NUTRITIONAL AND THERAPEUTIC SUPPLEMENT COMPOSITIONS

BACKGROUND OF THE INVENTION

REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent application 62/485,584, filed April 14, 2017, which are hereby incorporated by reference for all purposes as if fully set forth herein.

FIELD OF THE INVENTION

[0001] This invention relates generally to nutritional supplements and more specifically, to nutritional and therapeutic compositions for improving health, and treating and preventing disease in the digestive system.

BACKGROUND INFORMATION

[0002] Diseases in the digestive system can lead to malnutrition and deteriorated health. For example, gastroparesis is a condition in which one's stomach cannot empty itself of food in a normal fashion. It is caused by damage to the vagus nerve, which regulates the digestive system. A damaged vagus nerve prevents the muscles in the stomach and intestine from functioning, preventing food from moving through the digestive system properly. Often, the exact cause of gastroparesis is unknown. Possible causes can include uncontrolled diabetes, gastric surgery with injury to the vagus nerve, medications such as narcotics and some antidepressants, Parkinson's disease, multiple sclerosis, and rare conditions such as: amyloidosis (deposits of protein fibers in tissues and organs) and scleroderma (a connective tissue disorder that affects the skin, blood vessels, skeletal muscles, and internal organs).

[0003] Under normal circumstances, strong muscular contractions propel food through the digestive tracts. In gastroparesis, the stomach's motility works poorly or not at all, preventing the stomach from emptying properly. Gastroparesis can interfere with normal digestion, result in nausea and vomiting, and cause problems with blood sugar levels and nutrition. There is no cure for gastroparesis, but changes to one's diet, along with medication, can offer some relief. [0004] Symptoms relating to diseases in the digestive system such as

gastroparesis include but are not limited to vomiting, nausea, premature satiety (a feeling of fullness after eating just a few bites), abdominal bloating, abdominal pain, changes in blood sugar levels, lack of appetite and weight loss and malnutrition.

[0005] What is needed in the art are compositions that can provide the nutritional values to such patients while triggering few or no adverse effects.

[0006]

SUMMARY OF THE INVENTION

[0007] In one aspect, provided herein is a nutritional supplement, which may be in the form of a beverage. The supplement comprises a fluid base component accounting for about 15% to 30% of the total calories of the supplement; a protein component accounting for about 25% to 45% of the total calories of the supplement; a fat component accounting for about 15% to 50% of the total calories of the supplement; a carbohydrate component accounting for about 0% to 20% of the total calories of the supplement; and optionally one or more therapeutic additives.

[0008] In some embodiments, the nutritional supplement includes about 45% to 55% of the total calories of the supplement from fat, 15% to 25% of the total calories of the supplement from carbohydrates, and about 20% to 30% of the total calories of the supplement from protein.

[0009] In some embodiments, the supplement has an average caloric density of at least about 1.5 kcal per ml. In some embodiments, the supplement has an average caloric density of at least about 2.0 kcal per ml.

[0010] In some embodiments, the fluid base component is selected from the group consisting of a dairy-based beverage, an almond-based beverage, a coconut-based beverage, a grain-based beverage, a hazelnut-based beverage, a hemp-based beverage, a rice-based beverage, a soy-based beverage, and combinations thereof. In some embodiments, the grain- based beverage is selected from the group consisting of oat milk, spelt milk, rice milk, rye milk, einkorn wheat milk, quinoa milk and combinations thereof.

[0011] In some embodiments, the fluid base component accounts for about 20% to 25% of the total calories of the supplement.

[0012] In some embodiments, the protein component is selected from the group consisting of soy protein isolate, whey protein, casein protein, egg-white protein, hemp seed protein, rice protein, pea protein, and combinations thereof. [0013] In some embodiments, the protein component accounts for about 30% to 40% of the total calories of the supplement.

[0014] In some embodiments, the fat component is selected from the group consisting of almond oil coconut oil, canola oil, olive oil, palm oil, corn oil, cotton seed oil, grape seed oil, peanut oil, safflower oil, sunflower oil, sesame oil, soybean oil, pumpkin seed oil, watermelon seed oil, and combinations thereof.

[0015] In some embodiments, the fat component accounts for about 20% to 25% of the total calories of the nutritional and therapeutic supplement.

[0016] In some embodiments, the carbohydrate component is selected from the group consisting of com syrup, canned sugar, molasses, honey, glucose, fructose, sucrose, maltose, lactose, and combinations thereof.

[0017] In some embodiments, the fat component accounts for about 8% to 14% of the total calories of the nutritional and therapeutic supplement.

[0018] In some embodiments, the one or more therapeutic additives are selected from the group consisting of curcumin, ginger, soy protein isoflavones, glutamine, alpha lipoid acid, and combinations thereof.

[0019] In another aspect, provided herein is a method of treating gastroparesis, or a symptom thereof, in a subject. The method includes administering to the subject the nutritional supplement of the disclosure, thereby treating gastroparesis, or a symptom thereof, in the subj ect.

[0020] In embodiments, the symptom is one or more of vomiting, nausea, premature satiety, abdominal bloating, abdominal pain, fluctuations in blood sugar levels, lack of appetite, weight loss and malnutrition.

[0021] In some embodiments, the supplement is administered in a volume of between about 100 mL to 500 mL, for example, in a volume of about 100, 200, 300, 400 or 500 mL.

[0022] In some embodiments, the supplement is administered to the stomach or gastrointestinal tract of the subject, for example, via oral delivery.

[0023] In another aspect, provided herein is a kit which includes the nutritional supplement of the disclosure, instructions for administering the supplement to a subject, and optionally, a container. DETAILED DESCRIPTION OF THE INVENTION

[0024] Unless otherwise noted, terms are to be understood according to conventional usage by those of ordinary skill in the relevant art.

[0025] Provided herein are nutritional and therapeutic compositions for people suffering from diseases in the digestive system (e.g., gastroparesis). Ready-to-drink nutritional compositions are created to help provide patients living with digestive diseases (e.g., gastroparesis) and related disorders with sufficient nutrients in an effort to achieve optimal nutritional status and to alleviate symptoms related to their disease. In particular, provided herein are nutritional and therapeutic supplement compositions comprising major nutrients such as proteins, fat, carbohydrates, in addition to therapeutic additives. The therapeutic additives can reduce or eliminate symptoms relating to digestive diseases such as gastroparesis.

[0026] In one aspect, a composition provided herein is a nutritional and therapeutic supplement with sufficient caloric content to sustain the nutritional need of a patient while triggering few or no adverse symptoms in the patient.

[0027] In one aspect, a composition as disclosed herein is specifically designed for the unique needs of a patient who is unable to eat regular meals because of symptoms such as nausea, vomiting, fullness, early satiety or abdominal pain.

[0028] In another aspect, the unique properties of a composition as disclosed herein include natural ingredients that have anti-nausea, anti-inflammatory, and pro-motility effects on the digestive system.

[0029] In another aspect, a composition as disclosed herein comprises one or more nutritional components in addition to one or more therapeutic additives. In some embodiments, a nutritional component comprises a protein component, a fat component, a carbohydrate component, or combinations thereof. In some embodiments, a nutritional component comprises a protein component, a fat component, and a carbohydrate component. In some embodiments, the nutritional component further comprises one or more therapeutic additives that have anti-nausea, anti-inflammatory, and pro-motility effects on the digestive system.

[0030] In one aspect, the content of the nutritional and therapeutic composition disclosed herein is rich in calories. A calorically-dense composition is advantageous because it minimizes the volume that a patient has to consume, thus providing adequate nutrition while minimizing early satiety. [0031] In some embodiments, the caloric density of the nutritional and therapeutic composition is between about 1.5 kcal/ml to 3.5 kcal/ml; for example, about 1.5 kcal/ml or higher, about 1.6 kcal/ml or higher, about 1.7 kcal/ml or higher, about 1.8 kcal/ml or higher, about 1.9 kcal/ml or higher, about 2.0 kcal/ml or higher, about 2.1 kcal/ml or higher, about 2.2 kcal/ml or higher, about 2.3 kcal/ml or higher, about 2.4 kcal/ml or higher, about 2.5 kcal/ml or higher, about 2.6 kcal/ml or higher, about 2.7 kcal/ml or higher, about 2.8 kcal/ml or higher, about 2.9 kcal/ml or higher, about 3.0 kcal/ml or higher, about 3.1 kcal/ml or higher, about 3.2 kcal/ml or higher, about 3.4 kcal/ml or higher, or about 3.5 kcal/ml or higher. In some embodiment, the caloric density of the nutritional and therapeutic composition is higher than about 3.5 kcal/ml or higher; for example, at about 4.0 kcal/ml or higher, about 4.5 kcal/ml or higher, or even about 5.0 kcal/ml or higher. In some

embodiments, the caloric density of the nutritional and therapeutic composition is at least 2.0 kcal/ml.

[0032] In one aspect, the nutritional and therapeutic composition disclosed herein comprises a fluid base. The fluid base renders the entire composition drinkable. The fluid base may comprise nutrients such as protein, fat, carbohydrate, vitamin, ions and the like.

[0033] In some embodiments, the fluid base accounts for about 15% to 30% of the total calories of the entire composition. In some embodiments, the fluid base accounts for about 18% to 27% of the total calories of the entire composition. In some embodiments, the fluid base accounts for about 20% to 25% of the total calories of the entire composition. In some embodiments, the fluid base accounts for about 22% to 23% of the total calories of the entire composition.

[0034] In some embodiments, a concentrated fluid base is used to increase the caloric density of the fluid base. The concentration is increased, for example, by removing all or a portion of the water content from the fluid base.

[0035] In embodiments, all of the components may be in a dried powder form and combined to form a mixture. As such, in an embodiment, the supplement may be a dried powder composition to which fluid may be added for administration to a subject. Similarly, the mixture may be provided as a concentrated paste or spread.

[0036] In some embodiments, the fluid base can be one or more dairy-based beverages, one or more non-dairy based beverages, or a combination of one or more dairy- based and non-dairy based beverages. In some embodiments, dairy -based beverages results in adverse reactions from the digestive system especially for patients who are also lactose intolerant. In some embodiments, one or more non-dairy based beverages are used as the fluid base. Examples of non-diary based beverages include but are not limited to a nut-based beverage (e.g., an almond-based beverage, a hazelnut-based beverage or a coconut-based beverage), a grain-based beverage (e.g., a rice-based beverage), and a plant-based beverage such as hemp-based beverage, a soy -based beverage, or combinations thereof. More exemplary non-diary based beverages include but are not limited to almond milk, hazelnut milk, hemp milk, soy milk, rice milk, oat milk, spelt milk, rye milk, einkorn wheat milk, quinoa milk or combinations thereof. Advantageously, rice milk is hypoallergenic and triggers few adverse reaction in the digestive system.

[0037] In some embodiments, the fluid base is naturally or artificially flavored to render it palatable.

[0038] As disclosed herein, the nutritional and therapeutic composition comprises components from the major nutritional groups (protein, fat, carbohydrate, and etc.)

[0039] In one aspect, the nutritional and therapeutic composition disclosed herein comprises a protein component. The protein component is the primary source of protein in the supplement, however, it may contain additional nutrients such as fat, carbohydrate, vitamin, ions and the like, but in smaller quantity.

[0040] In some embodiments, the protein component accounts for about 25% to 45% of the total calories of the nutritional and therapeutic composition. In some

embodiments, the protein component accounts for about 30% to 40% of the total calories of the nutritional and therapeutic composition. In some embodiments, the protein component accounts for about 30% to 35% of the total calories of the nutritional and therapeutic composition. In some embodiments, the protein component accounts for about 40% to 45% of the total calories of the nutritional and therapeutic composition. Here, the caloric count includes contribution from non-protein nutrients in the protein component.

[0041] As disclosed herein, the protein component comprises one or more animal- based protein, one or more non-animal based protein, or combinations thereof. Exemplary protein components include but are not limited to soy protein isolate, whey protein, casein protein, egg-white protein, hemp seed protein, rice protein, pea protein, or combinations thereof.

[0042] In some embodiments, the protein component is soluble in the fluid base. In some embodiments, the protein component comprises fine powder that forms a smooth suspension in the fluid base. In some embodiments, when protein powder is used, the powder can be added at a quantity between about 10 to 100 grams, about 10 to 90 grams, about 10 to 80 grams, about 10 to 70 grams, about 10 to 60 grams, about 10 to 50 grams, 10 to 40 grams, about 10 to 30 grams or about 10 to 20 grams. For example, for an 8-ounce beverage, between about 25 grams and 65 grams of soy protein isolate powder can be added.

[0043] In one aspect, the nutritional and therapeutic composition disclosed herein comprises a fat component. The fat component is the primary source of protein in the supplement, however, it may contain additional nutrients such as protein, carbohydrate, vitamin, ions and the like.

[0044] In some embodiments, the fat component accounts for about 15% to 50% of the total calories of the nutritional and therapeutic composition. In some embodiments, the fat component accounts for about 20% to 30% of the total calories of the nutritional and therapeutic composition. In some embodiments, the fat component accounts for about 30% to 40% of the total calories of the nutritional and therapeutic composition. In some embodiments, the fat component accounts for about 30% to 50% of the total calories of the nutritional and therapeutic composition. In some embodiments, the fat component accounts for about 40% to 50% of the total calories of the nutritional and therapeutic composition. Here, the caloric count includes contribution from non-fat nutrients in the fat component. Exemplary fat component comprises but is not limited to an acai oil, a black seed oil, a blackcurrant seed oil, a borage seed oil, a flaxseed oil, a carob pod oil, an amaranth oil, apricot oil, an apple seed oil, an argan oil, an avocado oil, a babassu oil, a ben oil, a bomeo tallow nut oil, a cape chestnut oil, a cocoa butter, a cocklebur oil, a cohune oil, a coriander seed oil, a date seed oil, a dika oil, a false flax oil, a grape seed oil, a hemp oil, a kapok seed oil, a kenaf seed oil, a lallemantia oil, a mafura oil, a marula oil, a meadowfoam seed oil, a mustard oil, a niger seed oil, a poppyseed oil, a nutmeg butter, an okra seed oil, a papaya seed oil, a perilla seed oil, a persimmon seed oil, a pequi oil, a pili nut oil, a pomegranate seed oil, a pracaxi oil, a pracachy virgim oil, a prune kernel oil, a quinoa oil, ramtil oil, a rice bran oil, a royle oil, a sacha inchi oil, a sapote oil, seje oil, a taramira oil, a tea seed oil (camellia oil), a thistle oil, a tigernut oil (or nut-sedge oil), a tobacco seed oil, a tomato seed oil, a wheat germ oil, and combinations thereof.

[0045] As disclosed herein, the fat component is preferably in a liquid form. However, a fat component in dissolvable butter or solid form can also be used. For example, the fat component can be a major cooking or edible oil, a nut-based oil, a citrus-based oil, an oil from melon and gourd seeds, a food supplement oil, and other edible oils. In some embodiments, a blend of multiple oils is used as the fat component.

[0046] In one aspect, the nutritional and therapeutic composition disclosed herein comprises a carbohydrate component. The carbohydrate component is the primary source of protein in the supplement, however, it may contain additional nutrients such as protein, fat, vitamin, ions and the like.

[0047] In some embodiments, the carbohydrate component accounts for about 0% to 20% of the total calories of the nutritional and therapeutic composition. In some embodiments, the carbohydrate component accounts for about 5% to 15% of the total calories of the nutritional and therapeutic composition. In some embodiments, the carbohydrate component accounts for about 8% to 12% of the total calories of the nutritional and therapeutic composition. In some embodiments, the carbohydrate component accounts for about 10% to 15% of the total calories of the nutritional and therapeutic composition. In some embodiments, the carbohydrate component accounts for about 15% to 20% of the total calories of the nutritional and therapeutic composition. For example, a patient with diabetic tendency will be given a composition with less carbohydrate (e.g., sugar) content. Here, the caloric count includes contribution from non-carbohydrate nutrients in the fat component.

[0048] Exemplary carbohydrate components include but are not limited to corn syrup, canned sugar, molasses, honey, glucose, fructose, sucrose, maltose, lactose, and combinations thereof.

[0049] As disclosed herein, the carbohydrate component is preferably in a liquid form; for example, as a syrup such as honey, corn syrup or molasses. However, a carbohydrate component in dissolvable butter or solid form can also be used.

[0050] Advantageously, the calorically-dense composition is palatable and has a pleasant flavor. In some embodiments, the flavor of the composition comes from each individual component; for example, when rice milk is used as the fluid base, it is added with a vanilla flavor for palatability. In some embodiments, a particular component itself has a flavor. For example, coconut oil has a pleasant flavor and can be used to promote palatability. Any component as disclosed herein, when applicable, can be flavored with food flavors such as vanilla, chocolate, citrus, and etc.

[0051] As disclosed herein, a component in the nutritional and therapeutic supplement can comprises multiple nutrients (e.g., protein, fat, carbohydrate, and etc.).

Alternatively, the overall composition of a nutritional and therapeutic supplement disclosed herein can also be evaluated based on individual nutrients. In such cases, the total caloric count will be considered to mainly come from protein, fat and carbohydrate.

[0052] In some embodiments, the protein content in a nutritional and therapeutic supplement as disclosed herein accounts for between about 20% to 50% of the total calories, preferably about 30%. In some embodiments, the fat content in a nutritional and therapeutic supplement as disclosed herein accounts for between about 20% to 60% of the total calories, preferably about 30%, 40% or 50%. In some embodiments, the carbohydrate content in a nutritional and therapeutic supplement as disclosed herein accounts for between about 20% to 50% of the total calories, preferably about 20% or 30%. In some embodiments, the nutrient content in the nutritional and therapeutic supplement is managed to provide balanced nutrition to a patient. In some embodiments, a particular nutrient content in the nutritional and therapeutic supplement can have a higher amount based on the patient's nutritional needs.

[0053] In some embodiments, the nutritional supplement includes about 45% to 55% of the total calories of the supplement from fat, about 15% to 25% of the total calories of the supplement from carbohydrates, and about 20% to 30% of the total calories of the supplement from protein.

[0054] In some embodiments, the nutritional supplement includes about 48% to 52% of the total calories of the supplement from fat, about 18% to 23% of the total calories of the supplement from carbohydrates, and about 24% to 28% of the total calories of the supplement from protein.

[0055] In some embodiments, the nutritional supplement includes about 50% of the total calories of the supplement from fat, about 21% to 22% of the total calories of the supplement from carbohydrates, and about 26% to 27% of the total calories of the supplement from protein.

[0056] In one aspect, one or more optional therapeutic additives are added to a nutritional and therapeutic composition disclosed herein to promote therapeutic effects, for example to overcome the symptoms of nausea, vomiting, fullness, early satiety or abdominal pain.

[0057] Exemplary therapeutic additives include but are not limited to curcumin, ginger, soy protein isoflavones, glutamine, alpha lipoid acid, and combinations thereof.

[0058] In some embodiments, the therapeutic additive is an antiemetic (e.g., antinausea) agent. In one embodiment, the antiemetic agent is ginger. Examples of

useful antiemetic agents include, but are not limited to, aprepitant, dronabinol, perphenazine, palonosetron, trimethyobenzamide, metoclopromide, domperidone, prochlorperazine, promethazine, chlorpromazine, trimethobenzamide, ondansetron, granisetron, hydroxyzine, acetylleucine monoethanolamine, alizapride, azasetron, benzquinamide, bietanautine, bromopride, buclizine, clebopride, cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone, oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol, thiethylperazine, thioproperazine, tropisetron, droperidol, haloperidol, prochloperazine, metoclopramide, diphenhydramine, cannabis, midazolam, lorazepam, hyoscine, dexamethasone, emetrol, propofol, ginger, peppermint, muscimol, ajwain and mixtures thereof.

[0059] A therapeutic additive can be added in any form, for example, as a ground powder, an exact powder, or an extract liquid. As disclosed herein, a therapeutic additive is added in a quantity much smaller to that of the fluid based, protein component, fat component, or carbohydrate component. Additionally, caloric content from a therapeutic additive is considered minimum and not counted as a part of the total caloric content.

[0060] In some embodiments, about or less than a tea spoon of a therapeutic additive is added; for example, ginger in ground form can added at a quantity between a quarter teaspoon to a teaspoon. In some embodiments, about or less than one gram of a therapeutic additive is added; for example, soy isoflavone concentrate can be added at a quantity between about 50 mg to 500 mg, turmeric curcumin can be added at a quantity between about 250 mg to 1 ,000 mg, and/or ginger can be added at a quantity between about 250 mg to 1,000 mg. In one embodiment, the supplement includes about 550 mg ginger, 500 mg turmeric curcumin and 100 mg soy isoflavones.

[0061] In specific embodiments of the present invention, the foregoing components are present in particular ratios. A number of formulations may be prepared in accord with the present invention shown in the Tables below which lists compositional ranges for such formulations.

[0062] Table 1: Formulation Component Ranges

[0063] Table 2: Formulation Component Ranges

[0064] In an embodiment, the fluid base component is rice milk, the protein component is soy protein isolate, and the fat component is coconut having ranges as shown in Table 3.

[0065] Table 3: Formulation Component Ranges

[0066] Formulations based upon the ratios set forth in the Tables may further include therapeutic additives and ancillary ingredients such as preservatives, fragrances, coloring agents, viscosity control agents and the like.

[0067] In another aspect, provided herein is a method of treating gastroparesis, or a symptom thereof, in a subject. The method includes administering to the subject the nutritional supplement of the disclosure, thereby treating gastroparesis, or a symptom thereof, in the subject.

[0068] In some embodiments, the formulations of the invention are intended to be administered to the stomach or gastrointestinal tract, for example by oral delivery. As used herein, the terms "administration" or "administering" are defined to include an act of providing a supplement of the invention to a subject in need of treatment, preferably via the oral route. As such, in embodiments, the supplement is formulated for oral administration, such as in the form of a liquid, paste, gel, and the like. In one embodiment, the supplement is formulated in a concentrated form, such as a dried powder, to which fluid may be added to allow for oral administration.

[0069] As used herein, the term "ameliorating" or "treating" means that the clinical signs and/or the symptoms associated with gastroparesis are lessened as a result of the actions performed. A "symptom" relating to diseases in the digestive system such as gastroparesis include but are not limited to vomiting, nausea, premature satiety (a feeling of fullness after eating just a few bites), abdominal bloating, abdominal pain, changes in blood sugar levels, lack of appetite and weight loss and malnutrition.

[0070] As used herein, the term "subject" refers to a mammalian subject. As such, treatment of psoriasis of any animal in the order mammalian is envisioned. Such animals include, but are not limited to horses, cats, dogs, rabbits, mice, goats, sheep, non- human primates and humans. Thus, the method of the present disclosure is contemplated for use in veterinary applications as well as human use.

[0071] The term "therapeutically effective amount" or "effective amount" means the amount of a composition that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by the researcher, veterinarian, medical doctor or other clinician.

[0072] The formulations of the present invention can be prepared using well known methods by those having ordinary skill in the art, e.g., by mixing the recited components in the proper amounts. The components for inclusion in a formulation are generally commercially available.

[0073] The total amount of formulation to be administered in practicing a method of the invention can be administered to a subject as a single dose, for example by bolus or ingestion over a relatively short period of time. One skilled in the art would know that the amount of formulation depends on many factors including the age and general health of the subject as well as the route of administration and the number of treatments to be

administered. In view of these factors, the skilled artisan would adjust the particular dose as necessary. In general, the formulation of the pharmaceutical composition and the routes and frequency of administration are determined, initially, using Phase I and Phase II clinical trials.

[0074] In some embodiments, the supplement is administered in a volume of between about 100 mL to 500 mL, for example, in a volume of about 100, 200, 300, 400 or 500 mL over a relatively short amount of time, for example, less than 60, 50, 40, 30, 20, 10, or 5 minutes. The formulation may be administered at least once daily, or 2, 3, 4, 5 or more times daily depending on the needs of the subject. In some embodiments, the treatment regimen may be for months (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months), or years so long as gastroparesis, or symptoms thereof, are present. Further, the supplement may be administered prophylactically to prevent disease or symptoms thereof.

[0075] In another aspect, provided herein is a kit which includes the nutritional supplement of the disclosure, instructions for administering the supplement to a subject, and optionally, a container.

[0076] In some embodiments, a kit includes instructional materials disclosing, for example, means of use of the supplement of the invention. The instructional materials may be written, in an electronic form (e.g., computer diskette or compact disk) or may be visual (e.g., video files). The kits may also include additional components to facilitate the particular application for which the kit is designed. Thus, for example, the kit can include mixing containers, tools for measuring and mixing and other components routinely used for the practice of a particular disclosed method. Such kits and appropriate contents are well known to those of skill in the art.

[0077] Certain kit embodiments can include a carrier means, such as a box, a bag, a satchel, plastic carton (such as molded plastic or other clear packaging), wrapper (such as, a sealed or sealable plastic, paper, or metallic wrapper), or other container. In some examples, kit components will be enclosed in a single packaging unit, such as a box or other container, which packaging unit may have compartments into which one or more components of the kit can be placed.

[0078] The kits can further include software. Software may include a training video that may provide additional support including demonstration of administration and use, examples of results, or educational materials for performing the method according to the invention.

[0079] Having described the invention in detail, it will be apparent that modifications, variations, and equivalent embodiments are possible without departing the scope of the invention defined in the appended claims. Furthermore, it should be appreciated that all examples in the present disclosure are provided as non-limiting examples.

EXAMPLES

[0080] The following non-limiting examples are provided to further illustrate embodiments of the invention disclosed herein. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent approaches that have been found to function well in the practice of the invention, and thus can be considered to constitute examples of modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments that are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

EXAMPLE 1

FORMULA TION OF NUTRITIONAL SUPPLEMENT

[0081] In this example, a formulation for an 8-ounce supplement is provided as set forth in Table 4.

[0082] Table 4: Nutritional Supplement Formulation

[0083] Mixing Instructions

[0084] Pour rice milk into shaker bottle up to the 8 ounce line.

[0085] Add 2 tablespoons coconut oil.

[0086] Open and empty contents of 1 sachet into bottle.

[0087] Recap lid and shake vigorously for at least 10 seconds.

[0088] Serve over ice if desired.

[0089] Store leftovers in the refrigerator and discard after 24 hours. EXAMPLE 2

VARIA TIONS IN INDIVIDUAL COMPONENTS OF FORMULA TION

[0090] In this example, variations were made in connection with the formulation provided in Example 1. In particular, the quantities for rice milk, corn syrup, coconut oil, vanilla soy protein isolate powder, and various therapeutic additives were varied to explore acceptable ranges.

[0091] Table 5: Nutritional Supplement Formulation Variations

EXAMPLE 3

PALA TABILITY STUDY OF NUTRITIONAL SUPPLEMENT

[0092] In this example, a palatability study is disclosed which will test the palatability of a nutritional supplement formulation of the invention in connection with the treatment of gastroparesis.

[0093] Gastroparesis is a chronic, morbid and costly neuromuscular disorder of the stomach characterized by delayed gastric emptying in the absence of gross structural abnormalities. The periprandial symptoms associated with this disease can preclude adequate oral intake and often lead to weight loss and nutritional deficiencies. Intriguingly, these manifestations are partially due to impaired gastric accommodation of large volume meals and lagged transfer of mainly solid food boluses into the duodenum. Consequently, it is hypothesized that dietary supplementation with a low volume, hypercaloric, nutritional supplement as described herein can help prevent malnutrition, decrease symptom burden and improve health-related quality of life in this population. Due to the paucity of such a supplement, a novel nutritional supplement was developed specifically designed to maximize tolerability in patients with gastroparesis. The palatability of the nutritional supplement will be optimized using feedback from healthy volunteers.

[0094] The symptomatology of gastroparesis commonly includes nausea, vomiting, abdominal distention, postprandial fullness and early satiety. The frequent correlation between meal consumption and symptom exacerbation can lead patients to develop food aversion. Not surprisingly, the available literature suggests that to some degree, the diets of most gastroparesis patients lack adequate amounts of calories, protein, carbohydrates, vitamins and minerals. Moreover, consumption of these hypocaloric diets has been directly associated with the prevalence of postprandial symptoms. Lastly, it is also apparent that a significant proportion of these patients are unable to follow the current dietary recommendations of frequent, low-volume, hypercaloric, liquid meals. Reasons for noncompliance are unknown but probably include the logistical complexity of the aforementioned diet. Therefore, it is also speculated that developing a convenient formulation might also improve compliance with dietary recommendations.

[0095] Currently available nutritional drinks are not ideal for gastroparesis patients. This is mostly due to the large volumes (> 300ml) that need to be ingested in order to meet caloric goals. Furthermore, many formulations contain generous amounts of carbohydrates, which are not appropriate for the subset of patients with diabetic gastroparesis. [0096] Study procedures.

[0097] The study will be a single-dose, open-label, non-randomized, no placebo- controlled, palatability trial. A total of 10 volunteers will be recruited from the Johns Hopkins Medical Campus through IRB- approved flyers (included in the eIRB application), which will ask volunteers to contact the study team through a telephone call. During this call, a study nurse will use an IRB-approved script (included in the eIRB application) to provide an overview of the study. Additionally, she will explain that in order to participate in the study, participants will be asked not to eat or drink anything except water from 11 :59 pm on the evening preceding their study visit up until the moment they consume the nutritional drink. If the volunteer still wishes to participate, oral consent for eligibility screening will be obtained. If the volunteer meets basic eligibility criteria, the research nurse will obtain oral consent for pre-study visit fasting and will schedule a study visit at the volunteer's earliest convenience. The contact and screening information of volunteers that are successfully recruited through the telephone call will be documented, placed in the participant's study folder and stored in a locked cabinet in a research unit. Any information documented during the telephone screening process for volunteers who do not meet basic eligibility criteria or do not wish to participate will be immediately destroyed. If the volunteer initiated phone call is disconnected unexpectedly, the research nurses will not attempt to call the volunteer and will wait for the volunteer to call back. If after the call is disconnected the volunteer does not call back, no identifiable private information will be documented.

[0098] Upon arrival to the study visit, one of the research nurses will obtain informed consent for the rest of the study protocol described below. After consent is documented, participants will be asked to consume 300 ml of the nutritional supplement (Table 3) within a period of 30 minutes. Participants will be allowed to consume water as desired during and after the ingestion of the nutritional supplement. After consuming the maximum tolerated volume of the nutritional supplement, participants will be asked to complete by hand a palatability questionnaire. Participants will then be asked to remain under observation for 1 hour after ingesting the nutritional supplement in order to monitor them for the development of adverse events. In order to prevent confounding, they will be asked not to consume any other liquid or solid meals (only water) during the 6-hour period after consuming the nutritional supplement. A 6 hour period was chosen because it usually takes approximately 6 to 8 hours for a meal to pass through the stomach and small intestine. After this period of 6 hours, participants will be allowed to resume their regular diet. [0099] Before leaving the research unit, participants will be provided with a phone number to report adverse events during the 24 hours after consuming the dietary supplement. Study personnel will call participants 24 hours after consuming the nutritional supplement to assess for adverse events. After this final call, the participants will be administratively censored from the study.

[00100] Study duration and number of study visits required of research participants.

[00101] Each participant will be required to attend only one study visit. The study visit is expected to last approximately 2 hours in order to provide adequate time for the informed consent process.

[00102] Exclusion criteria.

[00103] The following individuals well be excluded from the study.

[00104] 1) Presently suffering from a gastrointestinal disorder (including gastroparesis, gastric reflux disease, dyspepsia, inflammatory bowel disease, irritable bowel syndrome, Celiac disease, non-celiac gluten sensitivity or gluten allergy).

[00105] 2) Self-reported past medical history of neuromuscular disorders

[00106] 3) Currently taking medications that affect gastric motility (including anticholinergic medications, narcotics, and benzodiazepines).

[00107] 4) Allergic to any of the ingredients of the nutritional supplement.

[00108] Current pregnancy.

[00109] Type I or Type 2 Diabetes mellitus.

[00110] Formulation

[00111] The ingredients for the nutritional supplement will be packaged and dispensed by the ICTR Nutrition Research nurses. The supplement will be prepared by pouring 240 ml of rice milk and 2 tablespoons of coconut oil into a shaker bottle. A plastic sachet containing approximately 85 grams of the premixed dry ingredients will be emptied into the shaker bottle. The bottle will then be recapped and shaken vigorously for at least 10 seconds. This process will yield a total of approximately 300 ml of the nutritional supplement, which will provide a total of 587 Kcal (1.96 Kcal/ml) of which 50.3% come from fat, 21.5% comes from carbohydrates and 26.5% from protein. Table 6 outlines the ingredients and nutritional value of the nutritional supplement. [00112] Table 6: Nutritional Supplement Formulation

[00113] Rationale for use of formulation.

[00114] In a hallmark study in gastroparesis, investigators performed gastric barostat studies on 58 patients to determine the role of proximal stomach dysfunction in the disorder. The study found that on average, gastroparesis patients perceive gastric distention at around 300 ml of volume and experience significant discomfort at > 500 ml. Therefore, many gastroparesis diet are based on frequent, < 300 ml meals. A meal size of 300 ml was chosen in order to minimize symptom generation. A liquid consistency was chosen because a recent randomized control trial determined that a small particle size diet reduces symptoms in gastroparesis patients. Ingredients that have been shown to provoke symptoms in gastroparesis patients was avoided. Furthermore, foods that had scientific evidence of improving symptoms of gastroparesis were included. Curcumin has been shown to increase gastric emptying in rats with streptozotocin-induced gastroparesis. Soy isoflavones have been shown to improve gastric emptying in type 2 diabetic patients with gastroparesis.

Ginger, in turn, is generally considered to have antiemetic properties.

[00115] Study statistics.

[00116] Primary outcome variable is palatability of nutritional supplement

[00117] Secondary outcome variables include safety and tolerability of nutritional supplement.

[00118] Statistical plan including sample size justification and interim data analysis is as follows. Inferential hypothesis testing will not be performed. Descriptive statistics will be used for the analysis of the measurements obtained from the palatability questionnaire. The means and standard deviations of the answers to each item in 10 questionnaires will be determined. Safety will be determined by the incidence of adverse events in the 24-hour period following ingestion of the nutritional supplement. Adverse events will be documented using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Furthermore, the proportion of each type of adverse event and each grade of adverse event will be calculated as described in the CTCAE (version 4.0). Tolerability will be determined by calculating the mean maximum volume of the nutritional supplement that was consumed by the participants. No interim data analysis will be performed.

EXAMPLE 4

EXEMPLARY VARIATIONS IN INDIVIDUAL COMPONENTS OF

FORMULATION

[00119] In this example, variations were made in connection with the formulation provided in Example 1.

[00120] Table 7: Nutritional Supplement Formulation Variations

[00121] Recipe Experimentation (5 ml = 1 tsp; 15 ml = 1 tbsp)

[00122] The various methods and techniques described above provide a number of ways to carry out the invention. Of course, it is to be understood that not necessarily all objectives or advantages described may be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the methods can be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as may be taught or suggested herein. A variety of advantageous and disadvantageous alternatives are mentioned herein. It is to be understood that some preferred embodiments specifically include one, another, or several advantageous features, while others specifically exclude one, another, or several disadvantageous features, while still others specifically mitigate a present disadvantageous feature by inclusion of one, another, or several advantageous features.

[00123] Furthermore, the skilled artisan will recognize the applicability of various features from different embodiments. Similarly, the various elements, features and steps discussed above, as well as other known equivalents for each such element, feature or step, can be mixed and matched by one of ordinary skill in this art to perform methods in accordance with principles described herein. Among the various elements, features, and steps some will be specifically included and others specifically excluded in diverse embodiments.

[00124] Although the invention has been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that the embodiments of the invention extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses and modifications and equivalents thereof.

[00125] Many variations and alternative elements have been disclosed in embodiments of the present invention. Still further variations and alternate elements will be apparent to one of skill in the art.

[00126] In some embodiments, the numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term "about." Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some

embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements. [00127] In some embodiments, the terms "a" and "an" and "the" and similar references used in the context of describing a particular embodiment of the invention (especially in the context of certain of the following claims) can be construed to cover both the singular and the plural. The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. "such as") provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[00128] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[00129] Furthermore, numerous references have been made to patents and printed publications throughout this specification. Each of the above cited references and printed publications are herein individually incorporated by reference in their entirety.

[00130] In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other

modifications that can be employed can be within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention can be utilized in accordance with the teachings herein. Accordingly, embodiments of the present invention are not limited to that precisely as shown and described.

[00131] Although the invention has been described with reference to the above example, it will be understood that modifications and variations are encompassed within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims.