BR112017010381B1 - USE OF MEDIUM CHAIN TRIGLYCERIDES FOR THE PREPARATION OF A FOOD COMPOSITION TO ENHANCE THE EFFECT OF AN ANTIEPILEPTIC DRUG IN THE TREATMENT OF EPILEPSY IN AN ANIMAL - Google Patents

Abstract

COMPOSITIONS AND METHODS INCLUDING MEDIUM CHAIN TRIGLYCERIDES FOR THE TREATMENT OF EPILEPSY. The present invention provides compositions and methods for treating epilepsy in an animal. In one embodiment, a dietary regimen suitable for enhancing the effect of an antiepileptic drug (AED) in an animal can comprise a food composition comprising a medium-chain triglyceride (MCT) and the antiepileptic drug, wherein the medium-chain triglyceride is present in the food composition in an amount effective to enhance the effect of the antiepileptic drug when the food composition and antiepileptic drug are administered to the animal.

Description

REFERENCE TO RELATED DEPOSIT REQUESTS

[001] This application claims priority over provisional application serial number US 62/088,797, filed on December 8, 2014, the content of which is incorporated herein by way of reference, in its entirety.

BACKGROUND OF THE INVENTION field of invention

[002] The invention relates, in general, to compositions and methods for treating epilepsy in an animal. Particularly, the present invention relates to compositions and methods using medium chain triglycerides for the treatment of epilepsy. More particularly, the present invention relates to compositions and methods comprising medium chain triglycerides for enhancing the effect of antiepileptic drugs in animals.

Description of related technique

[003] Epilepsy is the most common chronic neurological disorder in both humans and dogs with an estimated prevalence in dogs of 1 to 2% in a hospital referral population and 0.6% in first opinion practice. A higher prevalence of up to 18% has been reported in species-specific studies, with up to 33% being observed in certain families. Furthermore, epilepsy has been associated with a higher risk of premature and unexpected death, injuries, cognitive deterioration, neurobehavioral dysfunction and reduced quality of life. Despite ongoing research into understanding the pathophysiological manifestation of seizures and epilepsy, cellular mechanisms remain elusive. As a result, approaches to epileptic therapy are often directed toward seizure control, most commonly the chronic administration of antiepileptic drugs (AEDs) rather than the prevention of epileptogenesis or comorbidities. Some of the antiepileptic drugs routinely used in canine epilepsy include phenobarbital (PB), potassium bromide (KBr), imepitoin, benzodiazepines, gabapentin, and levetiracetam. Despite treatment with the appropriate antiepileptic drug, approximately one-third of dogs and humans with idiopathic epilepsy continue to experience difficulty controlling seizures. In addition, side effects related to antiepileptic drugs, such as ataxia, polyphagia, polyuria, polydipsia and incontinence, also contribute to the reduction of quality of life.

[004] A plethora of anecdotal reports and published literature have suggested the importance of dietary manipulation in seizure control. In particular, the ketogenic diet (KD) has been proposed as an alternative treatment strategy for canine epilepsy. The classic ketogenic diet consisting of high fat, low protein, and low carbohydrate, typically with ratios of up to 4:1 fat to protein to carbohydrate, was first introduced in the 1920s for use in human childhood epilepsy. The use of a ketogenic diet was initially suggested to mimic the metabolic state and biochemical changes associated with fasting, as fasting has been shown to have anticonvulsant properties. A randomized controlled trial in childhood epilepsy showed promising results with 38% and 9% of children on a ketogenic diet compared to a control diet, with a seizure reduction greater than 50% and 90%, respectively. Current practice in human medicine to use the "classic" ketogenic diet as a prescription therapy is based on structuring the ratio of macronutrients whereby the fat content to protein and carbohydrates in combination is 4 :1. The traditional ketogenic diet was developed to manage drug-resistant (refractory) epilepsy and typically contains a 4:1 ratio of fat to protein plus carbohydrates by weight (Kossoff and Rho, Ketogenic Diets: Evidence for Short and Long- term efficacy Neurotherapeutics 6:406-414, 2009). Furthermore, a ketogenic diet with 60% of calories from medium-chain triglycerides has shown antiepileptic benefits (Huttenlocher et al. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology 21:1097-1103, 1971). However, such diets were problematic due to the palatability or restrictiveness of certain foods.

[005] Despite the progress made, there is still a need to develop compositions and methods that can treat epilepsy in humans and other animals. Such therapies would be helpful in improving the overall quality of life for everyone involved. For companion animals, these therapies would lead to greater owner satisfaction, and improve the bond between owner and companion animal.

SUMMARY OF THE INVENTION

[006] It is, therefore, an object of the present invention to provide useful compositions and methods for the treatment of epilepsy in an animal based on the surprising observation that a well-balanced diet, rich in proteins and carbohydrates, and a relatively low percentage, by For example, 11% calories of medium chain triglycerides (MCTs) are able to improve the therapeutic efficacy of an existing antiepileptic drug (AED) in dogs compared to control diets with similar macronutrient ratios, with the exception that all Dietary fats come from long-chain triglycerides.

[007] In one embodiment, a dietary regimen suitable for enhancing the effect of an antiepileptic drug in an animal may encompass a food composition comprising a medium-chain triglyceride and the antiepileptic drug. Generally, the medium chain triglyceride is present in the food composition in an amount effective to enhance the effect of the antiepileptic drug when the food composition and the antiepileptic drug are administered to the animal.

[008] In another embodiment, a method of enhancing the effect of an antiepileptic drug (AED) in an animal comprises administering a food composition comprising a medium-chain triglyceride (MCT) together with an antiepileptic drug (AED) to the animal, wherein the medium chain triglyceride is administered in an amount effective to enhance the effect of the antiepileptic drug in the animal.

[009] In yet another embodiment, a pharmaceutical composition for enhancing the effect of an antiepileptic drug (AED) in an animal may comprise a medium chain triglyceride (MCT) and the antiepileptic drug. As noted earlier, medium chain triglyceride is generally present in an amount effective to enhance the effect of the antiepileptic drug when the pharmaceutical composition is administered to the animal.

[0010] Other objects, features and additional advantages of the present invention will be readily apparent to those skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION Definitions

[0011] The following abbreviations may be used in the present invention: MCT(s), medium chain triglyceride(s); AA, arachidonic acid; AED, antiepileptic drug; ALA, alpha-linolenic acid; ANOVA, analysis of variance DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; LCPUFA, long-chain polyunsaturated fatty acids (as used herein, LCPUFA refers to one or more such fatty acids); NO, nitric oxide; NORC, nitric oxide-releasing compound or compounds; and L-Arg, L-arginine.

[0012] The term "animal" means any animal that could benefit from one or more of the methods of the present invention, including the treatment of epilepsy. Generally, the animal is a human, avian, bovine, canine, equine, feline, hyrcine, lupine, murine, ovine, and porcine. A "pet" is a domestic animal and includes, but is not limited to, cats, dogs, rabbits, guinea pigs, ferrets, hamsters, mice, gerbils, horses, cows, goats, sheep/sheep, donkeys , pigs and the like. In various embodiments, the animal can be a human being or a pet such as a dog or cat.

[0013] The term "enhancing the effect of an antiepileptic drug (AED)" means one or more of increasing the potency or effectiveness of the antiepileptic drug in an animal or preventing, reducing or delaying epileptic seizures, seizure severity and /or the number of seizures within a seizure set in an animal and/or reducing the effective dose or dosing frequency of the antiepileptic drug for an animal. The term "medium chain triglyceride" or "MCT" means any glycerol molecule linked to three fatty acid molecules, with each fatty acid molecule having 5 to 12 carbon atoms. Medium chain triglycerides can be represented by the following general formula (Formula 1): in which R', R" and R'" are fatty acids having from 5 to 12 carbon atoms in the carbon backbone esterified to a glycerol backbone. The medium chain triglycerides of the invention can be prepared by any process known in the art, such as direct esterification, rearrangement, fractionation, transesterification or the like. For example, medium chain triglycerides can be prepared by rearranging a vegetable oil such as coconut oil. The length and chain length distribution may vary depending on the source oil. For example, MCTs containing 1 to 10% C6, 30 to 60% C8, 30 to 60% C10, 1 to 10% C12 are commonly derived from coconut or palm oils. Medium chain triglycerides containing greater than about 95% C8 in R', R" and R'" can be produced by semi-synthetic esterification of octanoic acid to glycerin. Also useful are mixtures comprising medium chain triglycerides with about 50% total C8 and/or about 50% total C10. Commercial sources for the aforementioned MCT compositions are available and known to the person skilled in the art. Such MCTs behave similarly and are encompassed within the term "MCTs" as used herein.

[0014] The term "long-chain polyunsaturated fatty acids" or "LCPUFA" means any one or more monocarboxylic acids having at least 20 carbon atoms and at least two double bonds. Examples of LCPUFA include (n-6) fatty acids such as arachidonic acid (AA) and (n-3) fatty acids such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). ).

[0015] The term "fish oil" means a fatty or oily extract, relatively rich in LCPUFA, crude or purified, obtained from a sea animal, for example, a cold-water fish such as, but not limited to, salmon, tuna, mackerel, herring, sea bass, striped sea bass, sole, catfish and sardines, as well as shark, shrimp and clams or any combination thereof. Fish oil is generally a technical term used by ingredient suppliers and encompasses a range or products of varying PUFA content and purity.

[0016] The term "nitric oxide releasing compounds" or "NORC" means any compound or compounds that cause or may result in the release of nitric oxide in an animal. Examples of such compounds include L-arginine, peptides and proteins containing L-arginine and analogues or derivatives thereof, which are known to or determined to release nitric oxide, such as arginine alpha-ketoglutarate, GEA 3175, sodium nitroprusside, glyceryl trinitrate , S-nitroso-N-acetyl-penicillamine, nitroglycerin, S-NO-glutathione, NO-conjugated nonsteroidal anti-inflammatory drugs (e.g., NO-naproxen, NO-aspirin, NO-ibuprofen, NO-diclofenac, NO- flurbiprofen and NO-ketoprofen), NO-releasing compound 7, NO-releasing compound 5, NO-releasing compound 12, NO-releasing compound 18, diazene diolates and derivatives thereof, diethylamine NONOate and any organic or inorganic compound, biomolecule or analogue, homologue, conjugate or derivative thereof, which causes the release of nitric oxide, particularly "free" NO, in an animal.

[0017] The term "effective amount" means an amount of a compound of the present invention that (i) treats or prevents a specific disease, condition or disorder, (ii) alleviates, improves or eliminates one or more symptoms of the disease , condition or disorder, or (iii) prevents or delays the onset of one or more symptoms of the specific disease, condition or disorder described herein. In one embodiment, the particular disease, condition or disorder can be epilepsy.

[0018] Dosages expressed herein are in milligrams per kilogram of body weight per day (mg/Kg/day), unless otherwise stated.

[0019] The term "aging" means being of advanced age, such that the animal has already exceeded 50% of the average life expectancy for its specific species and/or breed within a species. For example, if the average life expectancy for a particular breed of dog is 10 years, then a dog of that breed over 5 years old would be considered "aging" for purposes of the present invention. "Healthy animals in the aging process" are those that do not have known diseases, particularly epilepsy-related diseases, which could frustrate the results. In studies using healthy aging animals, cohort animals may also be healthy aging animals, although other healthy animals with adequate cognitive, motor, or behavioral functioning may be suitable for use as comparative specimens.

[0020] 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 that provides nutrition to the animal.

[0021] As used herein, a "food product formulated for human consumption" is any composition specifically intended for ingestion by a human being. The term "pet food" or "pet food composition" means a composition intended for consumption by animals, in one aspect, by pets. A "nutritionally balanced pet food" is one that contains all necessary nutrients known to the recipient or intended consumer of the food, in adequate amounts and proportions, based, for example, on the recommendations of recognized authorities in the field of nutrition. of pets. These foods are therefore capable of serving as a single source of dietary intake to maintain life or promote production, without the addition of supplemental nutritional sources. Pet food compositions are widely known and used in the art. The term includes any food, feed, treat, dietary supplement, treat, meal option or meal replacement intended for a human or other animal. Pet food includes food or a pet food intended for any domesticated or wild species. In some embodiments, an animal feed represents a complete feed composition, for example, a pelleted, extruded or dried feed. Examples of such pet foods include extruded pet foods such as dog and cat foods.

[0022] The term "food supplement" means a product that is intended to be ingested in addition to the animal's normal diet. Dietary supplements can be in any form, for example, solid, liquid, gel, tablets, capsules, powder and the like. In one aspect, they can be provided in convenient dosage forms. In some embodiments, they may be provided in bulk consumer packaging such as bulk powders, liquids, gels or oils. In other embodiments, supplements may be provided in bulk quantities that will be included in other food items such as snacks, treats, supplement bars, beverages and the like.

[0023] The term "dietary regimen" refers to a combination of compositions that can be administered to an animal to enhance the effect of an antiepileptic drug (AED). Generally, the compositions include a medium chain triglyceride and an antiepileptic drug, and can be administered separately, as a combination, or as a single composition.

[0024] The term "long-term administration" means periods of repeated administration or consumption greater than one month. Periods longer than two, three or four months may be used for certain modalities. Also, longer periods can be used and include more than 5, 6, 7, 8, 9 or 10 months. Periods over 11 months or 1 year can also be used. Long term use extending over 1, 2, 3 or more years are included in the invention. For certain aging animals, the animal may continue to consume on a regular basis for the remainder of its life. This can also be referred to as "extended" consumption.

[0025] The term "regular basis" means at least monthly dosing with the compositions or with consumption of the compositions, and in one aspect means at least weekly dosing. More frequent dosing or consumption, such as two or three times a week, can also happen in certain modalities. Yet, in other embodiments, regimens can be used that comprise at least one daily intake. One skilled in the art will understand that the blood level of a compound or certain metabolites of that compound, or that result after consumption of that compound, can be a useful tool for evaluating or determining dosing frequency. For example, to determine the dosage or a dosing frequency for compositions comprising medium chain triglycerides or antiepileptic drugs, the blood concentration of ketone bodies, a specific ketone body, an antiepileptic drug, or an antiepileptic drug metabolite can provide information. Useful. A frequency, whether expressly exemplified in the present invention, which enables maintenance of a desired blood level of the measured compound, such as a ketone body or antiepileptic drug, within acceptable ranges, is useful in the present invention. One skilled in the art will understand that the frequency of dosing will be a function of the composition being consumed or administered, and some compositions may require more or less frequent administration to maintain a desired blood level of the measured compound (e.g., a ketone body or AED).

[0026] The term "oral administration" or "orally administered" means that the animal ingests, or a human is directed to provide, or provides, to the animal one or more of the compositions described herein. When a human is directed to provide the composition, such direction may be to instruct and/or inform the human that use of the composition can, and/or will, provide the aforementioned benefit, e.g., reduction of seizures. This type of advice may be verbal advice (for example, via verbal instruction from, for example, a doctor, veterinarian or other health professional, or via radio or television communication (i.e. advertisements) , or written guidance (for example, through written guidance provided by, for example, a physician, a veterinarian or other healthcare professional (for example, prescriptions), a professional or a sales organization (for example, through advertising booklets, pamphlets, or other instructional items), written media (e.g., internet, electronic mail, website, or other computer-related media), and/or packaging associated with the composition (e.g., a label on a container containing the composition), or a combination thereof (e.g. label or leaflet on the package with directions to go to a website for more information).

[0027] The term "together" means that an MCT, an antiepileptic drug or another compound or composition of the present invention are administered to an animal (1) together in a single composition, or (2) separately at the same or different frequencies, using the same or different routes of administration at approximately the same time or periodically. "Periodically" means that the agent is administered on a dosing schedule acceptable for a specific agent, and that food is routinely fed to an animal as appropriate for the specific animal. "Around the same time" generally means that the food and agent are administered at the same time or within about 72 hours of each other. "In conjunction" specifically includes administration schedules in which an antiepileptic drug is administered for a prescribed period, and compositions comprising medium chain triglyceride are administered indefinitely.

[0028] The term "individual", when referring to an animal, means an individual animal of any species or type.

[0029] The term "microorganism" includes at least bacteria, amoeboid and other fungi, and yeast. Probiotics are beneficial microorganisms that can survive or even multiply and flourish in an animal's gastrointestinal tract. Probiotics can contribute to the overall health of an animal in general and particularly to the animal's gastrointestinal health.

[0030] The term "single package" means that the components of a kit are physically associated, in or with, one or more containers, being considered a unit for manufacture, distribution, sale or use. Containers include, but are not limited to, pouches, boxes or cartons, vials, packaging of any type or design or material, overwraps, heat-shrinkable films, affixed components (e.g. stapled, adhered or similar), or combinations of any of the aforementioned items. For example, a one-pack kit can contain containers of individual compositions and/or food compositions physically associated so that they are considered a unit for manufacture, distribution, sale or use.

[0031] The term "virtual packaging" means that the components of a kit are associated by directions on one or more physical or virtual components of the kit, instructing the user on how to obtain the other components, for example, in a bag or other container containing a component, and directions instructing the user to visit a website, contact a recorded message or fax return service, look at a visual message, or contact a caregiver or instructor for, for example, instructions on how to use the kit, or technical or safety information about one or more components of a kit. Examples of information that may be provided as part of a virtual kit include instructions for use: safety information such as material safety data sheets; toxicological information; information about potential adverse reactions; results of clinical studies; dietary information, such as food composition or caloric composition; general information about cognitive, behavioral or motor function; diseases that affect cognitive, behavioral or motor function, such as epilepsy; treatment of cognitive, behavioral or motor function; epilepsy treatment; or general information about treatments or preservation of cognitive, behavioral or motor function; Caregiver information for those who care for animals with challenges related to cognitive, behavioral or motor function, such as epilepsy; and the use, benefits, and potential side effects or contraindications of antiepileptic drugs.

[0032] All percentages expressed in the present invention are by weight of the composition on a dry matter basis, unless specifically stated otherwise. One skilled in the art will understand that the term "dry matter basis" means that the concentration or percentage of an ingredient in a composition is measured or determined after removing any free moisture present in the composition.

[0033] As used throughout the document, the ranges of values are used in the present invention in abbreviated form, to avoid the need to extend and describe each of the values within the range. Any suitable value within the range can be selected, where appropriate, such as the highest value, lowest value, or extreme point of the range.

[0034] As used in the present invention, embodiments, aspects and examples that use language "comprising(m)" or other unlimited language may be replaced with "consisting essentially" and "consisting of" embodiments.

[0035] As used herein and in the appended claims, the singular form of a word includes the plural, and vice versa, unless the context clearly dictates otherwise. Thus, the references "um", "uma", "the" and "the" are, in general, inclusive of the plurals of the respective terms. For example, reference to "a pup", "a method" or a "food" includes a plurality of such "puppies", "methods" or "food". Reference herein, for example, to "an MCT", includes a plurality of such medium chain triglycerides, while reference to "pieces" includes a single piece. Similarly, the words "comprehend", "comprises" and "comprising" will be interpreted inclusively rather than exclusively. Similarly, the terms "include", "including" and "or" are all to be understood as inclusive unless such a construction is clearly prohibited from the context. When used herein, the term "examples", particularly when followed by a list of terms, is exemplary and illustrative only, and should not be considered exclusive or all-encompassing.

[0036] The methods and compositions, as well as other advances disclosed herein, are not limited to a specific methodology, protocols and reagents described herein, since, as will be understood by those skilled in the art, these may vary. Additionally, the terminology used herein is for the purpose of describing specific embodiments only, and is not intended to, and does not, limit the scope of what is disclosed or claimed.

[0037] Except where otherwise defined, all technical and scientific terms, technical terms and acronyms used in the present invention have the meanings commonly understood by one skilled in the art in the field of invention, or the field in which the term is used. While any compositions, methods, articles of manufacture, or other means or materials similar or equivalent to those described herein may be used in practicing the present invention, certain compositions, methods, articles of manufacture, or other means or materials are described herein.

[0038] All patents, patent applications, publications, technical and/or academic articles and other references cited or mentioned herein are incorporated herein by reference, in their entirety, to the extent permitted by law. The discussion of these references is intended merely to summarize the claims made therein. No admission is made that any of the patents, patent applications, publications or references, or any portion thereof, are material, material or prior art. The right to challenge the accuracy and pertinence of any assertion of these patents, patent applications, publications and other references as relevant, important or prior art is specifically reserved. Full citations of publications not fully cited within the scope of the specification are provided at the end of the specification.

the invention

[0039] The present inventors have found that administration of a medium chain triglyceride (MCT) with an antiepileptic drug (AED) can provide a synergistic effect for the treatment of epilepsy in an animal. Furthermore, the present methods and composition can use low proportions of medium chain triglycerides and high proportions of dietary carbohydrates for dietary control of canine epilepsy compared to traditional ketogenic diets. As such, present epileptic treatments do not require a ketogenic diet, although the use of such diets is not proscribed. Such synergy can be measured against comparable diets lacking medium-chain triglycerides. In one embodiment, the present administration results in a reduction in the animal's seizure frequency by at least 50% relative to administering the antiepileptic drug with a food composition that does not contain the MCT. In various embodiments, such a reduction in seizures can be at least 10%, 20% 30% 40%, 50%, 60% 70%, 80%, 90% or, in a specific aspect, 100%.

[0040] As such, in one embodiment, a dietary regimen suitable for enhancing the effect of an antiepileptic drug (AED) in an animal may comprise a food composition comprising a medium chain triglyceride (MCT) and the antiepileptic drug. Generally, the medium chain triglyceride is present in the food composition in an amount effective to enhance the effect of the antiepileptic drug when the food composition and the antiepileptic drug are administered to the animal.

[0041] In another embodiment, a method of enhancing the effect of an antiepileptic drug (AED) in an animal may comprise administering a food composition comprising a medium-chain triglyceride (MCT) together with an antiepileptic drug (AED) to the animal , wherein the medium-chain triglyceride is administered in an amount effective to enhance the effect of the antiepileptic drug in the animal.

[0042] In yet another embodiment, a pharmaceutical composition for enhancing the effect of an antiepileptic drug (AED) in an animal may comprise a medium chain triglyceride (MCT) and the antiepileptic drug. As noted earlier, medium chain triglyceride is generally present in an amount effective to enhance the effect of the antiepileptic drug when the pharmaceutical composition is administered to the animal.

[0043] The medium chain triglycerides may be any medium chain triglyceride suitable for administration to an animal. MTCs can be obtained from any suitable source, synthetic or natural. Examples of natural sources of MCTs include plant sources such as coconuts and coconut oil, babassu and babassu oils, and animal sources such as milk from any of a variety of species. In one embodiment, the medium chain triglyceride can comprise a compound having the structure shown in Formula 1, where the R', R" and R'" esterified to the glycerol structure are separately independent fatty acids having 5 to 12 carbons. In certain embodiments, greater than 95% of the R', R" and R'" are 8 carbons in length. In another aspect, the remaining part of R', R" and R'" can have either 6-carbon or 10-carbon fatty acids. In other embodiments, more than at least or about 30, 40 or 50% of R', R" and R'" are C8, and/or more than at least or about 30, 40 or 50% of R ', R" and R"' are C10. In a specific embodiment, about 50% of R', R" and R"' are C8 and about 50% of R', R" and R'" are C10.

[0044] In the case of pet foods and pet products formulated for human consumption, the amount of MCTs as a percentage of the composition can be in the range of about 1% to about 15% of the composition, although a smaller or larger percentage can be provided. In various embodiments, the amount can be about or between any of the following: 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4, 0%, 4.5%, 5.0%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5% 15% or more of the composition. Dietary supplements may be formulated to contain several times the highest concentrations of MCTs, to be considered for administration to an animal in the form of a tablet, capsule, liquid concentrate or other similar dosage form, or to be diluted prior to administration. such as by dilution in water, sprinkling or drizzling over a pet food, and other similar modes of administration. For a dietary supplement, MCTs can be administered directly to the animal or applied directly to the animal's regular food. Dietary supplement formulations in various embodiments contain from about 30% to about 100% MCTs, although smaller amounts can also be used.

[0045] The antiepileptic drugs may be any antiepileptic drug suitable for the treatment of epilepsy in an animal. Examples of antiepileptic drugs include, without limitation, acetazolamide, carbamazepine, clorazepate, clobazam, clonazepam, diazepam, eslicarbazepine acetate, etisixunudem, ethosuximide, felbamate, gabapentin, imepitoin, keppra, lacosamide, lamotrigine, levetiracetam, methylphenobarbitone, nitrazepam, oxcarbazepine , perampanel , piracetam, phenobarbital, phenytoin, potassium bromide, pregabalin, primidone, retigabine, rufinamide, sodium bromide, sodium valproate, stiripentol, sultiam, tiagabine, topiramate, valproic acid, vigabatrin, zonisamide, their salts, their derivatives and mixtures thereof .

[0046] Generally, the antiepileptic drug can be administered to the animal in any amount that is sufficient for the treatment of epilepsy. In one embodiment, the antiepileptic drug can be administered in an amount of from about 0.1 mg/kg/day to about 50 mg/kg/day. In one aspect, the antiepileptic drug can be administered in an amount of 20 mg/Kg/day to 30 mg/Kg/day.

[0047] The present food compositions may comprise other ingredients that may be beneficial for cognitive function, such as LCPUFA, NORCs, B vitamins and antioxidants. The LCPUFA can be any LCPUFA suitable for administration to an animal. AGPICLS can be obtained from any suitable source, synthetic or natural. Sources of LCPUFA include natural sources of such fatty acids as, but not limited to, evening primrose; dark green vegetables such as spinach; seaweed and blue-green algae such as spirulina; plant seeds and oils derived from plants, such as flaxseed, canola, soybean, walnut, pumpkin, safflower, sesame, wheat germ, sunflower, corn and hemp; and fish, such as salmon, tuna, mackerel, herring, sea bass, striped sea bass, sole, catfish, sardines, shark, shrimp and shellfish; and oils extracted from any one or more of the foregoing items. LCPUFA can also be synthetic and, as such, can be produced by any suitable means in the art from any suitable starting material. It should be understood that the LCPUFA's may comprise a blend of any one or more LCPUFA's from any one or more sources, as exemplified above, natural or synthetic.

[0048] The NORCs can be any NORC suitable for administration to an animal. NORCs can be obtained from any suitable source, synthetic or natural. In various embodiments, NORC comprises arginine. Arginine sources include, but are not limited to, animal and plant proteins. Examples of plants considered to be rich in arginine content and suitable for use in the present invention include, but are not limited to, legumes such as soybeans, lupine and carob; grains, such as wheat and rice; and fruits such as grapes. Grains and oleaginous fruits from plants such as cocoa and peanuts are also considered to be rich in arginine content and are therefore useful in the present invention. Some examples of suitable animal proteins considered to be high in arginine content are poultry and fish products. NORC can also be produced synthetically, according to any means suitable in the art. As with LCPUFA, the NORC content of any composition disclosed herein may include a blend of any natural or synthetic NORC. Both LCPUFA and NORC, whether natural or synthetic, can be obtained directly from a commercial source, or they can be supplied by a commercial source.

[0049] The B-complex vitamins may be any B-complex vitamin suitable for administration to an animal. B-complex vitamins include vitamins B1 (thiamine), B2 (riboflavin), B3 (also known as P or PP) (niacin, including nicotinic acid and/or nicotinamide), B5 (pantothenic acid), B6 (pyridoxine), B7 (also known as H) (biotin), B8 (myo-inositol), B9 (also known as M or B-c) (folic acid), B12 (cobalamin) or salts, conjugates or derivatives thereof known to have vitamin activity of the B-complex. Combinations of any of the foregoing items may also be useful in the present invention and are sometimes referred to herein as "blends" of B-complex vitamins. Since vitamin requirements vary for different species, not all compounds listed are considered vitamins for all species. For example, myo-inositol can be synthesized by humans; therefore, it is no longer considered a vitamin, as it is not required for adequate human nutrition.

[0050] The antioxidants may be any antioxidant suitable for administration to an animal. Antioxidants are well known in the art, particularly in the art of food technology and food formulation. Natural antioxidant compounds include vitamins (such as A, C, and E, and derivatives, conjugates, or analogues thereof), as well as plant extracts, including extracts from fruits, vegetables, herbs, grains, and other types and/or parts of plants. Compounds such as α-lipoic acid, chlorophyll and derivatives thereof, glutathione, ubiquinols (eg coenzyme Q10), carotenoids (eg lycopene), flavonoids, phenolic acids and polyphenols, and pycnogenol are known to be excellent antioxidants. Some examples of plant sources of antioxidants include those that come from fruits such as berries (cherry, blackberry, strawberry, raspberry, cranberry, blueberry, cranberry/wild cranberry, blackcurrant), pomegranates, grapes, oranges , plums pineapples, kiwis and grapefruits; those originating from vegetables, including kale, chili, red cabbage, peppers, parsley, artichokes, Brussels sprouts, spinach, lemon, ginger, garlic and beets; those originating from dried fruits, such as apricots, prunes and dates; and legumes, including fava beans, pinto beans and soybeans. In addition, grains and oilseeds such as pecans, walnuts, hazelnuts, peanuts and sunflower seeds; and cereals such as barley, millet, oats and corn. Many natural antioxidants are also available from a wide variety of spices, including cloves, cinnamon, rosemary and oregano. Less widely known sources of antioxidants include ginkgo biloba and tropical plants such as uyaku (lindera strychnifolia) and papaya. The antioxidant properties of various teas and green tea, as well as fermented products such as red wine, have been of great interest in recent years, and they are suitable for use in the present invention. Selenium is an excellent oxygen scavenger and works well, especially with vitamins or tocopherol-related compounds. Synthetic dietary antioxidants include butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), which are commonly used in food products. Any of the aforementioned instruments, alone or in combination, are suitable for use herein, as combinations of natural and synthetic antioxidants.

[0051] LCPUFA, NORC, B vitamins and antioxidants, if included in the composition, may be present in individual amounts for general health, or to improve cognitive function. In some embodiments, the compositions may individually comprise from about 0.1% to about 50% LCPUFA, from about 0.1% to about 20% NORC, from about 0.1 to 40 times the recommended daily requirement (RDA) for B vitamins, and/or about 0.1 to 25 times the RDA for antioxidants. In various embodiments, compositions can comprise from about 1 to about 30% LCPUFA and, in one aspect, from about 1 to about 15% LCPUFA. In other embodiments, compositions can comprise from about 1 to about 15% NORC, and, in one aspect, from about 1 to about 10% NORC. In still other embodiments, the compositions can comprise B vitamins in an amount from about 1 to 20 times the RDA and, in one aspect, from about 4 to 10 times the RDA. In still other embodiments, the compositions can comprise antioxidants in an amount from about 0.01 to 15 times the RDA, in one aspect from about 0.01 to 5 times the RDA, and in a specific aspect from about 0.01 to 2 times the RDA.

[0052] The compositions may further comprise substances such as minerals, other vitamins, salts, functional additives including, for example, palatable elements, colorants, emulsifiers, antimicrobial agents or other preservatives. Minerals that may be useful in such compositions include, for example, calcium, phosphorus, potassium, sodium, iron, chloride, boron, copper, zinc, magnesium, manganese, iodine, selenium and the like. Examples of additional vitamins useful in the present invention include such fat-soluble vitamins as A, D, E and K. Inulin, amino acids, enzymes, coenzymes and the like may be useful to include in various embodiments.

[0053] In one embodiment, the food compositions can be formulated as human consumption compositions or pet food compositions. Such compositions include feed intended to meet the necessary dietary requirements for an animal, animal snacks (e.g. biscuits) or food supplements. The compositions can be a dry composition (eg, ground flour pellets), a semi-wet composition, a wet composition, or any mixture thereof. In another embodiment, the composition may be a food supplement such as a broth, drinking water, beverage, yogurt, powder, granule, paste, suspension, chewable item, morsel, treat, snack, pellet, pill, capsule, tablet or any other form of suitable release. The dietary supplement may include a high concentration of medium-chain triglycerides. This allows the supplement to be given to the animal in small amounts or, alternatively, it can be diluted prior to administration to the animal. The food supplement may require mixing with water, or it may be mixed with water or other diluent prior to administration to the animal.

[0054] In one embodiment, the compositions are refrigerated or frozen compositions. In another embodiment, the medium chain triglycerides are pre-mixed with the other components to provide the required beneficial amounts. In yet other embodiments, the medium chain triglycerides can be used to coat a food, snack, pet food composition or pet treat. In one embodiment, the medium chain triglycerides can be added to the composition just before offering it to the animal, for example using a powder or dusting mix. Such compositions may additionally comprise other ingredients, as discussed herein.

[0055] The compositions may optionally comprise one or more supplemental substances that promote or support general health. Such substances may be associated with better mental health or enhanced cognitive function, or they may be substances that inhibit, delay or lessen the loss of cognitive function, for example herbs or plants that enhance cognitive function.

[0056] In various embodiments, the pet food or pet treat compositions comprise from about 15% to about 50% crude protein. The crude protein material can comprise plant proteins such as soy meal, soy protein concentrate, corn gluten meal, wheat gluten, cottonseed and peanut meal, or animal proteins such as casein, whey, albumin and meat protein. Examples of meat proteins useful in the present invention include pork, lamb, horse, poultry, fish and mixtures thereof. Furthermore, in one aspect, the compositions can include any protein source used or known to be used for hypoallergenic purposes, including hydrolyzed protein sources.

[0057] The compositions may further comprise from about 5% to about 40% fat. The compositions may further comprise a carbohydrate source. Compositions can comprise from about 15% to about 60% carbohydrate. Examples of such carbohydrates include grains or cereals such as rice, corn, sorghum, alfalfa, barley, soybeans, canola, oats, wheat and mixtures thereof. Compositions may also optionally comprise other materials such as dried whey and other dairy by-products.

[0058] In some embodiments, the ash content of the composition is in the range of 1% to about 15%, and, in one aspect, from about 5% to about 10%.

[0059] The moisture content may vary depending on the nature of the composition. In one embodiment, the composition can be a complete and nutritionally balanced pet food. In another embodiment, the composition can be a hypoallergenic composition. In this embodiment, the pet food can be a "wet food", a "dry food" or a food with an intermediate moisture content. "Wet food" describes pet food that is typically sold in aluminum foil cans or bags and has a moisture content typically in the range of about 70% to about 90%. "Dry food" describes pet food of a similar composition to wet food, but which contains a limited moisture content, typically in the range of about 5% to about 15% or 20%, and therefore is present , for example, as small biscuit-like pellets. In one embodiment, the compositions can have a moisture content of from about 5% to about 20%. Dried food products include a variety of foods of various moisture contents so that they are relatively storage stable and resistant to microbial or fungal spoilage or contamination. Furthermore, dry food compositions are included, which are extruded food products such as pet food or snack foods for both humans and pets.

[0060] The compositions may also comprise one or more fiber sources. The term "fiber" includes all sources of "bulk" in food, whether in digestible or indigestible, soluble or insoluble, fermentable or non-fermentable form. Fiber can come from plant sources such as marine plants, but microbial sources of fiber can also be used. A variety of soluble or insoluble fibers can be used, as will be known to those skilled in the art. The source of fiber can be beet pulp (from beet sugar), gum arabic, tallow gum, psyllium, rice bran, locust bean gum, citrus pulp, pectin, fructooligosaccharide, short chain oligofructose, mannanoligofructose, soy, arabinogalactan, galato-oligosaccharide, arabinoxylan or mixtures thereof.

[0061] Alternatively, the fiber source may be a fermentable fiber. It has been previously described that fermentable fiber provides a benefit to a companion animal's immune system. Fermentable fibers or other compositions known to those skilled in the art that provide a prebiotic to enhance the growth of probiotics within the gut can also be incorporated into the composition to help enhance the benefit provided by the present invention to an animal's immune system.

[0062] In other embodiments, the compositions may further comprise prebiotics or probiotics. Probiotics are microorganisms that have a beneficial effect in the prevention and treatment of specific medical conditions when ingested. It is believed that probiotics exert biological effects through a phenomenon known as resistance to colonization. Probiotics facilitate a process by which native anaerobic flora limits the concentration of potentially harmful (mostly aerobic) bacteria in the digestive tract. Other modes of action, such as providing enzymes or influencing enzyme activity in the gastrointestinal tract, may also be responsible for some of the other functions that are attributed to probiotics. Prebiotics are non-digestible food ingredients that beneficially affect host health by selectively stimulating the growth and/or activity of bacteria in the colon. Prebiotics include fructo-oligosaccharides (FOS), xylo-oligosaccharides (XOS), galacto-oligosaccharides (GOS) and manno-oligosaccharides (typically for foods intended for ingestion by non-humans, such as pet food). The prebiotic fructo-oligosaccharide (FOS) is found naturally in many foods such as wheat, onions, bananas, honey, garlic and leeks. FOS can also be isolated from chicory root or enzymatically synthesized from sucrose. Fermentation of FOS in the colon results in an increased number of physiological effects that include increased numbers of bifid bacteria in the colon, increased calcium absorption, increased fecal weight, shortened gastrointestinal transit time, and possibly decreased of blood lipid levels. The increase in bifid bacteria is thought to benefit human health by producing compounds that inhibit potential pathogens, by reducing blood ammonia levels, and by producing vitamins and digestive enzymes. It is believed that probiotic bacteria, such as lactobacilli or bifid bacteria, positively affect the immune response by improving the intestinal microbial balance, leading to optimized antibody production and phagocytic (devouring or killing) activity of leukocytes. Bifidobacterium lactis may be an effective probiotic food supplement to improve some aspects of cellular immunity in the elderly. Probiotics enhance systemic cellular immune responses, and may be useful as a dietary supplement to support natural immunity in normally healthy adults. Probiotics include many types of bacteria, but are generally selected from four genera of bacteria: Lactobacillus acidophillus, Bifidobacteria, Lactococcus, and Pediococcus. Beneficial species include Enterococcus and Saccharomyces species. The amount of probiotics and prebiotics to be administered to the animal can be determined by one skilled in the art based on the type and nature of the prebiotic and probiotic, and the type and nature of the animal, e.g. age, weight, general health , gender, extent of microbial depletion, presence of harmful bacteria, and animal diet. In general, probiotics are administered to an animal in amounts of from about one to about twenty billion colony forming units (CFUs) per day for the maintenance of healthy intestinal microflora, and, in one aspect, from about 5 billion to about 10 billion live bacteria per day. Generally speaking, prebiotics are given in sufficient amounts to positively stimulate the healthy microflora present in the gastrointestinal tract and cause these "good" bacteria to reproduce. Typical amounts are about 10 grams per serving, or about 5% to about 40% of the daily dietary fiber recommendation for an animal. Probiotics and prebiotics can be produced as part of the composition by any suitable means. Generally, the agents are mixed with the composition or applied to the surface of the composition, for example by spraying or spraying. When agents are part of a kit, the agents can be mixed with other materials or in their own packaging.

[0063] Dietary compositions and supplements may be specially formulated for intended recipients or consumers, such as for adult animals, or for older or younger animals. For example, a composition adapted for puppies or kittens or for active, pregnant, nursing or aging animals can be prepared. In general, specialized compositions will comprise appropriate nutritional and energy requirements for animals at different stages of development or different ages.

[0064] Certain aspects of the invention can be used in combination with a complete and balanced food. In accordance with certain embodiments provided herein, compositions comprising the MCTs can be used with a high quality commercial feed. As used herein, "high quality commercial food" refers to a diet manufactured to produce essential nutrient digestibility of 80% or greater, as stipulated, for example, in the National Research Council recommendations for dogs , or the guidelines set forth by the Association of American Feed Control Officials. Similar high nutritional standards can be used for other animals.

[0065] In one embodiment, the food compositions comprise any of a variety of ingredients, or combinations thereof, selected for their contributions to the overall composition. Thus, a food technologist skilled in the art can choose between natural (eg, vegetable or plant-derived, animal or animal-derived, and microbial or microbial-derived) and synthetic ingredients or components. In specific embodiments, ingredients may include any of grains and cereal fractions or components thereof, meat and meat by-products, fish, shellfish or other seafood, other animal products or by-products, eggs from any source, vitamins , minerals, salts, sweeteners, fibers, flavors or other palatable elements, colorants and functional ingredients such as emulsifiers, stabilizers, emollients, functional coatings and the like. Cereals useful to the invention include all plants recognized as "cereal" crops, currently used in commercial agriculture or merely known in practice or botanically to be a "cereal". For example, the term "cereals" includes corn, wheat, barley, sorghum, millet, oats, rye, triticale, buckwheat, fonio and quinoa. One skilled in the art will understand that, in a given food composition, it is not uncommon to use one or more of these cereal products. Meats useful in the invention include products derived from any animal, in one aspect, from muscle tissue, such as chicken or other poultry, mutton, sheep, veal, beef or pork. Other animal products and by-products useful in the invention include dairy products or by-products derived from milk of any kind. Other important components or ingredients include fats, and those skilled in the art will recognize that many vegetable, animal or microbial fat sources are available for formulating food compositions. In one embodiment, the fat source can be a fat of vegetable origin, such as corn, soybean or canola oil. In another embodiment, an animal fat such as lard can be useful to provide calories from fat in addition to providing flavor to carnivorous animals. Obviously, combinations of any of the aforementioned ingredients, such as fats, are well known in the art and are useful for optimizing food compositions based on functional properties, in addition to price and availability.

[0066] The person skilled in the art will also understand that when formulating the food compositions of the invention, the formulation may vary slightly, in order to allow for consideration of the price and/or availability of certain ingredients in the compositions by the formulator, in addition to batch variation for batch analysis of certain ingredients. Thus, a given food composition or formulation may vary slightly from batch to batch, from plant to plant or even from season to season, depending on such factors. Despite such variation in specific ingredients selected for the manufacture of a specific batch of a food composition, the composition (e.g., analysis of protein, carbohydrate, fat, fiber or other components) can generally be held constant or at least substantially constant, for example, according to a classification claim, such as a claim or guarantee of a minimum or maximum percentage of a specific component.

[0067] One skilled in the art will know how to determine the proper amount of medium chain triglycerides and any other ingredients to be added to a given composition. The skilled formulator may consider animal species, age, size, weight, health and the like important in determining the best way to formulate a specific composition, food or pharmaceutical composition comprising the medium chain triglycerides and other components. Other factors that may be taken into consideration for formulation include the type of composition (e.g. pet food composition versus food supplement), desired dosage of each component (MCTs), average consumption of specific types of compositions by different animals (eg based on species, body weight, energy/activity demands and the like) and the manufacturing conditions under which the composition is prepared. In one embodiment, the concentrations of medium chain triglycerides and other ingredients to be added to the composition are calculated based on the energy and nutrient requirements of the animal. In formulating the compositions of the present invention, one skilled in the art can determine the amounts of medium chain triglycerides and other components of the compositions and other compounds or ingredients in, for example, a food composition, based on desired dosages and characteristics. of the animal.

[0068] In the case of pet foods and pet products formulated for human consumption, the amount of LCPUFA as a percentage of the composition can range from about 0.1% to about 13% of the composition, although a higher percentage can be provided. In various embodiments, the amount of LCPUFA can be about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8 %, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8 %, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8 %, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8 %, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8 %, 4.9%, 5.0% or more, for example, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or more of the composition. Up to 30, 40 or 50% LCPUFA can be used in certain embodiments.

[0069] In the case of pet food and pet products formulated for human consumption, the amount of NORC as a percentage of the composition can be in the range of about 0.1% to about 12% of the composition, although a higher percentage can be provided. In various embodiments, the amount of NORC can be about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8 %, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8 %, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8 %, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8 %, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8 %, 4.9%, 5.0% or more, for example 6%, 7%, 8%, 9%, 10%, 11%, 12% or more, up to about 15% or even 20% of composition. Dietary supplements may be formulated to contain several times the highest concentrations of LCPUFA and NORC to be considered susceptible for administration to an animal in the form of a tablet, capsule, liquid concentrate, emulsion, suspension, gel or other form of dosage, or to be diluted prior to administration, such as by dilution in water, or addition to a pet food (e.g., by sprinkling or splashing over it) and other modes of administration suitable for administering such food supplements.

[0070] In one embodiment, the amount of medium chain triglyceride or antiepileptic drug in the composition may be a function of an amount necessary to establish specified concentrations, or a desired range of concentrations, medium chain triglyceride and/or antiepileptic drug, or of a metabolite of the same, in the blood serum of the animal. The specified concentrations, or desired ranges, of medium-chain triglyceride and/or antiepileptic drug in blood serum can be calculated by determining the blood/serum levels of animals fed the recommended amounts of medium-chain triglyceride and/or specified antiepileptic drug above, as would be understood by one skilled in the art.

[0071] In one embodiment, the food compositions comprise a macronutrient composition suitable for the type of food being developed. In one aspect, the food composition is about 20 to 32% protein, about 30 to 50% carbohydrate, about 5% to 20% fat, and about 15% to 25% moisture. In another embodiment, the food composition may be a pet food composition, such as a premium (premium) or top quality (super premium) pet food composition. In one embodiment, the pet food can be formulated for dogs and has a protein content of about 20 to 30%, about 24 to 28% or even about 25 to 27%. In one embodiment, the protein content of a dog food composition can be about 26% by weight. In another mobility, the formulation can be for felines and can have a protein content of about 35 to 45%, 37 to 42% or even about 39 to 41%. In one embodiment, the protein content of a cat food composition can be about 40%. In another embodiment, the composition can be a food product comprising medium chain triglycerides, and further comprising from about 15% to about 50% protein, from about 5% to about 40% fat, from about 5% at about 10% ash content and at a moisture content of about 5% to about 20%.

[0072] In one embodiment, the food composition can be a wet food such as canned food, frozen food or a fresh food product. In another embodiment, the food composition may be sale stable. In another, it must be refrigerated. In other embodiments, the food composition can be an intermediate moisture product or a dry food product, as described above.

[0073] In one embodiment, the LCPUFA can be a fish oil and the NORC can be a derivative that releases arginine or nitric oxide therefrom. In certain embodiments, compositions can comprise from about 0.1% to about 50% fish oil, and from about 0.1% to about 20% arginine.

[0074] In one embodiment, the LCPUFA comprises one or more of a natural fish oil, ALA, EPA, DHA, DPA or other n-3 fatty acid from any source. Combinations of LCPUFA sources are, of course, envisaged for use in the present invention. LCPUFA with n-3 or n-6 are also envisaged for use in various modalities.

[0075] In one embodiment, the composition may be formulated for a pet, for example, a dog or cat. In other embodiments, the animal may be a human.

[0076] In other embodiments, pharmaceutical compositions may comprise one or more pharmaceutically acceptable carriers, diluents or excipients. In general, pharmaceutical compositions can be prepared by mixing a compound or composition with excipients, buffers, binders, plasticizers, colorants, diluents, blowing agents, lubricants, flavors, wetting agents and the like, including other known ingredients. by those skilled in the art as being useful for making pharmaceuticals and formulating compositions that are suitable for administration to an animal as pharmaceuticals. Optionally, the pharmaceutical compositions further comprise MCTs, LCPUFAs, NORCs, B vitamins and antioxidants.

[0077] In another aspect, the invention provides methods for treating epilepsy by administering the compositions described herein in an amount effective to treat epilepsy.

[0078] In some embodiments, the LCPUFA, MCTs, NORCs, B vitamins and antioxidants can be administered to the animal in the amounts given in the present invention when describing the compositions. In certain embodiments, the daily dose for the compositions ranges from about 5 mg/day to about 5000 mg/day, 10,000 mg/day, or 20,000 mg/day, or more per animal. In one aspect, the daily dose can range from about 30 mg/day to about 10,000 mg/day per animal, and, in a specific aspect, from about 750 mg/day to about 7,500 mg/day per animal. The daily dose of LCPUFA, NORC and MCTs can be measured in terms of grams of LCPUFA, NORC and MCTs per kilogram of animal body weight (BW). The daily dose of LCPUFA, NORC and MCTs thereof can range from about 0.001 g/kg to about 50 g/kg animal BW, although higher or lower doses can be given. In one embodiment, the daily dose of LCPUFA, NORC and MCTs can be from about 0.001 g/kg to about 25 g/kg animal BW. In another aspect, the daily dose of LCPUFA, NORC and MCTs thereof can be from about 0.001 g/kg to about 10 g/kg animal BW. In another aspect, the daily dose of LCPUFA, NORC and MCTs can be from about 0.001 g/kg to about 5 g/kg animal BW. In still other aspects, the daily dose of LCPUFA, NORC and MCTs can be from about 0.001 g/Kg to about 1 g/Kg animal BW, or from about 0.001 g/Kg to about 0.5 g/ kg BW of the animal.

[0079] Administration according to the methods may be on need basis or desired basis of varying or regular frequency. One objective of regular ingestion is to provide the animal with a regular and consistent dose of the composition or direct or indirect metabolites that result from such ingestion. Such regular and consistent dosing will tend to create constant blood levels of the components of the compositions or their direct or indirect metabolites. Thus, regular dosing can be once a month, once a week, once a day, or more than once a day. Similarly, administration can be every other day, every other week, or every other month, every third day, week, or month, every four day, week, or month, and the like. Administration can be multiple times a day. When used as a supplement to common dietary requirements, the composition can be administered directly to the animal, for example, orally or otherwise. The compositions may alternatively be placed in contact with, or mixed with, the feed or diary, including a fluid such as drinking water, or an intravenous connection, of an animal receiving such treatment. When used as a ration or diary, administration will be well known to those skilled in the art.

[0080] In accordance with the methods of the invention, administration of the compositions, including administration as part of a dietary regimen, can last for a period of time ranging from birth to adulthood of the animal. In various embodiments, the animal can be a human or a pet such as a dog or cat. In certain embodiments, the animal may be a young or growing animal. In other embodiments, the animal may be an aging animal. In some embodiments, administration begins, for example, on a regular or extended regular basis, when the animal has already exhibited signs of seizures or has otherwise been diagnosed with epilepsy.

[0081] Generally, the compositions can be administered to the animal together with one or more antiepileptic drugs in an amount effective in treating epilepsy. In a specific embodiment, the administered composition can be the pharmaceutical composition that includes the antiepileptic drug and the MCT. In one embodiment, the composition can be administered to the animal daily in a single dose.

[0082] In a further aspect, the invention provides kits suitable for administering a composition comprising medium chain triglycerides to an animal. Kits comprise, in separate containers in a single pack or in separate containers in a virtual pack, as appropriate for the kit component, one or more medium chain triglycerides and, optionally, one or more of (1) one or more ingredients suitable for consumption by an animal; (2) one or more antiepileptic drugs; (3) instructions on how to combine or prepare the MCTs and any other ingredients provided in the kit for administration to an animal; (4) instructions on how to use the combined kit components, prepared kit components, or other kit components for the benefit of an animal; and (5) a device for administering the combined or prepared kit components to an animal. Each of the components is supplied in separate containers in a single package or as mixtures of several components in different packages. Kits can comprise ingredients in various combinations. For example, the kit could comprise a mixture of one or more medium chain triglycerides and one or more food ingredients in one container, and one or more other ingredients in one or more containers. Likewise, the kit could comprise a single food composition containing the medium chain triglycerides with an additional compartment for an antiepileptic drug. Other combinations can be produced by the person skilled in the art based on the characteristics of the ingredients, their chemical and physical properties and their compatibilities.

[0083] In another aspect, the invention features means of communicating information or instructions for one or more of (1) using the compositions of the present invention to treat epilepsy; (2) mixing the medium chain triglycerides or the other components of the invention to produce a composition suitable for treating epilepsy; (3) using the kits of the present invention for the treatment of epilepsy; and (4) administering the compositions to an animal. The medium comprises one or more of a physical or electronic document, a digital storage medium, an optical storage medium, an audio presentation, an audio-visual display or a visual display containing the information or instructions. In one embodiment, the media may be selected from the group consisting of a display website, a visual display kiosk, a booklet, a product label, an enclosed flyer, an advertisement, a flyer, a public announcement, a ribbon audio tape, a videotape, a DVD, a CD-ROM, a computer-readable chip, a computer-readable card, a computer-readable disc, a USB device, a FireWire device, computer memory, and any combination of the same.

[0084] In another aspect, the invention provides methods for manufacturing a food composition comprising medium chain triglycerides and one or more ingredients suitable for consumption by an animal, for example, proteins, fats, carbohydrates, fibers, LCPUFAs, NORCs, B vitamins and antioxidants. The methods comprise mixing one or more ingredients suitable for consumption by an animal with medium chain triglycerides and possibly other ingredients. Alternatively, the methods comprise applying the MCTs, and other ingredients, if desired, separately or in any combination over the food composition, for example, as a coating or topping. MCTs can be added at any time during manufacturing and/or processing of the food composition. This includes, for example, mixing the medium chain triglycerides as part of the base formulation of the "body" of the food composition or applying them as a coating, i.e. essentially to the surface of the food composition after manufacture. The compositions can be made according to any method suitable in the art.

[0085] In another aspect, the present invention provides a package comprising a composition of the present invention and a label applied to the package containing a word, or words, a figure, a design, acronym, slogan, phrase or other device, or a combination thereof, which indicates that the package contents contain a composition suitable for the treatment of epilepsy in an animal. Typically, such a device comprises the words "treats epilepsy", "improves treatment of epilepsy", "intensifies treatment of epilepsy", or an equivalent expression printed on the packaging. Any package or packaging material suitable for containing the composition is useful in the present invention, for example, a pouch, box, vial, can, sachet, and the like, fabricated from paper, plastic, foil, metal, and the like. similar. In one embodiment, the package contains a food composition tailored for a specific animal, such as a human, dog or feline, as appropriate for the label, and, in one aspect, a pet food composition.

[0086] The pharmaceutical compositions of the invention can be administered to the animal using a variety of routes of administration. Such routes include oral, intranasal, intravenous, intramuscular, intragastric, transpyloric, subcutaneous, rectal, and the like. In one embodiment, the compositions can be administered orally.

Examples

[0087] The invention may be further illustrated by the following example, although it is understood that this example is included for illustrative purposes only, and is not intended to limit the scope of the invention, except where specifically indicated to the contrary.

Example 1 - Canine epilepsy study

[0088] A 6-month prospective, randomized, double-blind, placebo-controlled crossover diet trial comparing a diet containing medium-chain triglyceride with a standardized placebo diet not containing medium-chain triglycerides in canine epilepsy was performed. Subjects were fed medium-chain triglycerides or placebo for 3 months (day 1 to day 90 ± 2 days), followed by a respective subsequent diet change, for an additional 3 months (day 90 to day 180 ± 2 days). Relevant data were collected on the following variables at visit 1 (day 2), visit 2 (day 90 ± 2 days) and visit 3 (day 180 ± 2 days): seizure frequency; body weight; measurements of serum phenobarbital (PB) and/or KBr (potassium bromide) concentration, as appropriate; dynamic bile acids; complete blood cell count; standard clinical serum clinic; and adverse events Diet allocations were randomized and available only to the study nurse who was also the dispenser of the diet, and therefore, the owners, investigators and statisticians involved did not have this information throughout the study.

[0089] Subjects were recruited based on the following inclusion and exclusion criteria, which were verified through telephone interviews accompanied by physical and laboratory examinations: canine species of mixed or purebred animal breeds; suspected idiopathic epilepsy (normal anterior magnetic resonance imaging (MRI) scan and cerebrospinal fluid (CSF) analysis); age between 6 months and less than or equal to 12 years; weight between 4 kg and less than or equal to 65 kg; no clinically significant checks on hematology and clinical results, or on bile acid dynamics; has normal interictal neurological examinations for a dog on antiepileptic treatment; only one dog per household enrolled in the study; had at least 3 seizures in the last 3 months before starting the study; in at least one antiepileptic treatment; there was no use of drugs that could influence the metabolism of PB and KBr. Dogs intended for breeding less than two weeks from the start of the study; with known cause of epilepsy, such as brain neoplasm, brain trauma, encephalitis and meningitis; with acute or chronic renal, hepatic or cardiac insufficiency; with an acute or surgical condition at the time of enrollment, and female dogs that were pregnant or suspected to be pregnant or nursing were excluded from the study.

[0090] The medium-chain triglyceride diet was the commercially available ProPlan® Senior 7+ Chicken and Rice formula, manufactured in France and formulated to contain 5.6% medium-chain triglycerides, at least 26% crude protein, at less than 15% crude fat and 50% carbohydrates with less than 2% crude fiber. The placebo formula is similar in composition, except that no medium-chain triglycerides were added, and lard was used as a fat substitute to ensure that the formulas were isocaloric. Dogs were housed and fed primarily once a day at home and there were no restrictions on water consumption. Owners were educated to keep the diet consistent throughout the study period.

[0091] Seizure frequency refers to the number of seizures per month, and seizure days refers to the number of days in a month that a seizure occurs. The severity of seizures was analyzed using the McNemar test, comparing the presence of seizures in the group between the diet groups. Comparisons made between the standardized medium-chain triglyceride diet and placebo groups were made using paired matching Student's t-test for parametric data and the Wilcoxon test for non-parametric data, where both were used two-tailed, and P < 0.05 was considered significant. Non-parametric data are shown as median (25th to 75th percentile) and parametric data are shown as mean (+/-SD).

[0092] The present study used twenty-one dogs from 17 different canine breeds, including: American Bulldog; 2 beagles; 2 Border Collies; Boxer; Cavalier King Charles Spaniel; English Bull Terrier; English Springer Spaniel; German Shepherd; Golden retriever; Lhasa Apso; Mastiff; Rhodesian Ridgeback; St Bernard; Siberian Husky; Slovakian Pointer; Welsh Springer Spaniel and 3 cross species. The study population consisted of 15 males, of which 10 were castrated and 5 were intact and 6 females, of which 4 were castrated and 2 were intact. Dogs were 4.59 ± 1.73 years old and weighed 29.79 kg ± 14.73 kilograms at baseline. All 21 dogs received PB. Most dogs were also treated with KBr (n = 18). Some dogs were chronically treated with a third antiepileptic drug, imepitoin (n = 1) or levetiracetam (n = 4). Twelve owners had rectal diazepam or levetiracetam for home pulse therapy available for the acute treatment of serial seizure episodes. There was no difference for acute or chronic treatment regimens between the medium-chain triglyceride phase or placebo.

Effects on seizure frequency, seizure days, and seizure severity

[0093] The results revealed a significantly lower frequency of seizures when dogs were fed medium-chain triglyceride (2.8/month, 0 to 10/month) compared to the placebo diet (4.4/month , 0.3 to 22.9/month, p = 0.0195; Table 1). Three dogs were completely seizure free (100% reduction), 7 dogs had a 50% or greater reduction in seizure frequency (56.85%, 50.76 to 62.8%) and 5 dogs had a reduction overall in the frequency of seizures (38.87%, 35.68 to 43.27). Six dogs showed no response to medium chain triglyceride with an overall increase in seizure frequency. Table 1

[0094] There were also shown to be significantly fewer seizure days when dogs were on the MCT group compared to the placebo diet (p = 0.0216) with over 76% of the experimental population achieving a reduction in seizure days (table two). During medium-chain triglyceride treatment, 3 dogs achieved complete seizure-free (100% reduction) and 5 dogs achieved greater than 50% reduction in seizure days (67.14%, 58.22 to 75, 14), and 8 dogs achieved less than a 50% reduction in seizure days (29.68%, 6.839 to 41.22%). Five dogs showed no response to medium chain triglyceride, with an overall increase in the number of seizure days. Table 2

[0095] The medium-chain triglyceride diet resulted in a change in the distribution of monthly seizure frequencies with higher percentages of the entire population (n = 21) experiencing reduced frequencies compared to the standard placebo diet. The total number of seizures that occurred in the study population (n = 21) on each day of the MCT period was also reduced compared to the placebo diet (Table 3). The results also show a reduction in the number of subjects having seizure events during the MCT period with a stable distribution of about 3 subjects having seizure events per day. On the other hand, during the standardized placebo diet, the distribution varied more, with more individuals having seizures per day. There were no significant differences in the number of days with serial seizures between the diet groups (p = 0.6171). Table 3

Effect on body weight, serum antiepileptic drug concentration, complete blood count and clinical chemistry

[0096] There were no significant changes in serum concentrations of PB (26.50 μg/mL, 23.50 to 34.00 μg/mL v. 32.50 μg/mL, 25.00 to 36.75 μg /mL, p = 0.4233) and potassium bromide (1.23 mg/mL, 1.09 to 1.89 mg/mL v. 1.29 mg/mL, 1.02 to 1.61 mg/mL , p = 0.4037) or weight (29.79, ±15.16 kg v. 29.61 ± 15.51 kg, p = 0.2997) between the standardized diet with placebo and medium-chain triglyceride, respectively. Complete blood count and clinical chemistry results, including glucose, were not significantly different between diet groups.

[0097] In the descriptive report, typical embodiments of the invention were revealed. While specific terms are employed, they are used in a generic and descriptive sense only and are not intended to be limiting. The scope of the invention is presented in the claims. Obviously, many modifications and variations of the invention are possible in view of the above teachings. It is to be understood, therefore, that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described.

Claims (3)

1. Use of a medium-chain triglyceride (MCT), which has a formula (Formula 1): in which R', R" and R'", esterified to the main chain of glycerol, are each, independently, fatty acids having from 5 to 12 carbons, said use being characterized by the fact that it is for the preparation of a food composition for enhance the effect of an antiepileptic drug (AED) in a canine or feline; said food composition being suitable for administration together with the AED; wherein said food composition comprises from 2.5% to 7.5% by weight of said MCT; wherein greater than 95% of the R', R" and R'" are 8 carbons in length, or the remaining R', R" and R'" are either 6-carbon or 10-carbon fatty acids; and said food composition further comprising: from 15% to 50% of protein by weight, from 5% to 40% of fat by weight, from 5% to 10% by weight of ash content, and a moisture content from 5% to 20% by weight. 2. Use, according to claim 1, characterized in that said AED is selected from the group consisting of acetazolamide, carbamazepine, clorazepate, clobazam, clonazepam, diazepam, eslicarbazepine acetate, etisixunudem, ethosuximide, felbamate, gabapentin, imepitoin, keppra, lacosamide, lamotrigine, levetiracetam, methylphenobarbitone, nitrazepam, oxcarbazepine, perampanel, piracetam, phenobarbital, phenytoin, potassium bromide, pregabalin, primidone, retigabine, rufinamide, sodium bromide, sodium valproate, stiripentol, sultiam, tiagabine, topiramate, valproic acid, vigabatrin, zonisamide, their salts, derivatives and mixtures thereof. 3. Use according to claim 1, characterized in that said food composition is formulated as a food composition, a food composition for pets or a food supplement.