Polycation salts of phenolic compounds and uses thereof

Abstract

The present disclosure generally provides polyalkali metal salts of flavanones, dihydrochalcones and related polyphenolic compounds.In some embodiments, the present disclosure provides specific compositions that include the polyalkali metal salts of flavanones, dihydrochalcones and related polyphenolic compounds, such as compositions that include the polyalkali metal salts of flavanones, dihydrochalcones and related polyphenolic compounds and one or more sweeteners.In some other embodiments, the present disclosure provides methods for reducing the calorie content of sweetened goods, such as sweetened food and beverages.

Description

[Technical field]

[0001] The present disclosure generally provides polyalkali metal salts of flavanones, dihydrochalcones and related polyphenolic compounds.In some embodiments, the present disclosure provides specific compositions that include the polyalkali metal salts of flavanones, dihydrochalcones and related polyphenolic compounds, such as compositions that include the polyalkali metal salts of flavanones, dihydrochalcones and related polyphenolic compounds and one or more sweeteners.In some other embodiments, the present disclosure provides methods for reducing the calorie content of sweetened goods, such as sweetened food and beverages.

[0002] 2. Description of Related Art The gustatory system provides sensory information about the chemical composition of the external world. Taste transduction is one of the more sophisticated forms of chemically triggered sensation in animals. Taste signaling is found throughout the animal kingdom, from simple metazoans to the most complex vertebrates. There are thought to be five basic taste modalities in mammals: sweet, bitter, sour, salty and umami.

[0003] Sweetness is the taste most commonly perceived when eating foods that are high in sugar. Mammals generally perceive sweetness as pleasant, except when excessive. Caloric sweeteners such as sucrose and fructose are classic examples of sweet tastants. Although a variety of non-caloric and low-calorie substitutes exist, these caloric sweeteners remain the primary means by which edible products elicit the perception of sweetness upon consumption.

[0004] Metabolic disorders and related diseases, such as obesity, diabetes, and cardiovascular disease, are major public health problems worldwide, and their prevalence is increasing at an alarming rate in almost all developed countries. Caloric sweeteners are the main cause of this trend, and are included in various processed food and beverage products to make them more palatable to consumers. In many cases, non-caloric or low-caloric substitutes for sucrose and fructose can be used in foods and beverages. Nevertheless, these compounds impart a different sweetness to caloric sweeteners, and therefore many consumers are unable to consider them as suitable replacements. Furthermore, such compounds can be difficult to incorporate into certain products. In some cases, they are used as partial replacements for caloric sweeteners, but their presence alone can cause many consumers to perceive unpleasant off-tastes, such as astringent, bitter, metallic, or licorice-like. Thus, low-calorie sweeteners face certain challenges in their adoption.

[0005] Sweetness enhancement offers an alternative approach to overcome some of the adoption challenges faced by low-calorie sweeteners. Such compounds can be used in combination with sucrose or fructose to enhance sweetness, thereby reducing the use of such caloric sweeteners in various food and beverage products. However, such compounds not only enhance the perceived sweetness of the primary sweetener, but also change the perceived taste of the sweetener. Thus, many consumers find it less pleasurable to consume such sweetened products compared to high-calorie, unenhanced alternatives. Thus, there remains a need to discover compounds that enhance the sweetness of caloric sweeteners without altering the perceived taste in a way that diminishes the pleasure consumers experience when consuming products containing such sweeteners.

[0006] overview The present disclosure relates to the discovery that the use of lactase enzyme in combination with certain sweetness enhancers can improve the sweetness of dairy products without the need to add large amounts of caloric sweeteners such as sucrose or fructose.

[0007] In a first aspect, the present disclosure provides a compound of formula (I): [ka] [In the formula, R 1 , R 2 and R 3 are independently a hydrogen atom, -OH or -OCH 3 and R 1 , R 2 and R 3 at least one of is -OH; the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or combinations thereof; and the dotted lines represent any carbon-carbon double bonds.

[0008] In a second aspect, the present disclosure provides a compound of formula (II): [ka] [In the formula, R 11 , R 12 , R 13 and R 14 are independently a hydrogen atom, -OH or -OCH 3 and R 11 , R 12 , R 13 and R 14 at least one of is -OH; and the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or a combination thereof.

[0009] In a third aspect, the present disclosure provides a compound of formula (III): [ka] [In the formula, R 21 and R 22 are independently a hydrogen atom, -OH or -OCH 3 and R 21 and R 22 At least one of R is -OH; 23 is C 1~6 Alkyl or -CH 2 -R 24 ;R 24 -OH, -OCH 3 or combinations thereof; the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or combinations thereof.

[0010] In a fourth aspect, the disclosure provides for the use of a flavor modulating compound of any of the first, second or third aspects to enhance the sweetness of an ingestible composition. In some embodiments thereof, the ingestible composition comprises a caloric sweetener. In some other embodiments thereof, the ingestible composition comprises a non-caloric sweetener. In some embodiments, the sweetener is a high intensity sweetener. In certain related aspects, the disclosure provides a method of enhancing the sweetness of an ingestible composition, the method comprising introducing a flavor modulating compound of any of the first, second or third aspects into the ingestible composition.

[0011] In a fifth aspect, the present disclosure provides the use of a flavor modulating compound of any of the first, second or third aspects to reduce the bitterness of an ingestible composition. In some other embodiments thereof, the ingestible composition comprises a non-caloric sweetener, such as a non-caloric sweetener having a bitter or unpleasant aftertaste. In some embodiments, the ingestible composition comprises a bitter compound, such as nomellin, limonin, caffeine, vegetable protein, etc. In some embodiments, the sweetener is a high intensity sweetener. In certain related aspects, the present disclosure provides a method of reducing the bitterness of an ingestible composition, the method comprising introducing a flavor modulating compound of any of the first, second or third aspects into the ingestible composition.

[0012] In a sixth aspect, the present disclosure provides for the use of a flavor modulating compound of any of the first, second or third aspects to reduce the caloric content of an ingestible composition. In some embodiments thereof, the ingestible composition comprises a caloric sweetener at a concentration lower than that of an iso-sweet composition that does not comprise a flavor modulating compound disclosed herein. In certain related aspects, the present disclosure provides a method of reducing the caloric content of an ingestible composition, the method comprising introducing a flavor modulating compound of any of the first, second or third aspects into the ingestible composition.

[0013] In a seventh aspect, the present disclosure provides an ingestible composition comprising any of the flavor modulating compounds of the first, second or third aspects. In some embodiments, the ingestible composition is not a naturally occurring composition. In some embodiments, the ingestible composition comprises a sweetener. In some embodiments, the sweetener is a caloric sweetener, such as sucrose, fructose, glucose, xylitol, erythritol or a combination thereof. In some embodiments, the sweetener is a non-caloric sweetener, such as steviol glycosides, mogrosides, aspartame, sucralose, acesulfame K, saccharin or any combination thereof. In some embodiments, the ingestible composition comprises one or more high intensity sweeteners.

[0014] In an eighth aspect, the present disclosure provides a flavored product comprising any of the ingestible compositions of the seventh aspect. In some embodiments, the flavored product is a beverage, such as soda, flavored water, tea, etc. In some other embodiments, the flavored product is a food product, such as yogurt.

[0015] Further aspects and embodiments thereof are described in the following detailed description, drawings, abstract, and claims.

[0016] Detailed Description The following detailed description describes various aspects and embodiments provided herein. This description should be read from the perspective of a person skilled in the relevant art. As such, it may not necessarily include information that is known to such a person skilled in the art.

[0017] definition The following terms and phrases have the meanings set forth below unless otherwise indicated herein. This disclosure may use other terms and phrases not expressly defined herein. Such other terms and phrases have the meanings they have to one of ordinary skill in the art within the context of this disclosure. In some cases, a term or phrase may be defined in the singular or plural. In such cases, it is understood that a singular term may include its plural counterpart and vice versa, unless expressly indicated otherwise.

[0018] As used herein, "sweetener" refers to a compound or a edible acceptable salt thereof that induces a detectable sweet flavor in a subject, such as a compound that activates the human T1R2 or T1R3 receptor during an in vitro screening process or a compound that is reported to taste sweet in a sensory test with human subjects.

[0019] As used herein, "C a ~C b " or "C a~b " (where "a" and "b" are integers) refers to the number of carbon atoms in the specified group. That is, the group can contain from "a" to "b" carbon atoms. Thus, for example, "C 1 ~C 4 Alkyl" or "C 1~4 An "alkyl" group is any alkyl group having 1 to 4 carbons, i.e., -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH(CH 3 ) 2 , -CH 2 CH 2 CH 2 CH 3 , -CH(CH 3 )CH 2 CH 3 and -C(CH 3 ) 3 Refers to...

[0020] As used herein, "alkyl" refers to a straight or branched hydrocarbon chain that is fully saturated (i.e., contains no double or triple bonds). In some embodiments, the alkyl group has 1 to 20 carbon atoms (wherever it appears herein, a numerical range such as "1 to 20" refers to each integer within the given range; for example, "1 to 20 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to 20 carbon atoms, although this definition also covers occurrences of the term "alkyl" where no numerical range is specified). The alkyl group may also be a medium sized alkyl having 1 to 9 carbon atoms. The alkyl group may also be a lower alkyl having 1 to 4 carbon atoms. The alkyl group may also be a "C 1~4 Alkyl" or a similar designation. 1~4 "Alkyl" indicates that there are 1 to 4 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. Representative alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, and the like. Unless indicated to the contrary, the term "alkyl" refers to the group that is not further substituted.

[0021] It should be understood that the naming convention for a particular group may include either monovalent or divalent groups depending on the context. For example, if a substituent requires two points of attachment to the remainder of the molecule, then the substituent is understood to be a divalent group. For example, a substituent specified as alkyl that requires two points of attachment includes -CH 2 -, -CH 2 CH 2 -, -CH 2 CH(CH 3 )CH 2 -, and other divalent groups.

[0022] Where a substituent is depicted as a divalent group (i.e., having two points of attachment to the remainder of the molecule), it is to be understood that the substituent may be attached in any directional configuration unless otherwise indicated. Thus, for example, -AE- or [ka] Substituents designated as such include those oriented such that A is attached to the left-hand attachment point of the molecule, as well as those oriented such that A is attached to the right-hand attachment point of the molecule.

[0023] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, reference to "a substituent" encompasses not only a single substituent, but two or more substituents, and so forth.

[0024] As used herein, "for example, for instance," "such as," or "including" are intended to introduce examples that further clarify a more general subject matter. Unless expressly indicated otherwise, such examples are provided only as an aid in understanding the embodiments set forth in the present disclosure and are not intended to be limiting in any way. Additionally, these phrases do not imply any kind of selection of the disclosed embodiments.

[0025] As used herein, "comprise" or "comprises" or "comprising" or "comprised of" refers to an open group. This means that the group may contain additional elements in addition to those explicitly listed. For example, the phrase "comprising A" means that A must be present, but other elements may also be present. The terms "comprise", "having", "consisting of" and their grammatical variations have the same meaning. In contrast, "consist of" refers to a closed group. For example, the phrase "consisting of" means that A and only A are present.

[0026] As used herein, "optionally" means that the event described thereafter may or may not occur. In some embodiments, the optional event does not occur. In other embodiments, the optional event occurs one or more times.

[0027] As used herein, "or" should be given its broadest reasonable interpretation and should not be limited to an either / or configuration. Thus, the phrase "comprising A or B" means that A can be present and B cannot be present, or B is present and A is not present, or both A and B are present. Furthermore, it is possible that A may include more than one element, e.g., A 1 and A 2 When defining a classification that can have one or more elements of the classification, one or more elements of the classification can be present at the same time.

[0028] The attachment point of the group is generally indicated by a trailing dash (-) or asterisk ( * ) For example, * -CH 2 -CH 3 or -CH 2 -CH 3 Both groups represent an ethyl group.

[0029] Chemical structures are often shown using a "skeletal" format in which carbon atoms are not explicitly represented and hydrogen atoms attached to carbon atoms are omitted entirely. For example, the structure [ka] represents butane (i.e., n-butane). Additionally, aromatic groups such as benzene are represented by showing one of the contributing resonance structures. For example, the structure [ka] represents toluene.

[0030] Other terms not included in this subsection are defined elsewhere in this specification.

[0031] Flavor Modulating Compounds In certain embodiments, the present disclosure provides a compound of formula (I): [ka] [In the formula, R 1 , R 2 and R 3 are independently a hydrogen atom, -OH or -OCH 3 and R 1 , R 2 and R 3 at least one of is -OH; the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or combinations thereof; and the dotted lines represent any carbon-carbon double bonds.

[0032] R 1 , R 2 and R 3 can have any suitable value according to the options above. In some embodiments, R 3 is -OH. In some embodiments, R 1 and R 2One of the groups is -OH and the other is a hydrogen atom, -OH or -OCH 3 It is.

[0033] In some cases, R 1 and R 2 The value of can depend on whether any carbon-carbon double bonds are present or absent. In some embodiments, when any carbon-carbon double bonds are absent, R 1 is a hydrogen atom or -OCH 3 In some further such embodiments, when any carbon-carbon double bond is not present, R 1 is a hydrogen atom. In some alternative embodiments, when any carbon-carbon double bond is not present, R 1 HA-OCH 3 It is.

[0034] The optional carbon-carbon double bond may or may not be present. In some embodiments, the optional carbon-carbon double bond is present and the ring contains the optional carbon-carbon double bond. In other embodiments, the optional carbon-carbon double bond is not present and the ring does not contain the optional carbon-carbon double bond.

[0035] In some embodiments, the compound of formula (I) is naringenin, wherein R 1 and R 3 is -OH, and R 2 is a hydrogen atom and there are no carbon-carbon double bonds.

[0036] The flavor modulating compound is a dialkali metal salt or a trialkali metal salt. The term "salt" refers to both: (a) a solid-state form, where the dianion or trianion of the compound of formula (I) is placed in a solid-state matrix with sodium cations, potassium cations, or a combination thereof (in some embodiments, such solids are suspended in a liquid matrix, such as an aqueous matrix), and (b) a solvate, where the dianion or trianion of the compound of formula (I) is placed in a liquid medium, such as an aqueous medium, in which a sufficient number of sodium cations, potassium cations, or a combination thereof are present, thereby establishing a charge neutral balance. It should be noted that the molar ratio of cations to anions may not be exact. For example, a "dialkali metal salt" means that the net charge of the anion is about -2, and about 2 moles of sodium or potassium cations are present to balance the negative charge of the anion. Similarly, a "trialkali metal salt" means that the net charge of the anion is about -3, and about 3 moles of sodium or potassium cations are present to balance the negative charge of the anion.

[0037] The flavor modulating compound can be any suitable dialkali metal salt or trialkali metal salt of sodium, potassium or combinations thereof. In some embodiments, the flavor modulating compound is a disodium salt. In some embodiments, the flavor modulating compound is a disodium salt. In some embodiments, the flavor modulating compound is a trisodium salt. In some embodiments, the flavor modulating compound is a dipotassium salt. In some embodiments, the flavor modulating compound is a tripotassium salt.

[0038] In certain embodiments, the present disclosure provides a compound of formula (II): [ka] [In the formula, R 11 , R 12 , R 13and R 14 are independently a hydrogen atom, -OH or -OCH 3 and R 11 , R 12 , R 13 and R 14 at least one of is -OH; and the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or a combination thereof.

[0039] R 11 and R 12 can have any suitable value within the above parameters. In some embodiments, R 11 and R 12 and R are hydrogen atoms. 11 In some such embodiments, R 11 is -OH, and R 12 is a hydrogen atom. In some embodiments, R 11 -OCH 3 In some such embodiments, R 11 -OCH 3 and R 12 is a hydrogen atom or -OH.

[0040] R 13 can have any suitable value within the above parameters. In some embodiments, R 13 is a hydrogen atom. In some embodiments, R 13 is -OH. In some embodiments, R 13 -OCH 3 It is.

[0041] R 14 can have any suitable value within the above parameters. In some embodiments, R 14 is a hydrogen atom. In some embodiments, R 14is -OH. In some embodiments, R 14 -OCH 3 It is.

[0042] In some embodiments, the compound of formula (II) is phloretin.

[0043] The flavor modulating compound is a dialkali metal salt or a trialkali metal salt. The term "salt" refers to both: (a) a solid-state form, where the dianion or trianion of the compound of formula (I) is placed in a solid-state matrix with sodium cations, potassium cations, or a combination thereof (in some embodiments, such solids are suspended in a liquid matrix, such as an aqueous matrix), and (b) a solvate, where the dianion or trianion of the compound of formula (I) is placed in a liquid medium (such as an aqueous medium) in which a sufficient number of sodium cations, potassium cations, or a combination thereof are present, thereby establishing a charge neutral balance. It should be noted that the molar ratio of cations to anions may not be exact. For example, a "dialkali metal salt" means that the net charge of the anion is about -2, and about 2 moles of sodium or potassium cations are present to balance the negative charge of the anion. Similarly, a "trialkali metal salt" means that the net charge of the anion is about -3, and about 3 moles of sodium or potassium cations are present to balance the negative charge of the anion.

[0044] The flavor modulating compound can be any suitable dialkali metal salt or trialkali metal salt of sodium, potassium or combinations thereof. In some embodiments, the flavor modulating compound is a disodium salt. In some embodiments, the flavor modulating compound is a disodium salt. In some embodiments, the flavor modulating compound is a trisodium salt. In some embodiments, the flavor modulating compound is a dipotassium salt. In some embodiments, the flavor modulating compound is a tripotassium salt.

[0045] In certain embodiments, the present disclosure provides a compound of formula (III): [ka] [In the formula, R 21 and R 22 are independently a hydrogen atom, -OH or -OCH 3 and R 21 and R 22 At least one of R is -OH; 23 is C 1~6 Alkyl or -CH 2 -R 24 ;R 24 -OH, -OCH 3 or combinations thereof; the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or combinations thereof.

[0046] R 21 and R 22 can have any suitable value within the above parameters, provided that at least one is -OH. In some embodiments, R 21 is a hydrogen atom. In some embodiments, R 21 In some such embodiments, R 21 is -CH 3 In some embodiments, R 22 is a hydrogen atom. In some embodiments, R 22 In some such embodiments, R 22 is -CH 3 It is.

[0047] R 23 can have any suitable value within the above parameters. In some embodiments, R 23is C such as methyl, ethyl, propyl, butyl, pentyl, 2-methylpropyl or 3-methylbutyl. 1~6 In some embodiments, R 23 is -CH 2 -R 24 ;R 24 -OH, -OCH 3 or a combination thereof. 24 is an unsubstituted phenyl group, -OH, -OCH 3 or combinations thereof, such as a phenyl group substituted at the 3-position, the 4-position, or at both the 3- and 4-positions.

[0048] Table 1 shows non-limiting examples of compounds of formula (I), compounds of formula (II), and compounds of formula (III) that can form di- or tri-alkali metal salts.

[0049] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7]

[0050] It should be noted that stereochemistry is indicated for some of the compounds in Table 1. Where the stereochemistry is not explicitly stated in the structure, the structure includes the pure (R) form, the pure (S) form, and racemic mixtures of the two forms.

[0051] The compounds described may have isotopes. Each chemical element represented in the compound structure may include any isotope of said element. For example, in the compound structure, hydrogen atoms may be explicitly disclosed or understood to be present in the compound. At any position of the compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including but not limited to hydrogen-1 (protium) or hydrogen-2 (deuterium). Thus, reference to a compound herein encompasses all possible isotopic forms, unless the context clearly indicates otherwise.

[0052] Uses and Methods In certain aspects, the disclosure provides for the use of a flavor modulating compound of any of the preceding aspects to enhance the sweetness of an ingestible composition. In some embodiments thereof, the ingestible composition comprises a caloric sweetener. In some other embodiments thereof, the ingestible composition comprises a non-caloric sweetener. In some embodiments, the sweetener is a high intensity sweetener. In certain related aspects, the disclosure provides for a method of enhancing the sweetness of an ingestible composition, the method comprising introducing a flavor modulating compound of any of the preceding aspects into the ingestible composition. In some embodiments, the flavor modulating compound is used or introduced into the ingestible composition at a concentration ranging from 1 ppm to 1000 ppm, or 5 ppm to 1000 ppm, or 10 ppm to 1000 ppm, or 20 ppm to 1000 ppm, or 50 ppm to 1000 ppm, or 100 ppm to 1000 ppm, or 200 ppm to 800 ppm, based on the total weight of the ingestible composition. In some embodiments, the flavor modulating compound is the disodium salt of naringenin. In some embodiments, the flavor modulating compound is the dipotassium salt of naringenin. In some embodiments, the flavor modulating compound is the disodium salt of phloretin. In some embodiments, the flavor modulating compound is the dipotassium salt of phloretin.

[0053] In certain aspects, the disclosure provides for the use of a flavor modulating compound of any of the preceding aspects to reduce the bitterness of an ingestible composition. In some other embodiments thereof, the ingestible composition comprises a non-caloric sweetener, such as a non-caloric sweetener having a bitter or unpleasant aftertaste. In some embodiments, the ingestible composition comprises a bitter compound, such as nomeline, limonin, caffeine, non-animal protein, or active pharmaceutical ingredient. In some embodiments, the sweetener is a high intensity sweetener. In certain related aspects, the disclosure provides a method of reducing the bitterness of an ingestible composition, the method comprising introducing a flavor modulating compound of any of the preceding aspects into the ingestible composition. In some embodiments, the flavor modulating compound is introduced into the use or ingestible composition at a concentration ranging from 1 ppm to 1000 ppm, or 5 ppm to 1000 ppm, or 10 ppm to 1000 ppm, or 20 ppm to 1000 ppm, or 50 ppm to 1000 ppm, or 100 ppm to 1000 ppm, or 200 ppm to 800 ppm, based on the total weight of the ingestible composition. In some embodiments, the flavor modulating compound is the disodium salt of naringenin. In some embodiments, the flavor modulating compound is the dipotassium salt of naringenin. In some embodiments, the flavor modulating compound is the disodium salt of phloretin. In some embodiments, the flavor modulating compound is the dipotassium salt of phloretin.

[0054] In certain aspects, the disclosure provides for the use of a flavor modulating compound of any of the preceding aspects to reduce the caloric content of an ingestible composition. In some embodiments thereof, the ingestible composition comprises a caloric sweetener at a concentration lower than that of an iso-sweet composition not comprising a flavor modulating compound disclosed herein. In certain related aspects, the disclosure provides for a method of reducing the caloric content of an ingestible composition, the method comprising introducing a flavor modulating compound of any of the preceding aspects into the ingestible composition. In some embodiments, the flavor modulating compound is used or introduced into the ingestible composition at a concentration ranging from 1 ppm to 1000 ppm, or 5 ppm to 1000 ppm, or 10 ppm to 1000 ppm, or 20 ppm to 1000 ppm, or 50 ppm to 1000 ppm, or 100 ppm to 1000 ppm, or 200 ppm to 800 ppm, based on the total weight of the ingestible composition. In some embodiments, the flavor modulating compound is the disodium salt of naringenin. In some embodiments, the flavor modulating compound is the dipotassium salt of naringenin. In some embodiments, the flavor modulating compound is the disodium salt of phloretin. In some embodiments, the flavor modulating compound is the dipotassium salt of phloretin.

[0055] Ingestible Composition The above uses and methods generally include the use of a flavor modulating compound in a composition that includes one or more additional ingredients. For example, in at least one aspect, the present disclosure provides a composition comprising a flavor modulating compound of any of the above aspects, including any of the above embodiments or combinations thereof, wherein the flavor modulating compound comprises at least 50% by weight of the composition on a dry weight basis (e.g., relative to the total weight of the composition excluding the weight of any liquid carrier). In a related aspect, the present disclosure provides a solid composition comprising a flavor modulating compound of any of the above aspects, including any of the above embodiments or combinations thereof, wherein the flavor modulating compound comprises at least 50% by weight of the solid composition relative to the total weight of the composition. In another related aspect, the present disclosure provides an ingestible composition comprising a flavor modulating compound of any of the above aspects, including any of the above embodiments or combinations thereof, wherein the ingestible composition comprises a sweetener. In some such embodiments, the sweetener is a caloric sweetener, such as sucrose, fructose (e.g., high fructose corn syrup), glucose, or a combination thereof.

[0056] In certain embodiments of any of the aspects and embodiments described herein that refer to an ingestible composition, the ingestible composition is a non-naturally occurring product, such as a composition specially manufactured for the production of a flavored product, such as a flavored food or beverage product or a flavored pharmaceutical product.

[0057] In general, the flavor modulating compounds disclosed and described herein can be provided individually or in combination in a composition, such as an ingestible composition. In one embodiment, the flavor modulating compounds disclosed and described herein can be provided individually or in combination to impart a more sugar-like temporal or flavor profile to a sweetener composition by combining one or more compounds disclosed and described herein with one or more sweeteners in a sweetener composition. In another embodiment, the flavor modulating compounds disclosed and described herein can be provided individually or in combination to increase or enhance the sweetness of a composition by contacting the composition with a compound disclosed and described herein to form a modulating composition.

[0058] Thus, in some embodiments, the composition described in any of the above aspects (including any use or method) comprises a flavor modulating compound and a sweetener. In some embodiments, the composition further comprises a vehicle. In some embodiments, the vehicle is water. In some embodiments, the flavor modulating compound is present at a concentration below its sweetness perception threshold.

[0059] In some embodiments, when the ingestible composition includes a sweetener, the sweetener is present in an amount ranging from 0.1% to 12% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.2% to 10% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.3% to 8% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.4% to 6% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.5% to 5% by weight. In some embodiments, the sweetener is present in an amount ranging from 1% to 2% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.1% to 5% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.1% to 4% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.1% to 3% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.1% to 2% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.1% to 1% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.1% to 0.5% by weight. In some embodiments, the sweetener is present in an amount ranging from 0.5% to 10% by weight. In some embodiments, the sweetener is present in an amount ranging from 2% to 8% by weight. In some further embodiments of the embodiments described herein, the sweetener is sucrose, fructose, glucose, xylitol, erythritol, allulose, or a combination thereof.

[0060] In some other embodiments, the sweetener is present in an amount ranging from 10 ppm to 1000 ppm. In some embodiments, the sweetener is present in an amount ranging from 20 ppm to 800 ppm. In some embodiments, the sweetener is present in an amount ranging from 30 ppm to 600 ppm. In some embodiments, the sweetener is present in an amount ranging from 40 ppm to 500 ppm. In some embodiments, the sweetener is present in an amount ranging from 50 ppm to 400 ppm. In some embodiments, the sweetener is present in an amount ranging from 50 ppm to 300 ppm. In some embodiments, the sweetener is present in an amount ranging from 50 ppm to 200 ppm. In some embodiments, the sweetener is present in an amount ranging from 50 ppm to 150 ppm. In some further embodiments of the embodiments described herein, the sweetener is a steviol glycoside, e.g., renaudioside A, rebaudioside D, rebaudioside M, rebaudioside E, or any combination thereof. In some embodiments, the sweetener is a mogroside, e.g., mogroside III, mogroside IV, mogroside V, siamenoside I, isomogroside V, mogroside IV, E , Isomogroside IV, Mogroside III E , 11-oxomogroside V, the 1,6-α isomer of siamenoside I, and any combination thereof. In some embodiments, the sweetener is sucralose.

[0061] In addition to those specified above, the composition may contain any suitable sweetener or combination of sweeteners. In some embodiments, the sweetener is a sweetener composition that includes common saccharide sweeteners such as sucrose, fructose, glucose, and natural sugars such as corn syrup (including high fructose corn syrup) or other syrups or sweetener concentrates derived from natural fruit-based and vegetable-based sources. In some embodiments, the sweetener is sucrose, fructose, or a combination thereof. In some embodiments, the sweetener is sucrose. In some other embodiments, the sweetener is selected from rare natural sugars including D-allose, D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-albinose, D-turanose, and D-leucrose. In some embodiments, the sweetener is selected from semi-synthetic "sugar alcohol" sweeteners such as erythritol, isomalt, lactitol, mannitol, sorbitol, xylitol, maltodextrin, etc. In some embodiments, the sweetener is selected from artificial sweeteners such as aspartame, saccharin, acesulfame-K, cyclamate, sucralose, and alitame. In some embodiments, the sweetener is selected from the group consisting of cyclamic acid, mogrosides, tagatose, maltose, galactose, mannose, sucrose, fructose, lactose, neotame and other aspartame derivatives, glucose, D-tryptophan, glycine, maltitol, lactitol, isomalt, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysates (HSH), stevioside, rebaudioside A, other sweet stevia-based glycosides, chemically modified steviol glycosides (such as glucosylated steviol glycosides), mogrosides, chemically modified mogrosides (such as glucosylated mogrosides), karela and other guanidine-based sweeteners. In some embodiments, the sweetener is a combination of two or more of the sweeteners described in this section. In some embodiments, the sweetener may be a combination of two, three, four, or five sweeteners disclosed herein. In some embodiments, the sweetener may be a sugar.In some embodiments, the sweetener may be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, the sweetener is a sugar. In some embodiments, the sugar is cane sugar. In some embodiments, the sugar is beet sugar. In some embodiments, the sugar may be sucrose, fructose, glucose, or a combination thereof. In some embodiments, the sugar may be sucrose. In some embodiments, the sugar may be a combination of fructose and glucose.

[0062] Sweeteners may also include sweetener compositions containing one or more natural or synthetic carbohydrates, such as, for example, corn syrup, high fructose corn syrup, high maltose corn syrup, glucose syrup, sucralose syrup, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysates (HSH) or other syrups or sweetener concentrates derived from natural fruit- and vegetable-based sources, or semi-synthetic "sugar alcohol" sweeteners such as polyols. Non-limiting examples of polyols in some embodiments include erythritol, maltitol, mannitol, sorbitol, lactitol, xylitol, isomalt, propylene glycol, glycerol (glycerin), threitol, galactitol, palatinose, reduced isomaltooligosaccharides, reduced xylooligosaccharides, reduced gentiooligosaccharides, reduced maltose syrup, reduced glucose syrup, isomaltulose, maltodextrin, and the like, as well as sugar alcohols, or any other carbohydrate that can be reduced without adversely affecting the taste, or combinations thereof.

[0063] Sweeteners include, but are not limited to, agave inulin, agave nectar, agave syrup, amazake, brazzein, brown rice syrup, coconut crystals, coconut sugar, coconut syrup, date sugar, fructans (also called inulin fiber, fructooligosaccharides or oligofructose), green stevia powder, stevia rebaudiana, rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside E , rebaudioside F, rebaudioside I, rebaudioside H, rebaudioside L, rebaudioside K, rebaudioside J, rebaudioside N, rebaudioside O, rebaudioside M, and other sweet stevia-based glycosides, stevioside, stevioside extract, honey, Jerusalem artichoke syrup, licorice root, Monk fruit (fruit, powder or extract), Lucuma (fruit, powder or extract), maple sap (e.g. sugar maple (Acer saccharum, black maple (Acer nigrum), red maple (Acer rubrum), silver maple (Acer saccharinum), Norway maple (Acer platanoides), ash maple (Acer negundo), bigleaf maple (Acer macrophyllum), bigleaf maple (Acer grandidentatum), Rocky Mountain maple (Acer glabrum), and silver maple (Acer mono), maple syrup, maple sugar, walnut sap (e.g., Juglans cinerea, Juglans nigra, Juglans ailatifolia, and Juglans regia), birch sap (e.g., Betula alba), papyrifera), yellow birch (Betula alleghaniensis), sweet beach (Betula lenta), river birch (Betula nigra), gray birch (Betula populifolia), and silver birch (Betula pendula).Sycamore sap (e.g., sap extracted from the American sycamore tree (Platanus occidentalis)), ironwood sap (e.g., sap extracted from the American asada (Ostrya virginiana)), muscovado, molasses (e.g., blackstrap molasses), molasses sugar, monatin, monellin, cane sugar (also called natural sugar, unrefined cane sugar or sucrose), palm sugar, panocha, piloncillo, rapadura, raw sugar, rice syrup, sorghum, sorghum syrup, cassava syrup (also called tapioca syrup), thaumatin, yacon root, malt syrup, barley malt syrup, barley malt powder, beet sugar, cane sugar beta sugar, crystalline fruit juice crystals, caramel, carbitol, carob syrup, white sugar, hydrogenated starch hydrolysates, hydrolyzed canned juice, hydrolyzed starch, invert sugar, anethole, arabinogalactan, arop, syrup, P-4000, acesulfame potassium (also called acesulfame K or ace-K), alitame (also called acrame), advantame, aspartame, bayunoside, neotame, benzamide derivatives, bernadame, candelille, carreram. , and other guanidine-based sweeteners, vegetable fiber, corn sugar, coupling sugar, curculin, cyclamate, cyclocaryoside I, demerara, dextran, dextrin, maltodextrin, dulcin, sucrose, vulgin, dulcoside A, dulcoside B, emulin, enoxolone, maltodextrin, saccharin, estragole, ethyl maltol, glucine, gluconic acid, gluconolactone, glucosamine, glucoronic acid, glycerol, glycine, glycyphyllin, glycyrrhizin , glycyrrhetinic acid monoglucuronide, golden sugar, yellow sugar, golden syrup, granulated sugar, jiaogulan, hernandursin, isomerized liquid sugar, jalab, chicory root dietary fiber, kynurenine derivatives (N'-formyl-kynurenine, N'-acetyl-kynurenine, 6-chloro-kynurenine, etc.), galactitol, ritesse, ligicane, lycasin, ragduname, guanidine, falernum, mabinlin I, mabinlin II, maltol, multisorb,Maltodextrin, maltotriol, mannosamine, miraculin, starch syrup, mogrosides (such as mogroside IV, mogroside V, and neomogroside), mukurozioside, nanosugar, naringin dihydrochalcone, neohesperidin dihydrochalcone, nib sugar, nigerooligosaccharide, norbu, olgate syrup, osladin, pekmez, pentasine, periandrin I, perillaldehyde, perillartine, petphyllum, phenylalanine, phlomisoside I, phlorodizin, phyllodulcin, polyglycitol syrup, polypodoside A, pterocaryoside A, pterocaryoside B, rebiana, refiner syrup, love syrup, rubusoside, serigueine A, siamenoside I, siraitia grosvenorii), soy oligosaccharides, Splenda, SRI oxime V, steviol glycosides, steviolbioside, stevioside, strogin 1, 2, and 4, sucronate, sucrose, suosan, phloridzin, super aspartame, tetrasaccharide, threitol, molasses, trilobatin, D-tryptophan and derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, volemitol, birch syrup, aspartame-acesulfame, asgulin, aromadendrin-3-O-acetate, dihydrotamarixetin-3-O-acetate, and combinations or blends of any two or more thereof.

[0064] In yet another embodiment, the sweetener may be a chemically or enzymatically modified natural high-intensity sweetener. The modified natural high-intensity sweetener includes glycosylated natural high-intensity sweeteners such as glucosyl-, galactosyl- or fructosyl-derivatives containing 1-50 glycoside residues. The glycosylated natural high-intensity sweeteners can be produced by enzymatic transglycosylation reactions catalyzed by various enzymes with transglycosylation activity. In some embodiments, the modified sweeteners may be substituted or unsubstituted.

[0065] Additional sweeteners also include combinations of any two or more of any of the aforementioned sweeteners. In some embodiments, the sweetener may include a combination of two, three, four or five of the sweeteners disclosed herein. In some embodiments, the sweetener may be a sugar. In some embodiments, the sweetener may be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, the sweetener is a caloric sweetener, such as sucrose, fructose, xylitol, erythritol, or combinations thereof. In some embodiments, the ingestible composition is free or (in some embodiments) substantially free of stevia-derived sweeteners, such as steviol glycosides, glucosylated steviol glycosides, or rebaudiosides. For example, in some embodiments, the ingestible composition contains no stevia derived sweeteners, or contains stevia derived sweeteners at a concentration of 1000 ppm or less, or 500 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 20 ppm or less, or 10 ppm or less, or 5 ppm or less, or 3 ppm or less, or 1 ppm or less.

[0066] The flavor modulating compound may be present in the ingestible composition in any suitable amount. In some embodiments, the flavor modulating compound is present in an amount sufficient to enhance the taste of the composition (e.g., enhance sweetness, reduce sourness, or reduce bitterness). In some embodiments, the ingestible composition comprises a concentration of the flavor modulating compound ranging from 1 ppm to 1000 ppm, or 5 ppm to 1000 ppm, or 10 ppm to 1000 ppm, or 20 ppm to 1000 ppm, or 50 ppm to 1000 ppm, or 100 ppm to 1000 ppm, or 200 ppm to 800 ppm, based on the total weight of the ingestible composition. In embodiments in which a sweetener such as sucrose, glucose, or fructose is present, the weight to weight ratio of sweetener to flavor modulating compound in the ingestible composition ranges from 10:1 to 1000:1, or 10:1 to 500:1, or 10:1 to 100:1.

[0067] The flavor modulating compounds can be combined in any suitable manner. For example, in some embodiments, the ingestible composition or sweetener concentrate comprises a single flavor modulating compound of the above embodiments, such as the disodium salt of any one of compounds 1-51, or the dipotassium salt of any one of compounds 1-51, or the trisodium salt of any one of compounds 1-51, or the tripotassium salt of any one of compounds 1-51. In some other embodiments, the ingestible composition or sweetener concentrate comprises a mixture of two or more flavor modulating compounds of the above embodiments. For example, in some embodiments, the ingestible composition comprises the disodium salt of compound 6 and the disodium salt of compound 11. The two flavor modulating compounds can have any suitable weight ratio to each other, for example, 1:10 to 10:1.

[0068] In certain embodiments, the ingestible composition may also include any additional ingredient or combination of ingredients generally used in food and beverage products, including but not limited to the following: acids, such as citric acid, phosphoric acid, ascorbic acid, sodium sulfate, lactic acid, or tartaric acid; bitter ingredients such as caffeine, quinine, green tea, catechins, polyphenols, green robusta coffee extract, green coffee extract, potassium chloride, menthol, non-animal proteins (such as proteins and protein isolates derived from plants, algae, or fungi) or active pharmaceutical ingredients; Coloring agents such as caramel color, red #40, yellow #5, yellow #6, blue #1, red #3, purple carrot, black carrot juice, purple sweet potato, vegetable juice, fruit juice, beta carotene, turmeric curcumin, or titanium dioxide; preservatives, such as sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfite, sorbic acid, or benzoic acid; Antioxidants such as ascorbic acid, calcium disodium EDTA, alpha tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol, or sodium hexametaphosphate; For example, Resveratrol, Co-Q10, Omega-3 fatty acids, Theanine, Choline chloride (Cytocholine), Fibersol, Inulin (Chicory Root), Taurine, Ginseng extract, Guanana extract, Ginger extract, L-Phenylalanine, L-Carnitine, L-Tartrate, D-Glucoronolactone, Inositol, Bioflavonoids, Echinacea, Ginkgo biloba, Yerba mate, Flaxseed oil, Garcinia cambogia husk extract, White tea extract, Ribose, Milk thistle extract, Grape seed extract, Pyridoxine HCl (Vitamin B6), Cyanocobalamin (Vitamin B12), Niacinamide (Vitamin B13), vitamins or functional ingredients such as vitamin B3), biotin, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate, cupric sulfate, folic acid, ferric pyrophosphate, iron, magnesium lactate, magnesium carbonate, magnesium sulfate, monopotassium phosphate, monosodium phosphate, phosphorus, potassium iodide, potassium phosphate, riboflavin, sodium sulfate, sodium gluconate, sodium polyphosphate, sodium bicarbonate, thiamine mononitrate, vitamin D3, vitamin A palmitate, zinc gluconate, zinc lactate, or zinc sulfate; Opacifying agents such as ester gun, brominated vegetable oil (BVO), or sucrose acetate isobutyrate (SAIB); buffers, such as sodium citrate, potassium citrate, or salts; Flavors such as propylene glycol, ethyl alcohol, glycerin, gum arabic (gum acacia), maltodextrin, modified corn starch, dextrose, natural flavors, natural flavors including other natural flavors (natural flavors WONF), natural and artificial flavors, artificial flavors, silicon dioxide, magnesium carbonate, or tricalcium phosphate; or Starches and stabilizers such as pectin, xanthan gum, carboxymethylcellulose (CMC), polysorbate 60, polysorbate 80, medium chain triglycerides, cellulose gel, cellulose gum, sodium caseinate, modified food starch, gum arabic (gum acacia), inulin, or carrageenan may include.

[0069] The ingestible composition can have any suitable pH. In some embodiments, the flavor modulating compound enhances the sweetness of a sweetener over a wide range of pH, for example, from low to neutral pH. Low and neutral pH includes, but is not limited to, a pH of about 2.5 to about 8.5, about 3.0 to about 8.0, about 3.5 to about 7.5, and about 4.0 to about 7. In certain embodiments, the compounds disclosed and described herein, individually or in combination, can enhance the perceived sweetness of a fixed concentration of a sweetener in a taste test at a compound concentration of about 50 μM, 40 μM, 30 μM, 20 μM, or 10 μM, both at low and neutral pH values. In certain embodiments, the enhancement factor of the compounds disclosed and described herein, individually or in combination, at low pH is substantially similar to the enhancement factor of the compounds at neutral pH. Due to such consistent sweetness enhancement properties over a wide range of pH, the compounds disclosed and described herein can be used extensively, individually or in combination, in a variety of food and beverage products.

[0070] Ingestible compositions described according to any of the preceding embodiments, in certain embodiments, also include one or more additional flavor modulating compounds, such as a sweetness enhancing compound (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a bitterness blocking compound, an umami enhancing compound, a sour, licorice or astringency reducing compound, a saltiness enhancing compound, a cooling effect enhancing compound, a mouthfeel enhancing compound, or a combination of any of the foregoing.

[0071] In some embodiments, the ingestible composition comprises a sweetness enhancer. Any suitable sweetness enhancer can be used in the flavor modulating compositions disclosed herein, including synthetic sweetness enhancers, natural sweetness enhancers, or any combination thereof.

[0072] Examples of suitable synthetic sweetener enhancers include, but are not limited to, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)isonicotinamide or any of its edible acceptable salts, or any of the compounds described in U.S. Pat. Nos. 8,541,421; 8,815,956; 9,834,544; 8,592,592; 8,877,922; 9,000,054; and 9,000,051, and U.S. Patent Application Publication No. 2017 / 0119032.

[0073] Suitable examples of natural sweetener enhancers include, but are not limited to, hesperitin dihydrochalcone, hesperitin dihydrochalcone-4'-O' glucoside, neohesperitin dihydrochalcone, brazzein, hesperidin, phyllodulcin, naringenin, naringin, phloretin, glucosylated steviol glycosides, (2R,3R)-3-acetoxy-5,7,4'-trihydroxyflavanone, (2R,3R)-3-acetoxy-5,7,3'-trihydroxy-4'-methoxyflavanone, rubusoside, thaumatin, monellin, miraculin, glycyrrhizin and its food acceptable salts (such as the monoammonium salt), naringin dihydrochalcone, myricetin, nobiletin, polymethoxyflavones, mixed methoxy and hydroxyflavones, quercetin, certain amino acids, and the like. As used herein, the term "glucosylated steviol glycoside" refers to the product of enzymatic glucosylation of naturally occurring steviol glycoside compounds. Glucosylation generally occurs through glycosidic linkages such as α-1,2, α-1,4, α-1.6, β-1,2, β-1,4, and β-1,6.

[0074] In some embodiments of any of the preceding embodiments, the edible composition is 3-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propylpropanamide, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)isonicotinamide or a edible acceptable salt thereof. In some embodiments, the flavor modulating composition comprises N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)isonicotinamide or a edible acceptable salt thereof. In some embodiments, the flavor modulating composition comprises N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)isonicotinamide.

[0075] The sweetness enhancer may be present in the flavor modulating composition in any suitable amount relative to the flavor modulating composition, such as from 1:1 to 500:1, or from 2:1 to 500:1, or from 5:1 to 500:1, or from 10:1 to 500:1, or from 1:1 to 300:1, or from 2:1 to 300:1, or from 5:1 to 300:1, or from 10:1 to 300:1.

[0076] In some further embodiments, the ingestible composition comprises a flavor modulating compound disclosed herein according to any of the above embodiments or combinations of embodiments, in combination with one or more umami enhancing compounds. Such umami enhancing compounds include, but are not limited to, naturally occurring compounds such as (2R,4R)-1,2,4-trihydroxyheptadeca-16-ene, (2R,4R)-1,2,4-trihydroxyheptadeca-16-yne, [8]-gingerdiol diacetate,

[10] -gingerdiol diacetate, ericamide (FEMA 4877), rubemamine (FEMA 4310), rubecenamin (FEMA 4773), or synthetic compounds such as those described in U.S. Pat. Nos. 8,735,081; 8,124,121; and 8,968,708, such as N-(heptan-4-yl)benzo-[d][1,3]dioxole-5-carboxamide.

[0077] In some further embodiments, the ingestible composition comprises a flavor modulating compound disclosed herein according to any of the above embodiments or combinations of embodiments in combination with one or more cooling effect enhancing compounds. Such cooling effect enhancing compounds include, but are not limited to, naturally occurring compounds such as menthol or its analogs, or synthetic compounds such as those described in U.S. Patents 9,394,287 and 10,421,727.

[0078] In some further embodiments, the ingestible composition comprises the flavor modulating compound disclosed herein according to any of the above embodiments or combinations of embodiments in combination with one or more bitterness blocking compounds.Such bitterness blocking compounds include, but are not limited to, naturally occurring compounds, such as menthol or its analogs, or synthetic compounds, such as the compounds described in U.S. Patent Nos. 8,076,491; 8,445,692; and 9,247,759.In some embodiments, the bitterness blocking compound is 3-(1-((3,5-dimethylisoxazol-4-yl)-methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)-imidazolidine-2,4-dione.

[0079] In some further embodiments, the ingestible composition comprises a flavor modulating compound disclosed herein according to any of the above embodiments or combinations of embodiments in combination with one or more taste modulating compounds of sour taste.

[0080] In some further embodiments, the ingestible composition comprises a flavor modulating compound disclosed herein according to any of the above embodiments or combinations of embodiments in combination with one or more mouthfeel modifying compounds, such as polymethoxyflavones or mixed hydroxy and methoxyflavones.

[0081] In some further embodiments, the ingestible composition comprises a flavor modulating compound disclosed herein according to any of the above embodiments or combinations of embodiments in combination with one or more flavor masking compounds, including, but not limited to, cellulosic materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonates), and the like.

[0082] In some further embodiments, the flavor modulating composition comprises one or more mouthfeel modifying compounds, including, but not limited to, tannins, cellulosic materials, bamboo flour, and the like.

[0083] In some further embodiments, the flavor modulating composition comprises one or more flavor masking compounds, including, but not limited to, cellulosic materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonates), and the like.

[0084] In some embodiments, the flavor modulating compounds described above are included to improve other tastants that may be present in the edible composition itself or that may be included in a flavored product using such a composition, including sweeteners, umami tastants, kokumi tastants, bitter tastants, sour tastants, and the like.

[0085] In some embodiments, the ingestible composition comprises a yeast extract, such as a yeast lysate. Such an extract can be obtained from any suitable yeast strain, where such an extract is suitable for human consumption. Non-limiting examples of such yeasts include yeasts of the genus Saccharomyces, such as Saccharomyces cerevisiae or Saccharomyces pastorianus; yeasts of the genus Candida, such as Candida utilis; yeasts of the genus Kluyveromyces, such as Kluyveromyces lactis or Kluyveromyces marxianus; yeasts of the genus Pichia, such as Pichia pastoris; yeasts of the genus Debaryomyces hansenii, such as Debaryomyces spp. and Zygosaccharomyces yeast such as Zygosaccharomyces mellis. In some embodiments, the yeast is harvested after brewing beer, sake, or the like. In some embodiments, the yeast is harvested and then dried (dried yeast).

[0086] Such extracts can be produced by any suitable means. Generally, yeast extracts or lysates are produced by extracting the contents of yeast cells from cell wall material. In many cases, digestive enzymes in the cells (or additional enzymes added to the composition) break down proteins and polynucleotides in the yeast into amino acids, oligopeptides (e.g., 2-10 peptides), nucleotides, oligonucleotides (2-10 nucleotides), and mixtures thereof. Yeast lysates can be produced by dissolving yeast. For example, in some embodiments, yeast after culture is disrupted or dissolved by enzymatic degradation, autolysis, alkaline extraction, hot water extraction, acid degradation, ultrasonic disruption, homogenizer disruption, freeze-thawing, or the like (two or more of these may be used in combination) to obtain yeast lysates. Yeast can be cultured by conventional methods. In some embodiments, yeast after culture is heat-treated and then treated with a lytic enzyme to obtain enzymatic lysates. The heat treatment conditions are, for example, 80°C to 90°C for 5 to 30 minutes. As the lytic enzyme used in the enzymatic decomposition method, various enzymes can be used as long as they can lyse the yeast cell wall. The reaction conditions can be set to be optimal or suitable for the lytic enzyme used, and specific examples include a temperature of 50°C to 60°C and a pH of 7.0 to 8.0. The reaction time is not particularly limited, and can be, for example, 3 to 5 hours.

[0087] Compositions comprising yeast lysate can be obtained from a variety of commercially available sources. For example, in some embodiments, the yeast lysate is provided by a flavoring additive sold under the name MODUMAX (DSM Food Specialties BV, Delft, The Netherlands).

[0088] Flavored Products and Concentrates In certain aspects, the present disclosure provides a flavored product comprising the ingestible composition of any of the preceding aspects. In some embodiments, the flavored product is a beverage, such as soda, flavored water, tea, etc. In some other embodiments, the flavored product is a food product, such as yogurt.

[0089] In embodiments where the flavored product is a beverage, the beverage may be selected from the group consisting of fortified sparkling beverages, cola, lemon-lime flavored sparkling beverages, orange flavored sparkling beverages, grape flavored sparkling beverages, strawberry flavored sparkling beverages, pineapple flavored sparkling beverages, ginger ale, root beer, fruit juice, fruit flavored juice, fruit juice drink, nectar, vegetable juice, vegetable flavored juice, sports drink, energy drink, fortified water drink, vitamin fortified water, near water drink, coconut water, tea type beverage, coffee, cocoa drink, beverage containing dairy ingredients, beverage containing grain extract, and smoothie. In some embodiments, the beverage may be a soft drink.

[0090] In certain embodiments of any of the aspects and embodiments described herein relating to a flavored product, the flavored product is a non-naturally occurring product, such as a processed food or beverage product.

[0091] Further non-limiting examples of food and beverage products or formulations include sweet coatings, frostings, or glazes for such products or any of those included in the soup category, the dried processed food category, the beverage category, the ready meal category, the canned or preserved food category, the frozen processed food category, the refrigerated processed food category, the snack food category, the baked goods category, the confectionery category, the dairy category, the ice cream category, the meal replacement category, the pasta and noodle category, the sauces, dressings, condiments category, the baby food category, and / or the spreads category.

[0092] In general, the soup category refers to canned / preserved, dehydrated, instant, refrigerated, UHT, and frozen soups. For the purposes of this definition, soup means a liquid cooked food prepared from meat, poultry, fish, vegetables, grains, fruits, and other ingredients and may contain visible parts of some or all of these ingredients. It may be clear (as a broth) or thick (as a chowder), smooth, pureed, or filled, ready to drink, semi-concentrated, or concentrated, and may be served hot or cold, as the first or main dish of a meal, or as a snack between meals (sipped like a beverage). Soups can be used as an ingredient to prepare other meal components and may vary from broths (consomme) to sauces (cream or cheese-based soups).

[0093] The dehydrated and culinary food category generally refers to: (i) cooking aid products such as powders, granules, pastes, and concentrated liquid products, including concentrated bouillons, bouillons, and bouillon-like products in pressed cubes, tablets, powders, or granule form, sold separately as finished products or as ingredients in products, sauces, and recipe mixes (regardless of technology); (ii) meal solution products such as dehydrated soup mixes, dehydrated instant soups, dehydrated cooked soups, dehydrated or ambient cooked ready-made meals, and meals and portion-based meals, including pasta, potato, and rice dishes; and (iii) meal garnish products such as condiments, marinades, salad dressings, salad toppings, dips, bread crumbs, batter mixes, shelf-stable spreads, barbecue sauces, liquid recipe mixes, concentrates, and recipe mixes for salads, sold as finished products or as ingredients in products.

[0094] The beverage category generally refers to beverages, beverage mixes, and concentrates, including, but not limited to, carbonated and non-carbonated beverages, alcoholic and non-alcoholic beverages, ready-to-drink beverages, liquid concentrated formulations for preparing beverages such as sodas, and dry powdered beverage precursor mixes. The beverage category also includes alcoholic beverages, soft drinks, sports drinks, isotonic drinks, and hot drinks. Alcoholic beverages include, but are not limited to, beer, cider / perry, FAB, wine, and spirits. Soft drinks include, but are not limited to, carbonated beverages, such as cola and non-cola carbonated drinks; fruit juices, such as juices, nectars, juice drinks, and fruit-flavored drinks; bottled waters, such as sparkling water, spring water, and refined / table water; functional beverages, such as sports drinks, energy drinks, or elixirs, which may be carbonated or non-carbonated; concentrates, such as ready-to-drink liquid concentrates and powder concentrates. Hot or cold drinks include, but are not limited to, coffee or iced coffee, such as fresh coffee, instant coffee, and blended coffee; tea or iced tea, such as black tea, green tea, white tea, oolong tea, and flavored tea; and other beverages, such as flavored, malt, or plant-based powders, granules, blocks, or tablets mixed with milk or water.

[0095] The snack food category generally refers to any food that may be a light informal meal, such as, but not limited to, sweet and savory snacks and snack bars. Examples of snack foods include, but are not limited to, fruit snacks, chips / crisps, extruded snacks, tortilla / corn chips, popcorn, pretzels, nuts, and other sweet and savory snacks. Examples of snack bars include, but are not limited to, granola / muesli bars, breakfast bars, energy bars, fruit bars, and other snack bars.

[0096] The baked goods category generally refers to any edible product whose manufacturing process involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, rolls, cookies, muffins, cereals, toaster pastries, pastries, waffles, tortillas, biscuits, pies, bagels, tarts, quiches, cakes, any baked goods, and any combination thereof.

[0097] The ice cream category generally refers to frozen desserts that contain cream, sugar, and flavors. Examples of ice cream include, but are not limited to, store-bought ice cream; take-home ice cream; frozen yogurt and specialty ice cream; soy, oat, bean (e.g., red and mung bean), and rice-based ice cream.

[0098] The confectionery category generally refers to edible products that have a sweet taste. Examples of confectionery include, but are not limited to, candy, gelatin, chocolate confectionery, sugar confectionery, gum, and the like, and any combination of products.

[0099] The meal replacement category generally refers to any food product intended to replace a regular meal, especially for people with health and fitness concerns. Examples of meal replacements include, but are not limited to, weight loss and recovery products.

[0100] The ready meal category generally refers to any food that can be served as a meal without extensive preparation or processing. Ready meals include products where the manufacturer has added recipe "skill" and therefore are quick, complete, and convenient. Examples of ready meals include, but are not limited to, canned / preserved, frozen, dried, and refrigerated ready meals; dinner mixes; frozen pizza; refrigerated pizza; and pre-prepared salads.

[0101] The pasta and noodles category includes, but is not limited to, canned, dried, and refrigerated / fresh pasta; and any pasta and / or noodles, such as plain, instant, refrigerated, frozen, and snack noodles.

[0102] The canned / preserved food category includes, but is not limited to, canned / preserved meat and meat products, fish / seafood, vegetables, tomatoes, beans, fruit, ready meals, soups, pasta, and other canned / preserved foods.

[0103] Frozen processed food categories include, but are not limited to, frozen processed red meat, processed poultry, processed fish / seafood, processed vegetables, meat substitutes, processed potatoes, bakery products, desserts, ready meals, pizza, soups, noodles, and other frozen foods.

[0104] Dry packaged food categories include, but are not limited to, rice, dessert mixes, dry ready meals, dehydrated soups, instant soups, dry pastas, plain noodles, and instant noodles. Refrigerated packaged food categories include, but are not limited to, refrigerated processed meats, processed fish / seafood products, lunch kits, fresh cut fruit, ready meals, pizza, prepared salads, soups, fresh pastas, and noodles.

[0105] The sauces, dressings, and condiments category includes, but is not limited to, tomato paste and puree, bouillon / stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy-based sauces, pasta sauces, wet / cooking sauces, dry sauces / powder mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrettes, dips, pickles, and other sauces, dressings, and condiments.

[0106] Baby food categories include, but are not limited to, milk-based or soy-based formulas; as well as cooked, dried, and other baby foods.

[0107] Spread categories include, but are not limited to, jams and preserves, honey, chocolate spreads, nut-based spreads, and yeast-based spreads.

[0108] The dairy category generally refers to edible products made from mammalian milk. Examples of dairy products include, but are not limited to, drinking milk products, cheese, yogurt, and sour milk beverages, as well as other dairy products.

[0109] Further examples of flavoured products, in particular food and beverage products or formulations, are given below. Exemplary ingestible compositions include one or more of confectionery, chocolate confectionery, tablets, count lines, bagged self lined / soft lines, boxed assortments, standard boxed assortments, twist wrapped miniatures, seasonal chocolates, chocolates with toys, alfajores, other chocolate confectionery, mints, standard mints, strong mints, hard candies, lozenges, gums, jellies and chewing confectionery, toffees, caramels and nougat, medicated confectionery, lollipops, licorice, other sugar confectionery, bread, bagged / industrially produced bread, unbagged / specialty bread, sweet bread, cake, bagged / industrially produced cake, unbagged / specialty cake, cookies, chocolate coated biscuits, sandwich biscuits, filled biscuits, savory biscuits and crackers, bread substitutes, breakfast cereals, rte cereals, home breakfast cereals, flakes, muesli, other cereals, children's breakfast cereals, hot cereals, ice cream, ice cream for store consumption. Cream, individually packed dairy ice cream, individually packed ices, multipack dairy ice cream, multipack ices, takeaway ice cream, takeaway dairy ice cream, ice cream desserts, bulk ice cream, takeaway ice cream, frozen yogurt, specialty ice cream, dairy, milk, raw / pasteurized milk, raw / pasteurized full fat milk, raw / pasteurized semi-skimmed milk, long life / uht milk, long life / uht full fat milk, long life / uht semi-skimmed milk, long life / uht nonfat milk, goat's milk, condensed milk condensed milk / evaporated milk, plain condensed milk / evaporated milk, flavoured, functional and other condensed milk, flavoured dairy beverages, dairy only flavoured dairy beverages, flavoured dairy beverages with fruit juice, soy milk, sour milk beverages, cultured milk beverages, coffee whitener, milk powder, flavoured powdered dairy beverages, cream, cheese, processed cheese, spreadable processed cheese, non-spreadable processed cheese, non-processed cheese, spreadable non-processed cheese, hard cheese,Packaged hard cheese, Unpackaged hard cheese, Yogurt, Plain / natural yogurt, Flavoured yogurt, Yogurt with fruit, Probiotic yogurt, Drinkable yogurt, Drinkable yogurt, Probiotic drinkable yogurt, Refrigerated and shelf stable desserts, Dairy based desserts, Soy based desserts, Chilled snacks, Fromagee frais and quark, Plain fromagee frais and quark, Flavoured fromagee frais and quark, Salty fromagee frais and quark, Sweet and salty snacks, Fruit snacks, Chips / crisps, Extruded snacks, Tortilla / corn chips, Popcorn, Pretzels, Nuts, other sweet and salty snacks, Snack bars, Granola bars, Breakfast bars, Energy bars, Fruit bars, Other snack bars, Meal replacement products, Slimming products, Recovery drinks, Ready meals, Canned ready meals, Frozen ready meals, Dehydrated ready meals, Chilled ready meals, Dinner mixes, Frozen pizza, Refrigerated pizza, Soups, Canned soups, Dehydrated soups instant soup, chilled soup, hot soup, frozen soup, pasta, canned pasta, dried pasta, chilled / fresh pasta, noodles, plain noodles, instant noodles, cup / bowl instant noodles, pouch instant noodles, chilled noodles, snack noodles, canned food, canned meat and meat products, canned fish / seafood, canned vegetables, canned tomatoes, canned beans, canned fruit, canned ready meals, canned soup, canned pasta, other canned foods, frozen food, frozen processed red meat, frozen processed poultry, frozen processed fish / seafood, frozen processed vegetables, frozen meat substitutes, frozen potatoes, oven Baked Potato Chips, Other Oven Baked Potato Products, Non Oven Frozen Potatoes, Frozen Bakery Products, Frozen Desserts, Frozen Ready Meals, Frozen Pizza, Frozen Soups, Frozen Noodles, Other Frozen Foods, Dehydrated Foods, Dessert Mixes, Dehydrated Ready Meals, Dehydrated Soups, Instant Soups, Dehydrated Pasta, Plain Noodles, Instant Noodles, Cup / Bowl Instant Noodles, Pouch Instant Noodles, Refrigerated Foods, Refrigerated Processed Meats, Refrigerated Fish / Seafood Products, Refrigerated Processed Fish, Refrigerated Battered Fish, Refrigerated Smoked Fish, Refrigerated Lunch Kits, Refrigerated Ready Meals, Refrigerated Pizza,refrigerated soups, refrigerated / fresh pasta, refrigerated noodles, oils and fats, olive oil, vegetable and seed oils, cooking fats, butter, margarine, spreadable oils and fats, functional spreadable oils and fats, sauces, dressings and condiments, tomato paste and puree, bouillon / stock cubes, stock cubes, gravy granules, liquid stocks and fonds, herbs and spices, fermented sauces, soy based sauces, pasta sauces, wet sauces, dry sauces / powder mixes, ketchup, mayonnaise, regular mayonnaise, mustard, salad dressings, regular salad dressings, low fat salad dressings, vinaigrettes, dips, pickles, other sauces, dressings and condiments, baby food, formula, standard formula, follow-up formula, toddler formula, hypoallergen formula, prepared baby food, dry baby food, other baby food, spreads, jams and preserves, honey, chocolate spreads, nut based spreads, and yeast based spreads. Exemplary ingestible compositions also include confectionery, bakery products, ice cream, dairy products, sweet and savory snacks, snack bars, meal replacement products, ready meals, soups, pastas, noodles, canned foods, frozen foods, dry foods, refrigerated foods, fats and oils, baby foods, or spreads, or mixtures thereof. Exemplary ingestible compositions also include solid or liquid concentrate compositions for preparing breakfast cereals, sweetened drinks, or beverages, ideally to allow for reduced concentrations of known sugar sweeteners or artificial sweeteners.

[0110] Some embodiments provide chewable compositions that may or may not be intended to be swallowed. In some embodiments, the chewable compositions may be gums, chewing gums, sweetened gums, sugarless gums, functional gums, bubble gums, which contain the compounds disclosed and described herein, individually or in combination.

[0111] Typically, at least a sweet receptor modulating amount, a sweet receptor ligand modulating amount, a sweet flavor modulating amount, a sweet flavor imparting amount, a sweet flavor enhancing amount, or a therapeutically effective amount of one or more of the present compounds are added to an ingestible composition, optionally in the presence of a sweetener, such that the ingestible composition having a modulated sweet flavor has an increased sweetness compared to an ingestible composition produced without the compounds of the present invention, typically when judged by a human or animal, or, in the case of formulation testing, by a majority of a panel of at least eight human taste testers by procedures generally known in the art.

[0112] In some embodiments, the compounds disclosed and described herein, individually or in combination, modify the sweetness or other taste characteristics of other natural or synthetic sweet tastants and ingestible compositions made therefrom. In one embodiment, the compounds disclosed and described herein, individually or in combination, may be used or provided at concentrations that enhance their ligands. For example, the compounds disclosed and described herein, individually or in combination, may be present in amounts of 0.001 ppm to 100 ppm, or in amounts of 0.1 ppm to 50 ppm, 0.01 ppm to 40 ppm, 0.05 ppm to 30 ppm, 0.01 ppm to 25 ppm, or 0.1 ppm to 30 ppm, or 0.1 ppm to 25 ppm, or 1 ppm to 30 ppm, or 1 ppm to 25 ppm, or any of the narrower alternative ranges.

[0113] In some embodiments, the flavor modulating compounds disclosed and described herein can be provided individually or in combination in a flavored concentrated formulation suitable for further processing, for example, to produce a ready-to-use (i.e., ready-to-serve) product. A "flavored concentrated formulation" refers to a formulation that needs to be reconstituted with one or more dilution media to become a ready-to-use composition. The term "ready-to-use composition" is used interchangeably herein with "ingestible composition," which refers to any substance that can be taken orally, alone or together with other substances, whether or not it is intended for ingestion. In one embodiment, a ready-to-use composition includes a composition that can be directly ingested by humans or animals. A flavored concentrated formulation is used to impart one or more flavors to a dilution medium or to modulate one or more flavors, typically by mixing with or diluting with one or more dilution media, such as any consumable or ingestible ingredient or product. Such a process of use is often referred to as reconstitution. Reconstitution can be carried out in a domestic or industrial environment. For example, a frozen fruit juice concentrate can be reconstituted in the consumer's kitchen with water or other aqueous medium to obtain a ready-to-drink fruit juice beverage. In another example, soft drink syrup concentrates can be reconstituted with water or other aqueous media by large commercial scale manufacturers to produce ready-to-drink soft drinks. Because flavored concentrated formulations have higher concentrations of flavoring agents or flavor modulating agents than ready-to-use compositions, flavored concentrated formulations are typically not suitable for direct consumption without reconstitution. There are many advantages to using and producing flavored concentrated formulations. For example, one advantage is that flavored concentrated formulations can be reconstituted at the time of use by adding a suitable solvent, solid, or liquid, thus reducing weight and volume for transportation.

[0114] The flavored products described according to any of the foregoing embodiments, in certain embodiments, also include one or more additional flavor modulating compounds, such as a sweetness enhancing compound (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a bitterness blocking compound, an umami enhancing compound, a sourness reducing compound, a saltiness enhancing compound, a cooling effect enhancing compound, or a combination of any of the foregoing.

[0115] In certain embodiments of any of the aspects and embodiments described herein that refer to a sweetened or flavored concentrate, the sweetened or flavored concentrate is a non-naturally occurring product, such as a composition specially manufactured for the production of a flavored product, such as a food or beverage item.

[0116] In one embodiment, the flavored concentrated formulation comprises i) the compounds disclosed and described herein, either individually or in combination; ii) a carrier; and iii) optionally at least one auxiliary. The term "carrier" refers to a normally inert auxiliary substance, such as a solvent, binder, or other inert medium, which is used in combination with the compound and one or more optional auxiliary to form a formulation. For example, for flavored concentrated formulations, the carrier can be water or starch. In some embodiments, the carrier is the same as the dilution medium for reconstituting the flavored concentrated formulation; in other embodiments, the carrier is different from the dilution medium. The term "carrier" as used herein includes, but is not limited to, carriers that are acceptable for ingestion.

[0117] The term "auxiliary agent" refers to an additive that supplements, stabilizes, maintains, or enhances the intended function or effectiveness of an active ingredient, such as a compound of the present invention. In one embodiment, the at least one auxiliary agent comprises one or more flavoring agents. The flavoring agents may be any flavor known to a person skilled in the art or a consumer, such as flavors of chocolate, coffee, tea, mocha, French vanilla, peanut butter, chai, or combinations thereof. In another embodiment, the at least one auxiliary agent comprises one or more sweeteners. The one or more sweeteners may be any sweetener described in this application. In another embodiment, the at least one auxiliary agent comprises one or more ingredients selected from the group consisting of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, salts, and combinations thereof. Examples of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, and salts are described in U.S. Pat. No. 6,468,576, the contents of which are incorporated herein by reference in their entirety for all purposes.

[0118] In one embodiment, the flavored concentrated formulations may be in a form selected from the group consisting of liquids, including solutions and suspensions, solids, foamy materials, pastes, gels, creams, and combinations thereof, such as liquids containing a certain amount of solids. In one embodiment, the flavored concentrated formulations are in the form of liquids, such as aqueous and non-aqueous. In some embodiments, the flavored concentrated formulations may be carbonated or non-carbonated.

[0119] The flavored concentrated formulation may further include a freezing point depressant, a nucleating agent, or both as at least one adjuvant. A freezing point depressant is an ingestible compound or agent that can depress the freezing point of the liquid or solvent to which the compound or agent is added. That is, a liquid or solution containing the freezing point depressant has a lower freezing point than a liquid or solvent without the freezing point depressant. In addition to depressing the starting freezing point, the freezing point depressant can also reduce the water activity of the flavored concentrated formulation. Examples of freezing point depressants include, but are not limited to, carbohydrates, oils, ethyl alcohol, polyols such as glycerol, and combinations thereof. Nucleating agent refers to an ingestible compound or agent that can promote nucleation. The presence of a nucleating agent in the flavored concentrated formulation can improve the mouthfeel of the frozen blush of the frozen slush by increasing the number of desirable ice crystallization centers, and aid in maintaining the physical properties and performance of the slush at freezing temperatures. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide, and combinations thereof.

[0120] In one embodiment, the flavored concentrated formulation is formulated to have a low water activity to extend shelf life. Water activity is the ratio of the vapor pressure of water in the formulation to the vapor pressure of pure water at the same temperature. In one embodiment, the flavored concentrated formulation has a water activity of less than about 0.85. In another embodiment, the flavored concentrated formulation has a water activity of less than about 0.80. In another embodiment, the flavored concentrated formulation has a water activity of less than about 0.75.

[0121] In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least twice that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least 5 times that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least 10 times that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least 15 times that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least 20 times that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least 30 times that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least 40 times that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation comprises the compound at a concentration at least 50 times that of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation contains the compound at a concentration that is at least 60 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavored concentrated formulation contains the compound at a concentration that is up to 100 times the concentration of the compound in the ready-to-use composition.

[0122] The sweetened or flavored concentrates described according to any of the foregoing embodiments, in certain embodiments, also include one or more additional flavor modulating compounds, such as sweetness enhancing compounds (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), bitterness blocking compounds (e.g., eriodictyol, homoeriodictyol, sterubin, and salts or glycoside derivatives thereof, as well as vanillyl lignans, such as matairesinol and other compounds described in WO 2012 / 146584), umami enhancing compounds (e.g., rubemamine, rubesenamine, (E)-3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide, etc.), sour and / or licorice taste reducing compounds, salty taste enhancing compounds, cooling effect enhancing compounds, or any combination of the foregoing.

[0123] Manufacturing method The flavor modulating compounds disclosed herein can be synthesized by the methods described below or modifications of these methods. Modifications of the methodology include, among others, temperature, solvents, reagents, etc., known to those skilled in the art. Generally, in any of the methods for preparing the compounds disclosed herein, it may be necessary or desirable to protect sensitive or reactive groups on the molecules involved.

[0124] Non-animal protein materials and products made therefrom Products intended to replace or substitute meat and dairy products often rely on a variety of non-animal ingredients, such as starches and proteins derived from plants, algae, fungi, or combinations thereof, to mimic the texture and flavor of meat and dairy products. Non-limiting examples of non-animal proteins are plant proteins, such as soy protein, pea protein, bean protein, and grain protein. Due to compositional differences between such plant and animal-derived ingredients, such as the lack of glutamic acid-containing proteins and glutathione, these products may lack the umami and / or kokumi flavors that consumers traditionally associate with meat and dairy products.

[0125] Thus, in certain aspects, the present disclosure provides a flavored product comprising a plant-based material (such as a plant-based starch, a plant-based protein, or a combination thereof) and a flavor modulating compound disclosed herein. In some further embodiments, the flavored product may comprise any of the combinations of features described above for the ingestible compositions comprising the flavor modulating compounds disclosed herein. In some embodiments, the flavored product is a beverage, such as soy milk, almond milk, rice milk, oat milk, a protein drink, a meal replacement drink, or other similar products. In some other embodiments, the flavored product is a meat replacement product, such as a plant-based chicken product (such as a plant-based chicken nugget), a plant-based beef product (such as a plant-based burger), and the like. In some other embodiments, the flavored product is a protein powder, a meal replacement powder, a plant-based creamer for coffee or tea, and the like. In certain further embodiments, any such product may comprise additional ingredients and have additional features as typically used in the preparation and / or manufacture of such products. For example, the flavor modulating compounds disclosed herein may be combined with other flavors and taste modifiers and may be encapsulated within a particular material according to known techniques in the relevant art. Suitable concentrations of the flavor modulating compounds disclosed herein are described above.

[0126] In some embodiments, the flavored product comprises one or more plant-based proteins that impart a bitter taste that is at least partially reduced by the use of the flavor modulating compounds disclosed herein in the product. Such plant-based proteins include, but are not limited to, pea protein, soy protein, canola (rapeseed) protein, barley protein, chickpea protein, mycoprotein, algae protein, faba bean protein, sunflower protein, wheat protein.

[0127] In some alternative embodiments similar to the above embodiment, algae or fungal proteins or starches are used in place of oat protein, potato protein, etc. In some embodiments, these flavored products also include fiber to provide texture to the product. Fibers suitable for use include, but are not limited to, psyllium fiber, pea fiber, potato fiber, curdlan, soluble corn fiber (dextran and / or maltodextrin), citrus fiber, barley fiber, and combinations thereof. The flavor modulating compounds disclosed herein can be introduced into such products in any suitable manner. In some embodiments, the flavor modulating compounds disclosed herein are incorporated into a flavored emulsion, such as a water-in-oil emulsion, along with other flavoring ingredients.

[0128] Non-meat protein ingredients and products made therefrom Certain non-meat animal proteins, such as milk proteins and proteins from bone broth, are commonly used in food products and are also sold as the main ingredient of certain protein powders. Such proteins may impart bitter flavors that consumers may not want. This is particularly true for protein isolates, such as whey protein, collagen protein, casein protein, and other protein isolates. Thus, the present disclosure provides ingestible compositions comprising non-meat animal proteins and flavor modulating compounds disclosed herein. The flavor modulating compounds disclosed herein can be present in any suitable combination according to the embodiments described in the preceding sections of the present disclosure. In some embodiments, the non-meat animal protein is a bone protein, such as collagen protein, derived from the bones of animals such as cows, pigs, donkeys, horses, chickens, ducks, goats, geese, rabbits, lambs, sheep, buffalo, ostriches, camels, and the like. In some embodiments, the non-meat animal protein is a dairy protein, such as whey protein, casein protein, or any combination thereof. The milk may be from any suitable animal, such as cow, donkey, horse, sheep, buffalo, camel, and the like.

[0129] The flavor modulating compounds disclosed herein can also be incorporated into certain food or beverage products that contain milk or milk-derived ingredients, such as cheese, cheese spreads, yogurt, kefir, milk, processed dairy products, cottage cheese, sour cream, butter, and the like.

[0130] Blocking the bitterness of pharmaceutical ingredients Many drug compounds impart a bitter taste, limiting the ways in which they can be formulated and administered. Thus, in certain aspects, the present disclosure provides pharmaceutical compositions comprising a bitter tasting active pharmaceutical ingredient and a flavor modulating compound disclosed herein. Such pharmaceutical compositions can be in any form suitable for oral administration, such as tablets, lozenges, capsules, powders, solutions, suspensions, etc. Such pharmaceutical compositions can include any suitable pharmaceutical excipients, binders, etc., such as those described in Remington's Pharmaceutical Sciences. In some embodiments, the bitter tasting active pharmaceutical ingredient is an ion channel inhibitor, such as a proton channel inhibitor. Other examples of pharmaceutical active ingredients whose bitterness is reduced by the flavor modulating compounds disclosed herein include, but are not limited to, atropine, brinzolamide, chloramphenicol, chloroquine, clindamycin, dexamethasone, digoxin, diltiazem, diphenhydramine, docusate, dorzolamide, doxepin, doxylamine, enalapril, erythromycin, esomeprazole, famotidine, gabapentin, ginkgolide A, guaifenesin, L-histidine, lomefloxacin, methylprednisolone, ofloxacin, oleuropein, oxyphenonium, pirenzepine, prednisone, ranitidine, trapidil, trimethoprim, and cetirizine.

[0131] Use in oral care products Oral care products often contain ingredients that impart an astringent or bitter off-taste. Such ingredients include menthol, menthol analogs, mint extracts, sodium bicarbonate, alkali metal salts of peroxymonosulfate (potassium peroxymonosulfate), cetylpyridinium chloride, lauramidopropyl betaine, cocamidopropyl betaine, arginine, hydrogen peroxide, chlorhexidine gluconate, zinc phosphate, zinc chloride, zinc citrate, potassium nitrate, pentasodium triphosphate, tetrasodium pyrophosphate, stannous fluoride, thymol, methyl salicylate, eucalyptol, or any combination thereof. Suitable oral care products include toothpastes, mouthwashes, whitening agents, dentifrices, and the like. Thus, such oral care products may, in certain embodiments, include the flavor modulating compounds disclosed herein to mask the bitter or off-taste of such commonly used compounds.

[0132] Working Example The following examples are included to further illustrate the present invention. Of course, the examples should not be construed as specifically limiting the present invention. Variations of these examples within the scope of the claims are within the understanding of those skilled in the art, and are considered to be within the scope of the invention described and claimed herein. The reader will recognize that the skilled artisan and those skilled in the art who understand this disclosure can prepare and use the present invention without the exhaustive examples.

[0133] Example 1 - Disodium Salt of Naringenin (about 10% in water) Naringenin (500 mg, 1.84 mmol) was suspended in water (2 mL) and a solution of NaOH (2 eq) in water (3 mL) was added dropwise with stirring. After addition was complete, the reaction was bubbled with nitrogen and stirring was continued until the solution became homogeneous. This solution could be stored at room temperature under nitrogen for several days without significant change. [ka]

[0134] Example 2: Dipotassium Salt of Naringenin (about 10% aqueous solution) Naringenin (500 mg, 1.84 mmol) was suspended in water (2 mL) and a solution of KOH (2 eq) in water (3 mL) was added dropwise with stirring. After addition was complete, the reaction was bubbled with nitrogen and stirring was continued until the solution became homogeneous. This solution could be stored at room temperature under nitrogen for several days without significant change. [ka]

[0135] Example 3: Disodium salt of Flotellin (about 10% aqueous solution) Flotellin (500 mg, 1.82 mmol) was suspended in water (2 mL) and a solution of NaOH (2 eq) in water (3 mL) was added dropwise with stirring. After the addition was complete, the reaction was bubbled with nitrogen and stirring was continued until the solution became homogeneous. This solution could be stored at room temperature under nitrogen for several days without significant change. [ka]

[0136] Example 4: Dipotassium salt of Flotellin (about 10% aqueous solution) Flotellin (500 mg, 1.82 mmol) was suspended in water (2 mL) and a solution of KOH (2 eq) in water (3 mL) was added dropwise with stirring. After addition was complete, the reaction was bubbled with nitrogen and stirring was continued until the solution became homogeneous. This solution could be stored at room temperature under nitrogen for several days without significant change. [ka]

Claims

1. Formula (I): 【Chemistry 1】 [In the formula, R １ , R ２ and R ３ are independently a hydrogen atom, —OH or —OCH ３ and R １ , R ２ and R ３ at least one of is --OH; the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or combinations thereof; and the dotted lines represent any carbon-carbon double bonds.

2. 2. The flavor modulating compound of claim 1 which is a disodium or dipotassium salt of the compound of formula (I).

3. 3. The flavor modulating compound of claim 1 or 2, wherein the compound of formula (I) is naringenin, said naringenin being in its pure (S) form.

4. 3. The flavor modulating compound of claim 1 or 2, wherein the compound of formula (I) is naringenin, said naringenin being a racemic mixture of its (R) form and its (S) form.

5. Formula (II): 【Chemistry 2】 [In the formula, R １１ , R １２ , R １３ and R １４ are independently a hydrogen atom, —OH or —OCH ３ and R １１ , R １２ , R １３ and R １４ at least one of is --OH; and the alkali metal of the dialkali metal salts and trialkali metal salts is sodium, potassium or a combination thereof.

6. 6. The flavor modulating compound of claim 5 which is a disodium or dipotassium salt of the compound of formula (II).

7. R １１ is -OH or -OCH ３ and R １２ is a hydrogen atom or -OH, and R １３ is —OH, and R １４ The flavor-modulating compound according to claim 5 or 6, wherein is a hydrogen atom or -OH.

8. The flavor modulating compound of claim 7 , wherein the compound of formula (II) is phloretin.

9. Formula (III): 【Chemistry 3】 [In the formula, R ２１ and R ２２ are independently a hydrogen atom, —OH or —OCH ３ and R ２１ and R ２２ At least one of is —OH; R ２３ is C １～６ Alkyl or -CH ２ -R ２４ and R ２４ is -OH, -OCH ３ or combinations thereof; and the alkali metal in the dialkali metal salts and trialkali metal salts is sodium, potassium or combinations thereof.

10. 10. The flavor modulating compound of claim 9 which is a disodium or dipotassium salt of the compound of formula (III).

11. 10. Use of a flavor modulating compound according to any one of claims 1, 5 and 9 to enhance the sweetness of an ingestible composition.

12. 10. Use of a flavor modulating compound according to any one of claims 1, 5 and 9 to reduce the bitterness of an ingestible composition.

13. 10. Use of a flavour modulating compound according to any one of claims 1, 5 and 9 to reduce the calorie content of an ingestible composition.

14. 12. The use of claim 11, wherein the ingestible composition comprises a sweetener, a bitter tastant, or a combination thereof.

15. 11. An ingestible composition comprising the flavor modulating compound of any one of claims 1, 2, 5, 6, 9, and 10 and a sweetener, wherein the sweetener is a steviol glycoside, a mogroside, or a combination thereof.

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