Therapeutic suspension compositions

Description

1 / 37 “THERAPEUTIC SUSPENSION COMPOSITIONS” CROSS-REFERENCE TO RELATED DEPOSIT APPLICATIONS

[001] This application claims the benefit of U.S. Interim Application No. 63 / 493397, filed March 31, 2023, the full disclosure of which is incorporated herein by reference for all purposes. FIELD OF THE INVENTION

[002] The present invention relates to liquid compositions, more specifically to therapeutic suspension compositions. Furthermore, the present invention relates to a process for manufacturing the liquid compositions and to methods for relieving symptoms in human subjects by administering the liquid compositions. The liquid compositions, which may comprise one or more therapeutically active agents, are particularly useful in treating allergy symptoms, pain symptoms, cough and cold, including but not limited to pain, cough, nasal congestion, rhinitis and sore throat. BACKGROUND OF THE INVENTION

[003] Medications or pharmaceutical products administered orally are given to patients in many forms, including solid forms such as capsules, caplets, gel capsules or tablets, and liquid forms such as solutions, for example, syrups and elixirs, emulsions or suspensions. Children, older patients and many other patients, including disabled or incapacitated patients, have difficulty swallowing solid forms, for example, whole tablets and even capsules. Therefore, in cases where the dosage to be administered cannot be made in a very small tablet or capsule, it is desirable to provide the medication in chewable solid form or in liquid form. For many patients, including pediatric and geriatric patients, a liquid oral dosage form is preferable to the chewable dosage form due to the ease of swallowing without chewing of the liquid dosage form. Petition 870250088117, dated 09 / 29 / 2025, p. 20 / 60 2 / 37

[004] Suspensions are a two-phase system with solid particles of substantially water-insoluble active agent dispersed throughout the liquid medium. A suspension does not encompass emulsions, which are intended to describe liquids suspended within liquid vehicles or syrup formulations containing only substantially fully dissolved pharmaceutical active agents. As used herein, a “particle” may be a crystal, a granule, an agglomerate, or any undissolved solid material. The particles of the present invention preferably have a median particle size (d50%) of about 2 to about 150 microns, more preferably about 10 to about 100 microns. The challenges of keeping the substantially water-insoluble active agent suspended, ensuring the stability of the substantially water-insoluble active agent, and maintaining dose uniformity over an extended period of time have been previously addressed. See, for example, US patents nos. 5,409,907 and 5,374.659.

[005] In a pharmaceutical suspension, typically at least one active agent is present substantially in the form of undissolved solid particles, that is, the active agent is substantially insoluble in water. However, in any of these systems, a portion of such active agent may be in the dissolved state. When formulating such systems, it is advantageous to minimize the amount of drug present in the dissolved state. Minimizing the amount of active agent in solution is advantageous for both the taste and the chemical and / or physical stability of the product.

[006] A liquid dosage form may also be present in the form of a solution, in which the therapeutic ingredient or ingredients are substantially dissolved in the liquid mixture. When the dose of the therapeutic ingredient is less than 50 g / 5 mL, the therapeutic ingredient may be dissolved in the form of a solution.

[007] A common problem associated with liquid dosage forms is the often unpleasant taste of the active agents that manifests itself during the Petition 870250088117, dated 09 / 29 / 2025, page 21 / 60 3 / 37 time the liquid dosage form is in the mouth before swallowing. Although suspensions typically offer greater taste masking than other liquid forms, those skilled in the art are aware of the considerable technical difficulties in producing a stable and organoleptically acceptable suspension.

[008] Furthermore, solutions to such challenges must be reevaluated when over-the-counter (OTC) oral suspension or oral solution products are formulated or reformulated to use reduced ingredients or ingredients of natural origin. The term “clean” or “clean medicine” is a newly emerging trend for OTC pharmaceutical products. While there is no generally accepted definition for the term “clean,” it is generally understood by consumers to mean any of the following: free of artificial flavors, colors, preservatives, or sweeteners; sourced from nature; and / or free of artificial, chemical, or unnecessary ingredients.

[009] The formulation of “clean” oral solution or oral suspension products may limit or exclude certain ingredients that have been traditionally used in pharmaceutical suspensions to overcome the challenges of keeping substantially water-insoluble active agents suspended, ensuring the stability of substantially water-insoluble active agents, and maintaining dose uniformity over an extended period of time. New ingredients that fit the definition of “clean” should be identified and evaluated to ensure that such newly formulated pharmaceutical suspension or solution products meet the safety and efficacy standards that are required of all OTC pharmaceutical products.

[010] Dyes have traditionally been added to pharmaceutical suspensions for elegance and to mask discoloration. However, it has been found that some patients develop or have allergies or are sensitive to dyed suspensions. Dyed suspensions can additionally stain clothing, furniture, carpets and the like when spilled. Therefore, dye-free suspensions are much Petition 870250088117, dated 09 / 29 / 2025, page 22 / 60 4 / 37 desirable.

[011] Coloring agents are frequently added to liquid pharmaceutical products to produce pharmaceutically acceptable characteristics, to provide an identification factor, and also to provide consistency between batches of a product. Often, the color of the excipients used to manufacture an OTC product can contribute to products appearing inconsistent or “discolored” to a patient. The patient or consumer may perceive the inconsistency or color change as an indication that the product was improperly manufactured, is expired, or is generally ineffective, resulting in product rejection.

[012] In many cases, liquid dosage forms include solvents or vehicles to dissolve the active ingredient. Common liquid solvents include propylene glycol or polyethylene glycol. Some of these solvents and vehicles are artificial in nature or undergo significant chemical processing, even if they are derived from natural sources. Common bulk sweeteners include sugar alcohols in solution, such as sorbitol solution. In many cases, these solvents and bulk sweeteners are artificial in origin and not from natural plant sources, which many patients now prefer.

[013] Even when bulk solvents and sweeteners are derived from natural plant sources, these ingredients often have a high sugar content and / or a high glycemic index, which may be undesirable for consumers; in particular, young children, diabetic or pre-diabetic patients, or patients who are generally health-conscious. For example, GE Healthcare document US20210290532A1 discloses a stable pharmaceutical formulation or suspension that has a pharmaceutical active agent, agave, and a diluent. This formulation or suspension has adequate viscosity for drinking, however, it may have a high glycemic index due to the incorporation of agave syrup, which has a high fructose content.

[014] In addition, naturally derived solvents and sweeteners Petition 870250088117, dated 09 / 29 / 2025, page 23 / 60 5 / 37 bulk sweeteners can be difficult to incorporate, stabilize, or preserve in an oral suspension formulation. An example of a natural bulk sweetener is disclosed in Wild Valencia SA document US20080311272(A1), which describes a composition comprising carbohydrates obtained from carob and carbohydrates obtained from at least one additional fruit, including apple and grape. This natural bulk sweetener or similar bulk sweetener is sold by ADM Company under the trade name “Fruit-Up®”.

[015] Thus, there remains a need for liquid medicinal compositions comprising inactive materials that are derived from natural sources with relatively low glycemic indexes. Such a composition must act quickly and provide superior relief from sore throat pain over an extended period of time. SUMMARY OF THE INVENTION

[016] The present invention relates to liquid compositions that can be used to alleviate conditions such as those associated with allergies, colds with coughs, digestive health, or pain by carrying an active therapeutic ingredient. This active therapeutic ingredient may be an active pharmaceutical ingredient, homeopathic ingredient, herbal ingredient, or nutritional supplement. These compositions would comprise a substantial amount of inactive ingredients that are of natural origin or from natural sources.

[017] According to an example of the present invention, the liquid composition may include a therapeutic ingredient and a natural bulk sweetener having a fructose content of less than 50 percent of the natural bulk sweetener. The natural bulk sweetener may be selected from glycerin, allulose syrup, rice syrup, tapioca syrup, apple syrup, carob syrup, and combinations thereof. Furthermore, the liquid composition may have a total fructose content of less than 0.7 g / mL. Petition 870250088117, dated 09 / 29 / 2025, page 24 / 60 6 / 37

[018] According to one example, the therapeutic ingredient may be an active pharmaceutical ingredient. For example, the active pharmaceutical ingredient may be selected from the group consisting of acetaminophen, diphenhydramine, dextromethorphan, guaifenesin, ibuprofen, cetirizine, loperamide, and phenylephrine. According to one example, the therapeutic ingredient may be an analgesic.

[019] According to alternative examples, the therapeutic ingredient may be a homeopathic active ingredient and / or a nutritional supplement.

[020] The liquid composition may be in the form of a suspension or it may be in the form of a solution.

[021] According to one example, the liquid composition may additionally include a sensory agent.

[022] According to one example, the liquid composition may additionally include at least one thickening agent.

[023] In one example, the natural bulk sweetener may consist substantially of glycerin and a combination of apple syrup and carob syrup. A ratio between the combination of apple syrup and carob syrup and glycerin may be from about 2:1 to about 5:1. Alternatively, a ratio between the combination of apple syrup and carob syrup and glycerin may be from about 2.5:1 to about 3:5. A ratio between the combination of apple syrup and carob syrup and glycerin may be about 2.6:1. Alternatively, a ratio between the combination of apple syrup and carob syrup and glycerin may be about 3:1. Furthermore, alternatively, a ratio between the combination of apple syrup and carob syrup and glycerin may be about 4.1:1.

[024] In one example, the liquid composition may additionally include a preservative. The preservative may be, for example, potassium sorbate.

[025] In an alternative example, the liquid composition may be substantially free of a preservative. The liquid composition may be substantially Petition 870250088117, dated 09 / 29 / 2025, page 25 / 60 7 / 37 free of potassium sorbate.

[026] In one example, the liquid composition may be substantially free of agave syrup. In another example, the liquid composition may be substantially free of any ingredient with a fructose content greater than 15 percent.

[027] The present invention may further include a method for relieving a selected symptom from the group consisting of pain, fever, cough, nasal congestion, diarrhea, allergic rhinitis and sore throat in an individual, by administering a composition as described in the present application. DETAILED DESCRIPTION OF THE INVENTION

[028] It is believed that those skilled in the art can, based on the description contained in the present invention, use the present invention to its fullest extent. The following specific examples and embodiments should be considered merely illustrative and not limiting of the remainder of the disclosure in any way.

[029] Except where otherwise indicated, all documents cited are incorporated herein, in their relevant part, by way of reference; the citation of any document shall not be construed as an admission that it is prior art in relation to the present invention. Furthermore, all documents incorporated herein by way of reference are incorporated herein only to the extent that they are not inconsistent with this descriptive report.

[030] Except where otherwise defined, all technical and scientific terms used herein have the same meaning commonly understood by those skilled in the art to which the invention pertains. Furthermore, all publications, patent applications, patents, and other references mentioned in the present invention are incorporated herein by reference. As used herein, all percentages are by weight unless otherwise specified. In addition, all ranges presented herein are intended to include any combinations of values ​​between the two points. Petition 870250088117, dated 09 / 29 / 2025, page 26 / 60 8 / 37 finals, inclusive.

[031] For use in the present invention, the term “active ingredient” is used in the present invention in a broad sense and may encompass any material that confers a therapeutic effect. For example, the active ingredient may be a pharmaceutical compound, a nutraceutical, a vitamin, a dietary supplement, a nutrient, an herb, a food, a colorant, a food, a mineral, a supplement, an oral treatment agent or a flavoring agent (sensory agent) or similar and combinations thereof.

[032] The term “dosage form” applies to any solid composition designed to contain a specific predetermined amount (dose) of a certain ingredient, for example, an active ingredient as defined herein. Suitable dosage forms may be pharmaceutical drug delivery systems and systems for the delivery of minerals, vitamins and other nutraceuticals, oral treatment agents, flavorings, sensory agents and the like. In a particularly preferred example, the dosage form is an orally administered system for the delivery of an active pharmaceutical ingredient into the gastrointestinal tract of a human being.

[033] The term “liquid dosage forms” may include, but is not limited to, suspensions, syrups, solutions or elixirs, in which one or more of the active ingredients is in a dissolved, partially dissolved or undissolved state or suspended.

[034] “Therapeutic effect” means any effect or action of an active ingredient intended to diagnose, treat, cure, mitigate or prevent disease, or affect the structure or any function of the body.

[035] Except where otherwise indicated, percentages used to express quantities of ingredients are percentages by weight (referred to as “% weight”, “% w / w”, “% by weight” or “% (w / volume)”). Similarly, weight ratios Petition 870250088117, dated 09 / 29 / 2025, page 27 / 60 9 / 37 ratios used to express the relative proportions of ingredients are also determined using percentage by weight (that is, weight ratios are calculated by dividing the percentage by weight of one ingredient by the percentage by weight of another ingredient). Except where otherwise indicated, all ranges include endpoints, for example “from 4 to 9” includes endpoints 4 and 9.

[036] As used herein, the term “safe and effective amount” means an amount sufficient to induce the desired effect, but low enough to avoid serious side effects. The safe and effective amount of the compound, extract or composition will vary according to, for example, the age, health and environmental exposure of the end user, the duration and nature of the treatment, the specific extract, ingredient or composition employed, the particular vehicle used, and similar factors.

[037] As used herein, the term “about” means within 5% by weight, within 4% by weight, within 3% by weight, within 2.5% by weight, within 2% by weight, or within 1% by weight of a disclosed value.

[038] In certain embodiments, the present invention, as disclosed herein, can be practiced in the absence of any compound, method step or element (or group of compounds or elements) not specifically disclosed herein. ACTIVE INGREDIENT(S)

[039] The dosage form of the present invention preferably contains one or more (or at least one) active ingredients. Suitable active pharmaceutical ingredients include analgesics, anti-inflammatory agents, antiarthritics, anesthetics, antihistamines, antitussives, antibiotics, anti-infective agents, antipyretics, antivirals, anticoagulants, antidepressants, antidiabetic agents, antiemetics, antiflatulents, antifungals, antispasmodics, appetite suppressants, bronchodilators, cardiovascular agents, central nervous system agents, central nervous system stimulants, cough suppressants, decongestants, expectorants, oral contraceptives, diuretics, gastrointestinal agents, Petition 870250088117, dated 09 / 29 / 2025, page 28 / 60 10 / 37 preparations for migraine, motion sickness products, mucolytics, muscle relaxants, preparations for osteoporosis, poly(dimethyl-siloxanes), respiratory agents, sleeping pills, agents active on the urinary tract and pharmaceutically acceptable salts thereof, derivatives thereof, combinations thereof and mixtures thereof.

[040] According to one example, the active ingredient is selected from (or selected from the group consisting of) acetylsalicylic acid, acetic acid derivatives such as indomethacin, diclofenac, sulindac and tolmetin; fenamic acid derivatives such as mefenamic acid, meclofenamic acid and flufenamic acid; biphenylcarbodylic acid derivatives such as diflunisal and flufenisal; and oxicams such as piroxicam, sudoxicam, isoxicam and meloxicam; and pharmaceutically acceptable salts thereof, derivatives thereof, combinations thereof and mixtures thereof.

[041] Examples of useful nonsteroidal anti-inflammatory drugs (NSAIDs) include (as may be selected from the group consisting of) ibuprofen, naproxen, benoxaprofen, naproxen sodium, fenbufen, flurbiprofen, fenoprofen, fenbuprofen, ketoprofen, indoprofen, pirprofen, carpofen, oxaprofen, pranoprofen, microprofen, tioxaprofen, suprofen, alminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, celecoxib and pharmaceutically acceptable salts, derivatives thereof and combinations thereof.

[042] The composition of the present invention may also comprise acetaminophen. As used herein, the term “APAP” means acetaminophen or N-acetyl paraaminophenol, including, but not limited to, pharmaceutically acceptable salts, esters or derivatives thereof.

[043] Examples of active pharmaceutical ingredients for cough and cold (as they may be selected from or selected from the group consisting of) may include antihistamines, cough suppressants, decongestants and expectorants, and may include, but are not limited to, brompheniramine, Petition 870250088117, dated 09 / 29 / 2025, page 29 / 60 11 / 37 carbinoxamine, acetylcysteine, guaifenesin, carbocysteine, chlorcyclizine, dexbrompheniramine, bromohexane, phenindamine, pheniramine, pyrilamine, tonzylamine, pri-polidine, ephedrine, phenylephrine, pseudoephedrine, phenylpropanolamine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, astemizole, terfenadine, fexofenadine, naphazoline, oxymetazoline, montelukast, propyl hexadrine, triprolidine, clemastine, acrivastine, promethazine, oxomemazine, mequitazine, buclizine, bromhexine, ketotifen, terfenadine, ebastine, oxatamide, xylometazoline, loratadine, desloratadine, noscapine, clofedianol, Menthol, benzonatate, ethylmorphone, codeine, acetylcysteine, carbocysteine, ambroxol, belladonna alkaloids, sobrenol, guaiacol and cetirizine; and pharmaceutically acceptable salts thereof, derivatives thereof, combinations thereof and mixtures thereof.

[044] In another example, at least one active ingredient is an NSAID and / or acetaminophen, and pharmaceutically acceptable salts thereof.

[045] Examples of suitable gastrointestinal agents (as they may be selected from or selected from the group consisting of) may include antacids, such as calcium carbonate, magnesium hydroxide, magnesium oxide, magnesium carbonate, aluminum hydroxide, sodium bicarbonate, sodium dihydroxyaluminum carbonate; stimulant laxatives, such as bisacodyl, cascara sagrada, dantron, senna, phenolphthalein, aloe, castor oil, ricinoleic acid and dehydrocholic acid and mixtures thereof; H2 receptor antagonists, such as famotidine, ranitidine, cimetadine, nizatidine; proton pump inhibitors, such as omeprazole and lansoprazole; gastrointestinal cytoprotectives, such as sucralfate and misoprostol; gastrointestinal prokinetics, such as prucalopride, antibiotics for H.pylori, such as clarithromycin, amoxicillin, tetracycline and metronidazole; antidiarrheals, such as diphenoxylate, loperamide and racecadotril; glycopyrrolate; antiemetics, such as ondansetron; analgesics, such as mesalamine.

[046] Examples of suitable polydimethylsiloxanes (such as they may be Petition 870250088117, dated 09 / 29 / 2025, page 30 / 60 12 / 37 selected from or selected from the group consisting of) may include, but are not limited to, dimethicone and simethicone, as disclosed in U.S. Patents Nos. 4,906,478, 5,275,822 and 6,103,260, the content of which is expressly incorporated herein by reference. For use in the present invention, the term “simethicone” refers to the broader class of polydimethyl siloxanes, including, but not limited to, simethicone and dimethicone.

[047] The therapeutically effective amount of the active ingredient or active ingredients can be readily determined by someone skilled in the art.

[048] Suitable sensory elements include menthol, peppermint, mint flavors, fruit flavors, chocolate, vanilla, bubblegum flavors, coffee flavors, natural flavors, liquor flavors and combinations and the like.

[049] According to one example, the composition comprises a polymer also known as a mucoadhesive material. Suitable polymers include gelling material, such as hydrocolloids, for example, pectins, celluloses, alginates, carrageenans, etc.

[050] In one example, the mucoadhesive material is a thickener. Suitable thickeners include, but are not limited to, carboxymethylcellulose (CMC), microcrystalline cellulose, and mixtures of CMC and microcrystalline cellulose. Some suitable thickeners are of natural origin, including xanthan gum and konjac gum. Other thickeners include cellulosic polymers such as hypromellose, hydroxypropyl cellulose, and hydroxyethyl cellulose.

[051] According to one example, mucoadhesive material includes, but is not limited to, Avicel BV 2219, Avicel CL 611, Avicel Plus® LM 310 stabilizer, 40% solids, Avicel RC 591, Carbopol 971P, Aqualon® CMC-7M8SF-PH, HPMC E4M and Nutricol BV 5616.

[052] The composition may contain from about 0.05% by weight to about 3% by weight of polymer. The composition may contain from about 0.2% by weight to about Petition 870250088117, dated 09 / 29 / 2025, p. 31 / 60 13 / 37 of 2% by weight of polymer. These materials, which improve mucoadhesion, increase the duration of relief.

[053] In yet another example, the composition may contain a surface-active agent (also known as a surfactant). Suitable surfactants may include polyoxyethylene-polyoxypropylene block copolymers. In one example, the surfactant includes, but is not limited to, Lutrol F68 (Poloxamer® 188); Lutrol® F127 (Poloxamer® 407) and Tween 80.

[054] The composition may contain from about 0.05% by weight to about 2% by weight of surfactant. The composition may contain from about 0.1% by weight to about 1.5% by weight of surfactant. The composition may contain from about 0.5% by weight to about 1% by weight of surfactant. The surfactant further enhances the perceived coating effect of the composition.

[055] The resulting composition can be applied as a spray or a liquid. In one example, the composition may include an active ingredient. In another example, the composition may include a sensor. Bulk Sweeteners

[056] For the composition of the present invention, a substantial portion of the bulk liquid comprises a natural bulk sweetener. As used herein, a “natural bulk sweetener” is defined as one that is derived from a plant source. The natural bulk sweetener may also have additional properties, such as being from vegan sources, organic sources, non-GMO sources, or being substantially gluten-free or alcohol-free. As used herein, substantially free is defined as less than 0.1 percent, preferably less than 0.05 percent, preferably less than 0.001 percent, weight by volume. The natural bulk sweetener may be used in the present composition from about 20% by weight to about 99% by weight by volume of the total composition.

[057] The bulk sweetener, or natural bulk sweetener, of the present Petition 870250088117, dated 09 / 29 / 2025, page 32 / 60 14 / 37 The invention may also have a low glycemic load as well as a specific fructose content. For example, the bulk sweetener may have a fructose content of less than 75% by weight, less than 70% by weight, less than 50% by weight, less than 40% by weight, less than 30% by weight, less than 25% by weight, less than 20% by weight, or less than 15% by weight. In another example, the total fructose content of the liquid composition may be less than 0.9 g / mL or less than 0.7 g / mL. In yet another example, the composition may be substantially fructose-free. As used herein, substantially free is defined as less than 0.1 percent, preferably less than 0.05 percent, preferably less than 0.001 percent, weight by volume. In another example, the total amount of sugar in the composition may be less than 0.9 g / mL or less than 0.7 g / mL.

[058] Natural bulk sweeteners suitable for the present invention include, but are not limited to, allulose syrup, rice syrup, tapioca syrup; and apple and carob syrups and mixtures thereof, such as the combination of apple syrup and carob syrup sold commercially by ADM Company under the trade name “Fruit-Up®”.

[059] Other natural bulk sweeteners include glycerin. Glycerin may be present in the composition from about 10% by weight to about 70% by weight of the composition. Glycerin may also be combined with a second natural bulk sweetener.

[060] The composition may comprise a mixture of one or more of the bulk sweeteners in order to balance the sweetness and flavor profile of the final composition. An amount of the first bulk sweetener may be added from about 10% by weight to about 90% by weight of the composition, or from about 20% by weight to about 50% by weight of the composition; and an amount of the second bulk sweetener may be added from about 10% by weight to about 90% by weight of the composition, or from about 20% by weight to about 50% by weight of the composition. Petition 870250088117, dated 09 / 29 / 2025, page 33 / 60 15 / 37 The composition may also comprise a third natural bulk sweetener (i.e., a natural bulk sweetener different from the first and second natural bulk sweeteners), wherein an amount of the third bulk sweetener is added from about 5% by weight to about 30% by weight of the composition.

[061] According to one example, the natural bulk sweetener may be a combination of glycerin, apple syrup and carob syrup. The combination of apple syrup and carob syrup may be identical or similar to the product commercially sold under the trademark Fruit-Up® by Archer Daniels Midland (“ADM”) Company and / or as described in European Patent EP2002734B1 entitled “Carbohydrate Composition Obtainable from Mediterranean Fruits”, which is incorporated herein by reference; That is, apple and carob syrups may be incorporated so that 35 to 60%, optionally 35 to 50%, optionally 35 to 45%, optionally 35 to 40%, optionally 35% (w / w) of carbohydrates are obtained from carob, 35 to 50%, optionally 35 to 45%, optionally 35 to 40%, optionally 40% (w / w) of carbohydrates are obtained from at least one additional fruit (e.g., apple), wherein the percentages are based on dry matter.

[062] In one example, the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, may be present in the composition in a range of about 30% by weight to about 70% by weight, or about 35% by weight to about 65% by weight, for example, about 35% by weight, or about 50% by weight or about 65% by weight. Glycerin may be present in the composition in a range of about 20% by weight to about 35% by weight, or about 22% by weight to about 30% by weight, for example, about 22% by weight, or about 25% by weight, or about 29% by weight, or about 30% by weight. One ratio between the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, and glycerin may be... Petition 870250088117, dated 09 / 29 / 2025, p. 34 / 60 16 / 37 approximately 2:1 to approximately 3.5:1, or approximately 2.5:1 to approximately 3:1. The ratio between the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, and glycerin may be approximately 2.6:1, or it may be approximately 3:1. According to another example, the ratio between the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, and glycerin may be approximately 2:1 to approximately 5:1, or approximately 3:1 to approximately 5:1, or approximately 3.5:1 to approximately 4.5:1, or approximately 4.1:1.

[063] The composition may comprise a natural bulk sweetener plus a sugar alcohol solution. Suitable sugar alcohol solutions include, but are not limited to, sorbitol, maltitol, mannitol, xylitol, and erythritol. An amount of the first natural bulk sweetener may be added from about 10% by weight to about 90% by weight of the composition, or from about 20% by weight to about 50% by weight of the composition; and an amount of the second sugar alcohol solution may be added from about 10% by weight to about 90% by weight of the composition, or from about 20% by weight to about 50% by weight of the composition. Alternatively, the composition may be substantially free of a sugar alcohol solution.

[064] Table 1 shows the sugar content for various bulk sweeteners. Table 1: Sugar content for bulk sweeteners Sweetener Fructose content (%) Total carbohydrate content (g / 100g) Allulose syrup <0.15% 71.0 grams Brown rice syrup 0.0% 79.0 grams Combination of apple syrup and carob syrup1 10.54%2 57.96 grams Tapioca syrup 0.0% 73.9 grams High fructose corn syrup 55.0% 76.0 grams Agave syrup 80.0% 76.0 grams 1: Product commercially available under the trademark Fruit-Up® of ADM Company Petition 870250088117, dated 09 / 29 / 2025, page 35 / 60 17 / 37 2: Reported as 70% dry matter or Brix at 20°C, or the measure of dissolved solids in a liquid. PRESERVATIVES

[065] The composition of the present invention may include a natural preservative, an artificial preservative, or combinations thereof. Suitable natural preservatives include potassium sorbate and citrus extracts. Suitable artificial preservatives include sodium benzoate, edetate salts (also known as ethylenediaminetetraacetic acid, or EDTA, such as disodium edetate) and parabens (such as methyl, ethyl, propyl, and butyl p-hydroxybenzoic acid esters). The total preservative may be present from 0.01% by weight to 5% by weight. For example, the preservative in the composition may be potassium sorbate in an amount of about 0.1% by weight to about 0.5% by weight, or about 0.2% by weight. The present composition may also be substantially preservative-free. As used herein, substantially free is defined as less than 0.1 percent, preferably less than 0.05 percent, preferably less than 0.001 percent, weight by volume.

[066] If the composition is substantially preservative-free, the composition also has a water activity of less than 0.7 when tested using a water activity meter. The water activity (aw) of a composition is defined as the ratio of the vapor pressure of the composition, when in completely intact equilibrium with the surrounding air medium, to the vapor pressure of distilled water under identical conditions. Water activity is described in detail later in this description.

[067] In certain examples, the composition may be free of added water. Added water may be defined as water that is not present in the bulk sweetener or plant-based syrup. In some examples, the added water content is less than 5% by weight, or less than 2% by weight, or less than 1% by weight, or less than 0.5% by weight of added water. In some examples, the content Petition 870250088117, dated 09 / 29 / 2025, page 36 / 60 18 / 37 total water in the composition is less than 5% by weight, or less than 2% by weight, or less than 1% by weight, or less than 0.5% by weight of total water in the composition. Thickeners

[068] The suspensions of the present invention may employ suspension systems as known in the art which include, but are not limited to, at least one thickening component. The thickening component may include one or more thickening agents which may be selected from hydrophilic polymers, i.e., water-soluble, such as hydrocolloids, blowing or gelling polymers, and the like. In one example, the thickening component may combine the attributes of a structuring agent and a blowing agent. In another preferred example, the thickening component may combine the attributes of at least two structuring agents, for example, a primary structuring agent and a secondary structuring agent.

[069] A structuring agent, when introduced into a suitable aqueous environment, can form an ordered structure, which is believed to be stabilized by hydrogen bonding and molecular entanglement. Hydrocolloids are a particularly good type of structuring agent. Hydrocolloids are dispersions of particles around which water molecules and solvated ions form a shell-like structure; fluid absorption occurs mainly by expansion and enlargement of the structure.

[070] Examples of suitable hydrocolloids (as may be selected from the group consisting of) may include, but are not limited to, alginates, agar, guar gum, locust bean gum, carrageenan, tara, gum arabic, tragacanth, pectin, xanthan gum, gellan, maltodextrin, galactomannan, pustulan, laminarin, scleroglucan, gum arabic, inulin, karaya, wellana, ransana, zooglana, methylana, chitin, cyclodextrin, pectin, chitosan, cellulosic polymers such as microcrystalline cellulose, and derivatives and combinations thereof. In certain examples of the present invention, the Petition 870250088117, dated 09 / 29 / 2025, p. 37 / 60 19 / 37 Useful structuring agents can be selected from (or selected from the group consisting of) the hydrocolloids xanthan gum, microcrystalline cellulose, carboxymethylcellulose, and derivatives, coprecipitates, and combinations thereof. In a particularly useful embodiment, the thickening component includes xanthan gum as a primary structuring agent and a coprocessed combination of microcrystalline cellulose and carboxymethylcellulose (such as that commercially available from FMC as Avicel RC-591) as a secondary structuring agent.

[071] Xanthan gum is a high molecular weight natural carbohydrate, specifically a polysaccharide. The xanthan gum suitable for use in the present invention is a high molecular weight polysaccharide produced by Xanthomonas campestris. The techniques and strains for the production of this polysaccharide are described in US patents Nos. 4,752,580 and 3,485,719 (the descriptions of which are incorporated herein by reference). The xanthan gum used in the present invention needs to have a viscosity in a one percent saline solution of about 1000 to about 1700 cps (mPa-sec). The viscosity of the one percent solution needs to be measured at 25°C with a Brookfield Synchro-Lectric model LV viscometer at 60 rpm, spindle No. 3. Xanthan gum is available from several commercial suppliers such as RT Vanderbilt Company and CP Kelco. Examples of suitable xanthan gums are Keltrol, Keltrol F, Keltrol T, Keltrol TF, Xantural 180, and Vanzan NF-ST.In one example, xanthan gum can be used as a thickener in the composition in an amount of 0.1% by weight to 1% by weight, for example, in an amount of 0.14% by weight.

[072] In one example, the secondary structuring agent used in the present invention is a dry microcrystalline coprecipitate of cellulose and sodium carboxymethyl cellulose. Sodium carboxymethyl cellulose is commonly used as a coprecipitate in microcrystalline cellulose. It is particularly useful if the sodium carboxymethyl cellulose is included in the range of about 8 percent by weight to about 19 percent by weight. Petition 870250088117, dated 09 / 29 / 2025, pp. 38 / 60 20 / 37 of the total weight of microcrystalline cellulose is coprecipitated and sodium carboxymethyl cellulose. Useful are microcrystalline cellulose products having in the range of about 8 to about 14 percent by weight of sodium carboxymethyl cellulose. These mixtures as described above are commercially available from a variety of sources, including FMC under the trademarks Avicel® CL-611, Avicel® RC-581 and Avicel® RC591.

[073] The thickening component can be a blowing agent, which, when exposed to a suitable aqueous environment, expands and can interact with the structuring agent. Pregelatinized starch is a particularly good blowing agent. Pregelatinized starch, also called “instant” starch, is precooked so that it expands and begins to thicken instantly when added to cold water. A particularly suitable pregelatinized starch is prepared from modified, stabilized, waxy corn starch and commercially available from the National Starch Company as Instant Starch, Ultrasperse M. In one example, pregelatinized starch can be used in the composition as a structuring and / or thickening agent in a range of about 0.1% by weight to about 5.0% by weight, or about 1.0% by weight to about 2.0% by weight. In one example, pregelatinized starch can be used in the composition in an amount of about 1.75% by weight.

[074] In certain examples, an optional auxiliary suspending agent may be used. The auxiliary suspending agent may be selected from the group consisting of hydroxyethylcellulose and a pharmaceutically acceptable salt of carboxymethylcellulose. Suitable pharmaceutically acceptable salts of carboxymethylcellulose (as may be selected from or be selected from the group consisting of) may include sodium and calcium salts of a polycarboxymethyl ether of cellulose, commercially available as sodium carboxymethylcellulose, USP and calcium carboxymethylcellulose, NF. Sodium carboxymethylcellulose, USP contains between approximately Petition 870250088117, dated 09 / 29 / 2025, pp. 39 / 60 21 / 37 6.5 to approximately 7.5% by weight of sodium on a dry basis and is commercially available from Aqualon Co. under the product name Aqualon. Hydroxyethylcellulose is a partially substituted poly(hydroxyethyl) cellulose ether. Hydroxycellulose, NF is commercially available from Aqualon Co. under the product name Natrosol.

[075] In examples where the composition is a suspension, it may also include at least one thickening agent. In examples where the composition is an oral solution, it may be substantially free of a thickening agent. As used herein, substantially free is defined as less than 0.1 percent, preferably less than 0.05 percent, preferably less than 0.001 percent, weight by volume. Additional sweeteners

[076] In addition to the bulk sweetener, it may be advantageous to add a second sweetener. The second sweetener may be an artificial sweetener or a natural sweetener. Artificial sweeteners include, but are not limited to, aspartame, neotame, saccharin, and sucralose. Natural sweeteners include, but are not limited to, stevia or steviol glycosides, monk fruit extract, licorice root extract, and other licorice derivatives. The additional sweetener may be added from about 0.01% by weight to about 5% by weight, or from about 0.1% by weight to about 3% by weight of the total composition.

[077] According to one example, the composition may also exclude certain ingredients. The term “completely free of” refers to a composition with a complete absence of an ingredient.

[078] In one example, the composition is free of a bulk sweetener that has a fructose content greater than 75 percent, or greater than 70 percent, or greater than 50 percent. In another example, the total fructose content of the composition is less than 0.9 g / mL or less than 0.7 g / mL. In another example, the total amount of sugar in the composition is less than 0.9 g / mL or less than 0.7 g / mL. The present composition Petition 870250088117, dated 09 / 29 / 2025, pp. 40 / 60 22 / 37 may be substantially free or completely free of agave syrup. The present composition may be substantially free or completely free of corn syrup or high-fructose corn syrup. The present composition may be substantially free or completely free of fructose.

[079] The total amount of sugar administered can be determined within a dosing regimen or method of use of the composition of the present invention. The amount of sugar in a 24-hour dosing regimen may be less than 60 grams of sugar, or less than 50 grams of sugar, or less than 40 grams of sugar when calculated for the therapeutic amount of the composition. Total sugar is defined as the combined amount of sugars, including sucrose, maltose, lactose, glucose, and fructose. pH adjuster

[080] The composition may also include a pH adjuster, or acidulant, for example, anhydrous citric acid. In one example, anhydrous citric acid is present in an amount of about 0.01% by weight to about 1.5% by weight, or about 0.08% by weight. Stability

[081] The invention of the present composition may be stable when stored under accelerated conditions or ambient conditions for up to 24 months, or, under such conditions, up to 1 month, or up to 3 months, or up to 6 months, or up to 12 months, or up to 18 months. Accelerated conditions may include storage at 30°C, 40°C, 50°C, 60°C and under freeze-thaw conditions. Stability includes physical stability, such as, but not limited to, viscosity, water activity and density; chemical stability, such as degradation of the active ingredient; and microbial stability using antimicrobial effectiveness testing (AET). Water activity Petition 870250088117, dated 09 / 29 / 2025, page 41 / 60 23 / 37

[082] Water activity (aw) is a measure of the energy state of water in a system. It indicates how tightly water is “bound,” structurally or chemically, within a substance. Water activity is the relative humidity of air in equilibrium with a sample in a sealed measuring chamber. Water activity is defined as the ratio of the vapor pressure of water in the sample to the vapor pressure of pure water at the same temperature. The concept of water activity is of particular importance in determining product quality and safety.

[083] Water activity is the best index for microbial growth. A product may contain a relatively large percentage of moisture, but if the water is chemically “bound” to humectants or solutes, such as salts, sugars, or polyols, the water will be biologically unavailable for microbial growth. Water activity measures the amount of water available (unbound) for chemical and biochemical reactions and for microbial growth to occur. Every microorganism has a limiting water activity level below which it cannot grow.

[084] Knowledge of the water activity of pharmaceutical substances, i.e., drugs and excipients, is essential to obtain a product formulation with ideal chemical, physical, microbial and shelf-life properties. Water activity influences chemical stability, microbial stability, flow properties, compaction, hardness and dissolution rate of pharmaceutical dosage forms. Instrument / method for measuring water activity:

[085] Instrument: Aqualab Series 4TEV Dew Point Water Activity Meter (Uses a chilled mirror dew point sensor and a capacitance sensor to measure non-volatile and volatile substances, respectively). The instrument has the following attributes: Water activity range: 0.030 to 1.000 aw Water activity accuracy: ±0.003 (4TE dew point mode) Petition 870250088117, dated 09 / 29 / 2025, page 42 / 60 24 / 37 Water activity accuracy: ±0.015 (4TEV Capacitance Mode) Reading time 1: <5 min. Sample temperature range: 15 to 50°C Sample temperature accuracy: ±0.2°C Sample tray capacity: 15 ml (Full) Operating Environment: 5 to 50°C, 20 to 80% humidity

[086] The aw is performed after a verification of the Aqualab water activity calibration against known verification standards to ensure optimal performance and accuracy. The verification standards are specially prepared unsaturated saline solutions with a specific molality and water activity value that are accurately measurable. The calibration verification is performed using two known verification standards (0.760 aw and 0.250 aw) before use.

[087] The Aqualab water activity meter uses the chilled mirror dew point technique to measure the water activity of a sample. In an instrument that uses the dew point technique, the sample is equilibrated with the headspace of a sealed chamber containing a mirror and a means of detecting condensation on the mirror. At equilibrium, the relative humidity of the air in the chamber is the same as the water activity of the sample. In the AquaLab water activity meter, the temperature of the mirror is precisely controlled by a thermoelectric chiller. The detection of the exact point at which condensation first appears on the mirror is observed with a photoelectric cell. A beam of light is directed at the mirror and reflected onto a photodetector cell. The photodetector detects the change in reflectance when condensation occurs on the mirror. A thermocouple connected to the mirror records the temperature at which condensation occurs.The AquaLab water activity meter then beeps and displays the final water activity and temperature. In addition to the technique described above, the AquaLab water activity meter uses an internal fan that circulates air within the sample chamber to reduce... Petition 870250088117, dated 09 / 29 / 2025, pp. 43 / 60 25 / 37 equilibrium time. Since both the condensation point and the sample surface temperatures are measured simultaneously, the need for complete thermal equilibrium is eliminated, which reduces measurement times to less than five minutes. Examples

[088] The following examples presented below further illustrate examples of the present invention. The present invention is not limited to the examples described. Example 1: Acetaminophen suspension (Fruit-Up®:Glycerin Up ratio 1.2:1)

[089] The present example was prepared using the formula in Table 2. The ratio of the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, to glycerin in the present example is 1.2:1. Table 2. Acetaminophen suspension formulation comprising Fruit-Up® syrup_______________________________________________________________ Ingredient Function mg / 5 ml % W / V (g / 100 ml) Purified water Volume diluent 750.0 15 Acetaminophen API 160.0 3.2 Pregelatinized starch Structuring / thickening agent 87.375 1.7475 Xanthan gum Thickener 7.0 0.14 Combination of apple syrup and carob syrup1 Volume sweetener 1750.0 35.00 Anhydrous citric acid Acidulant (pH adjustment) 4.0 0.08 Potassium sorbate Preservative 10.0 0.2 Glycerin Volume sweetener 1500.0 30 Combination of apple syrup and carob syrup1 Volume sweetener QS2 QS for 100 ml TOTAL 100 mL 1: Product commercially available under the trademark Fruit-Up® of ADM Company Petition 870250088117, dated 09 / 29 / 2025, pp. 44 / 60 26 / 37 2; “QS” is a term to indicate that this material was used to complete up to a final target volume (sufficient quantity). Processing instructions 1. Purified water was added to a tared container equipped with a high-shear mixer to achieve a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum were added during mixing and stirred until dissolved. 3. Fruit-Up®, citric acid, potassium sorbate, and glycerin were added and mixed until dissolved. 4. Paracetamol was added and mixed until uniformly suspended. 5. The solution was brought (“QS’d”) to the final volume with Fruit-Up® syrup and mixed under vacuum to deaerate. Example 2: Acetaminophen suspension (Fruit-Up®:Glycerin Up ratio 3:1)

[090] The present example was prepared using the formula in Table 3. The ratio of the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, to glycerin in the present example is 3:1. Table 3. Acetaminophen suspension formulation Ingredient Function mg / 5 ml % PA / (g / 100 ml) Acetaminophen API 160.0 3.2 Pregelatinized starch Structuring / thickening agent 87.375 1.7475 Xanthan gum Thickener 7.0 0.14 Combination of apple syrup and locust bean syrup1 Bulking sweetener 3281.25 65.625 Anhydrous citric acid Acidulant (pH adjustment) 2.94 0.0588 Potassium sorbate Preservative 10.0 0.2 Glycerin Bulking sweetener 1093.75 21.875 Petition 870250088117, dated 09 / 29 / 2025, pp. 45 / 60 27 / 37 Combination of apple syrup and carob syrup1 Bulking sweetener QS2 QS per 100 ml TOTAL 100 mL 1: Product commercially available under the trademark Fruit-Up® from ADM2 Company; “QS” is a term to indicate that this material has been used to complete up to a final target volume (sufficient quantity). Processing instructions 1. Fruit-Up® syrup was added to a tared container fitted with a high-shear mixer to obtain a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum were added during mixing and stirred until dissolved. 3. Citric acid, potassium sorbate, and glycerin were added and mixed until dissolved. 4. Paracetamol was added and mixed until uniformly suspended. 5. The solution was brought (QS'd) to the final volume with Fruit-Up® syrup and mixed under vacuum to deaerate. Example 3: Acetaminophen suspension (Fruit-Up®:Glycerin ratio 3:1, without potassium sorbate)

[091] The present example was prepared using the formula in Table 4. In the present example, the ratio between the combination of apple syrup and carob syrup, for example, as sold commercially under the trademark Fruit-Up® from ADM Company, and glycerin was 3:1. Note further that the present example does not contain potassium sorbate. Table 4. Acetaminophen suspension formulation Ingredient Function mg / 5 ml % W / V (g / 100 ml) Acetaminophen API 160.0 3.2 Pregelatinized starch Structuring / thickening agent 87.375 1.7475 Xanthan gum Thickener 7.0 0.14 Petition 870250088117, dated 09 / 29 / 2025, pp. 46 / 60 28 / 37 Combination of apple syrup and carob syrup1 Sweetener by volume 3281.25 65.625 Glycerin Sweetener by volume 1093.75 21.875 Natural flavoring Flavoring 10.00 0.2 Combination of apple syrup and carob syrup1 Sweetener by volume QS2 QS for 100 ml TOTAL 100 mL 1: Product commercially available under the trademark Fruit-Up® of ADM Company 2; “QS” is a term to indicate that this material was used to complete up to a final target volume (sufficient quantity). Processing instructions 1. Fruit-Up® syrup was added to a tared container fitted with a high-shear mixer to obtain a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum were added during mixing and stirred until dissolved. 3. The flavoring and glycerin were added and mixed until dissolved. 4. Paracetamol was added and mixed until uniformly suspended. 5. The solution was brought (“QS’d”) to the final volume with Fruit-Up® syrup and mixed under vacuum to deaerate. Example 4: Acetaminophen suspension (Fruit-Up®:Glycerin ratio 2.6:1, with potassium sorbate)

[092] The present example was prepared using the formula in Table 5. In the present example, the ratio between the combination of apple syrup and carob syrup, for example, as sold commercially under the trademark Fruit-Up® from ADM Company, and the glycerins was 2.6:1. The present example also includes potassium sorbate. Table 5. Acetaminophen suspension formulation Ingredient Function mg / 5 ml % W / V (g / 100 ml) Petition 870250088117, dated 09 / 29 / 2025, pp. 47 / 60 29 / 37 Acetaminophen API 160.0 3.2 Pregelatinized starch Structuring / thickening agent 87.375 1.7475 Xanthan gum Thickener 7.0 0.14 Combination of apple syrup and carob syrup 11 Bulking sweetener 3281.25 65.625 Anhydrous citric acid Acidulant (pH adjustment) 2.94 0.0588 Potassium sorbate Preservative 10.0 0.2 Glycerin Bulking sweetener 1250.00 25.00 Combination of apple syrup and carob syrup1 Bulking sweetener QS2 QS for 100 ml TOTAL 100 mL 1: Product commercially available under the trademark Fruit-Up® of ADM Company 2; “QS” is a term to indicate that this material was used to complete up to a final target volume (sufficient quantity). Processing instructions 1. Fruit-Up® syrup was added to a tared container fitted with a high-shear mixer to obtain a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum were added during mixing and stirred until dissolved. 3. Citric acid, potassium sorbate, and glycerin were added and mixed until dissolved. 4. Paracetamol was added and mixed until uniformly suspended. 5. The solution was brought (“QS’d”) to the final volume with Fruit-Up® syrup and mixed under vacuum to deaerate. Example 5: Acetaminophen suspension (Fruit-Up®:Glycerin ratio 2.6:1, without potassium sorbate) [0 93] The present example was prepared using the formula in Table 6. The ratio of the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, in Petition 870250088117, dated 09 / 29 / 2025, pp. 48 / 60 The ratio of 30 / 37 to glycerin in this example is 2.6:1. This example does not include potassium sorbate. Table 6. Acetaminophen suspension formulation Ingredient Function mg / 5 ml % W / V (g / 100 ml) Acetaminophen API 160.0 3.2 Pregelatinized starch Structuring / thickening agent 87.375 1.7475 Xanthan gum Thickener 7.0 0.14 Combination of apple syrup and carob syrup1 Bulking sweetener 3281.25 65.625 Glycerin Bulking sweetener 1250.00 25.00 Natural flavoring Flavoring 10.00 0.2 Combination of apple syrup and carob syrup1 Bulking sweetener QS2 QS for 100 ml TOTAL 100 mL 1: Product commercially available under the registered trademark Fruit-Up® of ADM Company 2; “QS” is a term to indicate that this material was used to complete up to a final target volume (sufficient quantity). Processing instructions 1. Fruit-Up® syrup was added to a tared container fitted with a high-shear mixer to obtain a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum were added during mixing and stirred until dissolved. 3. The flavoring and glycerin were added and mixed until dissolved. 4. Paracetamol was added and mixed until uniformly suspended. 5. The solution was brought (“QS’d”) to the final volume with Fruit-Up® syrup and mixed under vacuum to deaerate. Example 6: Acetaminophen suspension (Fruit-Up®:Glycerin ratio 4.1:1, with potassium sorbate and sodium citrate) [0 94] The present example was prepared using the formula in Table 7. A Petition 870250088117, dated 09 / 29 / 2025, pp. 49 / 60 31 / 37 The ratio of the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, to glycerin in the present example is 4.1:1. Table 7. Acetaminophen suspension formulation Ingredient Function mg / 5 ml % W / V (g / 100 ml) Acetaminophen API 160.0 3.2 Pregelatinized starch Structuring / thickening agent 87.375 1.7475 Xanthan gum Thickener 7.0 0.14 Combination of apple syrup and locust bean syrup1 Bulking sweetener 5122.56 102.45 Glycerin Bulking sweetener 1250.00 25.00 Natural flavoring Flavoring 30.00 0.6 Potassium sorbate Preservative 10.00 0.2 Sodium citrate pH adjusting agent 1.63 0.0325 Anhydrous citric acid, USP pH adjusting agent 2.94 0.0588 Combination of apple syrup and locust bean syrup1 Bulking sweetener QS2 QS for 100 ml TOTAL 100 mL 1: Product commercially available under the registered trademark Fruit-Up® of ADM Company 2; “QS” is a term to indicate that this material was used to complete up to a final target volume (sufficient quantity). Processing instructions 1. Fruit-Up® syrup was added to a tared container fitted with a high-shear mixer to obtain a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum were added during mixing and stirred until dissolved. 3. The flavoring, potassium sorbate, sodium citrate, anhydrous citric acid, and glycerin were added and mixed until dissolved. 4. Paracetamol was added and mixed until uniformly suspended. 5. The solution was brought (“QS’d”) to the final volume with Fruit-Up® syrup and Petition 870250088117, dated 09 / 29 / 2025, pages 50 / 60 32 / 37 mixed under vacuum to deaerate. Example 7: Ibuprofen suspension (Fruit-Up®:Glycerin Up ratio 1.6:1)

[095] The present example was prepared using the formula in Table 8. The ratio of the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, to glycerin in the present example is 1.6:1. Table 8. Ibuprofen suspension formulation comprising syrup -ruit-Up® Ingredient Function mg / 5 ml % PA / (g / 100 ml) Purified water Volume diluent 750.0 15.0 Ibuprofen API 100.0 2.0 Pregelatinized starch Structuring / thickening agent 87.4 1.7475 Xanthan gum Thickener 7.0 0.14 Combination of apple syrup and locust bean syrup1 Volume sweetener 2450.0 49.0 Anhydrous citric acid Acidulant (pH adjustment) 4.0 0.08 Potassium sorbate Preservative 10.0 0.2 Glycerin Volume sweetener 1500.0 30.0 Fruit-Up® Volume sweetener QS2 QS for 100 ml TOTAL 100 mL 1: Product commercially available under the registered trademark Fruit-Up® of ADM Company 2; “QS” is a term to indicate that this material was used to complete up to a final target volume. Processing instructions 1. Purified water is added to a tared container equipped with a high-shear mixer to achieve a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum are added during mixing and mixed until dissolved. 3. Fruit-Up®, citric acid, potassium sorbate, and glycerin are Petition 870250088117, dated 09 / 29 / 2025, pp. 51 / 60 33 / 37 added and mixed until dissolved. 4. Ibuprofen is added and mixed until uniformly suspended. 5. The solution is brought (“QS’d”) to the final volume with Fruit-Up® syrup and mixed under vacuum to deaerate. Example 8: Fexofenadine suspension (Fruit-Up®:Glycerin Up ratio 1.6:1)

[096] The present example was prepared using the formula in Table 9. The ratio of the combination of apple syrup and carob syrup, for example, as commercially sold under the trademark Fruit-Up® from ADM Company, to glycerin in the present example is 1.6:1. Table 9. Fexofenadine suspension formulation comprising syrup -ruit-Up® Ingredient Function mg / 5 ml % PA / (g / 100 ml) Purified water Volume diluent 750.0 15.0 Fexofenadine HCl API 180.0 3.6 Pregelatinized starch Structuring / thickening agent 87.4 1.7475 Xanthan gum Thickener 7.0 0.14 Combination of apple syrup and locust bean syrup1 Volume sweetener 2370.0 47.4 Anhydrous citric acid Acidulant (pH adjustment) 4.0 0.08 Potassium sorbate Preservative 10.0 0.2 Glycerin Volume sweetener 1500.0 30.0 Fruit-Up® Volume sweetener QS2 QS for 100 ml TOTAL 100 mL 1: Product commercially available under the trademark Fruit-Up® of ADM Company 2; “QS” is a term to indicate that this material was used to complete up to a final target volume. Processing instructions 1. In a tared vessel equipped with a high-shear mixer, the Petition 870250088117, dated 09 / 29 / 2025, pp. 52 / 60 34 / 37 purified water is added to achieve a suitable volume for mixing. 2. Pregelatinized starch and xanthan gum are added during mixing and mixed until dissolved. 3. Fruit-Up®, citric acid, potassium sorbate, and glycerin are added and mixed until dissolved. 4. Fexofenadine HCl is added and mixed until uniformly suspended. 5. The solution is brought (“QS’d”) to the final volume with Fruit-Up® syrup and mixed under vacuum to deaerate. Example 9: Physical properties

[097] Data were collected on acetaminophen formulations for density, pH, water activity, and viscosity using variations of the formula in Examples 2, 3, 4, and 5; and are shown in Table 10. Petition 870250088117, dated 09 / 29 / 2025, pp. 53 / 60 35 / 37 Table 10. Physical properties Example No. Formulation Density (g / ml) Temperature at density (°C) pH (R1) / T (°C) pH (R2) / T (°C) Water activity Viscosity (cps1) 2 3:1 FruitUp® / glycerin 1.338 2 23.1 5.13 / 22.0 5.08 / 23.3 0.654 6980 3 3:1 FruitUp® / glycerin, without added potassium sorbate or citric acid 1.338 1 22.3 4.57 / 22.0 4.31 / 22.5 0.658 7400 4 2.6:1 FruitUp® / glycerin 1.334 3 22.7 4.72 / 22.0 4.75 / 22.8 0.640 6780 5 2.6:1 FruitUp® / glycerin, without potassium sorbate and citric acid 1.331 2 22.8 4.36 / 21.6 4.14 / 22.8 0.648 3060 6 4.1:1 FruitUp® / glycerin 1.234 9 22.8 4.90 / 24.8 N / AN / A 1480 1: cps refers to centipoise N / A: Not applicable

[098] Viscosity measurement was performed using a Brookfield DV2T LV type viscometer coupled to a small sample adapter kit and spindle #31. The measurement temperature of 25°C was maintained using a temperature-controlled water bath for all samples. For each measurement, 9 mL of sample were loaded without air bubbles. The spindle rotation speed was set to 1.5 RPM and readings were recorded in cps after 2 minutes of rotation. The data are shown in Table 10. Example 10: Testing and stability

[099] The formula in Example 6 was tested for acetaminophen. Petition 870250088117, dated 09 / 29 / 2025, pp. 54 / 60 36 / 37 and tested for stability at the following time points: Baseline (Time = 0), 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks, and stored under various conditions as shown in Table 11. The total amount of acetaminophen and degradation products was analyzed using a reference standard prepared at 100% of the dose claimed on the label. Samples were removed from the top and bottom of the vial and tested. The samples and standard were diluted and mixed in a diluent consisting of buffer:methanol at a ratio of 95:5. The buffer used for the diluent was 50 mM ammonium formate plus 0.1% formic acid.

[0100] Method: Acetaminophen and degradant assays were analyzed using ultra-high pressure liquid chromatography (UPLC) with the following parameters: Column: Waters Acquity UPLC HSS T3 1.8 pm, 150 x 2.1 mm ID

[0101] Mobile phase: Gradient method of a first mobile phase of 40 mM ammonium hexafluorophosphate (NH4PF6) in 15 mM Ammonium Formate Buffer and a second mobile phase of 80:20 ACN:40 mM NH4PF6 in 15 mM Ammonium Formate Buffer during a run time of 17 minutes. The method used a flow rate of 0.45 mL / min, an injection volume of 2.5 μL at a column temperature of 42°C and using a UV detector set to 272 nm. The suggested run time was 17 minutes.

[0102] Multiple degradants were examined for stability and the total degradants include 4-aminophenol and CC_Acetaminophen dimer. Table 11: Stability results in the acetaminophen assay for example 6______________________________________________________________ Time point (weeks, storage condition) Acetaminophen assay (%) Total degradation products (%) 0 98.1 (Top), 102.6 (Bottom) 0.0 (Top), 0.0 (Bottom) 1 week, 25°C / 60%RH1 100.8 (Top), 98.8 (Bottom) 0.0 (Top), 0.0 (Bottom) 1 week, 101.7 (Top), 100.5 0.0 (Top), 0.0 (Bottom) Petition 870250088117, dated 09 / 29 / 2025, pages 55 / 60 37 / 37 40°C / 75%RH1 (Lower) 1 week, 50°C 99.5 (Higher), 104.5 (Lower) 0.0 (Higher), 0.0 (Lower) 2 weeks, 25°C / 60%RH1 96.6 (Higher), 96.1 (Lower) 0.0 (Higher), 0.0 (Lower) 2 weeks, 40°C / 75%RH1 94.0 (Higher), 93.5 (Lower) 0.0 (Higher), 0.0 (Lower) 2 weeks, 50°C 95.1 (Higher), 111.2 (Lower) 0.0 (Higher), 0.0 (Lower) 4 weeks, 25°C / 60%RH1 97.2 (Higher), 98.3 (Lower) 0.0 (High), 0.0 (Low) 4 weeks, 40°C / 75%RH1 93.4 (High), 97.8 (Low) 0.0 (High), 0.0 (Low) 4 weeks, 50°C 98.0 (High), 101.9 (Low) 0.0 (High), 0.0 (Low) 6 weeks, 25°C / 60%RH1 96.2 (High), 96.0 (Low) 0.0 (High), 0.0 (Low) 6 weeks, 40°C / 75%RH1 97.9 (High), 97.4 (Low) 0.0 (High), 0.0 (Low) 6 weeks, 50°C 99.0 (High), 105.3 (Low) 0.0 (Upper), 0.0 (Lower) 8 weeks, 25°C / 60%RH1 93.8 (Upper), 98.4 (Lower) 0.0 (Upper), 0.0 (Lower) 8 weeks, 40°C / 75%RH1 98.8 (Upper), 101,3 (Lower) 0.0 (Top), 0.0 (Lower) 8 weeks, 50°C 99.8 (Top), 100.6 (Lower) 0.0 (Top), 0.0 (Lower), 1: RH = Relative humidity

[0103] It is understood that although the invention has been described in conjunction with the detailed description thereof, the above description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages and modifications are included in the claims. Petition 870250088117, dated 09 / 29 / 2025, pp. 56 / 60

Claims

1 / 3 CLAIMS 1. Liquid composition, CHARACTERIZED by comprising a therapeutic ingredient and a natural bulk sweetener having a fructose content of less than 50 percent of the natural bulk sweetener.

2. Liquid composition, according to claim 1, CHARACTERIZED in that the natural bulk sweetener is selected from glycerin, allulose syrup, rice syrup, tapioca syrup, apple syrup, carob syrup and combinations thereof.

3. Liquid composition, according to claim 1, CHARACTERIZED by having a total fructose level of less than 0.7 g / mL.

4. Liquid composition, according to claim 1, CHARACTERIZED in that the therapeutic ingredient is an active pharmaceutical ingredient.

5. Therapeutic liquid composition, according to claim 1, CHARACTERIZED in that the therapeutic ingredient is a homeopathic active ingredient.

6. Liquid composition, according to claim 1, CHARACTERIZED in that the therapeutic ingredient is a nutritional supplement.

7. Liquid composition according to claim 1, the liquid composition being characterized by being in the form of a suspension.

8. Liquid composition according to claim 1, the liquid composition being characterized by being in the form of a solution.

9. Liquid composition, according to claim 4, CHARACTERIZED in that the active pharmaceutical ingredient is selected from the group consisting of acetaminophen, diphenhydramine, dextromethorphan, guaifenesin, ibuprofen, cetirizine, loperamide and phenylephrine.

10. Liquid composition, according to claim 1, CHARACTERIZED in that the therapeutic ingredient is an analgesic. Petition 870250088117, dated 09 / 29 / 2025, pp. 57 / 60 2 / 3 11. Liquid composition, according to claim 1, CHARACTERIZED by further comprising a sensory agent.

12. Liquid composition, according to claim 1, CHARACTERIZED by further comprising at least one thickening agent.

13. Liquid composition, according to claim 2, CHARACTERIZED in that the natural bulk sweetener consists substantially of glycerin and a combination of apple syrup and locust bean syrup.

14. Liquid composition, according to claim 13, CHARACTERIZED by a ratio between the combination of apple syrup and locust bean syrup and glycerin being from about 2:1 to about 5:

1.

15. Liquid composition, according to claim 13, CHARACTERIZED by a ratio between the combination of apple syrup and locust bean syrup and glycerin being about 2.6:

1.

16. Liquid composition, according to claim 13, CHARACTERIZED by a ratio between the combination of apple syrup and locust bean syrup and glycerin being about 3:

1.

17. Liquid composition, according to claim 13, CHARACTERIZED by a ratio between the combination of apple syrup and locust bean syrup and glycerin being about 4.1:

1.

18. Liquid composition according to claim 1, CHARACTERIZED by further comprising a preservative.

19. Liquid composition according to claim 18, CHARACTERIZED in that the preservative comprises potassium sorbate.

20. Liquid composition according to claim 1, the liquid composition being CHARACTERIZED by being substantially free of a preservative. Petition 870250088117, dated 09 / 29 / 2025, pp. 58 / 60 3 / 3 21. Liquid composition according to claim 1, the liquid composition being characterized by being substantially free of potassium sorbate.

22. Liquid composition according to claim 1, the liquid composition being characterized by being substantially free of agave syrup.

23. Liquid composition, according to claim 1, CHARACTERIZED by being substantially free of any ingredient with a fructose content greater than 15 percent.

24. Method for relieving a selected symptom from the group consisting of pain, fever, cough, nasal congestion, diarrhea, allergic rhinitis and sore throat in an individual CHARACTERIZED by comprising administering the composition as defined in claim 1. Petition 870250088117, dated 09 / 29 / 2025, pp. 59 / 60