Chewable composition comprising pectin and urolithin

Abstract

The present invention relates to urolithin compositions and urolithin formulations comprising urolithin and pectin, in particular chewable formulations comprising urolithin and a gelling agent. The invention further comprises compositions and chewable formulations comprising urolithin in combination with other active ingredients, as well as processes for preparing such compositions and formulations. The invention further comprises methods of treating conditions and diseases and for promoting health and performance, such as improving muscle function, using such compositions and formulations.

Description

Technical Field

[0001] The present invention relates to urolithin compositions and urolithin preparations comprising urolithin and pectin, in particular chewable preparations comprising urolithin and a gelling agent. The present invention further encompasses compositions and chewable preparations comprising urolithin in combination with other active ingredients, as well as processes for preparing such compositions and preparations. The present invention further encompasses methods of using such compositions and preparations for treating conditions and diseases and for promoting health and performance, such as improving muscle function. Background Art

[0002] Urolithin has been proposed for treating various conditions associated with insufficient mitochondrial activity, including obesity, reduced metabolic rate, metabolic syndrome, diabetes, cardiovascular disease, hyperlipidemia, neurodegenerative diseases, cognitive impairment, mood disorders, stress, and anxiety disorders; for weight management or for improving muscle performance or mental performance. See WO2012 / 088519 (Amazentis SA). In WO2007 / 127263 (The Regents of the University of California), the use of urolithin for treating various neoplastic diseases is described.

[0003] International Patent Publication WO2014 / 004902 (from application PCT / US2013 / 48310) discloses a method of increasing autophagy in cells, particularly including mitophagy, the method comprising contacting the cells with an effective amount of urolithin or a pharmaceutically acceptable salt thereof, whereby autophagy in the cells is increased, particularly including mitophagy. A subject suffering from a disease or condition selected from the following may be administered: metabolic stress, cardiovascular disease, endothelial cell dysfunction, sarcopenia, muscle degenerative diseases, Duchenne muscular dystrophy, alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver or muscle injury, 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 diseases, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, age-related macular degeneration, mitochondrial diseases (including, for example, poor growth, loss of muscle coordination, muscle weakness, vision problems, hearing problems, heart disease, liver disease, kidney disease, gastrointestinal disorders, respiratory disorders, nerve problems, autonomic dysfunction (sometimes learning disabilities) and dementia (resulting from mitochondrial diseases), muscle diseases, cancer, cognitive impairment, stress and mood disorders.

[0004] Chewable products (gum preparations) are typically made from a gelatin or pectin matrix with sugar, glucose, corn syrup, flavorings, colorings, and citric acid and are a popular snack food product. The products (preparations) typically have a gel or gel-like structure and texture and are produced in a variety of shapes, colors, and flavors that are chewable upon consumption. Recently, gum products have been supplemented with vitamins, minerals, essential oils, and other nutritional supplements to provide nutritional supplements that appeal to children and adults who dislike swallowing or have difficulty swallowing tablets or capsules.

[0005] Gelatin is a soluble and gel-like protein that is extracted from animal bones, skin, tendons, and muscles and is then partially hydrolyzed by acid, base, or enzymes. Gelatin has been widely used in chewable preparations; however, recently the use of gelatin has decreased. This has been advocated due to its animal origin, as traditionally, vegetarian consumers and their religious advocates avoid animal-derived products. Recently, although the average consumer is not concerned with vegetarianism or religious preferences, they also tend to prefer foods that use another agent in place of gelatin, such as gums extracted from plants, for example, pectin.

[0006] However, although plant-based chewable formulations (such as those containing pectin) are a popular choice, they can be difficult to manufacture. Therefore, there is a current need to improve chewable formulations containing pectin, particularly in formulating novel active ingredients into chewable formulations. Summary of the Invention

[0007] According to one aspect of the present invention, there is provided a chewable formulation comprising:

[0008] a) a gelling component, and

[0009] b) a compound of formula (I) or a salt thereof:

[0010]

[0011] Wherein:

[0012] A, B, C and D are each independently selected from H and OH;

[0013] W, X and Y are each independently selected from H and OH; and

[0014] Z is selected from H and OH.

[0015] According to a further aspect of the present invention, there is provided a chewable formulation comprising:

[0016] a) a gelling component,

[0017] b) a compound of formula (I) or a salt thereof:

[0018] wherein the formulation does not include a sweetener system.

[0019] According to a further aspect of the present invention, there is provided a chewable formulation comprising:

[0020] a) a gelling component,

[0021] b) a compound of formula (I) or a salt thereof:

[0022] c) a sweetener system, wherein the sweetener system comprises one or more artificial sweeteners.

[0023] According to a further aspect of the present invention, there is provided a chewable formulation comprising:

[0024] a) a gelling component,

[0025] b) a compound of formula (I) or a salt thereof:

[0026] c) a sweetener system, wherein the sweetener system comprises allulose.

[0027] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0028] a) a gelling component,

[0029] b) a compound of formula (I) or a salt thereof:

[0030] c) a sweetener system, wherein the sweetener system comprises inulin.

[0031] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0032] a) a gelling component,

[0033] b) a compound of formula (I) or a salt thereof:

[0034] c) a sweetener system, wherein the sweetener system consists of one or more artificial sweeteners.

[0035] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0036] a) a gelling component,

[0037] b) a compound of formula (I) or a salt thereof, and

[0038] c) a pH buffer.

[0039] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0040] a) a gelling component,

[0041] b) a compound of formula (I) or a salt thereof, and

[0042] c) a pH of from about 2.7 to about 3.7.

[0043] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0044] a) a gelling component,

[0045] b) a compound of formula (I) or a salt thereof, and

[0046] c) a pH buffer, wherein the pH buffer maintains the pH at from about 2.7 to about 3.7.

[0047] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0048] a) a gelling component,

[0049] b) A compound of formula (I) or a salt thereof, and

[0050] c) A pH of from about 2.7 to about 4.0.

[0051] In a further aspect of the invention, there is provided a chewable preparation comprising:

[0052] a) A gelling component,

[0053] b) A compound of formula (I) or a salt thereof, and

[0054] c) A pH buffer, wherein the pH buffer maintains the pH at from about 2.7 to about 4.0.

[0055] In a further aspect of the invention, there is provided a chewable preparation comprising:

[0056] a) A gelling component,

[0057] b) A compound of formula (I) or a salt thereof, and

[0058] c) A fiber component, such as a soluble fiber component.

[0059] In a further aspect of the invention, there is provided a chewable preparation comprising:

[0060] a) A gelling component,

[0061] b) A compound of formula (I) or a salt thereof, and

[0062] c) A Brix of from about 75 degrees to about 85 degrees, for example, from about 77 degrees to about 82 degrees.

[0063] In a further aspect of the invention, there is provided a chewable preparation comprising:

[0064] a) A gelling component,

[0065] b) A compound of formula (I) or a salt thereof, and

[0066] c) A final boiling point of from about 108 °C to about 111 °C (from about 228 °F to about 231 °F).

[0067] In a further aspect of the invention, there is provided a low-calorie chewable preparation comprising:

[0068] a) A gelling component,

[0069] b) A compound of formula (I) or a salt thereof, and

[0070] wherein the preparation comprises less than about 30% (w / w) sugar.

[0071] According to a further aspect of the present invention, there is provided a low-calorie chewable preparation comprising:

[0072] a) a gelling component,

[0073] b) a compound of formula (I) or a salt thereof, and

[0074] wherein the preparation comprises less than about 50% (w / w) sugar, such as less than about 45% (w / w) sugar, such as less than about 40% (w / w) or less than about 30% (w / w) sugar.

[0075] According to a further aspect of the present invention, there is provided a low-calorie chewable preparation comprising:

[0076] a) a gelling component,

[0077] b) a compound of formula (I) or a salt thereof, and

[0078] wherein the preparation comprises from about 25% to about 40% sugar.

[0079] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0080] a) a gelling component,

[0081] b) a compound of formula (I) or a salt thereof, and

[0082] c) wherein the gelling component comprises pectin having an esterification range of from about 55% to about 75%, such as from 60% to about 68%.

[0083] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0084] a) a gelling component, the gelling component comprising high-methoxyl pectin, and

[0085] b) a compound of formula (I) or a salt thereof.

[0086] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0087] a) a gelling component, the gelling component comprising low-methoxyl pectin, and

[0088] b) a compound of formula (I) or a salt thereof.

[0089] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0090] a) a gelling component, said gelling component comprising amidated low-methoxyl pectin, and

[0091] b) a compound of formula (I) or a salt thereof.

[0092] According to a further aspect of the present invention, there is provided a chewable preparation comprising:

[0093] a) a gelling component, said gelling component comprising low-methoxyl pectin,

[0094] b) a compound of formula (I) or a salt thereof, and

[0095] c) a divalent cation, for example provided by a calcium salt, such calcium salts being selected from calcium chloride, calcium citrate and / or calcium sulphate.

[0096] In one embodiment, the preparation comprises a calcium salt in the range of from about 0.05% to about 0.1% (w / w).

[0097] Suitable gelling components are those which provide a cohesive gelled product when used alone or in combination with other gelling components. The gelling component may be selected from one or more gelling agents. For example, gelling agents 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 component is pectin. In a further embodiment, the gelling agent comprises gellan gum and carrageenan.

[0098] In a further embodiment, the preparation comprises from about 0.5% to about 5% (w / w) of the gelling component.

[0099] In a further embodiment, the preparation comprises from about 0.5% to about 4% (w / w) of 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) of pectin, such as from about 1% to about 2% (w / w), such as from about 1.2% to about 1.8% (w / w), such as about 1.4% (w / w), such as about 1.5% (w / w), such as about 1.6% (w / w), such as about 1.7% (w / w).

[0100] In one embodiment, the preparation is substantially free of animal-derived products, for example, substantially free of gelatin.

[0101] In a further embodiment, the gelling component is selected from one or more of the following: carrageenan, alginic acid, sodium alginate, xanthan gum, gellan gum, gum arabic, guar gum and locust bean gum.

[0102] In a further embodiment, the gelling agent is selected from one or more of the following: pectin and gelatin.

[0103] In one embodiment, the formulation comprises a gelling component, and the gelling component comprises pectin. In a further embodiment, the formulation comprises a gelling component consisting of pectin.

[0104] The pectin suitable for the formulations of the present invention is any pectin that provides the necessary gel strength for the formulations of the present invention. In one embodiment of the present invention, the pectin is high-methoxyl pectin. High-methoxyl pectin is pectin in which at least 50% of the galacturonic acid units are esterified with methoxy groups.

[0105] In one embodiment, the methoxyl pectin is esterified in the range of about 50% to about 75%, for example, about 55% to about 75%, about 55% to about 70% or about 65% to about 75% of the methoxyl pectin. 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 methoxyl pectin is esterified about 55%, esterified about 60%, esterified about 65% or esterified about 70%.

[0106] In a further embodiment of the present invention, the pectin is low-methoxyl pectin. Low-methoxyl pectin is pectin in which less than 50% of the galacturonic acid units are esterified with methoxy groups.

[0107] The formulations of the present invention may further comprise fibers. In one embodiment, natural-source fibers are used, for example, one or more selected from the following: natural-source inulin, inulin extract, synthetic inulin, the hydrolysis product of inulin commonly known as fructooligosaccharide, galactooligosaccharide, xylooligosaccharide, the oligomeric derivatives of starch, hulls, bran, 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.

[0108] In some embodiments, the fibers may include inulin, wheat dextrin or fructooligosaccharide. Inulin, wheat dextrin and fructooligosaccharide can also act as thickeners and improve the texture of the formulation. Dietary fibers can be incorporated into the formulation at various loading rates to produce an improved texture and, at a certain loading rate, can provide dietary benefits, including promoting a healthy digestive system, controlling blood sugar levels and providing probiotic benefits. Adding dietary fiber and the remaining components allows water to be added, which helps to replace the sugar in flavored chewy or gummy candies.

[0109] In a further embodiment, the fibers are selected from soluble tapioca flour, psyllium husk powder, apple fiber, dextrin, inulin or mixtures thereof.

[0110] In one embodiment, the fibers may be present in an amount of from about 10% to about 60% (w / w), alternatively from about 20% to about 60%, alternatively from about 30% to about 60%, alternatively from about 30% to about 50% (w / w), alternatively from about 30% to about 40%, such as about 35% (w / w), such as about 37% (w / w), such as about 40% (w / w).

[0111] Conventional chewable formulations contain no more than 6% (w / w) of the active ingredient. However, by carefully selecting 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 may include the following active components: from about 5% to about 25% (w / w) of the active ingredient, for example, from about 6% to about 25% 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, about 20% (w / w) of the active ingredient.

[0112] In one embodiment, compared to conventionally commercially available chewable formulations, the chewable formulations of the present invention have a reduced sugar content. For example, the chewable formulations of the present invention contain less than about 70% (w / w) of sugar, for example, less than about 60% (w / w), for example, less than about 50% (w / w), for example, less than about 40% (w / w), for example, less than about 30% (w / w), for example, less than about 25% of sugar, such as less than about 20% (w / w), less than about 15% of sugar, less than about 10%, less than about 5% or about 0% of sugar.

[0113] In one embodiment, the formulations of the present invention further comprise additives selected from the group consisting of: sweeteners, food acids, flavoring agents, coloring agents, humectants, fillers, fatty acids, triglycerides, plasticizers, emulsifiers, thickeners, preservatives, and / or mixtures thereof. In additional embodiments, the formulations of the present invention comprise additives selected from the group consisting of: sweeteners, food acids, flavoring agents, and coloring agents.

[0114] Sweetener

[0115] Generally, an effective amount of a sweetener can be utilized to provide the desired sweetness, and this amount can vary depending on the selected sweetener. The sweetener may include one or more monosaccharides or disaccharides. Examples include sugars, sucrose, invert sugar, dextrose, lactose, honey, malt syrup, malt syrup solids, maltose, fructose, granular fructose, maple syrup, rice syrup, rice syrup solids, sorghum syrup, refined syrup, corn syrup, corn syrup solids, high fructose corn syrup, molasses, or combinations thereof.

[0116] In one embodiment, the sweetener includes common sugars such as sucrose and glucose, polyols such as maltitol, erythritol, and isomaltulose, syrup sweeteners such as glucose syrup, corn syrup, high fructose corn syrup, and fruit juice concentrates. In additional embodiments, the sweetener includes allulose.

[0117] In one embodiment, artificial sweeteners can be used, such as acesulfame K, aspartame, sucralose, d-tagatose, neotame, monatin, and acesulfame potassium (Ace-K) or combinations thereof.

[0118] In additional embodiments, the sweetener includes saccharin, sodium saccharin, sodium cyclamate, acesulfame potassium, thaumatin, neohesperidin dihydrochalcone, ammonium glycyrrhizinate, and aspartame.

[0119] The sweeteners involved can 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. Without being limited to specific sweeteners, representative classes and examples include:

[0120] (a) Water-soluble sweeteners such as dihydrochalcone, monellin, stevioside, lu han guo, lu han guo derivatives, glycyrrhizin, dihydroflavonol, and sugar alcohols such as sorbitol, mannitol, maltitol, xylitol, erythritol, and L-amino dicarboxylic acid amino enoate amides, such as those disclosed in U.S. Patent No. 4,619,834, the disclosure of which is incorporated herein by reference, and mixtures thereof;

[0121] (b) Water-soluble artificial sweeteners such as soluble saccharin salts, namely sodium saccharin or calcium saccharin, cyclamate, the sodium, ammonium, or calcium salts of 3,4-dihydro-6-methyl-1,2,3-oxathiazin-4-one-2,2-dioxide, the 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;

[0122] (c) Dipeptide-based sweeteners, such as L-aspartic acid-derived sweeteners, such as methyl L-aspartyl-L-phenylalanine ester (aspartame), 1-methyl-N-[Nl-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine ester (neotame), and the materials described in U.S. Patent No. 3,492,131, L-α-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamide hydrate (alitame), methyl esters of L-aspartyl-L-phenylglycine and L-aspartyl-L-2,5-dihydrophenylglycine, L-aspartyl-2,5-dihydro-L-phenylalanine; L-aspartyl-L-(1-cyclohexene)-alanine and mixtures thereof;

[0123] (d) Water-soluble sweeteners, said water-soluble sweeteners being derived from naturally occurring water-soluble sweeteners, such as chlorinated derivatives of common sugar (sucrose), e.g., chlorodeoxysugar derivatives, such as chlorodeoxysucrose or derivatives of chlorodeoxygalactosucrose, e.g., those known under the product name sucralose; examples of chlorodeoxysucrose and chlorodeoxygalactosucrose derivatives include, but are not limited to: 1-thio-1'-deoxysucrose; 4-chloro-4-deoxy-α-D-galactopyranosyl-α-D-fructofuranoside or 4-chloro-4-deoxygalactosucrose; 4-chloro-4-deoxy-α-D-galactopyranosyl-1-chloro-1-deoxy-β-D-fructo-furanoside or 4,r-dichloro-4,r-dideoxygalactosucrose; 1',6'-dichloro-1',6'-dideoxysucrose; 4-chloro-4-deoxy-α-D-galactopyranosyl-1,6-dichloro-1,6-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-6,r,6'-trideoxysucrose; 4,6-dichloro-4,6-bisdeoxy-α-D-galactopyranosyl-1,6-dichloro-1,6-dideoxy-β-D-fructofuranoside or 4,6,r,6'-tetrachloro-4,6,r,6'-tetradeoxygalactosucrose; and 4,6,r,6'-tetradeoxysucrose and mixtures thereof;

[0124] (e) Protein-based sweeteners, such as thaumatococcus danielli (thaumatin I and II) and talin; and

[0125] (f) The sweetener monatin (2-hydroxy-2-(indol-3-ylmethyl)-4-aminopentanedioic acid) and its derivatives. High-intensity sweeteners can be used in many different physical forms well known in the art to provide an initial sweetness burst and / or a lasting sweetness sensation. Without limitation, such physical forms include the free form, spray-dried form, powder form, bead 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).

[0126] In some embodiments, the sweetener can be a polyol. Polyols can include, but are not limited to, glycerol, sorbitol, maltitol, maltitol syrup, mannitol, isomalt, erythritol, xylitol, hydrogenated starch hydrolysates, polyglycitol syrup, polyglycitol powder, lactitol, and combinations thereof.

[0127] Generally, an effective amount of a high-intensity sweetener can be utilized to provide the desired sweetness, and this amount can vary depending on the selected sweetener. Depending on the sweetener or combination of sweeteners used, the high-intensity sweetener can be present in the formulation in an amount of from about 0.001 wt% to about 3 wt%. The exact amount range for each type of sweetener can be selected by those skilled in the art.

[0128] In one embodiment, the formulation may include a sweetening agent, which includes, for example, sugars, glucose syrup, corn syrup, high fructose corn syrup, fruit juice concentrate, or mixtures thereof. In one embodiment, the sweetening agent comprises erythritol, xylitol, sugars, glucose syrup, corn syrup, high fructose corn syrup, fruit juice concentrate, tapioca syrup, agave syrup, brown rice syrup, high maltose syrup, invert sugar, artificial sweeteners, saccharin, saccharin sodium, cyclamic acid, cyclamate, aspartame, sucralose, acesulfame potassium, rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside E, dulcoside A, dulcoside B, rubusoside, stevia, stevioside, mogroside IV, mogroside V, momordica grosvenori sweetener, siamenoside, monatin and its salts (monatin SS, RR, RS, SR), curculin, glycyrrhizic acid and its salts, thaumatin, monellin, mabinlin, brazzein, hernandulcin, phyllodulcin, glycyphyllin, phloridzin, trilobatin, baiyunoside, osladin, polypodoside A, pterocaryoside A, pterocaryoside B, mukurozioside, phlomisoside I, periandrin I, abrusoside A, cyclocarioside I, sucralose, acesulfame potassium and other salts, aspartame, alitame, saccharin, neohesperidin dihydrochalcone, cyclamic acid, neotame, 1-methyl-N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine ester, 1-methyl-N-[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-L-α-aspartyl]-L-phenylalanine ester, 1-methyl-N-[N-[3-(3-methoxy-4-hydroxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine ester, its salts, licorice or its extract or isolate, or mixtures thereof.

[0129] Food acid

[0130] The pH of the formulation is from about 2.5 to about 4, for example, from about 2.7 to about 4, from about 2.8 to about 3.7. The pH can be adjusted by food acid, buffer, or both.

[0131] 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.

[0132] Suitable buffers include, but are not limited to: sodium ascorbate, sodium citrate, sodium malate, sodium fumarate, potassium sodium tartrate, and / or sodium tartrate.

[0133] Flavoring agent

[0134] In some embodiments, the formulation may further include a flavoring agent. Flavoring agents may include those spices known to those skilled in the art, such as natural and artificial flavors. These flavoring agents may be selected from synthetic flavor oils and flavoring aromatics and / or oils, oleoresins, and extracts derived from plants, leaves, flowers, fruits, etc., and combinations thereof.

[0135] In some embodiments, the flavorant can include mint, menthol, menthone, isomenthone, camphor, and cineole, eucalyptol, camphor, borneol, fenchone, menthone and isomenthone, isopulegol, monomenthyl succinate and menthyl lactate, menthone, isomenthone, borneol, fenchone, eucalyptus, eucalyptol, ethyl benzoate, neomenthol, d-fenchone, furfurylidene butyrate, bucchu fraction, 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 sage. Non-limiting representative flavor oils include spearmint oil, cinnamon oil, wintergreen oil (methyl salicylate), peppermint oil, Japanese peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, nutmeg oil, sweet pepper, sage oil, mace, bitter almond oil, and cassia oil. Also useful flavorants are artificial, natural, and synthetic fruit flavors such as vanilla, and citrus oils including lemon, orange, lime, grapefruit, pomelo, sudachi, and fruit essences including apple, pear, peach, grape, blueberry, strawberry, raspberry, cherry, plum, pineapple, apricot, banana, melon, apricot, ume, cherry, raspberry, blackberry, tropical fruits, mango, mangosteen, pomegranate, papaya, and the like. Other potential flavorings that can manage the release profile include milk flavor, butter flavor, cheese flavor, cream flavor, and yogurt flavor; vanilla flavor; tea or coffee flavors such as green tea flavor, oolong tea flavor, tea flavor, cocoa flavor, chocolate flavor, and coffee flavor; mint flavors such as peppermint flavor, spearmint flavor, and Japanese peppermint flavor; spicy flavors such as asafoetida flavor, bishop's weed flavor, fennel flavor, angelica flavor, cumin flavor, sweet pepper flavor, cinnamon flavor, chamomile flavor, mustard flavor, cardamom flavor, caraway flavor, cumin flavor, clove flavor, pepper flavor, coriander flavor, sassafras flavor, salty flavor, Sichuan pepper (Zanthoxyli Fructus) flavor, perilla flavor, juniper flavor, ginger flavor, star anise flavor, horseradish flavor, thyme flavor, tarragon flavor, dill flavor, chili flavor, nutmeg flavor, basil flavor, marjoram flavor, rosemary flavor, bay leaf flavor, and wasabi (Japanese horseradish) flavor; alcoholic 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 flavorants can be used in liquid or solid form and can be used alone or in combination. Commonly used flavorings include mint, such as peppermint, menthol, spearmint, artificial vanilla, cinnamon derivatives, and various fruit flavors, either alone or in combination.The flavoring can also provide breath freshening properties, particularly menthol flavoring when used in combination with a coolant as described below. In some embodiments, the flavorant can be selected from geraniol, linalool, nerol, nerolidol, citronellol, heliotropin, methyl cyclopentenolone, ethyl vanillin, maltol, ethyl maltol, furanone, oniony compounds, rose-type compounds such as phenylethyl alcohol, phenylacetic acid, nerol, styrallyl acetate, jasmine, sandalwood, patchouli, and / or cedarwood.

[0136] In some embodiments, other flavorants can be used, including aldehydes and esters such as cinnamyl acetate, cinnamaldehyde, citral diethyl acetal, dihydrocarvyl acetate, eugenyl formate, p-methylamisol, etc. Generally, any flavorant or food additive can be used, such as those described in Chemicals Used in Food Processing, 1274th Edition, pages 63 - 258, of the National Academy of Sciences. This publication is incorporated herein by reference. These can include natural as well as synthetic flavors.

[0137] Other examples of aldehyde flavorants include, but are not limited to, acetaldehyde (apple), benzaldehyde (cherry, almond), anisaldehyde (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), heliotropin, i.e., piperonal (vanilla, cream), vanillin (vanilla, cream), α-amylcinnamaldehyde (spicy fruit flavor), butyraldehyde (butter, cheese), valeraldehyde (butter, cheese), citronellal (modified, various types), decanal (citrus fruits), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), 2-ethylbutyraldehyde (berry fruits), hexenal, i.e., trans-2 (berry fruits), methylbenzaldehyde (cherry, almond), veratraldehyde (vanilla), 2,6-dimethyl-5-heptenal, e.g., melonal (melon), 2,6-dimethyloctanal (green fruits), and 2-dodecenal (citrus, citrus), cherry, grape, blueberry, blackberry, strawberry shortcake, and mixtures thereof.

[0138] In one embodiment, the flavoring agent comprises vanilla, peppermint oil, spearmint oil, eucalyptus oil, cinnamon oil, grapefruit oil, menthol, monomenthyl succinate, ethylene glycol monomethyl carbonate, menthone glycerin ketal, menthyl lactate, (-)-isopulegol, p-menthane-3,8-diol, (-)-methyl hydrogen glutarate, wintergreen oil (methyl salicylate), citrus oil, orange oil, fruit essence, rosemary oil, lavender oil, sage oil, clary sage oil, thyme oil, sandalwood oil, basil oil, coriander oil, cypress oil, fleabane oil, frankincense oil, geranium oil, anise oil, oregano oil, Dalmatian sage oil, tarragon oil, or a mixture or derivative thereof.

[0139] Colorant

[0140] The colorant can be used in an amount effective to produce the desired color. The colorant can include pigments, which can be incorporated at up to about 6 wt% of the formulation. The colorant can also include natural food colors and dyes suitable for food, pharmaceutical, and cosmetic applications. These colorants are known as F.D.&C. dyes and lakes. Materials acceptable for the foregoing uses are preferably water-soluble. Illustrative non-limiting examples include indigoid dyes known as F.D.&C. Blue No. 2, which is the disodium salt of 5,5-indigodisulfonic acid. Similarly, the dye known as F.D.&C. Green No. 1 contains a triphenylmethane dye and is the monosodium salt of 4-[4-(N-ethyl-N-p-sulfonium benzylamino)diphenylmethylene]-[1-(N-ethyl-N-p-sulfonium benz)-δ-2,5-cyclohexadienimine]. A complete description of all F.D.&C. colorants and their corresponding chemical structures can be found in Kirk-Othmer Encyclopaedia of Chemical Technology, 3rd Edition, Volume 5, pages 857-884, the text of which is incorporated herein by reference.

[0141] In some embodiments, one or more colorants may be included. As classified by the United States Food, Drug, and Cosmetic Act (21 C.F.R. 73), colorants may include exempt-certification colorants (sometimes referred to as natural colorants, even though they may be synthetically manufactured) and certified colorants (sometimes referred to as artificial) or combinations thereof. In some embodiments, exempt-certification or natural colorants may include, but are not limited to, annatto extract (E160b), carminic acid, norcarminic acid, astaxanthin, dehydrated beets (beet powder), betanin / betanin (E162), ultramarine blue, canthaxanthin (E161g), cryptoxanthin (E161c), violaxanthin (E161d), neoxanthin (E161e), taxaxanthin (E161f), caramel (E150(a-d)), β-apo-8'-carotenal (E160e), β-carotene (E160a), α-carotene, γ-carotene, β-apo-8-carotene ethyl ester (E160f), flavoxanthin (E161a), lutein (E161b), cochineal extract (E120); carmine (E132), acid red / azorubine (E122), sodium copper chlorophyllin (E141), chlorophyll (E140), roasted, partially defatted cottonseed meal, ferrous gluconate, ferrous lactate, grape color extract, grape skin extract (grape anthocyanins), anthocyanins (E163), haematococcus algae meal, synthetic iron oxides, iron oxides and hydroxides (E172), fruit juices, vegetable juices, dried seaweed powder, Aztec marigold powder and extract, carrot oil, corn germ oil, paprika, oleoresin of paprika, phaffia yeast, riboflavin (E101), saffron, titanium dioxide, turmeric (E100), oleoresin of turmeric, amaranth (E123), capsanthin / capsaicin (E160c), lycopene (E160d), and combinations thereof.

[0142] In some embodiments, certified colors can 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 (El 10), ponceau 4R (E124), erythrosine (E127), patent blue V (E131), titanium dioxide (E171), aluminum (E173), silver (E174), gold (E175), pigment rubine / lithol rubine BK (E180), calcium carbonate (E170), carbon black (E153), black PN / bright black BN (E151), green S / acid green BS (E142), and combinations thereof. In some embodiments, certified colors can include FD&C lake colors. These include aluminum salts of FD&C dyes extended on an insoluble substrate of aluminum hydrate. Additionally, in some embodiments, certified colors can include calcium salts.

[0143] In some embodiments, natural fruit or vegetable juices or extracts can be used as colorants. Examples include, but are not limited to, carrot juice, raspberry juice, blackberry juice, blueberry juice, and beet juice.

[0144] Humectants

[0145] Glycerin is a humectant and freezing point depressant. It also helps reduce the tendency to granulate and helps maintain softness. In some embodiments, glycerin or an equivalent material can be employed in an amount of about 1 wt% to about 5 wt%, such as 2 wt% to 3 wt%, of the final product.

[0146] Humectants that can provide a perception of oral hydration can be included. Such humectants can include, but are not limited to, glycerin, sorbitol, polyethylene glycol, erythritol, and xylitol. Additionally, in some embodiments, fats can provide a perception of oral wetness. Such fats can include medium-chain triglycerides, vegetable oils, fish oils, mineral oils, and combinations thereof.

[0147] Fillers

[0148] Suitable sugar fillers include monosaccharides, disaccharides, and polysaccharides such as xylose, ribulose, glucose (dextrose), lactose, mannose, galactose, fructose (levulose), sucrose (sugar), maltose, invert sugar, partially hydrolyzed starch, and corn syrup solids, and mixtures thereof.

[0149] Suitable sugar alcohol fillers include sorbitol, xylitol, mannitol, galactitol, lactitol, maltitol, erythritol, isomalt, and mixtures thereof. Suitable hydrogenated starch hydrolysates include those disclosed in U.S. Patent No. 4,279,931 and various hydrogenated glucose syrups and / or powders containing sorbitol, maltitol, hydrogenated disaccharides, hydrogenated higher polysaccharides, or mixtures thereof. Hydrogenated starch hydrolysates are prepared primarily by the 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 give different hydrogenated starch hydrolysates different properties. Mixtures of hydrogenated starch hydrolysates, such as the commercially available products LYCASIN.RTM. manufactured by Roquette Freres of France and HYSTAR.RTM. manufactured by SPI Polyols, Inc. of New Castle, Del., are also useful.

[0150] In one embodiment, the filler comprises maltitol syrup, polydextrose, sorbitol, soluble corn fiber, resistant starch, resistant maltodextrin, cellulose, hemicellulose, fructooligosaccharides, galactooligosaccharides, lactulose, xylooligosaccharide isomaltose, soy oligosaccharides, glucooligosaccharides, stachyose, lactosucrose, or combinations thereof.

[0151] Plasticizer

[0152] In some embodiments, the formulation may further include a plasticizer to modify the texture of the formulation. Texture modifiers may include particulate materials. Suitable particulate materials may include, but are not limited to, sucrose, polyols such as sorbitol, xylitol, mannitol, galactitol, lactitol, maltitol, erythritol, isomalt, hydrogenated starch hydrolysates, and mixtures thereof, starch, proteins, and combinations thereof. In some embodiments, the particulate material used as a texture modifying component is selected based on its ability or lack thereof to cause crystallization of the sugars in the sugar moiety. For example, when isomalt is included in the sugar moiety, sorbitol powder may be added to the formulation because it does not cause isomalt crystallization. Alternatively, when erythritol is included in the sugar moiety, erythritol powder may be added to the formulation because it will cause erythritol crystallization. Such particulates may be included in an amount of 5% to 35% w / w of the formulation.

[0153] Emulsifier

[0154] The formulation may include an emulsifier. The emulsifier may be present in the formulation in an amount of from about 0.001 wt% to about 5 wt%, alternatively from 0.001 wt% to 1 wt%, alternatively from 1 wt% to 3 wt%, alternatively from 3 wt% to 5 wt%. In some embodiments, the emulsifier is present in the formulation in an amount of from about 0 wt% to about 5 wt%, alternatively from 0.001 wt% to 1 wt%, alternatively from 1 wt% to 3 wt%, alternatively from 3 wt% to 5 wt%.

[0155] Exemplary emulsifiers include, but are not limited to, modified corn starch, monoglycerides and diglycerides, and lecithin.

[0156] The emulsifier can help keep the fat together with water and other components in a homogeneous formulation. In one embodiment, the emulsifier can help form a "water and oil" emulsion, which results in a smooth texture of the finished product.

[0157] Thickening agent

[0158] The formulation may further include a thickening agent to contribute to the viscosity of the final product. Some thickening agents are gelling agents. Others act as mechanical thixotropic additives where discrete particles adhere or interlock to resist strain.

[0159] In some embodiments, the thickening agent may be a polysaccharide or a protein. Examples of polysaccharide thickening agents include starch, vegetable gums, and pectin. Examples of starch-based thickening agents include arrowroot, corn starch, katakuri starch, potato starch, sago, tapioca, and starch derivatives thereof. Exemplary vegetable gum-based thickening agents may include alginate, guar gum, locust bean gum, and xanthan gum. Exemplary protein-based thickening agents include collagen, egg white, furcellaran, and gelatin. Sugar-based thickening agents may include agar and carrageenan.

[0160] Preservative

[0161] The preservative may 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 may include phenols (phenolic acids, polyphenols, tannins), isoflavones, 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.

[0162] In some embodiments, the formulation may include at least about 0 wt% to 2 wt% of the above preservative components or mixtures thereof in the formulation.

[0163] Gelling component

[0164] The gelling component may include one or more gelling agents. A variety of gelling agents can be utilized, including but not limited to gelatin, pectin, gum arabic, carrageenan, high-methoxyl pectin, alginate, gellan gum, modified or unmodified starch, modified starch wheat flour or concentrated wheat flour or bleached flour, or any type from natural sources or combinations thereof.

[0165] Other example gelling agents can include acacia, alginic acid, bentonite, (which is now carbomer), carboxymethyl cellulose, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, magnesium aluminum silicate methyl cellulose, poloxamer, ) polyvinyl alcohol, sodium alginate and tragacanth gum.

[0166] The amount of gelling agent used in the formulation depends on the desired texture, viscosity and softness of the product as well as other ingredients in the formulation. In some embodiments, the gelling agent can 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%.

[0167] In one embodiment, gelatin and pectin can be employed in a weight ratio that supplies at least 50% gelatin and at least 10% pectin, for example, about 70% to 85% gelatin and the remaining pectin.

[0168] In one embodiment, the pectin can be high-methoxyl pectin obtained from apples. In one embodiment, the gelatin can be type A gelatin 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.

[0169] In one embodiment, the combination of gelatin and pectin can be employed at a level of about 4.5 wt% to about 6 wt% of the final product, for example, about 5.5 wt% on this basis.

[0170] In one embodiment, the formulation can include gellan gum, carrageenan or both, providing a gelatin-free formulation. In one embodiment, based on the total weight of the formulation, the formulation can include about 0.25 wt% to about 0.75 wt% of gellan gum and about 2 wt% to about 3 wt% of carrageenan.

[0171] In one embodiment, based on the total weight of the product, a combination of about 0.25 wt% to about 0.75 wt% of gellan gum and about 2.5 wt% to about 3 wt% of carrageenan produces a jelly-like formulation having a TPA hardness value of more than 20 lb(f) as well as TPA cohesiveness and an elasticity value of 75% to 80%.

[0172] In one embodiment, the amount of gellan gum is from about 0.25 wt% to about 0.75 wt%, and from about 0.25 wt% to about 0.5 wt%. In one embodiment, the amount of carrageenan is from about 1.5 wt% to about 3 wt%, and from about 2.5 wt% to about 3 wt%.

[0173] According to a further aspect of the invention, there is provided a formulation comprising:

[0174] a) a compound of formula (I) or a salt thereof:

[0175]

[0176] wherein:

[0177] A, B, C and D are each independently selected from H and OH;

[0178] W, X and Y are each independently selected from H and OH; and

[0179] Z is selected from H and OH; and

[0180] b) pectin, for example, high-methoxyl pectin.

[0181] According to a further aspect of the invention, there is provided a formulation comprising:

[0182] (a) a compound of formula (I), for example, urolithin A, and

[0183] (b) pectin;

[0184] wherein the ratio of the compound of formula (I) to pectin is in the range of about 1:2 (w / w) to about 10:1 (w / w).

[0185] According to a further aspect of the invention, there is provided a formulation comprising:

[0186] (a) a compound of formula (I); for example, urolithin A,

[0187] (b) pectin; and

[0188] (c) soluble fiber, for example, soluble cassava flour fiber.

[0189] According to a further aspect of the invention, there is provided a formulation comprising:

[0190] (a) a compound of formula (I); for example, urolithin A,

[0191] (b) pectin; and

[0192] (c) A low-calorie sweetener, for example, allulose.

[0193] According to a further aspect of the present invention, there is provided a formulation comprising:

[0194] (a) A compound of formula (I); for example, urolithin A,

[0195] (b) Pectin; and

[0196] (c) Citric acid and / or citrate (e.g., sodium citrate), for example, citric acid and salts of citric acid (e.g., sodium citrate).

[0197] According to a further aspect of the present invention, there is provided a formulation comprising:

[0198] (a) A compound of formula (I); for example, urolithin A,

[0199] (b) Pectin;

[0200] (c) Soluble cassava flour fiber;

[0201] (d) Citric acid; and / or citrate (e.g., sodium citrate); and

[0202] (e) A low-calorie sweetener, for example, allulose.

[0203] According to a further aspect of the present invention, there is provided a formulation comprising:

[0204] (a) From about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A, and

[0205] (b) From about 0.5% to about 4% (w / w) of pectin;

[0206] According to a further aspect of the present invention, there is provided a formulation comprising:

[0207] (a) From about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A,

[0208] (b) From about 0.5% to about 4% (w / w) of pectin; and

[0209] (c) From about 25% to about 45% (w / w) of soluble cassava flour fiber.

[0210] According to a further aspect of the present invention, there is provided a formulation comprising:

[0211] (a) From about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A,

[0212] (b) From about 0.5% to about 4% (w / w) of pectin; and

[0213] (c) From about 25% to about 45% (w / w) of a low - calorie sweetener, for example, allulose.

[0214] According to a further aspect of the present invention, there is provided a formulation comprising:

[0215] (a) From about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A,

[0216] (b) From about 0.5% to about 4% (w / w) of pectin; and

[0217] (c) From about 1% to about 10% (w / w), for example, from about 1% to 5% or from about 2% to about 4% of a low - calorie sweetener, for example, allulose.

[0218] According to a further aspect of the present invention, there is provided a formulation comprising:

[0219] (a) From about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A,

[0220] (b) From about 0.5% to about 4% (w / w) of pectin; and

[0221] (c) From about 25% to about 60% (w / w) of a low - calorie sweetener, for example, one or more low - calorie sweeteners selected from the group consisting of: allulose, fructose, stevia and / or inulin.

[0222] According to a further aspect of the present invention, there is provided a formulation comprising:

[0223] (a) From about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A,

[0224] (b) From about 0.5% to about 4% (w / w) of pectin; and

[0225] (c) From about 0.5% to about 2% (w / w) of citric acid and / or citrate (e.g., sodium citrate), for example, citric acid and salts of citric acid (e.g., sodium citrate).

[0226] According to a further aspect of the present invention, there is provided a formulation comprising:

[0227] (a) From about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of the compound of formula (I); for example, urolithin A,

[0228] (b) From about 0.5% to about 4% (w / w) of pectin;

[0229] (c) From about 25% to about 45% (w / w) of soluble cassava flour fiber;

[0230] (d) From about 0.5% to about 2% (w / w) of citric acid; and / or citrate (e.g., sodium citrate); and

[0231] (e) From about 25% to about 45% (w / w) of a low-calorie sweetener, for example, allulose.

[0232] Embodiments of the present invention include the compound of formula (I) (e.g., urolithin A) in the range of about 5% to about 20% (w / w). For example, from about 5% to about 15%, for example from about 5% to about 10% (w / w).

[0233] Embodiments of the present invention include pectin (e.g., high-methoxyl pectin) in the range of from about 0.5% to about 10% (w / w), from about 0.5% to about 5% (w / w), from about 0.5% to about 4% (w / w), from about 0.5% to about 3% (w / w), and from about 0.5% to about 2% (w / w) of pectin. For example, from about 0.5% to about 1.5% (w / w), from about 0.8% to about 1.5% (w / w), for example, from about 1% to about 1.5% (w / w), for example from about 1% to about 4% or from about 2% to about 4% (w / w) of pectin.

[0234] Embodiments of the present invention include soluble cassava flour fiber (e.g., soluble cassava flour fiber syrup) in the range of from about 25% to about 45% (w / w). For example, from about 30% to about 40%, from about 32% to about 38% (w / w).

[0235] Embodiments of the present invention include citric acid; and / or citrate (e.g., sodium citrate) in the range of from about 0.5% to about 2% (w / w). For example, from about 0.8% to about 1.5%, from about 1% to about 1.5% (w / w). Citrates include sodium citrate, potassium citrate, calcium citrate, and ammonium citrate.

[0236] In a further aspect of the invention, the formulation comprises both citric acid and a salt of citric acid. Embodiments of the invention comprise citric acid in the range of from about 0.5% to about 2% (w / w). For example, from about 0.5% to about 1.5%, from about 0.8% to about 1.5%, from about 1% to about 1.5%, from about 0.8% to about 1.3% (w / w). Embodiments of the invention comprise a salt of citric acid (e.g., sodium citrate) in the range of from about 0.1% to about 1% (w / w). For example, from about 0.1% to about 0.8%, from about 0.1% to about 0.5% (w / w).

[0237] In a further aspect of the invention, the formulation comprises both malic acid and sodium hydrogen malate.

[0238] Embodiments of the invention comprise a low-calorie sweetener (e.g., allulose) in the range of from about 25% to about 45% (w / w). For example, from about 30% to about 40%, from about 32% to about 38% (w / w).

[0239] According to a further aspect of the invention, there is provided a formulation comprising:

[0240] (a) from about 1% to about 20% (w / w), for example, from about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A,

[0241] (b) from about 0.5% to about 4% (w / w) of pectin; and

[0242] (c) from about 25% to about 60% (w / w) of a low-calorie sweetener, for example, one or more low-calorie sweeteners selected from: allulose, fructose, monk fruit juice, stevia and / or inulin.

[0243] (d) from about 10% to about 30% of soluble fiber;

[0244] (e) from about 0.1% to about 2% sodium citrate, for example, from about 0.3% to about 1% sodium citrate;

[0245] (f) optionally a pH buffer, for example, malic acid and / or sodium hydrogen malate; and

[0246] (g) optionally a colorant.

[0247] Compound of formula (I) in amorphous form

[0248] The compound of formula (I) is present in a crystalline form. However, we have found that the compound of formula (I) in an amorphous form can be used to prepare a composition with higher bioavailability. Accordingly, in a further aspect of the invention, there is provided a compound of formula (I) in an amorphous form, for example, amorphous urolithin A.

[0249] In addition, we have found that bioavailability can be enhanced by adding one or more excipients. Thus, according to a further aspect of the present invention, there is provided a composition comprising a compound of formula (I) in amorphous form, for example, amorphous urolithin A and one or more excipients.

[0250] Excipients include one or more of the following: pectin, methylcellulose, hydroxypropylmethylcellulose (e.g., HPMC E5), gum arabic, alginate (e.g., sodium alginate), gelatin, mannitol, and sorbitol. In a further embodiment, the excipient further comprises: agar, starch, or modified starch.

[0251] In a further embodiment, the present invention provides a composition comprising a compound of formula (I) in amorphous form and an excipient, wherein the compound of formula (I) and the excipient are in a ratio of 1: about 1 to 1: about 10, a ratio of 1: about 2 to 1: about 10, a ratio of 1: about 2 to 1: about 9, a ratio of 1: about 2 to 1: about 8, a ratio of 1: about 2 to 1: about 7, a ratio of 1: about 2 to 1: about 6, a ratio of 1: about 2 to 1: about 5, for example, a ratio of 1: about 2 to 1: about 4, for example, a ratio of 1: about 3, for example, wherein the excipient is selected from one or more of the following: pectin, methylcellulose, hydroxypropylmethylcellulose (e.g., HPMC E5), gum arabic, alginate, and gelatin. In a further embodiment, the present invention provides a composition comprising a compound of formula (I) in amorphous form and an excipient, wherein the excipient is a mixture of pectin and methylcellulose.

[0252] In one embodiment, the present invention comprises a compound of formula (I) in amorphous form, for example, amorphous urolithin A and hydroxypropylmethylcellulose (e.g., HPMC E5) in a ratio of 1: about 3.

[0253] In one embodiment, the present invention comprises a compound of formula (I) in amorphous form, for example, amorphous urolithin A and methylcellulose in a ratio of 1: about 3.

[0254] In one embodiment, the present invention comprises a compound of formula (I) in amorphous form, for example, amorphous urolithin A and pectin in a ratio of 1: about 3, a ratio of 1: about 4, or a ratio of 1: about 5.

[0255] In one embodiment, the present invention comprises a compound of formula (I) in amorphous form, for example, amorphous urolithin A, and a mixture of excipients comprising pectin and methylcellulose. In one embodiment, the compound of formula (I), pectin, and methylcellulose are in a ratio of 1: about 3: about 2.

[0256] According to a further aspect of the present invention, there is provided a formulation comprising:

[0257] (a) a compound of formula (I), for example, urolithin A;

[0258] (b) pectin;

[0259] (c) a fiber source; for example, one or more fiber sources selected from tapioca starch, corn fiber, and inulin;

[0260] (d) one or more sweeteners, for example, allulose and / or stevia;

[0261] (e) water;

[0262] (f) citric acid and / or sodium citrate;

[0263] (g) optionally one or more colorants;

[0264] (h) optionally one or more flavorings.

[0265] According to a further aspect of the present invention, there is provided a formulation comprising:

[0266] (a) a compound of formula (I), for example, urolithin A;

[0267] (b) pectin;

[0268] (c) a fiber source; for example, tapioca starch;

[0269] (d) one or more sweeteners, for example, one or more sweeteners selected from allulose, stevia, and monk fruit juice;

[0270] (e) a pH regulator, for example, sodium hydrogen malate;

[0271] (f) sodium citrate;

[0272] (g) water;

[0273] (h) optionally one or more colorants;

[0274] (i) optionally one or more flavorings; and

[0275] (j) optionally a coating.

[0276] Spray-dried composition of the compound of formula (I)

[0277] It has been found that the composition can be prepared by dissolving the compound of formula (I) (for example, urolithin A) in a solvent and spray drying. Thus, according to a further aspect of the present invention, there is provided a spray-dried composition of a compound of formula (I) (for example, urolithin A).

[0278] Solvents suitable for spray drying include: ethanol and water.

[0279] In one embodiment, the solvent is water.

[0280] In a further embodiment, the solvent is ethanol.

[0281] In one embodiment, the excipient is pectin, for example, low-methoxyl pectin.

[0282] In a further embodiment, the excipient is a mixture of pectin and methylcellulose.

[0283] In a further embodiment, the excipient is methylcellulose.

[0284] In a further embodiment, the excipient is hydroxypropyl methylcellulose, for example, HPMC E5.

[0285] In a further embodiment, the excipient is gum arabic.

[0286] In a further embodiment, the solvent is water and the excipient is pectin.

[0287] In a further embodiment, the solvent is ethanol and the excipient is pectin.

[0288] In a further embodiment of the present invention, there is provided a spray-dried composition of a compound of formula (I) (for example, urolithin A), said spray-dried composition comprising an excipient, for example, one or more excipients selected from pectins, for example, high-methoxyl pectin, gum arabic, methylcellulose and hydroxypropyl methylcellulose, for example, HPMC-E5, sorbitol, mannitol and sodium alginate.

[0289] In a further embodiment of the present invention, there is provided a spray-dried composition of a compound of formula (I) (for example, urolithin A), said spray-dried composition comprising pectin, for example, high-methoxyl pectin.

[0290] In a further embodiment of the present invention, there is provided a spray-dried composition of a compound of formula (I) (for example, urolithin A), said spray-dried composition comprising methylcellulose.

[0291] In a further embodiment of the present invention, there is provided a spray-dried composition of a compound of formula (I) (for example, urolithin A), said spray-dried composition comprising gum arabic.

[0292] In a further embodiment of the invention, there is provided a spray-dried composition of a compound of formula (I) (e.g., urolithin A), said spray-dried composition comprising hydroxypropyl methylcellulose, e.g., HPMC E5.

[0293] According to a further embodiment of the invention, there is provided a process for preparing a composition comprising a compound of formula (I), said process comprising:

[0294] (a) dissolving the compound of formula (I) in a solvent to form a solution or suspending the compound of formula (1) in a solvent to form a suspension,

[0295] e.g., wherein the solvent is selected from ethanol and / or water;

[0296] (b) optionally stirring the resulting suspension or solution

[0297] (c) adding one or more excipients, e.g., one or more excipients selected from pectin, methylcellulose and hydroxypropyl methylcellulose;

[0298] (d) spray-drying the solution / suspension, optionally with stirring to form a powder; and

[0299] (e) optionally drying the powder.

[0300] According to a further embodiment of the invention, there is provided a composition which can be prepared by a process comprising:

[0301] (a) dissolving the compound of formula (I) in a solvent to form a solution or suspending the compound of formula (1) in a solvent to form a suspension,

[0302] e.g., wherein the solvent is selected from ethanol and / or water;

[0303] (b) optionally stirring the resulting suspension or solution

[0304] (c) adding one or more excipients, e.g., one or more excipients selected from pectin, methylcellulose and hydroxypropyl methylcellulose;

[0305] (d) spray-drying the solution / suspension, optionally with stirring to form a powder; and

[0306] (e) optionally drying the powder.

[0307] In a further embodiment of the invention, the spray-dried composition comprises a compound of formula (1) and low-methoxyl pectin.

[0308] In a further embodiment, the composition of the invention comprises:

[0309] Ingredient Range (w / w) Allulose 25％-45％ Soluble tapioca fiber syrup 25％-45％ Water 15％-25％ Urolithin A 5% to 15% Pectin 2% to 10% Citric acid, 1% to 2% Stevioside 0.005％-0.010％ Sodium citrate 0.1% to 0.5%

[0310] After adding any optional colorant, the ranges add up to at most 100%.

[0311] In a further embodiment, the composition of the invention comprises:

[0312] Raw material description Weight % (wet gum slurry) Allulose liquid 1% to 5% Fibersol liquid 2L 10% to 30% Fructose 45% to 65% Water 1% to 3% Urolithin A 5% to 15% Pectin 1% to 4% Sodium hydrogen malate 0.1% to 0.4% Momordica grosvenori concentrated fruit juice 0.1% to 1% Stevioside 0.05% to 0.3% Sodium citrate 0.1% to 1% Malic acid 0.1% to 1%

[0313] After adding any optional colorant, the ranges add up to at most 100%.

[0314] Urolithin

[0315] Urolithin is a metabolite produced by the action of mammalian (including human) gut microbiota on ellagitannins and ellagic acid. Ellagitannins and ellagic acid are compounds commonly found in foods such as pomegranates, nuts, and berries. Ellagitannins are minimally absorbed by the gut itself. Urolithin is a class of compounds with the representative structure (I) shown below. The structures of some particularly common urolithins are described in Table 1 below, with reference to structure (I).

[0316]

[0317] In fact, for commercial-scale products, it is convenient to synthesize urolithin. The synthetic routes are described, for example, in WO 2014 / 004902, WO 2015 / 100213, and WO 2019 / 168972.

[0318] Urolithin of any structure according to structure (I) can be used in the combination of the invention.

[0319] In one aspect of the combination of the invention, a suitable compound is a compound 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, preferably at least one of A, C, and Z is OH.

[0320] 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, and both A and B are H, and C, D, and Z are all OH, then the compound is urolithin C. When W, X, and Y are all H, and A, B, and C are all H, and both D and Z are OH, then the compound is urolithin A. Preferably, the urolithin used in the method of the present disclosure is urolithin A, urolithin B, urolithin C, or urolithin D. Most preferably, the urolithin used is urolithin A.

[0321]

[0322] According to one embodiment, a combination of the present invention is provided, wherein the compound of formula (I) is urolithin A.

[0323] According to one embodiment, a combination of the present invention is provided, wherein the compound of formula (I) is urolithin B.

[0324] According to one embodiment, a combination of the present invention is provided, wherein the compound of formula (I) is urolithin C.

[0325] According to one embodiment, a combination of the present invention is provided, wherein the compound of formula (I) is urolithin D.

[0326] In one embodiment, the urolithin does not include acylated urolithin or 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; urolithin C having at least one hydroxyl group substituted with a group containing a fatty acid). As used herein, the term "acyl" refers to a chemical substituent of the formula -C(0)-R, wherein R is alkyl, alkenyl, aryl, aralkyl, cycloalkyl, heterocyclic, heterocycloalkyl, heteroaryl or heteroaralkyl. Optionally substituted acyl is an acyl of each group R optionally substituted as described herein. Examples of acyl include fatty acid acyl (e.g., short-chain fatty acid acyl (e.g., acetyl)) and benzoyl.

[0327] The present invention also encompasses the use of suitable salts of the compound of formula (I), such as pharmaceutically acceptable salts. Suitable salts according to the present invention include those formed from organic or inorganic bases. Pharmaceutically acceptable base salts include ammonium salts, alkali metal salts such as those of potassium and sodium; alkaline earth metal salts such as those of calcium and magnesium; and salts with organic bases such as dicyclohexylamine, N-methyl-D-glucose, morpholine, thiomorpholine, piperidine, pyrrolidine; mono-lower alkylamine, di-lower alkylamine or tri-lower alkylamine such as ethyl-propylamine, tert-butyl-propylamine, diethyl-propylamine, diisopropyl-propylamine, triethyl-propylamine, tributyl-propylamine or dimethyl-propylamine; or mono-hydroxy-lower alkylamine, di-hydroxy-lower alkylamine or tri-hydroxy-lower alkylamine such as monoethanolamine, diethanolamine or triethanolamine.

[0328] Additional components in the formulations of the present invention:

[0329] The formulations according to the present invention may contain additional components other than urolithin and the gelling component. The additional components may be compounds providing health benefits, e.g., mineral formulations, antioxidant formulations or mitochondrial enhancing formulations.

[0330] In one embodiment, the antioxidant preparation comprises bioflavonoids, resveratrol, coenzyme Q10, quercetin, rutin, lycopene, L-glutathione, N-acetylcysteine, phenols, anthocyanins, flavonoids, anthracenes, carotenoids, zeaxanthin, astaxanthin, lutein, pomegranate, Ginkgo biloba extract, green tea, garlic, grape seeds, blackberries, elderberries, cranberries, blueberries, saffron, Sangre de grado (dragon's blood), lyceum barbarum (Gouqizi), its extracts, powders or isolates.

[0331] In one embodiment, the mitochondrial enhancing preparation comprises acetyl-L-carnitine, alpha-lipoic acid, coenzyme Q10 (CoQ10 or ubiquinone), nicotinamide riboside (NR), omega-3 fatty acids, magnesium, D-ribose or its derivatives or combinations thereof.

[0332] Creatinine has been described as having beneficial effects in treating muscle disorders. It can be included in the preparations of the present invention. β-Hydroxy-β-methylbutyrate (HMB) has been described as having beneficial effects in treating muscle disorders. It can be included in the preparations of the present invention.

[0333] In additional embodiments, the preparation further comprises spermidine.

[0334] Examples of mineral preparations include potassium, chromium picolinate, magnesium and selenium. In one embodiment, the mineral preparation can include ions of sodium, magnesium, chromium, iodine, iron, manganese, calcium, copper, fluoride, potassium, phosphorus, molybdenum, selenium, zinc and combinations thereof. Minerals can exist in the form of salts or chelates.

[0335] Treatment:

[0336] The preparations of the present invention can be used as a single treatment, or more commonly, as a series of treatments. In one example, a subject takes a certain dose before or after exercise. For subjects who are unable to exercise, for example, a certain dose of the preparation can be taken once, twice or three times a day, or once, twice, three times, four times, five times or six times a week. In another example, the intervention can be carried out by the subject, regardless of the subject's exercise ability or need. It should also be understood that the effective dose of the compound can be increased or decreased during a specific treatment course.

[0337] Medical and non-medical treatments:

[0338] The formulations of the present invention can be used as medicaments. The formulations can be used as dietary supplements, as functional foods, and as medical foods. Accordingly, the formulations of the present invention can be used to treat various diseases as well as health conditions not considered to be diseases. Specifically, the diseases and non-disease health conditions can be characterized by insufficient mitochondrial activity. The formulations can be used to treat both diseases and disease states. Accordingly, in one embodiment, the methods and uses of the formulations and compositions disclosed herein include non-therapeutic methods and uses. The formulations can be used to manage the normal physiological functions of healthy individuals or conditions characterized by poor physical performance, impaired endurance, and impaired muscle function. The formulations of the present invention can improve the physical performance of individuals (including young and old individuals) suffering from diseases. The formulations of the present invention can improve physical performance, e.g., the short-term or long-term performance of healthy individuals (including athletes, non-athletic individuals, sedentary individuals, and the elderly). Such improvement in performance can be measured by the time taken to walk or run a specific distance (e.g., improved performance during a 6-minute walk test (MWT)), improvement in the time taken to run a specific distance, improvement in the IPAQ score on an International Physical Activity Questionnaire, an increase in the number of times of standing up from a chair within a specific time, or another test designed to measure physical performance. In a further embodiment, the present invention provides the use of the formulations of the present invention for enhancing the muscle function of cancer survivors.

[0339] The formulations of the present invention further provide an improvement in endurance. Endurance refers to the time to fatigue when exercising at a constant workload (usually at an intensity < 80% VO 2 max). The formulations of the present invention can improve the endurance of individuals (including young and old individuals) suffering from diseases. The formulations of the present invention can improve the endurance of healthy individuals (including athletes, non-athletic individuals, sedentary individuals, and the elderly). The present invention provides a method of increasing the time to fatigue when performing a specific activity (e.g., fitness training, walking, running, swimming, or cycling). Such improvement in endurance can be evaluated by objective measurements (e.g., speed, oxygen consumption, or heart rate), or can be evaluated by self-reported measurements (e.g., using a validated questionnaire).

[0340] The present invention further provides a formulation for improving, maintaining, or reducing muscle function loss. The formulations of the present invention can improve, maintain, or reduce muscle function loss in individuals (including young and old individuals) suffering from diseases. The formulations of the present invention can improve, maintain, or reduce muscle function loss in healthy individuals (including athletes, non-athletic individuals, sedentary individuals, and the elderly). For example, the formulations of the present invention can increase muscle strength, which can be demonstrated by an improvement in performing physical activities (such as exercise), e.g., an increase in weightlifting ability or an increase in handgrip strength. In addition, the formulations of the present invention can improve muscle structure, e.g., increasing or maintaining muscle mass in cases of normal muscle function, decreased muscle function, or impaired muscle function.

[0341] The present invention further provides a formulation for improving an individual's perceived physical performance or endurance. For example, a reduction in perceived exertion or effort during exercise or activity as determined using a self-report questionnaire.

[0342] The present invention further provides a formulation of the present invention for treating a variety of 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, fatty liver disease (e.g., NAFLD and NASH), for improving liver function and for weight management. Specifically, the formulation of the present invention can be used to treat muscle-related pathological conditions. Thus, the present invention provides a formulation of the present invention for treating muscle-related pathological conditions. The present invention also provides a method of treating a muscle-related pathological condition in a subject, the method comprising administering to the subject an effective amount of the formulation of the present invention. Muscle-related conditions include both conditions that typically affect healthy individuals and pathological conditions. Such muscle conditions found in healthy or disease-affected individuals include musculoskeletal diseases or disorders; cachexia; muscle wasting; age-related decline in muscle function; pre-frailty; frailty; myopathy; neuromuscular diseases such as Duchenne muscular dystrophy and other dystrophies; age-related sarcopenia; acute sarcopenia; muscle atrophy and / or cachexia, such as muscle atrophy and / or cachexia associated with burns, bed rest, limb immobilization or major surgery (including thoracic, abdominal and / or orthopedic surgery); and muscle degenerative diseases.

[0343] Examples of age-related conditions that can be treated with the formulation of the present invention include sarcopenia and muscle wasting.

[0344] Myopathy can also be caused by dystrophy syndromes such as Duchenne muscular dystrophy.

[0345] WO2014 / 111580 reports that urolithin B (but not urolithin A) increased the average diameter of myotubes in vitro. This effect was not seen with urolithin A.

[0346] Non-medical and non-therapeutic treatments:

[0347] The formulation of the present invention can be used to enhance muscle performance. Thus, the present invention provides a formulation of the present invention for enhancing muscle performance. The present invention also provides a method of enhancing muscle performance by administering to a subject an effective amount of the formulation of the present invention. Administration can be self-administration. The enhanced muscle performance can be one or more of improved muscle function, improved muscle strength, improved muscle endurance and improved muscle recovery.

[0348] Accordingly, the formulations of the present invention can be used in methods for improving physical endurance (e.g., the ability to perform physical tasks such as exercise, physical labor, sports activities, etc.), inhibiting or delaying physical fatigue, enhancing work capacity and endurance, reducing muscle fatigue, and enhancing cardiac and cardiovascular function.

[0349] For elderly subjects with muscle function decline due to age-related diseases, improved muscle function can be particularly beneficial. For example, subjects who may benefit from improved muscle function may have experienced muscle function decline, which then leads to pre-frailty and frailty. In addition to their muscle function decline, such subjects do not necessarily experience muscle wasting. Some subjects do experience muscle wasting and muscle function decline, such as subjects with sarcopenia. The formulations of the present invention can be used to enhance muscle performance by administering the formulations of the present invention to frail or pre-frail subjects.

[0350] Muscle performance can be exercise performance, that is, the ability of an athlete to perform during a sports activity. Enhancement of exercise performance, intensity, speed, and endurance is measured by an increase in muscle contraction intensity, an increase in muscle contraction amplitude, or a shortening of the muscle reaction time between stimulation and contraction. An athlete is an individual who participates in sports at any level and seeks to improve the intensity, speed, or endurance level in their performance, such as bodybuilders, cyclists, long-distance runners, and sprinters. Enhanced exercise performance is manifested as the ability to overcome muscle fatigue, the ability to maintain activity for a long period of time, and more effective training.

[0351] Urolithin administration / dosing regimen

[0352] The combination of the present disclosure relates to orally administering a urolithin of formula (I) or a salt thereof to a subject in an amount in the range of 1.7 mmol to 6.0 mmol per day, e.g., 1.7 mmol to 2.7 mmol per day or 2.8 mmol to 6.0 mmol per day, for a period of 2 to 16 weeks prior to vaccination. As discussed below, administration in the range of 250 mg to 1000 mg of urolithin A (which corresponds to approximately 1.1 mmol to 4.4 mmol) is preferred compared to much higher doses of 2000 mg, which results in a surprisingly good pharmacokinetic profile. 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.

[0353] In additional embodiments, the administered dose is selected from:

[0354] - 250 mg, once or twice a day;

[0355] - 500 mg, once or twice a day;

[0356] - 750 mg, once or twice daily;

[0357] - 1000 mg, once or twice daily;

[0358] - 1250 mg, once or twice daily; or

[0359] - 1500 mg, once or twice daily.

[0360] The methods of the present disclosure involve administering a compound of formula (I) or a salt thereof, or a formulation comprising said compound or salt, once daily. That is, the compound or formulation is administered at least once per 24-hour period. In other embodiments, the compound or formulation comprising the compound is administered multiple times daily, such as twice, three times, or four times daily. In such cases, the daily dose is divided among these multiple doses. In one embodiment, the administration is once daily, in a second embodiment, the administration is twice daily, and in a third embodiment, the administration is three times daily.

[0361] The methods of the present disclosure generally require administering a compound of formula (I) or a salt thereof, or a formulation comprising said compound or salt, once daily for a period of several months. In some embodiments, the method may involve, for example, administering a compound of formula (I) or a salt thereof once daily for at least 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 12 weeks, 4 months, 6 months, or for at least one year. In some embodiments, the method comprises administering the compound or a salt thereof once daily 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 once daily for a period within the range of 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.

[0362] The method of the present disclosure requires administering a certain amount of the compound of formula (I) or a salt thereof per day, from 0.7 mmol to 2.7 mmol per day, or from 0.7 mmol to 2.7 mmol twice a day. In some embodiments, the amount administered is in the range of 2.0 mmol to 2.5 mmol. In some embodiments, the amount administered is approximately 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 approximately 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 method involves administering approximately 2.2 mmol per day or 2.2 mmol twice a day of the compound of formula (I) or a salt thereof (e.g., administering urolithin A). The exact weight of the compound administered depends on the molecular weight of the compound used. For example, urolithin A has a molecular weight of 228 g / mol (such that 2.20 mmol is 501.6 mg), and urolithin B has a molecular weight of 212 g / mol (such that 2.20 mmol is 466.4 mg).

[0363] In additional embodiments, the method of the present disclosure requires administering a certain amount of the compound of formula (I) or a salt thereof per day, from 2.8 mmol to 6.0 mmol per day, or administering twice a day. In some embodiments, the amount administered is in the range of 4.0 mmol to 4.8 mmol. In some embodiments, the amount administered is approximately 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 method involves administering approximately 4.4 mmol per day or twice a day of the compound of formula (I) or a salt thereof (e.g., administering urolithin A). The exact weight of the compound administered depends on the molecular weight of the compound used. For example, urolithin A has a molecular weight of 228 g / mol (such that 4.40 mmol is 1003.2 mg), and urolithin B has a molecular weight of 212 g / mol (such that 4.40 mmol is 932.8 mg).

[0364] In some embodiments, the method involves administering urolithin A in an amount in the range of 400 mg / day to 600 mg / day or 400 mg to 600 mg once daily. In a preferred embodiment, the method involves administering urolithin A in an amount in the range of 450 mg / day to 550 mg / day, more preferably about 500 mg / day.

[0365] In other embodiments, the method involves administering urolithin A in an amount in the range of 700 mg / day to 1300 mg / day, or in the range of 750 mg to 1250 mg, or in the range of 800 mg to 1200 mg, or in the range of 850 mg to 1150 mg, or in the range of 900 mg to 1100 mg. In a preferred embodiment, the method involves administering urolithin A in an amount in the range of 950 mg / day to 1150 mg / day, more preferably about 1000 mg / day.

[0366] In some preferred embodiments, the method involves administering urolithin A to a subject in an amount in the range of 4.5 mg / kg / day to 11 mg / kg / day, such as 4.5 mg / kg / day to 8.5 mg / kg / day. In another embodiment, the method involves administering urolithin A to a subject in an amount in the range of 5 mg / kg / day to 9 mg / kg / day. In another embodiment, the method involves administering urolithin A to a subject in an amount in the range of 6.0 mg / kg / day to 8 mg / kg / day.

[0367] In other preferred embodiments, the method involves administering urolithin A to a subject in an amount in the range of 9 mg / kg / day to 18 mg / kg / day, such as 9 mg / kg / day to 17 mg / kg / day. In another embodiment, the method involves administering urolithin A to a subject in an amount in the range of 10 mg / kg / day to 17 mg / kg / day. In another embodiment, the method involves administering urolithin A to a subject in an amount in the range of 11 mg / kg / day to 16 mg / kg / day.

[0368] A dosing regimen combining a 500 mg dose with a 1000 mg dose may be advantageous. For example, a twice-daily dosing regimen that combines a first dose of 1000 mg with a second dose of 500 mg several hours later. The 500 mg dose can be 6 - 18 hours after the 1000 mg dose, such as 8 - 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 invention, there is provided a method of treating a disease with a compound of formula (I), the method comprising a twice-daily dosing regimen that comprises a first dose of 1000 mg followed by a second dose of 500 mg, wherein the two doses are separated by 6 - 18 hours.

[0369] The compound of formula (I) or its salt, or a preparation of a compound containing a salt, can be administered at any suitable time, for example, it can be administered after waking up in the morning or in the evening. In some embodiments, it is preferred that the method is carried out at approximately the same time each day, such as within 15, 30, 60, or 120 minutes of a given time point.

[0370] The appropriate dose of the preparation of the present invention is selected by a treating physician or non - therapeutic treatment based on clinical indications.

[0371] In some preferred embodiments, the preparation of the present invention comprises a compound of formula (I) or its salt (such as urolithin A) having a preferred particle size distribution. The specific particle size distribution enables the compound of formula (I) to disperse or dissolve more quickly. The specific particle size distribution can be achieved by methods established in the art, for example, it can use compression force grinding, hammer milling, universal or needle milling, or jet milling (such as spiral jet milling or fluidized bed jet milling). Jet milling is particularly suitable. In addition, the specific particle size distribution can also be directly obtained by using a specific chemical process. If a specific particle size distribution is used, preferably the compound has a D 50 size less than 100 μm, that is, by mass, 50% of the compound has a particle size less than 100 μm. More preferably, the compound has a D less than 75 μm, such as less than 50 μm, such as less than 25 μm, such as less than 20 μm, such as less than 10 μm. 50 size. More preferably, the compound has a D in the range of 0.5 - 50 μm, such as 0.5 μm to 20 μm, such as 0.5 μm to 10 μm, such as 1.0 μm to 10 μm, such as 1.5 μm to 7.5 μm, such as 2.8 μm to 5.5 μm. 50 Preferably, the compound has a D less than 100 μm. 90Size. More preferably, the compound has a D of less than 75 μm, such as less than 50 μm, such as less than 25 μm, such as less than 20 μm, such as less than 15 μm 90 Size. The compound preferably has a D in the range of 5 μm to 100 μm, such as 5 μm to 50 μm, such as 5 μm to 20 μm, such as 7.5 μm to 15 μm, such as 8.2 μm to 16.0 μm 90 . Preferably, the compound has a D in the range of 0.5–1.0 μm 10 . Preferably, the compound of formula (I) or its salt (such as urolithin A) has a D in the range of 8.2 μm to 16.0 μm 90 , a D in the range of 2.8 μm to 5.5 μm 50 and a D in the range of 0.5 μm to 1.0 μm 10 .

[0372] In a further embodiment, the compound of formula (I) or its salt has a particle size distribution selected from one of the following:

[0373] (i) a D in the range of 0.5 μm to 50 μm 50 Size and a D in the range of 5 μm to 100 μm 90 Size,

[0374] (ii) the compound has a D in the range of 8.2 μm to 16.0 μm 90 Size, a D in the range of 2.8 μm to 5.5 μm 50 Size and a D in the range of 0.5 μm to 1.0 μm 10 Size;

[0375] (iii) the compound of formula (I) has a D in the range of 0.5 μm to 20 μm 50 Size and a D in the range of 5 μm to 50 μm 90 Size;

[0376] (iv) the compound of formula (I) has a D of less than 50 μm 50 Size and a D of less than 75 μm 90 Size;

[0377] (v) the compound of formula (I) has a D of less than 25 μm 50 Size and a D of less than 50 μm 90 Size;

[0378] (iv) the compound of formula (I) has a D of less than 10 μm 50 Size and a D of less than 20 μm 90 Size;

[0379] (v) The compound of formula (I) has a D size of less than 10 μm and a D size of less than 15 μm; or 50 size; or 90 or

[0380] (vi) The compound of formula (I) has a D size of 10 μm and a D size of 20 μm. 50 size. 90

[0381] A pharmaceutical preparation containing the compound of formula (I) or a salt thereof may include, for example, additional pharmaceutically active compounds.

[0382] The unit dose preparation used in the methods described herein preferably contains 250 mg or 500 mg of the compound of formula (I), such as 250 mg or 500 mg of urolithin A.

[0383] The term 'artificial sweetener' refers to any sweetener that does not occur in nature.

[0384] The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which a therapeutic agent is administered.

[0385] The term 'fiber' refers to plant-derived carbohydrates that cannot be broken down by the human digestive system.

[0386] When related to pectin, the term 'degree of esterification range' (DE - degree of esterification) refers to the percentage of esterified carboxyl groups in pectin relative to the total carboxyl groups. Pectins are classified as low - ester pectins (DE < 50%) and high - ester pectins (DE > 50%).

[0387] The term 'excipient' refers to a substance formulated together with the active ingredient of a drug, including, for example, for the purposes of long - term stability, swelling of solid formulations containing small amounts of potent active ingredients (thus often referred to as "fillers", "bulking agents", or "diluents") or conferring therapeutic enhancement to the active ingredient in the final dosage form (such as facilitating drug absorption, reducing viscosity, or enhancing solubility).

[0388] The term 'gelling component' refers to one or more components used to form a polymeric matrix that provides a chewable texture to the formulation.

[0389] The term "gum" 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 preparation' refers to a gum. A gum is different from a jelly, which is a much softer gel - like matrix made, for example, from agar.

[0390] The term 'healthspan' refers to the number of years that a person lives or can expect to live in reasonably good health.

[0391] The term 'pectin' refers to a mixture of complex polysaccharides present in the primary cell walls of plants and is abundant in the green parts of terrestrial plants. Pectin can be high-methoxyl pectin or low-methoxyl pectin. The term pectin further includes amidated pectin, for example, amidated low-methoxyl pectin.

[0392] The term "pharmaceutically acceptable" means approved by a regulatory agency of the federal or state government or listed in the U.S. Pharmacopeia or other recognized pharmacopeias for use in animals and, more particularly, in humans.

[0393] The term "separate" administration means administering each of two or more compounds to a patient simultaneously, substantially simultaneously, or in any order sequentially from a non-fixed-dose formulation. The administration of each compound may or may not have a specified time interval.

[0394] The term "sequential" administration means administering each of two or more compounds to a patient in separate acts from a non-fixed (separate) formulation. The acts of administration may or may not be linked by a specified time interval. For example, a compound is administered within a specified time, such as once every 14 to 21 days.

[0395] The term "simultaneous" administration means administering each of two or more compounds to a patient in a single act, such as where each compound is administered separately at substantially the same time or within a time interval that allows the compounds to exhibit a synergistic therapeutic effect.

[0396] The term'sweetener system' refers to a sweetener or a combination of sweeteners. Description of the Drawings

[0397] Figure 1 Comparison of the dissolution profiles in FaSSIF medium of a powder containing 10 mg of UA complexed with citrus pectin and a 10 mg pure UA powder using EtOH as the solvent. Left panel: Comparison of the formulation UA / pectin where the w / w ratio of the excipient is 1 / 1. Right panel: Comparison of the formulation UA / pectin where the w / w ratio of the excipient is 4 / 1.

[0398] Figure 2. Comparison of the dissolution profiles in FaSSIF medium of powders containing the equivalent of 10 mg UA complexed with citrus pectin with that of 10 mg of pure UA powder, using water as the solvent. Upper left: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 1 / 1. Upper right: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 4 / 1. Lower left: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 7 / 1. Lower right: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 10 / 1.

[0399] Figure 3 Comparison of the AUC in FaSSIF medium of powders containing the equivalent of 10 mg UA complexed with citrus pectin with that of 10 mg of pure UA powder, using water as the solvent. Data are expressed as mean + / - SD. Adjusted P value **** < 0.0001, one-way ANOVA.

[0400] Figure 4 Comparison of the solubility of different urolithin A formulations - comparing UA formulations prepared in ethanol or water to achieve the maximum concentration (Cmax) of urolithin A in solution.

[0401] Figure 5 Comparison of the dissolution profiles in FaSSIF medium of powders containing the equivalent of 10 mg UA physically mixed (without spray drying) with citrus pectin with that of 10 mg of pure UA powder, using water as the solvent. Upper left: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 1 / 1. Upper right: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 4 / 1. Lower left: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 7 / 1. Lower right: Comparison of the UA / pectin formulation with a w / w ratio of excipient of 10 / 1.

[0402] Figure 6 Comparison of the AUC in FaSSIF medium of powders containing the equivalent of 10 mg UA added as a physical mixture (without spray drying) with citrus pectin with that of 10 mg of pure UA powder, using water as the solvent. Data are expressed as mean + / - SD. Adjusted P value **** < 0.0001, one-way ANOVA.

[0403] Figure 7 : An overview of the PROCEPT spray dryer with a BF nozzle is shown.

[0404] Figure 8 : The XRPD spectrum of crystalline urolithin A is shown

[0405] Figure 9: The XRPD spectrum of the urolithin A preparation is shown, which is prepared by spray drying using water as a solvent and the excipient pectin, and urolithin A is compounded with the excipient at a ratio of 1:1.

[0406] Figure 10 : The XRPD spectrum of the urolithin A preparation is shown, which is prepared by spray drying using water as a solvent and the excipient pectin, and urolithin A is compounded with the excipient at a ratio of 4:1. Detailed Description

[0407] Examples

[0408] The present invention will now be described with reference to the following non-limiting examples.

[0409] Example 1: Pectin Preparation

[0410] The exemplary preparation of the present invention consists of the following:

[0411]

[0412]

[0413] Example 2: Method for Preparing the Preparation of Example 1

[0414] 1) Blend the fruit concentrate, puree, water, and sodium ascorbate together in a container large enough to hold them.

[0415] 2) Blend the pectin and 10 times its weight of allulose together in a container large enough to hold them.

[0416] 3) Blend the following dry ingredients together in a container large enough to hold them (i.e., the remaining allulose, urolithin A, all vitamins (except ascorbic acid), all minerals, and tapioca flour fiber).

[0417] 4) Measure out the lemon concentrate and add the natural flavor to it.

[0418] 5) Measure out the ascorbic acid.

[0419] 6) Measure out the pigment and blend it into just enough water to produce a viscous liquid.

[0420] 7) Add the ingredients from step 1 above to the confectionery pan at room temperature.

[0421] 8) Gradually stir the ingredients from step 2 above into the ingredients in the pan. Hydrate for 5 - 10 minutes and stir well again.

[0422] 9) Gradually stir the ingredients from step 3 above into the ingredients in the pan.

[0423] 10) When monitoring the temperature of the colloidal solution, heat relatively quickly while stirring the mixture, avoiding extreme temperatures that could cause burning.

[0424] 11) When the solution starts to boil, closely monitor the temperature, which should eventually rise to 230°F.

[0425] 12) Immediately remove the colloidal solution from the heat source at this time.

[0426] 13) After cooling to approximately 220°F, stir the following ingredients until homogeneous: lemon concentrate with natural flavor and ascorbic acid.

[0427] 14) Finally, add liquid colorant and stir until homogeneous.

[0428] 15) Transfer the well - mixed colloidal solution to a heated storage tank with a stirrer, ready for deposition into a mold. The temperature should be maintained so that the high - methoxyl pectin does not start to gel before molding.

[0429] 16) Cool the colloidal solution deposited in the mold until gelation occurs and the colloidal solution is firm enough to be demolded, and apply carnauba wax or other coating by a panner or other means to prevent the colloidal from adhering.

[0430] Example 3: Pectin Preparation

[0431] The exemplary preparation of the present invention comprises:

[0432] Ingredient g / dose Allulose crystalline powder, organic 1.84g Urolithin A 500 mg Soluble tapioca fiber powder, organic 0.21g Pectin, slow-setting high-methoxyl 0.14g Zinc glycine chelate 6 mg Selenomethionine 30 μg Vitamin C 226 mg Vitamin D3 100 CWD EU 11 μg Flavor Minimum 0.23%

[0433] The preparation further comprises water, apple juice concentrate, clarified lemon juice concentrate, elderberry juice concentrate, and apple puree, as well as a flavoring agent (minimum 0.23% (w / w)).

[0434] Example 4 - Preparation Results of Spray - Dried Urolithin A Composition

[0435] A stable UA suspension and a stable citrus pectin (lot number SLBV5461, Sigma Life Science) suspension were prepared using ethanol as the solvent. The two suspensions were stirred for 1 hour. The suspensions were mixed to obtain a suspension in which the w / w ratio of UA to citrus pectin was UA / pectin 1 / 3 or 1 / 1. After spray drying, the solubility of the two resulting UA / pectin powder formulations was analyzed when dissolved in a biorelevant medium that mimicked an intestinal-like environment (FaSSIF, pH = 6.5). 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 UA was added to the FaSSIF medium. At different time points after adding the powder to the FaSSIF medium, the solubility was analyzed by the UPLC method (Ultra Performance Liquid Chromatography). When compared to the pure UA powder, the UA / pectin powder showed a significantly enhanced solubility profile at both of the ratios tested ( Figure 3 ).

[0436] We further tested UA / pectin-based formulations using water instead of ethanol as the solvent. UA was dissolved in water to form a stable suspension. Citrus pectin (lot number SLBV5461, Sigma Life Science) was dissolved in water to form a solution. The UA suspension in water was combined with the citrus pectin solution (lot number SLBV5461, Sigma Life Science) at different ratios. One w / w ratio was UA / pectin 1 / 1, which showed positive data in the formulation using EtOH as the solvent. We also tested formulations with low pectin content, specifically formulations with the following UA / pectin ratios: 4 / 1 w / w, 7 / 1 w / w, 10 / 1 w / w.

[0437] The solubility profiles of powders containing an equivalent of 10 mg UA complexed with pectin at different ratios and 10 mg of pure UA powder were analyzed when dissolved in a biorelevant medium that mimicked an intestinal-like environment (FaSSIF, pH = 6.5). At different time points after adding the powder to the FaSSIF medium, the solubility was analyzed by the UPLC method (Ultra Performance Liquid Chromatography). The UA / pectin powder showed a significantly enhanced solubility profile at all of the ratios tested ( Figure 2 ). This was confirmed by calculating the area under the curve (AUC) of the dissolution curve to quantify the total presence of soluble UA over time. All of the UA / pectin powders showed a significant increase in AUC ( Figure 5)。Surprisingly, the increase in AUC was not proportional, where the ratio 1:1 showed the highest AUC, the ratios 1:4 and 1:7 showed similar curves, and solubility enhancement only started to decrease when the pectin ratio was reduced to UA / pectin 10 / 1( Figure 5 )。

[0438] To compare the ability of different formulations to enhance UA solubility, we also calculated the maximum concentration (Cmax) of UA achieved in solution compared to formulations with UA prepared in ethanol or in water.

[0439] For formulations using ethanol as the solvent, the Cmax of pure UA powder was 0.0009, that of UA / pectin 1 / 3 powder was 0.0038, and that of UA / pectin 1 / 1 powder was 0.0035. This indicates that using ethanol as the solvent and complexing UA with pectin can increase the solubility Cmax by 322% at the ratio of UA / pectin 1 / 3 and by 288% at the ratio of UA / pectin 1 / 1( Figure 5 )。

[0440] For formulations using water as the solvent, the Cmax of pure UA powder was 0.0009, that of UA / pectin 1 / 1 powder was 0.0049, that of UA / pectin 4 / 1 powder was 0.0046, that of UA / pectin 7 / 1 powder was 0.0045, and that of UA / pectin 10 / 1 powder was 0.0043. This indicates that using ethanol as the solvent and complexing UA with pectin can increase the solubility Cmax by 444% at the ratio of UA / pectin 1 / 1, by 411% at the ratio of UA / pectin 4 / 1, by 400% at the ratio of UA / pectin 7 / 1, and by 377.78% at the ratio of UA / pectin 10 / 1( Figure 6 )。

[0441] This data indicates that after spray drying, using water as the solvent makes the formulation have better UA solubility compared to using ethanol as the solvent.

[0442] The formulations tested above were produced from spray-dried solutions / suspensions of UA and pectin. The basic principle is to increase the solubility of UA by reducing the crystalline state of UA in favor of the amorphous state.

[0443] We also determined the solubility of UA after simple physical mixing (without spray drying) of UA and pectin. Surprisingly, all the formulations tested showed increased UA solubility despite not using spray drying( Figure 7 )。

[0444] This was confirmed by calculating the area under the curve (AUC) of the dissolution curve 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 ratio 7:1 showing the highest AUC ( Figure 8 ).

[0445] In summary, the data indicate that UA solubility can be significantly improved when UA is spray-dried with pectin as an excipient at a specific ratio. The solubility enhancement is more pronounced when using water as a solvent. Additionally, we found that even a simple physical mixture of UA and pectin at a specific ratio can improve UA solubility, with the ratio of UA / pectin 7 / 1 producing the best results.

[0446] Example 5: Method for preparing spray-dried urolithin A formulations

[0447] 1. Equipment setup

[0448] Spray-drying experiments were conducted 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 separator. An extension column was installed to increase the residence time of droplets / particles in the heating chamber. For all experiments, a two-fluid nozzle with a 1.0 mm orifice was used.

[0449] 2. Preparation of solutions and suspensions

[0450] All suspensions were prepared at a solid load of 4.00% (w / w) with a total amount of 50 g. For each formulation, this amount was completely spray-dried to yield 2 g of total administered solids. Different amounts of UA and pectin were added according to the UA / pectin w / w ratio used.

[0451] For the solvents ethanol and water, UA was first suspended in the solvent, and then the excipient pectin was added. If UA and / or the excipient did not dissolve, the formulation was spray-dried as a suspension. The suspension was magnetically stirred for at least 1 hour before processing. Additionally, the suspension was continuously stirred during the spray-drying process.

[0452] Non-spray-dried formulations were prepared by adding UA powder and pectin powder at the different ratios tested. The powders were mixed using a mortar and pestle until the contents were visually homogeneous.

[0453] Example 6 – XRPD evaluation of urolithin A samples

[0454] The crystallinity of urolithin A was measured using X-ray powder diffraction (XRPD). The XRPD diffraction pattern of crystalline urolithin A shows many peaks indicative of a crystal structure. In the amorphous material, these peaks disappear or are at least greatly reduced. For example, the XRPD diffraction pattern of crystalline urolithin A is shown in Figure 1 as shown.

[0455] XRPD analysis was carried out under the following conditions.

[0456] Equipment: Aeris diffractometer (PANalytical, malvern) equipped with a Cu tube Generator: 40 kV and 15 mA

[0457] Sample: zero-background sample holder

[0458] Method

[0459] - Continuous scan mode from 4° to 40°

[0460] - Step size = 0.0217°

[0461] - Counting time 500 seconds

[0462] Example 7 – UPLC method - Determination method

[0463] The release profile of the sample was analyzed using a CP piston pump (Sotax) coupled to an AT Xtend semi-automatic dissolution bath (Sotax). At a temperature of 37 °C, the USP II (paddle) method was used, with FaSSIF (pH 6.5) as the dissolution medium. The paddle was rotated at 50 rpm. Approximately 10 mg of UA was placed in 1000 ml of the medium, showing a maximum concentration of 0.01 mg / ml. At the set time points, samples (i.e., 1.5 mL) of the medium were directly sampled into UPLC vials by the piston pump. No dilution step was required and these samples were injected as such. Each sample was analyzed in triplicate. The concentration was calculated from the calibration curve of UA, which was prepared in an organic medium (dissolved in DMSO and diluted with ACN).

[0464] Chromatographic conditions:

[0465] System: UPLC

[0466] Detector: PDA (250 - 350 nm) - Optimal wavelength: 230 nm

[0467] Column: SunFire C18 column, 100A, 3.5 μm, 4.6 × 150 mm

[0468] Flow rate: 1.2 ml / min

[0469] Flow rate: 1.2 ml / min

[0470] Column temperature: 40 °C

[0471] Injection volume: 7 μl

[0472] Run time: 25 minutes

[0473] Needle wash (sample manager wash): MeOH / H2O (9 / 1, v / v)

[0474] Seal wash: MeOH / H2O (3 / 7, v / v)

[0475] Rinse solvent (sample manager rinse): MeOH / H2O (3 / 7, v / v)

[0476] Mobile phase: A: H2O containing 0.05% TFA (w / v)

[0477] B: ACN containing 0.05% TFA (w / v)

[0478] Time 0 2.0 10 12 12.1 15 % of A 95 95 10 10 95 95 % of B 5 5 90 90 5 5

[0479] Equivalents

[0480] The present invention has been described herein in a broad and general sense. Various other devices and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein will occur to those of ordinary skill in the art, and each such variation and / or modification is considered to be within the scope of the present invention. More generally, those skilled in the art will readily recognize that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary, and the actual parameters, dimensions, materials, and / or configurations will depend upon the one or more specific applications for which the teachings of the present invention are used. Those skilled in the art will recognize or be able to ascertain using only routine experimentation many equivalent forms of the specific embodiments of the invention described herein. Accordingly, it is to be understood that the foregoing embodiments are presented by way of example only and that the present invention may be practiced otherwise than as specifically described and claimed within the scope of the appended claims and their equivalents. The present invention pertains to each and every separate feature, system, article, material, kit, and / or method described herein. Additionally, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the scope of the present invention. Additionally, each of the narrower types and subgeneric groupings falling within the general disclosure also forms a part of the present invention. This includes the general description of the present invention, with the proviso or negative limitation of removing any subject matter from the subgenus, whether or not the excised material is specifically recited herein.

[0481] Incorporation by reference

[0482] The contents of articles, patents, and patent applications mentioned or cited herein, as well as all other documents and electronically available information, are hereby incorporated by reference in their entirety to the extent that each individual publication is specifically and individually indicated to be incorporated by reference. The applicant reserves the right to incorporate any and all materials and information from any such articles, patents, patent applications, or other physical and electronic documents into this application.

[0483] Embodiments of the present invention

[0484] 1. A chewable preparation, the chewable preparation comprising:

[0485] a) a gelling component,

[0486] b) a compound of formula (I) or a salt thereof:

[0487]

[0488] wherein:

[0489] A, B, C, and D are each independently selected from H and OH;

[0490] W, X, and Y are each independently selected from H and OH; and

[0491] Z is selected from H and OH; and

[0492] wherein the preparation does not include a sweetener system.

[0493] 2. The chewable preparation according to claim 1, further comprising:

[0494] c) a sweetener system, for example, wherein the sweetener system comprises one or more artificial sweeteners and / or comprises allulose.

[0495] 3. The chewable preparation according to claim 2, wherein the sweetener system consists of one or more artificial sweeteners.

[0496] 4. The chewable preparation according to any one of the preceding claims, wherein the gelling component comprises one or more of the following: pectin, gelatin, agar, corn starch, and modified starch.

[0497] 5. The chewable preparation according to claim 4, wherein the gelling component comprises pectin, for example, high-methoxyl pectin.

[0498] 6. The chewable preparation according to claim 5, wherein the high-methoxyl pectin has an esterification range of about 60% to about 68%.

[0499] 7. A chewable preparation according to any one of the preceding claims, wherein the preparation comprises from about 0.5% to about 5% (w / w) of a gelling component, such as from about 0.5% to about 3% (w / w) of pectin, such as from about 1.5% to about 3% (w / w) of pectin.

[0500] 8. A chewable preparation according to any one of the preceding claims, which further comprises:

[0501] d) a fiber component, such as, a soluble fiber component.

[0502] 9. The chewable preparation according to claim 8, wherein the fiber component is selected from: soluble tapioca starch, psyllium husk powder, apple fiber, or a mixture thereof.

[0503] 10. A chewable preparation according to any one of the preceding claims, wherein the preparation has a Brix of from about 75 degrees to about 85 degrees.

[0504] 11. A chewable preparation according to any one of the preceding claims, wherein the preparation has a final boiling point of from about 108 °C to about 111 °C.

[0505] 12. A chewable preparation according to any one of the preceding claims, wherein the preparation comprises less than about 30% (w / w) of sugar.

[0506] 13. A chewable preparation 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, such as, urolithin A.

[0507] 14. A chewable preparation 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.

[0508] 15. A chewable preparation according to any one of the preceding claims, the chewable preparation being used as a drug, dietary supplement, functional food, or medical food.

[0509] 16. A chewable preparation for use as a drug according to any one of the preceding claims, the drug being used for treating and / or preventing muscle-related pathological conditions, such as, wherein the muscle-related pathological conditions are selected from musculoskeletal diseases or disorders; muscle wasting; myopathy; neuromuscular diseases, such as Duchenne muscular dystrophy and other dystrophies; sarcopenia, such as, acute sarcopenia; muscle atrophy and / or cachexia.

[0510] 17. A method of enhancing muscle performance, improving endurance or improving, maintaining or reducing loss of muscle function, said method comprising administering to a subject an effective amount of a chewable preparation according to any one of claims 1 to 15, for example, wherein the subject has age-related muscle function decline, age-related sarcopenia, age-related muscle wasting, physical fatigue, muscle fatigue and / or is frail or pre-frail.

[0511] 18. Use of a chewable preparation according to any one of claims 1 to 15 in a method of improving physical performance, for example, wherein the improvement in physical performance is in a healthy individual or an elderly person.

[0512] 19. Use of a chewable preparation according to any one of claims 1 to 15 in a method of increasing muscle strength, increasing or maintaining muscle mass or improving muscle recovery.

[0513] 20. Use of a chewable preparation according to any one of claims 1 to 15 in a method of improving physical endurance.

[0514] 21. Use of a chewable preparation according to any one of claims 1 to 15 in a method of inhibiting or delaying physical fatigue, enhancing work capacity and endurance, reducing muscle fatigue, enhancing cardiac and cardiovascular function.

[0515] 22. Use of a chewable preparation according to any one of claims 1 to 15 in a method of enhancing athletic performance.

[0516] 23. Use of a chewable preparation according to any one of claims 1 to 15 for a non-disease health condition characterized by insufficient mitochondrial activity.

[0517] 24. A preparation according to any one of claims 1 to 15, said preparation for treating a disease condition characterized by insufficient mitochondrial activity.

Claims

1. A composition comprising: a). A compound of formula (I) or a salt thereof: in: 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; and Z is selected from H and OH; and (b) Pectin.

2. The composition according to claim 1, wherein the pectin is selected from low methoxy pectin, high methoxy pectin or amidated low methoxy pectin or a mixture thereof, for example, wherein the pectin is high methoxy pectin.

3. A composition according to claim 1 or claim 2, wherein the ratio of the compound of formula (I) to pectin is 1: about 1 to 1: about 10 (w / w).

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

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 according to 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 form or partially in amorphous form.

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

10. The composition according to any one of claims 4 to 9, further comprising one or more of the following: a). Soluble fiber, for example, soluble tapioca fiber; b) low-calorie sweeteners, such as allulose; and c). Citric acid and / or citrates (eg, sodium citrate), for example, citric acid and citric acid salts (eg, sodium citrate).

11. A composition according to any one of claims 4 to 9, comprising: a). about 5% to about 20% (w / w) of a compound of formula (I); for example, urolithin A; and b). about 0.5% to about 4% (w / w) pectin; And the composition further comprises one or more of the following: c). about 25% to about 45% (w / w) soluble fiber, for example, soluble tapioca fiber; d). about 25% to about 45% (w / w) of a low-calorie sweetener, e.g., allulose; and e). about 0.5% to about 4% (w / w) of citric acid and / or citrate (eg, sodium citrate), for example, citric acid and citric acid salts (eg, sodium citrate).

12. A chewable preparation, comprising: a) a gelling component, b) a compound of formula (I) or a salt thereof: in: 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; and Z is selected from H and OH.

13. The chewable formulation according to claim 12, further comprising: c) a sweetener system, for example, wherein the sweetener system comprises one or more sweeteners.

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

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

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

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, for example from about 0.5% to about 4% (w / w) pectin, such as from about 1.5% to about 3% (w / w) pectin.

18. The chewable formulation according to any one of claims 12 to 17, further comprising: d) A fiber component, such as a soluble fiber component.

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

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

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

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

23. A composition according to any one of claims 1 to 11 or a chewable formulation according to 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, for example, urolithin A.

24. A composition or formulation according to any preceding claim, wherein the compound of formula (I), e.g. urolithin A, is present in the range of 100 mg to 2500 mg.

25. 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. A composition or formulation according to any one of the preceding claims for use in treating and / or preventing a muscle-related pathological condition, for example, wherein the muscle-related pathological condition is selected from a musculoskeletal disease or disorder; muscle wasting; myopathy; neuromuscular diseases, such as Duchenne muscular dystrophy and other dystrophies; sarcopenia, for example, acute sarcopenia; muscle atrophy and / or cachexia.

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

28. Use of a composition or formulation according to any one of claims 1 to 24 in a method of improving physical performance, for example, 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 of 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 of improving physical endurance.

31. Use of a composition or chewable formulation according to any one of claims 1 to 24 in a method of inhibiting 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 of enhancing athletic performance.

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

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

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

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