Patent Description:
The present disclosure relates generally to methods and compositions containing medium-chain triglycerides to increase ketone bodies in an animal.

Medium-chain triglycerides ("MCT" or "MCTs") are lipid molecules that have been included for various purposes in food compositions for animals or humans. MCTs have been added to "wet" foods such as canned food and other prepared food and have been used to some extent in, or as coatings on, dry food. However, practical considerations appear to limit the amount of MCTs that can be used, particularly for dry foods. For example, while wet food compositions may incorporate a significant amount of MCTs, they may be subject to separation, flavor issues, and other problems. For dry foods, such as extruded and baked products, the compositions are strictly subject to limits wherein the MCTs cannot be increased above a certain threshold in many products. MCTs have thus been used as a coating or surface application for such foods. Surface application, such as coating, poses practical problems for packaging and reduces consumer appeal. For example, consumption or administration of such food compositions is far more cumbersome if a coating must be poured on or mixed in at the time of consumption or if the dry food has an oily appearance or feel. In addition, large quantities of MCTs not integrally incorporated into the food matrix can cause problems with palatability and tolerance of such food compositions.

Chemically, medium-chain triglycerides comprise a group of triglycerides having three medium-chain length (<NUM>-<NUM> carbon) fatty acid molecules esterified to a glycerol molecule. Such compositions are different, both physically and chemically, from the majority of fats typically used in food technology for formulating food products. MCTs tend to be shorter and have different functional properties for processing than their longer-chain counterparts. For example, MCTs are typically liquid at room temperature, unlike many other functional fats used by food technologists.

Even considering the above challenges, MCT containing compositions continue to be desired based on claimed associated health benefits of MCTs including: alternate energy source for the brain, associated cognition benefits, accelerated metabolic conversion, weight loss, enhanced exercise performance, enhanced endurance, muscle strength, activity, etc..

Therefore, research and development regarding MCTs continue to be sought.

<CIT> relates to a food composition having high protein levels, high fat levels, low carbohydrate levels and non-fermentable fiber, and methods of using these compositions for weight management in mammals. <NPL>) describes the safety of MCT when fed to beagles for <NUM> days at levels of <NUM>%, <NUM>%, <NUM>% and <NUM>% MCT added to conventional feed. <CIT> relates to a method of treating degenerative mitral valve disease (DMVD) in a companion animal having DMVD, the method including orally administering to the companion animal a composition containing medium triglycerides and one or more of omega-<NUM> fatty acids, vitamin E, lysine, taurine, magnesium or sulfur-containing amino-acids. <CIT> relates to a method for treating epilepsy in a companion animal comprising administering to the companion animal a food composition comprising a MCT. <CIT> utilizes MCTs to preserve or improve learning, attention, motor performance, cerebrovascular function, social behavior, and to increase activity levels, particularly in aging mammals. <CIT> describes compositions comprising MCTs for the treatment or prevention of conditions associated with brain energy deficiency condition or disease and neurological conditions. <CIT> relates to a method for preserving lean body mass and promoting fat loss during weight loss, comprising identifying an animal that is obese or overweight and administering to the animal a food composition in an amount less than the animal's baseline maintenance energy requirement (MER), the food composition comprising from <NUM>% to <NUM>% protein, from <NUM> to <NUM>% carbohydrate, and from <NUM>% to <NUM>% fat. <NPL>) describes the effects of dietary carbohydrate, fat and protein on growth, body composition and blood metabolite levels in dogs. <NPL>) describes the effects of the dietary protein and carbohydrate ratio on gut microbiomes in dogs of different body conditions.

The present disclosure relates to compositions comprising medium-chain triglycerides and methods comprising administering the compositions to an animal. More specifically, the present disclosure relates to compositions and methods for increasing ketone bodies in an animal.

Accordingly, a method of increasing ketone bodies in an animal, the method comprising orally administering a composition to the animal, wherein the composition comprises medium-chain triglycerides in an amount of <NUM>% to <NUM>%, protein in amount of <NUM>% to <NUM>%, fat in an amount of <NUM>% to <NUM>%, and carbohydrates in an amount of <NUM>% to <NUM>%, wherein the composition has a protein to carbohydrate ratio of at least <NUM>:<NUM>; wherein the animal is a canine; wherein the medium-chain triglycerides contain at least <NUM>% caprylic acid of the total medium chain fatty acids that are present; and wherein all percentages are by weight of the total weight of the composition on a dry matter basis unless expressed otherwise.

Further, in one embodiment, a pet food composition for increasing ketone bodies in a canine, comprising medium-chain triglycerides in an amount of <NUM>% to <NUM>%, protein in amount of <NUM>% to <NUM>%, fat in an amount of <NUM>% to <NUM>%, and carbohydrates in an amount of <NUM>% to <NUM>%, wherein the composition has a protein to carbohydrate ratio of at least <NUM>:<NUM>; wherein the medium-chain triglycerides contain at least <NUM>% caprylic acid of the total medium chain fatty acids that are present; and wherein all percentages are by weight of the total composition on a dry matter basis unless expressed otherwise.

Additional features and advantages are described herein and will be apparent from, the following Detailed Description and the Figures.

Some definitions are provided hereafter. Nevertheless, definitions may be located in the "Embodiments" section below, and the above header "Definitions" does not mean that such disclosures in the "Embodiments" section are not definitions.

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. " Where used herein, the term "example," particularly when followed by a listing of terms, is merely exemplary and illustrative, and should not be deemed to be exclusive or comprehensive.

All percentages expressed herein are by weight of the total weight of the composition unless expressed otherwise. All percentages for food compositions are by dry matter basis unless expressed otherwise. All ratios expressed herein are by weight unless expressed otherwise. When reference is made to the pH, values correspond to pH measured at <NUM> with standard equipment.

The terms "food," "food product" and "food composition" mean a product or composition that is intended for ingestion by an animal, including a human, and provides at least one nutrient to the animal. Further in this regard, these terms mean that the product or composition is in a form ready for consumption and is not merely an intermediate from which a consumable product or composition is made, although other food compositions can be added in some embodiments. The term "pet food" means any food composition intended to be consumed by a pet. The term "pet" means any animal that could benefit from or enjoy the compositions provided by the present disclosure. For example, the pet can be an avian, bovine, canine, equine, feline, hircine, lupine, murine, ovine, or porcine animal, but the pet can be any suitable animal. In the present invention, the pet is a canine.

The term "animal" refers to any animal including mammals such as humans and companion animals. In one embodiment, the term animal can refer to humans and companion animals. The term "companion animal" means a dog or a cat. As used herein, the term "dog" and "canine" can be used interchangeably. As used herein, the term "cat" and "feline" can be used interchangeably. In present invention, the companion animal is a canine.

"Wet food" means a pet food having a moisture content from <NUM>% to <NUM>%, and in one aspect, from <NUM>% to <NUM>%. "Dry food" means a pet food having a moisture content less than <NUM>%, and in one aspect, less than <NUM>%, and in a specific aspect, less than <NUM>%. "Semi-moist food" means a pet food having a moisture content from <NUM>% to <NUM>%, and in one aspect, from <NUM>% to <NUM>%. "Kibbles" means pieces of dry or semi-moist pet food which can have a pellet shape or any other shape. Non-limiting examples of kibbles include particulates; pellets; pieces of pet food, dehydrated meat, meat analog, vegetables, and combinations thereof; and pet snacks, such as meat or vegetable jerky, rawhide, and biscuits.

The compositions disclosed herein may lack any element that is not specifically disclosed herein. Thus, a disclosure of an embodiment using the term "comprising" includes a disclosure of embodiments "consisting essentially of" and "consisting of" the components identified. Similarly, the methods disclosed herein may lack any step that is not specifically disclosed herein. Thus, a disclosure of an embodiment using the term "comprising" includes a disclosure of embodiments "consisting essentially of" and "consisting of" the steps identified. Moreover, the description of some steps as "optional" does not imply that the other steps which are not explicitly described as optional are necessarily required.

Any embodiment disclosed herein can be combined with any other embodiment disclosed herein.

The relative terms "improved," "increased," "enhanced" and the like refer to the effects of the composition disclosed herein (a composition comprising an amount of medium-chain triglycerides, protein, and carbohydrates) relative to a composition having lower amounts of medium-chain triglycerides, protein, and/or carbohydrates, or lacking medium-chain triglycerides, protein, and/or carbohydrates, but otherwise identical.

A "medium-chain triglyceride" or "MCT" or "MCTs" is a lipid in which three fatty acids are bound by ester linkages to a glycerol backbone, and at least two and preferably all three of the 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:<NUM> or C6), caprylic acid (comprising eight carbon atoms or C8:<NUM> or C8), capric acid (comprising ten carbon atoms or C10:<NUM> or C10) and lauric acid (comprising twelve carbon atoms or C12:<NUM> or C12). In one embodiment, the medium-chain fatty acids are mainly (e.g., at least <NUM>%) in the form of triglycerides. In another embodiment, the medium-chain fatty acids of the MCTs is a mixture of caprylic acid and capric acid, where such medium-chain fatty acids comprise <NUM>% to <NUM>% of the total medium-chain fatty acids present in the MCTs. Such an embodiment refers to the total amount of medium-chain fatty acids that are bound to the glycerol backbones in the MCTs as a percent of all medium-chain fatty acids bound to the glycerol backbones in the MCTs. In the present invention, the medium chain fatty acids of the medium chain triglycerides includes at least <NUM>% caprylic acid of the total medium chain fatty acids that are present. In another embodiment, the medium chain fatty acids of the medium chain triglycerides can include at least <NUM>% caprylic acid of the total medium chain fatty acids that are present.

The term "maintenance energy requirement" or "MER" or "baseline maintenance energy requirement" means the minimum amount of a food composition that is needed to sustain the weight of an animal. In one embodiment, the MER can be determined over a period of <NUM> to <NUM> weeks using feeding trial; or indirect or direct calorimetry. Non-calorimetric methods can also be used.

One embodiment of the present disclosure is a method of increasing ketone bodies in an animal comprising orally administering a composition to the animal, wherein the composition comprises medium-chain triglycerides in an amount of <NUM>% to <NUM>%, protein in amount of <NUM>% to <NUM>%, fat in an amount of <NUM>% to <NUM>%, and carbohydrates in an amount of <NUM>% to <NUM>%. The composition has a protein to carbohydrate ratio of at least <NUM>:<NUM>. The animal is a canine, the medium chain triglycerides contain at least <NUM>% caprylic acid of the total medium chain fatty acids that are present, and all percentages are by weight of the total weight of the composition on a dry matter basis unless expressed otherwise.

Generally, the administration of the compositions described herein can provide an increase in ketone bodies in the animal. Such an increase in ketone bodies can determined by measuring postprandial beta-hydroxybutyrate (BHB) levels in the animal. The BHB can be measured at <NUM> hours postprandial, <NUM> hours postprandial, <NUM> hours postprandial, or even <NUM> hours postprandial. Additionally, an increase in ketone bodies can be determined by postprandial measuring acetoacetate or acetone in the blood of the animal including at the times discussed above.

The medium-chain triglycerides are present in an amount of <NUM>% to <NUM>% of the composition. In one aspect, the medium-chain triglycerides can be from <NUM>% to <NUM>% of the composition. In other aspects, the medium-chain triglycerides can be from <NUM>% to <NUM>%, from <NUM>% to <NUM>%, or from <NUM>% to <NUM>% of the composition. The medium-chain triglycerides may be prepared by any known process, such as direct esterification, rearrangement, fractionation and/or transesterification. For example, the medium-chain triglycerides may be prepared from a source of vegetable oil, such as coconut oil, through a rearrangement process. The chain length and distribution thereof may vary depending on the source oil. In some embodiments, at least a portion of the MCTs can be provided by coconut oil, but in other embodiments the composition does not contain coconut oil. MCTs containing at least <NUM>% C8 can be made by semi-synthetic esterification of octanoic acid to glycerin; in some embodiments thereof, the remainder of the fatty acids can be C6 and C10. Mixtures comprising MCTs with <NUM>% total C8 and/or <NUM>% total C10 can also be used herein. In one embodiment, the medium-chain fatty acids of the MCTs can be a mixture of caprylic acid, and capric acid, where such medium-chain fatty acids comprise <NUM>% to <NUM>% of the total medium-chain fatty acids present in the MCTs. In one embodiment, the MCTs can include those having at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, or even <NUM>%, caprylic acid.

Generally, the composition can be administered on a regular basis to the animal. In one aspect, the regular basis can be at least weekly, or in one specific aspect, at least daily. In one embodiment, the composition can be administered on a long-term basis to the animal. In one aspect, the long-term basis can be at least for <NUM> months, and in one specific aspect, for at least <NUM> year. In some embodiments, the composition can be administered to the animal for a time period of at least one week, at least one month, at least two, three, four, five or six months; and in some embodiments, for at least one year. During the time 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 per day or in multiple separate doses per day. In an embodiment, the composition can be administered in an amount that provides <NUM> to <NUM> of the MCTs per kg body weight of the animal per day. In one aspect, <NUM> to <NUM> of the MCTs per kg body weight of the animal can be administered per day.

As noted herein, the present disclosure provides a pet food composition for increasing ketone bodies in a canine, comprising medium-chain triglycerides in an amount of <NUM>% to <NUM>%, protein in amount of <NUM>% to <NUM>%, fat in an amount of <NUM>% to <NUM>%, and carbohydrates in an amount of <NUM>% to <NUM>%. The composition has a protein to carbohydrate ratio of at least <NUM>:<NUM>. The medium chain triglycerides contain at least <NUM>% caprylic acid of the total medium chain fatty acids that are present. All percentages are by weight of the total weight of the composition on a dry matter basis unless expressed otherwise. In one aspect, the protein to carbohydrate ratio can range from <NUM>:<NUM> to <NUM>:<NUM>. In other aspects, the ratio can range from <NUM>:<NUM> to <NUM>:<NUM>, <NUM>:<NUM> to <NUM>:<NUM>, <NUM>:<NUM> to <NUM>:<NUM>, or even <NUM>:<NUM> to <NUM>:<NUM>.

In one aspect, the composition can be a complete and nutritionally balanced pet food.

Additionally, the present compositions can include omeg-<NUM> fatty acids. Non-limiting examples of suitable omega-<NUM> fatty acids include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA) and mixtures thereof. In one embodiment, the omega-<NUM> fatty acids can range from <NUM>% to <NUM>% of the composition. In some embodiments, the omega-<NUM> fatty acids are at least <NUM>%, at least <NUM>%, or at least <NUM>%.

Regarding the pet food compositions disclosed herein, such compositions can be any food formulated for consumption by a dog. In an embodiment, the pet food composition provides complete nutrition as defined by the Association of American Feed Control Officials (AAFCO).

The pet food composition can comprise meat, such as emulsified meat. Examples of suitable meat include poultry, beef, pork, lamb and fish, especially those types of meats suitable for pets. The meat can include any additional parts of an animal including offal. Some or all of the meat can be provided as one or more meat meals, namely meat that has been dried and ground to form substantially uniform-sized particles and as defined by AAFCO. Additionally or alternatively, vegetable protein can be used, 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), rice protein (e.g., ground rice or rice gluten) and the like.

The pet food compositions disclosed herein can comprise one or more of a vegetable oil, a flavorant, a colorant or water. Non-limiting examples of suitable vegetable oils include soybean oil, corn oil, cottonseed oil, sunflower oil, canola oil, peanut oil, safflower oil and the like. In some embodiments, the lipids in the composition can consist of the MCTs and one or more of any vegetable oil, any fish oil, the lipid from any meat, and any omega-<NUM> fatty acids.

Non-limiting examples of suitable flavorants include yeast, tallow, rendered animal meals (e.g., poultry, beef, lamb, pork), flavor extracts or blends (e.g., grilled beef), animal digests, and the like. Non-limiting examples of suitable colorants include FD&C colors, such as blue no. <NUM>, blue no. <NUM>, green no. <NUM>, red no. <NUM>, red no. <NUM>, yellow no. <NUM>, yellow no. <NUM>, and the like; natural colors, such as caramel coloring, annatto, chlorophyllin, cochineal, betanin, turmeric, saffron, paprika, lycopene, elderberry juice, pandan, butterfly pea and the like; titanium dioxide; and any suitable food colorant known to the skilled artisan.

The pet food compositions disclosed herein can optionally include additional ingredients, such as starches, humectants, oral care ingredients, preservatives, amino acids, fibers, prebiotics, sugars, animal oils, aromas, other oils additionally or alternatively to vegetable oil, salts, vitamins, minerals, probiotic microorganisms, bioactive molecules or combinations thereof.

Non-limiting examples of suitable starches include a grain such as corn, rice, wheat, barley, oats, potatoes, peas, beans, cassava, and the like, and mixtures of these grains, and can be included at least partially in any flour. Non-limiting examples of suitable humectants include salt, sugars, propylene glycol and polyhydric glycols such as glycerin and sorbitol, and the like. Non-limiting examples of suitable oral care ingredients include alfalfa nutrient concentrate containing chlorophyll, sodium bicarbonate, phosphates (e.g., tricalcium phosphate, acid pyrophosphates, tetrasodium pyrophosphate, metaphosphates, and orthophosphates), peppermint, cloves, parsley, ginger and the like. Non-limiting examples of suitable preservatives include potassium sorbate, sorbic acid, sodium methyl para-hydroxybenzoate, calcium propionate, propionic acid, and combinations thereof.

Specific amounts for each additional ingredient in the pet food compositions disclosed herein will depend on a variety of factors such as the ingredient included in the first edible material and any second edible material; the animal's age, body weight, general health, sex, and diet; the animal's consumption rate; the purpose for which the food product is administered to the animal; and the like. Therefore, the components and their amounts may vary widely.

Yet another aspect of the present disclosure is a method of making a pet food, the method comprising adding MCTs to other comestible ingredients, including an ingredient(s) that include protein, carbohydrates, and/or fat, such that the composition can increase ketone bodies in the animal. For example, the MCTs can be added with food ingredients such that a single serving of the food can increase postprandial measured ketone bodies (e.g. BHB), in the blood of the animal.

By way of example and not limitation, the following non-limiting study is illustrative of compositions and methods for increasing ketone bodies in an animal, in one or more embodiments provided by the present disclosure.

A total of <NUM> Beagle dogs (mean age: <NUM> years, ranges from <NUM> to <NUM> years, <NUM> males and <NUM> females) with body condition scores (BCS) between <NUM> to <NUM> were recruited in this cross-over study. Each dog's maintenance energy requirement (MER) was determined by its current food intake that sustains its body weight. The dogs were randomized into two groups with <NUM> dogs per group based on their MER (MER = feed amount per day), BCS, gender, and age. The diets are listed in Tables <NUM> and <NUM>.

All dogs were fed <NUM>% of their maintenance energy requirement during the study. First, dogs in Group <NUM> were fed the Control MCT (Medium-chain triglyceride diet) diet containing <NUM>% protein, <NUM>% carbohydrate, and <NUM>% fat including <NUM>% MCTs, and dogs in Group <NUM> were fed the Test MCT diet (<NUM>% protein, <NUM>% carbohydrate, and <NUM> % fat including <NUM>% MCTs ) for <NUM> days. Then the dogs in Group <NUM> were switched to Test MCT diet for <NUM> days, and dogs in Group <NUM> were switched to the Control MCT diet for <NUM> days. The Test MCT diet was higher in protein (<NUM>% of the dietary energy), and low in carbohydrates, and contains only about <NUM>% of dietary energy as fat. Therefore, the test MCT diet is not a typical ketogenic diet as discussed further below.

The dogs were fed in the morning and <NUM> of blood was collected at <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> hours after feeding at the end of the each cross-over phases. Serum Separator tube (SST) or Red Top blood collection tubes were used. Serum samples (two tubes with <NUM> per tube per dog per collection ) were used for beta-hydroxybutyrate (BHB) assay.

The results showed that both diets had similar baseline ketone bodies measured as BHB (<NUM> vs <NUM>/dL), but the Test MCT diet resulted in significantly higher average postprandial BHB during the <NUM> hours after the meal (<NUM> vs <NUM>/dL) compared with the dogs fed the control MCT diet. At the end of the <NUM> hour sample collection, the dogs fed the Test MCT had more than <NUM> times of BHB compared with the dogs fed the Control MCT diet (<NUM> vs <NUM>/dL) as shown in Table <NUM>.

Notably, the MCT diet provided higher ketone body levels at each interval of <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> hours postprandial even though the dogs fed the control diet initially had a higher ketone body level before administration. Since both diets had identical inclusion rate of MCTs, the markedly increased ketone bodies cannot be solely attributed to the MCT content but to the entire diet including protein and carbohydrate amounts. Notably, the present test diet differs significantly from traditional ketogenic diets, MCT-containing ketogenic diets, and other modified ketogenic diets as shown in Tables <NUM> and <NUM>. These known ketogenic diets have dietary fat as the most predominant component, followed by dietary protein, and lastly carbohydrate. On the contrary, the present inventive compositions have protein as the most predominant component, followed by carbohydrate and lastly dietary fat (Table <NUM>). As such, in one embodiment, the present compositions can have an amount of protein that is greater than the amount of carbohydrate, where the amount of carbohydrate is greater than the amount of fat.

A traditional ketogenic diet (KD) usually contain a ratios of <NUM> or <NUM> parts of fat to <NUM> part of protein and carbohydrate (Bough and Rho, <NUM>; Dhamija et al. However, those ketogenic diets, which consists of up to <NUM>% fat, <NUM>% carbohydrate and <NUM>% protein, are not balanced diets with some side effects including constipation, vomiting, lack of energy, and hunger (Neal et al. , <NUM>; Dhamija et al. Three modified ketogenic diets were developed. A MCT ketogenic diet containing MCTs at <NUM>-<NUM>% of the dietary energy along with <NUM>%-<NUM>% carbohydrate, <NUM>% protein and <NUM>-<NUM>% LCT (Neal et al. , <NUM>; Dhamija et al. A modified Atkins Ketone Diet consists of <NUM>% fat, <NUM>% carbohydrate, and <NUM>% protein. Low glycemic index diet consists of <NUM>% fat, <NUM>% carbohydrate and <NUM>% protein (Dhamija et al.

The present compositions differ substantially from these known diets with the surprising effect of increasing ketone bodies markedly in the animal without using increased ketone-producing ingredients (e.g. MCTs) and/or limiting dietary protein.

Thirty dogs were used in this study. Fifteen dogs were fed <NUM>% MERs with a diet containing <NUM>% MCT with <NUM>% C8 and <NUM>% C10 (C8C10 MCT group) for two weeks, while <NUM> dogs were fed <NUM>% MERs with a diet containing <NUM>% C10 MCTs (C10 MCT group) for two weeks. Blood beta-hydroxybutyrate (BHB) levels are provided in Table <NUM>.

Claim 1:
A method of increasing ketone bodies in an animal, the method comprising orally administering
a composition to the animal, wherein the composition comprises,
medium-chain triglycerides in an amount of <NUM>% to <NUM>%,
protein in amount of <NUM>% to <NUM>%,
fat in an amount of <NUM>% to <NUM>%, and
carbohydrates in an amount of <NUM>% to <NUM>%;
wherein the composition has a protein to carbohydrate ratio of at least <NUM>:<NUM>,
wherein the animal is a canine,
wherein the medium chain triglycerides contain at least <NUM>% caprylic acid of the total medium chain fatty acids that are present; and
wherein all percentages are by weight of the total weight of the composition on a dry matter basis unless expressed otherwise.