Methods for providing health benefits in animals

Abstract

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

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application Serial No. 63 / 411,743 filed on September 30, 2022 and U.S. Provisional Application Serial No. 63 / 424,307 filed on November 10, 2022, the disclosures of which are incorporated herein by reference in their entirety. Background Art

[0003] Renal failure is one of the most common causes of death in dogs and cats. In animals with kidney disease, several blood indices are used to determine the severity of the disease. These indices include blood urea nitrogen (BUN) and creatinine. During the course of kidney failure, BUN and creatinine levels in the bloodstream increase because damage to the animal's kidneys causes the kidneys to inadequately filter waste products. Because inadequate filtering of waste products is the fundamental basis of kidney disease, BUN and creatinine are considered the main indicators of kidney disease.

[0004] Other clinical parameters important for animals suffering from nephropathy are phosphorus, carbon dioxide and triglyceride levels.Hyperphosphatemia (abnormally high blood phosphorus levels) often manifests during nephropathy.Previous scientific studies have indicated that the dietary intake of phosphorus is beneficial to alleviate the progression of nephropathy.However, previous commercial pet food formulas cannot yet provide low-level dietary phosphorus, and still meet all amino acid requirements of canines and felines, because the phosphorus component of this diet is mainly derived from high-protein ingredients.Therefore, reducing the phosphorus content of the diet requires that the protein component in the diet be reduced to a level that is not enough to supply the amino acid requirements of the animal.

[0005] Carbon dioxide levels are indicators of the level of metabolic buffering (acid-base balance) that occurs in animals. Metabolic acidosis is problematic for animals with nephropathy, and high carbon dioxide levels are indicators of a lack of buffering. Another important parameter in animals with nephropathy is the blood triglyceride level. This is important in animals with nephropathy because triglyceride levels are often higher than those in normal animals. It is desirable to be able to control these additional parameters in nephropathy patients through diet.

[0006] Current dietary therapies for reducing BUN, creatinine, and phosphorus levels include reducing the amount of dietary protein to a level where amino acids are present in insufficient amounts. Reducing the level of dietary protein reduces BUN because urea ultimately comes from protein. However, since the protein needs of animals are not met, such diets may cause animals to develop other problems. Therefore, there is still a need in the art for a therapy that can provide treatment for nephropathy and related symptoms. Summary of the invention

[0007] The present disclosure generally relates to methods and compositions for providing health benefits in animals. More specifically, the present disclosure relates to compositions comprising medium chain triglycerides (MCT), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), antioxidants, arginine and B vitamins. The present disclosure also relates to a method for treating glomerular hyperfiltration, reducing glycogen storage in animal tissues, or reducing uremic toxins in the animal, the method comprising orally administering to the animal a composition comprising MCT, EPA, DHA, arginine, antioxidants and B vitamins.

[0008] Additional features and advantages are described herein, and will be apparent upon reading the following detailed description. DETAILED DESCRIPTION

[0009] definition

[0010] Some definitions are provided below. However, definitions may be located in the "Implementation" section below, and the above heading "Definitions" does not indicate that such disclosure in the "Implementation" section is not a definition.

[0011] As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an ingredient" or "the ingredient" includes two or more ingredients. The term "and / or" used in the context of "X and / or Y" should be interpreted as "X" or "Y" or "X and Y." The term "example," when used herein, particularly when followed by a list of terms, is exemplary and illustrative only and should not be considered exclusive or comprehensive.

[0012] As used herein, "about" should be understood to refer to a number within a certain numerical range, such as a range of -10% to +10% of the mentioned number, preferably within a range of -5% to +5% of the mentioned number, more preferably within a range of -1% to +1% of the mentioned number, and most preferably within a range of -0.1% to +0.1% of the mentioned number. The range "between" two values ​​includes both values. In addition, all numerical ranges herein should be understood to include all integers or fractions within the range. In addition, these numerical ranges should be understood to provide support for claims involving any number or subset of numbers within the range. For example, the disclosure of 1 to 10 should be understood to support ranges of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0013] Unless otherwise indicated, all percentages expressed herein are by weight (wt%) based on the total weight of the composition on a dry matter basis.When pH is mentioned, the values ​​correspond to the pH measured at 25°C with standard equipment.

[0014] The terms "food," "food product," and "food composition" mean a product or composition that is intended for ingestion by an animal and that provides at least one nutrient to the animal. The term "pet food" means any food composition that is intended for consumption by a companion animal. Such food compositions may include main meals, treats, beverages, supplements, and the like.

[0015] The term "companion animal" means a dog or a cat. As used herein, the terms "cat" and "feline" are used interchangeably. Additionally, the terms "dog" and "canine" are used interchangeably. In one embodiment, the companion animal may be a cat.

[0016] The term "recommended daily requirement" or "recommended daily intake" or "RDA" refers to the daily amount of a vitamin or other nutrient recommended by an institution or standard recognized in the art, 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) report, the European Pet Food Industry Federation (FEDIAF), or the American Feed Control Association (AAFCO) as of January 1, 2023. In one aspect, RDA can refer to the minimum level defined by AAFCO for cats and / or dogs.

[0017] The term "old" refers to an animal that is old and has exceeded 50% of the average lifespan of its particular species and / or breed within a species. For example, if the average lifespan of a dog of a given breed is 10 years, then dogs of that breed that are older than 5 years old will be considered "old" for purposes of this article. In addition, for example, if the average lifespan of a cat of a certain breed is 15 years, then cats of that breed that are older than 7.5 years old will be considered "old" for purposes of this article. In one embodiment, the compositions and methods disclosed herein relate to elderly animals, such as elderly dogs or elderly cats. In the last 25% of the life of an animal (such as a dog and a cat), it is considered old. As described herein, the lifespan of a dog or cat depends on its size and / or its breed, and an elderly dog ​​or elderly cat can be determined based on the above calculations, but using a value of 75% so that the age threshold exceeds 75% of the average lifespan.

[0018] "Wet food" refers to pet food having a moisture content of about 50% to about 90%, and in one aspect about 70% to about 90%. "Dry food" refers to pet food having a moisture content of less than about 20%, and in one aspect less than about 15%, and in one specific aspect less than about 10%. "Semi-moist food" means pet food having a moisture content of about 20% to about 50%, and in one aspect about 25% to about 35%. "Kibble" means dry or semi-moist pet food pieces, which may have a pellet shape or any other shape. Non-limiting examples of kibble include: granules; pellets; pet food pieces, dehydrated meat, imitation meat products, vegetables, and combinations thereof; and pet snacks such as jerky or vegetable jerky, rawhide, and biscuits.

[0019] The compositions disclosed herein may not contain any elements not specifically disclosed herein. Therefore, the disclosure of embodiments using the term "comprising / including" includes disclosures of embodiments "consisting essentially of the specified components" and embodiments "consisting of the specified components". Similarly, the methods disclosed herein may not contain any steps not specifically disclosed herein. Therefore, the disclosure of embodiments using the term "comprising / including" includes disclosures of embodiments "consisting essentially of the specified steps" and embodiments "consisting of the specified steps". In addition, the fact that some steps are described as "optional" does not mean that other steps that are not explicitly described as optional are required steps.

[0020] Any embodiment disclosed herein may be combined with any other embodiment disclosed herein.

[0021] "Prevention" includes reducing the risk and / or severity of a condition or disorder. The terms "treatment" and "relief" include both preventive or prophylactic treatment (preventing and / or delaying the development of a target pathological condition or disorder), as well as curative, therapeutic or disease-modifying treatments, including therapeutic measures that cure, delay, alleviate symptoms of a confirmed pathological condition or disorder and / or interrupt its progression; and treatment of patients at risk of contracting a disease or suspected of contracting a disease, as well as treatment of patients who are ill or have been diagnosed with a disease or medical condition. The term does not necessarily mean that the subject is treated until full recovery. The term "treatment" also refers to health maintenance and / or promotion in individuals who do not suffer from the disease but may be prone to developing an unhealthy condition. The terms "treatment" and "relief" are also intended to include strengthening or otherwise enhancing one or more primary preventive or therapeutic measures. The terms "treatment" and "relief" are also intended to include dietary management of a disease or condition or dietary management for preventing or preventing a disease or condition. Treatment can be patient-related or doctor-related.

[0022] The relative terms "improve," "increase," "enhance," and the like refer to the effect of a composition disclosed herein having a particular active substance or blend (e.g., a composition comprising a therapeutically effective amount of medium chain triglycerides or a prophylactic dose of medium chain triglycerides) relative to a composition having a lesser amount or lacking that active substance or blend (e.g., medium chain triglycerides) but being the same in other respects.

[0023] The term "therapeutically effective amount" means an amount of a compound of the invention that has the following effects: (i) treats or prevents a specific disease, condition or disorder, (ii) alleviates, ameliorates or eliminates one or more symptoms associated with a specific disease, condition or disorder, or (iii) prevents or delays the onset of one or more symptoms of a specific disease, condition or disorder described herein. In one embodiment, a therapeutically effective amount can refer to the amount of a composition, active substance or blend used to treat any condition associated with kidney disease in an animal.

[0024] The term "long-term administration" means repeated administration or consumption for a period of more than one month. A period of more than two months, three months or four months may be used for certain embodiments. In addition, an extended period including more than 5 months, 6 months, 7 months, 8 months, 9 months or 10 months may be used. A period of more than 11 months or 1 year may also be used. Long-term use of more than 1 year, 2 years, 3 years or more may also be included in the present invention. For some elderly animals, these animals will continue to consume regularly throughout their remaining lives. This is sometimes referred to as "extended" period consumption.

[0025] The term "regular administration" refers to dosing a composition or consuming a composition at least once a month, and in some aspects, once a week. In certain embodiments, more frequent dosing or consumption may be used, such as twice, three times, or seven times a week. Nevertheless, other embodiments include such a regimen: the regimen includes at least one daily consumption. Those skilled in the art will recognize that the dosing frequency will vary with the composition being consumed or administered, and some compositions may require more or less frequent administration to maintain the desired level of hydration.

[0026] "Medium chain triglycerides" are lipids in which three medium chain fatty acids are ester-bonded to the glycerol backbone, and at least two and preferably all three fatty acids are each between six and twelve carbons in length. The medium chain fatty acids are caproic acid (comprising six carbon atoms or C6:0), caprylic acid (comprising eight carbon atoms or C8:0), capric acid (comprising ten carbon atoms or C10:0), and lauric acid (comprising twelve carbon atoms or C12:0). In one embodiment, the medium chain fatty acids of the medium chain triglycerides may include at least 50% caprylic acid of the total medium chain fatty acids present. In another embodiment, the medium chain fatty acids of the medium chain triglycerides may include at least 90% caprylic acid of the total medium chain fatty acids present.

[0027] Implementation

[0028] The present disclosure generally relates to methods and compositions for providing health benefits in animals. More specifically, in one embodiment, the composition may include medium chain triglycerides (MCT), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, antioxidants, and B vitamins. In another embodiment, a method for treating glomerular hyperfiltration, reducing glycogen storage in animal tissues, or reducing uremic toxins in the animal may include orally administering a composition comprising MCT, EPA, DHA, arginine, antioxidants, and B vitamins to the animal. In one aspect, the composition may be administered in a therapeutically effective amount.

[0029] The inventors have found that the compositions of the present invention can treat glomerular hyperfiltration and / or reduce glycogen storage and / or reduce uremic toxins in animals in need thereof. This effect can help treat animals suffering from kidney disease, obesity, diabetes, metabolic syndrome, hyaline degeneration, hypertension, hypothyroidism, neuropathy, cardiovascular disease, and combinations thereof.

[0030] These methods generally include orally administering to the animal a composition comprising medium chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, antioxidants, and B vitamins. In one embodiment, the composition may further include other omega-3 fatty acids, antioxidants, amino acids, and mixtures thereof. In one aspect, the composition includes a preservative. In various aspects, the composition may be a pet food, such as a moist pet food, a semi-moist pet food, or a dry pet food, such as a kibble; or a supplement, or a treat.

[0031] Generally speaking, medium chain triglycerides can be about 0.1% to about 60% by weight of the composition. In one aspect, medium chain triglycerides can be about 1% to about 20% by weight of the composition. In other aspects, medium chain triglycerides can be about 1% to about 15% by weight, about 1% to about 10% by weight, about 1% to about 7% by weight, or about 2% to about 10% by weight of the composition. Medium chain triglycerides can be prepared by any known method, such as direct esterification, rearrangement, fractionation and / or transesterification. For example, medium chain triglycerides can be prepared by rearrangement methods with vegetable oils such as coconut oil as the source. The length and distribution of its chain can vary depending on the oil source. For example, such MCTs can include fatty acids with 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.

[0032] The non-limiting examples of suitable ω-3 fatty acids include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA) and mixtures thereof. In one embodiment, ω-3 fatty acids can be in the range of about 0.1% by weight to about 5% by weight of compositions. In some embodiments, ω-3 fatty acids are at least about 0.1% by weight, at least about 0.5% by weight, at least about 1.0% by weight or at least 2.0% by weight. In one embodiment, DHA can be present in compositions with an amount of about 0.1% to about 5%. In other aspects, DHA can be present with about 0.1% by weight, 0.5% by weight, 1% by weight, 1.5% by weight, 2% by weight, 2.5% by weight or 3% by weight to about 0.5% by weight, 1% by weight, 1.5% by weight, 2% by weight, 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight or 5% by weight. In another embodiment, EPA can be present in the composition in an amount of about 0.05% to about 15% by weight. In other aspects, EPA can be present in an amount of about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, or 3% to about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5% by weight.

[0033] 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), 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, 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 aspects, niacin can 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 can be present at about 1, 2, 3, 4, 5, 10, or 15 times to about 2, 3, 4, 5, 10, 15, 20, 30, or 50 times the RDA; pyridoxine can be present at about 1, 2, 3, 4, 5, 10, 15, 20, 30, or 50 times the RDA. Thiamine can 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; thiamine can be present at about 1, 2, 3, 4, 5, 10, 15, 20, or 40 times to about 2, 3, 4, 5, 10, 15, 20, 60, 100, or 200 times the RDA; riboflavin can be present at about 1, 2, 3, 4, 5, 10, 15, 20, 60, 100, or 200 times the RDA; From about 1, 2, 3, 4, 5, 10, 15, 20, or 30 times the RDA to about 2, 3, 4, 5, 10, 15, 20, 25, 50, 80, or 100 times the RDA; Biotin may be present at about 1, 2, 3, 4, 5, 10, 15, or 20 times to about 2, 3, 4, 5, 10, 15, 20, 25, or 40 times the RDA; Folic acid The RDA may be present at about 1, 2, 3, 4, 5, 10, 15 or 20 times to about 2, 3, 4, 5, 10, 15, 20, 25, 30 or 50 times the RDA; and / or the cobalamin may be present at about 1, 2, 3, 4, 5, 10, 15 or 20 times to about 2, 3, 4, 5, 10, 15, 20, 25, 30 or 50 times the RDA.The RDA level from the dosage can be converted to a specific amount of the composition by adding the RDA per kg of the composition.

[0034] Typically, the composition may also include antioxidants, including but not limited to vitamin C, vitamin E, carotenoids such as beta-carotene and lycopene, and phenolic compounds such as quercetin, catechins, resveratrol, coumaric acid, anthocyanins.

[0035] In one embodiment, said 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 that can increase arginine level in vivo. In one embodiment, arginine can be about 1% by weight to about 10% by weight of composition. In other aspects, arginine can be present with about 1% by weight, 2% by weight or 3% by weight to about 5% by weight, 8% by weight or 10% by weight of composition. In one embodiment, vitamin E can be about 1 times to about 50 times of RDA. In other aspects, vitamin E can be present with about 1 times, 2 times, 3 times, 4 times, 5 times or 10 times of the RDA of composition to about 2 times, 3 times, 4 times, 5 times, 10 times, 15 times, 20 times, 25 times, 30 times or 50 times. In one embodiment, vitamin C can be about 0.001% by weight to about 1% by weight of composition. In other aspects, vitamin C can be present at about 0.001%, 0.005%, or 0.01% to about 0.5%, 0.8%, or 1% by weight of the composition.

[0036] In some embodiments, the composition may be administered to an animal for a period of at least one week, at least one month, at least two months, three months, four months, five months, or six months; and in some embodiments, for at least one year. During this period, the composition may be administered to the animal at least one day a week, at least two days a week, at least three days a week, four days, five days, or six days a week; or even seven days a week. The composition may be administered daily in a single dose or daily in multiple separate doses. In one embodiment, MCT may be about 0.1% by weight to about 50% by weight of the composition. In other aspects, MCT may be present in 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 may be administered daily in an amount providing about 10mg MCT / kg of the body weight of the animal to 5g MCT / kg of the body weight of the animal. In one aspect, 10mg MCT / kg of the body weight of the animal may be administered daily to about 500mg MCT / kg of the body weight of the animal.

[0037] In one embodiment, the animal can be a companion animal. In one aspect, the companion animal can be a cat. In another aspect, the companion animal can be a dog. In one embodiment, the animal can be a geriatric animal or an elderly animal. In one aspect, the animal can be a geriatric cat or a geriatric dog. In another aspect, the animal can be an elderly cat or an elderly dog.

[0038] In one embodiment, the composition described herein may be a pet food composition. The pet food composition disclosed herein may be any food formulated for pets such as cats. In an embodiment, the pet food composition provides complete nutrition as defined by the Association of American Feed Control Officials (AAFCO) on January 1, 2023, and the complete nutrition depends on the type of animal (e.g., cat) for which the composition is intended. In another embodiment, the composition may be a supplement. This supplement may be added to a food composition, or applied in combination with a food composition, or applied alone. Therefore, in some embodiments, the present composition may be a complete and nutritionally balanced pet food.

[0039] Generally speaking, pet food compositions may include protein, carbohydrates, fat, and ash. In various embodiments, pet food compositions may include from about 15% to about 50% crude protein. In some embodiments, such compositions may also include from about 5% to about 40% fat. In other embodiments, the compositions may also include from about 15% to about 60% carbohydrates. In other embodiments, the compositions may also include from about 0.1% to about 15% ash.

[0040] Pet food compositions can include meat, such as emulsified meat. Examples of suitable meat include poultry, beef, pork, mutton and fish, particularly those types of meat suitable for pets. Meat can include any other part of the animal, including viscera. Some or all of the meat can be provided as one or more meat meals, i.e., dried and ground to form substantially uniform granules and as defined by AAFCO. Additionally or alternatively, vegetable proteins can be used, such as pea protein, corn protein (e.g., corn flour or corn gluten), wheat protein (e.g., wheat flour or wheat gluten), soy protein (e.g., soy flour, soy concentrate, or soy isolate), rice protein (e.g., rice flour or rice gluten), etc.

[0041] The pet food compositions disclosed herein may include one or more of vegetable oils, flavoring agents, coloring agents, or water. Non-limiting examples of suitable vegetable oils include soybean oil, corn oil, cottonseed oil, sunflower oil, canola oil, peanut oil, safflower oil, etc. In some embodiments, the lipids in the composition may be composed of one or more of MCT and any vegetable oil, any fish oil, any meat lipid, and any omega-3 fatty acids.

[0042] Non-limiting examples of suitable flavoring agents include yeast, beef tallow, rendered bone meal (e.g., poultry, beef, lamb, and pork), flavor extracts or blends (e.g., roast beef), animal digests, etc. Non-limiting examples of suitable coloring agents include FD&C colors such as Blue No. 1, Blue No. 2, Green No. 3, Red No. 3, Red No. 40, Yellow No. 5, Yellow No. 6, etc.; natural colors such as caramel color, annatto, chlorophyllin, cochineal, betanin, turmeric, saffron, paprika, lycopene, elderberry juice, pandan extract, butterfly pea flower color, etc.; titanium dioxide; and any suitable food coloring agent known to the skilled artisan.

[0043] The pet food compositions disclosed herein may optionally include additional ingredients such as starches, humectants, oral care ingredients, preservatives, other amino acids, other antioxidants, fibers, prebiotics, sugars, animal oils, flavoring agents, other oils in addition to or in place of vegetable oils, salts, vitamins, minerals, probiotic microorganisms, bioactive molecules, or combinations thereof.

[0044] The non-limiting example of suitable starch includes cereals, such as corn, rice, wheat, barley, oats, potatoes, peas, beans, cassava, etc., and mixtures of these cereals, and may be at least partially contained in any powder. The non-limiting example of suitable wetting agents includes salt, sugar, propylene glycol, and polyols (such as glycerol and sorbitol) etc. The non-limiting example of suitable oral care ingredients includes alfalfa nutrient concentrate containing chlorophyll, sodium bicarbonate, phosphates (such as tricalcium phosphate, acid pyrophosphate, tetrasodium pyrophosphate, metaphosphate and orthophosphate), peppermint, cloves, parsley, ginger, etc. The non-limiting example of suitable preservatives includes potassium sorbate, sorbic acid, sodium methyl parahydroxybenzoate, calcium propionate, propionic acid, and combinations thereof.

[0045] The specific amount of each additional ingredient in the pet food compositions disclosed herein will depend on a variety of factors, such as the ingredients contained in the first edible substance and any second edible substance; the species of the animal; the age, weight, general health, sex, and diet of the animal; the feeding rate of the animal; the purpose for which the food product is administered to the animal; etc. Thus, the components and their amounts can vary widely.

[0046] Yet another aspect of the present disclosure is a method of preparing a pet food, the method comprising adding medium chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, vitamin E, vitamin C, and B vitamins to at least one other edible ingredient, wherein the medium chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, vitamin E, vitamin C, and B vitamins are added in an amount 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 B vitamins can be added in a therapeutically effective amount so that administration of the pet food is effective in treating or preventing glomerular hyperfiltration, reducing glycogen storage, or reducing uremic toxins in an animal.

[0047] Example

[0048] By way of example and not limitation, the following non-limiting studies illustrate compositions and methods for using MCTs to treat glomerular hyperfiltration, reduce glycogen storage in tissues, or reduce uremic toxins in animals in one or more embodiments provided in the present disclosure.

[0049] Example 1 - CKD mouse study

[0050] This study used 8-week-old db / db mice for 8 weeks of intervention. Mice were divided into 4 groups, 9-10 in each group, and different blends were applied to each group (standard AIN-93M diet was applied to the control group, standard AIN-93M fortified with 10mg / kg of dapagliflozin was applied to the Dapa group, standard diet fortified with renal protection blend was applied to the RPB group, and standard diet fortified with renal protection blend containing medium-chain triglycerides was applied to the RPB+ group); the diet is shown in Table 1. In addition, standard AIN-93M diet was applied to the group of 9db / db control mice; the diet is also shown in Table 1. These blends were applied to study glomerular hyperfiltration and glycogen storage in tissues. The final weekly food intake, final body weight, final blood glucose level, final lean body weight and final fat mass of each group are presented in Table 2. Also presented in Table 2 are GFR progression, urine albumin / creatinine ratio, urine protein / creatinine ratio, glomerulosclerosis score, periodic acid Schiff (PAS) staining score of distal convoluted tubule (DCT) lumen, PAS staining score of distal tubule with intranuclear inclusions, and PAS staining score of distal tubule with cytoplasmic aggregates.

[0051] Table 1

[0052]

[0053]

[0054] Table 2

[0055]

[0056] In addition to the measurements in Table 2, hyaline degeneration in mice was measured on a scoring system of no hyaline degeneration, moderate hyaline degeneration, or severe hyaline degeneration, where hyaline degeneration refers to thickening of the wall of the glomerular arteriole due to deposition of homogenous hyaline material. The RPB+ group was the only group with mice that had no severe hyaline degeneration except for the db / m mice. The control group had 1 mouse with no hyaline degeneration, 4 mice with moderate hyaline degeneration, and 4 mice with significant hyaline degeneration; the dapa group had 2 mice with no hyaline degeneration, 5 mice with moderate hyaline degeneration, and 2 mice with significant hyaline degeneration, the RPB group had 5 mice with no hyaline degeneration, 4 mice with moderate hyaline degeneration, and 1 mouse with significant hyaline degeneration, and the RPB+ group had 2 mice with no hyaline degeneration and 8 mice with moderate hyaline degeneration.

[0057] The effects of RPB and RPB+ on food intake were evaluated during 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. Therefore, there was no significant difference in food intake between db / db mice treated with RPB and RPB+ and db / db mice treated with vehicle. The effects of RPB and RPB+ on body weight were evaluated during the treatment period. As shown in Table 2, the final body weight of db / db mice treated with RPB and RPB+ was not significantly different from the final body weight of db / db mice treated with vehicle. RPB and RPB+ showed no significant difference in blood glucose levels compared to db / db treated with vehicle. The db / db mice treated with RPB+ showed an increase in lean body mass compared to db / db mice treated with vehicle. The db / db mice treated with RPB and RPB+ showed normalization of GFR progression. The db / db mice treated with RPB and RPB+ showed an improvement in the urine albumin / creatinine ratio. db / db mice treated with RPB and RPB+ showed improvements in urine protein / creatinine ratios. Compared with vehicle-treated db / db mice, db / db mice treated with RPB+ showed significant improvements in glomerulosclerosis in kidney tissue. Compared with vehicle-treated db / db mice, db / db mice treated with RPB showed improvements in DCT lumen, and db / db mice treated with RPB+ showed significant improvements in DCT lumen in kidney tissue. Compared with vehicle-treated db / db mice, db / db mice treated with RPB+ showed improvements in PAS intranuclear inclusions distal tubules in kidney tissue. Compared with vehicle-treated db / db mice, db / db mice treated with RPB+ showed significant improvements in PAS cytoplasmic aggregates distal tubules in kidney tissue.

[0058] In addition, uremic toxins were measured in db / db mice of the control group (vehicle), RPB group, and RPB+ group. The results are shown in Table 3 as the median value of each group.

[0059] Table 3

[0060]

[0061] As shown in Table 3, the RPB composition and the RPB+ composition reduced the levels of uremic toxins, with RPB+ being the most effective. As discussed herein, the difference between the RPB diet and the RPB+ diet was due only to the inclusion of MCTs in RPB+. Therefore, the present data show that MCTs are particularly effective in reducing uremic toxins, which is surprising and unexpected.

[0062] Example 2 - CKD Cat Study

[0063] 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). The samples were stored at -80°C until use. Targeted analysis was performed at Colorado State University to determine the concentrations of four uremic toxins. Authentic standards p-cresol sulfate (pCS) were purchased from APExBio Technology, indoxyl sulfate (IS) and IS-D5 were purchased from Cayman Chemical, trimethylamine N-oxide (TMAO) was purchased from Sigma-Aldrich, TMAO-D9 was purchased from Santa Cruz Biotechnology, pCS-D7 was purchased from Cambridge Isotope, and phenyl sulfate (PS) was purchased 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% methanol in water.

[0064] Serum samples (40 μL) were mixed with 10 μL of internal standard and 200 μL of cold methanol. The mixture was vortexed for 5 seconds and then incubated overnight at -20°C, followed by centrifugation at 15000 g and 4°C for 15 min. The supernatant (100 μL) was recovered and then 900 μL of 50% methanol was added thereto, which was then stored at -20°C until analysis. Small aliquots of sample extracts were pooled from each sample to generate quality control (QC) samples.

[0065] Urine samples (20 μL) were mixed with 80 μL of cold methanol and then incubated at -20°C overnight, followed by centrifugation at 15000 g and 4°C for 15 min. The supernatant (10 μL) was recovered and then 10 μL of internal standard and 1 mL of 50% methanol were added, which were then stored at -20°C until analysis. Small aliquots of sample extracts were pooled from each sample to generate quality control (QC) samples.

[0066] UPLC-MS / MS was performed on a Waters Acquity UPLC coupled to a Waters Xevo TQ-S triple quadrupole mass spectrometer. Chromatographic separations were 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. The retention time and peak area integration of each target analyte were visually inspected. The peak areas of the target compounds detected in the biological samples were extracted and normalized to the peak area of ​​the appropriate internal standard or surrogate in each sample. The absolute quantification (ug / mL) was calculated using the linear regression equation for each compound generated by the calibration curve.

[0067] The results of the samples are provided in Tables 4 and 5. Table 4 shows the serum uremic toxin levels of 28 healthy control cats (CON) vs. 5 cats with stage 1 CKD (CKD1) vs. 11 cats with stage 2 CKD (CKD2). Table 5 shows the urine uremic toxicity levels of 27 healthy control cats (CON), 5 cats with stage 1 CKD (CKD1), and 11 cats with stage 2 CKD (CKD2) normalized by the urine creatinine concentration of each cat; data are shown as means.

[0068] Table 4

[0069]

[0070] Table 5

[0071]

[0072] As shown in Tables 4 and 5, uremic toxins increase in the circulation and in the urine in proportion to the severity of CKD in cats. Excessive uremic toxins are known to lead to chronic inflammation, excessive free radical production, insulin resistance, apoptosis, and impaired intestinal barrier, which can lead to further kidney disease. Therefore, cats with CKD will benefit from the RPB compositions and RPB+ compositions disclosed herein.

[0073] It should be understood that various changes and modifications made to the presently preferred embodiments described herein will be apparent to those skilled in the art. These changes and modifications may be made without departing from the spirit and scope of the subject matter of the present invention and without diminishing its intended advantages. Therefore, such changes and modifications are intended to 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, the method comprising orally administering to the animal a composition comprising medium chain triglycerides, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arginine, an antioxidant, and B vitamins.

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

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

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

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

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

7. 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, the vitamin E is from about 1 to about 50 times the RDA, the vitamin C is from about 0.001% to 1% by weight of the composition, and the B vitamins are from about 1 to 100 times the RDA.

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

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

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

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

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

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

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

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

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