Methods for producing health benefits in animals

Abstract

The present disclosure provides methods and compositions for treating glomerular hyperfiltration, reducing glycogen storage in tissues, or reducing uremic toxins in an animal, comprising orally administering to the animal a composition comprising medium-chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, an antioxidant, and vitamin B.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 411,743, filed September 30, 2022, and U.S. Provisional Patent Application No. 63 / 424,307, filed November 10, 2022, the entire disclosures of which are incorporated herein by reference. [Background technology]

[0002]

[0002] Renal failure is one of the most common causes of death in dogs and cats. In animals suffering from kidney disease, several blood indicators are used to determine the severity of the disease. These indicators include blood urea nitrogen (BUN) and creatinine. When an animal's kidneys are damaged, the kidneys are unable to adequately filter waste products, resulting in increased BUN and creatinine levels in the bloodstream during the course of renal failure. Because inadequate filtration of waste products is the underlying principle of kidney disease, BUN and creatinine are considered the primary indicators of kidney disease.

[0003]

[0003] Other important clinical parameters for animals suffering from renal disease are phosphorus, carbon dioxide, and triglyceride levels. Hyperphosphatemia (abnormally high blood phosphorus levels) often occurs during renal disease. Previous scientific studies have shown that low dietary phosphorus intake is beneficial in mitigating the progression of renal disease. However, because the phosphorus content of such diets comes primarily from high protein components, conventional commercially available pet food formulations have been unable to provide low levels of dietary phosphorus and still meet all of the amino acid requirements of canines and felines. Therefore, reducing the phosphorus content of the diet required reducing the protein content of the diet to a level insufficient to supply the animal's amino acid requirements.

[0004]

[0004] Carbon dioxide levels are an indicator of the level of metabolic buffering (acid-base balance) occurring in animals. Metabolic acidosis is a problem in animals with renal disease, and high levels of carbon dioxide are an indicator of insufficient buffering. Another important parameter in animals with renal disease is blood triglyceride levels. Blood triglyceride levels are important because animals with renal disease often have higher triglyceride levels than normal animals. It is desirable to be able to control these additional parameters through diet in patients with renal disease.

[0005]

[0005] Current dietary therapies for reducing BUN, creatinine, and phosphorus levels involve reducing the amount of dietary protein to a level that results in insufficient amino acids being present. Because urea is ultimately derived from protein, reducing the level of dietary protein reduces BUN. However, such diets can lead to other problems for animals because their protein requirements are not met. Therefore, there remains a need in the art for therapies that can provide treatment for kidney disease and related conditions. Summary of the Invention

[0006]

[0006] The present disclosure relates to methods and compositions for producing a health benefit in an animal. More specifically, the disclosure relates to a composition comprising medium-chain triglycerides (MCTs), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), an antioxidant, arginine, and vitamin B. The disclosure also relates to a method for treating glomerular hyperfiltration, reducing glycogen storage in tissues in an animal, or reducing uremic toxins in an animal, comprising orally administering to the animal a composition comprising MCTs, EPA, DHA, arginine, an antioxidant, and vitamin B.

[0007]

[0007] Additional features and advantages are described herein, and will be apparent from the detailed description that follows. DETAILED DESCRIPTION OF THE INVENTION

[0008] definition

[0008] Below are some definitions. However, definitions may also be found in the "Embodiments" section below, and the heading "Definitions" above does not imply that such disclosure in the "Embodiments" section is not a definition.

[0009] As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context dictates otherwise. Thus, for example, reference to "one ingredient / an ingredient" or "the ingredient" encompasses two or more ingredients. The term "and / or" used in the context of "X and / or Y" should be interpreted as "X," "Y," or "X and Y." As used herein, the term "example," particularly when followed by a list of terms, is merely exemplary and illustrative, but should not be considered exclusive or inclusive.

[0010] As used herein, "about" should be understood to refer to a number within a certain numerical range, e.g., within -10% to +10% of the referenced number, preferably within -5% to +5% of the referenced number, more preferably within -1% to +1% of the referenced number, and most preferably within -0.1% to +0.1% of the referenced number. A range "between" two values ​​is inclusive of the two values. Furthermore, all numerical ranges herein should be understood to include all integers, whole numbers, or fractions within that range. Furthermore, these numerical ranges should be interpreted as supporting claims directed to any number or subset of numbers within that range. For example, a disclosure of 1 to 10 should be interpreted as corresponding to ranges of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0011] All percentages given herein are by weight of the total weight of the composition on a dry matter basis (wt %) unless otherwise stated. When reference is made to pH, the value corresponds to the pH measured at 25°C with standard equipment.

[0012] The terms "food," "food product," and "food composition" refer to a product or composition intended for consumption by an animal and providing the animal with at least one nutrient. The term "pet food" refers to any food composition intended for consumption by a companion animal. Such food compositions can include main meals, treats, beverages, supplements, etc.

[0013] The term "companion animal" means a dog or a cat. As used herein, the terms "cat" and "feline" can be used interchangeably. Additionally, the terms "dog" and "canine" can be used interchangeably. In one embodiment, the companion animal can be a cat.

[0014] The term "Recommended Daily Allowance" or "Recommended Daily Allowance" or "RDA" refers to the daily amount of a vitamin or other nutrient recommended by an art-recognized organization or standard, including, but not limited to, the National Institutes of Health (NIH), the Institute of Medicine of the National Academy of Sciences (IOM), the Dietary Reference Intake (DRI) Nutrition Report, the European Pet Food Industry Federation (FEDIAF), or the Association of American Feed Control Officials (AAFCO), as of January 1, 2023. In one aspect, the RDA can refer to the minimum level defined for cats and / or dogs by AAFCO.

[0015] The term "old" means that an animal is old, such that it exceeds 50% of the average lifespan of that particular species and / or breed within the species. For example, if the average lifespan of a given breed of dog is 10 years, a dog within that breed that is older than 5 years would be considered "old" for purposes of this specification. Furthermore, for example, if the average lifespan of a breed of cat is 15 years, a cat within that breed that is older than 7.5 years would be considered "old" for purposes of this specification. In one embodiment, the compositions and methods disclosed herein concern geriatric animals, such as geriatric dogs or geriatric cats. Animals such as dogs and cats are considered geriatric in the last 25% of their lifespan. As described herein, the lifespan of a dog or cat varies depending on its size and / or breed, and a geriatric dog or geriatric cat can be determined based on the above calculations, but using the 75% figure so that the age threshold is greater than 75% of the average lifespan.

[0016]

[0016] "Wet food" refers to pet food with a moisture content of about 50% to about 90%, and in one embodiment, about 70% to about 90%. "Dry food" refers to pet food with a moisture content of less than about 20%, in one embodiment, less than about 15%, and in a specific embodiment, less than about 10%. "Semi-moist food" refers to pet food with a moisture content of about 20% to about 50%, and in one embodiment, about 25% to about 35%. "Kibble" refers to small pieces of dry or semi-moist pet food, which may be in the form of pellets or any other shape. Non-limiting examples of kibble include granules; pellets; pet food chunks, dried meat, meat analogs, vegetables, and combinations thereof; and pet snacks, such as meat or vegetable jerky, rawhide, and biscuits.

[0017]

[0017] Compositions disclosed herein may be free of any element not specifically disclosed herein. Thus, disclosure of an embodiment using the term "comprising" includes disclosure of embodiments "consisting essentially of" the specified components, and embodiments "consisting of" the specified components. Similarly, methods disclosed herein may be free of any step not specifically disclosed herein. Thus, disclosure of an embodiment using the term "comprising" includes disclosure of embodiments "essentially comprising" the specified steps, and embodiments "consisting of" the specified steps. Additionally, the description of some steps as "optional" does not imply that other steps not expressly described as optional are necessarily required.

[0018]

[0018] Any embodiment disclosed herein can be combined with any other embodiment disclosed herein.

[0019] "Prevention" includes reducing the risk and / or severity of a condition or disease. The terms "treatment," "treat," and "to alleviate" include both prophylactic or preventive treatment (which prevent and / or delay the onset of the targeted condition or disorder) and curative, therapeutic, or disease-modifying treatment, including therapeutic measures that cure, delay, attenuate the symptoms, and / or halt the progression of a diagnosed condition or disease; and include treatment of patients who are ill or diagnosed as suffering from a disease or medical condition, as well as treatment of patients at risk of or suspected of having the disease. The term does not necessarily imply that a subject is treated to the point of cure. The terms "treatment" and "treating" also refer to maintaining and / or improving the health of individuals who are not afflicted with the disease but who may be susceptible to an ill health condition. The terms "treatment / therapy," "treat / treating," and "alleviating" are also intended to include synergistic or otherwise potentiating effects of one or more primary preventative or therapeutic measures. The terms "treatment / therapy," "treat / treating," and "alleviating" are further intended to include dietary management of a disease or condition, or dietary management for the prophylaxis or prevention of a disease or condition. Treatment may be patient-related or physician-related.

[0020]

[0020] Relative terms such as "improved," "enhanced," and "enhanced" refer to the effect of a composition disclosed herein having a particular active agent or blend (e.g., a composition comprising a therapeutically effective amount of medium-chain triglycerides or a prophylactic amount of medium-chain triglycerides) compared to an otherwise identical composition containing a lower amount of the active agent or blend (e.g., medium-chain triglycerides) or no active agent or blend.

[0021] The term "therapeutically effective amount" refers to an amount of a compound of the present invention that (i) treats or prevents a particular disease, condition, or disorder, (ii) relieves, ameliorate, or eliminates one or more symptoms of a particular disease, condition, or disorder in relation thereto, or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition, or disorder described herein. In one embodiment, a therapeutically effective amount may refer to the amount of a composition, active agent, or blend for treating any condition associated with kidney disease in an animal.

[0022] The term "long-term administration" refers to a period of repeated administration or intake of more than one month. In certain embodiments, periods of more than two, three, or four months can be used. Longer periods may also be used, including more than five, six, seven, eight, nine, or ten months. Periods of more than 11 months or one year may also be employed. Long-term use of one, two, three, or more years is also encompassed by the present invention. For certain elderly animals, the animal will likely continue regular intake for the remainder of its life. Such intake is sometimes referred to as "long-term" intake.

[0023] The term "regularly" refers to administering or ingesting the composition at least once a month, and in some aspects, once a week. In certain embodiments, more frequent administration or ingestion can be used, such as two, three, or seven times a week. Still other embodiments include regimens that include ingestion at least once a day. Those skilled in the art will understand that the frequency of administration will vary depending on the composition being ingested or administered, and that some compositions may require more or less frequent administration to maintain a desired level of hydration.

[0024]

[0024] "Medium-chain triglycerides" are lipids in which three medium-chain fatty acids are attached to a glycerol backbone by ester bonds, with at least two, and preferably all three, of the fatty acids being 6 to 12 carbon atoms in length. Medium-chain fatty acids include caproic acid (containing 6 carbon atoms, or C6:0), caprylic acid (containing 8 carbon atoms, or C8:0), capric acid (containing 10 carbon atoms, or C10:0), and lauric acid (containing 12 carbon atoms, or C12:0). In one embodiment, the medium-chain fatty acids of a medium-chain triglyceride may comprise at least 50% caprylic acid of the total medium-chain fatty acids present. In another embodiment, the medium-chain fatty acids of a medium-chain triglyceride may comprise at least 90% caprylic acid of the total medium-chain fatty acids present.

[0025] Embodiment

[0025] The present disclosure relates to methods and compositions for providing a health benefit in an animal. More specifically, in one embodiment, the composition can include medium-chain triglycerides (MCTs), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, an antioxidant, and vitamin B. In another embodiment, a method for treating glomerular hyperfiltration, reducing glycogen storage in tissues in an animal, or reducing uremic toxins in an animal can include orally administering to the animal a composition comprising MCTs, EPA, DHA, arginine, an antioxidant, and vitamin B. In one aspect, the composition can be administered to the animal in a therapeutically effective amount.

[0026] The present inventors have discovered that the present compositions can treat glomerular hyperfiltration and / or reduce glycogen storage and / or reduce uremic toxins in animals in need thereof. Such effects can be useful in treating animals suffering from kidney disease, obesity, diabetes, metabolic syndrome, hyalinosis, hypertension, hypothyroidism, neuropathy, cardiovascular disease, and combinations thereof.

[0027]

[0027] The method generally comprises orally administering to an animal a composition comprising medium-chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, an antioxidant, and vitamin B. In one embodiment, the composition can further comprise other omega-3 fatty acids, antioxidants, amino acids, and mixtures thereof. In one aspect, the composition comprises a preservative. In various aspects, the composition may be a pet food, e.g., a wet pet food, a semi-moist pet food, or a dry pet food, such as kibble; or a nutritional supplement or treat.

[0028] Generally, the medium-chain triglycerides can comprise from about 0.1% to about 60% by weight of the composition. In one embodiment, the medium-chain triglycerides can comprise from about 1% to about 20% by weight of the composition. In other embodiments, the medium-chain triglycerides can comprise from about 1% to about 15%, about 1% to about 10%, about 1% to about 7%, or about 2% to about 10% by weight of the composition. The medium-chain triglycerides can be prepared by any known method, such as direct esterification, rearrangement, fractionation, and / or interesterification. For example, the medium-chain triglycerides can be prepared from vegetable oil feedstocks, such as coconut oil, via a rearrangement process. The chain length and distribution of the medium-chain triglycerides can vary depending on the feedstock. For example, such MCTs can include those having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95%, or even 100% caprylic acid.

[0029] Non-limiting examples of suitable omega-3 fatty acids include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and mixtures thereof. In one embodiment, the omega-3 fatty acids may range from about 0.1% to about 5% by weight of the composition. In some embodiments, the omega-3 fatty acids may be at least about 0.1%, at least about 0.5%, at least about 1.0%, or at least about 2.0% by weight. In one embodiment, DHA may be present in the composition in an amount of from about 0.1% to about 5% by weight. In other embodiments, DHA may be present in an amount of about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, or 3% by weight, up to about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5% by weight. In another embodiment, EPA may be present in the composition in an amount of about 0.05% to about 15% by weight. In other embodiments, EPA may be present in an amount of about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, or 3% by weight, up to about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5% by weight.

[0030] Non-limiting examples of suitable B vitamins include B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid or pantothenate), B6 ​​(pyridoxine), B7 (biotin), B9 (folate or folic acid), and B12 (cobalamin). In one embodiment, the B vitamins may be present at about 1 to 100 times the recommended daily allowance (RDA). In various aspects, the B vitamins may be present at about 1, 5, or 10 times the RDA, to about 15, 30, 60, or 80 times the RDA, to about 20, 40, or 80 times the RDA. In one embodiment, niacin may be present at about 1 to about 30 times the RDA, pantothenate may be present at about 1 to about 50 times the RDA, pyridoxine may be present at about 1 to about 30 times the RDA, thiamine may be present at about 1 to about 200 times the RDA, riboflavin may be present at about 1 to about 100 times the RDA, biotin may be present at about 1 to about 40 times the RDA, folic acid may be present at about 1 to about 50 times the RDA, and cobalamin may be present at about 1 to about 50 times the RDA.In other embodiments, niacin may be present at about 1, 2, 3, 4, 5, 10, 15, or 20 times the RDA to about 2, 3, 4, 5, 10, 15, 20, 25, or 30 times the RDA; pantothenate may be present at about 1, 2, 3, 4, 5, 10, or 15 times the RDA to about 2, 3, 4, 5, 10, 15, 20, 30, or 50 times the RDA; pyridoxine thiamine may be present from about 1, 2, 3, 4, 5, 10, 15, 20, 25, or 30 times the RDA; thiamine may be present from about 1, 2, 3, 4, 5, 10, 15, 20, or 40 times the RDA to about 2, 3, 4, 5, 10, 15, 20, 60, 100, or 200 times the RDA; riboflavin may be present from about 1, 2, 3, 4, 5, 10, 15, 20, or 40 times the RDA to about 2, 3, 4, 5, 10, 15, 20, 60, 100, or 200 times the RDA; The riboflavin may be present at about 1x, 2x, 3x, 4x, 5x, 10x, 15x, 20x, or 30x, to about 2x, 3x, 4x, 5x, 10x, 15x, 20x, 25x, 50x, 80x, or 100x the RDA; biotin may be present at about 1x, 2x, 3x, 4x, 5x, 10x, 15x, or 20x, to about 2x, 3x, 4x, 5x, 10x, 15x, 20x, 25x, or 40x the RDA; and / or cobalamin may be present from about 1, 2, 3, 4, 5, 10, 15, or 20 times the RDA to about 2, 3, 4, 5, 10, 15, 20, 25, 30, or 50 times the RDA. RDA levels can be converted from dosage to specific amounts of composition by adding the RDA per kilogram of composition.

[0031]

[0031] Generally, the compositions may also contain antioxidants, including, but not limited to, vitamin C, vitamin E, carotenoids such as beta-carotene and lycopene, and phenolic compounds such as quercetin, catechin, resveratrol, coumaric acid, and anthocyanins.

[0032] In one embodiment, the composition can include arginine, vitamin C, and vitamin E. Generally, arginine includes any form of arginine and / or any substrate of nitric oxide synthase and / or any substrate capable of increasing arginine levels in the body. In one embodiment, arginine can be present in an amount ranging from about 1% to about 10% by weight of the composition. In other aspects, arginine can be present in an amount ranging from about 1%, 2%, or 3% by weight to about 5%, 8%, or 10% by weight of the composition. In one embodiment, vitamin E can be present in an amount ranging from about 1 to about 50 times the RDA. In other aspects, vitamin E can be present in an amount ranging from about 1, 2, 3, 4, 5, or 10 times the RDA of the composition to about 2, 3, 4, 5, 10, 15, 20, 25, 30, or 50 times the RDA of the composition. In one embodiment, vitamin C can be from about 0.001% to about 1% by weight of the composition. In other aspects, vitamin C can be present from about 0.001%, 0.005%, or 0.01% to about 0.5%, 0.8%, or 1% by weight of the composition.

[0033] In some embodiments, the composition can be administered to an animal for a period of at least one week, at least one month, at least two, three, four, five, or six months, and in some embodiments, at least one year. During this period, the composition can be administered to the animal at least one day per week, at least two days per week, at least three, four, five, or six days per week, or even seven days per week. The composition can be administered in a single dose once per day or in multiple divided doses per day. In one embodiment, the MCTs can be present in an amount of from about 0.1% to about 50% by weight of the composition. In other aspects, the MCTs can be present in an amount of from about 0.1%, 1%, or 3% by weight to about 5%, 10%, 15%, or 20% by weight of the composition. In another embodiment, the composition can be administered in an amount providing from about 10 mg to 5 g of MCTs per kg of animal body weight per day. In one embodiment, 10 mg to about 500 mg of MCT can be administered per kg of animal body weight per day.

[0034] In a particular embodiment, the animal may be a companion animal. In one aspect, the companion animal may be a cat. In another aspect, the companion animal may be a dog. In one embodiment, the animal may be a senior animal or a geriatric animal. In one aspect, the animal may be a senior cat or a geriatric dog. In another aspect, the animal may be a geriatric cat or a geriatric dog.

[0035] In one embodiment, the compositions described herein may be pet food compositions. The pet food compositions disclosed herein may be any food formulated for consumption by pets, such as cats. In one embodiment, the pet food composition provides complete nutrition as defined by the Association of American Feed Control Officials (AAFCO) on January 1, 2023, and according to the type of animal (e.g., cat) for which the composition is intended. In another embodiment, the composition may be a dietary supplement. Such dietary supplements may be added to the food composition, administered together with the food composition, or administered separately. Thus, in some embodiments, the composition may be a complete and nutritionally balanced pet food.

[0036] Generally, pet food compositions may comprise protein, carbohydrates, fat, and ash. In various embodiments, pet food compositions comprise from about 15% to about 50% crude protein. In some embodiments, such compositions may further comprise from about 5% to about 40% fat. In other embodiments, the compositions may further comprise from about 15% to about 60% carbohydrates. In other embodiments, the compositions may further comprise from about 0.1% to about 15% ash.

[0037] The pet food composition may include meat, such as emulsified meat. Examples of suitable meat include poultry, beef, pork, lamb, and fish, particularly those types of meat suitable for pets. The meat may also include any additional parts of an animal, including offal. Some or all of the meat may be provided as one or more meat meals, i.e., meat that has been dried and ground to form particles of substantially uniform size, as defined by AAFCO. Additionally or alternatively, vegetable proteins, such as pea protein, corn protein (e.g., ground corn or corn gluten), wheat protein (e.g., ground wheat or wheat gluten), soy protein (e.g., soybean meal, soy concentrate, or soy isolate), and rice protein (e.g., ground rice or rice gluten), may be used.

[0038] The pet food compositions disclosed herein may include one or more of a vegetable oil, a flavoring agent, a coloring agent, or water. Non-limiting examples of suitable vegetable oils include soybean oil, corn oil, cottonseed oil, sunflower oil, canola oil, peanut oil, and safflower oil. In some embodiments, the lipids in the composition may include MCTs and one or more of any vegetable oil, any fish oil, any meat-derived lipid, and any omega-3 fatty acid.

[0039]

[0039] Non-limiting examples of suitable flavoring agents include yeast, tallow, rendered animal meals (e.g., poultry, beef, lamb, and pork), flavor extracts or blends (e.g., grilled beef), and animal digests. Non-limiting examples of suitable coloring agents include FD&C coloring agents, such as Blue No. 1, Blue No. 2, Green No. 3, Red No. 3, Red No. 40, Yellow No. 5, and Yellow No. 6; natural coloring agents, such as caramel color, annatto, chlorophyllin, cochineal, betanin, turmeric, saffron, paprika, lycopene, elderberry juice, pandan, and butterfly pea; titanium dioxide; and any suitable food coloring agent known to those skilled in the art.

[0040]

[0040] The pet food compositions disclosed herein may optionally contain further ingredients, such as starches, humectants, oral care ingredients, preservatives, other amino acids, other antioxidants, fiber, prebiotics, sugars, animal fats, aromas, other oils, etc., in addition to or as an alternative to vegetable oils, salts, vitamins, minerals, probiotic microorganisms, bioactive molecules, or combinations thereof.

[0041]

[0041] Non-limiting examples of suitable starches include, for example, cereal grains such as corn, rice, wheat, barley, oats, potato, peas, beans, cassava, etc., and mixtures of these grains. Suitable starches can be at least partially comprised in any flour. Non-limiting examples of suitable humectants include salt, sugars, propylene glycol, and polyhydric glycols such as glycerin and sorbitol. Non-limiting examples of suitable oral care ingredients include alfalfa nutrient concentrate containing chlorophyll, baking soda, phosphates (e.g., tricalcium phosphate, acid pyrophosphate, tetrasodium pyrophosphate, metaphosphate, and orthophosphate), peppermint, cloves, parsley, and ginger. Non-limiting examples of suitable preservatives include potassium sorbate, sorbic acid, sodium methyl para-hydroxybenzoate, calcium propionate, propionic acid, and combinations thereof.

[0042] The specific amount of each additional ingredient in the pet food compositions disclosed herein will depend on a variety of factors, including the ingredients contained in the first food ingredient and any second food ingredient; the species of the animal; the age, weight, health, sex, and diet of the animal; the rate at which the animal eats and drinks; and the purpose for administering the food product to the animal. Thus, the ingredients and their amounts can vary widely.

[0043]

[0043] Yet another aspect of the present disclosure is a method of making pet food, comprising adding medium-chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, vitamin E, vitamin C, and vitamin B to at least one other edible ingredient, wherein the medium-chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, vitamin E, vitamin C, and vitamin B are added in amounts effective to provide the health benefits disclosed herein. For example, medium chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, vitamin E, vitamin C, and vitamin B can be added in therapeutically effective amounts such that administration of the pet food is effective to treat or prevent glomerular hyperfiltration, reduce glycogen stores, or reduce uremic toxins in the animal. [Example]

[0044]

[0044] By way of example and not limitation, the following non-limiting studies describe compositions and methods using MCTs for treating glomerular hyperfiltration, reducing glycogen storage in tissues, or reducing uremic toxins in animals in one or more embodiments provided by the present disclosure.

[0045] Example 1 CKD Mouse Study In this study, 8-week-old db / db mice were used for the 8-week intervention. The mice were divided into four groups of 9–10 mice each receiving different blends (the control group received a standard AIN-93M diet; the Dapa group received standard AIN-93M supplemented with 10 mg / kg dapagliflozin; the RPB group received a standard diet supplemented with a renal protection blend; and the RPB+ group received a standard diet supplemented with a renal protection blend containing medium-chain triglycerides); the diets are shown in Table 1. Additionally, a group of nine db / db control mice received a standard AIN-93M diet; these diets are also shown in Table 1. The blends were administered to test glomerular hyperfiltration and tissue glycogen storage. The final weekly food intake, final body weight, final blood glucose level, final lean body mass, and final fat mass of each group are shown in Table 2. Table 2 also shows GFR progression, urine albumin / creatinine ratio, urine protein / creatinine ratio, glomerulosclerosis score, periodic acid-Schiff (PAS) staining score of the distal convoluted tubule (DCT) lumen, PAS staining score of intranuclear inclusions in the distal tubule, and PAS staining score of cytoplasmic aggregates in the distal tubule.

[0046] [Table 1]

[0047] [Table 2]

[0048] In addition to the measurements in Table 2, mice were evaluated for hyalinosis using a scoring system of no hyalinosis, moderate hyalinosis, or severe hyalinosis. Here, hyalinosis refers to thickening of the walls of glomerular arterioles due to the deposition of homogeneous hyaline material. The RPB+ group was the only group other than db / m mice that contained mice without severe hyalinosis. The control group had 1 mouse with no hyalinosis, 4 with moderate hyalinosis, and 4 with severe hyalinosis; the dapa group had 2 with no hyalinosis, 5 with moderate hyalinosis, and 2 with severe hyalinosis; the RPB group had 5 with no hyalinosis, 4 with moderate hyalinosis, and 1 with severe hyalinosis; and the RPB+ group had 2 with no hyalinosis and 8 with moderate hyalinosis.

[0049] The effects of RPB and RPB+ on food intake were evaluated over the treatment period. As shown in Table 2, the final food intake of db / db mice treated with RPB and RPB+ was similar to that of db / db mice. As a result, there was no significant difference in food intake between RPB and RPB+-treated db / db mice and vehicle-treated db / db mice. The effects of RPB and RPB+ on body weight were evaluated over the treatment period. As shown in Table 2, the final body weights of RPB and RPB+-treated db / db mice were not significantly different from those of vehicle-treated db / db mice. RPB and RPB+ did not show significant differences in blood glucose levels compared to vehicle-treated db / db mice. RPB+-treated db / db mice showed an increase in lean body mass compared to vehicle-treated db / db mice. RPB and RPB+-treated db / db mice showed normalized GFR progression. RPB and RPB+-treated db / db mice showed an improvement in urinary albumin / creatinine ratio. RPB- and RPB+-treated db / db mice showed improved urinary protein / creatinine ratios. RPB+-treated db / db mice showed significant improvement in glomerulosclerosis in kidney tissue compared with vehicle-treated db / db mice. RPB-treated db / db mice showed improvement in DCT lumina, and RPB+-treated db / db mice showed significant improvement in DCT lumina in kidney tissue compared with vehicle-treated db / db mice. RPB+-treated db / db mice showed improvement in PAS-positive intranuclear inclusions in the distal tubules of kidney tissue compared with vehicle-treated db / db mice. RPB+-treated db / db mice showed significant improvement in PAS-positive cytoplasmic aggregates in the distal tubules of kidney tissue compared with vehicle-treated db / db mice.

[0050]

[0048] Furthermore, uremic toxins were measured in the control (vehicle), RPB, and RPB+ groups of db / db mice. The results are shown in Table 3 as the median values ​​for each group.

[0051] [Table 3]

[0052] As shown in Table 3, both the RPB and RPB+ compositions reduced levels of uremic toxins, with RPB+ being the most effective. As discussed herein, the difference between the RPB and RPB+ diets was due solely to the inclusion of MCTs in the RPB+. Thus, the data indicate that MCTs are particularly effective in reducing uremic toxins, which was surprising and unexpected.

[0053] Example 2 CKD Cat Study Serum and urine samples were collected from 28 healthy cats, 5 cats with stage 1 CKD, and 11 cats with stage 2 CKD. Cats with CKD were diagnosed and staged according to the IRIS guidelines (http: / / www.iris-kidney.com / guidelines / staging.html). Samples were stored at -80°C until use. Targeted analysis was performed at Colorado State University to measure the concentrations of four uremic toxins. Standard p-cresol sulfate (pCS) was purchased from APExBio Technology, indoxyl sulfate (IS) and IS-D5 from Cayman Chemical, trimethylamine N-oxide (TMAO) from Sigma-Aldrich, TMAO-D9 from Santa Cruz Biotechnology, pCS-D7 from Cambridge Isotope, and phenyl sulfate (PS) from TCI Chemicals. The uremic toxin internal standard mixture contained 12.5 μg / mL TMAO-D9, 250 μg / mL pCS-D7, 12 μg / mL IS-D5, and 1 μg / mL IAA (indole-3-acetic acid)-D5 dissolved in 50% aqueous methanol.

[0054]

[0051] A serum sample (40 μL) was mixed with 10 μL of internal standard and 200 μL of cold methanol. The mixture was vortexed for 5 seconds, then incubated overnight at -20°C, followed by centrifugation at 15,000 G and 4°C for 15 minutes. The supernatant (100 μL) was collected, and then 900 μL of 50% methanol was added, which was stored at -20°C until analysis. A small aliquot of sample extract was pooled from each sample to create a quality control (QC) sample.

[0055]

[0052] Urine samples (20 μL) were mixed with 80 μL of cold methanol, then incubated overnight at -20°C and centrifuged at 15,000 G for 15 minutes at 4°C. The supernatant (10 μL) was collected, and then 10 μL of internal standard and 1 mL of 50% methanol were added and stored at -20°C until analysis. Small aliquots of sample extract were pooled from each sample to create quality control (QC) samples.

[0056] UPLC-MS / MS was performed on a Waters Acquity UPLC coupled to a Waters Xevo TQ-S triple quadrupole mass spectrometer. Chromatographic separation was performed on a Waters UPLC T3 stationary phase (2.1 × 50 mm, 1.8 μM) column. All raw data files were imported into the Skyline open-source software package. Each target analyte was visually inspected for retention time and peak area integration. Peak areas were extracted for target compounds detected in biological samples and normalized to the peak area of ​​the appropriate internal standard or surrogate in each sample. Absolute quantification values ​​(μg / mL) were calculated using a linear regression equation generated from the calibration curve for each compound.

[0057] The sample results are shown in Tables 4 and 5. Table 4 shows the serum uremic toxin levels for 28 healthy control cats (CON), 5 cats with stage 1 CKD (CKD1), and 11 cats with stage 2 CKD (CKD2). Table 5 shows the urinary uremic toxin levels for 27 healthy control cats (CON), 5 cats with stage 1 CKD (CKD1), and 11 cats with stage 2 CKD (CKD2), normalized by each cat's urinary creatinine concentration. Data are shown as means.

[0058] [Table 4]

[0059] [Table 5]

[0060] As shown in Tables 4 and 5, uremic toxins increased in the circulating blood and urine in proportion to the severity of CKD in cats. Excess uremic toxins are known to cause chronic inflammation, excessive free radical production, insulin resistance, cellular apoptosis, and intestinal barrier damage, which can lead to further kidney disease. Therefore, cats with CKD will benefit from the RPB and RPB+ compositions disclosed herein.

[0061] It should be understood that various changes and modifications to the preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. Accordingly, it is intended that such changes and modifications be covered by the appended claims.

Claims

1. A method for treating glomerular hyperfiltration, reducing glycogen storage in tissues, or reducing uremic toxins in an animal, comprising orally administering to the animal a composition comprising medium-chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, an antioxidant, and vitamin B.

2. 10. The method of claim 1, wherein the B vitamins include niacin, pantothenate, pyridoxine, thiamine, riboflavin, biotin, folic acid, and cobalamin.

3. 3. The method of claim 2, wherein said niacin is about 1 to about 30 times the RDA, said pantothenate is about 1 to about 50 times the RDA, said pyridoxine is about 1 to about 30 times the RDA, said thiamine is about 1 to about 200 times the RDA, said riboflavin is about 1 to about 100 times the RDA, said biotin is about 1 to about 40 times the RDA, said folic acid is about 1 to about 50 times the RDA, and said cobalamin is about 1 to about 50 times the RDA.

4. 10. The method of claim 1, wherein the medium chain triglycerides are from about 0.1% to about 60% by weight of the composition.

5. 10. The method of claim 1, wherein the medium chain triglycerides are from about 1% to about 20% by weight of the composition.

6. 10. The method of claim 1, wherein the medium chain triglycerides comprise a medium chain fatty acid selected from the group consisting of caprylic acid, capric acid, and mixtures thereof.

7. 2. The method of claim 1, wherein the DHA is from about 0.1% to about 5.0% by weight of the composition, the EPA is from about 0.1% to about 5.0% by weight of the composition, the arginine is from about 1% to about 10% by weight of the composition, vitamin E is from about 1 to about 50 times the RDA, vitamin C is from about 0.001% to 1% by weight of the composition, and the vitamin B is from about 1 to 100 times the RDA.

8. 10. The method of claim 1, wherein the composition further comprises additional omega-3 fatty acids, antioxidants, preservatives, or mixtures thereof.

9. 10. The method of claim 1, wherein the composition is a complete and nutritionally balanced pet food.

10. 10. The method of claim 1, wherein the composition is a dietary supplement.

11. The method of claim 1 , wherein the animal is a companion animal.

12. 10. The method of claim 1, wherein the animal has a health condition selected from the group consisting of kidney disease, obesity, diabetes, metabolic syndrome, hyalinosis, hypertension, hypothyroidism, neuropathy, cardiovascular disease, and combinations thereof.

13. The method of claim 1, wherein the animal is an elderly animal.

14. 10. The method of claim 1, wherein the composition is administered to the animal daily for at least one week.

15. 10. The method of claim 1, wherein the composition is administered in an amount that provides from about 10 mg to about 500 mg of the MCTs per kg of body weight of the animal per day.

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