Pet food compositions

Abstract

To provide pet food compositions and methods for using them.SOLUTION: A pet food composition comprises: oleic acid present in an amount of 4 to 12 wt.% based on the dry weight of the pet food composition; and arachidonic acid present in an amount of 0.02 to 0.08 wt.% based on the dry weight of the pet food composition; where the weight ratio of oleic acid to arachidonic acid is between 160:1 and 190:1.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 091,531, filed on October 14, 2020, the content of which is hereby incorporated by reference in its entirety.

Background Art

[0002] The health of a raised animal is closely related to its feeding. Proper feeding should result in a lively and healthy pet. To achieve proper feeding, specific ingredients that have beneficial effects on the animal and the concentrations of those ingredients can be utilized. Such beneficial effects can include protection against inflammation, kidney disorders, renal insufficiency, cardiovascular diseases, and / or high urinary solute concentrations.

[0003] Kidney disease is common in dogs as they age. Some veterinarians recognize the interaction between kidney disorders and the cardiovascular system in health and disease, and as a result, have named this concept cardiorenal disorder (CvRD).

[0004] Arachidonic acid (AA) is a major component of cell membrane lipids and can be converted into various metabolites that induce an inflammatory response. (Wang T. et al., Int J Mol Sci., 2019, 20: 3683). In fact, there is increasing evidence of the involvement of AA metabolites in myocardial fibrosis (Levick SP et al., J Immunol., 2007, 178:641 - 46). Furthermore, it has been reported that the concentration of oleic acid in rat serum has an inverse correlation with the concentration of arachidonic acid (Hostmark and Haug, Lipids in Health and Disease, 2013, 12:40).

[0005] An increase in the plasma level of interleukin 8 (IL-8) has been shown to potentially be involved in the etiology of acute kidney injury (Liangos et al., Nephron Clin Pract., 2009, 113:c148-C154), and in the establishment and maintenance of an inflammatory microenvironment in the damaged vascular wall (Apostolakis S. et al., Cardiovasc Res., 2009, 84(3):353-60).

[0006] Accordingly, it is desirable to provide a pet food composition that can affect one or more of a decrease in the serum level of arachidonic acid, a decrease in the IL-8 level, a decrease in inflammation, and / or protection against cardio-renal disorders. SUMMARY OF THE INVENTION

[0007] This summary is intended to simply introduce some aspects of some embodiments of the present disclosure. Further areas to which the present disclosure is applicable will become apparent from the forms for carrying out the invention provided hereinafter in this specification. This summary is not an extensive overview, nor is it intended to identify key or decisive elements of the present teachings, nor to delineate the scope of the present disclosure. Rather, its purpose is merely to present one or more concepts in a simplified form as a prelude to the more detailed description that follows.

[0008] The applicant has discovered that the use of certain ingredients in pet food provides effective health benefits. In one aspect, the health benefit may be to increase beneficial metabolites in the animal. In another aspect, the health benefit may be to decrease one or more of the animal's harmful metabolites, interleukins, and prostaglandins. Accordingly, in one embodiment, the invention is a pet food composition comprising a ratio of a specific oleic acid to arachidonic acid.

[0009] In at least one embodiment, the present invention is directed to a pet food composition comprising oleic acid (OA) and arachidonic acid (AA), wherein the ratio of oleic acid to arachidonic acid is at least about 87.6:1. In certain embodiments, the ratio of oleic acid to arachidonic acid (OA:AA) is from about 140:1 to about 200:1. In certain embodiments, the OA:AA ratio is about 172:1. In certain embodiments, oleic acid is present in an amount of about 4% to about 12%, about 4% to about 10%, or about 4% to about 9% based on the dry weight of the pet food composition. In certain embodiments, arachidonic acid is present in an amount of about 0.02% to about 1%, about 0.02% to about 0.08%, or about 0.02% to about 0.06% based on the dry weight of the pet food composition. In certain embodiments, the composition further comprises one or more omega-3 fatty acids. In certain embodiments, the omega-3 fatty acids are present in an amount of about 0.1% to about 1%, about 0.1% to about 0.8%, or about 0.3% to about 0.8% based on the dry weight of the pet food composition. In certain embodiments, the composition further comprises one or more omega-6 fatty acids. In certain embodiments, the omega-6 fatty acids are present in an amount of about 1% to about 10%, about 1.5% to about 7%, or about 2% to about 5% based on the dry weight of the pet food composition. In certain embodiments, the ratio of omega-3 fatty acids to omega-6 fatty acids is from about 1:5 to about 1:10, about 1:6 to about 1:9, or about 1:7 to about 1:9.

[0010] In a further embodiment, the present invention is directed to a method for increasing oleic acid conjugated metabolites and decreasing arachidonic acid conjugated metabolites in dogs, comprising feeding an animal the pet food composition according to any one of claims 1 to 10. In certain embodiments, the method comprises feeding an animal the pet food composition as described in any of the preceding embodiments. In a further embodiment, the method is directed to decreasing the prostaglandin E2 (PGE2) level in the kidney tissue of dogs, comprising feeding an animal the pet food composition as described in any one of the preceding embodiments.

[0011] In a further embodiment, the present invention is A pet food composition is targeted that contains oleic acid (OA) and arachidonic acid (AA), and the ratio of oleic acid to arachidonic acid is about 38.0:1 or more. In certain embodiments, the OA:AA ratio is from about 38:1 to about 60:1. In certain embodiments, the OA:AA ratio is about 43:1. In certain embodiments, oleic acid is present in an amount of about 2% to about 8%, about 3% to about 7%, or about 4% to about 6% based on the dry weight of the pet food composition. In certain embodiments, arachidonic acid is present in an amount of about 0.05% to about 2%, about 0.05% to about 1%, or about 0.07% to about 0.3% based on the dry weight of the pet food composition. In certain embodiments, the composition further comprises one or more omega-3 fatty acids. In certain embodiments, the omega-3 fatty acids are present in an amount of about 0.05% to about 1%, about 0.05% to about 0.08%, or about 0.05% to about 0.5% based on the dry weight of the pet food composition. In certain embodiments, the composition further comprises omega-6 fatty acids. In certain embodiments, the omega-6 fatty acids are present in an amount of about 1% to about 10%, about 1.5% to about 5%, or about 2% to about 5% based on the dry weight of the pet food composition. In certain embodiments, the ratio of omega-3 fatty acids to omega-6 fatty acids is from about 1:10 to about 1:20, about 1:12 to about 1:18, or about 1:12 to about 1:16. In a further embodiment, the invention is a method for increasing oleic acid conjugated metabolites and decreasing arachidonic acid conjugated metabolites in cats, the method comprising feeding an animal a pet food composition as described in any one of the embodiments within this paragraph. In certain embodiments, the invention is a method for reducing the level of prostaglandin E2 (PGE2) in feline kidney tissue, the method comprising feeding an animal a pet food composition as described in any one of the embodiments within this paragraph.

[0012] Further areas to which the present invention is applicable will become apparent from the forms for carrying out the invention provided below. The forms for carrying out the invention and specific examples, while showing typical embodiments of the present invention, are intended for illustrative purposes only and are not intended to limit the scope of the present invention and should be understood as such.

Brief Description of the Drawings

[0013] A detailed description of the present invention will be better understood when read in conjunction with the accompanying drawings. However, it should be understood that the present invention is not limited to the exact arrangements and means of the embodiments shown in the drawings.

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Mode for Carrying Out the Invention

[0024] For illustrative purposes, the principles of the present invention are described by referring to its various illustrative embodiments. Although certain specific embodiments of the present invention are specifically described herein, those skilled in the art will readily recognize that the same principles are equally applicable to other uses and methods and can be employed in other uses and methods. It is understood that the present invention is not limited to the details of any particular embodiment shown in its application. The terms used herein are for purposes of description and do not limit the present invention, its application, or its use.

[0025] As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural references unless the context dictates otherwise. The singular form of any class of components refers to not only one chemical species within that class but also mixtures of those chemical species. The terms "a" (or "an"), "one or more", and "at least one" may be used interchangeably herein. The terms "comprising", "including", "containing", and "having" may be used interchangeably. The term "include" should be construed to mean "including but not limited to". The term "including" should be construed to mean "including but not limited to".

[0026] As used throughout, ranges are used as shorthand for any and all values within the range. Any value within the range can be selected as the terminus of the range.

[0027] Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in this specification are to be understood to refer to weight percentages of the total composition. References to molecules, or plural molecules, present "by weight %" refer to the amount of that molecule, or plural molecules, present in the composition based on the total weight of the composition.

[0028] According to the present application, the use of the term "about" associated with a numerical value refers to a value that may be + / −5% of that number. As used herein, the term "substantially free" is intended to mean an amount of less than about 5.0 wt%, less than 3.0 wt%, less than 1.0 wt%, preferably less than about 0.5 wt%, more preferably less than about 0.25 wt% of the composition.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents, patent applications, publications, other references cited or referred to herein are hereby incorporated by reference in their entirety for all purposes. In the event of a conflict between the definitions in this disclosure and those in the cited references, the disclosure shall control.

[0030] The present disclosure is directed to pet food compositions and methods of using such pet food compositions for the treatment of household pets. In certain embodiments, the pet is a dog. In other embodiments, the pet is a cat.

[0031] The inventors have surprisingly and unexpectedly discovered that providing animals with a pet food diet having a high ratio of oleic acid to arachidonic acid results in an improvement in the health benefits of the animals. Such improvement in health benefits can be exemplified by a number of aspects. In a first aspect, the improvement in health benefits is a synergistic effect for an increase in health-related biomarkers. By feeding the animal compositions described herein, the inventors observed a statistically significant linear relationship between the average of the sum of the changes in certain biomarkers and the ratio of OA:AA utilized. This relationship was observed by measuring the sum of oleic acid-containing metabolites and comparing it to the sum of arachidonic acid containing metabolites in companion animals fed various food compositions. Without being bound by theory, it is understood that an increase in the amount of arachidonic acid containing metabolites results in a pro-inflammatory effect, while an increase in the amount of oleic acid containing metabolites is less inflammatory.

[0032] Accordingly, in one aspect, the present disclosure provides a pet food composition comprising oleic acid and arachidonic acid in a specific ratio to each other. In dogs, the ratio of oleic acid to arachidonic acid may be about 87.6 or more. In cats, the ratio of oleic acid to arachidonic acid may be about 38.0 or more. The weight ratio used herein may be expressed as a mass fraction. For example, a weight ratio of oleic acid to arachidonic acid of 38.0:1 may be expressed as a mass fraction of 38. Similarly, a weight ratio of oleic acid to arachidonic acid of 87.6:1 may be expressed as a mass fraction of 87.6. In certain embodiments, the pet food is in a dry form. In certain embodiments, the pet food is in a moist form.

[0033] The pet food composition contains oleic acid (OA) and arachidonic acid (AA) in a specific ratio. For example, in some embodiments for dogs, the pet food composition has a weight ratio of oleic acid to arachidonic acid from about 87.6:1 to about 200:1, about 87.6:1 to about 180:1, about 87.6:1 to about 160:1, about 87.6:1 to about 150:1, about 87.6:1 to about 140:1, about 87.6:1 to about 130:1, about 87.6:1 to about 120:1, about 87.6:1 to about 110:1, about 87.6:1 to about 100:1, about 100:1 to about 200:1, about 100:1 to about 180:1, about 100:1 to about 160:1, about 100:1 to about 150:1, about 100:1 to about 140:1, about 100:1 to about 130:1, about 100:1 to about 120:1, about 100:1 to about 110:1, about 120:1 to about 200:1, about 120:1 to about 180:1, about 120:1 to about 160:1, about 120:1 to about 150:1, about 120:1 to about 140:1, about 130:1 to about 200:1, about 130:1 to about 180:1, about 130:1 to about 160:1, about 130:1 to about 150:1, about 130:1 to about 140:1, about 140:1 to about 200:1, about 140:1 to about 180:1, about 130:1 to about 160:1, about 130:1 to about 150:1, about 130:1 to about 140:1, about 140:1 to about 200:1, about 140:1 to about 180:1, about 140:1 to about 160:1, or about 140:1 to about 150:1, about 150:1 to about 200:1, about 150:1 to about 180:1, about 150:1 to about 160:1, about 160:1 to about 200:1, about 160:1 to about 180:1, about 170:1 to about 200:1, about 170:1 to about 180:1, about 180:1 to about 200:1, or about 190:1 to about 200:1 (including any range or sub-range therebetween).In some embodiments regarding cats, the pet food composition may have a weight ratio of oleic acid to arachidonic acid from about 38:1 to about 150:1, about 38:1 to about 125:1, about 38:1 to about 100:1, about 38:1 to about 80:1, about 38:1 to about 70:1, about 38:1 to about 60:1, about 38:1 to about 50:1, about 50:1 to about 150:1, about 50:1 to about 125:1, about 50:1 to about 100:1, about 50:1 to about 80:1, about 50:1 to about 70:1, about 50:1 to about 60:1, about 60:1 to about 150:1, about 60:1 to about 125:1, about 60:1 to about 100:1, about 60:1 to about 80:1, about 60:1 to about 70:1, about 70:1 to about 150:1, about 70:1 to about 125:1, about 70:1 to about 100:1, about 70:1 to about 80:1, about 80:1 to about 150:1, about 80:1 to about 125:1, about 80:1 to about 100:1, about 90:1 to about 150:1, about 90:1 to about 125:1, about 90:1 to about 100:1, about 100:1 to about 150:1, about 100:1 to about 125:1, about 110:1 to about 150:1, about 110:1 to about 125:1, about 120:1 to about 150:1, about 130:1 to about 150:1, or about 140:1 to about 150:1 (including any range or sub-range therebetween).

[0034] In certain embodiments, the OA:AA ratio is from about 140:1 to about 200:1. In another embodiment, the ratio of oleic acid to arachidonic acid (OA:AA) is about 172:1. In certain embodiments, the OA:AA ratio is from about 160:1 to about 200:1, about 160:1 to about 195:1, about 165:1 to about 190:1, or about 170:1 to about 185:1. In a further embodiment, the OA:AA ratio is about 172.2. In another embodiment, the OA:AA ratio is from about 38:1 to about 60:1, or about 43:1.

[0035] Oleic acid can be present in various amounts or concentrations. In one embodiment, oleic acid may be present in an amount of about 4% to about 12% based on the dry weight of the pet food composition. For example, oleic acid may be present in an amount of about 4.0 wt%, about 4.2 wt%, about 4.6 wt%, about 4.8 wt%, about 5.0 wt%, about 5.2 wt%, about 5.4 wt%, about 5.6 wt%, about 5.8 wt%, about 6.0 wt%, about 6.2 wt%, about 6.5 wt%, about 6.8 wt%, about 7.0 wt%, about 7.25 wt%, about 7.5 wt%, about 7.75 wt%, about 8.0 wt%, about 8.25 wt%, about 8.5 wt%, about 8.75 wt%, about 9.0 wt%, about 9.5 wt%, about 10.0 wt%, about 10.5 wt%, about 11.0 wt%, about 11.5 wt%, about 12.0 wt%, about 12.5 wt%, about 13.0 wt%, about 13.5 wt% or about 14.0 wt%. In another example, oleic acid may be present in an amount of about 4% to about 10%, about 4% to about 9.5%, or about 4% to about 9% based on the dry weight of the pet food composition. In a further embodiment, oleic acid is present in an amount of about 2% to about 8%, about 3% to about 7%, or about 4% to about 6% based on the dry weight of the pet food composition.

[0036] Arachidonic acid can be present in various amounts or concentrations. In one embodiment, arachidonic acid may be present in an amount of about 0.02% to about 1% based on the dry weight of the pet food composition. For example, arachidonic acid may be present in an amount of about 0.02% by weight, about 0.04% by weight, about 0.06% by weight, about 0.08% by weight, about 0.1% by weight, about 0.12% by weight, about 0.14% by weight, about 0.16% by weight, about 0.18% by weight, about 0.2% by weight, about 0.22% by weight, about 0.24% by weight, about 0.26% by weight, about 0.28% by weight, about 0.3% by weight, about 0.35% by weight, about 0.4% by weight, about 0.45% by weight, about 0.5% by weight, about 0.55% by weight, about 0.6% by weight, about 0.65% by weight, about 0.7% by weight, about 0.75% by weight, about 0.8% by weight, about 0.85% by weight, about 0.9% by weight, about 0.95% by weight, or about 1.0% by weight. In another example, arachidonic acid may be present in an amount of about 0.02% to about 0.08%, about 0.02% to about 0.06%, or about 0.02% to about 0.04% based on the dry weight of the pet food composition. In a further embodiment, arachidonic acid is present in an amount of about 0.05% to about 2%, about 0.05% to about 1%, or about 0.07% to about 0.3% based on the dry weight of the pet food composition.

[0037] In certain embodiments, the pet food further comprises one or more omega-3 fatty acids. The omega-3 fatty acids can be present in various amounts or concentrations. In one embodiment, the omega-3 fatty acids can be present in an amount of about 0.1% to about 1% based on the dry weight of the pet food composition. For example, the omega-3 fatty acids can be present in an amount of about 0.1 wt%, about 0.125 wt%, about 0.15 wt%, about 0.175 wt%, about 0.2 wt%, about 0.225 wt%, about 0.25 wt%, about 0.275 wt%, about 0.3 wt%, about 0.325 wt%, about 0.35 wt%, about 0.375 wt%, about 0.4 wt%, about 0.425 wt%, about 0.45 wt%, about 0.475 wt%, about 0.5 wt%, about 0.525 wt%, about 0.55 wt%, about 0.575 wt%, about 0.6 wt%, about 0.65 wt%, about 0.7 wt%, about 0.75 wt%, about 0.8 wt%, about 0.85 wt%, about 0.9 wt%, about 0.95 wt%, or about 1.0 wt%. In another example, the omega-3 fatty acids can be present in an amount of about 0.1% to about 0.8%, or about 0.1% to about 0.6% based on the dry weight of the pet food composition. In certain embodiments, the omega-3 fatty acids are present in an amount of about 0.05% to about 1%, about 0.05% to about 0.08%, or about 0.05% to about 0.5% based on the dry weight of the pet food composition.

[0038] In certain embodiments, the pet food further comprises one or more omega-6 fatty acids. The omega-6 fatty acids can be present in various amounts or concentrations. In one embodiment, the omega-6 fatty acids may be present in an amount of about 1% to about 10% based on the dry weight of the pet food composition. For example, the omega-6 fatty acids may be present in an amount of about 1 wt%, about 1.5 wt%, about 2.0 wt%, about 2.5 wt%, about 3.0 wt%, about 3.5 wt%, about 4.0 wt%, about 4.5 wt%, about 5 wt%, about 5.5 wt%, about 6 wt%, about 6.5 wt%, about 7 wt%, about 7.5 wt%, about 8 wt%, about 8.5 wt%, 9 wt%, 9.5 wt%, or about 10 wt%. In another example, the omega-6 fatty acids may be present in an amount of about 1.5% to about 7%, about 2% to about 7%, or about 2% to about 5% based on the dry weight of the pet food composition. In certain embodiments, the omega-6 fatty acids are present in an amount of about 1% to about 10%, about 1.5% to about 5%, or about 2% to about 5% based on the dry weight of the pet food composition.

[0039] In one embodiment, the ratio of omega-3 fatty acid(s) to omega-6 fatty acid(s) may vary. In certain embodiments, the ratio of omega-3 fatty acid(s) to omega-6 fatty acid(s) is about 1:5 to about 1:10, about 1:6 to about 1:9, or about 1:7 to about 1:9. In other embodiments, the ratio of omega-3 fatty acid(s) to omega-6 fatty acid(s) is about 1:8. In certain embodiments, the ratio of omega-3 fatty acid to omega-6 fatty acid is about 1:10 to about 1:20, about 1:12 to about 1:18, or about 1:12 to about 1:16.

[0040] In some embodiments, the pet food composition may include one or more additional fatty acids. The one or more fatty acids are preferably selected from fatty acids having 10 to 50 total carbon atoms, 10 to 40 total carbon atoms, or 10 to 30 total carbon atoms. In some embodiments, the pet food composition has a total number of carbon atoms of 10 to 30, 12 to 28, 14 to 26, 16 to 24, 16 to 22, or 16 to 20. One or more fatty acids selected from polyunsaturated fatty acids. In at least one embodiment, the composition includes a polyunsaturated fatty acid having a total of 18 carbon atoms.

[0041] The fatty acids may be derived from plant sources. Examples of plant sources for extracting or obtaining fatty acids include, for example, flaxseed, algae, avocado, hemp seed, pumpkin seed, sunflower seed, walnut, soybean, or a combination of two or more thereof. However, in some embodiments, the fatty acids are derived from animal sources or are synthesized.

[0042] The additional fatty acid(s) may consist of linolenic acid, stearic acid, arachidic acid, oleic acid, stearidonic acid, eicosapentaenoic acid, linolelaidic acid, cervonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paulic acid, elaidic acid, gondoic acid, erucic acid, nervonic acid, mead acid, or a combination of two or more thereof. In some examples, the additional fatty acid includes vaccenic acid, oleic acid, elaidic acid, linolelaidic acid, linoleic acid, stearidonic acid, or a combination of two or more thereof. The pet food composition may include linoleic acid selected from alpha-linolenic acid, gamma-linolenic acid, and combinations thereof.

[0043] The pet food composition may have an amount of additional fatty acid(s) of from about 0.5 to about 20 weight percent, based on the total weight of the composition. For example, the composition may have from about 0.5 to about 20 weight percent, from about 0.5 to about 15 weight percent, from about 0.5 to about 10 weight percent, from about 0.5 to about 8 weight percent, from about 0.5 to about 6 weight percent, from about 0.5 to about 5 weight percent, from about 0.5 to about 4 weight percent, from about 0.5 to about 3 weight percent, from about 1 to about 20 weight percent, from about 1 to about 15 weight percent, from about 1 to about 10 weight percent, from about 1 to about 8 weight percent, from about 1 to about 6 weight percent, from about 1 to about 5 weight percent, from about 1 to about 4 weight percent, from about 1 to about 3 weight percent, from about 1.5 to about 20 weight percent, from about 1.5 to about 15 weight percent, from about 1.5 to about 10 weight percent, from about 1.5 to about 8 weight percent, from about 1.5 to about 6 weight percent, from about 1.5 to about 5 weight percent, from about 1.5 to about 4 weight percent, from about 1.5 to about 3 weight percent, from about 2 to about 20 weight percent, from about 2 to about 15 weight percent, from about 2 to about 10 weight percent, from about 2 to about 8 weight percent, from about 2 to about 6 weight percent, from about 2 to about 5 weight percent, from about 2 to about 4 weight percent, from about 2 to about 3 weight percent, from about 2.5 to about 20 weight percent, from about 2.5 to about 15 weight percent, from about 2.5 to about 10 weight percent, from about 2.5 to about 8 weight percent, from about 2.5 to about 6 weight percent, from about 2.5 to about 5 weight percent, from about 2.5 to about 4 weight percent, from about 3 to about 20 weight percent, from about 3 to about 15 weight percent, from about 3 to about 10 weight percent, from about 3 to about 8 weight percent, from about 3 to about 6 weight percent, from about 3 to about 5 weight percent, or from about 3 to about 4 weight percent (including all ranges and subranges thereof) of one or more fatty acids.

[0044] The composition of the present invention may optionally contain additional ingredients suitable for use in a pet food composition. Examples of such ingredients include, but are not limited to, protein, fat, carbohydrate, dietary fiber, amino acids, minerals, trace elements, vitamins, additives.

[0045] Dietary fiber refers to the components of plants that are resistant to digestion by animal digestive enzymes. Dietary fibers include soluble fibers and insoluble fibers. Soluble fibers are resistant to digestion and absorption in the small intestine and are completely or partially fermented in the large intestine. Examples include beet pulp, guar gum, chicory root, burdock, pectin, blueberries, cranberries, pumpkins, apples, oats, legumes, citrus fruits, barley, or peas. Insoluble fibers can be supplied from any of a variety of raw material sources, including, for example, cellulose, whole wheat products, wheat oats, corn bran, flaxseeds, grapes, celery, green beans, cauliflower, potato skins, fruit skins, vegetable skins, peanut shells, and soy fiber. Crude fiber includes indigestible components contained in the cell walls and cell contents of plants such as grains, such as the husks of grains such as rice, corn, and legumes. The typical amount of fiber in the compositions of the present disclosure can be about 0-10%, or about 1%-about 5%.

[0046] Total dietary fiber can be present in various amounts or concentrations. In one embodiment, total dietary fiber can be present in an amount of less than about 20% based on the dry weight of the pet food composition. In certain embodiments, total dietary fiber is present in an amount of about 1% to about 20% based on the dry weight of the pet food composition. For example, total dietary fiber can be present in an amount of about 1 wt%, about 1.5 wt%, about 2.0 wt%, about 2.5 wt%, about 3.0 wt%, about 3.5 wt%, about 4.0 wt%, about 4.5 wt%, about 5.0 wt% - about 5.5 wt%, about 6.0 wt%, about 6.5 wt%, about 7.0 wt% or an amount in the range therebetween. In another example, total dietary fiber can be present in an amount of about 1 - about 10 wt%, about 2 - about 8 wt%, about 3 - about 8 wt%, about 4 - about 7 wt%, about 4 - about 6 wt%, or about 5 - about 6 wt% (including any range or sub-range therebetween) based on the dry weight of the pet food composition.

[0047] Amino acids containing essential amino acids can be added to the compositions of the present disclosure as free amino acids or can be supplied to the compositions of the present disclosure by any number of raw material sources (e.g., crude protein). Essential amino acids are amino acids that cannot be newly synthesized or can only be synthesized in insufficient amounts by living organisms and must therefore be supplied in the diet. Essential amino acids vary from species to species depending on the metabolism of the living organism. For example, it is generally understood that the essential amino acids for dogs and cats (as well as humans) are phenylalanine, leucine, methionine, lysine, isoleucine, valine, threonine, tryptophan, histidine, and arginine. In addition, taurine, although not technically an amino acid but a derivative of cysteine, is an essential nutrient for cats.

[0048] The composition may contain proteins in various amounts or concentrations. In one embodiment, the protein may be present in an amount of about 20% to about 45% based on the dry weight of the pet food composition. For example, the protein may be present in an amount of about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, or about 45 wt%. In another example, the protein may be present in an amount of about 25% to about 40%, about 30% to about 40%, or about 30% to about 35% based on the dry weight of the pet food composition. In certain embodiments, the protein is present in an amount of about 20% to about 35%, about 25% to about 35%, or about 28% to about 35% based on the dry weight of the pet food composition.

[0049] The pet food composition may contain protein and / or digestible crude protein. "Digestible crude protein" is a part of the protein that can be utilized or converted into available or free nitrogen (amino acids) after digestion by gastric enzymes. In vitro measurement of digestible crude protein may be achieved by using gastric enzymes such as pepsin, digesting the sample, and measuring the free amino acids after digestion. In vivo measurement of digestible crude protein may be achieved by measuring the protein level in the feed / food sample, feeding the sample to an animal, and measuring the amount of nitrogen collected in the animal's feces.

[0050] A portion of the protein in the composition may be digestible protein. For example, the composition may contain an amount of protein where about 40% by weight or more, about 50% by weight or more, about 60% by weight or more, about 70% by weight or more, about 80% by weight or more, or about 90% by weight or more of the protein is digestible protein. In some embodiments, for example when the desired composition promotes weight loss, the portion of the protein that is digestible protein is about 60% by weight or less, about 50% by weight or less, about 40% by weight or less, about 30% by weight or less, about 20% by weight or less, or about 10% by weight or less based on the total amount of protein in the composition. In further embodiments, the amount of protein that is digestible protein is about 10 to about 90% by weight, about 10 to about 70% by weight, about 10 to about 50% by weight, about 10 to about 30% by weight, about 20 to about 90% by weight, about 20 to about 70% by weight, about 20 to about 50% by weight, about 20 to about 40% by weight, about 20 to about 30% by weight, about 20 to about 25% by weight, about 23 to about 90% by weight, about 23 to about 70% by weight, about 23 to about 50% by weight, about 23 to about 40% by weight, about 23 to about 30% by weight, or about 23 to about 25% by weight (including the ranges and sub-ranges).

[0051] The composition of the present invention may optionally contain lipids. The term "lipid" generally refers to a lipid or mixture of lipids that may generally be solid or liquid at normal room temperature (e.g., 25 °C) and pressure (e.g., 1 atmosphere). In some cases, the lipid may be a viscous liquid or an amorphous solid at standard room temperature and standard pressure. Lipids can be supplied by any of a variety of raw material sources known to those skilled in the art, including meat, meat by-products, canola oil, fish oil, and plants. Vegetable fat sources include wheat, flaxseed, rye, barley, rice, sorghum, corn, oats, millet, wheat germ, corn germ, soybeans, peanuts, and cottonseed, as well as oils derived from these and other vegetable fat sources. The compositions of the present disclosure may contain at least about 9% (or from about 9% to about 35%, or from about 10% to about 25%, or from about 15% to about 22%) total lipids.

[0052] In some cases, the fat in the pet food composition is crude lipid. The crude lipid may be present in the pet food composition in an amount of about 10 to about 20 wt%, about 10 to about 18 wt%, about 10 to about 16 wt%, about 12 to about 20 wt%, about 12 to about 18 wt%, about 12 to about 16 wt%, about 12 to about 14 wt%, or about 12 to about 13 wt% based on the total weight of the composition. In some cases, it may be preferred that more than about 50 wt%, more than about 60 wt%, more than about 70 wt%, more than about 80 wt%, or more than about 90 wt% of the total lipids are obtained from animal sources. Alternatively, more than about 50 wt%, more than about 60 wt%, more than about 70 wt%, more than about 80 wt%, or more than about 90 wt% of the total lipids may be obtained from plant sources.

[0053] Carbohydrates can be supplied from any of a variety of raw material sources known to those skilled in the art, including oat fiber, cellulose, peanut hulls, beet pulp, parboiled rice, corn starch, corn gluten meal, and any combination of these raw material sources. Cereals that can supply carbohydrates include, but are not limited to, wheat, corn, barley, and rice. The carbohydrate content of the food can be determined by any number of methods known to those skilled in the art. Generally, the percentage of carbohydrates can be calculated as nitrogen-free extract (”NFE”), which can be calculated as follows. NFE = 100% - moisture% - protein% - lipid% - ash% - crude fiber%. The amount of carbohydrates present in the composition, e.g., the amount calculated as NFE, can be about 10 to about 90 wt%, about 10 to about 70 wt%, about 10 to about 50 wt%, about 10 to about 40 wt%, about 10 to about 30 wt%, about 10 to about 20 wt%, about 20 to about 90 wt%, about 20 to about 70 wt%, about 20 to about 50 wt%, about 20 to about 40 wt%, about 30 to about 90 wt%, about 30 to about 70 wt%, about 30 to about 50 wt%, about 30 to about 40 wt%, about 40 to about 90 wt%, about 40 to about 70 wt%, or about 40 to about 60 wt% based on the total weight of the composition.

[0054] The compositions of the present disclosure can also contain one or more minerals and / or trace elements having counterions, such as chlorides, iodides, fluorides, sulfides, or oxides, e.g., calcium, phosphorus, sodium, potassium, magnesium, manganese, copper, zinc, chromium, molybdenum, selenium, or iron salts, in amounts necessary to avoid deficiencies and maintain health. These amounts are known to those skilled in the art, for example, as provided in the Official Publication of the Associate of American Feed Control Officials, Inc. (”AAFCO”), Nutrient Requirements of Dogs and Cats, 2006. Typical amounts of minerals are about 0.1% to about 4%, or about 1% to about 2%.

[0055] The composition of the present invention can also contain vitamins in amounts necessary to avoid deficiencies and maintain health. These amounts and methods of measurement are known to those skilled in the art. For example, the Official Publication of the Associate of American Feed Control Officials, Inc. (”AAFCO”), Nutrient Requirements of Dogs and Cats, 2006 provides recommended amounts of such components for dogs and cats. As contemplated herein, vitamins can include, but are not limited to, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin H (biotin), vitamin K, folic acid, choline, inositol, niacin, and pantothenic acid. Typical amounts of vitamins in the composition of the present invention are from about 0% to about 3%, or from about 1% to about 2%.

[0056] The compositions of the present disclosure can additionally contain other additives, such as flavor enhancers and stabilizers, in amounts and combinations well known to those skilled in the art. Stabilizing substances include, for example, substances that tend to increase the shelf life of the composition. Other examples of such other additives that are potentially suitable for inclusion in the composition of the present invention include, for example, preservatives, colorants, antioxidants, flavorants, synergists and scavengers, packaging gases, stabilizers, emulsifiers, thickeners, gelling agents, and wetting agents. Examples of emulsifiers and / or thickeners include, for example, gelatin, cellulose ether, starch, starch ester, starch ether, and modified starch. The concentration of such additives in the composition can typically be up to about 5% by weight. In some embodiments, the concentration of such additives (especially when such additives are primarily nutrient balancers such as vitamins and minerals) is from about 0% by weight to about 2.0% by weight. In some embodiments, the concentration of such additives (again especially when such additives are primarily nutrient balancers) is from about 0% by weight to about 1.0% by weight.

[0057] Foods of any hardness or moisture content are contemplated, and for example, the compositions of the present invention can be, for example, dry, moist, or semi-moist animal food compositions. In some embodiments, the moisture content is from about 3% to about 90% of the total weight of the composition. "Semi-moist" refers to a food composition containing from about 25 to about 35% moisture. A "moist" food refers to a food composition having a moisture content of about 60 to 90% or more. A "dry" food refers to a food composition having a moisture content of about 3 to about 11%, and is often manufactured in the form of small pieces or kibble.

[0058] In certain embodiments, the present application further discloses a method of making any of the compositions of the present disclosure. In preparing the compositions of the present invention in wet or canned form, any ingredients (e.g., the desired OA:AA ratio) can generally be incorporated into the composition, for example, during processing of the formulation, such as during and / or after mixing of the other components of the composition. The distribution of these components into the composition can be achieved by conventional means. In some embodiments, the ground animal and poultry proteinaceous tissues are mixed with fish oil, cereal grains, other nutritionally balanced ingredients, other ingredients including special purpose additives (e.g., vitamin and mineral mixtures, inorganic salts, cellulose and beet pulp, bulking agents, and the like), and a sufficient amount of water is added for processing. These ingredients can be mixed in a suitable vessel for heating while blending the components. The heating of the mixture can be carried out in any suitable manner, such as by direct steam injection or by using a vessel equipped with a heat exchanger. Following the addition of the last ingredient, the mixture can be heated to a temperature range of about 50°F (10°C) to about 212°F (100°C). In some cases, the mixture can be heated to a temperature range of about 70°F (21°C) to about 140°F (60°C). Temperatures outside these ranges are generally acceptable but may be commercially impracticable without using other processing aids. When heated to an appropriate temperature, the material will typically be in the form of a thick liquid. This thick liquid can be filled into cans. Once filled into the cans, lids are attached and the containers are hermetically sealed. The sealed cans are then placed in conventional equipment designed to sterilize the contents. This is usually achieved by heating to a temperature above about 230°F (110°C) for an appropriate time, which depends, for example, on the temperature used and the composition.

[0059] Alternatively, the pet food composition can be prepared in a dry form using conventional processes. Typically, dry ingredients, such as for example animal proteins, vegetable proteins, grains, etc., are ground and mixed together. Then, wet or liquid ingredients, including lipids, oils, animal proteins, water, etc., are added to and mixed with the dry mixture. The mixture is then processed into kibble or similar dry pieces. Kibble is often formed using an extrusion process in which a mixture of dry and wet ingredients is mechanically worked at high pressure and temperature and then extruded through small openings and cut into kibble by a rotating knife. The wet kibble is then dried and optionally coated with one or more topical coatings, which may include, for example, flavorants, lipids, oils, powders, and the like. Kibble can also be made from dough using a process other than extrusion, in which the dough is placed in a mold and then heat dried.

[0060] In another aspect, the present disclosure provides a method for increasing a specific metabolite in a dog or cat, comprising feeding an animal the pet food composition described herein in an amount effective to increase a beneficial metabolite biomarker in the animal. In a preferred embodiment, such an increase in the beneficial metabolite biomarker is greater than when it occurs under conditions where one or more of the designated components are absent or not present in the desired ratio. In a preferred embodiment, the beneficial metabolite biomarker is an oleic acid conjugated metabolite.

[0061] In certain embodiments, the present disclosure provides a method for decreasing a specific metabolite in a dog or cat, comprising feeding an animal the pet food composition described herein in an amount effective to decrease a metabolite biomarker in the animal. In a preferred embodiment, such a decrease in the metabolite biomarker is greater than when it occurs under conditions where one or more of the designated components are absent or not present in the desired ratio. In a preferred embodiment, the metabolite biomarker is an arachidonic acid conjugated metabolite.

[0062] In certain embodiments, the present disclosure provides a method for reducing a specific cytokine in an animal, comprising feeding the animal the pet food composition described herein in an amount effective to reduce the cytokine in the animal. In preferred embodiments, such a reduction in cytokine is greater than when it occurs under conditions where one or more of the designated components are absent or are not present in the desired ratio. In preferred embodiments, the cytokine is interleukin-8 (IL-8).

[0063] In certain embodiments, the present disclosure provides a method for reducing a specific prostaglandin in an animal, comprising feeding the animal the pet food composition described herein in an amount effective to reduce the prostaglandin in the animal. In preferred embodiments, such a reduction in prostaglandin is greater than when it occurs under conditions where one or more of the designated components are absent or are not present in the desired ratio. In preferred embodiments, the prostaglandin is prostaglandin E2 (PGE2).

[0064] Figure 1 shows a comparison of various metabolites taken from canine serum. "S" indicates significance (P < 0.05) between diet comparisons as determined by the corresponding t-test, while "NS" indicates non-significance.

[0065] Figure 2 shows a comparison of various metabolites taken from canine serum. "S" indicates significance (P < 0.05) between diet comparisons as determined by the corresponding t-test, while "NS" indicates non-significance.

[0066] Figure 3 shows a model depicting the relationship between arachidonic acid and dysfunction and injury, as well as its relationship to cardiovascular risk (CV risk).

[0067] Figure 4 shows the eicosanoid biosynthesis pathway from arachidonic acid.

[0068] Figure 5 shows the MANOVA analysis of conjugated fatty acids of oleic acid and arachidonic acid in canine-derived serum.

[0069] Figure 6 shows the abundance of conjugated metabolites of oleic acid and arachidonic acid in canine serum. These values were determined by creating a variable that is the sum of the mean values (listed in Figure 6) of specific metabolites at specific time points.

[0070] Figure 7 shows the MANOVA analysis of conjugated fatty acids of oleic acid and arachidonic acid in feline-derived serum.

[0071] Figure 8 shows the abundance of conjugated metabolites of oleic acid and arachidonic acid in feline serum. These values were determined by creating a variable that is the sum of the mean values (listed in Figure 8) of specific metabolites at specific time points.

[0072] Figure 9 shows cytokine levels from the serum of dogs given either a control or experimental composition.

[0073] Figure 10 shows the mechanism by which a diet rich in oleic acid reduces renal insufficiency and cardiovascular risk in companion animals.

Example

[0074] The examples and other implementations described herein are illustrative and are not intended to limit the description to the full scope of the compositions and methods of the present disclosure. Equivalent changes, modifications, and variations of specific implementations, materials, compositions, and methods can be made within the scope of the present disclosure with substantially similar results.

[0075] (Example 1) Twenty-four healthy dogs aged 10.4 to 12.9 years and weighing 6.9 to 13.3 kg that had undergone ovariectomy or castration surgery were given a control diet containing chicken, wheat, barley, sorghum, corn, corn gluten meal, chicken meal, pork fat, beet pulp, soybean oil, vitamins and minerals for 4 weeks during the pre-feeding stage and then divided into one of two groups. In the first stage, the first group was given the control diet and the second group was given the test diet (Composition 1) for 8 weeks. (See Table 1 for detailed composition). Next, a washout period was implemented by re-feeding all dogs the maintenance diet for 4 weeks. Thereafter, in the second stage, the first group was given the test diet and the second group was given the control diet for 8 weeks. Blood / serum samples were collected at the end of each step (e.g., pre-feeding, first stage, washout, second stage) and stored at -80 °C until further analysis.

Table 1

[0076] Untargeted metabolomics analysis was performed on frozen serum samples collected from each dog. Briefly, serum samples were separated with methanol and the resulting extracts were divided into five aliquots and analyzed on four different platforms established by Metabolon Inc. (Morrisville, North Carolina). For serum metabolite and cytokine analysis, delta (treatment - baseline) values were calculated. These values were determined by creating a variable that is the sum of the mean values of specific metabolites at a specific time point (listed in Figures 6 and 8). For example, a sample collected from a specific animal at the end of treatment was subtracted from a sample collected from the same animal at the end of pre-feeding (baseline). Statistical analysis was performed using JMP Pro v14.0 (SAS, Cary, North Carolina).

[0077] Figure 1 shows a comparison of the results of conjugated metabolites. "S" indicates significance (P < 0.05) between diet comparisons by a paired t-test. "NS" indicates non-significance between diet comparisons by a paired t-test.

[0078] The different ratios of oleic acid to arachidonic acid (hereinafter, "OA:AA") resulted in significant differences across lipid classes containing oleic acid (hereinafter "OA") and arachidonic acid (hereinafter "AA") metabolites. These metabolites, or biomarkers, indicate a decrease in inflammatory signals. Inflammation is known as an essential element of the immune system in response to infection or injury. However, the inflammatory response is typically transient and, when chronic inflammation is brought about by circumstances, it is biologically excessive, which is an important factor in the etiology of a range of common chronic diseases. The compositions of the present invention brought about changes in the fatty acid moieties associated with a decrease in inflammation. For example, Composition 1 having an OA:AA ratio of 172.2 showed a significant increase in serum OA-conjugated metabolites compared to AA-conjugated metabolites (see Figures 1, 5, and 6). For example, the control diet having an OA:AA ratio of 64.8 showed a significant increase in AA-conjugated metabolites compared to OA-conjugated metabolites (see Figures 1, 5, and 6). However, Composition 2 having an OA:AA ratio of 87.60 showed no significant difference between OA-conjugated metabolites and AA-conjugated metabolites (see Figures 1, 5, and 6). These results suggest that when the OA:AA ratio is greater than 87.60, serum AA-conjugated metabolites decrease, and a ratio less than 87.60 increases serum AA-conjugated metabolites.

[0079] (Example 2) Twelve healthy dogs that had undergone ovariectomy or castration, aged 1.2 to 8.5 years and weighing 9.1 to 13.6 kg, were given the control diet for 4 weeks in the pre-feeding stage (the same as in Example 1), and then the dogs were given Composition 2 for 4 weeks in the treatment stage (see Table 1 for the detailed composition). Blood / serum samples were collected at the end of the pre-feeding stage and the treatment stage and stored at -80°C until further analysis.

[0080] Non-targeted metabolomics analysis was performed on frozen serum samples collected from each dog. Briefly, serum samples were separated with methanol, and the resulting extracts were divided into five aliquots and analyzed on four different platforms established by Metabolon Inc. (Morrisville, NC). For serum metabolite and cytokine analysis, delta (treatment-baseline) values were calculated. For example, samples collected from a particular dog or cat at the end of treatment were subtracted from samples collected from the same dog or cat at the end (baseline) before feeding. Statistical analysis was performed using JMP Pro v14.0 (SAS, Cary, NC).

[0081] The results show that compositions 2 and 1 significantly decrease plasma interleukin 8 (IL-8) expression levels compared to the control diet (Figure 9). Increases in plasma IL-8 have been shown to potentially be involved in the etiology of acute kidney injury (Liangos et al., Nephron Clin Pract., 2009, 113:c148-C154) and in the establishment and maintenance of an inflammatory microenvironment in the damaged vascular wall (Apostolakis S. et al., Cardiovasc Res., 2009, 84(3):353-60). Therefore, these results suggest that an OA:AA ratio of 87.60:1 or higher has an anti-inflammatory effect.

[0082] (Example 3) Thirty healthy cats aged 2.1 - 8.9 years and weighing 3.5 - 7.5 kg that had undergone ovariectomy or castration surgery were given a control diet containing chicken, wheat, corn gluten meal, pork fat, chicken meal, beet pulp, rice, soybean oil, vitamins, and minerals for 4 weeks at the pre - feeding stage and then divided into six groups. The treatment stage consisted of feeding each group one of three treatment diets (Composition 3, Composition 4, or Composition 5) in different orders based on the treatment group (see Table 2 for detailed compositions). This experiment was a Latin square design, which enabled each cat to be fed all the treatment foods, one at a time, during each period of the treatment stage. Since there were six groups in this test design, there was no bias based on the order of the foods. Each treatment diet was fed for 80 days and then changed to another treatment diet without a washout period. Blood / serum samples were collected before feeding and at the end of each individual treatment diet schedule (80 days) and stored at - 80 °C until further analysis.

Table 2

[0083] Untargeted metabolomics analysis was performed on the frozen serum samples collected from each cat. Briefly, the serum samples were separated with methanol, and the resulting extracts were divided into five aliquots and analyzed on four different platforms established by Metabolon Inc. (Morrisville, North Carolina). For example, samples collected from a particular animal at the end of treatment were subtracted from samples collected from the same animal at the end of pre - feeding (baseline). Statistical analysis was performed using JMP Pro v14.0 (SAS, Cary, North Carolina).

[0084] Figure 2 shows the comparison of the results of conjugated metabolites. "S" indicates significance (P < 0.05) between diet comparisons by the paired t - test. "NS" indicates non - significance between diet comparisons by the paired t - test.

[0085] The results indicate that in cats, different ratios of OA:AA resulted in significant differences across lipid classes containing either OA or AA. For example, the diet of Composition 3 with an OA:AA ratio of 43.5 showed a significant increase in serum OA conjugates compared to AA conjugate metabolites (see Figures 2, 7, and 8). Conversely, Diet Composition 5 with an OA:AA ratio of 22.44 showed a significant increase in AA conjugate metabolites compared to OA conjugate metabolites (see Figures 2, 7, and 8). However, Composition 4 with an OA:AA ratio of 38.0 showed no significant difference between OA conjugate metabolites and AA conjugate metabolites (see Figures 2, 7, and 8). These results suggest that when the OA:AA ratio is greater than 38.0, serum AA conjugate metabolites decrease, and a ratio less than 38.0 increases serum AA conjugate metabolites.

[0086] In summary, these results suggest that the OA:AA ratio affects host fatty acid metabolism, and higher ratios (above 87.60 in dogs and above 38.0 in cats) suppress AA metabolism, enhance OA metabolism, and potentially alleviate the CvRD / CRS syndrome. The proposed mechanism of action indicates that an increase in the OA:AA ratio in the diet decreases AA metabolism, affects PGE2 levels, reduces inflammation, alleviates chronic kidney injury or acute kidney injury, and attenuates cardio-renal axis disorders in companion animals (see Figure 10).

[0087] The present invention has been described with reference to several embodiments that are described in considerable detail for the purpose of providing a complete disclosure of the invention. However, these embodiments are merely illustrative and are not intended to limit or represent an exhaustive listing of all aspects of the invention. The scope of the invention should be determined from the claims appended hereto. Furthermore, it will be apparent to those skilled in the art that numerous modifications can be made in these details without departing from the spirit and principles of the invention.

Claims

[Claim 1] 1. A pet food composition comprising: oleic acid present in an amount of 4 to 12 weight percent based on the dry weight of the pet food composition; and arachidonic acid present in an amount of 0.02 to 0.08 wt.%, based on the dry weight of the pet food composition; A pet food composition having a weight ratio of oleic acid to arachidonic acid of from 160:1 to 190:1.

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