Compositions and methods for stabilizing at least one urolithin in an aqueous matrix using xanthan gum

Abstract

The present invention discloses a powder, which comprises xanthan gum and at least one urolithin, such as urolithin A; and the powder can be reconstituted in a liquid (such as water) to form a liquid composition for oral consumption, such as a beverage. The xanthan gum can keep most of at least one urolithin suspended in the beverage. The resulting liquid composition for oral consumption, as well as methods for preparing the powder, preparing the liquid composition for oral consumption, and prophylactic or therapeutic use of the powder or liquid composition are another aspect of the present disclosure.

Description

Background Art

[0001] The present disclosure generally relates to compositions and methods for using xanthan gum to stabilize at least one urolithin (e.g., urolithin A) in an aqueous matrix. For example, the compositions and methods disclosed herein can suspend the water-insoluble functional ingredient urolithin A in a beverage, such as a beverage made by reconstituting a powder containing at least a portion of urolithin A in water.

[0002] Urolithins are metabolites of ellagic acid, punicalagin (PA), punicaloside (PB), tellimagrandin (TL), and other ellagitannins (Cerda, Espin et al., 2004; Cerda, Periago et al., 2005). When these metabolites are absorbed, they undergo glucuronidation, and after reaching the liver, they are further metabolized to produce glucuronides and / or sulfates. Urolithin compounds can be used to treat and prevent various conditions, such as by enhancing muscle function. Summary of the Invention

[0003] The present disclosure addresses the inventors' recognition that urolithin A (UA) is insoluble in water, presenting a challenge for powders containing UA as a main functional ingredient to keep UA in suspension when the powder is reconstituted with water. In this regard, the insoluble UA almost immediately promotes the sedimentation of UA at the bottom of the reconstitution container. The present disclosure includes various ways to stabilize urolithin A in an aqueous matrix such that when a powder containing UA is reconstituted, UA remains in suspension.

[0004] Additional features and advantages are described herein and will be apparent from the following drawings and detailed description. Brief Description of the Drawings

[0005] Figure 1 The structural formula of urolithin is described, where A, B, C, and D are each independently selected from H and OH; W, X, and Y are each independently selected from H and OH; and Z is selected from H and OH.

[0006] Figure 2 The structural formula of urolithin A (UA) is described.

[0007] Figure 3A and Figure 3B is a table showing the results of the first experimental example disclosed herein, where various gums are tested in the presence and absence of citric acid with urolithin A.

[0008] Figure 4A and Figure 4B is a table showing the results of the second experimental example disclosed herein, where various gums are tested in the presence of citric acid with urolithin A.

[0009] Figure 5 It is a table showing the results of the third experimental example discussed herein, where different amounts of xanthan gum are tested in the presence of urolithin A and citric acid.

[0010] Figure 6A-6D It is a table showing the results of the fourth experimental example disclosed herein, where the stability of urolithin A and lemon - flavored or raspberry - pomegranate - flavored powders of xanthan gum is tested.

[0011] Figure 7 It is a table of suspensions of urolithin A in different milk - based beverages in the presence of xanthan gum.

[0012] Figure 8 It is a table of suspensions of urolithin A in different fruit - based beverages or carbonated beverages in the presence of xanthan gum.

[0013] Figure 9 It is a table of the effect of different levels of xanthan gum on urolithin A in the presence of creatine. Detailed Description

[0014] Definition

[0015] Some definitions are provided below. However, the definitions may be located in the "Embodiments" section below, and the above - titled "Definitions" does not imply that such disclosures in the "Embodiments" section are not definitions.

[0016] All percentages represented herein are by weight based on the total weight of the composition, unless otherwise indicated. As used herein, "about", "approximately", and "substantially" should be understood to refer to a number within a range of a numerical value, for example, within the range of - 10% to + 10% of the recited numerical value, preferably within the range of - 5% to + 5% of the recited numerical value, more preferably within the range of - 1% to + 1% of the recited numerical value, and most preferably within the range of - 0.1% to + 0.1% of the recited numerical value. All numerical ranges herein should be understood to include all integers or fractions within the range. Additionally, these numerical ranges should be understood to provide support for claims involving any number or subset of numbers within the range. For example, the disclosure of 1 to 10 should be understood to support ranges such as 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0017] As used in this disclosure and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a urolithin" or "the urolithin" refers to "at least one urolithin" and includes two or more urolithins.

[0018] The terms “comprising” and “including” shall each be construed as inclusive rather than exclusive. Similarly, the terms “comprising” and “including” and “or” shall all be regarded as inclusive unless the context clearly dictates otherwise. However, the compositions disclosed herein may exclude any element not specifically disclosed herein. Thus, the disclosure of an embodiment using the term “comprising” includes the disclosure of an embodiment “consisting essentially of the specified components” and the disclosure of an embodiment “consisting of the specified components”.

[0019] The terms “at least one” and “and / or” used in the respective contexts of “at least one of X or Y” and “X and / or Y” shall be construed as “X” or “Y” or “X and Y”. For example, “at least one of urolithin A or urolithin C” shall be construed as “urolithin A, without urolithin C” or “urolithin C, without urolithin A” or “both urolithin A and urolithin C”.

[0020] As used herein, the terms “example” and “such as” (especially when followed by a list of terms) are merely exemplary and illustrative and should not be regarded as exclusive or exhaustive. As used herein, a condition is “associated with” or “linked to” another condition if the conditions occur concurrently, preferably means that the conditions are caused by the same underlying condition, and most preferably means that one of the identified conditions is caused by the other identified condition.

[0021] A “liquid composition” can be a suspension, solution, emulsion, slurry, or other semi-solid liquid. The term “beverage” refers to a liquid composition intended for oral ingestion by an individual (such as a human) and that provides at least one nutrient to the individual. The beverage optionally contains at least one of the following: protein, lipid, carbohydrate, or one or more vitamins and minerals. The compositions of the present disclosure (including the various embodiments described herein) may contain, consist of, or consist essentially of the elements disclosed herein, as well as any additional or optional ingredients, components, or elements described herein or that can be used in a diet.

[0022] As used herein, the term “powder” refers to a substantially uniform plurality of solid particles having a moisture content of less than 5.0% by weight, preferably less than 4.0% by weight, more preferably less than 3.0% by weight, even more preferably less than 2.0% by weight, and most preferably less than 1.0% by weight.

[0023] "Prevention" includes reducing the risk and / or severity of a disease or disorder. The terms "treatment" and "alleviation" include both prophylactic or preventive treatment (preventing and / or delaying the development of a target pathological disease or disorder), and curative, therapeutic or disease-modifying treatment, including therapeutic measures to cure, delay, relieve the symptoms of a diagnosed pathological disease or disorder and / or interrupt its progression; and treating patients at risk of infection or suspected of being infected, as well as treating patients suffering from or diagnosed with a disease or medical condition. The term does not necessarily imply that the subject is treated until complete recovery. The term "treatment" also refers to health maintenance and / or promotion in individuals who do not have a disease but may be predisposed to developing an unhealthy condition. The terms "treatment" and "alleviation" also aim to include potentiating or otherwise enhancing one or more primary prophylactic or therapeutic measures. The terms "treatment" and "alleviation" also aim to include dietary management of a disease or disorder or dietary management for preventing or precluding a disease or disorder. Treatment can be patient-related or physician-related.

[0024] As used herein, a " therapeutically effective amount" or a " prophylactically effective amount" is an amount that prevents a deficiency in an individual, treats its disease or medical condition, or more generally, alleviates an individual's symptoms, manages the progression of its disease, or provides a nutritional, physiological, or medical benefit. When used to refer to the stability of the liquid compositions disclosed herein (liquid compositions comprising xanthan gum and at least one urolithin), the relative terms " improved", " increased", " enhanced", etc. mean that more of at least one urolithin is in suspension relative to a composition that does not contain xanthan gum (e.g., is replaced with another gum), but is otherwise identical and reconstituted under the same conditions. As used herein, " enhancing" at least one of muscle performance or mental performance means enhancing or inducing relative to the level prior to administration of the compositions disclosed herein.

[0025] The term " unit dosage form" as used herein refers to physically discrete units suitable as unit doses for human and animal subjects, each unit containing a predetermined quantity of the composition disclosed herein, associated with a pharmaceutically acceptable diluent, carrier, or vehicle, in an amount sufficient to produce the desired effect. The specifications of the unit dosage form depend on the particular compound used, the effect to be achieved, and the pharmacodynamics associated with each compound in the host.

[0026] " Subject" or " individual" is a mammal, preferably a human.

[0027] Embodiment

[0028] Ellagitannins and ellagic acid are compounds commonly found in foods such as pomegranates, nuts, and berries. Ellagitannins are minimally absorbed in the intestine itself. Urolithins are metabolites produced by the action of the intestinal microbiota of mammals (including humans) on ellagitannins and ellagic acid. Urolithins are a class of compounds having the aboveFigure 1 Compounds of the representative structures shown.

[0029] Any urolithin according to this structure can be used in the compositions and methods disclosed herein, and includes urolithins disclosed in the following patents: U.S. Patent No. 10,695,320, titled "Compositions Comprising Urolithin Compounds," published on June 30, 2020, and U.S. Serial No. 15 / 757,293, filed on August 26, 2016, which is incorporated herein by reference in its entirety, and U.S. Patent Application Publication No. 2018 / 0015069, titled "Enhancing Autophagy or Increasing Longevity by Administration of Urolithins or Precursors Thereof," published on January 18, 2018, and U.S. Serial No. 15 / 701,057, filed on September 11, 2017, which is also incorporated herein by reference in its entirety.

[0030] Particularly suitable compounds are naturally occurring urolithins. Thus, Z is preferably OH; and W, X, and Y are preferably all H.

[0031] Regarding particularly preferred urolithins, in urolithin C (UC): W, X, and Y are all H; and A and B are both H; and C, D, and Z are all OH. As Figure 2 shown, in urolithin A (UA): W, X, and Y are all H, and A, B, and C are all H; and D and Z are both OH. Preferably, the compositions and methods disclosed herein use at least one of urolithin A, urolithin B, urolithin C, or urolithin D, and even more preferably at least urolithin A (UA).

[0032] Comparative experimental data was generated to study the possibility of UA being stable in an aqueous matrix. Additionally, in this regard, it was found that UA is slightly soluble in oil. UA forms a good suspension in an oily matrix; but in a powder matrix, the oil powder does not suspend UA in the reconstituted beverage.

[0033] Example

[0034] Example 1: UA in suspension

[0035] Experiments were conducted to keep UA in suspension:

[0036] 1. The initially selected base material was brown rice syrup powder with UA added. Upon reconstitution, the UA will settle at the base of the container.

[0037] 2. UA forms a suspension in oil, so another experiment used brown rice syrup powder with canola oil powder and whey protein. This base material also did not achieve effective stability.

[0038] 3. A 100% canola oil powder base material was tried, which also did not provide effective stability.

[0039] 4. The expectation with lecithin and carrageenan was that they would stabilize the system, but this base material also did not achieve effective stability.

[0040] 5. MCT oil powder was used as the base material, but it did not provide effective stability.

[0041] Therefore, the conclusion is that the oil base material is not helpful in powder form. The UA will settle after reconstitution into an aqueous form, so the method becomes using gums to increase the viscosity of the reconstituted aqueous composition to keep the UA in suspension.

[0042] Specifically, different gums and gum concentrations were studied with UA and a filler of brown rice syrup powder:

[0043] 1. Guar gum

[0044] 2. PHGG

[0045] 3. A combination of guar gum and xanthan gum

[0046] 4. Acacia gum

[0047] 5. Gellan gum

[0048] 6. FMC gum blend

[0049] 7. Xanthan gum

[0050] Table 1 (below) lists the formulations of samples testing various gums with UA. Figure 3A and Figure 3B lists the results of these samples.

[0051]

[0052] Table 1

[0053] Some embodiments of the compositions disclosed herein include a fruit flavorant and thus include citric acid. Accordingly, the pH will be low in such compositions, and preferably protein can be excluded from the composition such that xanthan gum is stable and does not form a gel. Table 2 (below) lists the formulations of samples testing various gums with UA and citric acid.Figure 4A and Figure 4B lists the results of these samples.

[0054]

[0055]

[0056] Table 2

[0057] For each sample, after mixing the powder with water, after five minutes, the suspension was mixed again, and then the viscosity was measured. In various experiments, xanthan gum provided the best solution that not only kept UA in suspension but also had the desired viscosity, was easily soluble, and had no off-odor / odor in the product.

[0058] Then a range of xanthan gum amounts (Table 3 and Figure 5 ) was studied. In a specific non-limiting example, the final usage rate in the powder was 0.55 g xanthan gum / portion (4 g portion size) or 13.75 wt% in the powder. A range of 0.5 g to 0.65 g xanthan gum / portion (12.5 wt% to 16.25 wt% in the finished powder, dry weight basis) was effective, had a good taste and thickness, and UA could be well suspended when 4 g of the finished product was reconstituted in 8 fluid ounces of water.

[0059]

[0060] Table 3

[0061] Then stability was further tested in additional experiments, and Figure 6A-6D the results were listed. Specifically, the lemon-flavored powder of urolithin A and xanthan gum ( Figure 6A and Figure 6B ) and the raspberry-pomegranate flavored powder of urolithin A and xanthan gum ( Figure 6C and Figure 6D ) were tested as follows: 4 g of the powder was mixed in 8 fluid ounces of water and stirred well for 4 minutes, and the solution thickened and urolithin was well suspended; the reconstituted sample was allowed to stand at room temperature for 5 minutes; and the experiment was repeated for each flavor. As the results showed, the reconstituted urolithin remained well suspended even after standing at room temperature for 5 minutes.

[0062] Example 2: Urolithin stabilized with xanthan gum in reconstituted milk-based beverage

[0063] Xanthan gum can be used to stabilize urolithin A in reconstituted beverages. Experiments were conducted to observe the use of xanthan gum and some bulking agents (brown rice syrup powder) to stabilize urolithin A in other milk-based and fruit-based / carbonated beverages.

[0064] Experiments were also conducted to observe the stabilization of urolithin A in milk- and fruit-based / carbonated beverages using xanthan gum and some bulking agents (brown rice syrup powder) in the presence of creatine.

[0065] For milk-based beverages, Figure 7 different experiments and the observations are shown.

[0066] The results showed that urolithin A and xanthan gum could be added together with the bulking agent to milk-based beverages. The addition of urolithin A, brown rice syrup powder, and creatine had no effect on the taste. However, there was some effect on the mouthfeel, and using a higher amount of brown rice syrup powder as a bulking agent improved the mouthfeel. The gum did form some gel-like particles, which somewhat changed the mouthfeel. Experiments were conducted with whole milk, skim milk, Boost Vanilla RTD, Boost Chocolate RTD, and Muscle Milk (chocolate).

[0067] Example 3: Urolithin stabilized with xanthan gum in fruit-based beverage or carbonated beverage

[0068] Figure 8 The results in showed that urolithin A and xanthan gum could be added together with the bulking agent to fruit-based beverages or carbonated beverages. Urolithin A, the bulking agent, and xanthan gum had no effect on the taste, but the addition of creatine had a slight effect on the taste. The sourness seemed to be mild. The thickness of the product increased, and thus the mouthfeel also increased. Urolithin A had an effect on the color. In the case of carbonated beverages, some carbonation was lost due to agitation and thickening during agitation. This study was conducted on Gatorade, lemon juice, orange juice, sparkling water, and cola.

[0069] Example 4: Urolithin stabilized with xanthan gum and creatine in milk-based beverage

[0070] Creatine is a natural substance produced by our body by converting the amino acids glycine, arginine, and methionine contained in our food. Additional creatine can also be absorbed directly through our food, especially from fish and meat. Those who do not have a balanced diet and eat little fish and meat may have lower levels of creatine in their body.

[0071] Athletes who need additional creatine for muscle growth and faster recovery times after intense training can benefit from creatine supplementation in the form of dietary supplements. Food supplements containing creatine have been shown to have a positive effect on the energy supply to muscle cells during and between exercise sessions.

[0072] Creatine monohydrate dissolves slightly more slowly in cold water or other cold beverages. It is recommended to take creatine with a sugary beverage (e.g., grape juice) or with a meal, as your body's muscles can absorb creatine more easily when insulin is present. Figure 9Describes the effect of different levels of xanthan gum on urolithin A in the presence of creatine.

[0073] The creatine monohydrate used in the study was from Alzchem (trade name Creapure).

[0074] Each finished powder product (6 g portion) was developed using 250 mg of urolithin A and 1.5 g of creatine. Reconstituted to a 6 g portion mixed in 8 fluid ounces of water. The excess of creatine was 15%.

[0075] Xanthan gum was used to stabilize the formulation, and its range was 0.6 - 0.85 g / 6 g portion (10% - 14.17%).

[0076] This experiment also showed similar observations as in Example 2 above in the presence of added creatine, but thickened due to the thickening of the gum over time.

[0077] Example 5: Urolithin stabilized with xanthan gum and creatine in fruit-based beverage / carbonated beverage

[0078] The creatine monohydrate used in the study was from Alzchem (trade name Creapure).

[0079] Each finished powder product (6 g portion) was developed using 250 mg of urolithin A and 1.5 g of creatine. Reconstituted to a 6 g portion mixed in 8 fluid ounces of water. The excess of creatine was 15%.

[0080] Xanthan gum was used to stabilize the formulation, and its range was 0.6 - 0.85 g / 6 g portion (10% - 14.17%).

[0081] This experiment also showed similar observations as in Example 3 above in the presence of added creatine, but thickened due to the thickening of the gum over time.

[0082] Accordingly, various embodiments in the present disclosure include powders containing xanthan gum and at least one urolithin. Some embodiments include liquids (e.g., beverages) for oral consumption that contain xanthan gum and at least one urolithin, such as liquids for oral consumption prepared by reconstituting any of the powders disclosed herein. Some embodiments also include creatine.

[0083] Powders are generally used to supply nutritional and pharmaceutical compositions. Powders have the advantages that multiple doses can be provided in a simple container and different sized doses can be used from the same supply container. Powders generally have good storage properties. In addition to xanthan gum and at least one urolithin, the powders disclosed herein may also contain fillers or excipients conventional in the art. Excipients can, for example, provide shelf life, flavor, and moisture resistance, such that the composition has an acceptable taste, an appealing appearance, and good storage stability.

[0084] Optionally, the powder or liquid for oral consumption can be provided in unit dose form, which contains (i) a prophylactically or therapeutically effective amount of at least one urolithin and (ii) an amount of xanthan gum effective to maintain a majority of at least one urolithin in suspension after powder reconstitution. For example, after reconstituting 4 g of powder in 8 fluid ounces of water at about 20 °C, the amount of xanthan gum in the unit dosage form can effectively maintain a majority of at least one urolithin in suspension for at least five minutes.

[0085] In some embodiments, the present disclosure provides methods for producing such powders and methods for producing such liquids (e.g., beverages) for oral consumption. The method can include mixing at least one urolithin (e.g., in powder form) with xanthan gum (e.g., in powder form) to form a powder formulated for reconstitution in a liquid for oral consumption.

[0086] In some embodiments, the present disclosure provides methods of medical and / or non-medical treatment, wherein such a liquid (e.g., beverage) for oral consumption is orally administered to an individual, such as a mammal, e.g., a human, optionally by reconstituting the powder in a liquid such as water prior to administration.

[0087] In some embodiments, the composition is administered to an individual with impaired physical performance, impaired tolerance, and / or impaired muscle function. Improvement in muscle function can be particularly beneficial for elderly subjects experiencing muscle function decline due to age-related conditions. For example, subjects who may benefit from improvement in muscle function may experience muscle function decline, which subsequently leads to pre-frailty and frailty. In addition to their muscle function decline, such subjects may not necessarily experience muscle wasting. Some subjects do experience muscle atrophy and muscle function decline, such as subjects with sarcopenia. The composition can enhance muscle performance in subjects with frailty or pre-frailty.

[0088] In some embodiments, the powder or liquid for oral consumption preferably does not contain at least one of the following: guar gum, partially hydrolyzed guar gum (PHGG), acacia gum, gellan gum, cellulose, or modified cellulose; more preferably does not contain any of these gums; and in a particularly preferred embodiment, xanthan gum is the only gum in the powder or liquid for oral consumption.

[0089] Optionally, the powder may contain fillers such as one or more carbohydrates, for example one or more of the following: maltodextrin, hydrolyzed or modified starch or corn starch, glucose polymers, corn syrup, corn syrup solids, rice-derived carbohydrates, glucose, fructose, lactose, high fructose corn syrup, tapioca dextrin, isomaltulose, sucromalt, maltitol powder, glycerol, fructo-oligosaccharides, soy fiber, corn fiber, guar gum, konjac flour, polydextrose, honey, sugar alcohols (such as maltitol, erythritol, sorbitol) and combinations thereof.

[0090] Additionally or alternatively, the powder may contain a sweetener. High-potency non-nutritive carbohydrate sweeteners can be used, for example, selected from aspartame, sucralose, potassium acesulfame, saccharin, cyclamate, stevia, thaumatin and mixtures thereof.

[0091] Optionally, the powder may contain flavorants such as fruit flavorants. Non-limiting examples of suitable flavorants include strawberry, raspberry, blueberry, apricot, pomegranate, peach, pineapple, lemon, orange and apple. Generally, the fruit flavorant contains one or more of fruit extracts, jams or purees, and any combination of sweeteners, starches, stabilizers, natural and / or artificial flavorants, colorants, preservatives and citric acid or other suitable acids to control the pH.

[0092] Optionally, the powder may contain proteins such as proteins from one or more of milk, animals, grains or vegetables, for example one or more of the following: intact pea protein, intact pea protein isolate, intact pea protein concentrate, milk protein isolate, milk protein concentrate, casein protein isolate, casein protein concentrate, whey protein concentrate, whey protein isolate, sodium caseinate or calcium caseinate, whole milk, partially or fully skimmed milk, soy protein isolate and soy protein concentrate and combinations thereof.

[0093] In some embodiments, the powder may contain a flavorant such as a fruit flavorant containing citric acid. Preferably, the powder contains only one of protein or citric acid.

[0094] In some embodiments, the powder consists essentially of or consists of xanthan gum, at least one urolithin, optional filler and optional citric acid.

[0095] At least one urolithin can be provided by any of the compositions disclosed in the following patents: WO2012 / 088519, titled "Compositions and Methods for Improving Mitochondrial Function and Treating Neurodegenerative Diseases and Cognitive Disorders" (also published as U.S. Patent No. 9,872,850), WO2014 / 004902, titled "Enhancing Autophagy or Increasing Longevity by Administration of Urolithins or Precursors Thereof" (also published as U.S. Patent Application Publication No. 2014 / 0018415), WO2017 / 036992, titled "Compositions Comprising Urolithin Compounds", and WO2017 / 036993, titled "Compositions Comprising an Urolithin Compound", each of the above patents being incorporated herein by reference in its entirety. For example, xanthan gum can be added to any of these compositions in powder form.

[0096] At least one urolithin can be administered in a total amount of about 0.2 milligrams to 150 milligrams (mg) of urolithin per kilogram (kg) of subject body weight. Preferably, at least one urolithin is administered in a daily dose equal to or equivalent to 2 mg to 120 mg of urolithin / kg of subject body weight, more preferably 4 mg to 90 mg of urolithin / kg of subject body weight, and most preferably 8 mg to 30 mg of urolithin / kg of subject body weight. Any given dose can be given as a single dose or in divided doses.

[0097] In one embodiment, at least one urolithin is administered at a dose sufficient to achieve a peak serum level of at least 0.001 micromoles (μM), preferably at least 0.01 μM, more preferably at least 0.1 μM, most preferably at least 1 μM, at least 5 μM or at least 10 μM. In one embodiment, at least one urolithin is administered at a dose sufficient to achieve a sustained serum level of at least 0.001 micromoles (μM), preferably at least 0.01 μM, more preferably at least 0.1 μM, most preferably at least 1 μM, at least 5 μM or at least 10 μM. Any suitable method, such as high pressure liquid chromatography (HPLC) or HPLC-MS, can be used to measure the sustained serum level.

[0098] Preferably, at least one urolithin is micronized for more rapid dispersion or dissolution. If micronized urolithin is used, then preferably D 50 is less than 100 μm, i.e., 50% by mass of at least one urolithin has a particle size less than 100 μm. More preferably, at least one urolithin has a D 50 less than 75 μm, such as less than 50 μm, such as less than 25 μm, such as less than 20 μm, such as less than 10 μm. More preferably, the D 50 of at least one urolithin is in the range of 0.5 μm to 50 μm, such as 0.5 μm to 20 μm, such as 0.5 μm to 10 μm, such as 1.0 μm to 10 μm, such as 1.5 μm to 7.5 μm, such as 2.8 μm to 5.5 μm. Preferably, at least one urolithin has a D 90 less than 100 μm. More preferably, at least one urolithin has a D 90 less than 75 μm, such as less than 50 μm, such as less than 25 μm, such as less than 20 μm, such as less than 15 μm. At least one urolithin preferably has a D 90 in the range of 5 μm to 100 μm, such as 5 μm to 50 μm, such as 5 μm to 20 μm, such as 7.5 μm to 15 μm, such as 8.2 μm to 16.0 μm.

[0099] Preferably, at least one urolithin has a D 10 in the range of 0.5 μm to 1.0 μm. Preferably, at least one urolithin has a D 90 in the range of 8.2 μm to 16.0 μm, a D 50 in the range of 2.8 μm to 5.5 μm, and a D 10 in the range of 0.5 μm to 1.0 μm.

[0100] Micronization can be achieved by a method selected from the following: compression force milling, hammer milling, universal milling or pin milling, and jet milling such as spiral jet milling or fluidized bed jet milling. Jet milling is particularly preferred.

[0101] In view of the above disclosure, one aspect of the present disclosure is a powder that contains xanthan gum and also contains at least one compound of formula (I) or a salt thereof:

[0102]

[0103] wherein A, B, C, and D are each independently selected from H and OH; W, X, and Y are each independently selected from H and OH; and Z is selected from H and OH.

[0104] In a preferred embodiment, at least one urolithin is selected from urolithin A, urolithin B, urolithin C, urolithin D, and mixtures thereof. Most preferably, at least one urolithin comprises urolithin A.

[0105] By dry weight, the xanthan gum can be about 12.5 wt% to about 16.25 wt% of the powder. Optionally, the xanthan gum is the only gum in the powder. The powder can consist essentially of xanthan gum, at least one urolithin, an optional filler, and an optional citric acid.

[0106] In another aspect of the present disclosure, a method of preparing a liquid composition for oral consumption includes reconstituting any of the powders disclosed herein in a liquid. The liquid can be water, and the liquid composition can be a beverage. Preferably, when about 4 g of the powder is reconstituted in 8 fluid ounces of water at 20 °C, for at least 5 minutes after reconstitution, most of at least one urolithin is suspended in the beverage.

[0107] In another aspect of the present disclosure, a liquid composition for oral consumption is prepared by reconstituting any of the powders disclosed herein.

[0108] Another aspect of the present disclosure is a liquid composition for oral consumption that contains xanthan gum and also contains at least one urolithin.

[0109] Another aspect of the present disclosure is a method for preventing or treating a disease or disorder selected from the group consisting of metabolic syndrome, reduced metabolic rate, metabolic stress, cardiovascular disease, sarcopenia, muscle degenerative diseases, Duchenne muscular dystrophy, alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, drug-induced craving, anemia, α1-antitrypsin deficiency, ischemia / reperfusion injury, inflammation, skin aging, inflammatory bowel disease, Crohn's disease, obesity, metabolic syndrome, type II diabetes, hyperlipidemia, osteoarthritis, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, multiple sclerosis, anxiety disorder, ulcers, amyotrophic lateral sclerosis, age-related macular degeneration, cancer, cognitive impairment, stress, mood disorder, and combinations thereof. The method comprises orally administering to a subject suffering from or at risk of the disease or disorder a prophylactically or therapeutically effective amount of a beverage comprising xanthan gum and further comprising at least one urolithin.

[0110] In the method, the subject can be a human. Preferably, the method comprises reconstituting a powder comprising at least a portion of xanthan gum and at least a portion of at least one urolithin, wherein the powder is reconstituted in a liquid to form the beverage prior to administering the beverage to the subject.

[0111] Another aspect of the present disclosure is a method of achieving at least one outcome selected from the group consisting of: (i) managing body weight, (ii) promoting at least one of muscle performance or mental performance, (iii) maintaining at least one of muscle function, strength, or endurance, (iv) preventing muscle decline over time, (v) maintaining or enhancing mitochondrial function (mitophagy), and (vi) supporting or promoting at least one of cell renewal or cell protection. The method comprises orally administering to a subject in need thereof an effective amount of a beverage comprising xanthan gum and further comprising at least one urolithin.

[0112] In the method, the subject can be a human, such as a human at least 50 years of age, such as an elderly person. Preferably, the method comprises reconstituting a powder comprising at least a portion of xanthan gum and at least a portion of at least one urolithin, wherein the powder is reconstituted in a liquid to form the beverage prior to administering the beverage to the subject.

[0113] Another aspect of the present disclosure is a method of preparing a powder formulated for reconstitution in a liquid to form a liquid composition. The method comprises mixing xanthan gum and at least one urolithin. Preferably, one or both of the xanthan gum and the at least one urolithin are in powder form during the mixing process.

[0114] Another aspect of the present disclosure is a method for enhancing the stability of at least one urolithin in a liquid composition for oral consumption. At least a portion of the at least one urolithin is present in a powder that is formulated to be reconstituted in a liquid to form the liquid composition. The method includes incorporating xanthan gum in the powder.

[0115] It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the subject matter of the present invention and without diminishing its intended advantages. Accordingly, such changes and modifications are intended to be covered by the appended claims.

Claims

1. A powder comprising xanthan gum and further comprising at least one urolithin, wherein the at least one urolithin is selected from urolithin A, urolithin B, urolithin C, urolithin D, and mixtures thereof.

2. The powder according to claim 1, wherein the at least one urolithin comprises urolithin A.

3. The powder according to claim 1, wherein the xanthan gum is 12.5 wt% to 16.25 wt% of the powder by dry weight.

4. The powder according to claim 1, wherein the xanthan gum is the only gum in the powder.

5. The powder according to claim 1, the powder consisting of xanthan gum, at least one urolithin, optional filler, and optional citric acid.

6. The powder according to any one of claims 1 to 5, the powder further comprising creatine.

7. A method of preparing a liquid composition for oral consumption, the method comprising reconstituting the powder according to claim 1 in a liquid.

8. The method according to claim 7, wherein the liquid is water and the liquid composition is a beverage.

9. The method according to claim 8, wherein when about 4 g of the powder is reconstituted in 8 fluid ounces of water at 20 °C, most of the at least one urolithin is suspended in the beverage for at least 5 minutes after reconstitution.

10. A liquid composition for oral consumption, the liquid composition being prepared by reconstituting the powder according to claim 1 in a liquid.

11. The liquid composition for oral consumption according to claim 10, the liquid composition further comprising creatine.

12. Use of the powder according to any one of claims 1 to 6 or the liquid composition according to any one of claims 10 to 11 for the preparation of a medicament for preventing or treating a disease or disorder selected from metabolic syndrome, reduced metabolic rate, cardiovascular disease, muscle degenerative disease, alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, drug-induced craving, anemia, α1-antitrypsin deficiency, ischemia / reperfusion injury, inflammation, skin aging, obesity, type II diabetes, hyperlipidemia, neurodegenerative disease, anxiety disorder, ulcer, age-related macular degeneration, cancer, cognitive impairment, stress, mood disorder, and combinations thereof.

13. The use according to claim 12, wherein the stress is metabolic stress; the muscle degenerative disease is sarcopenia, Duchenne muscular dystrophy; the inflammation is inflammatory bowel disease, Crohn's disease, osteoarthritis; the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis.

14. The use according to claim 12, wherein the subject is a human.

15. Use of the powder according to any one of claims 1 to 6 or the liquid composition according to any one of claims 10 to 11 for preparing a composition for achieving at least one result selected from the following: (i) managing body weight, (ii) promoting at least one of muscle performance or mental performance, (iii) maintaining at least one of muscle function, strength or endurance, (iv) preventing muscle decline over age, (v) maintaining or enhancing mitochondrial function, and (vi) supporting or promoting at least one of cell renewal or cell protection.

16. Use according to claim 15, wherein the subject is a human.

17. Use according to claim 16, wherein the human has an age of at least 50 years.

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