Chewable Compositions Comprising Pectin and Urolithin

Abstract

The present invention relates to compositions of urolithins comprising urolithins and pectin, and to formulations of urolithins, specifically chewable formulations comprising urolithins and a gelling agent. The invention further includes compositions and chewable formulations comprising urolithins in combination with other active ingredients, and processes for preparing such compositions and formulations. The invention further includes methods of using such compositions and formulations in the treatment of conditions and diseases, and for promoting health and performance, such as improving muscle function.

Description

[Technical Field]

[0001] The present invention relates to compositions of urolithins comprising urolithins and pectin, and to formulations of urolithins, specifically chewable formulations comprising urolithins and a gelling agent. The invention further includes compositions and chewable formulations comprising urolithins in combination with other active ingredients, and processes for preparing such compositions and formulations. The invention further includes methods of using such compositions and formulations in the treatment of conditions and diseases, and for promoting health and performance, such as improving muscle function. [Background technology]

[0002] Urolithins have been proposed as treatments for various conditions associated with insufficient mitochondrial activity, including obesity, reduced metabolic rate, metabolic syndrome, diabetes, cardiovascular disease, hyperlipidemia, neurodegenerative diseases, cognitive disorders, mood disorders, stress, and anxiety disorders, for weight management, or to improve muscle or mental performance. See U.S. Patent No. 5,627,999 (Amazentis SA). The use of urolithins for the treatment of various neoplastic diseases is described in U.S. Patent No. 5,627,999 (The Regents of the University of California).

[0003] Patent document 3 (derived from International Application No. PCT / US2013 / 48310) discloses a method for increasing autophagy (specifically including mitosis) in a cell, comprising contacting a cell with an effective amount of a urolithin or a pharmaceutically acceptable salt thereof, thereby increasing autophagy (specifically including mitosis) in the cell. Administration may be to a subject having a disease or condition selected from metabolic stress, cardiovascular disease, endothelial cell dysfunction, sarcopenia, muscle degenerative disease, Duchenne muscular dystrophy, alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver or muscle damage, alpha 1-antitrypsin deficiency, ischemia / reperfusion injury, inflammation, skin aging, inflammatory bowel disease, Crohn's disease, obesity, metabolic syndrome, type II diabetes, hyperlipidemia, osteoarthritis, neurodegenerative disease, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, age-related macular degeneration, mitochondrial disease (including, for example, poor growth, loss of muscle coordination, muscle weakness, visual impairment, hearing impairment, heart disease, liver disease, kidney disease, gastrointestinal disorders, respiratory disorders, neurological disorders, autonomic dysfunction, and sometimes learning disabilities, and dementia (as a result of mitochondrial disease)), muscle disease, cancer, cognitive disorders, stress, and mood disorders.

[0004] Chewable products (gummy formulations), generally made with a gelatin or pectin matrix along with sugar, glucose, corn syrup, flavorings, colorings, and citric acid, have become popular snack foods. The products (formulations) typically have a gel or gel-like structure and texture and are produced in a variety of shapes, colors, and flavors that are chewable when consumed. In recent years, gummy products have been supplemented with vitamins, minerals, essential oils, and other dietary supplements to provide a dietary supplement that appeals to children and adults who prefer not to or have difficulty swallowing tablets or capsules.

[0005] Gelatin is a soluble and gelatinous protein extracted from animal bones, skin, tendons, and muscles, and then partially hydrolyzed by acid, alkali, or enzymes.Gelatin is widely used in chewable preparations, but in recent years, the use of gelatin has been declining.This has traditionally been attributed to its animal origin, since vegetarian consumers and religious advocates of avoiding animal-derived products.In recent years, ordinary consumers, who are not concerned about vegetarianism or religious preferences, have also tended to prefer foods in which gelatin is replaced by other active substances, such as gums extracted from plants, such as pectin. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2012 / 088519 [Patent Document 2] International Publication No. 2007 / 127263 [Patent Document 3] International Publication No. 2014 / 004902 Summary of the Invention [Problem to be solved by the invention]

[0007] However, while plant-based chewable formulations, such as those containing pectin, are a popular option, they can be difficult to manufacture. Thus, there is a continuing need for improved chewable formulations containing pectin, particularly for formulating new active ingredients as chewable formulations. [Means for solving the problem]

[0008] According to one aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; [ka] wherein A, B, C, and D are each independently selected from H and OH; W, X, and Y are each independently selected from H and OH; Chewable formulations are provided wherein Z is selected from H and OH.

[0009] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof, Chewable formulations are provided wherein the formulation does not include a sweetener system.

[0010] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) a sweetener system, wherein the sweetener system comprises one or more artificial sweeteners.

[0011] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) a sweetener system, wherein the sweetener system comprises allulose.

[0012] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) a sweetener system, wherein the sweetener system comprises inulin.

[0013] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; and c) a sweetener system, wherein the sweetener system consists of one or more artificial sweeteners.

[0014] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) a pH buffering agent.

[0015] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; and c) a pH of about 2.7 to about 3.7.

[0016] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) a pH buffering agent that maintains a pH of about 2.7 to about 3.7.

[0017] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; and c) a pH of about 2.7 to about 4.0.

[0018] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) a pH buffering agent that maintains a pH of about 2.7 to about 4.0.

[0019] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; and c) a fiber component, such as a soluble fiber component.

[0020] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) a Brix of about 75 degrees to about 85 degrees, for example, about 77 degrees to about 82 degrees.

[0021] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof; c) an end boiling point of about 108°C to about 111°C (about 228°F to about 231°F).

[0022] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof, A reduced calorie chewable formulation is provided, wherein the formulation contains less than about 30% (w / w) sugar.

[0023] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof, Low-calorie chewable formulations are provided, wherein the formulation comprises less than about 50% (w / w) sugar, e.g., less than about 45% (w / w) sugar, such as less than about 40% (w / w) or less than about 30% (w / w) sugar.

[0024] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof, A low-calorie chewable formulation is provided, wherein the formulation contains about 25% to about 40% sugar.

[0025] According to a further aspect of the present invention, a) a gelling component; b) a compound of formula (I) or a salt thereof, c) A chewable formulation is provided, wherein the gelling component comprises pectin having an esterification range of about 55% to about 75%, for example, 60% to about 68%.

[0026] According to a further aspect of the present invention, a) a gelling component comprising high methoxy pectin; b) a compound of formula (I) or a salt thereof.

[0027] According to a further aspect of the present invention, a) a gelling component comprising low methoxy pectin; b) a compound of formula (I) or a salt thereof.

[0028] According to a further aspect of the present invention, a) a gelling component comprising amidated low methoxy pectin; b) a compound of formula (I) or a salt thereof.

[0029] According to a further aspect of the present invention, a) a gelling component comprising low methoxy pectin; b) a compound of formula (I) or a salt thereof; and c) a divalent cation provided by a calcium salt, such as a calcium salt selected from calcium chloride, calcium citrate, and / or calcium sulfate.

[0030] In one embodiment, the formulation comprises a calcium salt in the range of about 0.05% to about 0.1% (w / w).

[0031] Suitable gelling ingredients are those that, when used alone or in combination with other gelling ingredients, provide a cohesive gelled product. The gelling ingredient can be selected from one or more gelling agents. For example, a gelling agent selected from pectin, gelatin, and modified starch. In one embodiment, the gelling agent is selected from pectin and gelatin. In a further embodiment, the gelling agent comprises pectin and gelatin. In a further embodiment, the gelling agent comprises pectin. In a further embodiment, the gelling ingredient is pectin. In a further embodiment, the gelling agent comprises gellan and carrageenan.

[0032] In a further embodiment, the formulation comprises about 0.5% to about 5% (w / w) of a gelling component.

[0033] In a further embodiment, the formulation comprises from about 0.5% to about 4% (w / w) pectin, such as from about 0.5% to about 5% (w / w), from about 0.5% to about 4%, from about 1.5% to about 3% (w / w) pectin, such as from about 1% to about 2% (w / w), for example, from about 1.2% to about 1.8% (w / w), such as about 1.4% (w / w), for example, about 1.5% (w / w), such as about 1.6% (w / w), for example, about 1.7% (w / w) pectin.

[0034] In one embodiment, the formulation is essentially free of animal-derived products, for example, essentially free of gelatin.

[0035] In further embodiments, the gelling ingredient is selected from one or more of carrageenan, alginic acid, sodium alginate, xanthan gum, gellan gum, gum arabic, guar, and locust bean gum.

[0036] In a further embodiment, the gelling agent is selected from one or more of pectin and gelatin.

[0037] In one embodiment, the formulation comprises a gelling component comprising pectin. In a further embodiment, the formulation comprises a gelling component consisting of pectin.

[0038] Pectins suitable for the formulations of the present invention are any pectins that provide the necessary gel strength for the formulations of the present invention. In one embodiment of the present invention, the pectin is a high methoxy pectin. A high methoxy pectin is one in which at least 50% of the galacturonic acid units are esterified with methoxy groups.

[0039] In one embodiment, the methoxypectin is esterified in the range of about 50% to about 75%, e.g., about 55% to about 75%, about 55% to about 70%, or about 65% to about 75% methoxypectin. In a further embodiment, the esterification range is about 60% to about 68%. In a further embodiment, the esterification range is about 63% to about 65%. In a further embodiment, the methoxypectin is about 55% esterified, about 60% esterified, about 65% esterified, or about 70% esterified.

[0040] In a further embodiment of the invention the pectin is a low methoxy pectin, which is one in which less than 50% of the galacturonic acid units are esterified with methoxy groups.

[0041] The formulations of the present invention may further comprise fiber. In one embodiment, naturally occurring fibers are used, such as one or more selected from the group consisting of naturally occurring inulin, inulin extract, synthetic inulin, inulin hydrolysis products commonly known as fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, starch, husk, bran, oligoderivatives of psyllium, polysaccharides, polycarbophil, lignin, arabinogalactan, chitosan, oat fiber, soluble corn fiber, indigestible corn dextrin, indigestible wheat dextrin, locust bean gum and derivatives of locust bean gum, hydroxypropyl methylcellulose (HPMC), pectin, and mixtures thereof.

[0042] In some embodiments, the fiber may include inulin, wheat dextrin, or fructooligosaccharides. Inulin, wheat dextrin, and fructooligosaccharides may also act as thickeners and improve the texture of the formulation. Various loading rates of dietary fiber may be incorporated into the formulation to produce improved texture, and certain loading rates may provide dietary benefits, including promoting a healthy digestive system, controlling blood sugar levels, and providing probiotic benefits. The addition of dietary fiber with the remaining ingredients allows for the addition of water, which helps replace sugar in flavored chewy or gummy confections.

[0043] In a further embodiment, the fiber is selected from soluble tapioca, psyllium husk powder, apple fiber, dextrin, inulin, or mixtures thereof.

[0044] In one embodiment, the fibers may be present in an amount of about 10% to about 60% (w / w), alternatively about 20% to about 60% (w / w), alternatively about 30% to about 60% (w / w), alternatively about 30% to about 50% (w / w), alternatively about 30% to about 40%, such as about 35% (w / w), for example, about 37% (w / w), for example, about 40% (w / w).

[0045] Conventional chewable formulations contain 6% (w / w) or less of the active ingredient. However, through careful selection of the active ingredient, the formulations of the present invention can contain more than about 20% (w / w) of the active ingredient. In some embodiments, the formulations can contain from about 5% to about 25% (w / w) of the active ingredient, for example, from about 6% to about 25% (w / w) of the active ingredient, for example, from about 10% to about 25% (w / w) of the active ingredient, for example, from about 15% to about 25% (w / w) of the active ingredient, for example, from about 10% to about 20% (w / w) or from about 6% to about 20% of the active ingredient, for example, from about 20% (w / w) of the active ingredient.

[0046] In one embodiment, the chewable formulations of the present invention have a reduced sugar content compared to conventional commercially available chewable formulations, such as less than about 70% (w / w) sugar, such as less than about 60% (w / w), such as less than about 50% (w / w), such as less than about 40% (w / w), such as less than about 30% (w / w), such as less than about 25% sugar, such as less than about 20% (w / w), less than about 15% sugar, less than about 10%, less than about 5%, or about 0% sugar.

[0047] In one embodiment, the formulations of the present invention further comprise an additive selected from sweeteners, food acids, flavoring agents, coloring agents, humectants, bulking agents, fatty acids, triglycerides, plasticizers, emulsifiers, thickeners, preservatives, and / or mixtures thereof. In a further embodiment, the formulations of the present invention comprise an additive selected from sweeteners, food acids, flavoring agents, and coloring agents.

[0048] sweetener Generally, an effective amount of sweetener can be utilized to provide the desired level of sweetness, and this amount can vary depending on the sweetener selected. The sweetener can include one or more monosaccharides or disaccharides. Examples include sugar, sucrose, invert sugar, dextrose, lactose, honey, malt syrup, malt syrup solids, maltose, fructose, granulated fructose, maple syrup, rice syrup, rice syrup solids, sorghum syrup, refiner syrup, corn syrup, corn syrup solids, high fructose corn syrup, molasses, or a combination thereof.

[0049] In one embodiment, sweeteners include common sugars such as sucrose and glucose, polyols such as maltitol, erythritol, and isomalt, syrup sweeteners such as glucose syrup, corn syrup, high fructose corn syrup, and concentrated juice, hi a further embodiment, the sweetener includes allulose.

[0050] In one embodiment, artificial sweeteners such as acesulfame K, aspartame, sucralose, d-tagatose, neotame, monatin, and acesulfame potassium (Ace-K), or combinations thereof, can be used.

[0051] In further embodiments, sweeteners include saccharin, saccharin sodium, sodium cyclamate, acesulfame potassium, thaumatin, neohesperidin dihydrochalcone, ammonium glycyrrhizinate, and aspartame.

[0052] The sweeteners involved may be selected from a wide range of materials, including water-soluble sweeteners, water-soluble artificial sweeteners, water-soluble sweeteners derived from naturally occurring water-soluble sweeteners, dipeptide-based sweeteners, and protein-based sweeteners, including mixtures thereof. While not limited to specific sweeteners, representative categories and examples include the following: (a) water-soluble sweeteners such as dihydrochalcones, monellin, stevioside, Momordica oleracea, Momordica oleracea derivatives, glycyrrhizin, dihydroflavonols, and sugar alcohols such as sorbitol, mannitol, maltitol, xylitol, erythritol, and L-aminodicarboxylic acids, aminoalkenoic acid ester amides such as those disclosed in U.S. Pat. No. 4,619,834, which is incorporated herein by reference, and mixtures thereof; b) Water-soluble artificial sweeteners such as soluble saccharin salts, i.e., saccharin sodium or calcium salt, cyclamate salts, sodium, ammonium, or calcium salt of 3,4-dihydro-6-methyl-1,2,3-oxathiazin-4-one-2,2-dioxide, potassium salt of 3,4-dihydro-6-methyl-1,2,3-oxathiazin-4-one-2,2-dioxide (acesulfame-K), the free acid form of saccharin, and mixtures thereof; (c) L-aspartic acid-derived sweeteners such as L-aspartyl-L-phenylalanine methyl ester (aspartame), N-[Nl-(3,3-dimethylbutyl)-L-alpha-aspartyl]-L-phenylalanine 1-methyl ester (neotame), and the materials described in U.S. Pat. No. 3,492,131; dipeptide sweeteners such as L-alpha aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamide hydrate (alitame), the methyl esters of L-aspartyl-L-phenylglycerin and L-aspartyl-L-2,5-dihydrophenylglycine, L-aspartyl-2,5-dihydro-L-phenylalanine, L-aspartyl-L-(l-cyclohexene)-alanine, and mixtures thereof; (d) Water-soluble sweeteners derived from naturally occurring water-soluble sweeteners, such as chlorinated derivatives of common sugar (sucrose), e.g., chlorodeoxysugar derivatives, e.g., derivatives of chlorodeoxysucrose or chlorodeoxygalactosucrose, known under the trade name sucralose (examples of chlorodeoxysucrose and chlorodeoxygalactosucrose derivatives include 1-chloro-l'-deoxysucrose, 4-chloro-4-deoxy-α-D-galactopyranosyl-α-D-fructofuranoside, or 4-chloro-4-deoxygalactosucrose, 4-chloro-4-deoxy-α-D-galactopyranosyl-l-chloro-l-deoxy-β-D-fructo-furanoside, or 4,r-dichloro-4,r-dideoxygalactosucrose, l',6'-dichlorol',6'-dideoxysucrose, 4-chloro-4-deoxy-α-D- Galactopyranosyl-l,6-dichloro-l,6-dideoxy-β-D-fructofuranoside, or 4,r,6'-trichloro-4,r,6'-trideoxygalactosucrose, 4,6-dichloro-4,6-dideoxy-α-D-galactopyranosyl-6-chloro-6-deoxy-β-D-fructofuranoside, or 4,6,6'-trichloro-4,6,6'-trideoxygalactosucrose, 6,r,6'-trichloro 4,6-dichloro-4,6-dideoxy-α-D-galactopyranosyl-l,6-dichloro-l,6-dideoxy-β-D-fructofuranoside, or 4,6,r,6'-tetrachloro-4,6,r,6'-tetradeoxygalactosucrose, and 4,6,r,6'-tetradeoxy-sucrose, and mixtures thereof), (e) protein-based sweeteners such as Thaumacoccus danielli (thaumatin I and II) and talin; and (f) Sweeteners: monatin (2-hydroxy-2-(indol-3-ylmethyl)-4-aminoglutaric acid) and derivatives thereof. High-intensity sweeteners may be used in many distinct physical forms known in the art to provide an initial burst of sweetness and / or a long-lasting sensation of sweetness. Such physical forms include, but are not limited to, free form, spray-dried form, powdered form, beaded form, encapsulated form, and mixtures thereof. In one embodiment, the sweetener is a high-intensity sweetener such as aspartame, sucralose, and acesulfame potassium (e.g., Ace-K or acesulfame-K).

[0053] In some embodiments, the sweetener may be a polyol, which may include, but is not limited to, glycerol, sorbitol, maltitol, maltitol syrup, mannitol, isomalt, erythritol, xylitol, hydrogenated starch hydrolysates, polyglycitol syrup, polyglycitol powder, lactitol, and combinations thereof.

[0054] Generally, an effective amount of high-intensity sweetener can be utilized to provide the desired level of sweetness, and this amount can vary depending on the sweetener selected. High-intensity sweeteners can be present in amounts of about 0.001% to about 3% by weight of the formulation, depending on the sweetener or combination of sweeteners used. The exact range of amounts for each type of sweetener can be selected by those skilled in the art.

[0055] In one embodiment, the formulation may include a sweetener, including, for example, sugar, glucose syrup, corn syrup, high fructose corn syrup, concentrated juice, or mixtures thereof. In one embodiment, the sweetener is erythritol, xylitol, sugar, glucose syrup, corn syrup, high fructose corn syrup, concentrated juice, tapioca syrup, agave syrup, brown rice syrup, high maltose syrup, invert sugar, artificial sweeteners, saccharin, saccharin salts, cyclamic acid, cyclamate salts, aspartame, sucralose, acesulfame, rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside B, rebaudioside C, rebaudioside C, rebaudioside D, rebaudioside E, rebaudioside F, rebaudioside G, rebaudioside I ... Udioside D, Rebaudioside E, Dulcoside A, Dulcoside B, Rubusoside, Stevia, Stevioside, Mogroside IV, Mogroside V, Luo Han Guo Sweetener, Siamenoside, Monatin and its salts (Monatin SS, RR, RS, SR), Curculin, Glycyrrhizic acid and its salts, Thaumatin, Monellin, Mabinlin, Brazzein, Hernandurucin, Phyllodulcin, Glyciphyllin, Phloridzin, Trilobatin, Bayunoside, Osla Gin, polypodoside A, pterocaryoside A, pterocaryoside B, mukuroziosid, phlomisoside I, periandrin I, abrusoside A, cyclocaryoside I, sucralose, acesulfame potassium and other salts, aspartame, alitame, saccharin, neohesperidin dihydrochalcone, cyclamate, neotame, N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-α-aspartyl]- Includes L-phenylalanine 1-methyl ester, N-[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, N-[N-[3-(3-methoxy-4-hydroxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, salts thereof, licorice or an extract or isolate thereof, or a mixture thereof.

[0056] food acid The pH of the formulation is about 2.5 to about 4, for example, about 2.7 to about 4, or about 2.8 to about 3.7. The pH can be adjusted with food acids, buffers, or both.

[0057] Suitable food acids include, but are not limited to, acetic acid, adipic acid, ascorbic acid, butyric acid, citric acid, formic acid, fumaric acid, lactic acid, phosphoric acid, malic acid, oxalic acid, succinic acid, tartaric acid, or combinations thereof.

[0058] Suitable buffering agents include, but are not limited to, sodium ascorbate, sodium citrate, sodium malate, sodium fumarate, potassium sodium tartrate, and / or sodium tartrate.

[0059] Flavoring agents In some embodiments, the formulation may further comprise a flavoring agent. The flavoring agent may include flavors known to those skilled in the art, such as natural and artificial flavors. These flavoring agents may be selected from synthetic flavor oils and flavor aromatics and / or oils, oleoresins and extracts derived from plants, leaves, flowers, fruits, etc., and combinations thereof.

[0060] In some embodiments, the flavoring agent may include mint, menthol, menthone, isomenthone, camphor and eucalyptol, eucalyptol, camphor, borneol, fenchone, menthone and isomenthone, isopulegol, monomenthyl succinate and menthyl lactate, menthone, isomenthone, borneol, fenchone, eucalyptol, ethyl benzoate, neomenthol, d-fenchone, furfurylidene butyrate, Butsch distillate, sage oil, corn mint oil, rosemary, monomenthyl succinate, amyl salicylate, eugenol, phellandrene, propyl furoate, ethyl 3-hydroxybutyrate, hexyl valerate, anisyl propionate, anisyl butyrate, dihydrocarveol, or clary sage. Non-limiting representative flavor oils include spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate), peppermint oil, mint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, nutmeg oil, allspice, sage oil, mace, bitter almond oil, and cassia oil. Also useful flavors are artificial, natural, and synthetic fruit flavors such as vanilla and citrus oils including lemon, orange, lime, grapefruit, yuzu, and sudachi, and fruit essences including apple, pear, peach, grape, blueberry, strawberry, raspberry, cherry, plum, pineapple, apricot, banana, melon, apricot, plum, cherry, raspberry, blackberry, tropical fruit, mango, mangosteen, pomegranate, papaya, and the like.Other potential flavors that can manage the release profile include milk flavors, butter flavors, cheese flavors, cream flavors, and yogurt flavors, tea or coffee flavors such as vanilla flavors, green tea flavors, oolong tea flavors, tea flavors, cocoa flavors, chocolate flavors, and coffee flavors, mint flavors such as peppermint flavors, spearmint flavors, and peppermint flavors, asafoetida flavors, ajwain flavors, anise flavors, angelica flavors, fennel flavors, allspice flavors, cinnamon flavors, chamomile flavors, mustard flavors, cardamom flavors, caraway flavors, cumin flavors, clove flavors, pepper flavors, coriander flavors, sassafras flavors. seasonings, including spicy flavors such as savory flavors, Japanese pepper flavor, shiso flavor, juniper berry flavor, ginger flavor, star anise flavor, horseradish flavor, thyme flavor, tarragon flavor, dill flavor, chili pepper flavor, nutmeg flavor, basil flavor, marjoram flavor, rosemary flavor, bay leaf flavor, and wasabi (Japanese horseradish) flavor; alcohol flavors such as wine flavor, whiskey flavor, brandy flavor, rum flavor, gin flavor, and liqueur flavor; floral flavors; and vegetable flavors such as onion flavor, garlic flavor, cabbage flavor, carrot flavor, celery flavor, mushroom flavor, and tomato flavor. These flavoring agents can be used in liquid or solid form and can be used individually or in admixture. Commonly used flavoring agents, whether employed individually or in admixture, include mints such as peppermint, menthol, spearmint, artificial vanilla, cinnamon derivatives, and various fruit flavors. Flavoring agents can also provide breath freshening properties, particularly mint flavoring, when used in combination with the cooling agents described below.In some embodiments, the flavoring agent may be selected from geraniol, linalool, nerol, nerolidal, citronellol, heliotropin, methylcyclopentenolone, ethyl vanillin, maltol, ethyl maltol, furaneol, allium compounds, phenethanol, phenylacetic acid, nerol, rose-type compounds such as linalyl esters, jasmine, sandalwood, patchouli, and / or cedarwood.

[0061] In some embodiments, other flavorings may be used, including aldehydes and esters such as cinnamyl acetate, cinnamaldehyde, citral diethyl acetal, dihydrocarbyl acetate, eugenyl formate, p-methylamisole, and the like. Generally, any flavoring and food additive may be used, such as those listed by the National Academy of Sciences in "Chemicals Used in Food Processing," publication 1274, pages 63-258. This publication is incorporated herein by reference. These may include natural and synthetic flavors.

[0062] Further examples of aldehyde flavorings include acetaldehyde (apple), benzaldehyde (cherry, almond), anisic aldehyde (licorice, anise), cinnamaldehyde (cinnamon), citral, i.e., α-citral (lemon, lime), neral, i.e., β-citral (lemon, lime), decanal (orange, lemon), ethyl vanillin (vanilla, cream), heliotrope, i.e., piperonal (vanilla, cream), vanillin (vanilla, cream), α-amylcinnamaldehyde (spicy fruit flavoring), butyralaldehyde (butter, cheese), valeraldehyde (butter, cheese), citral, methylparaben ... Examples of aldehydes include, but are not limited to, lonelal (modifiers, many types), decanal (citrus fruits), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), 2-ethylbutyraldehyde (berries), hexenal, i.e., trans-2 (berries), tolylaldehyde (cherries, almonds), veratraldehyde (vanilla), 2,6-dimethyl-5-heptenal, e.g., melon (melon), 2,6-dimethyloctanal (green fruits), and 2-dodecenal (citrus fruits, mandarin), cherries, grapes, blueberries, blackberries, strawberry shortcake, and mixtures thereof.

[0063] In one embodiment, flavoring agents include vanilla, peppermint oil, spearmint oil, eucalyptus oil, cinnamon oil, grapefruit oil, menthol, monomenthyl succinate, menthol ethylene glycol carbonate, menthone glycerol ketal, menthyl lactate, (-)-isopulegol, p-menthane-3,8-diol, (-)-monomethyl glutarate, wintergreen oil (methyl salicylate), citrus oil, orange oil, fruit essences, rosemary oil, lavender oil, sage oil, clary sage oil, thyme oil, sandalwood oil, basil oil, coriander oil, cypress oil, freeban oil, frankincense oil, geranium oil, fennel oil, oregano oil, dalmatian sage oil, tarragon oil, or mixtures or derivatives thereof.

[0064] coloring agent Colorants may be used in amounts effective to produce the desired color. Colorants may include pigments, which may be incorporated in amounts up to about 6% by weight of the formulation. Colorants may also include natural food colors and dyes suitable for food, drug, and cosmetic applications. These colorants are known as FD&C dyes and lakes. Materials acceptable for the aforementioned applications are preferably water-soluble. Illustrative, non-limiting examples include the indigoid dye known as FD&C Blue No. 2, which is the disodium salt of 5,5-indigotindisulfonic acid. Similarly, the dye known as FD&C Green No. 1 includes triphenylmethane dyes, which is the monosodium salt of 4-[4-(N-ethyl-p-sulfoniumbenzylamino)diphenylmethylene]-[1-(N-ethyl-Np-sulfoniumbenzyl)-delta-2,5-cyclohexadienimine]. A complete description of all FD&C colorants and their corresponding chemical structures can be found in the Kirk-Othmer Encyclopaedia of Chemical Technology, 3rd Edition, in volume 5 at pages 857-884, the text of which is incorporated herein by reference.

[0065] In some embodiments, one or more colors may be included. As classified by the U.S. Food, Drug, and Cosmetic Act (21 CFR 73), colors may include certification-exempt colors (sometimes referred to as natural, even though they may be synthetically produced) and certified colors (sometimes referred to as artificial), or combinations thereof. In some embodiments, certification-exempt or natural colors include annatto extract (E160b), bixin, norbixin, astaxanthin, dehydrated beets (beet powder), beetroot red / betanin (E162), ultramarine blue, canthaxanthin (E161g), cryptoxanthin (E161c), rubixanthin (E161d), violaxanthin (E161e), and the like. ), rhodoxanthin (E161f), caramel (E150(a-d)), β-apo-8'-carotenal (E160e), β-carotene (E160a), α-carotene, γ-carotene, β-apo-8'-carotenal ethyl ester (E160f), flavoxanthin (E161a), lutein (E161b), cochineal extract (E120), carmine (E132), carmoisine / azo These may include, but are not limited to, rubin (E122), sodium copper chlorophyllin (E141), chlorophyll (E140), toasted partially defatted heated cottonseed flour, ferrous gluconate, ferrous lactate, grape color extract, grape skin extract (Enocyanina), anthocyanins (E163), Haematococcus algae powder, synthetic iron oxide, iron oxide and hydroxide (E172), fruit juice, vegetable juice, dried algae powder, Tagetes (Aztec marigold) powder and extract, carrot oil, corn endosperm oil, paprika, paprika oleoresin, Phaffia yeast, riboflavin (E101), saffron, titanium dioxide, turmeric (E100), turmeric oleoresin, amaranth (E123), capsanthin / capsorubin (E160c), lycopene (E160d), and mixtures thereof.

[0066] In some embodiments, certified colors may include, but are not limited to, FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, FD&C Red No. 3, FD&C Red No. 40, FD&C Yellow No. 5, and FD&C Yellow No. 6, tartrazine (E102), quinoline yellow (E104), sunset yellow (E110), ponceau (E124), erythrosine (E127), patent blue V (E131), titanium dioxide (E171), aluminum (E173), silver (E174), gold (E175), the dyes rubin / lithol rubin BK (E180), calcium carbonate (E170), carbon black (E153), black PN / brilliant black BN (E151), green S / acid brilliant green BS (E142), and combinations thereof. In some embodiments, certified colors may include FD&C aluminum lakes, which contain aluminum salts of FD&C dyes spread on an insoluble substrate of alumina hydrate. Additionally, in some embodiments, certified colors may be included as calcium salts.

[0067] In some embodiments, natural fruit or plant juices or extracts may be used as colorants, including, but not limited to, carrot juice, raspberry juice, blackberry juice, blueberry juice, and beet juice.

[0068] moisturizer Glycerin is a humectant and freezing point depressant. It also reduces the tendency for granulation and helps maintain flexibility. In some embodiments, glycerin or an equivalent material may be employed at a level of about 1 to about 5%, e.g., 2 to 3%, by weight of the final product.

[0069] Moisturizing agents can be included that can provide the sensation of oral hydration. Such humectants can include, but are not limited to, glycerol, sorbitol, polyethylene glycol, litritol, and xylitol. In addition, in some embodiments, fats can provide the sensation of oral moisture. Such fats can include medium-chain triglycerides, vegetable oils, fish oils, mineral oils, and combinations thereof.

[0070] bulking agent Suitable sugar bulking agents include monosaccharides, disaccharides, and polysaccharides such as xylose, ribulose, glucose (dextrose), lactose, mannose, galactose, fructose (levulose), sucrose (table sugar), maltose, invert sugar, partially hydrolyzed starch and corn syrup solids, and mixtures thereof.

[0071] Suitable sugar alcohol bulking agents include sorbitol, xylitol, mannitol, galactitol, lactitol, maltitol, erythritol, isomalt, and mixtures thereof. Suitable hydrogenated starch hydrolysates include those disclosed in U.S. Pat. No. 4,279,931, as well as various hydrogenated glucose syrups and / or powders containing sorbitol, maltitol, hydrogenated disaccharides, hydrogenated higher polysaccharides, or mixtures thereof. Hydrogenated starch hydrolysates are primarily prepared by controlled catalytic hydrogenation of corn syrup. The resulting hydrogenated starch hydrolysates are mixtures of monomeric, dimeric, and polymeric sugars. The ratios of these different sugars impart different properties to different hydrogenated starch hydrolysates. Mixtures of hydrogenated starch hydrolysates, such as LYCASIN®, a commercially available product manufactured by Roquette Freres (France), and HYSTAR®, a commercially available product manufactured by SPI Polyols, Inc. (New Castle, Del.), are also useful.

[0072] In one embodiment, the bulking agent includes maltitol syrup, polydextrose, sorbitol, soluble corn fiber, resistant starch, resistant maltodextrin, cellulose, hemicellulose, fructooligosaccharides, galactooligosaccharides, lactulose, xyloisomaltooligosaccharides, soybean oligosaccharides, oligoglucose, stachyose, lactosucrose, or combinations thereof.

[0073] plasticizer In some embodiments, the formulation may further include a plasticizer to modify the texture of the formulation. The texture modifier may include a particulate material. Suitable particulate materials may include, but are not limited to, polyols, starches, proteins, and combinations thereof, such as sucrose, sorbitol, xylitol, mannitol, galactitol, lactitol, maltitol, erythritol, isomalt, hydrogenated starch hydrolysates, and mixtures thereof. In some embodiments, the particulate material that functions as the texture-modifying ingredient is selected based on its ability or lack of ability to crystallize the sugars in the sugar portion. For example, if isomalt is included in the sugar portion, sorbitol powder can be added to the formulation to prevent isomalt from crystallizing. Alternatively, if erythritol is included in the sugar portion, erythritol powder can be added to the formulation to crystallize the erythritol. Such particles may be included in an amount of 5% to 35% w / w of the formulation.

[0074] emulsifier The formulation may include an emulsifier. The emulsifier may be present in an amount of about 0.001% to about 5%, alternatively 0.001% to 1%, alternatively 1% to 3%, alternatively 3% to 5% by weight of the formulation. In some embodiments, the emulsifier is present in an amount of about 0% to about 5%, alternatively 0.001% to 1%, alternatively 1% to 3%, alternatively 3% to 5% by weight of the formulation.

[0075] Exemplary emulsifiers include, but are not limited to, modified corn starch, mono- and diglycerides, and lecithin.

[0076] Emulsifiers may help hold fat and water together in a homogeneous formulation and may also help hold other ingredients together, hi one embodiment, emulsifiers may aid in the formation of a "water and oil" emulsion that produces a smooth texture in the finished product.

[0077] thickener The formulation may further include a thickener to aid in the viscosity of the final product. Some thickeners are gelling agents. Others act as mechanical thixotropic additives, where discrete particles adhere or interlock to resist strain.

[0078] In some embodiments, the thickener may be a polysaccharide or protein. Exemplary polysaccharide thickeners include starch, vegetable gums, and pectin. Exemplary starch-based thickeners include arrowroot, corn starch, potato starch, sago, tapioca, and their starch derivatives. Exemplary vegetable gum thickeners may include arginine, guar gum, locust bean gum, and xanthan gum. Exemplary protein-based thickeners may include collagen, egg white, furcellaran, and gelatin. Exemplary sugar-based thickeners may include agar and carrageenan.

[0079] preservatives Preservatives can be natural or synthetic. Non-limiting examples of suitable preservatives include sodium benzoate, sodium citrate, sodium phosphate, potassium metabisulfite, sodium metabisulfite, sodium lactate, sodium sulfite, EDTA (ethylenediaminetetraacetic acid), methylparaben, TBHQ, tocopherol, and mixtures thereof. Natural preservatives include phenols (phenolic acids, polyphenols, tannins), isoflavonoids, organic acids (acetic acid, lactic acid, citric acid), and herbal extracts such as extracts of citrus fruits, oregano, thyme, sage, rosemary, clove, coriander, garlic, and onion.

[0080] In some embodiments, the formulation may comprise at least about 0% to 2% by weight of the formulation of a preservative ingredient from above, or a mixture thereof.

[0081] Gelling ingredient The gelling component may comprise one or more gelling agents. Several gelling agents may be utilized, including, but not limited to, gelatin, pectin, gum arabic, carrageenan, high methoxy pectin, alginate, gellan gum, modified or unmodified starch, modified starch flour or enriched flour or bleached flour, or any type of flour from natural sources, or combinations thereof.

[0082] Other exemplary gelling agents include acacia, alginic acid, bentonite, Carbopols® (now known as carbomer), carboxymethylcellulose, ethylcellulose, gelatin, hydroxyethylcellulose, hydroxypropylcellulose, magnesium aluminum silicate (Veegum®), methylcellulose, poloxamer (Pluronics®), polyvinyl alcohol, sodium alginate, and tragacanth.

[0083] The amount of gelling agent used in the formulation depends on the desired product texture, viscosity, and flexibility, as well as the other ingredients in the formulation. In some embodiments, the gelling agent may be used at a concentration of about 0.5% to about 10%, about 0.1% to about 7%, or about 0.2% to about 15%.

[0084] In one embodiment, gelatin and pectin may be employed in a weight ratio providing at least 50% gelatin and at least 10% pectin, for example, about 70-85% gelatin and the remainder pectin.

[0085] In one embodiment, the pectin can be a high methoxy pectin obtained from apples. In one embodiment, the gelatin can be a type A gelatin derived from porcine sources. The bloom value of the gelatin can be in the range of 100 to 280. In one embodiment, the bloom value is about 250.

[0086] In one embodiment, a combination of gelatin and pectin may be employed at a level of from about 4.5 to about 6% by weight of the final product, for example, about 5.5% on that basis.

[0087] In one embodiment, the formulation may include gellan gum, carrageenan, or both to provide a gelatin-free formulation. In one embodiment, the formulation may include about 0.25% to about 0.75% by weight of gellan gum and about 2% to about 3% by weight of carrageenan, based on the total weight of the formulation.

[0088] In one embodiment, a combination of about 0.25% to about 0.75% by weight gellan gum and about 2.5% to about 3% by weight carrageenan, based on the total weight of the product, produces a gummy formulation having a TPA hardness value of greater than 20 lbs(f) and TPA cohesiveness and elasticity values ​​of 75% to 80%.

[0089] In one embodiment, the amount of gellan gum is about 0.25% to about 0.75% by weight, and about 0.25% to about 0.5% by weight. In one embodiment, the amount of carrageenan is about 1.5% to about 3% by weight, and about 2.5% to about 3% by weight.

[0090] According to a further aspect of the present invention, a) a compound of formula (I) or a salt thereof, [ka] During the ceremony, A, B, C, and D are each independently selected from H and OH; W, X, and Y are each independently selected from H and OH; a compound or a salt thereof, wherein Z is selected from H and OH; b) pectin, for example, high methoxy pectin.

[0091] According to a further aspect of the present invention, (a) a compound of formula (I), e.g., urolithin A; and (b) pectin, Formulations are provided in which the ratio of the compound of formula (I) to pectin is within the range of about 1:2 (w / w) to about 10:1 (w / w).

[0092] According to a further aspect of the present invention, (a) a compound of formula (I), e.g., urolithin A; and (b) pectin; (c) a soluble fiber, such as soluble tapioca fiber.

[0093] According to a further aspect of the present invention, (a) a compound of formula (I), e.g., urolithin A; and (b) pectin; (c) a low-calorie sweetener, such as allulose.

[0094] According to a further aspect of the present invention, (a) a compound of formula (I), e.g., urolithin A; and (b) pectin; (c) Formulations are provided that include citric acid and / or a citrate salt (e.g., sodium citrate), for example, citric acid and a salt of citric acid (e.g., sodium citrate).

[0095] According to a further aspect of the present invention, (a) a compound of formula (I), e.g., urolithin A; and (b) pectin; (c) soluble tapioca fiber; (d) citric acid and / or citrate salts (e.g., sodium citrate); (e) a low-calorie sweetener, such as allulose, is provided.

[0096] According to a further aspect of the present invention, (a) about 1% to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin.

[0097] According to a further aspect of the present invention, (a) about 1% to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin; (c) about 25% to about 45% (w / w) soluble tapioca fiber.

[0098] According to a further aspect of the present invention, (a) about 1% to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin; (c) about 25% to about 45% (w / w) of a low-calorie sweetener, such as allulose.

[0099] According to a further aspect of the present invention, (a) about 1% to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin; (c) about 1% to about 10% (w / w), for example, about 1% to 5% or about 2% to about 4%, of a low-calorie sweetener, such as allulose.

[0100] According to a further aspect of the present invention, (a) about 1% to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin; (c) about 25% to about 60% (w / w) of a low-calorie sweetener, for example, one or more low-calorie sweeteners selected from allulose, fructulose, stevia, and / or inulin.

[0101] According to a further aspect of the present invention, (a) about 1% to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin; (c) A formulation is provided that includes about 0.5% to about 2% (w / w) citric acid and / or a citrate salt (e.g., sodium citrate), for example, citric acid and a salt of citric acid (e.g., sodium citrate).

[0102] According to a further aspect of the present invention, (a) about 1 to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin; (c) about 25% to about 45% (w / w) soluble tapioca fiber; (d) about 0.5% to about 2% (w / w) citric acid and / or a citrate salt (e.g., sodium citrate); (e) about 25% to about 45% (w / w) of a low-calorie sweetener, such as allulose.

[0103] Embodiments of the invention include a compound of formula (I) (e.g., urolithin A) in the range of about 5% to about 20% (w / w), for example, about 5% to about 15%, e.g., about 5% to about 10% (w / w).

[0104] Embodiments of the present invention include pectin (e.g., high methoxy pectin) in the range of about 0.5% to about 10% (w / w), about 0.5% to about 5% (w / w), about 0.5% to about 4% (w / w), about 0.5% to about 3% (w / w), about 0.5% to about 2% (w / w) pectin, for example, about 0.5% to about 1.5% (w / w), about 0.8% to about 1.5% (w / w), for example, about 1% to about 1.5% (w / w), for example, about 1% to about 4%, or about 2% to about 4% (w / w) pectin.

[0105] Embodiments of the present invention include soluble tapioca fiber (e.g., soluble tapioca fiber syrup) in the range of about 25% to about 45% (w / w), such as about 30% to about 40%, or about 32% to about 38% (w / w).

[0106] Embodiments of the present invention include citric acid and / or citrate salts (e.g., sodium citrate) in the range of about 0.5% to about 2% (w / w), such as about 0.8% to about 1.5%, or about 1% to about 1.5% (w / w). Salts of citric acid include sodium citrate, potassium citrate, calcium citrate, and triammonium citrate.

[0107] In a further aspect of the invention, the formulation includes both citric acid and a salt of citric acid. Embodiments of the invention include citric acid in the range of about 0.5% to about 2% (w / w). For example, about 0.5% to about 1.5%, about 0.8% to about 1.5%, about 1% to about 1.5%, or about 0.8% to about 1.3% (w / w). Embodiments of the invention include a salt of citric acid (e.g., sodium citrate) in the range of about 0.1% to about 1% (w / w). For example, about 0.1% to about 0.8%, or about 0.1% to about 0.5% (w / w).

[0108] In a further aspect of the invention, the formulation comprises both malic acid and sodium hydrogen malate.

[0109] Embodiments of the present invention include a low-calorie sweetener (e.g., allulose) in the range of about 25% to about 45% (w / w), such as about 30% to about 40%, or about 32% to about 38% (w / w).

[0110] According to a further aspect of the present invention, (a) about 1% to about 20% (w / w), for example, about 5% to about 20% (w / w), of a compound of formula (I), e.g., urolithin A; (b) about 0.5% to about 4% (w / w) pectin; (c) about 25% to about 60% (w / w) of a low-calorie sweetener, e.g., one or more low-calorie sweeteners selected from allulose, fructose, monk fruit juice, stevia, and / or inulin; (d) about 10% to about 30% soluble fiber; (e) about 0.1% to about 2% sodium citrate, for example, about 0.3% to about 1% sodium citrate; (f) optionally a pH buffer, such as malic acid and / or sodium hydrogen malate; (g) optionally, a colorant.

[0111] Amorphous form of the compound of formula (I) Although the compound of formula (I) exists in crystalline form, it has been found that amorphous forms of the compound of formula (I) are useful in preparing compositions with higher bioavailability. Thus, according to a further aspect of the present invention, there is provided an amorphous form of the compound of formula (I), e.g., amorphous urolithin A.

[0112] Furthermore, it has been found that bioavailability can be enhanced by the addition of one or more excipients. Thus, according to a further aspect of the invention, there is provided a composition comprising an amorphous compound of formula (I), e.g., amorphous urolithin A, and one or more excipients.

[0113] Excipients include one or more of pectin, methylcellulose, hydroxypropylmethylcellulose (e.g., HPMC E5), gum arabic, alginates (e.g., sodium alginate), gelatin, mannitol, and sorbitol. In further embodiments, the excipients further include agar, starch, or modified starch.

[0114] In a further embodiment, the present invention provides a composition comprising an amorphous compound of Formula (I) and an excipient, wherein the compound of Formula (I) and the excipient are in a ratio of about 1 to about 1 to about 10, about 2 to about 1 to about 10, about 2 to about 1 to about 9, about 2 to about 1 to about 8, about 2 to about 1 to about 7, about 2 to about 1 to about 6, about 2 to about 1 to about 5, such as a ratio of about 2 to about 1 to about 4, for example, a ratio of about 1 to about 3, e.g., wherein the excipient is selected from one or more of pectin, methylcellulose, hydroxypropylmethylcellulose (e.g., HPMC E5), gum arabic, alginate, and gelatin. In a further embodiment, the present invention provides a composition comprising an amorphous compound of Formula (I) and an excipient, wherein the excipient is a mixture of pectin and methylcellulose.

[0115] In one embodiment, the invention comprises an amorphous form of the compound of formula (I), e.g., amorphous urolithin A, and hydroxypropyl methylcellulose (e.g., HPMC E5), in a ratio of about 1 to 3.

[0116] In one embodiment, the invention comprises an amorphous form of the compound of formula (I), e.g., amorphous urolithin A, and methylcellulose in a ratio of about 1 to 3.

[0117] In one embodiment, the invention comprises an amorphous form of the compound of formula (I), e.g., amorphous urolithin A, and pectin in a ratio of about 1 to about 3, a ratio of about 1 to about 4, or a ratio of about 1 to about 5.

[0118] In one embodiment, the invention comprises a mixture of an amorphous compound of formula (I), e.g., amorphous urolithin A, and an excipient comprising pectin and methylcellulose. In one embodiment, the compound of formula (I), pectin, and methylcellulose are in a ratio of 1 to about 3 to about 2.

[0119] According to a further aspect of the present invention, (a) a compound of formula (I), e.g., urolithin A; and (b) pectin; (c) a fiber source, e.g., one or more fiber sources selected from tapioca, corn fiber, and inulin; (d) one or more sweeteners, such as allulose and / or stevia; (e) water; (f) citric acid and / or sodium citrate; (g) optionally, one or more colorants; and (h) optionally, one or more flavoring agents.

[0120] According to a further aspect of the present invention, (a) a compound of formula (I), e.g., urolithin A; and (b) pectin; (c) a fiber source, e.g., tapioca; (d) one or more sweeteners, e.g., one or more sweeteners selected from allulose, stevia, and monk fruit juice; (e) a pH adjuster, such as sodium hydrogen malate; (f) sodium citrate; (g) water; (h) optionally, one or more colorants; and (i) optionally, one or more flavoring agents; and (j) optionally, a coating.

[0121] Spray-dried compositions of compounds of formula (I) It has been found that compositions can be prepared by dissolving a compound of formula (I), e.g., urolithin A, in a solvent and spray drying. Thus, according to a further aspect of the invention, there is provided a spray-dried composition of a compound of formula (I), e.g., urolithin A.

[0122] Suitable solvents for spray drying include ethanol and water.

[0123] In one embodiment, the solvent is water.

[0124] In a further embodiment, the solvent is ethanol.

[0125] In one embodiment, the excipient is pectin, for example, low methoxy pectin.

[0126] In a further embodiment, the excipient is a mixture of pectin and methylcellulose.

[0127] In a further embodiment, the excipient is methylcellulose.

[0128] In a further embodiment, the excipient is hydroxypropyl methylcellulose, for example HPMC E5.

[0129] In a further embodiment, the excipient is gum arabic.

[0130] In a further embodiment, the solvent is water and the excipient is pectin.

[0131] In a further embodiment, the solvent is ethanol and the excipient is pectin.

[0132] In a further embodiment of the invention, there is provided a spray-dried composition of a compound of formula (I), e.g., urolithin A, comprising an excipient, e.g., an excipient selected from one or more of pectin, e.g., high methoxypeptin, gum arabic, methylcellulose, and hydroxypropylmethylcellulose, e.g., HPMC-E5, sorbitol, mannitol, and sodium alginate.

[0133] In a further embodiment of the invention, there is provided a spray-dried composition of a compound of formula (I), e.g., urolithin A, with pectin, e.g., high methoxy pectin.

[0134] In a further embodiment of the invention, there is provided a spray-dried composition of a compound of formula (I), e.g., urolithin A, comprising methylcellulose.

[0135] In a further embodiment of the invention, there is provided a spray-dried composition of a compound of formula (I), such as urolithin A, comprising gum arabic.

[0136] In a further embodiment of the invention, there is provided a spray-dried composition of a compound of formula (I), e.g., urolithin A, comprising hydroxypropyl methylcellulose, e.g., HPMC E5.

[0137] According to a further embodiment of the present invention there is provided a process for preparing a composition comprising a compound of formula (I), comprising: (a) dissolving a compound of formula (I) in a solvent to form a solution, or suspending a compound of formula (1) in a solvent to form a suspension; For example, the solvent is selected from ethanol and / or water; (b) optionally stirring the resulting suspension or solution; (c) adding one or more excipients, for example, one or more excipients selected from pectin, methylcellulose, and hydroxypropylmethylcellulose; (d) spray drying the solution / suspension, optionally with stirring, to form a powder; (e) optionally drying the powder.

[0138] According to a further embodiment of the present invention, (a) dissolving a compound of formula (I) in a solvent to form a solution, or suspending a compound of formula (1) in a solvent to form a suspension; For example, the solvent is selected from ethanol and / or water; (b) optionally stirring the resulting suspension or solution; (c) adding one or more excipients, for example, one or more excipients selected from pectin, methylcellulose, and hydroxypropylmethylcellulose; (d) spray drying the solution / suspension, optionally with stirring, to form a powder; (e) optionally drying the powder.

[0139] A further embodiment of the invention is a spray-dried composition comprising a compound of formula (1) and a low methoxy pectin.

[0140] In a further embodiment, the composition of the present invention comprises: [Table 1]

[0141] In a further embodiment, the composition of the present invention comprises: [Table 2]

[0142] Urolithin Urolithins are metabolites produced by the action of the intestinal microbiota of mammals, including humans, on ellagitannins and ellagic acid. Ellagitannins and ellagic acid are compounds commonly found in foods such as pomegranates, nuts, and berries. Ellagitannins themselves are minimally absorbed in the intestine. Urolithins are a class of compounds having a representative structure (I) shown below. The structures of some particularly common urolithins are set forth in Table 1 below with reference to structure (I). [ka] [Table 3]

[0143] In practice, it is convenient to synthesize urolithins for commercial-scale production, and synthetic routes are described, for example, in U.S. Patent No. 5,623,299, WO 2015 / 100213, and WO 2019 / 168972.

[0144] Urolithins of any structure according to structure (I) may be used in the combinations of the invention.

[0145] In one aspect of the combination of the present invention, suitable compounds are compounds of formula (I) wherein A, C, D, and Z are independently selected from H and OH, and B, W, X, and Y are all H, and preferably at least one of A, C, D, and Z is OH.

[0146] Particularly suitable compounds are naturally occurring urolithins. Thus, Z is preferably OH, and W, X, and Y are preferably all H. When W, X, and Y are all H, A and B are both H, and C, D, and Z are all OH, the compound is urolithin C. When W, X, and Y are all H, A, B, and C are all H, and D and Z are both OH, the compound is urolithin A. Preferably, the urolithin used in the methods of the disclosure is urolithin A, urolithin B, urolithin C, or urolithin D. Most preferably, the urolithin used is urolithin A. [ka]

[0147] According to one embodiment, there is provided a combination of the invention wherein the compound of formula (I) is urolithin A.

[0148] According to one embodiment, there is provided a combination of the invention wherein the compound of formula (I) is urolithin B.

[0149] According to one embodiment, there is provided a combination of the invention wherein the compound of formula (I) is urolithin C.

[0150] According to one embodiment, there is provided a combination of the invention wherein the compound of formula (I) is urolithin D.

[0151] In one embodiment, urolithin does not include an acylated urolithin or an optionally substituted acylated urolithin (e.g., acylated urolithin A, acylated urolithin B, acylated urolithin C, acylated urolithin D, acylated urolithin E, or acylated urolithin M5, or a urolithin C having at least one hydroxyl substituted with a fatty acid-containing group). The term "acyl," as used herein, refers to a chemical substituent of formula -C(0)-R, where R is alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl. An optionally substituted acyl is an acyl that is optionally substituted as described herein for each R group. Examples of acyl include fatty acyl (e.g., short-chain fatty acyl (e.g., acetyl)) and benzoyl.

[0152] The present invention also encompasses the use of suitable salts of the compounds of formula (I), for example, pharmaceutically acceptable salts. Suitable salts according to the present invention include those formed with organic or inorganic bases. Pharmaceutically acceptable base salts include ammonium salts, alkali metal salts, such as potassium and sodium salts, alkaline earth metal salts, such as calcium and magnesium salts, and salts with organic bases, such as dicyclohexylamine, N-methyl-D-glucamine, morpholine, thiomorpholine, piperidine, pyrrolidine, mono-, di-, or tri-lower alkylamines, such as ethyl, tert-butyl, diethyl, diisopropyl, triethyl, tributyl, or dimethylpropylamine, or mono-, di-, or trihydroxy lower alkylamines, such as mono-, di-, or triethanolamine.

[0153] Additional ingredients in the compositions of the present invention: Formulations according to the present invention may contain additional ingredients beyond the urolithin and gelling component. The additional ingredients may be compounds that provide health benefits, such as minerals, antioxidants, or mitochondrial boosting agents.

[0154] In one embodiment, the antioxidant formulation includes bioflavonoids, resveratrol, coenzyme Q10, quercetin, rutin, lycopene, L-glutathione, N-acetylcysteine, phenolics, anthocyanins, flavonoids, anthracene, carotenoids, zeaxanthin, astaxanthin, xanthin, pomegranate, ginkgo, green tea, garlic, grape seed, blackberry, elderberry, cranberry, blueberry, saffron, sangre de grado (dragon's blood), lycium barbarum (wolfberry), extracts, powders, or isolates thereof.

[0155] In one embodiment, the mitochondrial boosting agent includes acetyl L-carnitine, alpha-lipoic acid, coenzyme Q10 (CoQ10, or ubiquinone), nicotinamide riboside (NR), omega-3 fatty acids, magnesium, D-ribose, or derivatives or combinations thereof.

[0156] Creatine has been described as having beneficial effects in the treatment of muscle disorders and can be included in the formulations of the present invention. β-Hydroxyl-β-methylbutyric acid (HMB) has been described as having beneficial effects in the treatment of muscle disorders and can be included in the formulations of the present invention.

[0157] In a further embodiment, the formulation further comprises spermidine.

[0158] Examples of mineral preparations include potassium, chromium picolinate, magnesium, and selenium. In one embodiment, the mineral preparation may include ions of sodium, magnesium, chromium, iodine, iron, manganese, calcium, copper, fluoride, potassium, phosphorus, molybdenum, selenium, zinc, and combinations thereof. The minerals may be in the form of salts or chelates.

[0159] Treatment: The formulation of the present invention can be administered as a single treatment, or more generally as a series of treatments.In one example, the subject is administered a dose before or after exercise.For subjects who cannot exercise, the dosage of the formulation can be administered, for example, once, twice, or three times per day, or once, twice, three, four, five, or six times per week.In another example, intervention can be administered by a subject regardless of the subject's ability or need to exercise.It will also be understood that the effective dosage of the compound can increase or decrease during the course of a particular treatment.

[0160] Medical and non-medical treatment: The formulations of the present invention may be used as pharmaceuticals. The formulations can be used as dietary supplements, functional foods, and medical foods. Thus, the formulations of the present invention are useful for treating various diseases and conditions that are not considered diseases. In particular, disease and non-disease conditions can be characterized by insufficient mitochondrial activity. The formulations are used to treat both disease and medical conditions. Thus, in embodiments, the methods and uses of the formulations and compositions disclosed herein include non-therapeutic methods and uses. The formulations are used to manage normal physiological function in healthy individuals with conditions characterized by poor physical performance, reduced endurance, and impaired muscle function. The formulations of the present invention can improve physical performance in individuals with diseases, including young and elderly individuals. The formulations of the present invention can improve physical performance, for example, short-term performance or long-term performance, in healthy individuals, including athletes, non-athletes, sedentary individuals, and elderly individuals. This improvement in performance may be measured by the time it takes to walk or run a certain distance (e.g., improved performance during a 6-minute walk test (MWT)), improved time to run a certain distance, improved IPAQ score on the International Standardized Physical Activity Questionnaire, increased number of chair rises in a certain period of time, or another test designed to measure physical performance. In a further embodiment, the invention provides the use of a formulation of the invention for enhancing muscle function in people recovering from cancer.

[0161] The formulations of the present invention further provide improved endurance. Endurance refers to the time to fatigue when exercising at a given workload, typically at an intensity less than 80% of VO2max. The formulations of the present invention can improve endurance in individuals with diseases, including young and elderly individuals. The formulations of the present invention can improve endurance in healthy individuals, including athletes, non-athletes, sedentary individuals, and the elderly. The present invention provides a method for increasing the time to fatigue during specific activities, such as fitness training, walking, running, swimming, or cycling. This improvement in endurance can be assessed by objective measures (e.g., speed, oxygen consumption, or heart rate) or can be a self-reported measure (e.g., using a validated questionnaire).

[0162] The present invention further provides a formulation for improving or maintaining muscle function or reducing loss of muscle function. The formulation of the present invention can improve or maintain muscle function or reduce loss of muscle function in individuals with diseases, including young and elderly individuals. The formulation of the present invention can improve or maintain muscle function or reduce loss of muscle function in healthy individuals, including athletes, non-athletes, sedentary individuals, and elderly individuals. For example, the formulation of the present invention can increase muscle strength, as evidenced by an improvement in performing physical activities such as exercise, for example, an increased ability to lift weights or an increased grip strength. The formulation of the present invention can also improve muscle structure, for example, by increasing or maintaining muscle mass in conditions of normal muscle function, reduced muscle function, or impaired muscle function.

[0163] The present invention further provides formulations for improving physical performance or endurance as perceived by an individual, for example, by reducing the perception of exertion or effort during exercise or activity as determined using a self-report questionnaire.

[0164] The present invention further provides formulations of the present invention for use in the treatment of various conditions, including conditions associated with insufficient mitochondrial activity, including obesity, reduced metabolic rate, metabolic syndrome, diabetes, cardiovascular disease, hyperlipidemia, memory decline, neurodegenerative diseases, cognitive impairment, mood disorders, stress and anxiety disorders, and fatty liver disease (e.g., NAFLD and NASH), for improving liver function and for weight management. In particular, the formulations of the present invention are used in the treatment of muscle-related conditions. Thus, the present invention provides formulations of the present invention for use in the treatment of muscle-related conditions. The present invention also provides a method for treating muscle-related conditions in a subject, comprising administering to the subject an effective amount of a formulation of the present invention. Muscle-related conditions include both conditions and pathologies that affect generally healthy individuals. Such muscle conditions found in healthy people or those affected by disease include musculoskeletal diseases or disorders, cachexia, muscle wasting, age-related decline in muscle function, pre-weakness, frailty, myopathy, neuromuscular diseases such as Duchenne muscular dystrophy and other dystrophies, age-related sarcopenia, acute sarcopenia, muscle atrophy and / or cachexia, for example, associated with burns, bed rest, limb immobilization, or major surgery, including thoracic, abdominal, and / or orthopedic surgery, and muscle degenerative diseases.

[0165] Examples of age-related conditions that may be treated with the formulations of the present invention include sarcopenia and muscle wasting.

[0166] Myopathy can also be caused by muscular dystrophy syndromes such as Duchenne.

[0167] WO 2014 / 111580 reports that urolithin B (but not urolithin A) increased the mean diameter of myotubes in vitro, an effect not seen with urolithin A.

[0168] Non-medical and non-therapeutic treatments: The formulations of the present invention are useful for enhancing muscle performance. Accordingly, the present invention provides the formulations of the present invention for use in enhancing muscle performance. The present invention also provides a method for enhancing muscle performance by administering an effective amount of the formulations of the present invention to a subject. The administration can be self-administration. The enhancement of muscle performance can be one or more of improved muscle function, improved muscle strength, improved muscle endurance, and improved muscle recovery.

[0169] Thus, the formulations of the present invention can be used in methods to improve physical endurance (e.g., the ability to perform physical tasks such as exercise, manual labor, sports activities, etc.), prevent or delay physical fatigue, enhance work capacity and endurance, reduce muscle fatigue, and enhance cardiac and cardiovascular function.

[0170] Improving muscle function can be particularly beneficial for elderly subjects whose muscle function has decreased as a result of age-related conditions.For example, subjects who can benefit from improving muscle function may experience a decrease in muscle function that leads to pre-frailty and frailty.Such subjects may not necessarily experience muscle wasting in addition to the decrease in muscle function.Some subjects, such as subjects with sarcopenia, experience both muscle wasting and decreased muscle function.The formulations of the present invention can be used to enhance muscle performance by administering the formulations of the present invention to subjects who are frail or pre-frail.

[0171] Muscle performance can be sports performance, i.e., the ability of an athlete's muscles to perform when participating in sports activities. Enhanced sports performance, strength, speed, and endurance are measured by increasing muscle contraction strength, increasing muscle contraction amplitude, or shortening muscle reaction time between stimulation and contraction. Athletes refer to individuals who participate in sports at any level and aim to achieve improved strength, speed, or endurance levels in their performance, such as bodybuilders, cyclists, long-distance runners, and sprinters. Enhanced sports performance is manifested by the ability to overcome muscle fatigue, maintain activity for longer periods, and train more effectively.

[0172] Urolithin Administration / Dosage Regime The disclosed combinations involve orally administering a urolithin of formula (I) or a salt thereof to a subject at a daily dose ranging from 1.7 to 6.0 mmol per day, e.g., 1.7 to 2.7 mmol per day, or 2.8 to 6.0 mmol per day, for a period of 2 to 16 weeks prior to vaccination. As discussed below, administration of urolithin A in the range of 250 mg to 1000 mg (corresponding to approximately 1.1 to 4.4 mmol) is preferred, which results in a surprisingly favorable pharmacokinetic profile compared to the much higher dose of 2000 mg. In one embodiment, the dose is 250 mg / day; in an alternative embodiment, the dose is 500 mg / day; and in another embodiment, the dose is 1000 mg / day.

[0173] In a further embodiment, the administered dose is selected from the following: -250 mg once or twice daily -500 mg once or twice daily -750 mg once or twice daily -1000mg once or twice daily 1250 mg once or twice daily, or -1500mg once or twice daily

[0174] The disclosed methods involve daily administration of a compound of formula (I) or a salt thereof, or a formulation containing the compound or salt. In some embodiments, the compound or formulation is administered once per day, i.e., the compound or formulation is administered at least once per 24-hour period. In other embodiments, the compound or formulation containing the compound is administered multiple times per day, for example, twice per day, or three or four times per day. In such cases, the daily dosage is divided into these multiple doses. In one embodiment, administration is once per day, in a second embodiment, administration is twice per day, and in a third embodiment, administration is three times per day.

[0175] The disclosed methods typically require daily administration of a compound of Formula (I) or a salt thereof, or a formulation containing the compound or salt, for a period of several months. In some embodiments, the methods may involve daily administration of a compound of Formula (I) or a salt thereof for, for example, at least 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 12 weeks, 4 months, 6 months, or at least 1 year. In some embodiments, the methods include daily administration of a compound or a salt thereof for a period of up to 3 months, up to 6 months, up to 1 year, up to 2 years, or up to 5 years. In some embodiments, the method comprises administering the compound or salt daily for a period ranging from 21 days to 5 years, 21 days to 2 years, 21 days to 1 year, 21 days to 6 months, 21 days to 12 weeks, 28 days to 5 years, 28 days to 2 years, 28 days to 1 year, 28 days to 6 months, 28 days to 4 months, 28 days to 12 weeks, 6 weeks to 2 years, 6 weeks to 1 year, 8 weeks to 1 year, or 8 weeks to 6 months.

[0176] The disclosed methods involve daily administration of a compound of Formula (I) or a salt thereof in an amount ranging from 0.7 mmol per day to a maximum of 2.7 mmol per day, or from 0.7 mmol twice per day to a maximum of 2.7 mmol twice per day. In some embodiments, the amount administered is in the range of 2.0 to 2.5 mmol. In some embodiments, the amount administered is about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, or 2.7 mmol per day. In other embodiments, the amount administered is about 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0 mmol per day. In some preferred embodiments, the methods involve administration of about 2.2 mmol per day, or 2.2 mmol twice per day, of the compound of Formula (I) or a salt thereof (e.g., urolithin A). The exact weight of the compound administered will depend on the molecular weight of the compound used. For example, urolithin A has a molecular weight of 228 g / mol (so that 2.20 mmol is 501.6 mg), and urolithin B has a molecular weight of 212 g / mol (so that 2.20 mmol is 466.4 mg).

[0177] In further embodiments, the disclosed methods involve daily administration of an amount of a compound of Formula (I) or a salt thereof from 2.8 mmol per day to a maximum of 6.0 mmol per day, or twice per day. In some embodiments, the amount administered is within the range of 4.0 to 4.8 mmol. In some embodiments, the amount administered is about 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0 mmol. In some preferred embodiments, the methods involve administering about 4.4 mmol of a compound of formula (I) or a salt thereof (e.g., urolithin A) per day, or twice per day. The exact weight of the compound administered will depend on the molecular weight of the compound used. For example, urolithin A has a molecular weight of 228 g / mol (so that 4.40 mmol is 1003.2 mg), and urolithin B has a molecular weight of 212 g / mol (so that 4.40 mmol is 932.8 mg).

[0178] In some embodiments, the methods involve administration of urolithin A in an amount ranging from 400 to 600 mg per day, or 400 to 600 mg once per day. In preferred embodiments, the methods involve administration of urolithin A in an amount ranging from 450 to 550 mg, more preferably about 500 mg per day.

[0179] In other embodiments, the methods involve administration of urolithin A in an amount within the range of 700-1300 mg / day, or within the range of 750-1250 mg / day, or within the range of 800-1200 mg / day, or within the range of 850-1150 mg / day, or within the range of 900-1100 mg / day. In preferred embodiments, the methods involve administration of urolithin A in an amount within the range of 950-1150 mg / day, more preferably about 1000 mg / day.

[0180] In some preferred embodiments, the methods involve administering urolithin A to the subject in an amount ranging from 4.5 to 11 mg / kg / day, such as 4.5 to 8.5 mg / kg / day. In other embodiments, the methods involve administering urolithin A to the subject in an amount ranging from 5 to 9 mg / kg / day. In other embodiments, the methods involve administering urolithin A to the subject in an amount ranging from 6.0 to 8 mg / kg / day.

[0181] In other preferred embodiments, the methods involve administering urolithin A to the subject in an amount ranging from 9 to 18 mg / kg / day, such as 9 to 17 mg / kg / day. In another embodiment, the methods involve administering urolithin A to the subject in an amount ranging from 10 to 17 mg / kg / day. In another embodiment, the methods involve administering urolithin A to the subject in an amount ranging from 11 to 16 mg / kg / day.

[0182] A dosage regime combining a 500 mg dose and a 1000 mg dose may be advantageous. For example, a twice-daily dosage regime combining a first dose of 1000 mg followed several hours later by a second dose of 500 mg. The 500 mg dose may be 6 to 18 hours after the 1000 mg dose, for example, 8 to 12 hours after the 1000 mg dose. For example, about 12 hours after the 1000 mg dose. Thus, according to a further aspect of the present invention, there is provided a treatment of a disease with a compound of formula (I) comprising a twice-daily dosage regime comprising a first dose of 1000 mg followed by a second dose of 500 mg, the two doses being separated by 6 to 18 hours.

[0183] The compound of formula (I) or its salt, or a formulation containing the compound of the salt, can be administered at any suitable time, for example, in the morning or evening after sleep. In some embodiments, it may be preferable to perform the method at approximately the same time every day, for example, within 15, 30, 60, or 120 minutes of a given time point.

[0184] The appropriate dose of the formulation of the present invention will be selected based on clinical indications by the treating physician or non-therapeutic treatment.

[0185] In some preferred embodiments, the formulations of the present invention contain a compound of Formula (I) or a salt thereof (e.g., urolithin A) having a preferred particle size distribution. A specific particle size distribution allows the compound of Formula (I) to disperse or dissolve more rapidly. A specific particle size distribution can be achieved by methods established in the art, such as compressive force milling, hammer milling, universal or pin milling, or jet milling (e.g., spiral jet milling or fluidized bed jet milling). Jet milling is particularly preferred. Furthermore, a specific particle size distribution can also be directly derived by using a specific chemical process. When a specific particle size distribution is used, preferably, the compound has a D of less than 100 μm. 50 More preferably, the compound has a particle size of less than 75 μm, such as less than 50 μm, for example less than 25 μm, such as less than 20 μm, for example less than 10 μm. 50 More preferably, the compound has a size D in the range of 0.5 to 50 μm, such as 0.5 to 20 μm, for example, 0.5 to 10 μm, for example, 1.0 to 10 μm, for example, 1.5 to 7.5 μm, for example, 2.8 to 5.5 μm. 50 Preferably, the compound has a D of less than 100 μm. 90 More preferably, the compound has a size of less than 75 μm, such as less than 50 μm, for example less than 25 μm, for example less than 20 μm, for example less than 15 μm. 90 The compound preferably has a size D in the range of 5 to 100 μm, for example, 5 to 50 μm, for example, 5 to 20 μm, for example, 7.5 to 15 μm, for example, 8.2 to 16.0 μm. 90 Preferably, the compound has a D in the range of 0.5 to 1.0 μm. 10 Preferably, the compound of formula (I) or a salt thereof (e.g., urolithin A) has a D in the range of 8.2 to 16.0 μm. 90 , D in the range of 2.8 to 5.5 μm 50 , and D in the range of 0.5 to 1.0 μm 10 It has.

[0186] In a further embodiment, the compound of formula (I) or salt thereof has a particle size distribution selected from one of the following: (i) D in the range of 0.5 to 50 μm 50 Size and D in the range of 5 to 100 μm 90 size, (ii) The compound has a D in the range of 8.2 to 16.0 μm. 90 Size, D in the range of 2.8 to 5.5 μm 50 Size and D in the range of 0.5 to 1.0 μm 10 having a size (iii) The compound of formula (I) has a D in the range of 0.5 to 20 μm. 50 Size and D in the range of 5 to 50 μm 90 having a size (iv) Compounds of formula (I) have a D of less than 50 μm 50 Size, and D less than 75 μm 90 having a size (v) The compound of formula (I) has a D of less than 25 μm 50 Size, and D less than 50 μm 90 having a size (iv) Compounds of formula (I) have a D of less than 10 μm 50 Size, and D less than 20 μm 90 having a size (v) The compound of formula (I) has a D of less than 10 μm 50 Size, and D less than 15 μm 90 having a size, or (vi) The compound of formula (I) has a D of 10 μm 50 size, and D of 20 μm 90 It has a size.

[0187] Pharmaceutical formulations containing a compound of formula (I) or a salt thereof may, for example, contain additional pharmaceutically active compounds.

[0188] Unit dose formulations used in the methods described herein preferably contain 250 mg or 500 mg of the compound of formula (I), for example, 250 mg or 500 mg of urolithin A.

[0189] The term "artificial sweetener" refers to any sweetener that does not occur in nature.

[0190] The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic is administered.

[0191] The term "fiber" refers to plant-derived carbohydrates that the human digestive system cannot break down.

[0192] The term "esterification range" (DE - degree of esterification), when referring to pectin, refers to the ratio of esterified carboxyl groups to the total carboxyl groups in the pectin. Pectins are divided into low-ester pectins (DE<50%) and high-ester pectins (DE>50%).

[0193] The term "excipient" refers to a substance formulated with an active ingredient of a pharmaceutical agent, e.g., to bulk up a solid formulation containing a small amount of a potent active ingredient for purposes of long-term stabilization (and therefore often referred to as a "bulking agent," "filler," or "diluent"), or to impart a therapeutic enhancement to the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility.

[0194] The term "gelling component" refers to one or more components that help form the polymeric matrix that provides the formulation with a chewy texture.

[0195] The term "gummy" refers to a dosage form that retains its integrity and texture when chewed, does not initially break down into discrete solid particles when chewed, utilizes a gelling matrix, and is intended to be swallowed. The term "chewable formulation" refers to gummies. The term gummies is distinct from jellies, for example, made with agar, which are much softer gelatinous matrices.

[0196] The term "healthy life expectancy" refers to the number of years that a person will live or can expect to live in reasonably good health.

[0197] The term "pectin" refers to a mixture of complex polysaccharides present in the primary cell walls of plants and abundant in the green parts of terrestrial plants. Pectin can be high methoxy pectin or low methoxy pectin. The term pectin further includes amidated pectins, e.g., amidated low methoxy pectin.

[0198] The term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or state government, or listed in the United States Pharmacopoeia or other generally recognized pharmacopeia, for use in animals, and more particularly in humans.

[0199] The term "separate" administration means that each of two or more compounds is administered to a patient simultaneously, substantially simultaneously, or sequentially in any order from non-fixed dose forms. There may or may not be a specified time interval between the administration of each compound.

[0200] The term "sequential" administration means administering each of two or more compounds to a patient in separate acts from non-fixed (separate) dosage forms. The acts of administration may or may not be related by a specified time interval. For example, administering the compounds over a specified period of time, such as once every 14 to 21 days.

[0201] The term "concurrent" administration means that each of two or more compounds is administered to a patient in a single action, e.g., where each compound is administered independently at substantially the same time or separately within a time interval that allows the compounds to exert a synergistic therapeutic effect.

[0202] The term "sweetener system" refers to a sweetener or combination of sweeteners. [Brief explanation of the drawings]

[0203] [Figure 1] Dissolution profiles of powder containing 10 mg UA complexed with citrus pectin in FaSSIF medium compared to 10 mg pure UA powder using EtOH as solvent. Left graph: Comparison of UA / pectin formulations with a 1 / 1 w / w ratio of excipients. Right graph: Comparison of UA / pectin formulations with a 4 / 1 w / w ratio of excipients. [Figure 2] Dissolution profiles of powders containing the equivalent of 10 mg UA complexed with citrus pectin in FaSSIF medium compared to 10 mg of pure UA powder using water as the solvent. Top left graph: Comparison of formulation UA / pectin with a 1 / 1 w / w ratio of excipients. Top right graph: Comparison of formulation UA / pectin with a 4 / 1 w / w ratio of excipients. Bottom left graph: Comparison of formulation UA / pectin with a 7 / 1 w / w ratio of excipients. Bottom right graph: Comparison of formulation UA / pectin with a 10 / 1 w / w ratio of excipients. [Figure 3] AUC of powder containing the equivalent of 10 mg UA complexed with citrus pectin in FaSSIF medium compared to 10 mg pure UA powder using water as the solvent. Data presented as mean + / - SD. Adjusted P-value ****<0.0001, one-way ANOVA. [Figure 4] Comparison of the solubility of different urolithin A formulations—maximum concentration of urolithin A in solution (Cmax) achieved compared to formulations containing UA prepared in ethanol or water. [Figure 5] Dissolution profiles of powders containing the equivalent of 10 mg of UA after physical mixing (without spray drying) with citrus pectin in FaSSIF medium compared to 10 mg of pure UA powder using water as the solvent. Top left graph: Comparison of formulation UA / pectin with a 1 / 1 w / w ratio of excipients. Top right graph: Comparison of formulation UA / pectin with a 4 / 1 w / w ratio of excipients. Bottom left graph: Comparison of formulation UA / pectin with a 7 / 1 w / w ratio of excipients. Bottom right graph: Comparison of formulation UA / pectin with a 10 / 1 w / w ratio of excipients. [Figure 6]AUC of powder containing the equivalent of 10 mg UA added as a physical mixture with citrus pectin in FaSSIF medium without spray drying compared to 10 mg of pure UA powder using water as the solvent. Data presented as mean + / - SD. Adjusted P-value ****<0.0001, one-way ANOVA. [Figure 7] Figure 1 shows a general overview of a PROCEPT spray dryer equipped with a BF nozzle. [Figure 8] 1 shows an XRPD spectrum of crystalline urolithin A. [Figure 9] FIG. 1 shows an XRPD spectrum of a urolithin A formulation complexed at a 1:1 ratio of urolithin A to excipient and prepared by spray drying using water as the solvent and pectin as the excipient. [Figure 10] FIG. 1 shows an XRPD spectrum of a urolithin A formulation complexed at a 4:1 urolithin A to excipient ratio and prepared by spray drying using water as the solvent and pectin as the excipient. [Example]

[0204] The invention will now be described with reference to the following non-limiting examples.

[0205] Example 1: Pectin formulation An exemplary formulation of the present invention consists of: [Table 4]

[0206] Example 2: Process for preparation of the formulation of Example 1 1) Combine the fruit concentrate, puree, water, and sodium ascorbate together in a container large enough to hold them. 2) Combine pectin and 10 times its weight of allulose in a container large enough to hold them. 3) Combine the following dry ingredients in a container large enough to hold them (i.e., remaining allulose, urolithin A, all vitamins (except ascorbic acid), all minerals, and tapioca fiber). 4) Measure out the lemon concentrate and add the natural flavor to it. 5) Weigh out the ascorbic acid. 6) Measure out the color and mix it into just enough water to create a thick liquid. 7) Add ingredients from #1 above to a pastry pan at room temperature. 8) Gradually add the ingredients from #2 above to the ingredients in the large pot and whisk. Allow to hydrate for 5-10 minutes, then whisk again. 9) Gradually add the ingredients from #3 above to the ingredients in the large pot and whisk. 10) While monitoring the temperature of the gummy solution, stir the mixture and heat relatively quickly while avoiding extreme temperatures that may cause burning. 11) Once the solution begins to boil, pay close attention to the temperature, which should eventually rise to 230°F. 12) At this point, immediately remove the gummy solution from the heat. 13) Once cooled to approximately 220°F, stir the following ingredients until homogenous: lemon concentrate with natural flavor and ascorbic acid. 14) Finally, add the liquid color and stir until homogenous. 15) Transfer the well-mixed gummy solution to a heated holding tank equipped with an agitator in preparation for depositing into molds. The temperature should be maintained so that the high methoxyl pectin does not begin to gel prior to molding. 16) The deposited gummy solution is cooled in the mold until gelation occurs and it is firm enough to be demolded, and carnauba wax or other coating is applied via panner or other means to prevent the gummies from sticking.

[0207] Example 3: Pectin formulation Exemplary formulations of the invention include: [Table 5]

[0208] The formulation further comprises water, concentrated apple juice, purified concentrated lemon juice, concentrated elderberry juice, and apple puree, and flavorings (minimum 0.23% (w / w)).

[0209] Example 4 - Results of preparation of spray-dried urolithin A composition Stable UA suspensions and stable citrus pectin (Lot No. SLBV5461, Sigma Life Science) suspensions were prepared using ethanol as the solvent. Both suspensions were stirred for a minimum of 1 hour. The suspensions were mixed to obtain suspensions containing UA and citrus pectin at either a 1 / 3 or 1 / 1 UA / pectin w / w ratio. After spray drying, the two resulting UA / pectin powder formulations were analyzed for solubility when dissolved in a biorelevant medium (FaSSIF, pH = 6.5), which mimics a gut-like environment. The solubility of the UA / pectin formulations was compared to that of pure UA powder. For both the pure UA powder and the UA / pectin formulations, an equivalent dose of 10 mg of UA was added to FaSSIF medium. Solubility was analyzed by UPLC (ultra-performance liquid chromatography) at different time points after powder addition to FaSSIF medium. The UA / pectin powder exhibited significantly enhanced solubility profiles at both ratios tested when compared to pure UA powder (Figure 3).

[0210] Additionally, UA / pectin-based formulations were tested using water instead of ethanol as the solvent. UA was dissolved in water to form a stable suspension. Citrus pectin (Lot No. SLBV5461, Sigma Life Science) was dissolved in water to form a solution. The UA suspension in water was complexed with citrus pectin solution (Lot No. SLBV5461, Sigma Life Science) at different ratios. One w / w ratio was UA / pectin 1 / 1, which showed positive data in formulations using EtOH as the solvent. Formulations with lower pectin content were also tested, specifically UA / pectin ratios of 4 / 1 w / w, 7 / 1 w / w, and 10 / 1 w / w.

[0211] Powders containing the equivalent of 10 mg of UA complexed with pectin at different ratios and 10 mg of pure UA powder were analyzed for their solubility profiles when dissolved in a biorelevant medium (FaSSIF, pH = 6.5), which mimics a gut-like environment. Solubility was analyzed by ultra-performance liquid chromatography (UPLC) at different time points after addition of the powder to FaSSIF medium. UA / pectin powders exhibited significantly enhanced solubility profiles at all ratios tested (Figure 2). This was confirmed by calculating the area under the curve (AUC) of the dissolution profile to quantify the total presence of soluble UA over time. All UA / pectin powders exhibited significant increases in AUC (Figure 5). Surprisingly, the increase in AUC was not proportional; a 1:1 ratio exhibited the highest AUC, while ratios of 1:4 and 1:7 exhibited similar profiles. The solubility enhancement only began to decrease when the UA / pectin ratio was reduced to 10:1 (Figure 5).

[0212] To compare the ability of the different formulations to increase UA solubility, we also calculated the maximum concentration of UA in solution (Cmax) achieved compared to formulations containing UA prepared in ethanol or water.

[0213] For formulations using ethanol as the solvent, the Cmax was 0.0009 for pure UA powder, 0.0038 for UA / pectin 1 / 3 powder, and 0.0035 for UA / pectin 1 / 1 powder, indicating that complexing UA with pectin using ethanol as the solvent allows for an increase in solubility Cmax of 322% for the UA / pectin 1 / 3 ratio and 288% for the UA / pectin 1 / 1 ratio (Figure 5).

[0214] For formulations using water as the solvent, the Cmax was 0.0009 for pure UA powder, 0.0049 for UA / pectin 1 / 1 powder, 0.0046 for UA / pectin 4 / 1 powder, 0.0045 for UA / pectin 7 / 1 powder, and 0.0043 for UA / pectin 10 / 1 powder. This indicates that complexing UA with pectin using ethanol as the solvent allows for an increase in solubility Cmax of 444% for UA / pectin 1 / 1, 411% for UA / pectin 4 / 1, 400% for UA / pectin 7 / 1, and 377.78% for UA / pectin 10 / 1 (Figure 6).

[0215] This data shows that using water as a solvent leads to formulations with better UA solubility after spray drying compared to using ethanol as a solvent.

[0216] The formulations tested above were produced by spray drying a solution / suspension of UA and pectin, the rationale being to improve the solubility of UA by reducing its crystalline state in favor of an amorphous state.

[0217] We also determined the solubility of UA after simple physical mixing of UA and pectin without spray drying. Surprisingly, all formulations tested showed increased UA solubility, even though spray drying was not used (Figure 7).

[0218] This was confirmed by calculating the area under the curve (AUC) of the dissolution profile to quantify the total presence of soluble UA over time. All UA / pectin powders showed a significant increase in AUC (Figure 6). Surprisingly, the increase in AUC was not proportional, with the 7:1 ratio showing the highest AUC (Figure 8).

[0219] In summary, the data show that spray-drying UA with pectin at a certain ratio can significantly increase UA solubility. The solubility enhancement is more pronounced when water is used as the solvent. In addition, even simple physical mixing of UA and pectin at a certain ratio can improve UA solubility, with a UA / pectin ratio of 7 / 1 being the best.

[0220] Example 5: Method for preparation of spray-dried urolithin A formulations 1. Device Settings Spray drying tests were carried out on a PROCEPT 4M8-TRIX spray dryer open-loop system (i.e., atmospheric conditions / compressed gas) (Figure 10). The spray dryer was equipped with a large cyclone. An extension column was installed to increase the residence time of the droplets / particles in the heated chamber. For all tests, a two-fluid nozzle with a 1.0 mm orifice was used.

[0221] 2. Preparation of Solutions and Suspensions All suspensions were prepared in a total amount of 50 g with a solids loading of 4.00% (w / w). For each formulation, this amount was completely spray dried, resulting in a total dose of 2 g. Different amounts of UA and pectin were added depending on the UA / pectin w / w ratio used.

[0222] For the solvents ethanol and water, UA was first suspended in the solvent, followed by the addition of the excipient pectin. If UA and / or the excipient did not dissolve, the formulation was spray-dried as a suspension. The suspension was magnetically stirred for a minimum of 1 hour before processing. The suspension was also continuously stirred during the spray-drying process.

[0223] Non-spray dried formulations were prepared by adding UA powder and pectin powder in different ratios tested. The powders were mixed using a mortar and pestle until the contents were visually uniform.

[0224] Example 6 – XRPD Characterization of Urolithin A Samples X-ray powder diffraction (XRPD) was used to measure the crystallinity of urolithin A. The XRPD diffractogram of crystalline urolithin A shows several peaks indicative of a crystalline structure. In amorphous material, these peaks are missing, or at least greatly reduced. For example, an XRPD diffractogram of crystalline urolithin A is shown in Figure 1.

[0225] XRPD analysis was carried out under the following conditions: Instrument: Aeris diffractometer (PANalytical, Malvern) equipped with a Cu tube (Kα λ=1.5418 Å) Generator: 40kV and 15mA Sample: Zero background sample holder method -4°~40° continuous scan mode -Step size = 0.0217° -Count time 500 seconds

[0226] Example 7 - UPLC Method - Assay Method The release profiles of the samples were analyzed using an AT Xtend semi-automatic dissolution bath (Sotax) coupled with a CP piston pump (Sotax). The USP II (paddle) method was used with FaSSIF (pH 6.5) as the dissolution medium at a temperature of 37°C. The paddle was rotated at 50 rpm. Approximately 10 mg of UA was placed in 1000 ml of medium, representing a maximum concentration of 0.01 mg / ml. Medium samples (i.e., 1.5 mL) were collected directly into UPLC vials at set time points using the piston pump. No dilution step was required; these samples were injected directly. Each sample was analyzed in triplicate. Concentrations were calculated using a calibration curve of UA prepared in organic medium (dissolution in DMSO and dilution with ACN).

[0227] Chromatography conditions: System: UPLC Detector: PDA (250-350nm) - Optimal wavelength: 230nm Column: SunFire C18 column, 100A, 3.5μm, 4.6×150mm Flow rate: 1.2mL / min Column temperature: 40℃ Injection volume: 7μl Run time: 25 minutes Needle wash (sample manager wash): MeOH / HO (9 / 1, v / v) Seal wash: MeOH / HO (3 / 7, v / v) Purge solvent (sample manager purge): MeOH / HO (3 / 7, v / v) Mobile phase: A: 0.05% TFA (w / v) in HO B: 0.05% TFA (w / v) in ACN [Table 6]

[0228] equivalent The invention has been described broadly and comprehensively herein. Those skilled in the art will readily envision various other means and / or structures for performing the functions and / or obtaining the results and / or one or more advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the specific application(s) for which the teachings of the invention are used. 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 invention described herein. Accordingly, the foregoing embodiments are presented by way of example only, and it should be understood that, within the scope of the appended claims and their equivalents, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods is within the scope of the invention, provided that such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent. Moreover, each of the narrower species and subgeneric groupings falling within the scope of the generic disclosure also form part of the invention. This includes the generic description of the invention with a provisio or negative limitation removing any subject matter from the genus, regardless of whether the deleted material is specifically recited herein.

[0229] Incorporation by Reference The contents of the articles, patents, and patent applications, and all other documents and electronically available information mentioned or cited herein are incorporated by reference herein in their entirety, as if each individual publication were specifically and individually indicated to be incorporated by reference. Applicants reserve the right to physically incorporate into this application any and all materials and information from such articles, patents, patent applications, or other physical and electronic documents.

[0230] Embodiments of the present invention 1. A chewable formulation comprising: a) a gelling component; b) a compound of formula (I) or a salt thereof; [ka] wherein A, B, C, and D are each independently selected from H and OH; W, X, and Y are each independently selected from H and OH; Z is selected from H and OH; A chewable formulation, wherein the formulation does not contain a sweetener system.

[0231] 2. 2. The chewable formulation of claim 1, further comprising: c) a sweetener system, for example, the sweetener system comprising one or more artificial sweeteners and / or comprising allulose.

[0232] 3. The chewable formulation of claim 2, wherein the sweetener system consists of one or more artificial sweeteners.

[0233] 4. A chewable formulation according to any one of the preceding claims, wherein the gelling component comprises one or more of pectin, gelatin, agar, corn starch, and modified starch.

[0234] 5. The chewable formulation of claim 4, wherein the gelling component comprises pectin, such as high methoxy pectin.

[0235] 6. The chewable formulation of claim 5, wherein the high methoxy pectin has an esterification range of about 60% to about 68%.

[0236] 7. A chewable formulation according to any one of the preceding claims, wherein the formulation comprises from about 0.5% to about 5% (w / w) of a gelling component, for example from about 0.5% to about 3% (w / w) pectin, such as from about 1.5% to about 3% (w / w) pectin.

[0237] 8. d) A chewable formulation according to any one of the preceding claims, further comprising a fibre component, such as a soluble fibre component.

[0238] 9. The chewable formulation of claim 8, wherein the fiber component is selected from soluble tapioca, psyllium husk powder, apple fiber, or a mixture thereof.

[0239] 10. A chewable formulation according to any one of the preceding claims, wherein the formulation has a Brix of from about 75 degrees to about 85 degrees.

[0240] 11. A chewable formulation according to any one of the preceding claims, wherein the formulation has a terminal boiling point of from about 108°C to about 111°C.

[0241] 12. A chewable formulation according to any one of the preceding claims, wherein the formulation comprises less than about 30% (w / w) sugar.

[0242] 13. A chewable formulation according to any one of the preceding claims, wherein the compound of formula (I) is selected from urolithin A, urolithin B, urolithin C, or urolithin D, e.g., urolithin A.

[0243] 14. A chewable formulation according to any one of the preceding claims, wherein the compound of formula (I) is present in the range of 100 mg to 2500 mg.

[0244] 15. A chewable formulation according to any one of the preceding claims for use as a drug, dietary supplement, functional food or medical food.

[0245] 16. A chewable formulation according to any one of the preceding claims for use as a medicament for use in the treatment and / or prevention of a muscle-related condition, for example wherein the muscle-related condition is selected from a musculoskeletal disease or disorder, muscle wasting, myopathy, neuromuscular disease such as Duchenne muscular dystrophy and other dystrophies, sarcopenia, for example acute sarcopenia, muscle atrophy and / or cachexia.

[0246] 17. A method for enhancing muscle performance, improving endurance, or improving muscle function, maintaining muscle function, or reducing loss of muscle function, for example, comprising administering to a subject an effective amount of the chewable formulation of any one of claims 1 to 15, wherein the subject suffers from age-related decline in muscle function, age-related sarcopenia, age-related muscle wasting, physical fatigue, muscle wasting, and / or is frail or pre-frail.

[0247] 18. Use of a chewable formulation according to any one of claims 1 to 15, for example in a method for improving physical performance, wherein the improvement in physical performance is in healthy individuals or elderly individuals.

[0248] 19. Use of a chewable formulation according to any one of claims 1 to 15 in a method for increasing muscle strength, increasing or maintaining muscle mass, or improving muscle recovery.

[0249] 20. Use of a chewable preparation according to any one of claims 1 to 15 in a method for improving physical endurance.

[0250] 21. Use of a chewable preparation according to any one of claims 1 to 15 in a method for preventing or delaying physical fatigue, enhancing work capacity and endurance, reducing muscle fatigue, and enhancing cardiac and cardiovascular function.

[0251] 22. Use of a chewable formulation according to any one of claims 1 to 15 in a method for enhancing sports performance.

[0252] 23. Use of a chewable formulation according to any one of claims 1 to 15 for a non-disease condition characterized by insufficient mitochondrial activity.

[0253] 24. A formulation according to any one of claims 1 to 15 for use in the treatment of a disease state characterised by insufficient mitochondrial activity.

Claims

1. 1. A composition comprising: a) A compound of formula (I) or a salt thereof, 【Chemistry 1】 During the ceremony, A, B, C, and D are each independently selected from H and OH; W, X, and Y are each independently selected from H and OH; a compound or a salt thereof, wherein Z is selected from H and OH; (b) pectin.

2. 2. The composition of claim 1, wherein the pectin is selected from low methoxy pectin, high methoxy pectin, or amidated low methoxy pectin, or mixtures thereof, e.g., the pectin is high methoxy pectin.

3. 3. The composition of claim 1, wherein the compound of formula (I) and pectin are in a ratio of about 1 to about 1 to about 10 (w / w).

4. The composition according to any one of claims 1 to 3, wherein the composition is a gummy candy.

5. The composition according to any one of claims 1 to 3, wherein the composition is a powder.

6. The composition according to any one of claims 1 to 3 and 5, wherein the composition is a mixture.

7. The composition of any one of claims 1 to 3 and 5, wherein the composition is prepared by spray drying.

8. The composition according to any one of claims 1 to 7, wherein the compound of formula (I) is in amorphous or partially amorphous form.

9. 9. The composition of claim 7 or 8 when dependent on claim 7, wherein the composition is prepared by spray drying in a solvent selected from ethanol and water.

10. below: a). Soluble fiber, such as soluble tapioca fiber; b). Low-calorie sweeteners, such as allulose, and c) The composition of any one of claims 4 to 9, further comprising one or more of citric acid and / or a citrate salt (e.g., sodium citrate), such as citric acid and a salt of citric acid (e.g., sodium citrate).

11. a). about 5% to about 20% (w / w) of a compound of formula (I), e.g., urolithin A; b). about 0.5% to about 4% (w / w) pectin; below: c). about 25% to about 45% (w / w) soluble fiber, e.g., soluble tapioca fiber; d). about 25% to about 45% (w / w) of a low-calorie sweetener, such as allulose; and e) The composition of any one of claims 4 to 9, further comprising about 0.5% to about 4% (w / w) of citric acid and / or a citrate salt (e.g., sodium citrate), such as one or more of citric acid and a salt of citric acid (e.g., sodium citrate).

12. A chewable formulation comprising: a) a gelling component; b) a compound of formula (I) or a salt thereof; 【Chemistry 2】 wherein A, B, C, and D are each independently selected from H and OH; W, X, and Y are each independently selected from H and OH; A chewable formulation wherein Z is selected from H and OH.

13. 13. The chewable formulation of claim 12, further comprising: c) a sweetener system, e.g., the sweetener system comprising one or more sweeteners.

14. 14. The chewable formulation of claim 12 or 13, wherein the gelling component comprises one or more of pectin, gelatin, and modified starch.

15. 15. The chewable formulation of claim 14, wherein the gelling component comprises pectin, such as high methoxy pectin.

16. 16. The chewable formulation of claim 15, wherein the high methoxy pectin has an esterification range of about 50% to about 75%.

17. 17. A chewable formulation according to any one of claims 12 to 16, wherein the formulation comprises from about 0.5% to about 5% (w / w) of a gelling component, such as from about 0.5% to about 4% (w / w) of pectin, such as from about 1.5% to about 3% (w / w) of pectin.

18. 18. A chewable formulation according to any one of claims 12 to 17, further comprising d) a fibre component, for example a soluble fibre component.

19. 19. The chewable formulation of claim 18, wherein the fiber component is selected from soluble tapioca, psyllium husk powder, apple fiber, or mixtures thereof.

20. 20. The chewable formulation of any one of claims 12 to 19, wherein the formulation has a Brix of about 75 degrees to about 85 degrees.

21. 21. The chewable formulation of any one of claims 12 to 20, wherein the formulation has a final boiling point of about 108°C to about 111°C.

22. 10. A chewable formulation according to any one of the preceding claims, wherein the formulation comprises less than about 30% (w / w) sugar.

23. The composition of any one of claims 1 to 11; or the chewable formulation of any one of claims 12 to 22, wherein the compound of formula (I) is selected from urolithin A, urolithin B, urolithin C, or urolithin D, such as urolithin A.

24. 10. A composition or formulation according to any one of the preceding claims, wherein the compound of formula (I), such as urolithin A, is present in the range of 100 mg to 2500 mg.

25. 10. A composition or formulation according to any one of the preceding claims for use as a medicament, dietary supplement, functional food or medical food.

26. 10. A composition or formulation according to any one of the preceding claims for use in the treatment and / or prevention of a muscle-related condition, e.g., said muscle-related condition is selected from musculoskeletal diseases or disorders, muscle wasting, myopathy, neuromuscular diseases such as Duchenne muscular dystrophy and other dystrophies, sarcopenia, e.g., acute sarcopenia, muscle atrophy and / or cachexia.

27. A method for enhancing muscle performance, improving endurance, or improving muscle function, maintaining muscle function, or reducing loss of muscle function, for example comprising administering to a subject an effective amount of a composition or formulation described in any one of claims 1 to 24, wherein the subject suffers from age-related decline in muscle function, age-related sarcopenia, age-related muscle wasting, physical fatigue, muscle wasting, and / or is frail or pre-frail.

28. For example, use of a composition or formulation according to any one of claims 1 to 24 in a method for improving physical performance, wherein the improvement in physical performance is in healthy individuals or elderly individuals.

29. Use of a composition or chewable formulation according to any one of claims 1 to 24 in a method for increasing muscle strength, increasing or maintaining muscle mass or improving muscle recovery.

30. Use of a composition or chewable formulation according to any one of claims 1 to 24 in a method for improving physical endurance.

31. Use of a composition or chewable formulation according to any one of claims 1 to 24 in a method for preventing or delaying physical fatigue, enhancing work capacity and endurance, reducing muscle fatigue, and enhancing cardiac and cardiovascular function.

32. Use of a composition or chewable formulation according to any one of claims 1 to 24 in a method for enhancing sports performance.

33. Use of a composition or chewable formulation according to any one of claims 1 to 24 for improving a non-disease condition characterized by insufficient mitochondrial activity.

34. A composition or chewable formulation according to any one of claims 1 to 24 for use in the treatment of a disease state characterised by insufficient mitochondrial activity.

35. A composition or chewable formulation according to any one of claims 1 to 24 for enhancing healthspan.

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