Dandelion extract to improve reproductive performance in animals and methods of use
Dandelion extract, when added to the feed of lactating sows, stimulates IGF-1 levels, thereby enhancing reproductive performance across multiple parities by improving feed intake, body condition, and ovulation rates.
Patent Information
- Application Number
- PCT/US2024/054263
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-11-01
- Filing Date
- 2024-11-01
- Publication Date
- 2025-05-08
AI Technical Summary
Current technologies lack an effective solution to enhance reproductive performance in sows across multiple parities, particularly in stimulating insulin-like growth factor-1 (IGF-1) levels which are crucial for ovulation and follicle development.
The use of dandelion extract as a natural nutritional supplement in animal feed, which stimulates a favorable IGF-1 signaling pathway, thereby improving reproductive performance in sows. The extract is incorporated into a basal animal diet at varying concentrations to achieve optimal results.
Administration of dandelion extract to lactating sows results in increased IGF-1 levels, leading to improved feed intake, body condition, ovulation rate, follicular development, and overall reproductive performance, with benefits extending to subsequent parities.
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Figure US2024054263_08052025_PF_FP_ABST
Abstract
Description
DANDELION EXTRACT TO IMPROVE REPRODUCTIVEPERFORMANCE IN ANIMALS AND METHODS OF USECROSS-REFERENCE TO APPLICATIONS
[0001] The present application claims priority to US provisional application number 63 / 595,253 filed on November 1, 2023, the entirety of which is incorporated herein.FIELD
[0002] The present disclosure generally relates to a feed additive composition and methods for modifying behavior in an animal. More particularly, the present disclosure is concerned with a feed additive composition comprising dandelion extract, and the use of such composition to improve reproductive performance in sows across multiple parities.BACKGROUND
[0003] Insulin-like growth factor-1 (IGF-1) is a member of a family of growth factors which are structurally closely related to pro-insulin. The similarity is so great that IGF-1 can bind to and activate insulin receptors. One of the key actions of growth hormone (GH) is to stimulate the production of IGF-1 which is produced primarily by the liver as an endocrine hormone. Production of IGF-1 can be slowed by undemutrition, growth hormone insensitivity, lack of growth hormone receptors, or failures of the downstream signaling pathway post GH receptor.
[0004] Over the last few decades, detailed and extensive studies have established the essential role played by the insulin / IGF family in mammalian sexual development and reproduction. It is now understood that insulin / IGF signaling plays an important role in the female reproductive function, with it being known that IGF-1 is essential for ovulation and follicle development by amplifying gonadotropin hormone action (Behl and Kaul, 2022). Stimulating IGF-1 levels could be beneficial for subsequent fertility, as sows with high IGF- 1 levels at weaning had larger follicles, and earlier studies have shown a relationship between subsequent embryo development and even piglet birth weight (Han et al., 2020).
[0005] Dandelion leaf extract powder Taraxacum officinale)' contains bioactive compounds, such as polyphenols, flavonoids, terpenoids, and polysaccharides, which have been associated with various health benefits (Wirngo et al., 2016). However, it is noteworthythat the specific insulin-like growth factor 1 (IGF-1) response from dandelion extract has not been previously documented in livestock and poultry.
[0006] The invention presented herein encompasses the use of dandelion extract as a natural nutritional supplement for enhancing sow reproductive performance across multiple parities, through a novel insulin-like growth factor 1 (IGF-1) response. By administering dandelion extract to lactating animals as a dietary supplement, a favorable IGF-1 signaling pathway is stimulated, which results in higher feed intake during lactation, better body condition and metabolic status, increased ovulation rate, enhanced follicular development, and ultimately improved sow reproductive performance. The beneficial effects of dandelion extract extend beyond the current parity, impacting subsequent parities as well.
[0007] The identification and characterization of this unique IGF-1 response to dandelion extract may have significant implications for the all-mammalian species and aquatic creatures, providing a novel approach to optimize reproductive efficiency.SUMMARY OF THE PRESENT INVENTION
[0008] The following embodiments and aspects thereof are described and illustrated in conjunction with systems, tools and methods which are meant to be exemplary and illustrative, not limiting in scope. In various embodiments, one or more of the abovedescribed problems have been reduced or eliminated, while other embodiments are directed to other improvements.
[0009] It is an object of the present invention to provide feed composition for the improvement of reproductive performance in animals. The composition preferably comprises a basal animal diet supplemented with Taraxacum extract. In some aspects, the Taraxacum extract may be dandelion leaf powder.
[0010] Another object of the present invention is to provide a method for improving reproductive behavior in non-human animals. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum, wherein after administration of the feed composition, the non-human animals show improved reproductive behavior not exhibited by administering the feed composition without extract from Taraxacum.
[0011] Another object of the present invention is to provide a method for improving IGF-1 response in non-human animals. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum wherein after administration of the feed composition, the non-human animals show improved IGF-1 response not exhibited by administering the feed composition without extract from Taraxacum.
[0012] Another object of the present invention is to provide a method for improving growth performance in piglets. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to a lactating sow wherein after administration of the feed composition, the piglets show improved growth performance not exhibited by administering the feed composition without extract from Taraxacum.
[0013] Another object of the present invention is to provide a method for improving growth performance in non-human offsprings during pre-weaning and post-weaning period. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human animal wherein after administration of the feed composition, the non-human offsprings during pre-weaning and post-weaning period show improved growth performance not exhibited by administering the feed composition without extract from Taraxacum.
[0014] Another object of the present invention is to provide a method for improving livability in non-human offsprings during pre-weaning and post-weaning period. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human animal wherein after administration of the feed composition, the non-human offsprings during pre-weaning and post- weaning period show improved livability not exhibited by administering the feed composition without extract from Taraxacum.
[0015] Another object of the present invention is to provide a method for improving survivability in non-human offsprings during pre-weaning and post-weaning period. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human animal wherein afteradministration of the feed composition, the non-human offsprings during pre-weaning and post-weaning period show improved survivability not exhibited by administering the feed composition without extract from Taraxacum.
[0016] Another object of the present invention is to provide a method for improving weight gain in non-human offsprings during pre-weaning and post-weaning period. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the non-human offsprings during pre-weaning and post-weaning wherein after administration of the feed composition, the non-human offsprings during pre-weaning and post-weaning period show improved weight gain not exhibited by administering the feed composition without extract from Taraxacum .
[0017] Another object of the present invention is to provide a method for improving IGF-1 response and reducing wean to estrus in non-human animals, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the non-human animals wherein after administration of the feed composition, the non-human animals have improved IGF-1 response and reduced wean to estrus not exhibited by the feed composition without extract from Taraxacum.
[0018] Another object of the present invention is to provide a method for improving IGF-1 response and increasing litter weight gain in non-human animals. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the non-human animals wherein after administration of the feed composition, the non-human animals have improved IGF-1 response and increased litter weight gain not exhibited by administering the feed composition without extract from Taraxacum.
[0019] Another object of the present invention is to provide a method for improving IGF-1 response and survivability in piglets. The method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the piglets wherein after administration of the feed composition, the piglets have improved IGF-1 response and survivability not exhibited by administering the feed composition without extract from Taraxacum .
[0020] Another object of the present invention is to provide a method for improving milk fat and milk quality in lactating animals. The method comprises administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the lactating animals wherein after administration of the feed composition, the lactating animals have milk improved fat and milk quality not exhibited by administering the feed composition without extract from Taraxacum.
[0021] Another object of the present invention is to provide a method for improving IGF-1 response and increasing litter weight gain in non-human animals. The method includes administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum and green coffee bean to the non-human animals wherein after administration of the feed composition, the non-human animals have improved IGF-1 response and increased litter weight gain not exhibited by administering the feed composition using Taraxacum alone.
[0022] Various objects and advantages of this use will become apparent from the following description taken in conjunction with the accompanying drawings wherein, by way of illustration and example, certain embodiments of this disclosure are set forth.BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 is a bar chart showing serum IGF-1 in lactating sows fed dandelion extract according to some embodiments of the present disclosure.
[0024] FIG. 2 is a plot showing a positive correlation between serum IGF-1 with sow body weight change during lactation according to some embodiments of the present disclosure.
[0025] FIG. 3 is a plot showing a negative correlation between serum IGF-1 with sow wean-estrus interval according to some embodiments of the present disclosure.
[0026] FIG. 4 is a graphical representation showing that the Serum Brix index in piglets is positively correlated with pig body weight at weaning according to some embodiments of the present disclosure.DETAILED DESCRIPTION
[0027] The present disclosure is based on the discovery that administering a feed composition comprising dandelion leaf powder extract to animals improves reproductive performance across multiple parities.
[0028] Additional embodiments and features are set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the specification or may be learned by the practice of the embodiments discussed herein. A further understanding of the nature and advantages of certain embodiments may be realized by reference to the remaining portions of the specification the drawings, the chemical structures, and descriptions, which forms a part of this disclosure. Any description of any R- group or chemical substituent, alone or in any combination, may be used in any chemical Formula described herein, and Formulae include all conformational and stereoisomers, including diastereomers, epimers, and enantiomers. Moreover, any feature of a composition disclosed herein may be used in combination with any other feature of a composition disclosed herein.I. Feed Composition
[0029] One aspect of the present disclosure encompasses feed compositions for nonhuman animals, in particular for female non-human animals, for example, sows. The compositions comprise a basal animal diet supplemented with Taraxacum (dandelion) leaf powder extract. Taraxacum includes but is not limited to Taraxacum albidum. Taraxacum algarbiense, Taraxacum aphrogenes, Taraxacum arcticum, Taraxacum balticum, Taraxacum brachyceras, Taraxacum brevicorniculatum, Taraxacum californicum, Taraxacum carneocoloratum, Taraxacum cenirasiaticum. Taraxacum ceratophorum, Taraxacum coreanum, Taraxacum desertorum, Taraxacum erythrospermum, Taraxacum farinosum, Taraxacum holmboei, Taraxacum hybernum. Taraxacum japonicum, Taraxacum kok-saghyz, Taraxacum laevigatum, Taraxacum lissocarpum, Taraxacum minimum , Taraxacum irabile. Taraxacum officinale, Taraxacum pankhurstianum, Taraxacum platycarpum, Taraxacum pseudoroseum, and / or Taraxacum rubifolium, and / or Taraxacum suecicum.
[0030] Another aspect of the present disclosure encompasses feed compositions comprising a basal animal diet supplemented with a combination of Taraxacum (dandelion) leaf powder extract, fennel seed extract, and sodium acetate.
[0031] Another aspect of the present disclosure encompasses feed compositions comprising a basal animal diet supplemented with a combination of Taraxacum (dandelion) and green coffee beans.
[0032] The incorporation of dandelion and a combination of dandelion, fennel seed extract, and sodium acetate has surprisingly been found to be extremely effective in improving reproductive behaviors and IGF-1 response in non-human animals. The incorporation of dandelion has surprisingly been found to be extremely effective in improving reproductive behaviors in sows. a. Dandelion Leaf Powder Extract
[0033] The amount of dandelion leaf powder extract in a feed composition can and will vary depending on the body weight, age, and medical condition of the non-human animal and can be determined experimentally. Generally, the amount of dandelion leaf powder extract present in the formulation will be at an effective amount to modulate an IGF-1 response in the non-human animal. The term “effective amount” describes an amount of dandelion leaf powder extract present in a feed composition sufficient to produce a noticeable effect, for example the engaging in reproductive behaviors by the subject sow, as determined according to behavioral observations described herein. The effective amount will depend on factors such as individual animal parameters including age, physical condition, size and weight; concurrent treatments; the frequency of treatment; or the mode of administration. These factors are well known to those of ordinary skill in the art.
[0034] Preferably, the amount of dandelion leaf powder extract present in the formulation may be at a concentration of about 0.1 Ib / ton to about 20 Ib / ton feed. For example, the amount of dandelion leaf powder extract may be from about 0.5 Ib / ton to about19.5 Ib / ton, about 1.0 Ib / ton to about 19.0 Ib / ton, about 1.5 Ib / ton to about 18.5 Ib / ton, about 2.0 Ib / ton to about 18.0 Ib / ton, about 2.5 Ib / ton to about 17.5 Ib / ton, about 3.0 Ib / ton to about 17.0 Ib / ton, about 3.5 Ib / ton to about 16.5 Ib / ton, about 4.0 Ib / ton to about 16.0 Ib / ton, about4.5 Ib / ton to about 15.5 Ib / ton, about 5.0 Ib / ton to about 15.0 Ib / ton, about 5.5 Ib / ton to about14.5 Ib / ton, about 6.0 Ib / ton to about 14.0 Ib / ton, about 6.5 Ib / ton to about 13.5 Ib / ton, about 7.0 Ib / ton to about 13.0 Ib / ton, about 7.5 Ib / ton to about 12.5 Ib / ton, about 8.0 Ib / ton to about 12.0 Ib / ton, about 8.5 Ib / ton to about 11.5 Ib / ton, about 9.0 Ib / ton to about 11.0 Ib / ton, or about 9.5 Ib / ton to about 10.5 Ib / ton. In some embodiments, the amount of dandelion may be about 0.2 Ib / ton, about 0.3 Ib / ton, or about 0.4 Ib / ton.
[0035] The amount of fennel seed extract in a feed composition can and will vary depending on the body weight, age, and medical condition of the non-human animal and can be determined experimentally. Generally, the amount of fennel seed extract present in the formulation will be at an effective amount to modulate an IGF-1 response in the non-human animal. The term “effective amount” describes an amount of fennel seed extract present in a feed composition sufficient to produce a noticeable effect, for example the engaging in reproductive behaviors by the subject sow, as determined according to behavioral observations described herein. The effective amount will depend on factors such as individual animal parameters including age, physical condition, size and weight; concurrent treatments; the frequency of treatment; or the mode of administration. These factors are well known to those of ordinary skill in the art.
[0036] Preferably, the amount of fennel seed extract present in the formulation may be at a concentration of about 0.01 Ib / ton to about 10 Ib / ton feed. For example, the amount of fennel seed extract may be from about 0.05 Ib / ton to about 9.5 Ib / ton, about 0.1 Ib / ton to about 9.0 Ib / ton, about 0.5 Ib / ton to about 8.5 Ib / ton, about 1.0 Ib / ton to about 8.0 Ib / ton, about 1.5 Ib / ton to about 7.5 Ib / ton, about 2.0 Ib / ton to about 7.0 Ib / ton, about 2.5 Ib / ton to about 6.5 Ib / ton, about 3.0 Ib / ton to about 6.0 Ib / ton, about 3.5 Ib / ton to about 5.5 Ib / ton, or about 4.0 Ib / ton to about 5.0 Ib / ton. In some embodiments, the amount of fennel seed extract may be about 0.2 Ib / ton, about 0.3 Ib / ton, or about 0.4 Ib / ton.
[0037] The amount of sodium acetate in a feed composition can and will vary depending on the body weight, age, and medical condition of the non-human animal and can be determined experimentally. Generally, the amount of sodium acetate present in the formulation will be at an effective amount to modulate an IGF-1 response in the non-human animal. The term “effective amount” describes an amount of fennel seed extract present in a feed composition sufficient to produce a noticeable effect, for example the engaging inreproductive behaviors by the subject sow, as determined according to behavioral observations described herein. The effective amount will depend on factors such as individual animal parameters including age, physical condition, size and weight; concurrent treatments; the frequency of treatment; or the mode of administration. These factors are well known to those of ordinary skill in the art.
[0038] Preferably, the amount of sodium acetate present in the formulation may be at a concentration of about 0.1 Ib / ton to about 10 Ib / ton feed. For example, the amount of sodium acetate may be from about 0.5 Ib / ton to about 9.5 Ib / ton, about 1.0 Ib / ton to about 9.0 Ib / ton, about 1.5 Ib / ton to about 8.5 Ib / ton, about 2.0 Ib / ton to about 8.0 Ib / ton, about 2.5 Ib / ton to about 7.5 Ib / ton, about 3.0 Ib / ton to about 7.0 Ib / ton, about 3.5 Ib / ton to about 6.5 Ib / ton, about 4.0 Ib / ton to about 6.0 Ib / ton, about 4.5 Ib / ton to about 5.5 Ib / ton, or about 5.0 Ib / ton to about 5.2 Ib / ton. In some embodiments, the amount of fennel seed extract may be about 0.2 Ib / ton, about 0.3 Ib / ton, or about 0.4 Ib / ton.
[0039] The amount of green coffee bean in a feed composition can and will vary depending on the body weight, age, and medical condition of the non-human animal and can be determined experimentally. Generally, the amount of green coffee bean present in the formulation will be at an effective amount to modulate an IGF-1 response in the non-human animal. The term “effective amount” describes an amount of green coffee bean present in a feed composition sufficient to produce a noticeable effect, for example the engaging in reproductive behaviors by the subject sow, as determined according to behavioral observations described herein. The effective amount will depend on factors such as individual animal parameters including age, physical condition, size and weight; concurrent treatments; the frequency of treatment; or the mode of administration. These factors are well known to those of ordinary skill in the art.
[0040] Preferably, the amount of green coffee bean present in the formulation may be at a concentration of about 0.01 Ib / ton to about 10 Ib / ton feed. For example, the amount of fennel seed extract may be from about 0.05 Ib / ton to about 9.5 Ib / ton, about 0.1 Ib / ton to about 9.0 Ib / ton, about 0.5 Ib / ton to about 8.5 Ib / ton, about 1.0 Ib / ton to about 8.0 Ib / ton, about 1.5 Ib / ton to about 7.5 Ib / ton, about 2.0 Ib / ton to about 7.0 Ib / ton, about 2.5 Ib / ton to about 6.5 Ib / ton, about 3.0 Ib / ton to about 6.0 Ib / ton, about 3.5 Ib / ton to about 5.5 Ib / ton, orabout 4.0 Ib / ton to about 5.0 Ib / ton. In some embodiments, the amount of green coffee bean may be about 0.05 Ib / ton, about 0.2 Ib / ton, about 0.25 Ib / ton, about 0.3 Ib / ton, or about 0.4 Ib / ton. b. Basal Animal Diet
[0041] A basal animal diet suitable for a feed composition of the disclosure can and will vary depending on the intended animal, the weight of the animal, and the stage of development of the animal among other variables.
[0042] The terms “feed”, “food”, and “feed formulation” are used herein interchangeably and may refer to any feed composition normally fed to an animal. Basal animal diets normally fed to an animal are known in the art. A basal animal diet may include one or more components of an animal feed. Non-limiting examples of feed matter or animal feed matter may include, without limitation: com or a component of corn, such as, for example, corn meal, com fiber, corn hulls, com DDGS (distiller’s dried grain with solubles), silage, ground com, com germ, com gluten, com oil, or any other portion of a com plant; soy or a component of soy, such as, for example, soy oil, soy meal, soy hulls, soy silage, ground soy, or any other portion of a soy plant; wheat or any component of wheat, such as, for example, wheat meal, wheat fiber, wheat hulls, wheat chaff, ground wheat, wheat germ, or any other portion of a wheat plant; rice or any component of rice, such as, for example, rice meal, rice fiber, rice hulls, rice chaff, ground rice, rice germ, or any other portion of a rice plant; canola, such as, for example, canola oil, canola meal, canola protein, canola hulls, ground canola, or any other portion of a canola plant; sunflower or a component of a sunflower plant; sorghum or a component of a sorghum plant; sugar beet or a component of a sugar beet plant; cane sugar or a component of a sugarcane plant; barley or a component of a barley plant; palm oil, palm kernel or a component of a palm plant; glycerol; com steep liquor; a waste stream from an agricultural processing facility; lecithin; rumen protected fats; molasses; soy molasses; flax; peanuts; peas; oats; grasses, such as orchard grass and fescue; fish meal, meat & bone meal; feather meal; and poultry byproduct meal; and alfalfa and / or clover used for silage or hay, and various combinations of any of the feed ingredients set forth herein, or other feed ingredients generally known in the art.
[0043] As it will be recognized in the art, a basal animal diet may further be supplemented with amino acids, vitamins, minerals, and other feed additives such as other types of enzymes, organic acids, essential oils, probiotics, prebiotics, antioxidants, pigments, anti-caking agents, and the like, as described further below. A basal animal diet may be formulated for administration to any animal subject. Animal subjects may be as described below.
[0044] The basal animal diets may optionally comprise at least one additional nutritive and / or pharmaceutical agent. For instance, the at least one additional nutritive and / or pharmaceutical agent may be selected from the group consisting of vitamin, mineral, amino acid, antioxidant, probiotic, essential fatty acid, and pharmaceutically acceptable excipient. The compositions may include one additional nutritive and / or pharmaceutical component or a combination of any of the foregoing additional components in varying amounts. Suitable examples of each additional component are detailed below. i. vitamins
[0045] Optionally, the animal feed formulation may include one or more vitamins. Suitable vitamins for use in the dietary supplement include vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin. The form of the vitamin may include salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of a vitamin, and metabolites of a vitamin.
[0046] The animal feed formulation may include one or more forms of an effective amount of any of the vitamins described herein or otherwise known in the art. Exemplary vitamins include vitamin K, vitamin D, vitamin C, and biotin. An “effective amount” of a vitamin typically quantifies an amount at least about 10% of the United States Recommended Daily Allowance ("RDA") of that particular vitamin for a subject. It is contemplated, however, that amounts of certain vitamins exceeding the RDA may be beneficial for certain animals. For example, the amount of a given vitamin may exceed the applicable RDA by 100%, 200%, 300%, 400%, 500% or more.ii. minerals
[0047] Generally, the animal feed formulation may include one or more minerals or mineral sources. Non-limiting examples of minerals include, without limitation, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.
[0048] Generally speaking, the animal feed formulation may include one or more forms of an effective amount of any of the minerals described herein or otherwise known in the art. An “effective amount” of a mineral typically quantifies an amount at least about 10% of the United States Recommended Daily Allowance ("RDA") of that particular mineral for a subject. It is contemplated, however, that amounts of certain minerals exceeding the RDA may be beneficial for certain subjects. For example, the amount of a given mineral may exceed the applicable RDA by 100%, 200%, 300%, 400%, 500% or more. Typically, the amount of mineral included in the dietary supplement may range from about 1 mg to about 1500 mg, about 5 mg to about 500 mg, or from about 50 mg to about 500 mg per dosage. iii. essential fatty acids
[0049] Optionally, the animal feed formulation may include a source of an essential fatty acid. The essential fatty acid may be isolated or it may be an oil source or fat source that contains an essential fatty acid. In one embodiment, the essential fatty acid may be a polyunsaturated fatty acid (PUFA), which has at least two carbon-carbon double bonds generally in the cis-configuration. The PUFA may be a long chain fatty acid having at least 18 carbons atoms. The PUFA may be an omega-3 fatty acid in which the first double bond occurs in the third carbon-carbon bond from the methyl end of the carbon chain (i.e., opposite the carboxyl acid group). Examples of omega-3 fatty acids include alpha-linolenic acid (18:3, ALA), stearidonic acid (18:4), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5; EPA), docosatetraenoic acid (22:4), n-3 docosapentaenoic acid (22:5; n-3DPA), and docosahexaenoic acid (22:6; DHA). The PUFA may also be an omega-5 fatty acid, in which the first double bond occurs in the fifth carbon-carbon bond from the methyl end. Exemplaryomega-5 fatty acids include myristoleic acid (14: 1), myristoleic acid esters, and cetyl myristoleate. The PUFA may also be an omega-6 fatty acid, in which the first double bond occurs in the sixth carbon-carbon bond from the methyl end. Examples of omega-6 fatty acids include linoleic acid (18:2), gamma-linolenic acid (18:3), eicosadienoic acid (20:2), dihomo-gamma-linolenic acid (20:3), arachidonic acid (20:4), docosadienoic acid (22:2), adrenic acid (22:4), and n-6 docosapentaenoic acid (22:5). The fatty acid may also be an omega-9 fatty acid, such as oleic acid (18: 1), eicosenoic acid (20: 1), mead acid (20:3), erucic acid (22: 1), and nervonic acid (24: 1).
[0050] In another embodiment, the essential fatty acid source may be a seafood-derived oil. The seafood may be a vertebrate fish or a marine organism, such that the oil may be fish oil or marine oil. The long chain (20C, 22C) omega-3 and omega-6 fatty acids are found in seafood. The ratio of omega-3 to omega-6 fatty acids in seafood ranges from about 8: 1 to 20: 1. Seafood from which oil rich in omega-3 fatty acids may be derived include, but are not limited to, abalone scallops, albacore tuna, anchovies, catfish, clams, cod, gem fish, herring, lake trout, mackerel, menhaden, orange roughy, salmon, sardines, sea mullet, sea perch, shark, shrimp, squid, trout, and tuna.
[0051] In yet another embodiment, the essential fatty acid source may be a plant- derived oil. Plant and vegetable oils are rich in omega-6 fatty acids. Some plant-derived oils, such as flaxseed oil, are especially rich in omega-3 fatty acids. Plant or vegetable oils are generally extracted from the seeds of a plant, but may also be extracted from other parts of the plant. Plant or vegetable oils that are commonly used for cooking or flavoring include, but are not limited to, acai oil, almond oil, amaranth oil, apricot seed oil, argan oil, avocado seed oil, babassu oil, ben oil, blackcurrant seed oil, Borneo tallow nut oil, borage seed oil, buffalo gourd oil, canola oil, carob pod oil, cashew oil, castor oil, coconut oil, coriander seed oil, corn oil, cottonseed oil, evening primrose oil, false flax oil, flax seed oil, grapeseed oil, hazelnut oil, hemp seed oil, kapok seed oil, lallemantia oil, linseed oil, macadamia oil, meadowfoam seed oil, mustard seed oil, okra seed oil, olive oil, palm oil, palm kernel oil, peanut oil, pecan oil, pequi oil, perilla seed oil, pine nut oil, pistachio oil, poppy seed oil, prune kernel oil, pumpkin seed oil, quinoa oil, ramtil oil, rice bran oil, safflower oil, sesameoil, soybean oil, sunflower oil, tea oil, thistle oil, walnut oil, or wheat germ oil. The plant- derived oil may also be hydrogenated or partially hydrogenated.
[0052] In still a further embodiment, the essential fatty acid source may be an algae- derived oil. Commercially available algae-derived oils include those from Crypthecodinium cohnii and Schizochytrium sp. Other suitable species of algae, from which oil is extracted, include Aphanizomenonflos-aquae, Bacilliarophy sp., Botryococcus braunii, Chlorophyceae sp., Dunaliella tertiolecta, Euglena gracilis, Isochrysis galhana, Nannochloropsis salina, Nannochloris sp., Neochloris oleoabundans, Phaeodactyhim tricornutum, Pleurochrysis carterae, Prymnesium parvum, Scenedesmus dimorphus, Spirulina sp., and Tetraselmis chui. iv. amino acids
[0053] The animal feed formulation may optionally include from one to several amino acids. Suitable amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine or their hydroxy analogs. In certain embodiments, the amino acid will be selected from the essential amino acids. An essential amino acid is generally described as one that cannot be synthesized de novo by the organism, and therefore, must be provided in the diet. By way of non-limiting example, the essential amino acids for humans include: L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-valine and L-threonine. v. antioxidants
[0054] The animal feed formulation may include one or more suitable antioxidants. As will be appreciated by a skilled artisan, the suitability of a given antioxidant will vary depending upon the species to which the dietary supplement will be administered. Nonlimiting examples of antioxidants include ascorbic acid and its salts, ascorbyl palmitate, ascorbyl stearate, anoxomer, N-acetylcysteine, benzyl isothiocyanate, o-, m- or p-amino benzoic acid (o is anthranilic acid, p is PABA), butylated hydroxyanisole (BHA), butylated hydroxy toluene (BHT), caffeic acid, canthaxantin, alpha-carotene, beta-carotene, beta- caraotene, beta-apo-carotenoic acid, carnosol, carvacrol, catechins, cetyl gallate, chlorogenic acid, citric acid and its salts, p-coumaric acid, curcurin, 3,4-dihydroxybenzoic acid, N,N'- diphenyl-p-phenylenediamine (DPPD), dilauryl thiodipropionate, distearyl thiodipropionate,2,6-di-tert-butylphenol, dodecyl gallate, edetic acid, ellagic acid, erythorbic acid, sodium erythorbate, esculetin, esculin, 6-ethoxy-l,2-dihydro-2,2,4-trimethylquinoline, ethyl gallate, ethyl maltol, ethylenediaminetetraacetic acid (EDTA), eugenol, ferulic acid, flavonoids, flavones (e.g., apigenin, chrysin, luteolin), flavonols (e.g., datiscetin, myricetin, daemfero), flavanones, fraxetin, fumaric acid, gallic acid, gentian extract, gluconic acid, glycine, gum guaiacum, hesperetin, alpha-hydroxybenzyl phosphinic acid, hydroxycinammic acid, hydroxy glutaric acid, hydroquinone, N-hydroxysuccinic acid, hydroxytryrosol, hydroxyurea, lactic acid and its salts, lecithin, lecithin citrate; R-alpha-lipoic acid, lutein, lycopene, malic acid, maltol, 5-methoxy tryptamine, methyl gallate, monoglyceride citrate; monoisopropyl citrate; morin, beta-naphthofl avone, nordihydroguaiaretic acid (NDGA), octyl gallate, oxalic acid, palmityl citrate, phenothiazine, phosphatidylcholine, phosphoric acid, phosphates, phytic acid, phytylubichromel, propyl gallate, polyphosphates, quercetin, trans-resveratrol, rosmarinic acid, sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate, syringic acid, tartaric acid, thymol, tocopherols (i.e., alpha-, beta-, gamma- and delta-tocopherol), tocotrienols (i.e., alpha-, beta-, gamma- and del ta-tocotri enols), tyrosol, vanilic acid, 2,6-di- tert-butyl-4-hydroxymethylphenol (i.e., lonox 100), 2,4-(tris-3',5'-bi-tert-butyl-4'- hydroxybenzyl)-mesitylene (i.e., lonox 330), 2,4, 5 -trihydroxybutyrophenone, ubiquinone, tertiary butyl hydroquinone (TBHQ), thiodipropionic acid, trihydroxy butyrophenone, tryptamine, tyramine, uric acid, vitamin K and derivates, vitamin Q10, zeaxanthin, or combinations thereof.
[0055] Natural antioxidants that may be included in the dietary supplement include, but are not limited to, apple peel extract, blueberry extract, carrot juice powder, clove extract, coffee berry, coffee bean extract, cranberry extract, eucalyptus extract, ginger powder, grape seed extract, green tea, olive leaf, parsley extract, peppermint, pimento extract, pomace, pomegranate extract, rice bran extract, rosehips, rosemary extract, sage extract, tart cherry extract, tomato extract, turmeric, and wheat germ oil. vi. anti-inflammatory agents
[0056] The animal feed formulation may optionally include at least one antiinflammatory agent. In one embodiment, the anti-inflammatory agent may be a synthetic non-steroidal anti-inflammatory drug (NSAID) such as acetylsalicylic acid, dichlophenac,indomethacin, oxamethacin, ibuprofen, indoprofen, naproxen, ketoprofen, mefamanic acid, metamizole, piroxicam, and celecoxib. In an alternate embodiment, the anti-inflammatory agent may be a prohormone that modulates inflammatory processes. Suitable prohormones having this property include prohormone convertase 1, proopiomelanocortin, prohormone B- type natriuretic peptide, SMR1 prohormone, and the like. In another embodiment, the antiinflammatory agent may be an enzyme having anti-inflammatory effects. Examples of antiinflammatory enzymes include bromelain, papain, serrapeptidase, and proteolytic enzymes such as pancreatin (a mixture of trypsin, amylase and lipase).
[0057] In still another embodiment, the anti-inflammatory agent may be a peptide with anti-inflammatory effects. For example, the peptide may be an inhibitor of phospholipase A2, such as antiflammin-1, a peptide that corresponds to amino acid residues 246-254 of lipocortin; antiflammin-2, a peptide that corresponds to amino acid residues 39-47 of uteroglobin; S7 peptide, which inhibits the interaction between interleukin 6 and interleukin 6 receptor; RP1, a prenyl protein inhibitor; and similar peptides. Alternatively, the antiinflammatory peptide may be cortistatin, a cyclic neuropeptide related to somatostatin, or peptides that correspond to an N-terminal fragment of SV-IV protein, a conserved region of E-, L-, and P-selectins, and the like. Other suitable anti-inflammatory preparations include collagen hydrolysates and milk micronutrient concentrates (e g., MicroLactin® available from Stolle Milk Biologies, Inc., Cincinnati, OH), as well as milk protein hydrolysates, casein hydrolysates, whey protein hydrolysates, and plant protein hydrolysates.
[0058] In a further embodiment, the anti-inflammatory agent may be a probiotic that has been shown to modulate inflammation. Suitable immunomodulatory probiotics include lactic acid bacteria such as acidophilli, lactobacilli, and bifidophilli. In yet another embodiment, the anti-inflammatory agent may be a plant extract having anti-inflammatory properties. Non-limiting examples of suitable plant extracts with anti-inflammatory benefits include blueberries, boswella, black catechu and Chinese skullcap, celery seed, chamomile, cherries, devils claw, eucalyptus, evening primrose, ginger, hawthome berries, horsetail, Kalopanax pictus bark, licorice root, turmeric, white wallow, willow bark, and yucca.vii. herbals
[0059] The animal feed formulation may optionally include at least one herb or herbal derivative. Suitable herbals and herbal derivatives, as used herein, refer to herbal extracts, and substances derived from plants and plant parts, such as leaves, flowers, and roots, without limitation. Non-limiting exemplary herbals and herbal derivatives include agrimony, alfalfa, aloe vera, amaranth, angelica, anise, barberry, basil, bayberry, bee pollen, birch, bistort, blackberry, black cohosh, black walnut, blessed thistle, blue cohosh, blue vervain, boneset, borage, buchu, buckthorn, bugleweed, burdock, capsicum, cayenne, caraway, cascara sagrada, catnip, celery, centaury, chamomile, chaparral, chickweed, chicory, chinchona, cloves, coltsfoot, comfrey, comsilk, couch grass, cramp bark, culver's root, cyani, cornflower, damiana, dandelion, devils claw, dong quai, echinacea, elecampane, ephedra, eucalyptus, evening primrose, eyebright, false unicorn, fennel, fenugreek, figwort, flaxseed, garlic, gentian, ginger, ginseng, golden seal, gotu kola, gum weed, hawthorn, hops, horehound, horseradish, horsetail, hoshouwu, hydrangea, hyssop, iceland moss, irish moss, jojoba, juniper, kelp, lady's slipper, lemon grass, licorice, lobelia, mandrake, marigold, marjoram, marshmallow, mistletoe, mullein, mustard, myrrh, nettle, oatstraw, Oregon grape, papaya, parsley, passion flower, peach, pennyroyal, peppermint, periwinkle, plantain, pleurisy root, pokeweed, prickly ash, psyllium, quassia, queen of the meadow, red clover, red raspberry, redmond clay, rhubarb, rose hips, rosemary, rue, safflower, saffron, sage, St. John’s wort, sarsaparilla, sassafras, saw palmetto, skullcap, senega, senna, shepherd's purse, slippery elm, spearmint, spikenard, squawvine, stillingia, strawberry, taheebo, thyme, uva ursi, valerian, violet, watercress, white oak bark, white pine bark, wild cherry, wild lettuce, wild yam, willow, wintergreen, witch hazel, wood betony, wormwood, yarrow, yellow dock, yerba santa, yucca and combinations thereof. viii. pigments
[0060] The animal feed formulation may optionally include at least one pigment. Suitable non-limiting pigments include actinioerythrin, alizarin, alloxanthin, P-apo-2'- carotenal, apo-2-lycopenal, apo-6'-lycopenal, astacein, astaxanthin, azafrinaldehyde, aacterioruberin, aixin, a-carotine, P-carotine, y-carotine, P-carotenone, canthaxanthin, capsanthin, capsorubin, citranaxanthin, citroxanthin, crocetin, crocetinsemialdehyde, crocin,crustaxanthin, cryptocapsin, a-cryptoxanthin, P-cryptoxanthin, cryptomonaxanthin, cynthiaxanthin, decaprenoxanthin, dehydroadonirubin, diadinoxanthin, l,4-diamino-2,3- dihydroanthraquinone, 1 ,4-dihydroxyanthraquinone, 2,2'-diketospirilloxanthin, eschscholtzxanthin, eschscholtzxanthone, flexixanthin, foliachrome, fucoxanthin, gazaniaxanthin, hexahydrolycopene, hopkinsiaxanthin, hydroxyspheriodenone, isofucoxanthin, loroxanthin, lutein, luteoxanthin, lycopene, lycopersene, lycoxanthin, morindone, mutatoxanthin, neochrome, neoxanthin, nonaprenoxanthin, OH-Chlorobactene, okenone, oscillaxanthin, paracentrone, pectenolone, pectenoxanthin, peridinin, phleixanthophyll, phoeniconone, phoenicopterone, phoenicoxanthin, physalien, phytofluene, pyrrhoxanthininol, quinones, rhodopin, rhodopinal, rhodopinol, rhodovibrin, rhodoxanthin, rubixanthone, saproxanthin, semi-a-carotenone, semi- -carotenone, sintaxanthin, siphonaxanthin, siphonein, spheroidene, tangeraxanthin, torularhodin, torularhodin methyl ester, torularhodinaldehyde, torulene, 1,2,4-trihydroxyanthraquinone, triphasiaxanthin, trollichrome, vaucheriaxanthin, violaxanthin, wamingone, xanthin, zeaxanthin, a- zeacarotene, or combinations thereof. ix. pharmaceutical acceptable agents
[0061] The animal feed formulation may optionally include at least one pharmaceutical acceptable agent. Suitable non-limiting pharmaceutically acceptable agents include an acid / alkaline-labile drug, a pH dependent drug, or a drug that is a weak acid or a weak base. Examples of acid-labile drugs include statins (e.g., pravastatin, fluvastatin and atorvastatin), antiobiotics (e.g., penicillin G, ampicillin, streptomycin, erythromycin, clarithromycin and azithromycin), nucleoside analogs (e.g., dideoxyinosine (ddl or didanosine), dideoxyadenosine (ddA), dideoxycytosine (ddC), salicylates (e.g., aspirin), digoxin, bupropion, pancreatin, midazolam, and methadone. Drugs that are only soluble at acid pH include nifedipine, emonapride, nicardipine, amosulalol, noscapine, propafenone, quinine, dipyridamole, josamycin, dilevalol, labetalol, enisoprost, and metronidazole. Drugs that are weak acids include phenobarbital, phenytoin, zidovudine (AZT), salicylates (e.g., aspirin), propionic acid compounds (e.g., ibuprofen), indole derivatives (e.g., indomethacin), fenamate compounds (e.g., meclofenamic acid), pyrrolealkanoic acid compounds (e.g., tolmetin), cephalosporins (e.g., cephalothin, cephalaxin, cefazolin, cephradine, cephapirin,cefamandole, and cefoxitin), 6-fluoroquinolones, and prostaglandins. Drugs that are weak bases include adrenergic agents (e.g., ephedrine, desoxyephedrine, phenylephrine, epinephrine, salbutamol, and terbutaline), cholinergic agents (e.g., physostigmine and neostigmine), antispasmodic agents (e.g., atropine, methantheline, and papaverine), curariform agents (e.g., chlorisondamine), tranquilizers and muscle relaxants (e.g., fluphenazine, thioridazine, trifluoperazine, chlorpromazine, and triflupromazine), antidepressants (e.g., amitriptyline and nortriptyline), antihistamines (e.g., diphenhydramine, chlorpheniramine, dimenhydrinate, tripelennamine, perphenazine, chlorprophenazine, and chlorprophenpyridamine), cardioactive agents (e.g., verapamil, diltiazem, gallapomil, cinnarizine, propranolol, metoprolol and nadolol), antimalarials (e.g., chloroquine), analgesics (e.g., propoxyphene and meperidine), antifungal agents (e.g., ketoconazole and itraconazole), antimicrobial agents (e.g., cefpodoxime, proxetil, and enoxacin), caffeine, theophylline, and morphine. In another embodiment, the drug may be a biphosphonate or another drug used to treat osteoporosis. Non-limiting examples of a biphosphonate include alendronate, ibandronate, risedronate, zoledronate, pamidronate, neridronate, olpadronate, etidronate, clodronate, and tiludronate. Other suitable drugs include estrogen, selective estrogen receptor modulators (SERMs), and parathyroid hormone (PTH) drugs. In yet another embodiment, the drug may be an antibacterial agent. Suitable antibiotics include aminoglycosides (e.g., amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, and tobramycin), carbecephems (e.g., loracarbef), a carbapenem (e.g., certapenem, imipenem, and meropenem), cephalosporins (e.g., cefadroxil cefazolin, cephalexin, cefaclor, cefamandole, cephalexin, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, and ceftriaxone), macrolides (e.g., azithromycin, clarithromycin, dirithromycin, erythromycin, and troleandomycin), monobactam, penicillins (e.g., amoxicillin, ampicillin, carbenicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, and ticarcillin), polypeptides (e.g., bacitracin, colistin, and polymyxin B), quinolones (e.g., ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lorn efloxacin, moxifloxacin, norfloxacin, ofloxacin, and trovafl oxaci n), sulfonamides (e.g., mafenide, sulfacetamide, sulfamethizole, sulfasalazine, sulfisoxazole, and trimethoprim-sulfamethoxazole), and tetracyclines (e.g., demeclocy cline, doxycycline, minocycline, and oxytetracycline). In an alternate embodiment, the drug may be an antiviral protease inhibitor (e.g., amprenavir, fosamprenavir, indinavir, lopinavir / ritonavir, ritonavir, saquinavir, and nelfinavir). In still another embodiment, the drug may be a cardiovascular drug. Examples of suitable cardiovascular agents include cardiotonic agents (e.g., digitalis (digoxin), ubidecarenone, and dopamine), vasodilating agents (e.g., nitroglycerin, captopril, dihydralazine, diltiazem, and isosorbide dinitrate), antihypertensive agents (e.g., alphamethyldopa, chlortalidone, reserpine, syrosingopine, rescinnamine, prazosin, phentolamine, felodipine, propanolol, pindolol, labetalol, clonidine, captopril, enalapril, and lisonopril), beta blockers (e.g., levobunolol, pindolol, timolol maleate, bisoprolol, carvedilol, and butoxamine), alpha blockers (e.g., doxazosin, prazosin, phenoxybenzamine, phentolamine, tamsulosin, alfuzosin, and terazosin), calcium channel blockers (e.g., amlodipine, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, lacidipine, lercanidipine, verapamil, gallopamil, and diltiazem), monensin, avilamycin, salinomycin, narasin, diclaserol, tylosin, bacitracin, bacitracin zinc, and anticlot agents (e.g., dipyrimadole). x. excipients
[0062] A variety of commonly used excipients in animal feed formulation may be selected on the basis of compatibility with the active ingredients. Non-limiting examples of suitable excipients include an agent selected from the group consisting of non-effervescent disintegrants, a coloring agent, a flavor-modifying agent, an oral dispersing agent, a stabilizer, a preservative, a diluent, a compaction agent, a lubricant, a fdler, a binder, taste masking agents, an effervescent disintegration agent, and combinations of any of these agents.
[0063] In one embodiment, the excipient is a binder. Suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinyl alcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, polypeptides, oligopeptides, and combinations thereof. The polypeptide may be any arrangement of amino acids ranging from about 100 to about 300,000 daltons.
[0064] In another embodiment, the excipient may be a filler. Suitable fillers include carbohydrates, inorganic compounds, and polyvinylpirrolydone. By way of non-limitingexample, the filler may be calcium sulfate, both di- and tri-basic, starch, calcium carbonate, magnesium carbonate, microcrystalline cellulose, dibasic calcium phosphate, magnesium carbonate, magnesium oxide, calcium silicate, talc, modified starches, lactose, sucrose, mannitol, and sorbitol.
[0065] The excipient may comprise a non-effervescent disintegrant. Suitable examples of non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, microcrystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, and tragacanth.
[0066] In another embodiment, the excipient may be an effervescent disintegrant. By way of non-limiting example, suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid and sodium bicarbonate in combination with tartaric acid.
[0067] The excipient may comprise a preservative. Suitable examples of preservatives include antioxidants, such as a-tocopherol or ascorbate, and antimicrobials, such as parabens, chlorobutanol or phenol.
[0068] In another embodiment, the excipient may include a diluent. Diluents suitable for use include pharmaceutically acceptable saccharides such as sucrose, dextrose, lactose, microcrystalline cellulose, fructose, xylitol, and sorbitol; polyhydric alcohols; a starch; premanufactured direct compression diluents; and mixtures of any of the foregoing.
[0069] The excipient may include flavors. Flavors incorporated into the outer layer may be chosen from synthetic flavor oils and flavoring aromatics and / or natural oils, extracts from plants, leaves, flowers, fruits, and combinations thereof. By way of example, these may include cinnamon oils, oil of Wintergreen, peppermint oils, clover oil, hay oil, anise oil, eucalyptus, vanilla, citrus oil, such as lemon oil, orange oil, grape and grapefruit oil, fruit essences including apple, peach, pear, strawberry, raspberry, cherry, plum, pineapple, and apricot.
[0070] In another embodiment, the excipient may include a sweetener. By way of nonlimiting example, the sweetener may be selected from glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalconecompounds, glycyrrhizin; Stevia Reb audi ana (Stevioside); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, sylitol, and the like.
[0071] In another embodiment, the excipient may be a lubricant. Suitable non-limiting examples of lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.
[0072] The excipient may be a dispersion enhancer. Suitable dispersants may include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.
[0073] Depending upon the embodiment, it may be desirable to provide a coloring agent in the outer layer. Suitable color additives include food, drug and cosmetic colors (FD&C), drug and cosmetic colors (D&C), or external drug and cosmetic colors (Ext. D&C). These colors or dyes, along with their corresponding lakes, and certain natural and derived colorants, may be suitable for use in the present invention depending on the embodiment.
[0074] The excipient may include a taste-masking agent. Taste-masking materials include, e.g., cellulose hydroxypropyl ethers (HPC) such as Klucel®, Nisswo HPC and PrimaFlo HP22; low- substituted hydroxypropyl ethers (L-HPC); cellulose hydroxypropyl methyl ethers (HPMC) such as Seppifilm-LC, Pharmacoat®, Metolose SR, Opadry YS, PrimaFlo, MP3295A, Benecel MP824, and Benecel MP843; methylcellulose polymers such as Methocel® and Metolose®; Ethylcelluloses (EC) and mixtures thereof such as E461, Ethocel®, Aqualon®-EC, Surelease; Polyvinyl alcohol (PVA) such as Opadry AMB; hydroxyethylcelluloses such as Natrosol®; carboxymethylcelluloses and salts of carboxymethylcelluloses (CMC) such as Aualon®-CMC; polyvinyl alcohol and polyethylene glycol co-polymers such as Kollicoat IR®; monoglycerides (Myverol), triglycerides (KLX), polyethylene glycols, modified food starch, acrylic polymers and mixtures of acrylic polymers with cellulose ethers such as Eudragit® EPO, Eudragit® RD 100, and Eudragit® El 00; cellulose acetate phthalate; sepifilms such as mixtures of HPMC and stearic acid, cyclodextrins, and mixtures of these materials. In other embodiments, additional taste-masking materials contemplated are those described in U.S. Pat. Nos. 4,851,226; 5,075,114; and 5,876,759, each of which is hereby incorporated by reference in its entirety.
[0075] In various embodiments, the excipient may include a pH modifier. In certain embodiments, the pH modifier may include sodium carbonate or sodium bicarbonate.
[0076] The amount and types of ingredients and other excipients useful in the animal feed formulation are described further in the examples.II. Feed Additive Composition
[0077] One aspect of the present disclosure encompasses feed additive compositions for non-human animals comprising dandelion leaf powder extract. Another aspect of the present disclosure encompasses feed additive compositions for non-human animals comprising dandelion leaf powder extract, sodium acetate, and fennel seed extract. Another aspect of the present disclosure encompasses feed additive compositions for non-human animals comprising dandelion leaf powder extract and green coffee bean. Other optional additives may be further included. The feed additive composition may be added to a basal animal diet for administration to the non-human animals. The feed additive composition may be formulated with basal animal diets to prepare the feed compositions described in Section I
[0078] In some embodiments, dandelion extract in a basal animal diet comprises about 0.0025% to about 0.16% dandelion extract, preferably about 0.005% to about 0.08% dandelion extract, and more preferably about 0.01% to about 0.04% dandelion extract.
[0079] In various embodiments, a feed additive composition may be introduced to a basal animal diet by way of various methods, depending on whether the feed additive composition is in a liquid or solid form. Non-limiting examples of introducing the feed additive composition to a basal animal diet may be formulating the feed additive composition into the basal animal diet, top-dressing the solid composition of a basal animal diet, spraying a liquid feed additive composition onto a basal animal diet, or combinations thereof. It will be recognized that, when the feed additive is introduced to a basal animal diet, the amount of the feed additive introduced to a basal animal diet is sufficient to provide the therapeutically effective amount of the dandelion leaf powder extract in the diet of the animal.
[0080] In addition to dandelion leaf powder extract, a feed additive composition may further comprise at least one additional ingredient such as vitamins, minerals, amino acids, antioxidants, probiotics, essential fatty acids, and pharmaceutically acceptable excipients. Such ingredients may be as described in Section 1(b) above.III. Methods of Using
[0081] Another aspect of the disclosure encompasses methods of using a feed composition. The methods comprise administering the animal feed composition to nonhuman animals, in particular female non-human animals, for example, sows. Preferably, a feed composition is administered orally to non-human animals. A feed composition may be as described in Section (I).
[0082] In various embodiments, the non-human animal may be of varying age and health. Generally, the non-human animal may be a livestock mammal, an avian species or poultry, aquaculture organisms, or mariculture organisms. The aquaculture organisms or mariculture organisms may be fresh or saltwater organisms. Non-limiting example of suitable livestock mammals may be beef cattle, horses, dairy cattle, veal, pigs, goats, sheep, bison, llama, or alpaca. Non-limiting examples of suitable avian species or poultry may be chickens, including broilers, layers, and breeders, ducks, game hens, geese, guinea fowl / hens, quail, and turkeys. Non-limiting species of aquaculture species may be carp, salmon, tilapia, catfish, Bluefin tuna, shrimp, prawns, crawfish, crabs, oysters, mussels, abalone, aquatic reptiles, aquatic amphibians, sea cucumbers, sea urchins, or shellfish. Non-limiting examples of pigs include sow, lactating sow, or piglets.
[0083] The timing and duration of administration of a composition of the invention to an animal can and will vary. The feed composition may be administered throughout the period of feeding the animal. Alternatively, the feed composition may be administered at specific periods during the growth and development of the animal, for instance, during periods of lactation. A composition may also be administered at various intervals. For instance, a composition may be administered daily, weekly, monthly, or over a number of months. In some embodiments, a composition is administered weekly. In other embodiments, a composition is administered monthly. In preferred embodiments, acomposition is administered daily. As it will be recognized in the art, the duration of treatment can and will vary depending on the growth and health of the animal.
[0084] In some embodiments, after administration of the feed composition, the nonhuman animals may show improved reproductive behavior not exhibited by administering the feed composition without extract from Taraxacum. The improved reproductive behavior includes but is not limited to minimizing body weight loss of lactating animals, maintaining feed intake, reducing wean-estrus intervals, reducing non-productive days, improving ovulation rate, improving conception rate, improving farrowing rate, and / or improving breeding rate.
[0085] In some embodiments, after administration of the feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to non-human animals, the non-human animals may show improved IGF-1 response not exhibited by the feed composition without extract from Taraxacum.
[0086] In some embodiments, after administration of the feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human maternal animal, the non-human offsprings may show improved growth performance not exhibited by the feed composition without extract from Taraxacum. In some embodiments, administering the feed composition to the non-human maternal animal may provide passive immunity to the non-human offspring. In some embodiments, the growth performance may be measured by measuring body weight, growth rate, feed intake, and / or feed conversion.
[0087] In some embodiments, the feed composition may be administered to a lactating sow. In some embodiments, administering the feed composition to a lactating sow provides passive immunity to piglets. In some embodiments, the piglets may show improved growth performance not exhibited by the feed composition without extract from Taraxacum. The improved growth performance may be measured by body weight, growth rate, feed intake, and / or feed conversion.
[0088] In some embodiments, administering the feed composition to non-human offsprings during pre-weaning and post-weaning may result in improved growth performance not exhibited by the feed composition without extract from Taraxacum.
[0089] In some embodiments, administering the feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human may result in improved livability in the non-human offsprings during pre-weaning and post-weaning period, wherein the improved livability is not exhibited when the feed composition without extract from Taraxacum is administered. Livability may be determined by measuring mortality and / or morbidity.Definitions
[0090] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this disclosure belongs at the time of filing. If specifically defined, then the definition provided herein takes precedent over any dictionary or extrinsic definition. Further, unless otherwise required by context, singular terms shall include pluralities, and plural terms shall include the singular. Herein, the use of “or” means “and / or” unless stated otherwise. All patents and publications referred to herein are incorporated by reference.
[0091] When introducing elements of the present disclosure or the embodiments(s) thereof, the articles “a,” "an,” “the,” and “said” are intended to mean that there are one or more of the elements. The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.
[0092] Although the disclosure described herein is susceptible to various modifications and alternative iterations, specific embodiments thereof have been described in greater detail above. It should be understood, however, that the detailed description is not intended to limit the disclosure to the specific embodiments disclosed. Rather, it should be understood that the disclosure is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure as defined by the claim language.EXAMPLES
[0093] The following examples illustrate various embodiments of the invention.Example 1: Feeding dandelion extract to lactating sows improved IGF-1 concentration
[0094] Three batches of dandelion leaf extract were characterized to determine the amount of chicoric acid by HPLC and flavonoid derivatives by UV.
[0095] Batch B2317101 : 16.2 mg / g of Chicoric acid by HPLC; 0.196% total flavonoids derivates expressed by UV.
[0096] Batch A1121201 : 23.13mg / g of Chicoric acid by HPLC; 0.384% total flavonoids derivates expressed by UV.
[0097] Batch U1087401 : 24.8mg / g of Chicoric acid by HPLC; 0.35% total flavonoids derivates expressed by UV.
[0098] Serum IGF-1 was measured in primiparous and multiparous sows fed dandelion extract at 0.4 Ib / ton on day 10-14 lactation. FIG. 1 shows increased serum IGF-1 concentrations in both primiparous and multiparous sows, with greater improvement (31.2%) in primiparous sows. IGF-1 is involved in ovarian function and follicular development. In addition, the data also suggested serum IGF-1 was significantly correlated with sow lactation body weight change (FIG. 2) and wean-estrus interval (FIG. 3). Lactating sows may undergo a catabolic status during lactation due to the high energy demands associated with producing milk for their piglets. This catabolic state is characterized by the sow's body breaking down its own energy reserves, such as fat and muscle tissue, to meet the energy requirements of milk production. Large losses in body condition can potentially lead to a prolonged wean- estrus interval, especially in parity 1 and 2 females, and poor ovulation rate and litter size in subsequent parity (Vargas et al., 2009). Therefore, maintaining sow body condition and minimizing body reserves losses during lactation are crucial for reproductive performance. Collectively, the increased IGF-1 levels observed in sows fed dandelion during lactation are indicative of improved body condition and wean-estrus interval, suggesting enhanced reproductive and metabolic health, which could potentially result in higher ovulation rates and larger litters in the subsequent parity.Example 2: Meta-analysis - feeding dandelion extract to lactating sows improved sow reproductive performance in current and subsequent parity
[0099] Three experiments were conducted following the same procedure to evaluate the effects of feeding dandelion leaf extract to lactating sows on reproductive performanceT1during current lactation and subsequent performance in the next parity. In each experiment, lactating sows (average parity = 3.6) from a commercial herd were randomly allotted to either a Control lactation diet (CON) or a lactation diet containing dandelion leaf extract at 0.4 Ib / ton, resulting in a total of 351 sows on CON and 355 sows on dandelion treatment over four experiments. Experimental diets were fed from the day when sows were moved to their individual farrowing crates until the day of weaning. After weaning, retained sows were moved back to individual gestation stalls and a common gestation diet was offered until farrowing at the next parity. Data from the three experiments were compiled for meta-analysis using the MIXED procedure of SAS.
[0100] Meta-analysis of three studies suggested that sow average daily feed intake (ADFI) during lactation was consistently improved in sows fed dandelion in each of the studies, leading to 5.7% greater lactation ADFI of sows fed dandelion compared to sows fed Control diet in meta-analysis (13.46 vs. 12.74 Ib / day, P = 0.03; Table 1). The greater lactation ADFI in sows fed dandelion was accompanied with less body weight loss during lactation (2.88 vs. -2.48 lb for sows fed dandelion extract and control diets, respectively, P = 0.02) Moreover, greater feed intake in sows fed dandelion also resulted in 8.2% lower pre-weaning mortality (7.92 vs. 8.63% for sows fed dandelion extract and control diets, respectively, P = 0.26), 1.6% greater average daily litter weight gain (5.55 vs. 5.40 Ib / day for sows fed dandelion extract and control diets, respectively, P = 0.10) and 2.0% heavier litter weight at weaning (142.85 vs. 140.11 lb for sows fed dandelion extract and control diets, respectively, P = 0.09).
[0101] In addition to the beneficial changes in the current lactation, sows fed dandelion also showed 11.1% reduced wean to estrus interval (6.02 vs. 6.78 d for sows fed dandelion extract and control diets, respectively, P = 0.05), 0.7% higher re-breeding rate (95.6 vs. 94.9% for sows fed dandelion extract and control diets, respectively, P = 0.92) and greater total bom (15.9 vs. 15.2, P = 0.01), born alive (14.5 vs. 13.8 for sows fed dandelion extract and control diets, respectively, P = 0.007) and reduced stillborns (5.1 vs. 5.8%, P = 0.63) in the subsequent party compared to sows on Control treatment (Table 2). The reduced wean to estrus interval and improved litter size in the subsequent parity suggested positive impact on ovulation rate and follicle development from dietary supplementation of dandelion extract in previouslactation phase. Reduced still birth rates from sows fed dandelion extract may suggest better metabolic status of the sows since high still birth rates are typically associated with long labor and poor energy status of the sows.Table 1. Effects of feeding dandelion leaf extract on sow and litter performance during lactationItem Meta-analysisTable 2. Effects of feeding dandelion leaf extract on sow subsequent performance in the next parityExample 3. Feeding dandelion extract to lactating sows improved passive immunity, weight gain and livability in the offspring
[0102] Pigs from sows fed dandelion extract showed 4.2% higher Brix Index compared to those from sows fed Control diet (P = 0.03; Table 3). Brix Index, when measured in serum of suckling piglets, is an indicator of IgG transfer and passive immunity in piglets. Brix Index is positively correlated with pig growth performance (FIG. 4) and livability (Fleming, 2021). The elevated Brix Index in piglets from sows fed dandelion extract, likely attributed to an IGF-1 response, indicated improved passive immunity. Consequently, this led to higher pig weaning weights, a reduced percentage of smaller pigs (P = 0.05), and a decreased preweaning mortality rate (P = 0.08; Table 3).Table 3. Effects of feeding dandelion leaf extract to lactating sows on passive immunity, livability and growth performance of their offspringExample 4. Feeding dandelion extract, sodium acetate, and fennel seed extract to improve milk fat and milk quality in sows.
[0103] Dandelion was included at 0.4 Ib / ton of feed, sodium acetate was included at 2.0 Ib / ton of feed, and fennel seed extract was included at 0.15 Ib / ton of feed during lactation.
[0104] As shown in Table 4 below, feeding dandelion extract, sodium acetate, and fennel seed extract improved milk fat and milk quality in sows.
[0105] Table 4. Effects of feeding dandelion extract, sodium acetate, and fennel seed extract on milk fat concentration in lactating sows.Treatment1Example 5. Feeding dandelion extract and green coffee bean to lactating sows.
[0106] Lactating sows were fed either a control diet or diet containing dandelion leaf extract at 0.4 Ib / ton with 0, 0.05, or 0.25 Ib / ton of green coffee bean. Experimental diets were fed from the day when sows were moved to their individual farrowing crates until the day of weaning.
[0107] As shown in Table 5, sows fed the combination of dandelion at 0.4 Ib / ton and green coffee bean at 0.25 Ib / ton resulted in highest litter weaning weight, pig weaning weight and litter weight gain compared to sows fed control diet and diet containing dandelion or green coffee bean by itself. The combination of dandelion extract and green coffee bean provided another formulation as a method to improve litter performance when fed together to lactating sows.
[0108] One skilled in the art would readily appreciate that the methods, compositions, and products described herein are representative of exemplary embodiments, and not intended as limitations on the scope of the disclosure. It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the present disclosure disclosed herein without departing from the scope and spirit of the disclosure.
[0109] The present disclosure illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations that are not specifically disclosed herein. The terms and expressions which have been employed are used as terms ofdescription and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the present disclosure claimed. Thus, it should be understood that although the present disclosure has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this disclosure as defined by the appended claims.Table 5. Effects of feeding dandelion leaf extract with green coffee bean on sow and litter performance during lactation.
Claims
CLAIMS1. A method for improving reproductive behavior in non-human animals, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum, wherein after administration of the feed composition, the non-human animals show improved reproductive behavior not exhibited by administering the feed composition without extract from Taraxacu .
2. The method of claim 1, wherein Taraxacum comprises Taraxacum albidum, Taraxacum algarbiense, Taraxacum aphrogenes, Taraxacum arcticum, Taraxacum balticum, Taraxacum brachyceras, Taraxacum brevicorniculatum, Taraxacum californicum , Taraxacum carneocoloratum, Taraxacum centrasiaticum, Taraxacum ceratophorum , Taraxacum coreanum, Taraxacum desertorum, Taraxacum erythrospermum, Taraxacum farinosum, Taraxacum holmboei, Taraxacum hybernum, Taraxacum japonicum , Taraxacum kok-saghyz, Taraxacum laevigatum, Taraxacum lissocarpum, Taraxacum minimum, Taraxacum mirabile, Taraxacum officinale, Taraxacum pankhurstianum, Taraxacum platycarpum, Taraxacum pseudoroseum, and / or Taraxacum rubifolium, Taraxacum sued cum.
3. The method of claim 2, wherein the Taraxacum is Taraxacum officinale.
4. The method of claim 1, wherein the Taraxacum is present in the feed composition at a concentration of about 0.1 Ib / ton to about 20 Ib / ton feed.
5. The method of claim 4, wherein the Taraxacum is present in the feed composition at a concentration of about 0.1 Ib / ton to about 0.5 Ib / ton feed.
6. The method of claim 1, wherein the non-human animal is selected from a group comprising pigs, cattle, poultry, alpaca, bison, camel, donkey, goat, horse, llama, mule, rabbit, sheep, goat, deer, aquaculture fish, aquaculture crustaceans, aquaculture mollusks, aquaculture echinoderms, or combinations thereof.
7. The method of claim 6, wherein the pig is a sow or a lactating sow.
8. The method of claim 6, wherein the pig is a piglet.
9. The method of claim 1, wherein the reproductive behavior is exhibited by minimizing body weight loss of lactating animals, maintaining feed intake, reducing wean-estrus intervals, reducing non-productive days, improving ovulation rate, improving conception rate, improving farrowing rate, and / or improving breeding rate.
10. A method for improving IGF-1 response in non-human animals, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum wherein after administration of the feed composition, the non-human animals show improved IGF-1 response not exhibited by administering the feed composition without extract from Taraxacu .
11. The method of claim 10, wherein Taraxacum comprises Taraxacum albidum, Taraxacum algarbiense, Taraxacum aphrogenes, Taraxacum arcticum, Taraxacum balticum, Taraxacum brachyceras, Taraxacum brevicorniculatum, Taraxacum californicum , Taraxacum carneocoloratum, Taraxacum centrasiaticum. Taraxacum ceratophorum, Taraxacum coreanum, Taraxacum desertorum, Taraxacum e rythrospermum , Taraxacum farinosum, Taraxacum holmboei, Taraxacum hybernum, Taraxacum japonicum, Taraxacum kok-saghyz, Taraxacum laevigatum, Taraxacum lissocarpum, Taraxacum minimum, Taraxacum mirabile, Taraxacum officinale, Taraxacum pankhurstianum, Taraxacum platycarpum, Taraxacum pseudoroseum, and / or Taraxacum rubifolium, Taraxacum suecicum.
12. The method of claim 11, wherein the Taraxacum is Taraxacum officinale.
13. The method of claim 10, wherein the Taraxacum is present in the feed composition at a concentration of about 0.1 Ib / ton to about 20 Ib / ton feed.
14. The method of claim 13, wherein the Taraxacum is present in the feed composition at a concentration of about 0.1 Ib / ton to about 0.5 Ib / ton feed.
15. A method for improving growth performance in piglets, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to a lactating sow wherein after administration of the feed composition, the piglets show improved growth performance not exhibited by administering the feed composition without extract from Taraxacum.
16. The method of claim 15, wherein the growth performance comprises body weight, growth rate, feed intake, and / or feed conversion.
17. A method for improving growth performance in non-human offsprings during preweaning and post-weaning period, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human animal wherein after administration of the feed composition, the non-human offsprings during pre-weaning and post-weaning period show improved growth performance not exhibited by administering the feed composition without extract from Taraxacum.
18. The method of claim 17, wherein the growth performance is determined by measuring body weight, growth rate, feed intake, and / or feed conversion.
19. A method for improving livability in non-human offsprings during pre-weaning and post-weaning period, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human animal wherein after administration of the feed composition, the non-human offsprings during pre-weaning and post-weaning period show improved livability not exhibited by administering the feed composition without extract from Taraxacum.
20. The method of claim 19, wherein livability comprises mortality and / or morbidity.
21. A method for improving survivability in non-human offsprings during pre-weaning and post-weaning period, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to maternal non-human animal wherein after administration of the feed composition, the non-humanoffsprings during pre-weaning and post-weaning period show improved survivability not exhibited by administering the feed composition without extract from Taraxacum.
22. A method for improving weight gain in non-human offsprings during pre-weaning and post-weaning period, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the non- human offsprings during pre-weaning and post-weaning wherein after administration of the feed composition, the non-human offsprings during pre-weaning and post-weaning period show improved weight gain not exhibited by administering the feed composition without extract from Taraxacu .
23. A method for improving IGF-1 response and reducing wean to estrus in non-human animals, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the non-human animals wherein after administration of the feed composition, the non-human animals have improved IGF-1 response and reduced wean to estrus not exhibited by the feed composition without extract from Taraxacum.
24. A method for improving IGF-1 response and increasing litter weight gain in non- human animals, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the non-human animals wherein after administration of the feed composition, the non-human animals have improved IGF-1 response and increased litter weight gain not exhibited by administering the feed composition without extract from Taraxacum.
25. A method for improving IGF-1 response and survivability in piglets, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the piglets wherein after administration of the feed composition, the piglets have improved IGF-1 response and survivability not exhibited by administering the feed composition without extract from Taraxacum .
26. A method for improving milk fat and milk quality in lactating animals, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum to the lactating animals wherein after administration of the feed composition, the lactating animals have milk improved fat and milk quality not exhibited by administering the feed composition without extract from Taraxacum .
27. A method for improving IGF-1 response and increasing litter weight gain in nonhuman animals, the method comprising administering a feed composition consisting of a basal animal diet supplemented with extract from Taraxacum and green coffee bean to the non-human animals wherein after administration of the feed composition, the nonhuman animals have improved IGF-1 response and increased litter weight gain not exhibited by administering the feed composition using Taraxacum alone.
Citation Information
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