JP2026511252A - Flavor-modifying composition and its use - Google Patents

Abstract

Flavor-modifying compositions and their use for reducing unpleasant tastes in flavored products are described herein. This disclosure further provides flavored products containing such flavor-modifying compositions and one or more unpleasant taste substances. The flavor-modifying compositions described herein are suitable for use in food products, beverage products, or oral care products, such as toothpaste, dental gels, mouthwashes, mouth sprays, toothpaste tablets, and toothpaste powders.

Description

Cross-reference of related applications: This application claims priority to U.S. Provisional Application No. 63/492,535 filed on 28 March 2023 and European Application No. 23183763.4 filed on 6 July 2023, which are incorporated herein by reference as if they were included herein by reference.

This disclosure generally provides flavor-modifying compositions and their uses for reducing unpleasant tastes in flavored products. This disclosure further provides flavored products containing such flavor-modifying compositions and unpleasant taste substances. The flavor-modifying compositions described herein are suitable for use in food products, beverage products, or oral care products, such as toothpaste, dental gels, mouthwashes, mouth sprays, toothpaste tablets, toothpaste powders, and the like.

Background Technology The taste system provides sensory information about the chemical composition of the external environment. Taste transmission is one of the more sophisticated forms of chemically induced sensation in animals. Taste signaling is found throughout the animal kingdom, from simple metazoans to the most complex vertebrates. Mammals are thought to have five basic tastes: sweet, bitter, sour, salty, and umami.

Oral care products often contain many active ingredients, such as antibacterial, whitening, and anti-sensitivity agents, which can cause off-notes in the product. The inclusion of such active ingredients can lead to off-tastes that users find unpleasant. Limiting the concentration of such ingredients is a possible strategy to reduce any unpleasant taste. However, higher concentrations of these ingredients are often desirable for improved effectiveness.

Off-note masking agents exist to meet consumer needs for masking off-notes resulting from these ingredients. However, some off-note masking agents are incompatible with, or insoluble in, flavor oils typically used in food, beverage, or oral care products. This prevents the combination of off-note masking agents and flavor oils into a single flavor delivery system that can be conveniently handled and incorporated into the final product.

Therefore, there is a continuous need for a flavor delivery system containing off-note masking agents and flavor oils that is easy to handle, stable at room temperature for extended periods (i.e., clear and without precipitation).

Summary of the Invention In the first aspect, the present disclosure is:
a) One or more flavored oils,
b) One or more off-note masking agents,
c) One or more nonpolar surfactants,
d) One or more polar surfactants,
e) Water and,
f) The present invention relates to a flavor-modifying composition comprising one or more water-miscible cosolvents.

In a second aspect, this disclosure relates to flavored products containing the flavor-modifying compositions and unpleasant taste substances described herein.

In a third aspect, this disclosure relates to the use of the flavor-modifying compositions described herein for reducing unpleasant tastes in flavored products.

Modes for Carrying Out the Invention The following modes for carrying out the invention describe various aspects and embodiments provided herein. The description should be read from the perspective of those skilled in the art. Therefore, information that is well known to such people will not necessarily be included. It will be apparent to those skilled in the art that the various aspects and embodiments provided herein may be combined in any way without departing from the spirit of this disclosure.

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 will have the meanings they would have in the context of this disclosure to those skilled in the art. In some cases, a term or phrase may be defined in the singular or plural form. In such cases, it is understood that any singular term may include its plural counterpart, and vice versa, unless expressly indicated otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as generally understood by those skilled in the art to whom this disclosure relates.

As used herein, the terms "a," "an," or "the" mean "one or more" or "at least one," unless otherwise specified.

While compositions and methods are described in terms of “composing,” “containing,” or “including” various components or processes, compositions and methods may also “consistently of” or “consistently of” various components, substances, and processes. As used herein, the term “consistently of” shall be interpreted as including additional components, substances, or processes that do not substantially affect the basic and novel properties of the enumerated components, substances, or processes, as well as the composition or method. In some embodiments, compositions according to embodiments of this disclosure that “consistently of” the enumerated components or substances do not include any additional components or substances that alter the basic and novel properties of the composition.

It should be understood that any numerical range enumerated herein is intended to include all subranges contained therein. For example, the range "1 to 10" is intended to include all subranges between the enumerated minimum value of 1 and the enumerated maximum value of 10, and including those subranges, i.e., all subranges having a minimum value of 1 or greater and a maximum value of 10 or less. Since the disclosed numerical ranges are continuous, they include all values between the minimum and maximum values. Unless otherwise specified, the various numerical ranges specified in this application are approximations.

As used herein, the terms “about” or “approximately” mean, unless otherwise indicated, an acceptable error in a particular value as determined by those skilled in the art, the error of which depends in part on how the value is measured or determined. In certain embodiments, the terms “about” or “approximately” mean within one, two, three, or four standard deviations. In certain embodiments, the terms “about” or “approximately” mean within 50%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.05% of a given value or range.

As used herein, "optionally" means that the events described below may or may not occur. In some embodiments, the optional events do not occur. In some other embodiments, the optional events occur one or more times.

Throughout this disclosure, various publications may be incorporated by reference. If the meaning of any wording in such incorporated publications conflicts with the meaning of the wording in this disclosure, the meaning of the wording in this disclosure shall prevail unless otherwise indicated.

As used herein, “or” should be given its broadest reasonable interpretation and should not be limited to a binary configuration. Thus, the phrase “including A or B” means that A may exist and B does not exist, or B exists and A does not exist, or both A and B exist. Furthermore, if, for example, A defines a class that may have multiple members, such as _A1 and _A2 , then one or more members of the class may exist simultaneously.

Where used herein, “for example,” “for instance,” “such as,” or “including” means to introduce examples that further clarify a more general subject matter. Unless otherwise specified, such examples are provided solely to aid in understanding the embodiments shown in this disclosure and are not intended to limit them in any way. These phrases do not indicate any preference of any kind for the embodiments disclosed.

In the first aspect, this disclosure is:
a) One or more flavored oils,
b) One or more off-note masking agents,
c) One or more nonpolar surfactants,
d) One or more polar surfactants,
e) Water and,
f) The present invention relates to a flavor-modifying composition comprising one or more water-miscible cosolvents.

One or more flavor oils suitable for use in the flavor-modifying compositions described herein may be any flavor oils known to those skilled in the art. These flavor oils may be selected from synthetic flavor oils and flavoring agents or flavoring oils, oleoresins, and extracts derived from plants, leaves, flowers, fruits, etc., as well as combinations thereof. Examples of non-specific representative flavor oils include spearmint oil, cinnamon oil, wintergreen oil (methyl salicylate), peppermint oil, Japanese mint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, nutmeg oil, allspice, sage oil, mace, bitter tonsil oil, cassia oil, and citrus oils (e.g., lemon, orange, lime, grapefruit, yuzu, sudachi), as well as fruit essential oils (apple, pear, peach, grape, blueberry, strawberry, raspberry, cherry, plum, pineapple, watermelon, apricot, banana, melon, apricot, plum, cherry, raspberry, blackberry, tropical fruits, mango, mangosteen, pomegranate, papaya, etc.).

In one embodiment, one or more flavoring oils are selected from the group consisting of mint oils such as spearmint oil, peppermint oil, and Japanese mint oil; cinnamon oil, wintergreen oil (methyl salicylate), clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, nutmeg oil, allspice, sage oil, mace, bitter tonsil oil, cassia oil, and citrus oils. In one embodiment, one or more flavoring oils include mint oil.

In some embodiments, the flavor-modifying composition may contain two or more flavoring oils.

The amount of one or more flavoring oils present in the flavor-modifying composition is not particularly limited. However, in some embodiments, the flavor-modifying compositions of this disclosure allow for considerably high concentrations of flavoring oils. In one embodiment, one or more flavoring oils are present in an amount of 20% to 60% by weight, typically 40% to 55% by weight, based on the total weight of the composition.

One or more off-note masking agents suitable for use in the flavor-modifying compositions described herein may be any off-note masking agents known to those skilled in the art. An off-note is an undesirable taste note that may be present in a flavor-modifying composition or in a flavored product into which a flavor-modifying composition may be incorporated. Examples of off-notes include, but are not limited to, bitter notes, medicinal notes, metallic notes, or any combination thereof, and are typically caused by the presence of unpleasant taste substances. The perception of unpleasant tastes can be reduced using off-note masking agents known to those skilled in the art. Examples of off-note masking agents include, but are not limited to, glucosylated natural steviol glycosides.

As used herein, the term “natural steviol glycoside” refers to steviol glycosides naturally found in plants of the species Stevia rebaudiana, Stevia phlebophylla, or Rubus chingii. Such compounds are glycosides of the diterpene steviol. Some non-limiting examples include stevioside, rebaudioside A, rebaudioside C, and dulcoside A. As used herein, the term “glucosylated natural steviol glycoside” refers to compounds obtained by enzymatic glucosylation of natural steviol glycosides to increase the degree of glucosylation. As used herein, the term “GSG” is used interchangeably with “glucosylated natural steviol glycoside.”

In various embodiments and models disclosed herein, any suitable GSG can be used. Therefore, the GSG can have any suitable further degree of glucosylation and any suitable type of glucosylation. In some embodiments, the GSG used in the flavor-modifying composition has a glucosylation degree of at least 1.0, meaning that at least 1 mole of glucose is enzymatically added to the natural steviol glycoside per mole of natural steviol glycoside. In some other embodiments, the GSG used in the flavor-modifying composition has a glucosylation degree of at least 1.1, or at least 1.2, or at least 1.3, or at least 1.4, or at least 1.5, or at least 1.6, or at least 1.7, or at least 1.8, or at least 1.9, or at least 2.0, or at least 2.1, or at least 2.2, or at least 2.3, or at least 2.4, or at least 2.5. The glucosylation can be of any suitable type. For example, in some embodiments, the glucose enzymatically added to the natural steviol glycoside is α-glucose, β-glucose, or a combination thereof. In some embodiments, the glucose enzymatically added to the natural steviol glycoside is α-glucose. In some embodiments, the glucose enzymatically added to the natural steviol glycoside is β-glucose. In some embodiments, the glucose enzymatically added to the natural steviol glycoside is a combination of α-glucose and β-glucose. The glucose added by enzymatic glucosylation can be incorporated via any suitable linkage. Typically, the added glucose unit is attached to another glucose unit already present on the natural steviol glycoside. In some embodiments, the enzymatically added glucose unit is attached via a 1,6 linkage, meaning the glucose unit is attached via position 1 of the added glucose unit and position 6 of a glucose unit already present on the natural steviol glycoside. In some other embodiments, the enzymatically added glucose unit is attached via a 1,4 linkage. In some other embodiments, the enzymatically added glucose unit is attached via a 1,2 linkage.

In one embodiment, one or more off-note masking agents include one or more glucosylated natural steviol glycosides.

The amount of one or more off-note masking agents in the flavor-modifying composition according to this disclosure is not particularly limited. However, in suitable embodiments, one or more off-note masking agents are present in an amount of 0.01% to 5% by weight, typically 0.2% to 4% by weight, based on the total weight of the composition.

One or more nonpolar surfactants suitable for use in the flavor-modifying compositions described herein may be any nonionic surfactant having a hydrophilic-lipophilic balance (HLB) value of 10 or less.

As used herein, hydrophilic-lipophilic balance (HLB) refers to the balance between the hydrophilic (water-loving) and lipophilic (oil-loving) properties of a surfactant molecule. A surfactant is a molecule that has both a hydrophilic and a lipophilic part. The HLB value of a surfactant is a numerical value that indicates its relative hydrophilic and lipophilic characteristics. A high HLB value (typically 10 or higher) indicates a more hydrophilic surfactant, while a low HLB value (typically less than 10) indicates a more lipophilic surfactant. The HLB value is often used to determine the effectiveness of a surfactant in a particular application, such as emulsifying oil in water or water in oil, and is therefore a practical guideline in formulation. HLB can also be used to describe the relationship between the molecular weight of the hydrophilic and lipophilic portions of amphiphilic molecules (Griffin, W.C. Classification of surface-active agents by HLB. J. Soc. Cosmet. Chem. 1, 1949, 311-326).

Examples of nonpolar surfactants typically include, but are not limited to, sorbitan fatty acid esters selected from the group consisting of sorbitan monostearate (Span 60), sorbitan tristearate (Span 65), sorbitan monolaurate (Span 20), sorbitan monooleate (Span 80), sorbitan monopalmitate (Span 40), and sorbitan trioleate (Span 85); lecithin, typically soy lecithin; (poly)glyceryl esters, typically glycerol monooleate; and mixtures thereof.

The amount of one or more nonpolar surfactants is not particularly limited. However, in suitable embodiments, one or more nonpolar surfactants are present in an amount of 1% to 40% by weight, typically 5% to 35% by weight, relative to the total weight of the composition.

One or more polar surfactants suitable for use in the flavor-modifying compositions of this disclosure may be any nonionic surfactant having a hydrophilic-lipophilic balance (HLB) value greater than 10.

Examples of polar surfactants include, but are not limited to, poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers, typically triblock copolymers (poloxamer 407) consisting of a central hydrophobic block of polypropylene glycol with two hydrophilic blocks of polyethylene glycol on the sides; one or more PEG sorbitan fatty acid esters typically selected from the group consisting of PEG sorbitan monolaurate (polysorbate 20), PEG sorbitan monooleate (polysorbate 80), PEG sorbitan monopalmitate (polysorbate 40), and PEG sorbitan stearate (polysorbate 60); PEG-modified hydrogenated castor oil (Cremophor RH 40); sugar esters, typically sucrose monopalmitate and sucrose monolaurate; (poly)glyceryl esters, e.g., decaglyceryl monooleate, alkyl glucosides, and mixtures thereof.

The amount of one or more polar surfactants is not particularly limited. However, in suitable embodiments, one or more polar surfactants are present in an amount of 1% to 40% by weight, typically 5% to 35% by weight, relative to the total weight of the composition.

One or more water-miscible cosolvents suitable for use in the flavor-modifying compositions of this disclosure may be any solvent or blend of solvents that are miscible with water. Examples of water-miscible cosolvents include, but are not limited to, propylene glycol, glycerol, ethanol, triethyl citrate, triacetin, ethyl lactate, ethyl acetate, propanol, isopropanol, and mixtures thereof.

In some cases, ethanol may not be used in the flavor-modifying compositions of this disclosure, for example, to meet consumer demand for less astringent oral care products. Therefore, in one embodiment, the flavor-modifying compositions of this disclosure are ethanol-free. As used herein, the phrase "ethanol-free" means the absence of external additions of the material referred to by that phrase, and the absence of any detectable amount of the material that can be observed by analytical techniques known to those skilled in the art, such as gas chromatography.

The amount of one or more water-miscible cosolvents is not particularly limited. However, in suitable embodiments, one or more water-miscible cosolvents are present in an amount of 0.01% to 30% by weight, typically 5% to 25% by weight, relative to the total weight of the composition.

The flavor-modifying compositions of this disclosure can be characterized by the weight ratio of one or more flavor oils to one or more off-note masking agents. In one embodiment, the weight ratio of one or more flavor oils to one or more off-note masking agents is in the range of 20:1 to 100:1.

In some embodiments, the flavor-modifying composition is in the form of a water-in-oil microemulsion.

As those skilled in the art will understand, emulsions such as macroemulsions, nanoemulsions, or microemulsions are mixtures of two liquids that are immiscible due to their differing polarities (hydrophobic vs. hydrophilic). In an emulsion, one liquid (dispersed phase, discontinuous phase, or internal phase) is dispersed in another liquid (outer phase or continuous phase). One liquid is typically polar, and the other is typically nonpolar. Therefore, a nonpolar phase may be dispersed within a polar phase, or a polar phase may be dispersed within a nonpolar phase. When the nonpolar phase, typically an oil phase, is dispersed within the polar phase, typically an aqueous phase, such an emulsion is an oil-in-water emulsion. When the polar phase is dispersed within the nonpolar phase, the emulsion is a water-in-oil emulsion.

Bi-emulsions having three distinct phases are known, such as water-in-oil (WOW) emulsions and their opposite, oil-in-water (OWO) emulsions. In the WOW type, the three distinct phases consist of a polar phase droplet, a non-polar phase in which it is dispersed, and a continuous polar phase surrounding it. Such a three-phase emulsion is not intended in this disclosure. Therefore, the emulsions of this disclosure are not bi-emulsions; that is, the emulsions of this disclosure are neither water-in-oil (WOW) emulsions nor oil-in-water (OWO) emulsions.

In one embodiment, the water-in-oil microemulsion is
a') A discontinuous aqueous phase comprising one or more off-note masking agents and water,
b') A continuous oil phase containing one or more flavored oils.

The compositions according to this disclosure are clear at room temperature (RT) and are stable over a wide temperature range (e.g., RT ± 10 to 20°C, typically 10°C to 45°C, more typically 3°C to 45°C) for extended periods, typically several days, more typically several weeks, and even more typically several months or longer.

The term "transparent" means that a mixture without colorants or fluorescent agents has a transmittance value of 100% visible light (500–800 nm) over a path length of 1 cm, relative to desalinated water.

The term "stable" means that a mixture does not undergo phase separation and remains clear without any detectable signs of turbidity, cloudiness, or precipitation.

The flavor-modifying compositions described herein can be prepared according to methods known to those skilled in the art. One suitable method is:
a') A step of preparing an oil phase by mixing one or more flavoring oils, one or more nonpolar surfactants, one or more polar surfactants, and one or more water-miscible solvents, and optionally heating the combination at a temperature typically between 30°C and 50°C while stirring until a homogeneous liquid is obtained.
b') A step of preparing an aqueous phase by mixing one or more off-note masking agents with water and stirring, typically at room temperature, until one or more off-note masking agents are completely dissolved.
c') The process includes mixing the oil phase prepared in step a') and the aqueous phase prepared in step b') while stirring, typically at room temperature, until a homogeneous liquid, typically a water-in-oil microemulsion, is obtained.

In a second aspect, this disclosure relates to flavored products containing the flavor-modifying compositions and unpleasant taste substances described herein.

The amount of flavor-modifying composition in the flavored product is not particularly limited. In one embodiment, the flavor-modifying composition is present in an amount of 0.001% to 5% by weight, typically 0.01% to 1% by weight, and more typically 0.1% to 0.5% by weight, relative to the total weight of the flavored product.

In one embodiment, the flavored product is a food product, a beverage product, an oral care product, or a pharmaceutical product.

In some embodiments, the flavored product further comprises cooling compounds, cooling-enhancing compounds, sweeteners other than steviol glycosides or mogrosides, or combinations thereof.

As used herein, "cooling compound" refers to a compound that modulates the TRPM8 receptor.

Exemplary cooling compounds include (-)-menthol, N-ethyl-p-menthyl-3-carboxamide, cubebol, isopulegol, 3-(L-menthoxy)propane-1,2-diol, cis/trans-p-menthane-3,8-diol, 3-(L-menthoxy)-2-methylpropane-1,2-diol, 2-[2-(p-menthane-3-yloxy)ethoxy]ethanol, and menthoxyethanol. (1R,2R,4R)-1-(2-hydroxy-4-methylcyclohexyl)ethenone, (1R,2R,5R)-N-ethyl-5-methyl-2-(propa-1-en-2-yl)-cyclohexanecarboxamide, N-(3-hydroxy-4-methoxyphenyl)-2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-[4-(cyanomethyl)phenyl]-2-isopropyl-5, 5-Dimethylcyclohexanecarboxamide, N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethylcyclohexane-1-carboxamide, L-menthol lactate, (-)-menthylethylene glycol carbonate, (-)-menthone 1,2-glycerol ketal, D/L-menthone 1,2-glycerol ketal, (-)-menthyl-1-propylene glycol carbonate, (-)-menthyl-2-propylene glycol carbonate, D/L-menthyl-1-propylene glycol carbonate, D/L-menthyl-2-propylene glycol carbonate, (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide, menthyl ethylamide oxalate, (E)-3-benzo[1,3]dioxose L-5-yl-N,N-diphenyl-2-propenamide, 3,4-methylenedioxycinnamic acid, N,N-diphenylamide, N,N-dimethyl(-)-menthylsuccinimide, (1R,2S,5R)-N-(4-(carbamoylmethyl)phenyl)-menthylcarboxamide, (-)-menthylpyrrolidone carboxylate, L-phenylephrine p-menthanecarboxamide, (1R,2S,5R)-N - (4-(cyanomethyl)-phenyl)menthylcarboxamide, (1R,2S,5R)-N-(2-(pyridine-2-yl)ethyl)menthylcarboxamide, 6-isopropyl-3,9-dimethyl-1,4-dioxaspiro[4.5]decane-2-one, (1R,2R,4S)-dihydroumbellol, N-ethyl-p-menthane-3-carboxamide, 2-isopropyl-N,2,3-trimethyl Examples of compounds selected from the group consisting of tilamide, ethyl 3-(p-menthane-3-carboxamide) acetate, N-ethyl-2,2-diisopropylbutanamide, N-(1,1-dimethyl-2-hydroxyethyl)-2,2-dimethylbutanamide, N-cyclopropyl-5-methyl-2-isopropyl-cyclohexanecarbonecarboxamide, (-)-menthyl acetoacetate, (-)-menthyl succinate, (-)-menthyl(S)-3-hydroxybutyrate, (-)-menthyl glutarate, 1-[2-hydroxyphenyl]-4-[2-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one, di-(-)-menthyl glutarate, N-(2-hydroxyethyl)-2,3-dimethyl-2-isopropylbutanamide, and any combination thereof, are not limited to these.

In some embodiments, the cooling compound is one of the cooling compounds described in International Publication No. 2021/074281, for example, (2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)(1,2,3-thiadiazole-5-yl)methanone, (2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)(thietan-3-yl)methanone, (2,2-dimethylcyclopropyl)(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)methanone, (2-ethoxycyclopropyl)(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H- (Imidazole-2-yl)piperidine-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)methanone, (2S)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, (5-methyltetrahydrofuran-3-yl)(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)methanone, (E)-1-(2-(5-(3,4-difluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbuta-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2- (Iyl)piperidine-1-yl)buta-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)penta-3-en-1-one, (R)-2-(methylthio)-1-((R)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propane-1- On, (S)-2-(methylthio)-1-((R)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, (S)-2-methyl-1-((R)- 2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, (tetrahydrofuran-3-yl)(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)methanone, 1-(2-(1H-benzo[d]imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propane n-1-one, 1-(2-(4-(1-methyl-1H-pyrazole-4-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio )propan-1-one, 1-(2-(4-(2,3-dihydrobenzofuran-5-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydrobenzofuran-6-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,5-dimethylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-chlorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-cyclopropyloxazo (Ill-5-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-fluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxyphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylaminomethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2- (methylthio)propan-1-one, 1-(2-(4-(3,5-dimethylisoxazole-4-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-chloro-4-methylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxidethiomorpholino)methyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1- On, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethoxy)-3-fluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-( 4-(tert-butyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclobutylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazole-2-yl)piperidine- 1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-((dimethylaminomethyl)thiophen-2-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan n-1-one, 1-(2-(4-(5-methylpyridine-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridine-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(benzo[b]thiophen-6-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-methyl-5-phenyl-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine -1-yl)-2-((trifluoromethyl)thio)ethane-1-one, 1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)hexa-3,5-dien-1-one, 1-(2-(4-phenyl-1H-imidazole- 2-yl)piperidine-1-yl)penta-4-en-1-one, 1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 1-(2-(5-(2,3-difluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2, 4-difluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-fluoro-4-methoxyphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-fluoro-4-methylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidine-5-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidine-5-yl)-1H-imidazole-2-yl)piperidine-1-yl) Lysine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-(methylamino)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbuta-3-en-1-one, 1-(2-(5-(3,4-dimethoxyphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3, 4-dimethylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyisothiazole-4-yl)-1H-imidazole-2-yl )piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(2-methoxyethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(aminomethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one,
1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-acetylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-aminophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chloro-3-fluorophenyl)-1H-imidazole-2-yl) Piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-ethylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-fluorophenyl)-4H-1,2,4-triazole-3-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4- (Methoxyphenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridine-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophen-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridine-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(benzo[d][1,3]dioxol-5-yl)- 1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 1-(2-(5-benzyl-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-bromo-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 2-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-5-yl)benzonitrile, 2-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-carbonyl)cyclo Propan-1-carbonitride, 2-(5-methylfuran-2-yl)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(allylthio)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(ethylthio)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan N-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)ethane-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(furan-3-yl)-1-(2-(4-phenyl-1H-yl (midazole-2-yl)piperidine-1-yl)ethane-1-one, 2-(furan-3-yl)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-5-yl (L)phenyl)acetamide, 2-(methylsulfinyl)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)ethane-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(2-(p-tolyl)-2H-tetrazole-5-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(3-phenyl-1,2,4-oxadiazole-5-yl)piperidine-1-yl) Propan-1-one, 2-(methylthio)-1-(2-(4-(1-(trifluoromethyl)-1H-pyrazole-4-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(4-(morpholinomethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1 -one, 2-(methylthio)-1-(2-(4-(5-methylthiophen-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(m-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(o-to (Lyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridine-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridine-4-yl)-1H-imidazole-2-yl)piperidine-1-yl (L)propan-1-one, 2-(methylthio)-1-(2-(4-(pyrimidine-5-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(quinoxaline-6-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)ethane-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazole- 2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one , 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-propylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazole (-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)azepan-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)- 1-(2-(5-(p-tolyl)-4H-1,2,4-triazole-3-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)isoxazole-3-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)oxazole-2-yl)piperidine -1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)thiazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazole-2-yl)pyrrolidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazole-3-yl)piperidine-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyloxazole-2-yl)piperidine-1-yl)propan-1-one, 2-(methylthio) -1-(4-(5-(p-tolyl)-1H-imidazole-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3-trimethyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)buta-3-en-1-one, 2,2,3-trimethyl-1-(2-(5-(p-tolyl)-1H-imidazole-2 (-yl)piperidine-1-yl)butan-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-3-en-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2,3-dimethoxy-1- (2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2,5-difluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-4-yl)benzonitrile, 2-amino-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-cyclobutyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2-(4-phenyl-1
H-imidazole-2-yl)piperidine-1-yl)ethane-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)ethane-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-cyclopropyl-2-methoxy-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1- (Iyl)ethane-1-one, 2-ethoxy-1-(2-(5-(3-fluorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)buta-2-en-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2-fluoro-4-(2-(1-(2 (methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-5-yl)benzonitrile, 2-mercapto-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine (-1-yl)propan-1-one, 2-methoxy-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-methyl-1-(2-(5-(p-tolyl) (-1H-imidazole-2-yl)piperidine-1-yl)buta-3-en-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1,3-dione, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl )pentan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-2-en-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-methyl- 3-(methylthio)-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-methylene-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 3-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl (phenyl-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 3,3,4,4,4-pentafluoro-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 3,3-difluoro-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 3-fluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl) (L)-1H-imidazole-5-yl)benzonitrile, 3-methyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-2-en-1-one, 3-methyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-4-yl)benzonitrile, 4-(2-( 1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-5-yl)benzaldehyde, 4,4,4-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, bicyclo[1.1.1]pentan-1-yl(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)methanone, cyclobutyl(2-(5-(3-fluorophenyl Nyl)-1H-imidazole-2-yl)piperidine-1-yl)methanone, cyclopentyl(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)methanone, cyclopropyl(2-(4-phenyl-1H-imidazole-2-yl)piperidine-1-yl)methanone, methyl4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-5-yl)benzoate, N-(2-hydroxy Ethyl)-4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-4-yl)benzenesulfonamide, 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, N-(4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-4-yl)phenyl)methanesulfonamide D, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 1-(sec-butylsulfinyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-(isopropylsulfinyl)-2-(5-(p-tolyl)-1H-yl (Midar-2-yl)piperidine, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-((2-(methylthio)propane-2-yl) (P-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-((2-(methylthio)propane-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-(buta-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-(buta-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imi Dazole-2-yl)piperidine, 1-(penta-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-(penta-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-((2-methylbuta-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-((2-methylbuta (T-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 2-(methylsulfonyl)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 1-(4-hydroxy-2-(5-(p (p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(p (p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, (2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfonyl)propan-1-one, (4-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfonyl)propan-1-one, (5-hydroxyl C-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 1-(2-H Droxy-6-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 1- (3-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)2-(methyls (Ruffinyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl) Lysine-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(4-hydroxy -2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl) Lysine-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl) Phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutanoyl)piperidine-2-yl)-1H-imidazole-5-yl)benzaldehyde, 4-(2-(1-(2-(methylthio)propanoyl)piperidine-2-yl)-1H-imidazole-5-yl)benzoic acid, 4-(2-(1-(2-methylbutanoyl)piperidine-2-yl)-1H-imidazole-5-yl (L)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)methanone, 1-(2-(5-bromo-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1-one, 2-(4-(2-(1-(2-(methylthio)p (lopanoyl)piperidine-2-yl)-1H-imidazole-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutanoyl)piperidine-2-yl)-1H-imidazole-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutanoyl)piperidine-2-yl)-1H-imidazole-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazole (2-yl)piperidine-1-yl)butan-1-one, 2-methyl-1-(2-(5-(o-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazole-2-yl)piperidine-1-yl)-2-methylbutan-1 -one, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine, 2-methyl-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazole (Piperadin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(p-tolyl)oxazole-2-yl)piperidine-1-yl)propan-1-one, 2-methyl-1-(2-(4-(p-tolyl)oxazole-2-yl)piperidine-1-yl)butan-1-one, their derivatives, for example, those described in International Publication No. 2022/170519, or any combination thereof.

In some embodiments, the cooling compound may be 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)propan-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazole-2-yl)piperidine-1-yl)buta-3-en-1-one, or a combination thereof.

In some embodiments, the cooling compound may be 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole), or any combination thereof.

As used herein, “cooling-enhancing compound” refers to a compound that can enhance the cooling sensation provided by a flavored product containing a cooling compound, but which can also provide a cooling sensation on its own. Such cooling-enhancing compounds include, but are not limited to, naturally occurring compounds such as menthol or its analogues, or synthetic compounds such as any compounds described in U.S. Patent No. 9,394,287 and U.S. Patent No. 10,421,727. Examples of cooling-enhancing compounds include N-ethyl-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide; N-(1H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide; 2-(4-fluorophenoxy)-N-(1H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)acetamide; 2-(2-hydroxy-4-methylphenoxy)-N-(1H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)acetamide; 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)acetamide; 2-((2,3-dihydro) Examples include, but are not limited to, compounds selected from the group consisting of those derivatives, such as those described in International Publication No. 2022/170519, and any combination thereof. (The text is incomplete and appears to be a fragment of a larger, unrelated collection of compounds.)

Flavored products may further contain sweeteners. Sweeteners may include low-calorie, zero-calorie, or high-intensity sweeteners. The term "high-intensity sweetener" refers to a sweetener sweeter than sucrose, for example, a sweetener that is at least 10 times, or at least 20 times, or at least 50 times, or at least 100 times, or at least 250 times, or at least 500 times, or at least 750 times, or at least 1000 times, or at least 2500 times, or at least 5000 times, or at least 7500 times, or at least 10000 times sweeter than sucrose. In this context, a sweetener being x times sweeter than sucrose means that a concentration of 1/x times by weight of the sweetener in an aqueous solution of the sweetener produces the same sweetness as sucrose.

Examples of suitable sweeteners are described in more detail below. In some embodiments, the sweetener is sucralose, which refers to 1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α-D-galactopyranoside. In some embodiments, the sweetener is sodium saccharin. Sodium saccharin can be present at any suitable concentration. In some embodiments, the concentration of sodium saccharin is in the range of 10 ppm to 10,000 ppm, or 50 ppm to 5,000 ppm, or 100 ppm to 3,000 ppm.

In some embodiments, the sweetener may include caloric sugars such as sucrose, glucose, fructose (e.g., in the form of high-fructose corn syrup), or any combination thereof. In some embodiments, the sweetener may include one or more high-intensity artificial sweeteners such as acesulfame potassium, aspartame, cyclamate, or neotame. Where any such high-intensity artificial sweetener is present, their concentrations are approximately the same as those described above for sucralose. In some other embodiments, the sweetener may include one or more low-calorie carbohydrates or sugar alcohols such as allulose, xylitol, or erythritol.

Various other sweeteners may also be included in the flavored products of this disclosure. Non-limiting examples include D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-arabinose, D-turanose, D-leucose, isomalt, lactitol, mannitol, sorbitol, maltodextrin, saccharin, alitame, cyclamic acid, tagatose, maltose, galactose, mannose, lactose, D-tryptophan, glycine, maltitol, lactitol, isomalt, hydrolyzed hydrogenated starch (HSH), chemically modified mogrosides (such as glucosylated mogrosides), carrelame and other guanidine-based sweeteners, honey, Jerusalem artichoke syrup, Spanish licorice root, monk fruit (fruit, powder or extract), lucuma (fruit, powder or extract), maple sap (e.g., Acer saccharum). Examples of sap include that extracted from Acer saccharum, Acer nigram, Acer rubrum, Acer saccharinum, Acer platanoides, Acer negundo, Acer macrophyllum, Acer grandidentatum, Acer glabrum, and Acer mono), maple syrup, maple sugar, and walnut sap (e.g., Jugrans cinerea, Jugrans nigra). Examples include sap extracted from trees such as *Juglans nigra*, *Juglans ailatifolia*, and *Juglans regia*, birch sap (for example, sap extracted from *Betula papyrifera*, *Betula alleghaniensis*, *Betula lenta*, *Betula nigra*, *Betula populifolia*, and *Betula pendula*), and fig sap (for example, *Platanus occidentalis*). Sap extracted from occidentalis, etc.), ironwood sap (for example, Ostrya virginiana) (Sap extracted from Virginiana, etc.), Muscovado, molasses (e.g., waste molasses), molasses sugar, monatin, monellin, cane sugar (also called natural sugar, unrefined cane sugar, or sucrose), palm sugar, panocha, pironchilo, lapadula, raw sugar, rice syrup, sorghum, sorghum syrup, cassava syrup (also called tapioca syrup), thaumatin, yacon root, malt syrup, barley malt syrup, barley malt flour, beet sugar, cane sugar, crystalline fruit juice crystals, caramel, carbitol, carob syrup, caster sugar, hydrogenated starch aqueous extract, hydrolyzed canned juice, hydrolyzed starch, invert sugar, anethole, arabino Galactan, Arope syrup, P-4000, Acesulfame potassium (also known as Acesulfame K or Ace K), Alitame (also known as Acreme), Advantame, Aspartame, Bayunoside, Neotame, Benzamide derivatives, Bernadame, Canderel, Carrelame and other guanidine-based sweeteners, Vegetable fiber, Corn sugar, Coupling sugars, Curculin, Cyclamate, Cyclocarioside I, Demerara, Dextran, Dextrin, Saccharified malt, Dulcin, Sucrose, Varzin, Dulcoside A, Dulcoside B, Emulin, Enoxolone, Maltodextrin, saccharin, estragole, ethylmaltol, glycine, gluconic acid, gluconolactone, glucosamine, glucoronic acid, glycerol, glycine, glycifylline, glycyrrhizin, glycyrrhetinic acid monoglucuronide, golden sugar, yellow sugar, golden syrup, granulated sugar, ginostema, hernandarsin, isomerized liquid sugar, jalab, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, and 6-chloro-kynurenine), galactitol, litesse, ligicane, lycacin, ragdune, g Anidin, Phalernum, Mavinrin I, Mavinrin II, Maltol, Multisorb, Maltodextrin, Maltotriol, Mannosamine, Miraculin, Starch Syrup, Muclodiol, Nano Sugar, Naringin Dihydrochalcone, Neohesperidin Dihydrochalcone, Nib Sugar, Nigero-Oligosaccharide, Norbu, Orgate Syrup, Osradin, Pekmez, Pentadin, Periandrin I, Perillaldehyde, Perillartin, Petophyllum, Phenylalanine, Florisoside I, Florozidine, Phylodulcin, Polyglycitol Syrup, Polypodoside A, Pterocarioside A, Pterocarioside B, Reviana, Refined Syrup, Rub Syrup Examples include syrup, rubusoside, selliguein A, sugar, siamenoside I, silaitia grosvenori, soybean oligosaccharides, Splenda, SRI oxime V, steviol glycosides, steviol bioside, stevioside, strogins 1, 2, and 4, sucronate, scrononate, sugar, suosan, phlorizin, super aspartame, tetrasaccharide, slaytol, treacle, trilobutain, tryptophan and its derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, boremitol, chanoxyl syrup, aspartame-acesulfame, asgurin, and any combination or blend of any two or more of these.

In some embodiments, the flavored product may contain 4-amino-5,6-dimethylthieno[2,3-d]pyrimidine-2(1H)-one or any suitable salt thereof. In some embodiments, the flavored product disclosed herein may contain a hydrochloride salt of 4-amino-5,6-dimethylthieno[2,3-d]pyrimidine-2(1H)-one.

In some embodiments of any of the embodiments described above, the flavored product may contain lactones. Any suitable lactone or combination of lactones can be used. In some embodiments, the lactones include lactone rings having 3 to 8 members in the ring, such as 3-membered lactone rings, 4-membered lactone rings, 5-membered lactone rings, 6-membered lactone rings, 7-membered lactone rings, or 8-membered lactone rings.

In some embodiments, the lactone comprises a five-membered lactone ring having or not having an unsaturated bond, such as a carbon-carbon double bond (excluding unsaturation of an oxo substituent on the ring). In some embodiments, the lactone comprises a five-membered lactone ring containing at least one unsaturated bond (e.g., one carbon-carbon double bond). Non-limiting examples of lactones containing a five-membered lactone ring having at least one unsaturated bond include angelicalactone α, angelicalactone β, mintlactone, 5,5-dimethyl-2(5H)-furanone, 5-ethyl-2(5H)-furanone, 5-pentyl-2(5H)-furanone, 5-hexyl-2(5H)-furanone, 5-pentyl-2(3H)-furanone, 4-methyl-3-pentyl-2(5H)-furanone, and 2(5H)-furanone. In some embodiments, the lactone comprises a five-membered lactone ring that does not have any unsaturated bonds. Non-exclusive examples of such lactones include butyrolactone γ, valerolactone γ, hexalactone γ, heptalactone γ, octalactone γ, undecalactone γ, decalactone γ, dihydrojasmonlactone, and dihydromintlactone (3,6-dimethyl-hexahydro-2(3H)-benzofuranone).

In some embodiments, the lactone comprises a six-membered lactone ring with or without an unsaturated bond. In some embodiments, the lactone comprises a six-membered lactone ring containing at least one unsaturated bond. Non-limiting examples of lactones containing a six-membered lactone ring with at least one unsaturated bond include δ-2-decenolactone, coumarin, and 6-methylcoumarin. In some other embodiments, the lactone comprises a six-membered lactone ring without any unsaturated bonds. Non-limiting examples of lactones containing a six-membered lactone ring without any unsaturated bonds include decalactone δ, dodecalactone δ, and cyclohexyllactone.

In certain embodiments, the flavored product further includes, but is not limited to, one or more food additives:
Acids, such as citric acid, phosphoric acid, ascorbic acid, sodium bisulfate, lactic acid, or tartaric acid;
Bitter components, such as caffeine, quinine, green tea, catechins, polyphenols, green robusta coffee extract, green coffee extract, potassium chloride, menthol, or proteins (proteins and protein isolates derived from plants, algae, or fungi);
Coloring agents, such as caramel, Red No. 40, Yellow No. 5, Yellow No. 6, Blue No. 1, Red No. 3, purple carrot juice, black carrot juice, purple sweet potato juice, vegetable juice, fruit juice, beta-carotene, turmeric curcumin, or titanium dioxide;
Preservatives, such as sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfate, sorbic acid, or benzoic acid;
Antioxidants, such as ascorbic acid, disodium calcium EDTA, alpha-tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol, or sodium hexametaphosphate;
Vitamins or functional ingredients, such as resveratrol, CoQ10, omega-3 fatty acids, theanine, choline chloride (citocolin), fibersol, inulin (chicory root), taurine, ginseng extract, guanana extract, ginger extract, L-phenylalanine, L-carnitine, L-tartrate, D-gluconolactone, inositol, bioflavonoids, echinacea, ginkgo, yerba mate, flaxseed oil, Garcinia cambogia rind extract, white tea extract, ribose, milk thistle extract, grape seed extract, pyrodyxin HCl (vitamin B6), cyanocobalamin (cyanocobalamin) n) Vitamin B12, niacinamide (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, etc.
Whitening agents, such as ester gun, brominated vegetable oil (BVO), or sucrose acetate isobutyrate (SAIB);
Buffering agents, such as sodium citrate, potassium citrate, or salt;
Fragrances, such as natural fragrances, natural fragrances containing other natural fragrances (natural fragrances WONF), natural and artificial fragrances, artificial fragrances, etc.; 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 (acacia gum), inulin or carrageenan, etc.

In some further embodiments, the flavored products disclosed herein include one or more other umami or flavor-enhancing compounds. Such umami-enhancing compounds include, but are not limited to, naturally occurring compounds such as ericamide, or synthetic compounds such as any compounds described in U.S. Patent No. 8,735,081, U.S. Patent No. 8,124,121, and U.S. Patent No. 8,968,708.

In some further embodiments, the flavored products disclosed herein may contain one or more anti-bitter compounds. Such anti-bitter compounds include, but are not limited to, naturally occurring compounds such as menthol or its analogues, or synthetic compounds such as any compounds described in U.S. Patent No. 8,076,491, U.S. Patent No. 8,445,692, and U.S. Patent No. 9,247,759.

In some further embodiments, the flavored products disclosed herein may contain one or more texture-modifying compounds. Such texture-modifying compounds include, but are not limited to, tannins, cellulosic materials, and bamboo powder.

In some further embodiments, the flavored products disclosed herein may contain one or more flavor-masking compounds. Such flavor-masking compounds include, but are not limited to, cellulosic materials, fungal extracts, plant extracts, citric acid, and carbonates (or carbonates).

In certain embodiments, the flavored products disclosed herein may contain cyclosal. If cyclosal is present, it is present in a relative concentration similar to that of the lactones described herein.

In some embodiments, the flavored product comprises one or more flavorings or any other additives described in H. Mitchell, Sweeteners and Sugar Alternatives in Food Technology, Blackwell Publishing Ltd, 2006. Useful flavorings include artificial, natural, and synthetic fruit flavors, such as vanilla. Other potential flavors include milk, butter, cheese, cream, and yogurt; vanilla; tea or coffee flavors, e.g., green tea, oolong tea, tea, cocoa, chocolate, and coffee; mint flavors, e.g., peppermint, spearmint, and Japanese mint; spicy flavors, e.g., asafoetida, ayowan, anise, angelica, fennel, allspice, cinnamon, chamomile, mustard, cardamom, caraway, cumin, clove, pepper, coriander, sassafras, savory, and sansho (Japanese pepper). Fructus flavorings, shiso flavorings, juniper berry flavorings, ginger flavorings, star anise flavorings, horseradish flavorings, thyme flavorings, tarragon flavorings, dill flavorings, chili pepper flavorings, nutmeg flavorings, basil flavorings, marjoram flavorings, rosemary flavorings, bay leaf flavorings, and wasabi (Japanese horseradish) flavorings; alcoholic flavorings, such as wine flavorings, whiskey flavorings, brandy flavorings, rum flavorings, gin flavorings, and liqueur flavorings; floral flavorings; and vegetable flavorings, such as onion flavorings, garlic flavorings, cabbage flavorings, carrot flavorings, celery flavorings, mushroom flavorings, and tomato flavorings. These flavorings may be used in liquid or solid form, individually or in combination.

Furthermore, when used in combination with refrigerants, flavorings can provide breath-freshening properties, particularly mint flavorings. These flavorings may be used in liquid or solid form, individually or in combination. Other useful flavorings include aldehydes and esters such as cinnamyl acetate, cinnamaldehyde, citral diethyl acetal, dihydrocarbyl acetate, eugenyl formate, and p-methylamizole, which may also be used. Generally, any flavoring or food additive, such as those described in *Chemicals Used in Food Processing*, publication 1274, pp. 63–258, by the National Academy of Sciences, can be used.

Further examples of aldehyde flavorings include acetaldehyde (apple), benzaldehyde (cherry, almond), anisaldehyde (Spanish licorice, anise), cinnamaldehyde (cinnamon), citral, i.e., α-citral (lemon, lime), neral, i.e., β-citral (lemon, lime), decanal (orange, lemon), ethyl vanillin (vanilla, cream), heliotrope, i.e., piperonal (vanilla, cream), vanillin (vanilla, cream), α-amyl cinnamaldehyde (spicy fruity flavoring), butyraldehyde (butter, cheese), varellealdehyde (butter, cheese), Examples of flavorings include, but are not limited to, citronellal (modified, many types), decanal (citrus fruits), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), 2-ethylbutyraldehyde (berries), hexenal, i.e., trans-2 (berries), tollaldehyde (cherries, almonds), veratrolaldehyde (vanilla), 2,6-dimethyl-5-heptenal, i.e., melonal (melon), 2,6-dimethyloctanal (green fruits), and 2-dodecenal (citrus fruits, mandarin), cherry, grape, strawberry shortcake, and mixtures thereof. This list of flavorings is illustrative and not intended to limit the term “flavoring” or the scope of this disclosure in general.

The flavored product may be any flavored product according to the embodiments and models described below. In some embodiments, the flavored product is a beverage product such as 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, juice beverages, nectar, vegetable juice, vegetable-flavored juice, sports drinks, energy drinks, fortified water drinks, vitamin-fortified water, near-water drinks, coconut water, tea-type beverages, coffee, cocoa beverages, beverages containing dairy ingredients, beverages containing cereal extracts, and smoothies. In some other embodiments, the flavored product is a food product such as packaged meals, canned foods, or meal replacement products. In some embodiments, the flavored product is an oral care product such as toothpaste, mouthwash, or teeth whitening composition, for example, a composition disclosed in U.S. Patent Application Publication No. 2019/0167545, which is incorporated herein by reference.

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, juice beverages, nectar, vegetable juice, vegetable-flavored juice, sports drinks, energy drinks, fortified water drinks, vitamin-fortified water, near-water drinks, coconut water, tea-type beverages, coffee, cocoa beverages, beverages containing dairy components, beverages containing cereal extracts, and smoothies. In some embodiments, the beverage may be a soft drink.

Flavored products can be in any suitable physical form. For example, in some embodiments, the flavored product may be in a solid form such as a powder. In further such embodiments, the flavored product is a toothpaste, such as toothpaste for whitening teeth or removing stains (e.g., tobacco stains). In some other embodiments, the flavored product may be a paste or slurry, such as toothpaste. In some other embodiments, the flavored product may be in the form of a cream or gel, such as a tooth gel, skin cream, or tooth cream. In some other embodiments, the flavored product may be a liquid suspension or solution, for example, containing an aqueous carrier. In some embodiments, the flavored product may be in the form of an emulsion, such as a microemulsion or nanoemulsion, which may contain surfactants, emulsifiers, etc. In some embodiments, the flavored product is a personal care product, such as a product for application to the skin, face, lips, gums, mouth, etc. Such a personal product may be for any suitable use, such as skin whitening or teeth whitening.

In some embodiments, the flavored product is an oral care product. “Oral care product” means a personal care product or other product that, in the normal course of use, is held in the oral cavity for a sufficient time to come into contact with substantially all tooth surfaces and/or oral tissues for the purpose of oral activity, rather than being intentionally swallowed for the purpose of systemic administration of a particular therapeutic agent. Oral care compositions can be in various forms, including toothpaste, toothpaste, toothpaste, tooth gel, subgingival gel, mouth rinse, mousse, foam, mouth spray, lozenges, chewable tablets, chewing gum, or denture products. Oral care compositions may also be incorporated into strips or films for direct application to or adhesion to oral surfaces.

In some embodiments, the flavored product is a pharmaceutical product, such as a product designed to carry or deliver a specific active pharmaceutical ingredient (API). Such APIs may be acetaminophen, as well as other over-the-counter (OTC) medications such as cough and cold medicines. In some embodiments, the API is a prescription-based drug.

In any aspect and specific embodiment of the embodiments described herein, a flavored product is a product that does not exist naturally, such as a packaged food or beverage product.

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

Generally, the soup category refers to canned/preserved, dehydrated, instant, chilled, UHT, and frozen soups. For the purposes of this definition, soup means a food prepared from meat, poultry, fish, vegetables, grains, fruits, and other raw material ingredients, cooked in a liquid that may contain some or all visible parts of these ingredients. Soup may be clear (like a broth) or thick (like a chowder), smooth, pureed, or lumpy, ready to serve, semi-condensed, or condensed, and may be served hot or cold as a dish, a main course, or a snack between meals (to be drunk little by little like a beverage). Soup may be used as a cooking element for other meal components and may range from broths (consommé) to sauces (cream or cheese-based soups).

The dehydrated and prepared foods category typically means: (i) cooking aids, e.g., powders, granules, pastes, concentrated liquid products, e.g., concentrated bouillons, bouillons, and bouillon-like products in compressed cube, tablet, powder, or granular form, sold separately as finished products or as elements within products, sauces, and recipe mixes (regardless of technology); (ii) meal solution products, e.g., dehydrated and freeze-dried soups, including dehydrated soup mixes; dehydrated instant soups; dehydrated ready-to-cook (ready) products. (y-to-cook) Meals and main dishes for one serving, including soups, dehydrated or shelf-stable preparations of ready-made meals, pasta, potato and rice dishes, and (iii) condiments, marinades, salad dressings, salad toppings, dips, breadcrumbs, batter mixes, shelf-stable spreads, barbecue sauces, liquid recipe mixes, concentrates, sauces, or sauce mixes, such as salad recipe mixes, sold as finished products or as components within a product (whether dehydrated, liquid or frozen).

The beverage category typically refers to beverages, beverage mixes, and concentrates, and includes, but is not limited to, carbonated and non-carbonated beverages, alcoholic and non-alcoholic beverages, ready-to-drink beverages, liquid concentrate formulations for preparing beverages such as soda, and dry powdered beverage pre-mixes. The beverage category also includes alcoholic beverages, soft drinks, sports drinks, isotonic beverages, and hot drinks. Alcoholic beverages include, but are not limited to, beer, cider/perry, FAB, wine, and spirits. Soft drinks include carbonated drinks, e.g., cola and non-cola carbonated drinks; fruit juices, e.g., juices, nectars, juice beverages, and fruit-flavored beverages; bottled water, e.g., sparkling water, spring water, and purified water/table water; functional beverages, e.g., carbonated or still, such as sports drinks, energy drinks, or elixir drinks; and concentrates, e.g., ready-to-drink liquid and powder concentrates, but are not limited to these. Examples of hot or cold drinks include, but are not limited to, coffee or iced coffee, such as freshly brewed, instant, and blended coffee; tea or iced tea, such as black tea, green tea, white tea, oolong tea, and flavored tea; and other beverages containing flavoring-based, malt-based, or plant-based powders, granules, blocks, or tablets mixed with milk or water.

The snack food category generally refers to any food that can be an informal snack, including 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, tortillas/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.

The baked goods category generally refers to any edible product whose cooking process involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, buns, cookies, muffins, cereals, toaster pastries, pastries, waffles, tortillas, biscuits, pies, bagels, tarts, quiches, cakes, any baked food, and any combination thereof. Further examples include, but are not limited to, packaged/industrial bread, unpackaged/artisan bread, packaged/industrial cakes, unpackaged/artisan cakes, cookies, chocolate-coated biscuits, sandwich biscuits, filling biscuits, savory biscuits and crackers, bread substitutes, breakfast cereals, RTE cereals, family breakfast cereals, flakes, muesli, other cereals, children's breakfast cereals, and hot cereals.

The ice cream category generally refers to frozen desserts containing cream, sugar, and flavorings. Examples of ice cream include, but are not limited to, impulse ice cream; takeaway ice cream; frozen yogurt and artisan ice cream; and soy, oat, bean (e.g., adzuki beans and mung beans) and rice-based ice cream. Further examples of ice cream include, but are not limited to, single-serving dairy ice cream, single-serving water ice cream, multi-pack dairy ice cream, multi-pack water ice cream, takeaway dairy ice cream, ice cream desserts, bulk ice cream, and takeaway water ice cream.

The confectionery category generally refers to edible products that have a sweet taste. Examples of confectionery include, but are not limited to, candies, gelatin, chocolate confectionery, sugar confectionery, gum, and any combination products. Further examples include, but are not limited to, tablets, countlines, self-packaged/softlines, boxed assortments, standard boxed assortments, twist-wrapped miniatures, seasonal chocolates, chocolates with toys, alfajores, other chocolate confectionery, mints, standard mints, power mints, boiled sweets, pastilles, gum, jelly and chew, toffee, caramel and nougat, medicinal confectionery, lollipops, Spanish licorice, and other sugar confectionery.

The meal replacement category generally refers to any food product intended to replace a regular meal, particularly for people with health or fitness concerns. Examples of meal replacements include, but are not limited to, slimming products and recovery beverages and products.

The ready meal category generally refers to any food product that can be served as a meal without extensive cooking or processing. Ready meals include products where manufacturers have added recipe "skills" to provide a high degree of readiness, completeness, and convenience. Examples of ready meals include, but are not limited to, canned/preserved, frozen, dried, and chilled ready meals; dinner mixes; frozen pizzas; chilled pizzas; and prepared salads.

The pasta and noodle category includes, but is not limited to, canned, dried, and chilled/fresh pasta; plain, instant, chilled, frozen, and snack noodles; and all other types of pasta and/or noodles.

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

The frozen processed foods category includes, but is not limited to, frozen processed red meat, processed poultry, processed fish/seafood, processed vegetables, meat substitutes, processed potatoes, bakery products, desserts, ready meals, pizzas, soups, noodles, and other frozen foods.

The dried processed foods category includes, but is not limited to, rice, dessert mixes, dried ready meals, dehydrated soups, instant soups, dried pasta, plain noodles, and instant noodles. The chilled processed foods category includes, but is not limited to, chilled processed meats, processed fish/seafood products, lunch kits, fresh cut fruit, ready meals, pizzas, prepared salads, soups, fresh pasta, and fresh noodles.

The Sauces, Dressings, and Condiments category includes, but is not limited to, tomato pastes and purees, bouillon/stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy-based sauces, pasta sauces, wet/cooked sauces, dry sauces/powdered mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrettes, dips, pickle products, and other sauces, dressings, and condiments.

The baby food category includes, but is not limited to, milk or soy-based formulations; as well as cooked, dried, and other baby foods.

The spread category includes, but is not limited to, jams and preserves, honey, chocolate spreads, nut-based spreads, and yeast-based spreads.

The dairy category generally refers to edible products produced from the milk of mammals. Examples of dairy products include, but are not limited to, drinking milk, cheese, yogurt, and sour milk drinks, as well as other dairy products. Further examples of dairy products include, but are not limited to, raw milk/pasteurized milk, whole raw milk/pasteurized milk, semi-skimmed raw milk/pasteurized milk, long-life/UHT milk, whole long-life/UHT milk, semi-skimmed long-life/UHT milk, fat-free long-life/UHT milk, goat milk, condensed milk/unsweetened condensed milk, plain condensed milk/unsweetened condensed milk, flavored, functional and other condensed milk, flavored milk beverages, dairy-only flavored milk beverages, fruit juice-flavored milk beverages, soy milk, fermented dairy beverages, coffee whiteners, powdered milk, flavored powdered milk beverages, cream, processed cheese, spreadable processed cheese, unspreadable processed cheese, unprocessed cheese, spreadable unprocessed cheese, hard cheese, packaged hard cheese, unpackaged hard cheese, plain yogurt/natural yogurt, flavored yogurt, fruit yogurt, probiotic yogurt, drinking yogurt, regular drinking yogurt, and probiotic drinking yogurt.

In some embodiments, the flavored product is one or more confectionery, chocolate confectionery, tablets, countlines, self-packaged lines/softlines, boxed assortments, standard boxed assortments, twist-wrapped miniatures, seasonal chocolates, chocolates with toys, alfajores, other chocolate confectionery, mints, standard mints, power mints, boiled sweets, pastilles, gum, jelly and chew, toffee, caramel and nougat, medicinal confectionery, lollipops, Spanish licorice, other sugar confectionery, bread, packaged/industrial bread, unpackaged/artisan bread, pastries, cakes, packaged/industrial cakes, unpackaged/artisan cakes, cookies, chocolate-coated biscuits, sandwich biscuits, filling biscuits, savory biscuits and crackers, bread substitutes, breakfast Edible cereals, RTE cereals, family breakfast cereals, flakes, muesli, other cereals, kids' breakfast cereals, hot cereals, ice cream, impulse ice cream, single serving dairy ice cream, single serving water ice cream, multi-pack dairy ice cream, multi-pack water ice cream, takeaway ice cream, takeaway dairy ice cream, ice cream desserts, bulk ice cream, takeaway water ice cream, frozen yogurt, artisan ice cream, dairy products, milk, raw milk/pasteurized milk, whole milk/pasteurized milk, semi-skimmed milk/pasteurized milk, long-life milk Fat-free long-life milk, whole-fat long-life milk, semi-skimmed long-life milk, non-fat long-life milk, goat milk, condensed milk/unsweetened condensed milk, plain condensed milk/unsweetened condensed milk, flavored, functional and other condensed milk, flavored milk beverages, dairy-only flavored milk beverages, fruit juice-flavored milk beverages, soy milk, sour milk drinks, fermented dairy beverages, coffee whiteners, powdered milk, flavored powdered milk beverages, cream, cheese, processed cheese, spreadable processed cheese, unspreadable processed cheese, unprocessed cheese, spreadable unprocessed cheese, hard cheese, packaged hard cheese, unpackaged hard cheese, yogurt Plain yogurt/natural yogurt, flavored yogurt, fruit yogurt, probiotic yogurt, drinking yogurt, regular drinking yogurt, probiotic drinking yogurt, chilled storage stable desserts, dairy-based desserts, soy-based desserts, chilled snacks, fromage frais and quark, plain fromage frais and quark, flavored fromage frais and quark, savory fromage frais and quark, sweet snacks and savory snacks, fruit snacks, chips/crisps, extruded snacks, tortillas/corn chips Popcorn, pretzels, nuts, other sweet and savory snacks, snack bars, granola bars, breakfast bars, energy bars, fruit bars, other snack bars, meal replacements, slimming products, recovery beverages, ready meals, canned ready meals, frozen ready meals, dried ready meals, chilled ready meals, dinner mixes, frozen pizzas, chilled pizzas, soups, canned soups, dehydrated soups, instant soups, chilled soups, hot soups, frozen soups, pasta, canned pasta, dried pasta, chilled/fresh pasta, noodles, plain noodles, instant noodles, cup/bowl instant noodles, pouches Instant noodles, chilled noodles, snack noodles, canned foods, canned meat and meat products, canned fish/seafood, canned vegetables, canned tomatoes, canned beans, canned fruit, canned ready meals, canned soups, canned pasta, other canned foods, frozen foods, 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, dried foods, dessert mixes, dried ready meals, dehydrated soups, instant soups, dried pasta, and more. Noodles, instant noodles, cup/bowl instant noodles, pouch instant noodles, chilled foods, chilled processed meat, chilled fish/seafood products, chilled processed fish, chilled coated fish, chilled smoked fish, chilled lunch kits, chilled ready meals, chilled pizza, chilled soup, chilled/fresh pasta, chilled noodles, oils and fats, olive oil, vegetable seed oil, cooking oils and 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, large This includes bean-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, pickle products, other sauces, dressings and condiments, baby food, formula, standard formula, follow-on formula, toddler formula, hypoallergenic formula, pre-cooked baby food, dried baby food, other baby food, spreads, jams and preserves, honey, chocolate spread, nut-based spreads, and yeast-based spreads.

Some embodiments provide chewable, flavored products that may or may not be intended to be swallowed. In some embodiments, the chewable, flavored products may be gums, chewing gums, sugared gums, sugar-free gums, functional gums, or bubble gums, individually or in combination, containing the compounds disclosed and described herein.

The flavored products disclosed herein contain one or more compounds that users of those products perceive as having an undesirable taste, such as bitter, medicinal, or metallic. As used herein, such compounds are referred to as distaste substances. In some embodiments, the flavored product contains a distaste substance, which is 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, sodium bicarbonate, thymol, menthol, methyl salicylate, eucalyptol, or any combination thereof. In some further embodiments, the distaste substance is thymol, menthol, methyl salicylate, eucalyptol, or any combination thereof. In some embodiments, the distaste substance is cetylpyridinium chloride, lauramidopropyl betaine, cocamidopropyl betaine, or any combination thereof. In some embodiments, the unpleasant taste substance is arginine. In some embodiments, the unpleasant taste substance is hydrogen peroxide. In some embodiments, the unpleasant taste substance is chlorhexidine gluconate. In some embodiments, the unpleasant taste substance is zinc phosphate, zinc chloride, zinc citrate, potassium nitrate, pentasodium triphosphate, tetrasodium pyrophosphate, stannous fluoride, or any combination thereof. In some embodiments, the unpleasant taste substance is sodium bicarbonate.

Distaste substances can be present in any appropriate amount in the flavored product. For example, in embodiments where the flavored product is an oral care product, the distaste substances can be present in any amount typical for use in similar types of oral care products.

In a third aspect, this disclosure relates to the use of the flavor-modifying compositions described herein for reducing unpleasant tastes in flavored products. Unpleasant tastes often result from the presence of one or more compounds (discomfort substances) that users of those products perceive as having an undesirable taste, such as bitter, medicinal, or metallic. Methods for reducing unpleasant tastes in flavored products having one or more discomfort substances, comprising adding a flavor-modifying composition to the flavored product, are also referred to.

The compositions, products, and uses described herein are further illustrated by the following non-limiting examples.

Example 1. Flavor-Modifying Compositions Flavor-modifying compositions according to several embodiments of the present disclosure were prepared and summarized in Tables 1a and 1b below. Unless otherwise indicated, the amounts of each component are given as a weight percentage of the total weight of the composition.

Samples 1-7 were prepared as follows:
Preparation of the oil phase: Flavoring oil, nonpolar surfactant and polar surfactant, and a water-miscible solvent were mixed and heated with gentle stirring (45°C) until a homogeneous liquid was obtained.

Preparation of the aqueous phase: GSG was mixed with water and stirred at room temperature until the GSG was completely dissolved.

Preparation of water-in-oil microemulsion: The oil phase and aqueous phase were mixed and stirred at room temperature until a homogeneous liquid was obtained.

The resulting composition was clear at room temperature (RT) and remained stable for at least three months.

Example 2. Sensory Evaluation Samples 3 and 4 were evaluated by sensory testing. Two comparative toothpastes and two toothpastes according to several embodiments of the present disclosure were prepared using the toothpaste bases shown in Table 2. The two comparative toothpastes and the two toothpastes according to several embodiments of the present disclosure are summarized in Table 3.

A panel of four experts was asked to perform the following: (a) apply approximately 1-2 g of the sample to a toothbrush; (b) rinse the toothbrush under running water for 5 seconds to moisten the paste and soften the bristles; (c) brush around the teeth for 1 minute, minimizing brushing of the gums; and (d) evaluate the off-note intensity during brushing and 3 minutes after brushing using an intensity scale of 0-5 (0 indicating no intensity, 5 indicating very strong intensity). The results are shown in Table 4.

The disclosed subject matter is described with reference to specific details of its particular embodiments. Such details are not intended to be considered limitations on the scope of the disclosed subject matter, except to the extent they are included in the appended claims.

Therefore, the exemplary embodiments described herein are well adapted to achieve the purposes and benefits mentioned, as well as those inherent to them. The exemplary embodiments described herein may be modified and implemented in different but equivalent ways, which would be obvious to those skilled in the art who are interested in the teachings herein; therefore, the specific embodiments disclosed above are merely illustrative. Furthermore, nothing is intended to limit the structural or design details shown herein except as provided in the following claims. Accordingly, it is clear that the specific exemplary embodiments disclosed above may be modified, combined, or altered, and all such variations are considered to fall within the scope and spirit of the exemplary embodiments described herein. The exemplary embodiments described herein, as provided herein, can be adequately implemented in the absence of any elements not specifically disclosed herein, and/or any optional elements disclosed herein.

Claims (19)

a) One or more flavored oils,
b) One or more off-note masking agents,
c) One or more nonpolar surfactants,
d) One or more polar surfactants,
e) Water and,
f) A flavor-modifying composition comprising one or more water-miscible cosolvents. The flavor-modifying composition according to claim 1, wherein the one or more flavor oils are selected from the group consisting of mint oils such as spearmint oil, peppermint oil, and Japanese mint oil; cinnamon oil, wintergreen oil (methyl salicylate), clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, nutmeg oil, allspice, sage oil, mace, bitter tonsil oil, cassia oil, and citrus oils. The flavor-modifying composition according to claim 1 or 2, wherein one or more flavor oils are present in an amount of 20% to 60% by weight, typically 40% to 55% by weight, relative to the total weight of the composition. The flavor-modifying composition according to any one of claims 1 to 3, wherein the one or more off-note masking agents comprises one or more glucosylated natural steviol glycosides. The flavor-modifying composition according to any one of claims 1 to 4, wherein the one or more off-note masking agents are present in an amount of 0.01% to 5% by weight, typically 0.2% to 4% by weight, relative to the total weight of the composition. The flavor-modifying composition according to any one of claims 1 to 5, wherein each of the one or more nonpolar surfactants has a hydrophilic-lipophilic balance (HLB) value of 10 or less. The flavor-modifying composition according to any one of claims 1 to 6, wherein the one or more nonpolar surfactants typically comprises one or more sorbitan fatty acid esters selected from the group consisting of sorbitan monostearate (Span 60), sorbitan tristearate (Span 65), sorbitan monolaurate (Span 20), sorbitan monooleate (Span 80), sorbitan monopalmitate (Span 40), and sorbitan trioleate (Span 85); lecithin, typically soy lecithin; (poly)glyceryl esters, typically glycerol monooleate; or mixtures thereof. The flavor-modifying composition according to any one of claims 1 to 7, wherein one or more nonpolar surfactants are present in an amount of 1% to 40% by weight, typically 5% to 35% by weight, relative to the total weight of the composition. The flavor-modifying composition according to any one of claims 1 to 8, wherein each of the one or more polar surfactants has a hydrophilic-lipophilic balance (HLB) value greater than 10. The flavor-modifying composition according to any one of claims 1 to 9, wherein the one or more polar surfactants are selected from the group consisting of: one or more triblock copolymers (poloxamer 407) comprising a poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymer, typically a central hydrophobic block of polypropylene glycol with two hydrophilic blocks of polyethylene glycol on the sides; one or more PEG sorbitan fatty acid esters, typically selected from the group consisting of PEG sorbitan monolaurate (polysorbate 20), PEG sorbitan monooleate (polysorbate 80), PEG sorbitan monopalmitate (polysorbate 40), and PEG sorbitan stearate (polysorbate 60); PEG-modified hydrogenated castor oil (Cremophor RH 40); sugar esters, typically sucrose monopalmitate and sucrose monolaurate; (poly)glyceryl esters, for example decaglyceryl monooleate, alkyl glucoside, and mixtures thereof. The flavor-modifying composition according to any one of claims 1 to 10, wherein one or more polar surfactants are present in an amount of 1% to 40% by weight, typically 5% to 35% by weight, relative to the total weight of the composition. The flavor-modifying composition according to any one of claims 1 to 11, wherein the one or more water-miscible cosolvents are selected from the group consisting of propylene glycol, glycerol, ethanol, triethyl citrate, triacetin, ethyl lactate, ethyl acetate, propanol, isopropanol, and mixtures thereof. The flavor-modifying composition according to any one of claims 1 to 12, wherein the one or more water-miscible cosolvents are present in an amount of 0.01% to 30% by weight, typically 5% to 25% by weight, relative to the total weight of the composition. The flavor-modifying composition according to any one of claims 1 to 13, wherein the weight ratio of the one or more flavor oils to the one or more off-note masking agents is within the range of 20:1 to 100:1. A flavor-modifying composition according to any one of claims 1 to 14, in the form of a water-in-oil microemulsion. The aforementioned water-in-oil microemulsion
a') A discontinuous aqueous phase comprising one or more of the above-mentioned off-note masking agents and water,
b') The flavor-modifying composition according to claim 15, comprising a continuous oil phase containing one or more of the above-mentioned flavor oils. A flavored product comprising the taste-modifying composition and unpleasant taste substance described in any one of claims 1 to 16. A flavored product according to claim 17, which is an oral care product. Use of the flavor-modifying composition according to any one of claims 1 to 16 for reducing the unpleasant taste of a flavored product.