Edible compositions for use in dysphagia patients

Abstract

Edible foods which include a selection food and provided in a form that improves swallowing in the subject are provided. The compositions include an effective combination of foods that function as TRP agonists, to provide improve swallowing in a subject in need thereof. In some forms, the compositions include: (a) hydrocolloid such as gelatin and (b) liquid juice (preferably including electrolytes) / soup component, optionally in combination with one or more additional ingredients selected from (c) a spice, (d) sweetening agent, (e) an oil, (f) a flavoring acid, (g) cocoa and (h) a pepper.

Description

[0001] ATTORNEY DOCKET NO. CMCC 4482 PCT

[0002] EDIBLE COMPOSITIONS AND METHODS OF USE THEREOF FOR HYDRATION

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to U. S. Provisional Application No. 63 / 724,035, filed November 22, 2024, the entire content of which is hereby incorporated herein by reference for all purposes in its entirety.

[0004] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0005] This invention was made with government support under DK097112 and DK133679, awarded by The National Institutes of Health. The government has certain rights in the invention.

[0006] FIELD OF THE INVENTION

[0007] The disclosed invention is generally in the field of swallowing dysfunction and specifically in the area of compositions of materials to hydrate, nourish and improve swallowing function in the setting of swallowing dysfunction.

[0008] BACKGROUND OF THE INVENTION

[0009] Swallowing problems in humans include difficulty in swallowing, inability to swallow, and discomfort in swallowing. These problems are collectively termed dysphagia. Dysphagia is a common unfortunate secondary condition that accompanies (i.e., is concomitant with) many primary human disease states such as prematurity, cerebral palsy, genetic syndromes, Trisomy 21, neonatal swallowing dysfunction, laryngeal clefts, chiari malformations, spina bifida, blunt throat injury, surgery caused impairment, stroke, multiple sclerosis, Asperger’s syndrome, esophageal cancer, laryngeal cancer, chagas disease, celiac, cystic fibrosis, Huntington's disease, Niemann-Pick disease, neurological conditions such as amyotrophic lateral sclerosis, Alzheimer’s and Parkinson's disease, obesity, Riley-Day syndrome, high cholesterol, food allergies, scleroderma, and diabetes.

[0010] Dysphagia is pervasive, as between about five and about fifteen million people in the United States suffer from dysphagia. People with dysphagia generally lack proper muscle control and coordination to properly seal the windpipe or they lack the ability to properly propel the entire bolus of food and / or beverage to the stomach. If this condition goes unnoticed, sufferers are prone to foodstuff and beverages going into the sufferer's lungs rather than being routed properly to their stomach. When routing to the lungs occurs, the patient sufferer is at increased risk for growing unhealthy bacteria in the lungs which raises the prospect of aspiration 45803511.1 1 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0011] pneumonia (with its accompanying attendant risks and hospitalization), bronchiectasis, pneumonitis, and / or even fatal asphyxiation.

[0012] Despite advances in the technology of food administration to patients, it is highly desired to have a composition which can be effectively administered to alleviate at least one of difficulty in swallowing, inability to swallow, and discomfort in swallowing, to a dysphagic patient, especially for the pediatric population. A child with dysphagia may have trouble swallowing food or liquids, including saliva. The child may also experience pain while swallowing. It is difficult for a child with a swallowing disorder to get the correct amount of nutrients into their body, which can affect the child’s ability to stay hydrate, grow and gain weight.

[0013] There remains a need for edible compositions for treating dysphagia, especially in children in order for them to stay hydrated and nourished on a regular basis, and when they are sick

[0014] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each claim of this application.

[0015] BRIEF SUMMARY OF THE INVENTION

[0016] Edible food products which include a selection of foods and provided in a form that improves swallowing in the subject, are provided. Compositions for preparing the disclosed edible food products are also disclosed.

[0017] The compositions include an effective combination of high viscosity foods that also function as Transient Receptor Potential (TRP) agonists, to provide improved swallowing in a subject in need thereof.

[0018] In some forms, the compositions include: (a) hydrocolloid such as gelatin and (b) liquid juice (preferably including electrolytes) / soup component, optionally in combination with one or more additional ingredients selected from (c) a spice, (d) sweetening agent, (e) an oil, (f) a flavoring acid, (g) cocoa and (h) a pepper.

[0019] In some forms, the composition is a semi-solid, meaning it holds its shape but can still slightly jiggle when moved, preferably, having the consistency of a viscous gel, achieving at minimum viscosity equivalent of IDDSI class 4 (extremely thick) or higher. The composition can in some forms, have a viscosity >2000 centipoise, >3000, >4000, >5000 centipoise.

[0020] 45803511.1 2 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0021] In some forms, the hydrocolloid component is selected from the group consisting of agar, fish gelatin, beef gelatin, pectin, konjac, carrageenan or any other gelling agents such as starch, locust bean gum, gum arabic, gum karaya, and gum tragacanth.

[0022] Gelatine is a protein derived from collagen, primarily bovine or porcine in origin. Pectin is a galactomannan hydrocolloid obtained from fruit, typically by extraction of citrus peels or apple pomace. Agar (also referred to as agar agar) is a galactose polymer extracted from red algae which forms a firm gel at low concentrations of around 0.1 to 0.5 wt.%.

[0023] In some forms, the liquid juice component is selected from the group consisting of mango juice, peach juice, orange juice, grapefruit juice, grape juice, prune juice, cherry juice, pear juice or combination of fruit / vegetable juice. In some forms, the liquid soup component is selected from the group consisting of miso soup bone broth, chicken broth and beef broth.

[0024] In some forms, the spice is ginger. In these forms, the ginger can be powdered ginger, crystallized ginger, pressed fresh ginger (pulp or juice).

[0025] In some forms the spice can be turmeric, powder or pressed.

[0026] In some forms the spice can be selected from the group consisting of cinnamon cloves, cardamom, and curry powder.

[0027] In some forms, the pepper is provided in the form of a hot sauce, cayenne pepper or black pepper.

[0028] The disclosed compositions are used to provide hydration to a subject in need thereof, for example, a subject diagnosed with dysphagia. In preferred embodiments, the subject is a child needing an International Dysphagia Diet Standardization Initiative (IDDSI) level 4 or higher meaning that the nutraceutical is of a high viscosity which further helps to improve swallow function

[0029] Additional advantages of the disclosed method and compositions will be set forth in part in the description which follows, and in part will be understood from the description, or can be learned by practice of the disclosed method and compositions. The advantages of the disclosed method and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.

[0030] 45803511.1 3 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0031] BRIEF DESCRIPTION OF THE DRAWING

[0032] The accompanying drawing illustrates several embodiments of the disclosed method and compositions and, together with the description, serve to explain the principles of the disclosed method and compositions.

[0033] FIG 1. shows the IDDSI Framework (reproduced from https: / / iddsi.org / framework / IDDSI-framework).

[0034] DETAILED DESCRIPTION OF THE INVENTION

[0035] The disclosed method and compositions can be understood more readily by reference to the following detailed description of particular embodiments and the Example included therein and to the Figures and their previous and following description.

[0036] Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. Thus, values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (c.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. All parameter ranges disclosed include the endpoints and all values in between, unless otherwise specified.

[0037] It is to be understood that the disclosed method and compositions are not limited to specific synthetic methods, specific analytical techniques, or to particular reagents unless otherwise specified, and, as such, can vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0038] A. DEFINITIONS

[0039] The term ‘hydrocolloid’ is commonly used to describe a group of water-soluble naturally occurring polymers found abundantly in nature. They have evolved to perform many different functions, e.g. act as structural agents and energy reserves in plants and animals, to facilitate cell recognition and adhesion processes, to provide lubrication in bone joints, to act as ion exchangers and blood anticoagulants. Their key function in food products is to control texture and organoleptic properties mainly by enhancing the viscosity and gel characteristics.

[0040] 45803511.1 4 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0041] Use of the term “about” is intended to describe values either above or below the stated value in a range of approx. + / - 10%; in other forms the values may range in value either above or below the stated value in a range of approx. + / - 5%; in other forms the values may range in value either above or below the stated value in a range of approx. + / - 2%; in other forms the values may range in value either above or below the stated value in a range of approx. + / - 1%. The preceding ranges are intended to be made clear by context, and no further limitation is implied.

[0042] The terms “a,” “an,” or “the” are used to include one or more than one unless the context clearly dictates otherwise. The term “or” is used to refer to a nonexclusive “or” unless otherwise indicated.

[0043] The term “for example,” “for instance,” “such as,” or “including” as used herein is meant to introduce examples that further clarify more general subject matter. Unless otherwise specified, these examples are provided only as an aid for understanding the applications illustrated in the present disclosure and are not meant to be limiting in any fashion.

[0044] B. COMPOSITION

[0045] The disclosed compositions are edible and include a selection of foods provided in a form that improves swallowing in the subject.

[0046] The compositions include an effective combination of foods that function as TRP agonists, to provide improve swallowing in a subject in need thereof.

[0047] In some forms, the compositions include: (a) a gel-forming agent for example, a hydrocolloid such as gelatin and (b) liquid juice (preferably including electrolytes) / a soup component, optionally in combination with one or more additional ingredients selected from (c) a spice, (d) sweetening agent, (e) an oil, (f) a flavoring acid, (g) cocoa and (h) a pepper.

[0048] 1. Hydrocolloid

[0049] The term hydrocolloid encompasses a large group of polysaccharides and proteins that go into solution in water as colloids and demonstrate a high propensity for forming gels.

[0050] Hydrocolloids are a heterogeneous group of long chain polymers (polysaccharides and proteins) characterized by their property of forming viscous dispersions and / or gels when dispersed in water. Presence of a large number of hydroxyl (-OH) groups markedly increases their affinity for binding water molecules rendering them hydrophilic compounds. Further, they produce a dispersion, which is intermediate between a true solution and a suspension, and exhibits the properties of a colloid. Considering these two properties, they are aptly termed as ‘hydrophilic colloids’ or ‘hydrocolloids’. While all hydrocolloids thicken and impart stickiness to aqueous dispersions, a few biopolymers also have another major property of being able to form gels. Gel 45803511.1 5 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0051] formation is the phenomenon involving the association or cross-linking of the polymer chains to form a three dimensional network that traps or immobilizes the water within it to form a rigid structure that is resistant to flow. In other words, it becomes viscoelastic exhibiting both characteristics of a liquid and a solid.

[0052] Gels may also be defined as a form of matter intermediate between solid and liquid and show mechanical rigidity (Aguilera 1992). They consist of polymer molecules cross-linked to form tangled and interconnected molecular network immersed in a liquid medium, which in food system is water. Food technologists use the word ‘gel’ for high moisture foods that more or less retain their shape when released from their container. However, the most commonly used definition of gel is a rheological one, obtained from dynamic viscometry. According to this definition, a gel is a viscoelastic system with a ‘storage modulus’ (G') larger than the ‘loss modulus’ (G"). Hydrocolloids form gels by physical association of their polymer chains through hydrogen bonding, hydrophobic association and cation mediated cross-linking and differ from synthetic polymer gels, which normally consist of covalently cross-linked polymer chains.

[0053] Hence, hydrocolloid gels are often referred to as “physical gels” (reviewed in Saha, et al., J Food Sci Technol. 2010;47(6):587-597).

[0054] In some forms, the hydrocolloid component is selected from the group consisting of agar, gelatin, such as fish gelatin or beef gelatin, pectin, konjac, carrageenan or any other gelling agents such as starch, locust bean gum, gum arabic, gum karaya, and gum tragacanth.

[0055] Hydrocolloids that arc commonly used as thickening arc starch, xanthan, guar gum, locust bean gum, gum karaya, gum tragacanth, gum Arabic and cellulose derivatives. Examples of gelling type hydrocolloids include, but are not limited to alginate, pectin, carrageenan, gelatin, gellan, agar, modified starch, methyl cellulose and hydroxypropyl methyl cellulose. Agents such xanthan and guar gum), can be combined with carrageenan and locust bean gum to achieve increased viscosity or superior properties of food gels, such as higher elasticity. Xanthan and galactomannans together, form gels because of synergistic interactions. Xanthan shows quite spectacular synergistic interactions with other non-gelling polysaccharides of galactomannan family leading to increase in viscosity and gel formation. The distinction between increased viscosity and gelation lies on the mannose-galactose ratio of the galactomannan. At higher concentrations, soft and elastic gels are formed with locust bean gum (LBG). Xanthan gum-LBG gel is thermally reversible and it melts between 55 and 60 °C while dispersions of xanthan-guar mixtures can be gelled at room temperature. Mixtures of xanthan and LBG require heating to 90-95 °C. The interaction of xanthan gum with galactomannan is dependent on the ratio of the 45803511.1 6 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0056] mixture, pH and ionic environment. Optimum gum ratios are 80:20 for guar gum: xanthan gum and 50:50 for LBG: xanthan gum. Generally, the synergistic interaction with galactomannans is at its maximum in deionized water at neutral pH and it gets reduced at high salt concentrations and low pH.

[0057] Gelatin is a protein derived from collagen, primarily bovine or porcine in origin. Gelatin is an irreversibly hydrolyzed form of collagen, wherein the hydrolysis reduces protein fibrils into smaller peptides; depending on the physical and chemical methods of denaturation, the molecular weight of the peptides falls within a broad range. Most hydrocolloids are extracted from plants and in general, only gelatin is extracted from animals. Pig, cow, and fish collagens are the primary sources of gelatin. Gelatin contains 19 amino acids, glycine (27-35%), proline, and hydroxyproline (20-24%) being the predominant amino acids. Gelatin approximately contains protein (88%), moisture (10%), and salts (1-2%), and on a dry-weight basis, the protein content is 98-99%. Gelatin has an isoelectric point at pH 4.8-9.4; gelatins processed by acidic treatments have a higher isoelectric point than gelatin processed by alkaline treatments. It is a blend of diverse molecular weight chains such as a- chains, P- chains, and y- chains having a molecular weight of (80 ~ 125 kDa), (160 ~ 250 kDa), and (240 ~375 kDa), respectively. The primary amino acids present in the gelatin are glycine (27-35%), proline, and hydroxyproline (20-24%) (reviewed in Rather, et al. Food Packaging and Shelf Life, Volume 34, 2022, 100945, ISSN 2214-2894).

[0058] Pectin is a galactomannan hydrocolloid obtained from fruit, typically by extraction of citrus peels or apple pomace. Pectin is nature's structurally most complex polysaccharide. The molecule is a galacturonic acid polymer comprising homogalacturonan (HG), rhamnogalacturonan-I (RG-I), rhamnogalacturonan-II (RG-II), arabinogalacturonan (AG), and xylogalacturonan (XGA) regions. Approximately, the polymer consists of repeating units of (1 4)-a-D-GalA (galactopyranosyluronic acid) residues, partly methyl-esterified at O-6 position (and at lower extent also acetyl-esterified at O-2 or O-3), interrupted by branched regions composed of (1 — > 2)-a-l-rhamnose units (RG-I regions) further binding neutral sugars including galactose, arabinose, xylose, and fructose. In general, pectin extracted via the conventional acidextraction process is high methoxyl (HM) pectin, namely pectin with degree of esterification (DE)>50%. Low methoxyl (LM) pectin having degree of esterification (DE) < 50% (produced by controlled hydrolysis of HM pectin) is more valued than HM pectin, because it is able to gel without requiring sugar in a broad pH range in the presence of small amounts of Ca2+ ions coordinating with free carboxylate groups via the “egg box” cross-linking mechanism. Gelling of 45803511.1 7 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0059] HM pectins, on the other hand, requires both high concentration of sugar (usually >55%) and acidic conditions (pH < 3.5) (Criminna et al., Food Hydrocolloids, Volume 127, 2022, 107483, ISSN 0268-005X; https: / / doi. Org / 10.1016 / j.foodhyd.2022.107483).

[0060] Agar (also referred to as agar agar) is a galactose polymer extracted from red algae which forms a firm gel at low concentrations of around 0.1 to 0.5 wt.%.

[0061] Alginate, a natural polysaccharide derived primarily from marine algae, has become popular in biomedical research due to its versatile gelation properties and biocompatibility. Alginate is a biopolymer found in nature, primarily obtained from brown algae that belong to the Phaeophyceae class. Alginate is characterized as a linear polysaccharide made up of two unique uronic acids: P-D-mannuronic acid (M) and a-L-guluronic acid (G). The ratio of M to G can differ depending on the specific source of the alginate. For instance, the alginate extracted from Laminaria digitata has an M / G ratio of 1.16, while that from Ascophyllum nodosum has a ratio of 1.82. Alginate gels induced by ions primarily form through electrostatic interactions between the negatively charged carboxyl groups in alginate and positively charged cations such as H+, Ca2+, Cu2+, and Ba2+. This interaction leads to the creation of polyelectrolyte complexes. The gelation properties and characteristics can vary depending on the type of ions involved Carrageenan is a sulfated polygalactan containing ester-sulfate (15-40%), making it an anionic polysaccharide. Carrageenan is sourced from red seaweed of the Rhodophyceae family by extraction, typically from genera such as Eucheuma, Agardhiella, Solieria, Iridaea, Cripus, Hypnea, Chondrus, Sarconema, Gigartina, and Stellat. Carrageenan mainly consists of 3 types, distinguished by their degree of sulfation, (i) Kappa (K)-carrageenan is a specific type of carrageenan that exhibits a structural composition characterized by alternating 3 -linked P-d-galactose 4-sulfate and 4-linked 6-anhydro-a-galactopyranose units within its repeating disaccharide moieties. This arrangement results in the presence of one negative charge per repeating disaccharide unit, which contributes to the unique physicochemical properties and functional characteristics of K-carrageenan. Kappa-carrageenan is a gelling agent, the synergistic interactions of which, with other hydrocolloids have been exploited in several food formulations. Hot dispersions of K-carrageenan- locust bean gum form strong elastic gels with low syneresis when cooled below 50 °C. The maximum interaction, and hence, peak rupture gel strength occurs at ratios between 60:40 and 40:60 of K-carrageenan to locust bean gum. Iota (t)-carrageenan consists of two sulfate groups in each repeating disaccharide moiety.28,53Iota and kappa carrageenan have similar properties. In aqueous solutions, both K- and r-carrageenan experience thermoreversible conformational changes at higher temperatures. The gelling and 45803511.1 8 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0062] network-forming properties of certain carrageenan's, such as iota (r)- and kappa ( )-types, are influenced by their structural characteristics and interactions with cations in the surrounding environment, where at lower temperatures, they form robust networks through interactions involving sulfate groups and the 3,6-anhydro-d-galactopyranosyl ring, while their gelation behaviour is also strongly affected by the concentration and type of cations, such as K+ and Ca2+, as well as the overall biopolymer concentration, highlighting the versatility and tailor ability of these sulfated polysaccharides in various applications where controlled gelation and network formation are desirable. Lambda carrageenan consists of 3 sulfate groups per disaccharide unit, but there is no 3, 6-anhydride bridge, contrary to other types.55 / .-Carrageenan shows random conformations at all temperatures and is unable to form a gel. (reviewed in Jabeen et al., RSC Adv.;15(27):22035-22062).

[0063] Exemplary concentrations (% w / w) of agar when used as a gelling agent can be from about 0.1 to about 2%. Exemplary concentrations (% w / w) of alginate when used as a gelling agent can be from about 1 to about 2%. Exemplary concentrations (% w / w) of Carrageenan when used as a gelling agent can be from about 0.5 to about 3%. Exemplary concentrations (% w / w) of high methoxy pectin when used as a gelling agent can be from about 1 to about 4%. Exemplary concentrations (% w / w) of low methoxy pectin when used as a gelling agent can be from about 0.1 to about 4%. Exemplary concentrations (% w / w) of gelatin when used as a gelling agent can be from about 0.1 to about 5%. Exemplary concentrations (% w / w) of gelatin when used as a gelling agent can be from about 0.5 to about 1.5%.

[0064] 2. Liquid Component

[0065] In some forms, the liquid component is a juice is selected from the group consisting of mango juice, peach juice, orange juice, grapefruit juice, grape juice, prune juice, cherry juice, pear juice or combination of fruit / vegetable juice. Other examples of juices include, but are not limited to juice from berries, banana, tomato, bean, cereal seeds, cucumber, apricot, nuts, passion fruit. Examples of berries include but are not limited to woodland or garden berries such as blueberries, blackberries, cranberries, blackcurrants, redcurrants, or raspberries.

[0066] In some forms the liquid component is provided by milk, which can be airy milk or nondairy milk, for example, coconut milk, almond milk, oat milk, soy milk or pea milk. Some forms, the composition does not include diary or non-diary milk.

[0067] In some forms, the liquid component is a soup selected from the group consisting of miso soup, bone broth, chicken broth and beef broth.

[0068] 45803511.1 9 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0069] Miso soup is a traditional Japanese soup consisting of miso in a dashi stock. Optional ingredients based on region and season may be added, such as wakame, tofu, negi, abura-age, and mushrooms. Miso is a traditional Japanese seasoning. It is a thick paste produced by fermenting soybeans with salt and kbji (the fungus Aspergillus oryzae), and sometimes rice, barley, seaweed, or other ingredients. Dashi is a family of stocks used in Japanese cuisine. The most common form of dashi is a simple broth made by heating water

[0070] containing kombu (edible kelp) and kezurikatsuo (shavings of katsuobushi — preserved, fermented skipjack tuna — or bonito) to near-boiling, then straining the resultant liquid: dried anchovies or sardines may be substituted (Kaneko, Amy. Let's Cook Japanese Food!: Everyday Recipes for Home Cooking, p. 15.). Other kinds of dashi are made by soaking kelp, niboshi, or shiitake in water for many hours or by heating them in near-boiling water and straining the resulting broth. Kombu dashi is made by soaking or gently simmering kelp in water; soaking is traditional and fit for making baby food while simmering is a more modem practice, Niboshi dashi is made by pinching off the heads and entrails of small dried sardines (to prevent bitterness) and soaking the rest in water. Shiitake dashi is made by soaking dried shiitake mushrooms in water. Miso soup is commercially available.

[0071] Bone broth is considered a nutritious stock that is made by simmering animal bones and contains a large amount of protein, mostly in the form of collagen, and several micronutrients. Bone broth is commercially available. Alternatively, methods of making bone broth are known in the art, as described for example, in Mar-Solis, ct al., (Mcdicina (Kaunas). 2021 Oct 20;57(ll): 1138)).

[0072] Chicken broth, which is used as a base for many soups, is a liquid, water-based food solution that is traditionally prepared by slowly simmering a combination of chicken bones, meat, and sometimes vegetables. Chicken broth is commercially available and its methods of preparation are known in the art as described for example, in Hawkins, et al., J Oral Facial Pain Headache. 2018 Mar 6;32(2):208— 21. In brief, broth can be prepared by chopping raw chicken carcasses (after removal of legs, breast meat, skin, and wings) into small pieces and adding 1.5 parts water in a pan. Components were brought to a boil and cooked at a light boil for 45 minutes. The product then simmered for 1.25 hours. The broth was separated from solids by pouring through a screen, and visible fat was removed after chilling.

[0073] 3. Spice / Seasoning

[0074] The disclosed compositions in some forms include at least one seasoning / spice. A spice is a specific dried plant part (root, seed, bark, etc.) that adds flavor, while seasoning is a broader 45803511.1 10 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0075] term for any mixture of flavorings, which can include spices, herbs, salt, and other ingredients like sugar or acids. Herbs are generally defined as the green, leafy, non- woody parts of plants, including flowers, stems, and leaves whereas spices are derived from various parts of plants, such as roots, bark, seeds, fruits, or flowers. Spices can be buds and flowers (saffron, cloves), leaves (rosemary, bay leaves, coriander, mint, parsley, sage, thyme, oregano, tarragon, lemongrass leaves), plant bark (cinnamon, cassia), roots (turmeric, ginger), fruits (cloves, chili, allspice, black pepper), seeds (fennel, fenugreek, dill, mustard, cumin, coriander), bulbs (onion, garlic, leek), or arils (mace) (reviewed in Al-Habsi, et al., J. Functional Foods, 129:2025, 106882, https: / / doi.org / 10.1016 / j.jff.2025.106882.; see esp. Table, 1 (incorporated herein by reference, which lists various herbs / spices and their scientific names). Turmeric is a rhizomatous herbaceous perennial plant (Curcuma longa) of the ginger family. Curcumin is a natural polyphenol, that is extracted from a type of turmeric and is also known as diferuloylmethane (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione).

[0076] In some forms, the spice is ginger. In these forms, the ginger can be powdered ginger, crystallized ginger, pressed fresh ginger (pulp or juice).

[0077] In some forms the spice can be turmeric, powder or pressed.

[0078] In some forms the spice can be selected from the group consisting of cinnamon cloves, cardamom, and curry powder.

[0079] In some forms, the spice is a pepper is provided in the form of a hot sauce, cayenne pepper, chili pepper (such as Capsicum annum, C. frutescens, and their varieties) or black pepper. Hot sauce, commonly called chili sauce, is a condiment used as a flavor enhancer to improve food taste due to the induction of pleasurable spicy sensations. In North and South America, hot sauces are mostly made of cayenne, chipotle, habanero, and jalapeno peppers. Gochujang and red peppers are popular among Korean seasonings, and Sriracha sauce is a conventional hot sauce from Thailand. The U. S. Department of Agriculture (USDA) [5] classifies hot sauce as a hot or spicy sauce (Type I) and determines that it should be red to reddish-brown colored with a pungent odor. This type of hot sauce should also meet analytical requirements regarding the non-volatile solid’s concentration (7.5-18.0%), salt content (4.9-12.0%), acidity (2.4-5.0%), and capsaicin concentration (>43 ppm) levels, (reviewed in Tufariello, et al., Foods;12(2):369. doi: 10.3390 / foods12020369). Hot sauces are commercially available. Examples, include, but are not limited to Cholula Original Hot Sauce, Tabasco Green Pepper Sauce, Trader Joe’s Habanero Hot Sauce, Dat’l Do-It Datil Pepper Hot Sauce (available on Amazon.com), TRUFF Black Truffle Infused Hot Sauce, Secret Aardvark Habanero Hot 45803511.1 11 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0080] Sauce, Zab’s Original Datil Pepper Hot Sauce, Huy Fong Foods Sriracha Hot Chili Sauce, Louisiana brand Hot Sauce, Chuffed Sweet Heat, Yellowbird Sauce Habanero Hot Sauce (available on Amazon.com), etc.

[0081] 4. Sweetening agents

[0082] The term “sweetening agent” as used herein refers to a product or a composition which is in a form where it can be directly applied for sweetening of food, beverage and / or medication products for human consumption. The sweetening agent may comprise a single active ingredient, i.e., a single substance having a sweet taste, or it may comprise several of such active ingredients, i.e. a blend of substances contributing to the sweet taste.

[0083] Sweetening agent may include, but is not limited to, one or more of the following: sugars (e.g., trehalose, glucose, dextrose, fructose, galactose, sucrose, lactose, maltose, palatinose, isomaltulose, cane sugar, beet sugar, rice syrup, invert sugar, honey, agave syrup, maple syrup, high fructose com syrup, combinations thereof, and the like), and / or sugar alternatives such as high intensity sweeteners (e.g., steviol glycosides, mogrosides, sucralose, acesulfame potassium (acesulfame K), aspartame, saccharin or brazzein, combinations thereof, and the like) combined with bulking agents (e.g., resistant dextrin, inulin, or fructooligosaccharides (FOS)), combinations thereof, and the like), and / or polyols / low or no-calorie sweeteners (e.g., isomalt, tagatose, erythritol, maltitol, lactitol, sorbitol, mannitol, allulose, xylitol, hydrogenated starch hydrolysates, combinations thereof, and the like).

[0084] In some forms, the sweetening agent is selected from the group consisting of sugar (maple and non-maple sugar), agave syrup, maple syrup, honey, coconut sugar (low glycemic option), stevia (low calorie option). In come forms, the sweetening agent is or comprises sucrose (also referred to herein as “sugar” in the singular and also known as table sugar).

[0085] 5. Oil

[0086] The disclosed compositions in some forms include an oil. The oil can be a vegetable oil. The vegetable oil can be selected from the group, consisting of sunflower oil, high oleic sunflower oil, safflower oil, high oleic safflower oil, soybean oil, maize oil, cotton seed oil, arachidic oil, olein-fractions of natural oils, such as palm oil olein, MCT (Medium-chain triglyceride) oils. In some forms, the oil is peppermint oil / extract. Peppermint extract is an extract of peppermint made from the essential oil of peppermint leaves. Peppermint oil is obtained from the leaves of the perennial herb, Mentha piperita L. and M. arvensis var. piperascens a member of the labiatae family. It is a colorless, pale yellow or pale greenish- yellow liquid having characteristic odor and taste followed by a sensation of cold, freely soluble in ethanol (70%). The solution may show an 45803511.1 12 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0087] opalescence. The oil is found on the undersides of the leaves, is extracted by steam distillation and is generally followed by rectification and fractionation before use (reviewed in Alankar, Asian Journal of Pharmaceutical and Clinical Research, 2:27-33 (2009)). Peppermint oil is commercially available from numerous sources.

[0088] 6. Flavoring agent

[0089] The disclosed compositions include a flavoring agent, which is preferably, a natural flavoring agent. Thus, in some forms, the composition does not include an artificial flavoring agent which does not occur in nature.

[0090] " Natural" is a term that many people tend to associate with wellness and sustainability; in reality, it simply means "from nature”. When applied to the world of flavor science, it has a slightly more complicated definition.

[0091] According to the CFR (Code of Federal Regulations), a natural flavor (or natural flavoring) refers to "the essential oil, oleoresin, essence or extractive, protein hydrolysate, distillate, or any product of roasting, heating or enzymolysis, which contains the flavoring constituents derived from a spice, fruit or fruit juice, vegetable or vegetable juice, edible yeast, herb, bark, bud, root, leaf or similar plant material, meat, seafood, poultry, eggs, dairy products, or fermentation products thereof, whose significant function in food is flavoring rather than nutritional." Simply, a natural flavor is a substance derived from a natural source (through plant or animal matter) whose function is for flavor, not nutrition. There are three forms of a natural flavor. Using lemon as an example: Natural Lemon Flavor — FTNF is the acronym for "from the named food," meaning all the flavor ingredients used must be derived from the natural named source (in this case, lemon). Natural Lemon Flavor WONF — WONF is shorthand for "with only (or other) natural flavors," meaning the flavor must contain any amount of a natural derivative from lemon. All other flavor ingredients used must be natural but do not necessarily have to come from lemon. Natural Lemon-Type Flavor or Natural Flavor For Lemon — All flavor ingredients used must be natural but do not need to come from the named food. This flexibility allows a flavor using natural compounds that are more readily available in other sources. For example, citral can be extracted from lemongrass to make this Natural Lemon-Type Flavor.

[0092] By contrast, an artificial flavor (or artificial flavoring) refers to "any substance, the function of which is to impart flavor, which is not derived from a spice, fruit or fruit juice, vegetable or vegetable juice, edible yeast, herb, bark, bud, root, leaf or similar plant material, meat, fish, poultry, eggs, dairy products, or fermentation products thereof." Simply put, artificial 45803511.1 13 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0093] flavors are additives designed to mimic the taste of natural ingredients. Made with synthetically derived raw materials, an artificial flavor in some forms structurally mirrors the natural compound, offering manufacturers a cost-efficient way to achieve a specific profile. Examples, or flavorings that occur in nature, but can be created artificially, include, but are not limited to: Methyl anthranilate: this is grape flavor, which occurs naturally in grapes; Isoamyl acetate: this is banana flavor, and it's found in many plants; Cinnamaldehyde: this is cinnamon flavor, which occurs naturally in cinnamon; ethyl decadienoate: this is pear flavor, and it naturally occurs in apples, pears, and grapes; 2,4-dithiapentane: this is truffle or garlic flavor, and it occurs naturally in some truffles.

[0094] Some artificial flavoring agents do not have a naturally occurring counterpart, and in some forms, are excluded from the disclosed compositions. Examples include, but are not limited to styrene, benzophenone, ethyl acrylate, eugenyl methyl ether, myrcene, pulegone, and pyridine.

[0095] The flavoring agent is preferably a sour flavoring agent for example, citric acid, lemon / lime juice (which replace some of the liquid juice in non-lemonade optionsj. The disclosed compositions can include cocoa powder. The disclosed compositions can also include protein powder, for example, about 2-5 g protein per serving.

[0096] One embodiment provides a composition including / made from a combination of beef gelatin, water, cocoa powder, sugar, cinnamon, vinegar, cayenne pepper + / - peppermint.

[0097] One embodiment provides a composition including / made from a combination of beef gelatin, cranberry juice, powdered ginger, cinnamon, maple syrup powder.

[0098] One embodiment provides a composition including / made from a combination of beef gelatin, water, lemon juice, sugar, powdered ginger, citric acid.

[0099] One embodiment provides a composition including / made from a combination of beef gelatin, water, apple juice, cinnamon, powdered ginger, citric acid.

[0100] The disclosed compositions preferably exclude artificial additives, including, but not limited to, dyes such as, Red dye 3, 40, dyes — FD& C Green No. 3, FD& C Red No. 40, FD& C Yellow No. 5, FD& C Yellow No. 6, FD& C Blue No. 1, and FD& C Blue No. 2, orange B and citrus red No. 2 or any petroleum based food additives. An Exemplary combination of ingredients is shown in Table 1.

[0101] 45803511.1 14 Table 1: ingredient combinations for TRP agonist food combinations

[0102] Gelatin Fluid Powdered Cinnamon Maple Pepper Citric acid Sugar Cocoa Hol Total Macronutrient Calories Ginger sugar mint flavoring Powd sauce Volume Ranges

[0103] oil or er (mL) CHO % Fat % Protein % extract

[0104] 1 TBS 2 cups cranberry 1 / 8 tsp-lTBS l / 8 tsp-lTBS 1 / 8 tsp- 1 / 2 1 tsp-1 / 2 cup 196-74 ImL 89-96 1-2 3-10 247-775 juice cocktail:up

[0105] 15mL 474mL 3.63- 15mL 3.63-15mL 5-118.5mL

[0106] (2-3%) (64-96%) (<1 - 2%) (<1 - 2%) 3.63- (1-16%)

[0107] 118.5mL

[0108] ;<1 - 16%)

[0109] 1 TBS 2 cups lemonade 1 tsp- 1 / 2 cup 494- 91-95 0 5-9 261-489 15mL (lemon 5-118.5mL 507.5mL

[0110] (2-3%) juice+water+sugar) (1-20%)

[0111] 474mL

[0112] (78-96%)

[0113] 1 TBS 2 cups Apple juice 1 / 8 tsp-lTBS l / 8 tsp-lTBS 1 / 8 tsp-lTBS 1 tsp- 1 / 2 cup 496- 88-94 2 5-10 252-557 15mL 474mL 3.63- 15mL 3.63- 15mL 0.63-15mL 5-118.5mL 552.5mL

[0114] 2-3% (73-96%) (<l-2%) (<l-2%);<l-2%) (1-18%)

[0115] 1 TBS 2 cups water l / 8 tsp-lTBS 1 / 8 tsp-lTBS 1ml 1-4 TBS 2-4 TBS l / 8tsp -1 536-654mL 0-82 0-8 10-99 23-335 15mL 474mL 3.63-15mL 3.63-15mL (<1%) 15-60mL 30-60mL TBS

[0116] 2-3% (72-88%) (<l-2%);<i-2%) (3-9%) (6-9%) 3.63- 15mL

[0117] (<l-2%)

[0118] 1 TBS 2 cups nondairy l / 8 tsp-lTBS 1 / 8 tsp-lTBS ImL 1-4 TBS 2-4 TBS 536-639mL 8-61 29-56 9-36 97-637 milk 3.63-15mL 3.63- 15mL 15-60mL 30-60mL

[0119] 15mL (coconut / almond / oat (<1%) (3-9%) (6-9%)

[0120] 2% milk, soy milk, pea (<l-2%);<i-2%)

[0121] milk)

[0122] 474mL

[0123] (74-88%)

[0124] 1 TBS 2 cups daily milk l / 8 tsp-lTBS 1 / 8 tsp-lTBS 1ml 1-4 TBS 2-4 TBS 536-639mL 26-65 3-45 22-72 178-617 15mL (high protein option 3.63- 15mL 3.63-15mL (<1%) 15-60mL 30-60mL

[0125] 2% Fairlife) (<l-2%):<i-2%) (3-9%) (6-9%)

[0126] 474mL

[0127]

[0128] (74-88%) 1 TBS 1.5 cups water + 0.5 1 tsp - Vi cup 1-6 TBSP 5O9-698mL 72-96 0 4-28 83-601 15mL cups juice + 5-118.5mL 15-90mL

[0129] 2-3% electrolytes (100- (<1-17%) (2-13%)

[0130] 350 mg magnesium

[0131] + 200-600 mg

[0132] sodium + 500-1000

[0133] mg potassium)

[0134] 474mL

[0135] (68-93%)

[0136] 1 TBS 2 cups tomato juice 1 / 8tsp- 2 59-63 10-11 27-31 137-171 15mL or V8 TBS

[0137] (3%) 474mL 0.63-30mL

[0138] (89%-96%) (<l-5%)

[0139] 1 TBS Miso soup (2-3 TBS 1 / 8 tsp- 2 1 / 8 tsp- 490-534 32-43 26-31 31-37 186-215 15mL miso to 2 cups TBS 1TBS

[0140] (3%) water) 3.63-30mL 3.63-15mL

[0141] 474mL (<l-6%) (<l-3%)

[0142]

[0143] (89-96%)

[0144] *all ingredients can be added at “about” the amounts listed; for example, 1TB means about 1 TBS; 350 mg means “about 350 mg”, etc.

[0145] 1 cup= 237mL

[0146] 1 / 2 cup= 118.5mL

[0147] 1 tablespoon- 15mL

[0148] 1 teaspoon— 5mL

[0149] l / 8tsp— 0.63mL ATTORNEY DOCKET NO. CMCC 4482 PCT

[0150] Table 1 provides an exemplary combination of ingredients to provide an edible product, which while not being bound by theory, are effective to stimulate the oropharyngeal sensory pathway through activation of one or more Transient Receptor Potential (TRP) receptors, and improve swallowing in the subject.

[0151] The process for the manufacture of gummy or jelly confectionery varies depending upon the hydrocolloid or mixture of hydrocolloids used and may involve mixing the bulk sweetener and the hydrocolloid or mixture of hydrocolloids, together with any additional ingredients such as flavorings, spices and acids, followed by heating, with stirring, and then cooling to the appropriate setting temperature for the hydrocolloid, and for a period sufficient to achieve the required water content. In recipes where the hydrocolloid is gelatine, typically a gelatine solution is added to a cooled sugar syrup.

[0152] The cooked composition is then formed into the final product shape. Typical processes include: i) pouring the fluid mass onto a slab, allowing the mixture to cool and then cutting into the desired shape; and ii) depositing into molds, typically starch molds.

[0153] C. METHODS OF USE

[0154] The disclosed compositions are used to provide hydration to a subject in need thereof. In some forms, the subject is a subject diagnosed with dysphagia.

[0155] In preferred embodiments, the subject is a child needing an International Dysphagia Diet Standardization Initiative (IDDSI) level 4 or higher.

[0156] International Dysphagia Diet Standardization Initiative

[0157] IDDSI was created in 2013 to provide more consistent terminology and easily accessible testing methods. The world first heard about IDDSI in 2015 when it was published, providing clear guidelines for testing methods and texture modification of foods and liquids. The goal was to create globally standardized terminology and descriptions for diet modification across all ages, care settings, and cultures, providing clear consistency guidelines and simple carry-over with easily accessible testing tools. The IDDSI Framework provides a common terminology to describe food textures and drink thickness (References: https: / / iddsi.org / ). Thus, the IDDSI provides a common terminology for describing food textures and drink thicknesses to improve safety for individuals with swallowing difficulties.

[0158] The IDDSI framework (FIG. 1) consists of a continuum of 8 levels (0 - 7), where drinks are measured from Levels 0 - 4, while foods are measured from Levels 3 - 7.

[0159] 45803511.1 17 ATTORNEY DOCKET NO. CMCC 4482 PCT

[0160] Dysphagia

[0161] The term dysphagia refers to difficulty swallowing. It is used to describe a variety of swallowing disorders. Depending on which part of the swallowing process is affected, dysphagia can be described as: Oral dysphagia — when the problem is in the mouth, usually due to the movement of the tongue; Pharyngeal or oropharyngeal dysphagia — when the problem is regarding food passing through the throat; and Esophageal dysphagia — when food is unable to move down through the esophagus. Dysphagia can result in aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The goals of dysphagia treatment are to maintain adequate nutritional intake for the patient and to maximize airway protection.

[0162] Thus, the disclosed compositions are effective in improving swallowing following administration to a subject in need thereof.

[0163] References

[0164] Tomsen, et al., IntJ. Mol. Sci.. 2022, 23, 10773.

[0165] It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these can vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.

[0166] Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, many equivalents to the specific embodiments of the method and compositions described herein. Such equivalents are intended to be encompassed by the following claims.

[0167] 45803511.1 18

Claims

ATTORNEY DOCKET NO. CMCC 4482 PCTCLAIMSWe claim:

1. An edible composition comprising: (a) a hydrocolloid and (b) a liquid component selected from the group consisting of a juice or a soup, wherein the compositions optionally comprise one or more additional ingredients selected from (c) a spice, (d) sweetening agent, (e) an oil, (f) a flavoring acid, (g) cocoa and (h) a pepper component.

2. The composition of claim 1 wherein the hydrocolloid component is selected from the group consisting of agar, fish gelatin, beef gelatin, pectin, konjac, carrageenan or any other gelling agents such as starch, locust bean gum, gum arabic, gum karaya, and gum tragacanth.

3. The composition of claim 1 or claim 2 comprising (c) a spice, (d) sweetening agent, (e) an oil, (f) a flavoring acid, (g) cocoa powder and (h) a pepper component.

4. The composition of claim 3, wherein the liquid juice component is selected from the group consisting of mango juice, peach juice, orange juice, grapefruit juice, grape juice, prune juice, cherry juice, pear juice or combination of fruit / vegetable juice.

5. The composition of claim 3 or claim 4, wherein the liquid soup is selected from the group consisting of miso soup bone broth, chicken broth and beef broth.

6. The composition of any one of claims 3-5, wherein the spice is selected from the group consisting of ginger, cinnamon, cardamom, curry and cloves.

7. The composition of any one of claims 3-6, wherein the pepper component is selected from the group consisting of a hot sauce, cayenne pepper and black pepper.

8. The composition of any one of claims 3-7, wherein the sweetening agent is selected from the group consisting of sugar, agave syrup, maple syrup, honey, coconut sugar (low glycemic option) and stevia (low calorie option).

9. The composition of any one of claims 3-8, wherein the flavoring agent is citric acid, lemon juice or lime juice.

10. The composition of claim 1, wherein the hydrocolloid is gelatin at a concentration of 2-3%, and the juice is cranberry juice, the composition further comprising ginger, cinnamon, maple sugar, and citric acid flavoring.

11. The composition of claim 1, wherein the hydrocolloid is gelatin at a concentration of 2-3%, and the juice is lemonade, the composition further comprising citric acid flavoring at a concentration of 1-20%.45803511.1 19ATTORNEY DOCKET NO. CMCC 4482 PCT12. The composition of claim 1, wherein the hydrocolloid is gelatin at a concentration of 2-3% and the juice is apple juice, the composition further comprising ginger, cinnamon, maple sugar, and citric acid flavoring.

13. The composition of claim 1, comprising gelatin at a concentration of 2-3% and water, the composition further comprising cinnamon, maple sugar, peppermint extract, nonmaple sugar, cocoa powder and hot sauce14. The composition of claim 1, comprising gelatin at a concentration of 2-3% and milk, the composition further comprising cinnamon, maple sugar, peppermint extract, non-maple sugar, and cocoa powder.

15. The composition of claim 1, comprising gelatin at a concentration of 2-3%, and water comprising electrolytes and a juice selected from the group consisting of mango juice, peach juice, orange juice, grapefruit juice, grape juice, prune juice, cherry juice, pear juice or combination of fruit and vegetable juice, citric acid flavoring and non-maple sugar.

16. The composition of claim 1, wherein the hydrocolloid is gelatin at a concentration of 2-3% and the juice is tomato juice, the composition further comprising hot sauce at <1 % to about 6%.

17. The composition of claim 15, wherein the electrolytes comprise about 100-350 mg magnesium, about 200-600 mg sodium and about 500-1000 mg potassium.

18. The composition of claim 15, comprising citric acid flavoring at <1% to about 17% of the composition, wherein the composition comprises citric acid.

19. The composition of claim 1, wherein the hydrocolloid is gelatin at a concentration of 2-3%, the composition comprising about 2-3% miso soup and hot sauce at <1% to about 3% of the composition.

20. The composition of any one of claims 1-19, further comprising about 2-5 g of protein powder.

21. A method of treating a subject in need of improved swallowing, method comprising administering the composition of any one of claims 1 -20, to the subject.

22. The method of claim 21, wherein the subject has been diagnosed with dysphagia.

23. The method of claim 22, wherein the subject is a child needing an International Dysphagia Diet Standardization Initiative (IDDSI) level 4 or higher.45803511.1 20

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