.[000152] 48. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises grass.[000153] 49. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises fresh grass.[000154] 50. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises alfalfa.[000155] 51. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises hay.[000156] 52. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises hay from grass.[000157] 53. The animal feed composition of clause 40, wherein the TMR forage ingredient comprises hay from alfalfa.[000158] 54. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 10% (w / w) of the feed.[000159] 55. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 15% (w / w) of the feed.[000160][000161] 56. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 20% (w / w) of the feed.[000162] 57. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 25% (w / w) of the feed.[000163] 58. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 30% (w / w) of the feed.[000164] 59. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 50% (w / w) of the feed.[000165] 60. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 70% (w / w) of the feed.[000166] 61. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 90% (w / w) of the feed.[000167] 62. The animal feed composition of any of clauses 40 through 53, wherein the TMR forage ingredient comprises at least 98% (w / w) of the feed.[000168] 63. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 5-150 g / ton.[000169] 64. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 13-150 g / ton.[000170] 65. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 50-150 g / ton.[000171] 66. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 50-130 g / ton.[000172] 67. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 50-100 g / ton.[000173] 68. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 50-80 g / ton.[000174] 69. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 15-25 g / ton.[000175] 70. The animal feed composition of any of clauses 22 through 62, wherein narasin is present in the animal nutrient composition at between 5-13 g / ton.[000176] 71. The animal feed composition of any of clauses 22 through 70, wherein the animal nutrient composition comprises a plurality of ionophores, and wherein the plurality of ionophores comprises narasin and at least one secondary ionophore.[000177] 72. The animal feed composition of clause 71, wherein the secondary ionophore is selected from a list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, and a combination thereof.[000178] 73. The animal feed composition of clause 71, wherein the secondary ionophore is monensin.[000179] 74. The animal feed composition of any of clauses 71 through 73, wherein the secondary ionophore is present in the animal nutrient composition at between 5-1200 g / ton.[000180] 75. The animal feed composition of any of clauses 71 through 73, wherein the secondary ionophore is present in the animal nutrient composition at between 5-500 g / ton. [000181] 76. The animal feed composition of any of clauses 71 through 73, wherein the secondary ionophore is present in the animal nutrient composition at between 25-400 g / ton. [000182] 77. The animal feed composition of any of clauses 71 through 73, wherein the secondary ionophore is present in the animal nutrient composition at between 50-250 g / ton. [000183] 78. The animal feed composition of any of clauses 71 through 73, wherein the secondary ionophore is present in the animal nutrient composition at between 100-200 g / ton.[000184] 79. A method for increasing performance of an animal, the method comprising: administering an animal nutrient composition comprising narasin or an animal feed composition comprising narasin and an animal nutrient composition to the animal, wherein the administration of the animal nutrient composition or the administration of the animal feed composition increases the performance of the animal.[000185] 80. The method of clause 79, wherein the increase in performance of the animal is selected from the list consisting of an increase in feed efficiency in the animal, an increase in average daily gain in the animal, an increase in hot carcass weight of the animal, an optimization of rumen flora of the animal, optimization of volatile fatty acid production in the animal, optimization of propionic acid production in the animal, and a combination thereof. [000186] 81. The method of clause 79, wherein the increase in performance of the animal comprises an increase in feed efficiency in the animal.[000187] 82. The method of clause 79, wherein the increase in performance of the animal comprises an increase in average daily gain in the animal.[000188] 83. The method of clause 79, wherein the increase in performance of the animal comprises an increase in hot carcass weight of the animal.[000189] 84. The method of clause 79, wherein the increase in performance of the animal comprises an optimization of rumen flora of the animal.[000190] 85. The method of clause 79, wherein the increase in performance of the animal comprises optimization of volatile fatty acid production in the animal.[000191] 86. The method of clause 79, wherein the increase in performance of the animal comprises optimization of propionic acid production in the animal.[000192] 87. The method of any of clauses 79 through 86, wherein the animal nutrient composition or the animal feed composition is administered for at least 14 days.[000193] 88. The method of any of clauses 79 through 86, wherein the animal nutrient composition or the animal feed composition is administered for at least a month.[000194] 89. The method of any of clauses 79 through 86, wherein the animal nutrient composition or the animal feed composition is administered for at least 3 months.[000195] 90. The method of any of clauses 79 through 86, wherein the animal nutrient composition or the animal feed composition is administered for at least 6 months.[000196] 91. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 5-150 g / ton.[000197] 92. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 13-150 g / ton.[000198] 93. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 50-150 g / ton.[000199] 94. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 50-130 g / ton.[000200] 95. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 50-100 g / ton.[000201] 96. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 50-80 g / ton.[000202] 97. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 15-25 g / ton.[000203] 98. The method of any of clauses 79 through 90, wherein the narasin is present in the animal nutrient composition or the animal feed composition at between 5-13 g / ton.[000204] 99. The method of any of clauses 79 through 98, wherein the method comprises administering the animal nutrient composition comprising narasin to the animal. [000205] 100. The method of clause 99, wherein the animal nutrient composition comprises a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, and a combination thereof.[000206] 101. The method of any of clause 99, wherein the animal nutrient composition comprises a diet composition.[000207] 102. The method of any of clause 99, wherein the animal nutrient composition comprises a supplement composition.[000208] 103. The method of clause 99, wherein the animal nutrient composition comprises a mineral composition.[000209] 104. The method of any of clauses 79 through 98, wherein the method comprises administering the animal feed composition comprising narasin to the animal, wherein the animal feed composition further comprises a feed.[000210] 105. The method of clause 104, wherein the feed comprises a feed selected from the list consisting of a Type A feed, a Type B feed, a Type C feed, and a combination thereof.[000211] 106. The method of clause 104, wherein the feed comprises a Type A feed.[000212] 107. The method of clause 104, wherein the feed comprises a Type B feed.[000213] 108. The method of clause 104, wherein the feed comprises a Type C feed.[000214] 109. The method of any of clauses 104 through 108, wherein the feed comprises a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, and a combination thereof.[000215] 110. The method of any of clauses 104 through 108, wherein the feed comprises corn.[000216] 111. The method of any of clauses 104 through 108, wherein the feed comprises cotton seed.[000217] 112. The method of any of clauses 104 through 108, wherein the feed comprises soybean.[000218] 113. The method of any of clauses 104 through 108, wherein the feed comprises soybean meal.[000219] 114. The method of any of clauses 104 through 108, wherein the feed comprises soybean oil.[000220] 115. The method of any of clauses 104 through 108, wherein the feed comprises rapeseed.[000221] 116. The method of any of clauses 104 through 108, wherein the feed comprises rapeseed oil.[000222] 117. The method of any of clauses 104 through 108, wherein the feed comprises a mineral mix.[000223] 118. The method of any of clauses 104 through 117, wherein the feed comprises a total mixed ration (TMR) forage ingredient.[000224] 119. The method of clause 118, wherein the TMR forage ingredient is selected from the list consisting of corn silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and a combination thereof.1000225] 120. The method of clause 118, wherein the TMR forage ingredient is corn silage.[000226] 121. The method of clause 118, wherein the TMR forage ingredient is grass silage.[000227] 122. The method of clause 118, wherein the TMR forage ingredient is oat silage.[000228] 123. The method of clause 118, wherein the TMR forage ingredient is alfalfa silage.[000229] 124. The method of clause 118, wherein the TMR forage ingredient is wheat silage.[000230] 125. The method of clause 118, wherein the TMR forage ingredient is straw.[000231] 126. The method of clause 118, wherein the TMR forage ingredient is fresh grass.[000232] 127. The method of clause 118, wherein the TMR forage ingredient is alfalfa.[000233] 128. The method of clause 118, wherein the TMR forage ingredient is hay.[000234] 129. The method of clause 118, wherein the TMR forage ingredient is hay from grass.[000235] 130. The method of clause 118, wherein the TMR forage ingredient is hay from alfalfa.[000236] 131. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 10% (w / w) of the feed.[000237] 132. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 15% (w / w) of the feed.[000238] 133. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 20% (w / w) of the feed.[000239] 134. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 25% (w / w) of the feed.[000240] 135. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 30% (w / w) of the feed.[000241] 136. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 50% (w / w) of the feed.[000242] 137. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 70% (w / w) of the feed.[000243] 138. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 90% (w / w) of the feed.[000244] 139. The method of any of clauses 118 through 130, wherein the TMR forage ingredient comprises at least 98% (w / w) of the feed.[000245] 140. The method of any of clauses 79 through 139, wherein the animal nutrient composition or the animal feed composition comprises a plurality of ionophores, wherein the plurality of ionophores comprises narasin and at least a secondary ionophore, and wherein the administration of the combination of narasin and the at least one secondary ionophore synergistically increases the performance of the animal.[000246] 141. The method of clause 140, wherein the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, other similarly non-toxic ionophores, or some combination thereof.[000247] 142. The method of clause 140, wherein the secondary ionophore is monensin.[000248] 143. The method of any of clauses 140 through 142, wherein the animal wherein the secondary ionophore is present in the animal nutrient composition or is present in the animal feed composition at between 5-1200 g / ton.[000249] 144. The method of any of clauses 140 through 142, wherein the animal wherein the secondary ionophore is present in the animal nutrient composition or is present in the animal feed composition at between 5-500 g / ton.[000250] 145. The method of any of clauses 140 through 142, wherein the animal wherein the secondary ionophore is present in the animal nutrient composition or is present in the animal feed composition at between 25-400 g / ton.[000251] 146. The method of any of clauses 140 through 142, wherein the animal wherein the secondary ionophore is present in the animal nutrient composition or is present in the animal feed composition at between 50-250 g / ton.[000252] 147. The method of any of clauses 140 through 142, wherein the animal wherein the secondary ionophore is present in the animal nutrient composition or is present in the animal feed composition at between 100-200 g / ton.[000253] 148. The method of any of clauses 79 through 147, wherein the animal is a ruminant.[000254] 149. The method of clause 148, wherein the ruminant is selected from the list consisting of a bovine, an ovine, and a caprine.[000255] 150. The method of clause 148, wherein the ruminant is a bovine.[000256] 151. The method of clause 150, wherein the bovine is selected from a list consisting of cattle, bison, African buffalo, water buffalo, and antelope.1000257] 152. The method of clause 150, wherein the bovine is a cattle.[000258] 153. The method of clause 150, wherein the bovine is a bison.[000259] 154. The method of clause 150, wherein the bovine is an African buffalo.[000260] 155. The method of clause 150, wherein the bovine is a water buffalo.[000261] 156. The method of clause 150, wherein the bovine is an antelope.[000262] 157. The method of clause 152, wherein the cattle is selected from the list consisting of a heifer, a steer, a bull, and a cow.[000263] 158. The method of clause 152, wherein the cattle is a heifer.[000264] 159. The method of clause 152, wherein the cattle is a steer.[000265] 160. The method of clause 152, wherein the cattle is a bull.[000266] 161. The method of clause 152, wherein the cattle is a cow.[000267] 162. A method for decreasing methane production of an animal, the method comprising: administering an animal nutrient composition comprising narasin or an animal feed composition comprising narasin and an animal nutrient composition to the animal, wherein the administration decreases methane production from the animal.[000268] 163. The method of clause 162, wherein the decrease in methane production comprises an absolute decrease in methane.[000269] 164. The method of any of clauses 162 through 163, wherein the decrease in methane production is relative to the animal’s body weight (BW).[000270] 165. The method of any of clauses 162 through 164, wherein the decrease in methane production is relative to the animal’s dry matter (DM) intake.[000271] 166. The method of any of clauses 162 through 165, wherein the decrease in methane production comprises an indirect decrease in methane.[000272] 167. The method of any of clauses 162 through 166, wherein the decrease in methane production is associated with a decrease in methanogenesis in the animal.[000273] 168. The method of any of clauses 162 through 167, wherein the decrease in methane production is associated with an improvement in the ratio of volatile fatty acids (VFAs).[000274] 169. The method of any of clauses 162 through 168, wherein the decrease in methane production is associated with an improvement in the production of propionate relative to other volatile fatty acids (VFAs).[000275] 170. The method of any of clauses 162 through 169, wherein the animal nutrient composition or the animal feed composition is applied to the animal for at least 14 days.1000276] 171. The method of any of clauses 162 through 169, wherein the animal nutrient composition or the animal feed composition is applied to the animal for at least a month.[000277] 172. The method of any of clauses 162 through 169, wherein the animal nutrient composition or the animal feed composition is applied to the animal for at least 3 months.[000278] 173. The method of any of clauses 162 through 169, wherein the animal nutrient composition or the animal feed composition is applied to the animal for at least 6 months.[000279] 174. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 5-150 g / ton.[000280] 175. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 13-150 g / ton.[000281] 176. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 50-150 g / ton.[000282] 177. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 50-130 g / ton.[000283] 178. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 50-100 g / ton.[000284] 179. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 50-80 g / ton.[000285] 180. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 15-25 g / ton.[000286] 181. The method of any of clauses 162 through 173, wherein narasin is present in the animal nutrient composition or the animal feed composition at between 5-13 g / ton.1000287] 182. The method of any of clauses 162 through 181, wherein the animal nutrient composition or the animal feed composition comprises a plurality of ionophores, wherein the plurality of ionophores comprises narasin and a secondary ionophore, and wherein the administration of narasin and the secondary ionophore synergistically provides the decrease in methane production in the animal.[000288] 183. The method of clause 182, wherein the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, or a combination thereof.[000289] 184. The method of clause 182, wherein the secondary ionophore is monensin.[000290] 185. The method of any of clauses 182 through 184, wherein the secondary ionophore is present in the animal nutrient composition or the animal feed composition at between 5-1200 g / ton.[000291] 186. The method of any of clauses 182 through 184, wherein the secondary ionophore is present in the animal nutrient composition or the animal feed composition at between 5-500 g / ton.[000292] 187. The method of any of clauses 182 through 184, wherein the secondary ionophore is present in the animal nutrient composition or the animal feed composition at between 25-400 g / ton.[000293] 188. The method of any of clauses 182 through 184, wherein the secondary ionophore is present in the animal nutrient composition or the animal feed composition at between 50-250 g / ton.[000294] 189. The method of any of clauses 182 through 184, wherein the secondary ionophore is present in the animal nutrient composition or the animal feed composition at between 100-200 g / ton.[000295] 190. The method of any of clauses 162 through 189, wherein the animal is selected from a list consisting of a ruminant, an ovine, and a caprine.[000296] 191. The method of clause 190, wherein the animal is a ruminant.[000297] 192. The method of clause 191, wherein the ruminant is selected from the list consisting of a bovine, an ovine, and a caprine.[000298] 193. The method of clause 192, wherein the ruminant is a caprine.[000299] 194. The method of clause 192, wherein the ruminant is an ovine.[000300] 195. The method of clause 192, wherein the ruminant is a bovine.[000301] 196. The method of clause 195, wherein the bovine is selected from the list consisting of cattle, bison, African buffalo, water buffalo, and antelope.[000302] 197. The method of clause 196, wherein the bovine is a bison.1000303] 198. The method of clause 196, wherein the bovine is an African buffalo.[000304] 199. The method of clause 196, wherein the bovine is a water buffalo.[000305] 200. The method of clause 196, wherein the bovine is an antelope.[000306] 201. The method of clause 196, wherein the bovine is a cattle.[000307] 202. The method of clause 201, wherein the cattle is selected from a list consisting of a heifer, a steer, a bull, and a cow.[000308] 203. The method of clause 202, wherein the cattle is a heifer.[000309] 204. The method of clause 202, wherein the cattle is a steer.[000310] 205. The method of clause 202, wherein the cattle is a bull.[000311] 206. The method of clause 202, wherein the cattle is a cow.[000312] 207. The method of any of clauses 162 through 206, wherein the animal nutrient composition is administered to the animal.[000313] 208. The method of clause 207, wherein the animal nutrient composition comprises a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, and a combination thereof.[000314] 209. The method of clause 208, wherein the animal nutrient composition comprises the diet composition.[000315] 210. The method of clause 209, wherein the animal nutrient composition comprises the supplement composition.[000316] 211. The method of clause 209, wherein the animal nutrient composition comprises the mineral composition.[000317] 212. The method of any of clauses 162 through 206, wherein the animal feed composition is administered to the animal, and wherein the animal feed composition comprises a feed.[000318] 213. The method of clause 212, wherein the feed is selected from a list consisting of a Type A feed, a Type B feed, a Type C feed, and a combination thereof.[000319] 214. The method of clause 213, wherein the feed comprises a Type A feed.[000320] 215. The method of clause 213, wherein the feed comprises a Type B feed.[000321] 216. The method of clause 213, wherein the feed comprises a Type C feed.[000322] 217. The method of any of clauses 212 through 216, wherein the feed comprises a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, and a combination thereof.[000323] 218. The method of clause 217, wherein the feed comprises corn.[000324] 219. The method of clause 217, wherein the feed comprises cotton seed.[000325] 220. The method of clause 217, wherein the feed comprises soybean.1000326] 221. The method of clause 217, wherein the feed comprises soybean meal.[000327] 222. The method of clause 217, wherein the feed comprises soybean oil.[000328] 223. The method of clause 217, wherein the feed comprises rapeseed.[000329] 224. The method of clause 217, wherein the feed comprises rapeseed oil.[000330] 225. The method of clause 217, wherein the feed comprises the mineral mix.[000331] 226. The method of any of clauses 212 through 225, wherein the feed comprises a total mixed ration (TMR) forage ingredient.[000332] 227. The method of clause 226, wherein the TMR forage ingredient is selected from the list consisting of corn silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and a combination thereof.[000333] 228. The method of clause 227, wherein the TMR forage ingredient is corn silage.[000334] 229. The method of clause 227, wherein the TMR forage ingredient is grass silage.[000335] 230. The method of clause 227, wherein the TMR forage ingredient is oat silage.[000336] 231. The method of clause 227, wherein the TMR forage ingredient is alfalfa silage.[000337] 232. The method of clause 227, wherein the TMR forage ingredient is wheat silage.[000338] 233. The method of clause 227, wherein the TMR forage ingredient is straw.[000339] 234. The method of clause 227, wherein the TMR forage ingredient is grass.[000340] 235. The method of clause 227, wherein the TMR forage ingredient is fresh grass.[000341] 236. The method of clause 227, wherein the TMR forage ingredient is alfalfa.[000342] 237. The method of clause 227, wherein the TMR forage ingredient is hay.[000343] 238. The method of clause 227, wherein the TMR forage ingredient is hay from grass.[000344] 239. The method of clause 227, wherein the TMR forage ingredient is hay from alfalfa.[000345] 240. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 10% (w / w) of the feed.[000346] 241. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 15% (w / w) of the feed.[000347] 242. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 20% (w / w) of the feed.[000348] 243. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 25% (w / w) of the feed.[000349] 244. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 30% (w / w) of the feed.245. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 50% (w / w) of the feed.[000350] 246. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 70% (w / w) of the feed.[000351] 247. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 90% (w / w) of the feed.[000352] 248. The method of any of clauses 226 through 239, wherein the TMR forage ingredient comprises at least 98% (w / w) of the feed.[000353] 249. A kit comprising narasin.[000354] 250. The kit of clause 249, wherein the kit is configured to be administered to an animal as an animal nutrient composition or as an animal feed composition.[000355] 251. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 5-150 g / ton.[000356] 252. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 13-150 g / ton.[000357] 253. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 50-150 g / ton.[000358] 254. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 50-130 g / ton.[000359] 255. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 50-100 g / ton.[000360] 256. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 50-80 g / ton.[000361] 257. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 15-25 g / ton.[000362] 258. The kit of clause 250, wherein narasin is present in the animal nutrient composition, the animal feed composition, or the kit at between 5-13 g / ton.[000363] 259. The kit of any of clauses 249 through 258, wherein the kit comprises a plurality of ionophores, and wherein the plurality of ionophores comprises narasin and at least one secondary ionophore.1000364] 260. The kit of clause 259, wherein the kit comprises a secondary ionophore selected from a list consisting of monensin, lasalocid, salinomycin, maduramicin, laidlomycin, semduramycin, flavomycin, virginiamycin, and a combination thereof.[000365] 261. The kit of clause 259, wherein the secondary ionophore is monensin.[000366] 262. The kit of any of clauses 259 through 261, wherein the secondary ionophore is present in the animal nutrient composition, the animal feed composition, or the kit at between 5-1200 g / ton.[000367] 263. The kit of any of clauses 259 through 261, wherein the secondary ionophore is present in the animal nutrient composition, the animal feed composition, or the kit at between 5-500 g / ton.[000368] 264. The kit of any of clauses 259 through 261, wherein the secondary ionophore is present in the animal nutrient composition, the animal feed composition, or the kit at between 25-400 g / ton.[000369] 265. The kit of any of clauses 259 through 261, wherein the secondary ionophore is present in the animal nutrient composition, the animal feed composition, or the kit at between 50-250 g / ton.[000370] 266. The kit of any of clauses 259 through 261, wherein the secondary ionophore is present in the animal nutrient composition, the animal feed composition, or the kit at between 100-200 g / ton.[000371] 267. The kit of any of clauses 249 through 266, wherein the kit further comprises the animal nutrient composition, and wherein the kit is configured to be administered to the animal as an animal nutrient composition.[000372] 268. The kit of clause 267, wherein the animal nutrient composition comprises a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, and a combination thereof.[000373] 269. The kit of clause 268, wherein the animal nutrient composition comprises the diet composition.[000374] 270. The kit of clause 268, wherein the animal nutrient composition comprises the supplement composition.[000375] 271. The kit of clause 268, wherein the animal nutrient composition comprises the mineral composition.[000376] 272. The kit of any of clauses 249 through 266, wherein the kit further comprises the animal feed composition, wherein the animal feed composition comprises the animal nutrient composition and a feed, and wherein the kit is configured to be administered to the animal as an animal feed composition.[000377] 273. The kit of clause 272, wherein the feed is selected from the list consisting of a Type A feed, a Type B feed, a Type C feed, or a combination thereof.[000378] 274. The kit of clause 272, wherein the feed comprises a Type A feed.[000379] 275. The kit of clause 272, wherein the feed comprises a Type B feed.[000380] 276. The kit of clause 272, wherein the feed comprises a Type C feed.[000381] 277. The kit of any of clauses 272 through 276, wherein the feed comprises a material selected from the list consisting of corn, cotton seed, soybean, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mix, and a combination thereof.[000382] 278. The kit of clause 277, wherein the feed comprises com.[000383] 279. The kit of clause 277, wherein the feed comprises cotton seed.[000384] 280. The kit of clause 277, wherein the feed comprises soybean.[000385] 281. The kit of clause 277, wherein the feed comprises soybean meal.[000386] 282. The kit of clause 277, wherein the feed comprises soybean oil.[000387] 283. The kit of clause 277, wherein the feed comprises rapeseed.[000388] 284. The kit of clause 277, wherein the feed comprises rapeseed oil.[000389] 285. The kit of clause 277, wherein the feed comprises the mineral mix.[000390] 286. The kit of any of clauses 272 through 285, wherein the feed comprises a total mixed ration (TMR) forage ingredient.[000391] 287. The kit of clause 286, wherein the feed comprises a TMR forage ingredient selected from the list consisting of corn silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, hay from grass, hay from alfalfa, and a combination thereof.[000392] 288. The kit of clause 287, wherein the TMR forage ingredient is corn silage.[000393] 289. The kit of clause 287, wherein the TMR forage ingredient is grass silage.[000394] 290. The kit of clause 287, wherein the TMR forage ingredient is oat silage.[000395] 291. The kit of clause 287, wherein the TMR forage ingredient is alfalfa silage.[000396] 292. The kit of clause 287, wherein the TMR forage ingredient is wheat silage.[000397] 293. The kit of clause 287, wherein the TMR forage ingredient is straw.[000398] 294. The kit of clause 287, wherein the TMR forage ingredient is grass.[000399] 295. The kit of clause 287, wherein the TMR forage ingredient is fresh grass.[000400] 296. The kit of clause 287, wherein the TMR forage ingredient is alfalfa.[000401] 297. The kit of clause 287, wherein the TMR forage ingredient is hay.1000402] 298. The kit of clause 287, wherein the TMR forage ingredient is hay from grass.[000403] 299. The kit of clause 287, wherein the TMR forage ingredient is hay from alfalfa.[000404] 300. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 10% (w / w) of the feed.[000405] 301. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 15% (w / w) of the feed.[000406] 302. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 20% (w / w) of the feed.[000407] 303. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 25% (w / w) of the feed.[000408] 304. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 30% (w / w) of the feed.[000409] 305. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 50% (w / w) of the feed.[000410] 306. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 70% (w / w) of the feed.[000411] 307. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 90% (w / w) of the feed.[000412] 308. The kit of any of clauses 286 through 299, wherein the TMR forage ingredient comprises at least 98% (w / w) of the feed.[000413] WHAT IS CLAIMED IS:
Claims
1. Nutritional composition for animals containing narasin.
2. The nutritional composition for animals according to claim 1, wherein narasin is present in an amount of 5-150 g / t, optionally present in an amount of 13-150 g / t, optionally present in an amount of 50-150 g / t, optionally present in an amount of 50-130 g / t, optionally present in an amount of 50-100 g / t, optionally present in an amount of 50-80 g / t, optionally present in an amount of 50-130 g / t, optionally present in an amount of 15-25 g / t or optionally present in an amount of 5-13 g / t.
3. The nutritional composition for animals according to claim 1 or 2, wherein the nutritional composition for animals comprises a composition selected from the list consisting of a diet composition, a supplement composition, a mineral composition, and a combination thereof.
4. The animal nutritional composition of any one of claims 1-3, wherein the animal nutritional composition comprises a plurality of ionophores, wherein the plurality of ionophores comprises narasin and at least one secondary ionophore, and wherein the secondary ionophore is selected from the list consisting of monensin, lasalocid, salinomycin, maduramicin, laylomycin, semduramicin, flavomycin, virginiamycin and a combination thereof.
5. The nutritional composition for animals according to claim 4, wherein the secondary ionophore is monensin.
6. The animal nutritional composition according to claim 4 or 5, wherein the secondary ionophore is present in the animal nutritional composition in an amount of 5-1200 g / t, optionally 5-500 g / t, optionally 25-400 g / t, optionally 50-250 g / t, or optionally 100-200 g / t.
7. A method for increasing the productivity of an animal, wherein the method comprises administering to the animal a nutritional composition for animals containing narasin according to any one of claims 1-6, wherein the administration of the nutritional composition for animals increases the productivity of the animal.
8. The method according to claim 7, wherein increasing the productivity of the animal is selected from a list consisting of increasing the efficiency of feed utilization in the animal, increasing the average daily gain in the animal, increasing the mass of the hot carcass of the animal, optimizing the rumen flora of the animal, optimizing the production of volatile fatty acids in the animal, optimizing the production of propionic acid in the animal, and a combination thereof.
9. The method according to claim 7 or 8, wherein the nutritional composition for animals is administered for at least 14 days, optionally for at least one month, optionally for at least 3 months, or optionally for at least 6 months.
10. The method according to any one of claims 7-9, wherein administering the animal nutritional composition to the animal further comprises administering feed to the animal.
11. The method of claim 10, wherein the feed comprises a feed selected from a list consisting of feed type A, feed type B, feed type C, and a combination thereof.
12. The method according to claim 10 or 11, wherein the feed comprises a material selected from the list consisting of corn, cottonseed, soybeans, soybean meal, soybean oil, rapeseed, rapeseed oil, a mineral mixture, and a combination thereof.
13. The method of any one of claims 10-12, wherein the feed comprises a TMR bulk feed ingredient, wherein the TMR bulk feed ingredient is selected from the list consisting of corn silage, grass silage, oat silage, alfalfa silage, wheat silage, straw, grass, fresh grass, alfalfa, hay, grass hay, alfalfa hay, and combinations thereof.
14. The method of claim 13, wherein the TMR bulk feed ingredient comprises at least 10% w / w of the feed, optionally at least 15% w / w of the feed, optionally at least 20% w / w of the feed, optionally at least 25% w / w of the feed, optionally at least 30% w / w of the feed, optionally at least 50% w / w of the feed, optionally at least 70% w / w of the feed, optionally at least 90% w / w of the feed, or optionally at least 98% w / w of the feed.
15. The method according to any one of paragraphs 7-14, wherein the animal is a ruminant; and it is not necessary that the ruminant animal be selected from a list consisting of a representative of the bovine family, a representative of the ovine family, and a representative of the caprine family; wherein the animal is not necessarily a bovine selected from the list consisting of cattle, bison, African buffalo, Asian buffalo, and antelope; and and the animal need not necessarily be a bovine animal, selected from a list consisting of a heifer, an ox, a bull, and a cow.