Formulations comprising urolithin and uses thereof

Abstract

The present invention relates to an aqueous formulation comprising urolithin, in particular a water-based formulation comprising urolithin and maltodextrin. The invention also relates to compositions for mixing with water, to processes for preparing such aqueous formulations, and to the use of such formulations for the treatment of diseases, disorders and conditions, such as diseases, disorders or conditions characterized by mitochondrial insufficiency, and for administration of both to general healthy individuals, such as those characterized by mitochondrial insufficiency. For example, for improving health and improving muscle function and performance.

Description

[0001] This invention relates to aqueous formulations containing urolithin, particularly water-based formulations containing urolithin and maltodextrin. The invention also relates to compositions for mixing with water, methods for preparing such aqueous formulations, and uses of such formulations, for example, for improving muscle function.

[0002] Urolithin has been proposed for the treatment of various conditions associated with insufficient mitochondrial activity, including obesity, decreased metabolic rate, metabolic syndrome, diabetes, cardiovascular disease, hyperlipidemia, neurodegenerative diseases, cognitive impairment, mood disorders, stress, and anxiety; for weight management or to improve muscle function or psychological performance (see WO2012 / 088519, Amazentis SA). Urolithin has also been described for the treatment of various oncological diseases (see WO2007 / 127263, The Regents of the University of California).

[0003] Urolithin has also been disclosed for increasing autophagy in cells, particularly mitophagy, which involves contacting cells with an effective amount of urolithin or a pharmaceutically acceptable salt thereof, thereby increasing autophagy in the cells, particularly mitophagy (see WO2014 / 004902, Amazentis SA).

[0004] As disclosed above, urolithiasis has been shown to improve muscle function. Good muscle performance is important for healthy individuals as well as those with illnesses (especially the elderly) to live effectively at all stages of life. Improving muscle performance is also of particular interest to athletes. For example, increasing muscle contraction strength, increasing muscle contraction amplitude, and shortening the muscle response time between stimulus and contraction are all beneficial to individuals, especially athletes.

[0005] Urolithin is only slightly soluble in aqueous solution, which poses a problem for preparing formulations for delivering urolithin to subjects. Such formulations are required to be applicable to individuals such as patients or healthy individuals such as athletes. However, it has been surprisingly found that it is possible to develop aqueous formulations of urolithin, and aqueous dispersible compositions containing urolithin and maltodextrin, such as aggregated maltodextrin, have been developed for use, for example, in beverages such as sports drinks.

[0006] According to a first embodiment of the present invention, a composition is provided, the composition comprising:

[0007] (a) A compound of formula (I) or a salt thereof;

[0008] (I)

[0009] in:

[0010] A, B, C, D, W, X, Y, and Z are each independently selected from H and OH; and

[0011] (b) Maltodextrin, such as agglomerated maltodextrin.

[0012] According to another embodiment of the present invention, a composition for mixing with water is provided, the composition comprising:

[0013] (a) A compound of formula (I) or a salt thereof;

[0014] (I)

[0015] in:

[0016] A, B, C, D, W, X, Y, and Z are each independently selected from H and OH; and

[0017] (b) Maltodextrin, such as agglomerated maltodextrin.

[0018] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0019] (a) A compound of formula (I), wherein the compound of formula (I) is a urolithin, such as urolithin A, urolithin B, urolithin C, or urolithin D, such as urolithin A; and

[0020] (b) Maltodextrin, such as agglomerated maltodextrin.

[0021] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0022] (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and

[0023] (b) Maltodextrin in the range of about 100 mg to about 6000 mg, such as agglomerated maltodextrin.

[0024] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0025] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0026] (b) About 0.04 mmol to about 7.24 mmol of maltodextrin, such as agglomerated maltodextrin.

[0027] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0028] (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and

[0029] (b) Maltodextrin in the range of about 100 mg to about 6000 mg, such as agglomerated maltodextrin.

[0030] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0031] (i) Approximately 1:1 to approximately 1:3;

[0032] (ii) about 1:1.5 to about 1:2.5; or

[0033] (iii) Approximately 1:2.5 to approximately 1:3.5.

[0034] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0035] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0036] (b) About 0.04 mmol to about 7.24 mmol of maltodextrin, such as agglomerated maltodextrin.

[0037] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0038] (i) Approximately 1:1 to approximately 1:3;

[0039] (ii) about 1:1.5 to about 1:2.5; or

[0040] (iii) Approximately 1:2.5 to approximately 1:3.5.

[0041] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0042] (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and

[0043] (b) Maltodextrin in the range of about 200 mg to about 4000 mg, such as agglomerated maltodextrin.

[0044] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0045] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0046] (b) About 0.08 mmol to about 4.83 mmol of maltodextrin, such as agglomerated maltodextrin.

[0047] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0048] (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and

[0049] (b) Maltodextrin in the range of about 200 mg to about 4000 mg, such as agglomerated maltodextrin;

[0050] The weight ratio of the compound of formula (I) to maltodextrin is between 1:1.5 and about 1:2.5 by weight.

[0051] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0052] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0053] (b) About 0.08 mmol to about 4.82 mmol of maltodextrin, such as agglomerated maltodextrin.

[0054] The weight ratio of the compound of formula (I) to maltodextrin is between 1:1.5 and about 1:2.5 by weight.

[0055] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0056] (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and

[0057] (b) Maltodextrin in the range of about 100 mg to about 2000 mg, such as agglomerated maltodextrin.

[0058] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0059] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0060] (b) About 0.04 mmol to about 2.41 mmol of maltodextrin, such as agglomerated maltodextrin.

[0061] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0062] (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and

[0063] (b) Maltodextrin in the range of about 100 mg to about 2000 mg, such as agglomerated maltodextrin.

[0064] The weight ratio of the compound of formula (I) to maltodextrin is between 1:1 and about 1:1.5 by weight.

[0065] In another embodiment of the invention, a composition for mixing with water is provided, the composition comprising:

[0066] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0067] (b) About 0.04 mmol to about 2.41 mmol of maltodextrin, such as agglomerated maltodextrin.

[0068] The weight ratio of the compound of formula (I) to maltodextrin is between 1:1 and about 1:1.5 by weight.

[0069] Those skilled in the art will understand that compositions for mixing with water can be prepared in batches. Therefore, compositions for mixing with water as defined above also include compositions encompassing several of the above-described ranges, such as compositions for mixing with water comprising:

[0070] (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and

[0071] (b) Maltodextrins in the range of approximately 100 mg to approximately 6000 mg, such as agglomerated maltodextrin.

[0072] It also includes a composition for mixing with water, the composition comprising:

[0073] (a) Compounds of formula (I) ranging from about 1 g to about 20 g, such as urolithin A; and

[0074] (b) Maltodextrins between approximately 1 g and 60 g, such as agglomerated maltodextrins.

[0075] And a composition for mixing with water, said composition comprising:

[0076] (a) Compounds of formula (I) ranging from about 10 g to about 200 g, such as urolithin A; and

[0077] (b) Maltodextrin in the range of about 10 g to about 600 g, such as agglomerated maltodextrin.

[0078] In another embodiment of the invention, a composition for mixing with water or an aqueous formulation is provided, the composition comprising:

[0079] (a) about 1 part by weight to about 20 parts by weight of a compound of formula (I), such as urolithin A; and

[0080] (b) About 1 part by weight to about 60 parts by weight of maltodextrin, such as agglomerated maltodextrin.

[0081] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0082] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0083] (b) Maltodextrin in the range of about 1 part by weight to about 3 parts by weight.

[0084] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0085] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0086] (b) Maltodextrin in the range of about 2 parts by weight to about 3 parts by weight.

[0087] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0088] (a) 1 part of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0089] (b) Maltodextrin in amounts between about 1.5 parts and about 2.5 parts.

[0090] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0091] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0092] (b) Maltodextrin between about 1 part and about 1.5 parts.

[0093] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0094] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0095] (b) Approximately 1 part by weight of maltodextrin.

[0096] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0097] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0098] (b) Approximately 2 parts by weight of maltodextrin.

[0099] According to another aspect of the invention, a composition for mixing with water is provided, the composition comprising:

[0100] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0101] (b) Approximately 3 parts by weight of maltodextrin.

[0102] According to another aspect of the invention, a pouch is provided that contains the composition of the invention.

[0103] The compositions of the present invention are administered in water to subjects, such as amateur or professional athletes or elderly subjects. The compositions can be administered to generally healthy subjects, such as generally healthy middle-aged or elderly subjects, or to subjects suffering from diseases or symptoms, such as hospitalized patients. For example, the compositions can be added to water, yogurt, smoothies, or protein shakes. Therefore, according to another aspect of the invention, an aqueous formulation is provided, comprising...

[0104] (a) A compound of formula (I) or a salt thereof;

[0105] (I)

[0106] in:

[0107] A, B, C, D, W, X, Y, and Z are each independently selected from H and OH; and

[0108] (b) Maltodextrin, such as agglomerated maltodextrin.

[0109] According to another aspect of the invention, an aqueous formulation is provided, the aqueous formulation comprising...

[0110] (a) A compound of formula (I), wherein the compound of formula (I) is a urolithin, such as urolithin A, urolithin B, urolithin C, or urolithin D, such as urolithin A; and

[0111] (b) Maltodextrin, such as agglomerated maltodextrin.

[0112] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0113] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0114] (b) Approximately 100 mg to approximately 6000 mg of maltodextrin.

[0115] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0116] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0117] (b) Approximately 100 mg to approximately 6000 mg of maltodextrin,

[0118] The ratio of compound (I) to maltodextrin is between about 1:1 and about 1:3.

[0119] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0120] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0121] (b) About 0.04 mmol to about 7.24 mmol of maltodextrin, such as agglomerated maltodextrin.

[0122] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0123] (a) about 0.4 mmol to about 8.8 mmol of a compound of formula (I), such as urolithin A; and

[0124] (b) Approximately 0.04 mmol to approximately 7.24 mmol of maltodextrin, such as agglomerated maltodextrin.

[0125] The ratio of compound (I) to maltodextrin is between about 1:1 and about 1:3.

[0126] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0127] (a) about 0.4 mmol to about 8.8 mmol of compound (I); and

[0128] (b) Approximately 0.04 mmol to approximately 7.24 mmol of maltodextrin.

[0129] The ratio of compound (I) to maltodextrin is between any of the following:

[0130] (i) Approximately 1:1 to approximately 1:3;

[0131] (ii) about 1:1.5 to about 1:2.5; or

[0132] (iii) Approximately 1:2.5 to approximately 1:3.5.

[0133] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0134] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0135] (b) Approximately 100 mg to approximately 6000 mg of maltodextrin.

[0136] The ratio of the compound of formula (I) to maltodextrin is between about 1:2.5 and about 1:3.5.

[0137] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0138] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0139] (b) Approximately 200 mg to approximately 4000 mg of maltodextrin.

[0140] The ratio of the compound of formula (I) to maltodextrin is between about 1:1.5 and about 1:2.5.

[0141] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0142] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0143] (b) Approximately 100 mg to approximately 2000 mg of maltodextrin.

[0144] The ratio of the compound of formula (I) to maltodextrin is between about 1:1 and about 1:1.5.

[0145] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0146] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0147] (b) Maltodextrin in the range of about 1 part by weight to about 3 parts by weight.

[0148] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0149] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0150] (b) Maltodextrin in the range of about 2 parts by weight to about 3 parts by weight.

[0151] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0152] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0153] (b) Maltodextrin in amounts between about 1.5 parts by weight and about 2.5 parts by weight.

[0154] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0155] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0156] (b) Maltodextrin in the range of about 1 part by weight to about 1.5 parts by weight.

[0157] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0158] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0159] (b) Approximately 1 part by weight of maltodextrin.

[0160] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0161] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0162] (b) Approximately 2 parts by weight of maltodextrin.

[0163] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0164] (a) 1 part by weight of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0165] (b) Approximately 3 parts by weight of maltodextrin.

[0166] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0167] (a) about 25% (w / w) to about 50% (w / w) of compound (I); and

[0168] (b) Approximately 50% (w / w) to approximately 75% (w / w) maltodextrin.

[0169] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0170] (a) about 25% (w / w) to about 50% (w / w) of compound (I); and

[0171] (b) Approximately 50% (w / w) to approximately 75% (w / w) maltodextrin,

[0172] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0173] (iv) Approximately 1:1 to approximately 1:3;

[0174] (v) about 1:1.5 to about 1:2.5; or

[0175] (vi) about 1:2.5 to about 1:3.5.

[0176] The aqueous formulation of the present invention, when ingested by subjects, such as amateur or professional athletes, is in the range of about 400 ml to about 1000 ml, for example, about 500 ml to about 800 ml, such as about 200 ml, about 250 ml, about 300 ml, about 400 ml, about 500 ml, about 600 ml, about 700 ml, about 800 ml, about 900 ml, or about 1000 ml, such as between about 400 ml and about 600 ml.

[0177] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0178] (a) about 0.4 mmol to about 8.8 mmol of compound (I); and

[0179] (b) Approximately 0.06 mmol to approximately 3.66 mmol of maltodextrin.

[0180] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0181] (a) about 0.4 mmol to about 8.8 mmol of compound (I); and

[0182] (b) Approximately 0.06 mmol to approximately 3.66 mmol of maltodextrin.

[0183] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0184] (a) about 0.8 mmol to about 17.6 mmol of compound (I); and

[0185] (b) Approximately 0.12 mmol to approximately 7.32 mmol of maltodextrin.

[0186] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0187] (a) about 1.6 mmol to about 35.2 mmol of compound (I); and

[0188] (b) Approximately 0.24 mmol to approximately 14.6 mmol of maltodextrin.

[0189] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0190] (a) about 100 mg / L to about 8000 mg / L of compound (I); and

[0191] (b) Approximately 100 mg / L to approximately 24 g / L of maltodextrin.

[0192] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0193] (a) about 400 mg / L to about 8000 mg / L of compound (I); and

[0194] (b) Approximately 800 mg / L to approximately 24 g / L of maltodextrin.

[0195] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0196] (a) about 400 mg / L to about 8000 mg / L of compound (I); and

[0197] (b) Approximately 800 mg / L to approximately 24 g / L of maltodextrin.

[0198] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0199] (i) by weight approximately 1:1 to approximately 1:3;

[0200] (ii) by weight approximately 1:1.5 to approximately 1:2.5; or

[0201] (iii) By weight, approximately 1:2.5 to approximately 1:3.5.

[0202] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0203] (a) about 400 mg / L to about 8000 mg / L of compound (I); and

[0204] (b) Approximately 800 mg / L to approximately 16 g / L of maltodextrin.

[0205] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0206] (a) about 400 mg / L to about 8000 mg / L of compound (I); and

[0207] (b) Approximately 800 mg / L to approximately 16 g / L of maltodextrin.

[0208] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0209] (i) by weight approximately 1:1 to approximately 1:3;

[0210] (ii) by weight approximately 1:1.5 to approximately 1:2.5; or

[0211] (iii) By weight, approximately 1:2.5 to approximately 1:3.5.

[0212] The compositions of the present invention can be added to sports drinks, for example, bottles containing about 500 ml to 1000 ml of sports drink. Such sports drinks may already contain maltodextrin, for example, about 6% to about 10% (w / v) maltodextrin. Therefore, according to another embodiment of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0213] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0214] (b) Approximately 36.1 g to approximately 106 g of maltodextrin.

[0215] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0216] (a) about 0.4 mmol to about 8.8 mmol of compound (I); and

[0217] (b) Approximately 14.7 mmol to approximately 128 mmol of maltodextrin.

[0218] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0219] (a) about 0.8 mmol to about 17.6 mmol of compound (I); and

[0220] (b) Approximately 29.4 mmol to approximately 256 mmol of maltodextrin.

[0221] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0222] (a) about 1.6 mmol to about 35.2 mmol of compound (I); and

[0223] (b) Approximately 58.8 mmol to approximately 512 mmol of maltodextrin.

[0224] According to another embodiment of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0225] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0226] (b) Approximately 36.3 g to approximately 106 g of maltodextrin.

[0227] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0228] (a) about 0.4 mmol to about 8.8 mmol of compound (I); and

[0229] (b) Approximately 14.8 mmol to approximately 128 mmol of maltodextrin.

[0230] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0231] (a) about 0.8 mmol to about 17.6 mmol of compound (I); and

[0232] (b) Approximately 29.6 mmol to approximately 256 mmol of maltodextrin.

[0233] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0234] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0235] (b) Approximately 30.2g to approximately 104g of maltodextrin.

[0236] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0237] (a) about 0.4 mmol to about 8.8 mmol of compound (I); and

[0238] (b) Approximately 12.3 mmol to approximately 125 mmol of maltodextrin.

[0239] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0240] (a) about 0.8 mmol to about 17.6 mmol of compound (I); and

[0241] (b) Approximately 24.6 mmol to approximately 250 mmol of maltodextrin.

[0242] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0243] (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof, such as urolithin A; and

[0244] (b) Approximately 30.1g to approximately 102g of maltodextrin.

[0245] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0246] (a) about 0.4 mmol to about 8.8 mmol of compound (I); and

[0247] (a) Approximately 12.3 mmol to approximately 123 mmol of maltodextrin.

[0248] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0249] (a) about 1.7 mmol to about 35 mmol of compound (I); and

[0250] (b) Approximately 24.6 mmol to approximately 246 mmol of maltodextrin.

[0251] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0252] (a) about 1.7 mmol to about 35 mmol of compound (I); and

[0253] (b) Approximately 0.244 mmol to approximately 1.464 mmol of maltodextrin.

[0254] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0255] (a) about 1.7 mmol to about 35 mmol of compound (I); and

[0256] (b) Approximately 0.244 mmol to approximately 1.464 maltodextrin.

[0257] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0258] (i) Approximately 1:1 to approximately 1:3;

[0259] (ii) about 1:1.5 to about 1:2.5; or

[0260] (iii) Approximately 1:2.5 to approximately 1:3.5.

[0261] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0262] (a) about 400 mg / L to about 8000 mg / L of compound (I); and

[0263] (b) Approximately 800 mg / L to approximately 24 g / L of maltodextrin.

[0264] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0265] (a) about 400 mg / L to about 8000 mg / L of compound (I); and

[0266] (b) Approximately 800 mg / L to approximately 24 g / L of maltodextrin.

[0267] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0268] (i) Approximately 1:1 to approximately 1:3;

[0269] (ii) about 1:1.5 to about 1:2.5; or

[0270] (iii) Approximately 1:2.5 to approximately 1:3.5.

[0271] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0272] (a) about 400 mg / L to about 4000 mg / L of compound (I); and

[0273] (b) Approximately 800 mg / L to approximately 12 g / L of maltodextrin.

[0274] According to another aspect of the present invention, an aqueous formulation is provided, the aqueous formulation comprising:

[0275] (a) about 400 mg / L to about 4000 mg / L of compound (I); and

[0276] (b) Approximately 800 mg / L to approximately 12 g / L of maltodextrin.

[0277] The weight ratio of compound (I) to maltodextrin is between any of the following:

[0278] (i) Approximately 1:1 to approximately 1:3;

[0279] (ii) about 1:1.5 to about 1:2.5; or

[0280] (iii) Approximately 1:2.5 to approximately 1:3.5.

[0281] In another embodiment, a composition for mixing with water, such as for mixing with a sports drink, is provided, the composition comprising:

[0282] (a) Approximately 1000 mg of a compound of formula (I), such as urolithin A; and

[0283] (b) Maltodextrin, such as agglomerated maltodextrin, such as agglomerated maltodextrin with a DE of about 10.

[0284] In one example embodiment, the sports drink comprises 6 liters of aqueous solution, such as milk, like oat milk, 2 kg of maltodextrin, such as agglomerated maltodextrin, and a flavoring agent, such as a chocolate flavoring agent. Such sports drinks are provided in approximately 30 portions, to which the composition of the present invention may be added.

[0285] In another embodiment, the sports drink comprises 6 liters of aqueous solution, such as 4 liters of water and 2 liters of carbonated beverage, 2 kg of maltodextrin, such as agglomerated maltodextrin, and a flavoring agent, such as strawberry flavoring. Such a sports drink is provided in approximately 30 portions, to which the composition of the present invention may be added.

[0286] The compositions of the present invention may be powders or may be added to water, yogurt, smoothies, or protein shakes. In another embodiment of the invention, the aqueous formulation may be a pellet. The term 'pellet' refers to a concentrated beverage with a volume of less than about 100 ml, for example, a volume ranging from about 30 ml to about 90 ml. Example pellets of the present invention with a volume of about 30 ml to about 90 ml, for example, volumes of about 30 ml, about 40 ml, about 50 ml, about 60 ml, about 70 ml, about 80 ml, or about 90 ml, contain an aqueous formulation comprising:

[0287] (a) about 100 mg to about 1000 mg of a compound of formula (I), such as urolithin A; and

[0288] (b) Approximately 100 mg to approximately 3000 mg of maltodextrin.

[0289] The compositions of the present invention can also be ingested in powder form.

[0290] The formulations and compositions of the present invention can be used for a variety of purposes and indications, including improving mitochondrial function, promoting muscle health and performance, and treating diseases, conditions and symptoms, particularly those associated with changes in muscle function.

[0291] Therefore, according to another aspect of the invention, an aqueous formulation or composition of the invention is provided for increasing or maintaining mitochondrial function, for example, a method for increasing or maintaining mitochondrial function in a generally healthy subject.

[0292] According to another aspect of the invention, formulations or compositions of the invention are provided for the treatment, prevention, or management of mitochondrial-related conditions associated with altered mitochondrial function or reduced mitochondrial density.

[0293] According to another aspect of the invention, formulations or compositions of the invention are provided for the treatment, prevention or management of mitochondrial-related diseases.

[0294] According to another aspect of the invention, formulations or compositions of the invention are provided for increasing or maintaining mitochondrial function, for example, increasing or maintaining mitochondrial function in generally healthy subjects.

[0295] In another embodiment of the invention, a method for enhancing muscle performance is provided, the method comprising administering the formulation or composition of the invention to a subject. In another embodiment, the enhancement of muscle performance is selected from one or more of the following: improved muscle function, reduced muscle function decline, improved muscle strength, improved muscle endurance, and improved muscle recovery. In another embodiment, in the method for enhancing muscle performance, the subject suffers from age-related muscle function decline, age-related sarcopenia, age-related muscle wasting, physical fatigue, muscle fatigue, and / or is frail or pre-frail. In another embodiment of the method for enhancing muscle performance, the subject suffers from physical fatigue or muscle fatigue, and / or the subject is frail or pre-frail.

[0296] In another embodiment of the invention, a method for improving, maintaining, or reducing muscle function loss is provided, the method comprising administering the formulation or composition of the invention to a subject.

[0297] In another embodiment of the invention, a method for improving endurance is provided, the method comprising administering the formulation or composition of the invention to a subject.

[0298] In another embodiment of the invention, a method for enhancing physical performance is provided, the method comprising administering the formulation or composition of the invention to a subject.

[0299] In another embodiment of the invention, a method for increasing muscle strength, increasing or maintaining muscle mass, or muscle recovery is provided, the method comprising administering the formulation or composition of the invention to a subject.

[0300] In another embodiment of the invention, a method for improving physical endurance is provided, the method comprising administering the formulation or composition of the invention to a subject.

[0301] In another embodiment of the invention, a method is provided to inhibit or delay physical fatigue, enhance work capacity and endurance, and / or reduce muscle fatigue, the method comprising administering the formulation or composition of the invention to a subject.

[0302] In another embodiment of the invention, a method for enhancing athletic performance is provided, the method comprising administering the formulation or composition of the invention to a subject.

[0303] In the method of the present invention, the loss of muscle function or the improvement of endurance occurs in healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and the elderly.

[0304] In another embodiment of the invention, formulations or compositions of the invention are provided for use as pharmaceuticals.

[0305] In another embodiment, the formulation or composition is used as a medicament for treating muscle-related pathological conditions. In another embodiment, muscle-related pathological conditions are selected from musculoskeletal diseases or disorders; muscle wasting; myopathy; neuromuscular diseases, sarcopenia; for example, acute sarcopenia and muscle atrophy or cachexia, or a combination of atrophy and cachexia.

[0306] In another embodiment, muscle atrophy or cachexia, or a combination of atrophy and cachexia, is selected from muscle atrophy or cachexia associated with burns, bed rest, limb immobilization, or major chest, abdominal, and / or orthopedic surgery.

[0307] Compound of formula (I) (urolithin)

[0308] Compounds of formula (I) (urolithin) are metabolites produced by ellagitannins and ellagic acids in mammals, including humans, through the action of the gut microbiota. Ellagannins and ellagic acids are compounds commonly found in foods such as pomegranates, nuts, and berries. Ellagannins themselves are minimally absorbed by the intestines. Urolithin is a class of compounds with representative structures (I) shown below. The structures of some particularly common urolithins are described in Table 1 below, referring to structure (I).

[0309]

[0310] (I)

[0311]

[0312] In fact, urolithin is readily synthesized for commercial-scale production. Synthetic routes are described, for example, in WO 2014 / 004902, WO 2015 / 100213 and WO 2019 / 168972.

[0313] Urolithin of any structure according to structure (I) can be used in the formulations and compositions of the present invention.

[0314] In one aspect of the formulation of the composition of the present 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.

[0315] A particularly suitable compound is naturally occurring urolithin. Therefore, 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, 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, the compound is urolithin A. Preferably, the urolithin used in the method of this disclosure is urolithin A, urolithin B, urolithin C, or urolithin D. Most preferably, the urolithin used is urolithin A.

[0316]

[0317] Urolithin A

[0318] According to one embodiment, formulations, compositions, uses, or methods of the present invention are provided, wherein the compound of formula (I) is urolithin A.

[0319] According to one embodiment, formulations, compositions, uses, or methods of the present invention are provided, wherein the compound of formula (I) is urolithin B.

[0320] According to one embodiment, formulations, compositions, uses, or methods of the present invention are provided, wherein the compound of formula (I) is urolithin C.

[0321] According to one embodiment, formulations, compositions, uses, or methods of the present invention are provided, wherein the compound of formula (I) is urolithin D.

[0322] In one embodiment, the compound of formula (I) comprises 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; or urolithin C having at least one hydroxyl group substituted with a fatty acid group). As used herein, the term "acyl" denotes a chemical substituent of formula -C(O)-R, wherein R is alkyl, alkenyl, aryl, aralkyl, cycloalkyl, heterocyclic, heterocycloalkyl, heteroaryl, or heteroarylalkyl. Optionally substituted acyl groups are acyl groups of each optionally substituted group R as described herein. Examples of acyl groups include fatty acid acyl groups (e.g., short-chain fatty acid acyl groups (e.g., acetyl)) and benzoyl groups. In one embodiment, the acylated urolithin is substituted with one or more C... 1-4 Alkyl carbonyl-substituted urolithin, more examples, are substituted by one or two Cs. 1-4 Urolithin A substituted with an alkyl carbonyl group (e.g., formyl, acetyl, or propionyl), such as urolithin A acetate or urolithin A diacetate.

[0323] The present invention also covers the use of suitable salts of compounds of formula (I), such as pharmaceutically acceptable salts. Suitable salts according to the 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 having an organic base, such as dicyclohexylamine, N-methyl-D-glucose, morpholine, thiomorpholine, piperidine, pyrrolidine; mono-, di-, or tri-alkylamines, such as ethyl-propylamine, tert-butyl-propylamine, diethyl-propylamine, diisopropyl-propylamine, triethyl-propylamine, tributyl-propylamine, or dimethyl-propylamine; or mono-, di-, or tri-alkylamines, such as monoethanolamine, diethanolamine, or triethanolamine.

[0324] Urolithiasis administration / dosage regimen

[0325] Administration of the formulations of the present invention preferably involves oral administration to a subject of urolithin of formula (I) or a salt thereof at a daily dose ranging from 1.7 mmol to 6.0 mmol, for example from about 1.7 mmol to about 2.7 mmol per day or from about 2.8 mmol to about 6.0 mmol per day. As discussed below, administration of urolithin A in the range of 250 mg to 2000 mg (which corresponds to about 1.1 mmol to 8.8 mmol), for example 250 mg to 1500 mg, such as 250 mg to 1000 mg, is preferred, which produces 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. In yet another embodiment, the dose is 1500 mg / day. In yet another embodiment, the dose is 2000 mg / day.

[0326] In another embodiment, the dosage is selected from:

[0327] - 250 mg, once or twice daily;

[0328] - 500 mg, once or twice daily;

[0329] - 750 mg, once or twice daily;

[0330] - 1000 mg, once or twice daily;

[0331] - 1250 mg, once or twice daily; or

[0332] - 1500 mg, once or twice daily.

[0333] The uses and methods of the present invention relate to the daily application of a formulation comprising a compound of formula (I) or a salt thereof. In some embodiments, the formulation is applied once daily, i.e., at least once every 24-hour period. In other embodiments, the formulation comprising the compound is applied multiple times daily, such as twice daily, or three or four times daily. In such cases, the daily dose is distributed among these multiple doses. In one embodiment, the application is once daily; in a second embodiment, the application is twice daily; and in a third embodiment, the application is three times daily.

[0334] The methods disclosed herein typically require daily application of a formulation containing a compound of formula (I) or a salt thereof, or application of a formulation containing said compound or salt thereof, for a period of several months. In some embodiments, the method may involve, for example, daily application of a formulation containing a compound of formula (I) or a salt thereof, 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 daily application of a formulation containing a compound of formula (I) or a salt thereof, for a period of up to 3 months, up to 6 months, up to 1 year, up to 2 years, or up to 5 years. In some embodiments, the method comprises daily application of a formulation containing a compound or salt for a period of time ranging from 21 days to 5 years, 21 days to 2 years, 21 days to 1 year, 21 days to 6 months, 21 days to 12 weeks, 28 days to 5 years, 28 days to 2 years, 28 days to 1 year, 28 days to 6 months, 28 days to 4 months, 28 days to 12 weeks, 6 weeks to 2 years, 6 weeks to 1 year, 8 weeks to 1 year, or 8 weeks to 6 months.

[0335] The use or method disclosed herein requires the daily administration of a formulation containing a compound of formula (I) or a salt thereof, from 0.7 mmol to 2.7 mmol daily, or twice daily from 0.7 mmol to twice daily from 2.7 mmol. 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 mmol, 1.2 mmol, 1.3 mmol, 1.4 mmol, 1.5 mmol, 1.6 mmol, 1.7 mmol, 1.8 mmol, 1.9 mmol, 2.0 mmol, 2.1 mmol, 2.2 mmol, 2.3 mmol, 2.4 mmol, 2.5 mmol, 2.6 mmol, or 2.7 mmol. In some preferred embodiments, the use or method involves administering a formulation containing approximately 2.2 mmol daily or twice daily from a compound of formula (I) or a salt thereof (e.g., administration of urolithiasis 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 (making 2.20 mmol equal to 501.6 mg), and urolithin B has a molecular weight of 212 g / mol (making 2.20 mmol equal to 466.4 mg).

[0336] In another embodiment, the method of this disclosure requires daily administration of a formulation containing a certain amount of a compound of formula (I) or a salt thereof, at a dose of 2.8 mmol to 6.0 mmol per day, or twice daily. 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 mmol, 2.9 mmol, 3.0 mmol, 3.1 mmol, 3.2 mmol, 3.3 mmol, 3.4 mmol, 3.5 mmol, 3.6 mmol, 3.7 mmol, 3.8 mmol, 3.9 mmol, 4.0 mmol, 4.1 mmol, 4.2 mmol, 4.3 mmol, 4.4 mmol, 4.5 mmol, 4.6 mmol, 4.7 mmol, 4.8 mmol, 4.9 mmol, 5.0 mmol, 5.1 mmol, 5.2 mmol, 5.3 mmol, 5.4 mmol, 5.5 mmol, 5.6 mmol, 5.7 mmol, 5.8 mmol, 5.9 mmol, or 6.0 mmol. In some preferred embodiments, the use or method involves administering a formulation comprising approximately 4.4 mmol daily or twice daily of a compound of formula (I) or a salt thereof (e.g., administration of urolithiasis A). The exact weight of the compound applied depends on the molecular weight of the compound used. For example, urolithin A has a molecular weight of 228 g / mol (making 4.40 mmol equal to 1003.2 mg), and urolithin B has a molecular weight of 212 g / mol (making 4.40 mmol equal to 932.8 mg).

[0337] In some embodiments, the method involves administering a formulation containing urolithin A at a dose ranging from 400 mg / day to 600 mg / day or twice daily at a dose ranging from 400 mg to 600 mg. In a preferred embodiment, the method involves administering urolithin A at a dose ranging from 450 mg to 550 mg, more preferably about 500 mg daily or twice daily.

[0338] In other embodiments, the method involves administering a formulation containing urolithin A in an amount ranging from 700 mg / day to 1300 mg / day twice daily, or from 750 mg to 1250 mg, or from 800 mg to 1200 mg, or from 850 mg to 1150 mg, or from 900 mg to 1100 mg / day or twice daily. In a preferred embodiment, the method involves administering urolithin A in an amount ranging from 950 mg / day to 1150 mg / day or twice daily, more preferably about 1000 mg / day or twice daily.

[0339] In some preferred embodiments, the use or method involves administering a formulation containing urolithin A to a subject in an amount ranging from 4.5 mg / kg / day to 11 mg / kg / day, such as from 4.5 mg / kg / day to 8.5 mg / kg / day. In another embodiment, the use or method involves administering a formulation containing urolithin A to a subject in an amount ranging from 5 mg / kg / day to 9 mg / kg / day. In yet another embodiment, the use or method involves administering a formulation containing urolithin A to a subject in an amount ranging from 6.0 mg / kg / day to 8 mg / kg / day.

[0340] In other preferred embodiments, the use or method involves administering a formulation containing urolithin A to a subject in an amount ranging from 9 mg / kg / day to 18 mg / kg / day, such as from 9 mg / kg / day to 17 mg / kg / day. In another embodiment, the use or method involves administering a formulation containing urolithin A to a subject in an amount ranging from 10 mg / kg / day to 17 mg / kg / day. In yet another embodiment, the use or method involves administering a formulation containing urolithin A to a subject in an amount ranging from 11 mg / kg / day to 16 mg / kg / day.

[0341] Dosing regimens combining 500 mg and 1000 mg doses may be advantageous. For example, a twice-daily dosing regimen combining a first dose of 1000 mg with a second dose of 500 mg several hours later. The 500 mg dose may be 6-18 hours after the 1000 mg dose, for example, 8-12 hours after the 1000 mg dose. For example, about 12 hours after the 1000 mg dose. Therefore, according to another aspect of the invention, a formulation comprising a compound of formula (I) is provided for the treatment of diseases, conditions, or symptoms comprising a twice-daily dosing regimen comprising a first dose of 1000 mg followed by a second dose of 500 mg, wherein the two doses are spaced 6-18 hours apart.

[0342] Formulations containing a compound of formula (I) or a salt thereof may be applied at any suitable time, such as after going to bed in the morning or at night. In some embodiments, it is preferred that the method be performed at approximately the same time each day, such as within 15 minutes, 30 minutes, 60 minutes, or 120 minutes of a given time point.

[0343] Formulas containing compound (I) and maltodextrin can be administered before, after, or during exercise. Such formulas are useful for both amateur and professional athletes.

[0344] To avoid any doubt in this application, when referring to 'urolithin', it means one or more urolithins, such as a mixture of urolithin A and urolithin B.

[0345] maltodextrin

[0346] Maltodextrin is a polysaccharide composed of polymers of variable-length D-glucose units, typically consisting of a mixture of chains ranging from 3 to 20 glucose units in length. Maltodextrin is classified by D (glucose equivalent), with DE ranging from 3 to 20. Higher DE values ​​indicate shorter glucose chains, higher sweetness, higher solubility, and lower heat resistance. Maltodextrin used in formulations and compositions of the present invention typically contains maltodextrin with DE ranging from about 1 to about 20, for example, about 1 to about 15, about 5 to about 15, about 7 to about 13, about 8 to about 12, about 9 to about 11, or about 10.

[0347] In an embodiment of the present invention, the maltodextrin is an aggregated maltodextrin.

[0348] The aqueous formulation of the present invention contains maltodextrin, such as agglomerated urolithin A, in the range of 200 mg to 6000 mg.

[0349] In another embodiment of the invention, a unit dose of the aqueous formulation of the invention comprises between 0.04 mmol and about 0.724 mmol of maltodextrin.

[0350] In another embodiment of the invention, the aqueous formulation of the invention comprises maltodextrin at a concentration between about 0.163 mmol and about 2.896 mmol.

[0351] In another embodiment of the invention, the aqueous formulation comprises urolithin and maltodextrin in a weight ratio of about 1:1 to about 1:3. In one embodiment, the aqueous formulation comprises urolithin and maltodextrin in a weight ratio of about 1:about 1. In another embodiment, the aqueous formulation comprises urolithin and maltodextrin in a weight ratio of about 1:about 2. In another embodiment, the aqueous formulation comprises urolithin and maltodextrin in a weight ratio of about 1.5:about 2.5. In another embodiment, the aqueous formulation comprises urolithin and maltodextrin in a weight ratio of about 1.5:about 2.5. In yet another embodiment, the aqueous formulation comprises urolithin and maltodextrin in a weight ratio of about 1:about 3. In another embodiment, the aqueous formulation comprises urolithin and maltodextrin in a weight ratio of about 2.5:3.5.

[0352] In another embodiment of the invention, the composition of the invention for mixing with water comprises maltodextrin at a concentration between about 0.04 mmol and about 0.724 mmol or multiples thereof.

[0353] Other / combination therapies

[0354] The compositions of the present invention may contain one or more additional active agents for treating or preventing diseases, conditions or symptoms, or for promoting muscle health and performance in healthy individuals, or for improving mitochondrial function, or for treating other conditions disclosed in this application, or for medical treatment or administration to healthy individuals.

[0355] Any known useful active agent, or active agent that has been or is currently used to treat or prevent diseases, conditions or symptoms, or to promote muscle health and performance in healthy individuals, or to improve mitochondrial function, may be used in combination with the present invention. See, for example, Gilman et al., *Goodman and Gilman's: The Pharmacological Basis of Therapeutics*, 13th ed., McGraw-Hill, New York, 2017; *The Merck Manual of Diagnosis and Therapy*, Robert S. Porter, MD et al. (eds.), 20th ed., Merck Sharp & Dohme Research Laboratories, Rahway, NJ, 2018; *Cecil Textbook of Medicine*, 25th ed., Goldman and Schafer (eds.), Elsevier, 2015; and *Physicians' Desk Reference*. (71st edition 2016) to obtain information about treatments (e.g., preventative or therapeutic agents) that are already in use or are being used.

[0356] Other examples of such agents include, but are not limited to: caffeine, omega-3 polyunsaturated fatty acids, resveratrol, spermidine, pyrrolquinone, quinone, genistein, hydroxytyrosol, L-creatine, L-arginine, curcumin, vitamin D, quercetin, trehalose, and antioxidants (such as L-carnitine, coenzyme Q10, and MitoQ). 10Other mitochondrial-targeting antioxidants), N-acetylcysteine ​​(NAC), vitamin C, vitamin E, vitamin K1, one or more B vitamins (e.g., thiamine, folic acid), B50 or B100 (B vitamin complex), sodium pyruvate and alpha-lipoic acid, NAD precursors (e.g., niacin, nicotinamide, tetrahydrofolate and amino acids).

[0357] use

[0358] The compositions and formulations of the present invention can be used for both therapeutic and non-therapeutic purposes, and have been found to be effective in treating a variety of diseases as well as health conditions not considered diseases. Specifically, disease conditions may be characterized by insufficient mitochondrial activity, and improvements in non-disease health may be characterized by enhanced mitochondrial function. Therefore, according to one embodiment of the invention, a composition of the invention is provided for use as a medicament for treating disease symptoms or conditions. According to another embodiment of the invention, a non-therapeutic method using the composition of the invention is provided.

[0359] The compositions of the present invention can be used as dietary supplements, as functional foods, and as medicinal foods. The compositions of the present invention can also be used as foods for specific medical purposes.

[0360] The compositions of the present invention can be used to treat diseases, conditions, and symptoms. Therefore, according to another aspect of the present invention, compositions of the present invention are provided for use as medicaments for treating diseases, conditions, or symptoms.

[0361] According to another aspect of the invention, compositions of the invention are provided for the treatment, prevention, or management of mitochondrial-related conditions associated with altered mitochondrial function or reduced mitochondrial density.

[0362] According to another aspect of the invention, non-treatment methods are provided for the prevention or management of mitochondrial-related symptoms associated with alterations in mitochondrial function (such as reduced mitochondrial function, including due to mitochondrial reduction and / or mitochondrial damage) or reduced mitochondrial density, said methods comprising administering an effective amount of the composition of the invention.

[0363] According to another aspect of the invention, formulations or compositions of the invention are provided for the treatment, prevention, or management of mitochondrial-related diseases associated with altered mitochondrial function or reduced mitochondrial density.

[0364] According to another aspect of the invention, compositions of the invention are provided for the treatment, prevention, or management of mitochondrial-related diseases.

[0365] According to another aspect of the invention, formulations or compositions of the invention are provided for increasing or maintaining mitochondrial function.

[0366] According to another aspect of the invention, a non-therapeutic method for increasing or maintaining mitochondrial function is provided, the method comprising administering an effective amount of the composition of the invention.

[0367] According to another aspect of the invention, compositions of the invention are provided for treating or preventing inflammation.

[0368] Therapeutic uses

[0369] Neurological disorders

[0370] According to one embodiment of the present invention, a composition of the invention is provided for treating neurological disorders, including neurodegenerative disorders. Examples of neurological disorders include: cognitive decline, memory decline, anxiety, depression, epilepsy, stroke, amyotrophic lateral sclerosis (ALS), dementia (e.g., vascular dementia and Alzheimer's disease), Parkinson's disease, and Huntington's disease.

[0371] According to another embodiment of the invention, compositions of the invention are provided for the prevention or treatment of disease states caused or characterized by (i) cognitive decline; or (ii) mood disorders. Such disease states may include, but are not limited to, neurodegenerative diseases, cognitive impairment, mood disorders, and anxiety disorders.

[0372] An embodiment of the present invention is a method for improving cognitive function. The method includes the step of administering an effective amount of urolithiasis or its precursor to a subject in need to improve cognitive function. In one embodiment, cognitive function is selected from the group consisting of: perception, memory, attention, speech comprehension, speech production, reading comprehension, image creation, learning, and reasoning. In another embodiment, cognitive function is selected from the group consisting of: perception, memory, attention, and reasoning. In yet another embodiment, cognitive function is memory.

[0373] According to another embodiment, a composition of the present invention is provided for protection against brain oxidative stress.

[0374] According to another embodiment, a composition of the present invention is provided for reducing brain inflammation.

[0375] According to another embodiment, compositions of the present invention are provided for treating mood disorders, stress, and / or anxiety disorders.

[0376] Immune function

[0377] In another embodiment of the invention, the use of the compositions of the invention for supporting and / or enhancing immune function during or after cancer treatment is provided.

[0378] In another embodiment of the invention, the use of the compositions of the invention for supporting and / or enhancing immune function remission following cancer treatment is provided.

[0379] In another embodiment of the invention, the use of the compositions of the invention for supporting and / or enhancing immune function during and after hospitalization is provided.

[0380] Aging / Healthy Lifespan

[0381] According to another embodiment of the invention, a composition of the invention is provided for increasing healthy lifespan.

[0382] In another embodiment of the invention, a composition of the invention is provided for slowing down aging.

[0383] According to another embodiment of the invention, a composition of the invention is provided for increasing lifespan.

[0384] In one embodiment, an increase in healthy lifespan is considered to be at least 5% longer than that in the placebo-controlled or untreated group. In various specific embodiments, an increase in healthy lifespan is considered to be at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50% longer than that in the placebo-controlled or untreated group. In some embodiments, the increase in healthy lifespan is at least 10% compared to the placebo-controlled or untreated group. In some embodiments, the increase in healthy lifespan is at least 20% compared to the placebo-controlled or untreated group. In some embodiments, healthy life expectancy increased by at least 30% compared to the placebo-controlled or untreated group. In some embodiments, healthy life expectancy increased by at least 40% compared to the placebo-controlled or untreated group. In some embodiments, healthy life expectancy increased by at least 50% compared to the placebo-controlled or untreated group.

[0385] skin

[0386] In another embodiment of the invention, a composition of the invention is provided for use in the prevention, management and / or treatment of skin conditions, diseases or ailments.

[0387] In another embodiment of the invention, a composition of the invention is provided for treating skin conditions, diseases, or ailments that are associated with insufficient mitochondrial activity.

[0388] In some embodiments, skin diseases, conditions, or symptoms are selected from the group consisting of: melasma, chloasma, hyperpigmentation, skin aging, freckles, age spots, skin inflammation, skin irritation, skin infection, warts, psoriasis, and protection of the skin from damage caused by environmental and / or treatment. Skin diseases, conditions, or symptoms are also selected from melanosis, dermatitis, lines over melanocyticus, and endocrine disorders such as Addison's and Cushing's syndrome.

[0389] As mentioned above, the compositions of the present invention can be used in methods for preventing skin conditions, diseases, or ailments. That is, they are suitable for subjects with skin prone to the minor ailments mentioned herein, such as subjects with intermittent skin problems, such as skin prone to sunburn, acne, and inflammation. The compositions can be used for the management and prevention of conditions.

[0390] In another embodiment of the invention, a composition of the invention is provided for treating symptoms selected from acne, eczema, psoriasis and rosacea.

[0391] In another embodiment of the invention, compositions of the invention are provided for the prevention and treatment of skin susceptible to conditions selected from acne, eczema, psoriasis and rosacea.

[0392] treat:

[0393] The compositions of the present invention can be used as a single treatment, or more commonly, as a series of treatments. In one instance, a subject takes a dose before or after exercise. For subjects who cannot exercise, a dose of the composition may be taken once, twice, or three times daily, or once, twice, three times, four times, five times, or six times weekly. In another instance, the intervention may be performed by the subject regardless of the subject's ability or need to exercise. It should also be understood that the effective dose of the compound may be increased or decreased during a particular treatment.

[0394] Recovery after treatment

[0395] The compositions of the present invention can also be used for patients recovering from diseases, symptoms, or conditions, whether at home or in a hospital. Therefore, according to further embodiments of the invention, compositions of the present invention are provided for assisting patients in recovering from diseases, symptoms, or conditions, such as those selected from cancer, bacterial or viral infections, or other serious illnesses, or physical injuries such as car accidents.

[0396] Non-therapeutic use

[0397] The compositions of the present invention can be used as nutritional supplements, functional foods, medical nutrition products, and equivalents. These include treatments for non-therapeutic conditions, i.e., treatments for conditions in generally healthy subjects.

[0398] Muscle function, performance, endurance

[0399] The compositions can be used to manage normal physiological functions in healthy individuals or conditions characterized by poor physical performance, impaired endurance, and impaired muscle function. The compositions of the present invention can improve the physical performance of individuals with diseases, including both young and older individuals. The compositions of the present invention can improve physical performance, for example, the short-term or long-term performance of healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and older adults. Such improvement 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), improved time to run a specific distance, improved IPAQ scores on the International Physical Activity Questionnaire, an increase in the number of times one stands up from a chair within a specific time period, or another test designed to measure physical performance.

[0400] The compositions of the present invention further provide improvements in endurance. Endurance refers to the time to fatigue during exercise under a constant workload (typically intensity <80% VO2max). The compositions of the present invention can improve endurance in individuals with diseases, including young and older individuals. The compositions of the present invention can improve endurance in healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and older adults. The present invention provides a method for increasing the time to fatigue during specific activities, such as fitness training, walking, running, swimming, or cycling. This improvement in endurance can be assessed by objective measurements (e.g., speed, oxygen consumption, or heart rate) or by self-reported measurements (e.g., using validated questionnaires).

[0401] The present invention further provides a composition for improving, maintaining, or reducing muscle function loss. The compositions of the present invention can improve, maintain, or reduce muscle function loss in individuals with disease, including both young and older individuals. The compositions of the present invention can improve, maintain, or reduce muscle function loss in healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and older adults. For example, the compositions of the present invention can increase muscle strength, which can be demonstrated by improvements in physical activity such as exercise, for example, increased weightlifting ability or increased hand grip strength. Furthermore, the compositions of the present invention can improve muscle structure, for example, increasing or maintaining muscle mass in cases of normal muscle function, decreased muscle function, or impaired muscle function.

[0402] The present invention further provides compositions that improve an individual's perceived physical performance or endurance. For example, a reduction in perceived fatigue or effort during exercise or activity, as determined using a self-report questionnaire.

[0403] Immune health

[0404] In another embodiment of the invention, the use of the compositions of the invention for maintaining or enhancing immune health is provided.

[0405] In another embodiment of the invention, the use of the compositions of the invention for reducing or alleviating inflammation is provided.

[0406] In another embodiment of the invention, the use of the compositions of the invention for slowing down immune aging is provided.

[0407] In another embodiment of the invention, the use of the compositions of the invention for reducing the aging of immune cells is provided.

[0408] In another embodiment of the invention, the use of the compositions of the invention for enhancing immune function is provided.

[0409] In another embodiment of the invention, the use of the compositions of the invention for supporting a healthy immune system is provided.

[0410] In another embodiment of the invention, the use of the compositions of the invention for the prevention or management of colds and / or influenza is provided.

[0411] In another embodiment of the invention, the use of the compositions of the invention for treating infections is provided.

[0412] In another embodiment of the invention, the use of the compositions of the invention for improving vaccination response is provided.

[0413] In another embodiment of the invention, the use of the compositions of the invention for enhancing the immune response to infection is provided.

[0414] In another embodiment of the invention, the composition of the invention is provided for use in preventing infection, such as preventing colds and influenza.

[0415] In another embodiment of the invention, the use of the compositions of the invention for immune support is provided.

[0416] In another embodiment of the invention, the use of the compositions of the invention for reducing the risk of respiratory infections (e.g., colds, flu, or pneumonia) is provided.

[0417] In another embodiment of the invention, the use of the compositions of the invention for improving the recovery speed of respiratory infections (e.g., colds, influenza, or pneumonia) is provided.

[0418] In another embodiment of the invention, the use of the compositions of the invention for increasing CD8-positive T cells, such as primordial CD8-positive T cells, is provided.

[0419] Brain health

[0420] According to another embodiment of the invention, the compositions of the invention are provided for use in maintaining or enhancing brain health.

[0421] According to another embodiment of the invention, the composition of the invention is provided for use in promoting healthy brain function.

[0422] According to another embodiment, a composition of the present invention is provided for optimizing brain health.

[0423] According to another embodiment, compositions of the present invention are provided for improving, protecting, and maintaining brain function and cognition.

[0424] According to another embodiment, compositions of the present invention are provided for enhancing mental alertness, such as mental accuracy and clearer / sharper thinking.

[0425] According to another embodiment, a composition of the present invention is provided for increasing psychomotor speed and / or reaction time.

[0426] According to another embodiment, a composition of the present invention is provided for enhancing / improving memory.

[0427] According to another embodiment, a composition of the present invention is provided for enhancing / improving learning.

[0428] According to another embodiment, compositions of the present invention are provided for enhancing / improving reasoning, such as facilitating mental processing.

[0429] According to another embodiment, compositions of the present invention are provided for enhancing / improving focus, such as concentration, complex attention, and / or sustained attention.

[0430] According to another embodiment, the composition of the present invention is provided for use in relieving stress and / or anxiety.

[0431] According to another embodiment, the composition of the present invention is provided for use in treating stress and / or anxiety.

[0432] According to another embodiment, the composition of the present invention is provided for use in treating depression.

[0433] According to another embodiment, the composition of the present invention is provided for use in improving mood.

[0434] According to another embodiment, the composition of the present invention is provided for use in enhancing sleep and / or relaxation.

[0435] skin

[0436] In other embodiments of the invention, compositions of the invention are provided for managing or maintaining skin health and / or reducing the effects of biotic aging over time. Furthermore, uses of the compositions of the invention for preventing or managing aging skin are provided.

[0437] In another embodiment of the invention, the use of the compositions of the invention for maintaining or enhancing the skin health of a generally healthy subject is provided.

[0438] According to another embodiment of the present invention, the compositions of the present invention are provided for use in one or more of the following applications:

[0439] a) Improves skin health;

[0440] b) Used to maintain or enhance skin energy;

[0441] c) Used to maintain or enhance skin collagen;

[0442] d) Used to reduce skin biological aging;

[0443] e) Supports healthy skin aging;

[0444] f) Reduce skin wrinkles and / or fine lines;

[0445] g) Improves skin mitochondrial function;

[0446] h) Improves skin hydration;

[0447] i) Promotes the replenishment of skin ceramide levels;

[0448] j) Improves skin elasticity and barrier function;

[0449] k) Prevent free radical damage; and / or

[0450] l) Improves dry skin;

[0451] m) Improves photodamaged skin;

[0452] n) Improves skin health for skin that is prone to redness, inflammation, acne, or dryness.

[0453] According to another embodiment of the present invention, the compositions of the present invention are provided for use in one or more of the following applications:

[0454] a) Maintain or enhance skin health and appearance;

[0455] b) Maintain or improve skin hydration;

[0456] c) Enhance skin elasticity;

[0457] d) Reduce wrinkles and fine lines;

[0458] e) Support healthy skin aging;

[0459] f) Helps replenish ceramide reserves;

[0460] g) Helps prevent free radical damage;

[0461] h). Supports sunlight damage;

[0462] i) Used as an antioxidant;

[0463] j) Maintaining or promoting healthy skin, hair, and nails; and / or

[0464] k) Skin barrier support.

[0465] hair

[0466] In another embodiment of the invention, compositions of the invention are provided for managing or maintaining hair health. In another embodiment of the invention, compositions of the invention are provided, such as compositions comprising urolithin A, said compositions being used for one or more of the following purposes:

[0467] (a) Maintain or increase hair thickness;

[0468] (b) Hair follicle cell regeneration;

[0469] (c) Hair follicle cell survival;

[0470] (d) Hair follicle stem cell growth and / or regeneration;

[0471] (e) Hair cell survival;

[0472] (f) Prevent hair loss;

[0473] (g) Hair maintenance;

[0474] (h) Improve scalp health;

[0475] (i) Improve or maintain hair strength; and / or

[0476] (j) Promotes hair growth recovery.

[0477] In another embodiment of the invention, compositions of the invention are provided, such as compositions comprising urolithin A, said compositions being used for one or more of the following purposes:

[0478] a) Maintain or increase hair thickness;

[0479] b) Hair follicle cell regeneration;

[0480] c) Hair follicle cell survival;

[0481] d) Hair follicle stem cell growth and / or regeneration;

[0482] e) Hair cell survival;

[0483] f) Prevent hair loss;

[0484] g) Improve scalp health; and / or

[0485] h) Promotes hair growth recovery.

[0486] In another embodiment, a method is provided for the following:

[0487] a) Maintain or increase hair thickness;

[0488] b) Hair follicle cell regeneration;

[0489] c) Hair follicle cell survival;

[0490] d) Hair follicle stem cell growth and / or regeneration;

[0491] e) Hair cell survival;

[0492] f) Prevent hair loss;

[0493] g) Promotes new hair growth;

[0494] h) Improve scalp health;

[0495] i) Used to improve the survival rate of hair transplants; and / or

[0496] j) Promotes hair growth recovery.

[0497] In another embodiment of the invention, compositions of the invention are provided, such as compositions comprising urolithin A, said compositions being used for one or more of the following purposes:

[0498] a) Enhance the function of hair follicle stem cells;

[0499] b) Enhances hair follicle elongation;

[0500] c) Enhance hair matrix proliferation, for example, as measured by Ki67 levels;

[0501] d) Prolong the hair growth phase (extend the duration of the anagen phase);

[0502] e) Hair matrix proliferation;

[0503] f) Inhibit apoptosis of hair stromal cells; and

[0504] g) Reduce melanin accumulation, for example, in pigment units, such as in hair follicle pigment units.

[0505] In another embodiment of the invention, compositions of the invention are provided, such as compositions comprising urolithin A, said compositions being used for one or more of the following purposes:

[0506] a) Improve the healthy lifespan of hair; and / or

[0507] b) Improve hair lifespan.

[0508] Muscle performance

[0509] The compositions of the present invention can be used to enhance muscle performance. Therefore, the present invention provides compositions for enhancing muscle performance. The present invention also provides a method for enhancing muscle performance by administering an effective amount of the compositions of the present invention to a subject. Administerment may be self-administered. Enhancement of muscle performance may be one or more improvements in muscle function, improved muscle strength, improved muscle strength, improved muscle endurance, and improved muscle recovery.

[0510] Therefore, the compositions of the present invention can be used to improve physical endurance (e.g., the ability to perform physical tasks such as exercise, manual labor, sports activities, etc.), inhibit or delay physical fatigue, enhance work capacity and endurance, reduce muscle fatigue, and enhance heart and cardiovascular function.

[0511] Improved muscle function may be particularly beneficial for older subjects whose muscle function declines due to age-related conditions. For example, subjects who may benefit from improved muscle function may have experienced muscle decline, which then leads to pre-frailty and frailty. Such subjects do not necessarily experience muscle wasting in addition to their muscle decline. Some subjects do experience muscle wasting and muscle decline, such as those with sarcopenia. The compositions of the present invention can be used to enhance muscle performance by administering the compositions of the present invention to frail or pre-frail subjects.

[0512] Muscle performance can be considered athletic performance, that is, an athlete's ability to utilize their muscles during physical activity. Improvements in athletic performance, intensity, speed, and endurance are measured by increases in the strength of muscle contractions, the amplitude of muscle contractions, or the shortening of the muscle response time between stimulus and contraction. An athlete is an individual participating in any level of sport who seeks to improve their strength, speed, or endurance levels in their performance; examples include bodybuilders, cyclists, long-distance runners, and sprinters. Improved athletic performance manifests as the ability to overcome muscle fatigue, the ability to sustain activity for extended periods, and more effective training.

[0513] Muscle use of the formulations and compositions of the present invention

[0514] The formulations and compositions of this invention can be used to improve muscle performance, improve muscle function, prevent muscle function decline, increase muscle mass, and / or reduce muscle loss. Improving muscle performance, improving or maintaining muscle function, increasing muscle mass, and / or reducing muscle loss can be part of a medical treatment, or it can be for personal preference (“lifestyle”) or cosmetic reasons. The formulations and compositions of this invention can be used as pharmaceuticals. The formulations and compositions can be used as dietary supplements, as functional foods, as functional beverages, or as medical foods. Enhanced muscle performance can be one or more improvements in muscle function, improved muscle strength, improved muscle endurance, and improved muscle recovery.

[0515] Formulas and compositions can be used to treat both diseases and disease states. Formulas and compositions can be used to manage normal physiological functions in healthy individuals or symptoms characterized by poor physical performance, impaired endurance, and impaired muscle function. Formulas and compositions of the present invention can improve the physical performance of individuals with diseases, including young and old individuals, or generally healthy individuals. Formulas and compositions of the present invention can improve physical performance, for example, the short-term or long-term performance of healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and older adults. 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), improved time to run a specific distance, improved IPAQ scores on the International Physical Activity Questionnaire, an increase in the number of times one stands up from a chair within a specific time period, or another test designed to measure physical performance.

[0516] The formulations and compositions of the present invention further provide improvements in endurance. Endurance refers to the time to fatigue during exercise under a constant workload (typically intensity < 80% VO2max). The formulations and compositions of the present invention can improve the endurance of individuals with diseases, including young and older individuals. The formulations and compositions of the present invention can improve the endurance of healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and older adults. The present invention provides a method for increasing the time to fatigue during specific activities, such as fitness training, walking, running, swimming, or cycling. This improvement in endurance can be assessed by objective measurements (e.g., speed, oxygen consumption, or heart rate) or by self-reported measurements (e.g., using validated questionnaires).

[0517] This invention further provides formulations or compositions for improving muscle function, maintaining muscle function, reducing muscle function loss, reducing post-exercise muscle inflammation, or enhancing post-exercise muscle recovery. The formulations and compositions of this invention can improve, maintain, or reduce muscle function loss in individuals with disease, including both young and older individuals. The formulations and compositions of this invention can improve, maintain, or reduce muscle function loss in healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and older adults. For example, the formulations or compositions of this invention can improve, maintain, or reduce muscle function loss in individuals who are frail or pre-frail. For example, the formulations or compositions of this invention can increase muscle strength, which can be demonstrated by improvements in physical activities such as exercise, for example, increased weightlifting ability or increased hand grip strength. Furthermore, the formulations or compositions of this invention can improve muscle structure, for example, increasing or maintaining muscle mass in cases of normal muscle function, decreased muscle function, or impaired muscle function.

[0518] The present invention further provides formulations or compositions that improve an individual's perceived physical performance or endurance. For example, a reduction in perceived fatigue or effort during exercise or activity, as determined using a self-report questionnaire.

[0519] Methods to enhance physical performance

[0520] According to another embodiment of the invention, a method for enhancing the physical performance of subjects, such as elite or sub-elite athletes, is provided.

[0521] In some embodiments, enhancing physical performance includes at least one effect selected from the group consisting of: enhanced athletic performance, enhanced running performance, enhanced muscle performance, enhanced aerobic endurance, enhanced perceived exertion, reduced post-exercise fatigue, enhanced muscle recovery, reduced exercise-induced muscle damage, reduced muscle soreness, and enhanced repair of exercise-induced muscle damage. In another embodiment, enhancing physical performance includes enhancing muscle performance during high-intensity aerobic activity. In yet another embodiment, enhancing physical performance includes improving aerobic endurance during high-intensity aerobic activity. In still another embodiment, enhancing physical performance includes increasing resting metabolic rate (RMR). In some embodiments, enhancing physical performance improves athletic performance. In another embodiment, enhancing physical performance improves race completion time. In yet another embodiment, enhancing physical performance reduces perceived exertion (RPE).

[0522] In one embodiment, enhancing physical performance includes enhancing muscle performance during high-intensity aerobic activity.

[0523] In one embodiment, enhancing physical performance includes improving aerobic endurance during high-intensity aerobic activity.

[0524] In one embodiment, enhancing physical performance includes increasing the resting metabolic rate (RMR).

[0525] In one embodiment, enhancing physical performance leads to improved athletic performance.

[0526] In one embodiment, enhanced physical performance improves race completion time.

[0527] In one embodiment, enhanced physical performance reduces perceived exertion level (RPE).

[0528] Methods to enhance physical recovery

[0529] According to another embodiment of the invention, a method for enhancing the physical recovery of subjects, such as elite or sub-elite athletes, is provided.

[0530] In some embodiments, enhanced recovery following high-intensity aerobic activity is achieved. In other embodiments, enhanced recovery includes at least one effect selected from the group consisting of: enhanced muscle recovery, enhanced athletic performance, enhanced running performance, enhanced muscle performance, enhanced aerobic endurance, enhanced perceived exertion, reduced post-exercise fatigue, enhanced muscle recovery, reduced exercise-induced muscle damage, reduced muscle soreness, and enhanced repair of exercise-induced muscle damage. In yet another embodiment, enhanced recovery includes enhanced muscle recovery following high-intensity aerobic activity. In still another embodiment, enhanced recovery includes reduced muscle soreness following high-intensity aerobic activity. In some embodiments, enhanced recovery includes reducing creatine kinase (CK) levels in the subject after aerobic activity (compared to baseline), such as by the area under the plasma concentration-time curve (AUC) of CK. CK The measurement was taken from the plasma concentration-time area (AUC). In another embodiment, enhanced recovery included reducing C-reactive protein (CRP) levels in the subject after aerobic activity (compared to baseline), as measured by the AUC. CRP ) Measured.

[0531] In one embodiment, the enhanced physical recovery occurs after high-intensity aerobic exercise.

[0532] In one embodiment, enhancing physical recovery includes enhancing muscle recovery after high-intensity aerobic activity.

[0533] In one embodiment, enhancing physical recovery includes reducing muscle soreness after high-intensity aerobic activity.

[0534] In one embodiment, enhancing physical recovery involves reducing creatine kinase (CK) levels in subjects after aerobic activity (compared to baseline), as measured by the area under the plasma concentration-time curve (AUC) of CK. CK ) Measured.

[0535] In one embodiment, enhanced recovery includes reducing C-reactive protein (CRP) levels in the subject after aerobic activity (compared to baseline), as measured by the area under the plasma concentration-time curve (AUC). CRP ) Measured.

[0536] Methods to improve physical endurance

[0537] According to another embodiment of the invention, a method for enhancing the endurance of subjects, such as elite or sub-elite athletes, is provided.

[0538] In some embodiments, the method includes enhancing physical endurance during high-intensity aerobic activity. In other embodiments, enhancing physical endurance includes at least one effect selected from the group consisting of: enhanced muscle recovery, enhanced athletic performance, enhanced running performance, enhanced muscle performance, enhanced aerobic endurance, enhanced perceived exertion, reduced post-exercise fatigue, enhanced muscle recovery, reduced exercise-induced muscle damage, reduced muscle soreness, and enhanced repair of exercise-induced muscle damage. In yet another embodiment, enhancing physical endurance includes enhancing muscular endurance. In still another embodiment, enhancing physical endurance includes increasing the subject's maximum oxygen uptake (VO2 max). 2max ).

[0539] In one embodiment, the enhanced physical recovery occurs during high-intensity aerobic exercise.

[0540] In one embodiment, enhancing physical endurance includes enhancing muscular endurance.

[0541] In one embodiment, enhancing physical endurance includes increasing the subject's maximum oxygen consumption (VO2max).

[0542] In some embodiments, the method of this disclosure comprises administering an effective amount of the formulation or composition of the invention to a subject in need, wherein the subject is an elite or sub-elite athlete. In some such embodiments, the subject is an elite athlete. In some embodiments, the subject has a VO of greater than 65 mL kg⁻¹ min⁻¹. 2max In another embodiment, the subject's personal best time for a 3 km run was less than 9 minutes. In other embodiments, the subject was a sub-elite athlete. In some such embodiments, the subject had a VO2 max of approximately 60 mL kg⁻¹ min⁻¹ to approximately 65 mL kg⁻¹ min⁻¹. 2max In another embodiment, the subject's personal best time for a 3 km run was approximately 9 to 10 minutes. In some embodiments, the subject's age was approximately 18 to 45 years.

[0543] Medical treatment:

[0544] The formulations or compositions of the present invention can be used as medicines or medical foods. The formulations or compositions of the present invention can be used to treat muscle-related pathological conditions. Therefore, the present invention provides formulations or compositions of the present invention for treating muscle-related pathological conditions. The present invention also provides a method for treating a subject with muscle-related pathological conditions, the method comprising administering an effective amount of the formulation or composition of the present invention to the subject. Muscle-related pathological conditions include both conditions that generally affect healthy individuals and pathological conditions. Such muscle conditions found in healthy individuals or those affected by disease include musculoskeletal diseases or conditions; cachexia; muscle wasting; myopathy; age-related decline in muscle function; pre-debilitation; debility; neuromuscular diseases such as Duchenne muscular dystrophy and other malnutritions; sarcopenia, such as acute sarcopenia; muscle atrophy and / or cachexia, such as muscle atrophy and / or cachexia associated with burns, bed rest, limb immobilization, or major chest, abdominal, and / or orthopedic surgery; and degenerative muscle diseases.

[0545] Examples of age-related diseases that can be treated with the formulations or compositions of the present invention include sarcopenia and muscle wasting.

[0546] Muscle performance:

[0547] The formulations or compositions of the present invention can be used to enhance muscle performance. Therefore, the present invention provides formulations or compositions of the present invention for enhancing muscle performance. The present invention also provides a method for enhancing muscle performance by administering an effective amount of the formulations or compositions of the present invention to a subject. Administerment may be self-administered.

[0548] Enhanced muscle performance can be caused by improvements in one or more muscle functions, reduced muscle function decline, improved muscle strength, improved muscle endurance, and improved muscle recovery.

[0549] Therefore, the formulations or compositions of the present invention can be used to improve physical endurance (e.g., the ability to perform physical tasks such as exercise, manual labor, sports activities, etc.), inhibit or delay physical fatigue, enhance work capacity and endurance, and reduce muscle fatigue.

[0550] Improved muscle function may be particularly beneficial for older subjects whose muscle function declines due to age-related conditions. For example, subjects who may benefit from improved muscle function may have experienced muscle decline, which then leads to pre-frailty and frailty. Such subjects do not necessarily experience muscle wasting in addition to their muscle decline. Some subjects do experience muscle wasting and muscle decline, such as those with sarcopenia. The formulations or compositions of the present invention can be used to enhance muscle performance by administering the compositions of the present invention to frail or pre-frail subjects.

[0551] Muscle performance can be considered athletic performance, that is, an athlete's ability to utilize their muscles during physical activity. Improvements in athletic performance, intensity, speed, and endurance are measured by increases in the strength of muscle contractions, the amplitude of muscle contractions, or the shortening of the muscle response time between stimulus and contraction. An athlete is an individual participating in any level of sport who seeks to improve their strength, speed, or endurance levels in their performance; examples include bodybuilders, cyclists, long-distance runners, and sprinters. Improved athletic performance manifests as the ability to overcome muscle fatigue, the ability to sustain activity for extended periods, and more effective training.

[0552] animal

[0553] The compositions of this invention are applicable to mammals other than humans, appropriately adjusted to the size of non-human mammals. For example, adjustments can be made according to the following table:

[0554]

[0555] Therefore, according to another aspect of the invention, a composition for use in non-human mammals is provided, wherein the dosage is adjusted according to the table above.

[0556] formulations and compositions

[0557] The use and methods of the present invention preferably relate to the oral administration of the aqueous formulations of the present invention. Aqueous formulations typically include additional excipients. Therefore, the formulation or composition is administered in the form of an oral formulation and one or more excipients suitable for oral administration. Oral compositions are typically provided in powder or tablet form for dispersion in an aqueous medium, such as water, milk, or energy or sports drinks.

[0558] In other embodiments of the invention, the formulation of the invention is administered by any method of administration known to those skilled in the art, such as intramuscular, sublingual, skin, and ocular administration. Oral administration is preferred.

[0559] Aqueous formulations can be in the form of pharmaceuticals, medicinal foods, dietary supplements, or beverages, each intended for oral consumption. Aqueous formulations can be solutions, emulsions, slurries, or other semi-liquids. For example, excipients in liquid compositions can provide shelf life, visual appearance, flavor, and mouthfeel, resulting in an acceptable taste, appealing appearance, and good storage stability. With some degree of dilution, subjects may need to shake the beverage before consumption to maintain a uniform suspension of the active ingredient.

[0560] In some preferred embodiments, the use or method comprises applying a formulation containing a micronized form of a compound of formula (I) or a salt thereof (e.g., urolithin A). Micronization allows the compound of formula (I) to disperse or dissolve more quickly. Micronization can be achieved by methods established in the art, such as compression milling, hammer milling, general or pin milling, or jet milling (e.g., helical jet milling or fluidized bed jet milling). Jet milling is particularly suitable. If a micronized compound is used, preferably, the D of the compound... 50 The particle size is less than 100 μm, meaning that, by mass, 50% of the compounds have a particle size less than 100 μm. More preferably, the compound's D... 50 The size is less than 75 μm, for example less than 50 μm, for example less than 25 μm, for example less than 20 μm, for example less than 10 μm. More preferably, the compound's D 50 Within the range of 0.5-50 μm, for example 0.5 μm to 20 μm, for example 0.5 μm to 10 μm, for example 1.0 μm to 10 μm, for example 1.5 μm to 7.5 μm, for example 2.8 μm to 5.5 μm. Preferably, the compound's D 90 Size less than 100 μm. More preferably, the compound's D 90 The size is less than 75 μm, for example less than 50 μm, for example less than 25 μm, for example less than 20 μm, for example less than 15 μm. The compound preferably has a D... 90 Within the range of 5 μm to 100 μm, for example 5 μm to 50 μm, for example 5 μm to 20 μm, for example 7.5 μm to 15 μm, for example 8.2 μm to 16.0 μm. Preferably, the compound's D 10 Within the range of 0.5 - 1.0 µm. Preferably, the D-type of the compound of formula (I) or its salt (e.g., urolithin A) is... 90 Within the range of 8.2 µm to 16.0 µm, D 50 Within the range of 2.8 µm to 5.5 µm and D 10 Within the range of 0.5 µm to 1.0 µm.

[0561] In another embodiment, the size distribution of the compound of formula (I) or its salt is selected from one of the following:

[0562] (i) D in the range of 0.5 μm to 50 μm 50 Size and D in the range of 5 μm to 100 μm 90 size,

[0563] (ii) The D of the compound 90Sizes ranging from 8.2 μm to 16.0 μm, D 50 Sizes range from 2.8 μm to 5.5 μm and D 10 Size ranges from 0.5 μm to 1.0 μm;

[0564] (iii) D of compound (I) 50 Sizes ranging from 0.5 μm to 20 μm and D 90 Sizes range from 5 μm to 50 μm;

[0565] (iv) D of compound (I) 50 Size less than 50 μm and D 90 Size less than 75 μm;

[0566] (v) D of compound (I) 50 Size less than 25 μm and D 90 Size less than 50 μm;

[0567] (iv) D of compound (I) 50 Size less than 10 μm and D 90 Size less than 20 μm;

[0568] (v) D of compound (I) 50 Size less than 10 μm and D 90 Size less than 15 μm; or

[0569] (vi) Formula (I) Compound D 50 Size is 10 μm and D 90 The size is 20 μm.

[0570] The term 'about' refers to a tolerance of ±20% of the relevant value, for example, ±15% of the relevant value, such as ±10% or ±5% of the relevant value.

[0571] The term "elite" athlete can refer to VO 2max Greater than 65 mL Kg -1 min -1 Subjects whose personal best time for a 3 km run was less than 9 minutes or both.

[0572] The term 'excipient' refers to a substance formulated together with an active ingredient, including, for example, to swell a solid formulation containing a small amount of potent active ingredient for long-term stability (hence often referred to as a 'filler,' 'diluent,' or 'filler') or to impart therapeutic enhancements to the active ingredient in the final dosage form (such as promoting absorption, reducing viscosity, or enhancing solubility).

[0573] The term 'healthy lifespan' refers to the period of an individual's life during which they are generally healthy and free from serious or chronic diseases.

[0574] As used in this article, the term "lifespan" refers to the lifespan of an individual organism, such as a human being.

[0575] The term "pharmaceutical acceptable" means that a substance approved by a federal or state regulatory agency or listed in the United States Pharmacopeia or other recognized pharmacopoeia for use in animals, and more specifically for use in humans.

[0576] The term "sub-elite" athlete can refer to VO (Volume Olympiad) athletes. 2max 60 mL Kg -1 min -1 Up to 65 mL Kg -1 min -1 Subjects whose personal best time for a 3 km run was 9 to 10 minutes or both.

[0577] As used herein, the term "therapeuticly effective amount" refers to an amount of one or more compounds that, when administered, is sufficient to prevent the development of one or more symptoms of the targeted disease or to alleviate those symptoms to some extent. The specific dosage of each compound administered according to the invention will, of course, be determined by the specific conditions surrounding the case, including the compound administered, the route of administration, the specific circumstances of the treatment, and considerations such as the age, weight, and sex of the treated subject.

[0578] To avoid any ambiguity, when the text refers to the ratio between X and Y, the ratio includes the exact values ​​of X and Y, except when it immediately follows X and immediately precedes Y.

[0579] To avoid any doubt, when the description of the invention relates to the use of the compositions of the invention, the description also relates to the use of the formulations of the invention.

[0580] equivalent

[0581] The invention is described broadly and generally herein. Various other means and / or structures for performing the functions described herein and / or obtaining these results and / or one or more of these advantages will readily conceive of those skilled in the art, and each of such variations and / or modifications is considered to be within the scope of the invention. More generally, those skilled in the art will readily recognize that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and actual parameters, dimensions, materials, and / or configurations will depend on one or more specific applications in which the teachings of the invention are applied. Those skilled in the art will recognize, or use, many equivalents of the specific embodiments of the invention described herein that can be determined only through routine experimentation. Therefore, it should be understood that the foregoing embodiments are described by way of example only, and that the invention may be practiced in ways different from the specific description and requirements within the scope of the appended claims and their equivalents. The invention relates to each individual feature, system, article, material, kit, and / or method described herein. Furthermore, any combination of two or more such features, systems, articles, materials, kits, and / or methods, provided that such features, systems, articles, materials, kits, and / or methods do not contradict each other, is included within the scope of the invention. Furthermore, each of the more specific types and subgroups falling within the general disclosure also forms part of this invention. This includes the general description of the invention, which is conditionally or negatively limited to the removal of any subject matter from the subgenus, regardless of whether the removed material is specifically described herein.

[0582] By incorporating via reference

[0583] The contents of any articles, patents, and patent applications mentioned or cited herein, as well as all other documents and electronically available information, are hereby incorporated in their entirety by reference as if each separate publication were 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.

[0584] The invention will now be described with reference to the following non-limiting embodiments.

[0585] Figure 1 The plasma pharmacokinetic parameters of the maltodextrin formulation tested after a single oral dose are shown, as well as the plasma concentrations of urolithin A at different time points before and after administration.

[0586] Example 1: Urolithiasis A Solubility Test

[0587] method

[0588] Experiments were conducted to identify components that could improve the solubility of urolithin A. Three different components that could be identified as candidate carriers were tested. Urolithin A was mixed in different ratios to find the optimal dry mixture that is soluble in water, as shown below.

[0589] The following downloader was tested:

[0590] Carrier 1: Maltodextrin DE 10 Maltrin M100

[0591] Carrier 2: Maltodextrin DE 10 Maltrin QD M500 (aggregation)

[0592] Carrier 3: Organic gum arabic - TICORGANIC spray dry powder

[0593] Use the following ratio:

[0594]

[0595] In the experiment, 1 g of urolithin A was used per sample, as shown below:

[0596]

[0597] In the experiment, the dry mixture was mixed in 200 mL of room temperature water (22°C).

[0598] result:

[0599]

[0600] Results and discussion

[0601] Matrin QD M500 exhibits optimal solubility when mixed with urolithin A at a 2:1 ratio. It is designed for use in dry blends of instant beverages and performs very well. Maltrin M100 can be used in dry blends, but requires vigorous stirring, and some lumps may still form on the surface. Gum arabic is not designed as a carrier for dry blends and is difficult to use.

[0602] Example 2: A Phase II study to determine the bioavailability of urolithin A in human subjects when administered in the form of maltodextrin formulations.

[0603] A phase II clinical trial was conducted to determine the bioavailability of urolithin A when administered to human subjects in the form of a formulation containing maltodextrin.

[0604] Specifically, the pharmacokinetic parameters of the compound were investigated in an open-label, parallel-group, randomized, single-time-period, single-dose pharmacokinetic study. Subjects were recruited from healthy male and female volunteers aged 18 to 45 years. Compound details and clinical procedures are described in the Methods section below.

[0605] Subjects were administered a single oral dose of the maltodextrin formulation (Table 2). The formulation was administered to deliver a total dose of 500 mg urolithin A per dose. Plasma samples were collected at consecutive time points before and after administration: 1 hour, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, and 72 hours. Maternal plasma urolithin A levels were determined and expressed as pg / ml.

[0606] Surprisingly, the maltodextrin formulations exhibited surprisingly good pharmacokinetic profiles. Table 1 and Figure 1 The pharmacokinetic results shown demonstrate that the formulation containing maltodextrin is highly bioavailable. The Tmax was 1397 pg / ml at 6 hours, the Cmax was 1397 pg / ml, and the total AUC (area under the curve) was 1283 pg / mL / hr.

[0607] Table 1. Blood urolithiasis concentrations (mean ± standard deviation), n = 12 subjects

[0608]

[0609] method:

[0610] Research participants

[0611] The study recruited a total of 24 participants (12 participants in each group). Participants were healthy male and female participants. Participants were selected after screening and met all of the following criteria: age between 18 and 45 years; body mass index (BMI) between 18.50 and 30.00 kg / m².

[0612] Test product information and dosage

[0613] Maltodextrin formulation (urolithin A powder containing maltodextrin): half a scoop (1.5 g) of powder containing 500 mg of urolithin A. The composition is described in Table 2.

[0614] Administration: After an overnight fast, participants should take the powder orally in a seated, empty stomach. Mix the powder with 240 ± 2 mL of milk, shake well, and consume. Ensure all liquid is swallowed and no residue remains in the mouth.

[0615] Table 2. Composition of the research product – Professional athlete muscle recovery powder containing maltodextrin

[0616]

[0617] Food and fluid intake

[0618] Fasting for at least 12 hours prior to administration and for at least 4 hours after administration is required. Participants should maintain standard fluid intake throughout the study. Fluid intake should be maintained between approximately 3 and 3.5 liters for up to 24 hours to ensure adequate urine flow from the hospital day to the ambulatory visit day. Water intake should be restricted (no fluids except for water given at the time of administration) for at least 1 hour before administration and for at least 1 hour after administration.

[0619] During the study period, participants consumed only the food provided while confined to the clinical facility (hospital). At least 4 hours after administration, all participants were provided with a standard meal (a vegan balanced diet of protein, carbohydrates, and fats recommended by the hospital nutritionist). Additional meals / snacks were provided at appropriate times after 4 hours of administration.

[0620] Participants were prohibited from consuming foods rich in urolithin A precursors, starting at least seven days before their admission to the inpatient facility and continuing until the end of their outpatient visits. These foods included fruits such as pomegranates, peaches, persimmons, and plums, as well as nuts such as walnuts, hazelnuts, pistachios, acorns, chestnuts, pecans, almonds, and peanuts. Additionally, participants avoided berries such as strawberries, raspberries, blackberries, blueberries, cloudberries, and camu camu, as well as mascarpone grapes, oak-aged wines and spirits, medicinal herbs and decoctions (such as geraniums and oak leaves), and their derivatives such as juices, jams, and jellies.

[0621] Participants are advised to avoid consuming dietary supplements that may affect muscle or mitochondrial function, such as resveratrol, pomegranate and ellagitannins, nicotinamide nucleoside, whey protein, leucine, isoleucine, L-carnitine, creatine, coenzyme Q10, vitamin A, niacin, folic acid, vitamin C, vitamin E, and probiotic foods and supplements, for two weeks prior to enrollment and throughout the study.

[0622] In another embodiment, the compositions and formulations of the present invention further comprise an electrolyte.

[0623] Clinical research methods

[0624] This study was an open-label, parallel-group, single-time-period, single-dose, randomized study in which each participant received an oral dose of the study product while seated. The formulation was administered while seated with approximately 240 mL of whole milk (3% fat content).

[0625] Study duration

[0626] ● Screening and assessment (Day -29 to Day -2)

[0627] ●Day 1: Hospitalization

[0628] ●Day 01: Administration (on the day of administration) / PK sample collection

[0629] ●Day 02: Collect / release PK samples from the study site.

[0630] ●Day 4: PK Sample Collection / End of Study

[0631] The trial was conducted in accordance with the Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects, 64th World Medical Association Congress, Fortaleza, Brazil, October 2013), ICH-GCP, AYUSH Good Clinical Practice, New Drugs and Clinical Trials Rules, 14 October 2022, Indian Ministry of Health and Family Welfare, Indian Council of Medical Research (Ethical Guidelines for Biomedical Research Involving Human Subjects, 2017), and other applicable regulatory requirements.

[0632] Pharmacokinetic blood sampling:

[0633] PK blood samples were collected before administration and at 1, 4, 6, 8, 12, 24, and 72 hours after administration. PK blood samples were collected via direct venipuncture or using an intravenous cannula. When multiple blood samples were scheduled to be collected from the same participant on the same day, the investigator decided at their discretion to insert the intravenous cannula and collect blood samples from it to avoid multiple punctures. Similarly, an intravenous (IV) cannula was placed in a vein in the participant's forearm or on the back of the hand. The indwelling IV cannula was held in place for the required time by injecting 0.3 mL of normal saline or heparinized saline (to prevent cannula clogging). Because the cannula contained stagnant blood and normal or heparinized saline, it was removed before collecting the pharmacokinetic blood sample, and similarly, 0.3 mL (or as appropriate depending on the size and length of the cannula) of blood diluted with normal saline / heparinized saline was discarded before collecting the next PK sample. If the indwelling cannula became clogging or malfunctioning, the investigator decided at their discretion to remove it and perform a reintubation procedure, or to collect blood samples via direct venipuncture. Collect or transfer all PK blood samples (if collected in a syringe) into a K2-EDTA blood collection tube.

[0634] plasma sample transportation

[0635] The samples were sent to the laboratory for pharmacokinetic parameter analysis. Transportation was carried out using a specialized carrier on dry ice. Temperature was monitored throughout the transportation process using a data logger.

[0636] Bioanalytical methods

[0637] After collection, PK blood samples were centrifuged at 4000 RPM for 10 minutes at 4°C ± 2°C. Plasma was separated and transferred to labeled polypropylene tubes and stored at -80°C ± 10°C. Pharmacokinetic parameters of urolithin A were calculated from concentration-v / time data using Phoenix® WinNonlin® professional software (version 8.1.1 or later) (Certara, Princeton, New Jersey, USA).

Claims

1. A composition for mixing with water, said composition comprising: (a) A compound of formula (I) or a salt thereof; （I） in: A, B, C, D, W, X, Y, and Z are each independently selected from H and OH; and (b) Maltodextrin.

2. The composition according to claim 1, comprising: (a) about 25% (w / w) to about 50% (w / w) of compound (I); and (b) Approximately 50% (w / w) to approximately 75% (w / w) maltodextrin.

3. The composition according to claim 1, comprising: (a) 1 part by weight of compound (I); and (b) About 1 part by weight to about 3 parts by weight of maltodextrin.

4. The composition according to claim 1, comprising: (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and (b) Maltodextrin in the range of about 100 mg to about 6000 mg, such as agglomerated maltodextrin. The weight ratio of compound (I) to maltodextrin is between any of the following: (i) Approximately 1:1 to approximately 1:3; (ii) about 1:1.5 to about 1:2.5; or (iii) Approximately 1:2.5 to approximately 1:3.

5.

5. The composition according to claim 1, comprising: (a) Compounds of formula (I) ranging from about 100 mg to about 2000 mg, such as urolithin A; and (b) Maltodextrin in the range of about 150 mg to about 5000 mg, such as agglomerated maltodextrin. The weight ratio of compound (I) to maltodextrin is about 1:1.5 to about 1:2.

5.

6. The composition according to claim 1, comprising: (a) Compounds of formula (I) ranging from about 500 mg to about 1500 mg, such as urolithin A; and (b) Maltodextrins in the range of about 750 mg to about 3750 mg, such as agglomerated maltodextrin. The weight ratio of compound (I) to maltodextrin is about 1:1.5 to about 1:2.

5.

7. An aqueous formulation comprising: (a) The compound of formula (I) according to claim 1, or a salt thereof; and (b) Maltodextrin.

8. The aqueous formulation according to claim 7, comprising... (a) 1 part by weight of compound (I); and (b) About 1 part by weight to about 3 parts by weight of maltodextrin.

9. The aqueous formulation according to claim 7, comprising: (a) about 100 mg to about 2000 mg of a compound of formula (I) or a salt thereof; and (b) Approximately 100 mg to approximately 6000 mg of maltodextrin. The weight ratio of compound (I) to maltodextrin is between any of the following: (a) Approximately 1:1 to approximately 1:3; (b) about 1:1.5 to about 1:2.5; or (c) Approximately 1:2.5 to approximately 1:3.

5.

10. The aqueous formulation according to claim 7, comprising: (a) about 100 mg / L to about 8000 mg / L of compound (I); and (b) Approximately 100 mg / L to approximately 24 g / L of maltodextrin.

11. The aqueous formulation according to claim 7, comprising any one of the following: （i） (a) about 0.4 mmol to about 8.8 mmol of compound (I); and (b) Approximately 0.06 mmol to approximately 3.66 mmol of maltodextrin; Or (ii) (a) about 0.8 mmol to about 17.6 mmol of compound (I); and (b) Approximately 0.12 mmol to approximately 7.31 mmol of maltodextrin; Or (iii) (a) about 0.4 mmol to about 8.8 mmol of compound (I); and (b) Approximately 0.24 mmol to approximately 7.32 mmol of maltodextrin.

12. A sports drink further comprising the composition according to any one of claims 1 to 6.

13. The aqueous formulation according to claim 7, comprising any one of the following: （i） (a) about 0.4 mmol to about 8.8 mmol of compound (I); and (b) Approximately 14.7 mmol to approximately 128 mmol of maltodextrin; Or (ii) (a) about 0.8 mmol to about 17.6 mmol of compound (I); and (b) Approximately 29.4 mmol to approximately 256 mmol of maltodextrin; Or (iii) (a) about 1.6 mmol to about 35.2 mmol of compound (I); and (b) Approximately 58.8 mmol to approximately 512 mmol of maltodextrin.

14. The formulation or composition according to any one of the preceding claims, wherein the compound of formula (I) is selected from urolithin A, urolithin B, urolithin C and / or urolithin D, for example urolithin A.

15. The formulation or composition according to any one of the preceding claims, wherein the maltodextrin has a DE (glucose equivalent) between about 5 and about 15, for example, a DE of about 10.

16. The formulation or composition according to any one of the preceding claims, wherein the maltodextrin is an aggregated maltodextrin.

17. The formulation or composition according to any one of the preceding claims, used for: a) Methods to increase or maintain mitochondrial function; b) Treatment, prevention, or management of mitochondrial-related symptoms associated with altered mitochondrial function or decreased mitochondrial density; and / or c) Treatment, prevention, or management of mitochondrial-related diseases.

18. A method for enhancing muscle performance, the method comprising administering to a subject a formulation or composition, such as that claimed in any one of claims 1 to 16, wherein the enhancement of muscle performance is selected from one or more of the following: improved muscle function, reduced muscle function decline, improved muscle strength, improved muscle endurance, and improved muscle recovery.

19. A method for improving, maintaining, or reducing muscle function loss, the method comprising administering to a subject a formulation or composition according to any one of claims 1 to 16.

20. A method for increasing muscle strength, increasing or maintaining muscle mass, or muscle recovery, the method comprising administering to a subject a formulation or composition according to any one of claims 1 to 16.

21. A method for improving athletic performance, physical performance, and / or endurance, the method comprising administering to a subject a formulation or composition according to any one of claims 1 to 16.

22. A method for inhibiting or delaying physical fatigue, enhancing work capacity and endurance, and reducing muscle fatigue, the method comprising administering to a subject a formulation or composition according to any one of claims 1 to 16.

23. A method to enhance the following: a) Physical manifestations; b) Physical recovery; and / or c) Physical endurance; The method comprises administering to a subject, such as an elite or sub-elite athlete, the formulation or composition according to any one of claims 1 to 16.

24. The method for enhancing physical performance according to claim 23, wherein enhancing physical performance comprises at least one effect selected from the group consisting of: enhancing athletic performance, enhancing running performance, enhancing muscle performance, enhancing aerobic endurance, enhancing perceived exertion, reducing post-exercise fatigue, enhancing muscle recovery, reducing exercise-induced muscle damage, reducing muscle soreness, and enhancing the repair of exercise-induced muscle damage.

25. The method for enhancing physical recovery according to claim 23, wherein enhancing physical recovery comprises at least one effect selected from the group consisting of: enhancing muscle recovery, enhancing athletic performance, enhancing running performance, enhancing muscle performance, enhancing aerobic endurance, enhancing perceived exertion, reducing post-exercise fatigue, enhancing muscle recovery, reducing exercise-induced muscle damage, reducing muscle soreness, and enhancing the repair of exercise-induced muscle damage.

26. The method for enhancing physical endurance according to claim 23, wherein enhancing physical recovery comprises at least one effect selected from the group consisting of: enhancing muscle recovery, enhancing athletic performance, enhancing running performance, enhancing muscle performance, enhancing aerobic endurance, enhancing perceived exertion, reducing post-exercise fatigue, enhancing muscle recovery, reducing exercise-induced muscle damage, reducing muscle soreness, and enhancing the repair of exercise-induced muscle damage.

27. The composition or formulation according to any one of claims 1 to 16, for maintaining or enhancing skin health and / or reducing the effects of aging over time on biological aging.

28. The composition or formulation according to any one of claims 1 to 16, for maintaining or enhancing hair health.

29. The composition or formulation according to any one of claims 1 to 16, for maintaining or enhancing immune health.

30. The composition or formulation according to any one of claims 1 to 16, for maintaining or enhancing brain health.

31. The composition or formulation according to any one of claims 1 to 16, used for maintaining or enhancing recovery after treatment.

32. The composition or formulation according to any one of claims 1 to 16, for increasing healthy lifespan.

33. The composition or formulation according to any one of claims 1 to 16, for slowing aging and / or increasing lifespan.

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