WO2025090574A1

WO2025090574A1 - Salt enhancing compounds

Info

Publication number: WO2025090574A1
Application number: PCT/US2024/052517
Authority: WO
Inventors: Devin PETERSON; Edisson Tello Camacho; Ningyi Wang
Original assignee: Ohio State Innovation Foundation
Current assignee: Ohio State Innovation Foundation
Priority date: 2023-10-23
Filing date: 2024-10-23
Publication date: 2025-05-01
Anticipated expiration: 2026-04-23

Abstract

Disclosed herein are compounds and compositions for enhancing the salty flavor of a consumable article. In certain implementations the compounds and compositions are substantially free of curcumin and/or cuminaldehyde.

Description

SALT ENHANCING COMPOUNDS

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of US Provisional Applications 63/592,248, filed October 23, 2023, and 63/557,760, filed February 26, 2024, the contents of each are hereby incorporated in their entirety.

BACKGROUND

[0002] A main driver of mortality across the world is poor diet, and inappropriate salt consumption represents a significant proportion of poor diet choices. Many people, for flavor reasons, consume far more sodium than 2 g/day that is typically recommended by medical professionals. Excess salt intake is linked to many different diseases, including stroke, hypertension, kidney disease, congestive heart failure and others. There remains a need for foods and beverages with reduced sodium levels that still provide sufficiently salty flavor such that people will choose to eat them. While certain

DETAILED DESCRIPTION

[0003] Before the present methods and systems are disclosed and described, it is to be understood that the methods and systems are not limited to specific synthetic methods, specific components, or to particular compositions. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0004] As used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, another embodiment includes- from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.

[0005] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. [0006] Throughout the description and claims of this specification, the word "comprise" and variations of the word, such as "comprising" and "comprises," means "including but not limited to," and is not intended to exclude, for example, other additives, components, integers or steps. "Exemplary" means "an example of" and is not intended to convey an indication of a preferred or ideal embodiment. "Such as" is not used in a restrictive sense, but for explanatory purposes.

[0007] Disclosed are components that can be used to perform the disclosed methods and systems. These and other components are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these components are disclosed that while specific reference of each various individual and collective combinations and permutation of these may not be explicitly disclosed, each is specifically contemplated and described herein, for all methods and systems. This applies to all aspects of this application including, but not limited to, steps in disclosed methods. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods.

[0008] Compounds disclosed herein may be provided in the form of acceptable salts. Examples of such salts are acid addition salts formed with inorganic acids, for example, hydrochloric, hydrobromic, sulfuric, phosphoric, and nitric acids and the like; salts formed with organic acids such as acetic, oxalic, tartaric, succinic, maleic, fumaric, gluconic, citric, malic, methanesulfonic, p-toluenesulfonic, napthalenesulfonic, and polygalacturonic acids, and the like; salts formed from elemental anions such as chloride, bromide, and iodide; salts formed from metal hydroxides, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, and magnesium hydroxide; salts formed from metal carbonates, for example, sodium carbonate, potassium carbonate, calcium carbonate, and magnesium carbonate; salts formed from metal bicarbonates, for example, sodium bicarbonate and potassium bicarbonate; salts formed from metal sulfates, for example, sodium sulfate and potassium sulfate; and salts formed from metal nitrates, for example, sodium nitrate and potassium nitrate.

[0009] The term "curcumin" refers to a compound having the formula:

or a mixture thereof.

[0010] The term "alkyl" refers to a radical of a straight-chain or branched hydrocarbon group having a specified range of carbon atoms (e.g., a "Ci-i₆ alkyl" can have from 1 to 16 carbon atoms). An alkyl group can be saturated or unsaturated, i.e., an alkenyl or alkynyl group. Unless specified to the contrary, an "alkyl" group includes both saturated alkyl groups and unsaturated alkyl groups.

[0011] When a range of values is listed, it is intended to encompass each value and subrange within the range. For example, "Ci.₆ alkyl" is intended to encompass Ci, C₂, C₃, C₄, C₅, CB, C16, Ci s, C14, C1 3, C12, C26, C25, C2-4, C2-3, C36, C35, C34, C46, C4-5, and CS B alkyl.

[0012] As used herein, the term "null," when referring to a possible identity of a chemical moiety, indicates that the group is absent, and the two adjacent groups are directly bonded to one another. By way of example, for a genus of compounds having the formula CH3-X-Y- CH₃, if X and Y are both null, then the resulting compound has the formula CH3-CH3.

[0013] The term "aryl" refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 n electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system ("Ce-14 aryl"). "Aryl" also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each instance of an aryl group is independently unsubstituted (an "unsubstituted aryl") or substituted (a "substituted aryl") with one or more substituents.

[0014] "Aralkyl" is a subset of "alkyl" and refers to an alkyl group substituted by an aryl group, wherein the point of attachment is on the alkyl moiety.

[0015] The term "heteroaryl" refers to a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 n electrons shared in a cyclic array) having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-14 membered heteroaryl"). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings. "Heteroaryl" includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. "Heteroaryl" also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl/heteroaryl) ring system. Polycyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring that does not contain a heteroatom (e.g., 5-indolyl).

[0016] Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible isomer, e.g., each enantiomer, diastereomer, and meso compound, and a mixture of isomers, such as a racemic or scalemic mixture. Unless stated to the contrary, a formula depicting one or more stereochemical features does not exclude the presence of other isomers.

[0017] Disclosed herein salt enhancing compounds of Formula (1):

[Formula (1)], or a salt thereof, wherein

X is null, CHj, or CH2CH2;

L is null, CH2, or CH2CH2;

R is H, Ci.₃alkyl, or C(=O)Ci.₃alkyl;

Ar optionally substituted C₆-ioaryl or Ci-ioheteroaryl;

Z¹ and Z² are either both null, or Z¹ is OR^Z or N(R^Z)₂ and Z² is H, wherein R² is in each case independently selected from H and Ci-₃alkyl; Y¹ and Y² are either both null, or Y¹ is OR^V or N(R^V)₂ and Y² is H, wherein R^y is in each case independently selected from H and Chalky I; providing that Z² and Y² are not both H.

[0018] In some implementations, one or more compounds of Formula (1) may be provided in a composition. In some implementations, the composition does not contain any curcumin. In certain implementations the compositions contain curcumin in amount no more than 0.01 wt.%, no more than 0.001 wt.%, no more than 0.0001 wt.%, no more than 0.0001 wt.%, no more than 0.000001 wt.%, or no more than 0.0000001 wt.%. As used herein, no more than a given amount includes 0 wt.%

[0019] In certain implementations, the composition does not include any cuminaldehyde, a compound having the formula:

[0020] In certain implementations the compositions contain cuminaldehyde in amount no more than 0.01 wt.%, no more than 0.001 wt.%, no more than 0.0001 wt.%, no more than 0.0001 wt.%, no more than 0.000001 wt.%, or no more than 0.0000001 wt.%. As used herein, no more than a given amount includes 0 wt.%

[0021] In some implementations, one or more compounds of Formula (1) may be provided in a composition, wherein the compound(s) of Formula (1) are present in an amount of at least 90% by weight, at least 95% by weight, at least 98% by weight, or at least 99% by weight, relative to the total mass of the composition.

[0022] In some implementations, one or more compounds of Formula (1) may be provided in a composition, wherein the composition contains only the compound(s) of Formula (1), water, and optionally a buffer or preservative. The composition may be buffered to a pH from 2-7, 3-7, 4-7, 5-7, 6-7, 2-4, 3-5, 4-6, or 6-8. are present in an amount of at least 90% by weight, at least 95% by weight, at least 98% by weight, or at least 99% by weight, relative to the total mass of the composition.

[0023] In some implementations, X is CH₂ or CH₂CH₂, preferably CH₂.

[0024] In some implementations, R is H.

[0025] In some implementations L is null or CH₂, preferably CH₂.

[0026] In some implementations, Ar is an unsubstituted phenyl ring, a monosubstituted phenyl ring, a disubstituted phenyl ring, or a trisubstituted phenyl ring. In some implementations, Ar has the formula:

wherein

R¹ is selected from R¹*, OR¹’, COOR¹*, wherein R¹* is selected from H and C_Malkyl; and R² is selected from R²*, OR²*, COOR²*, wherein R²* is selected from H and Ci^alkyl.

[0027] In certain implementations Ar can have the formula:

[0028] In further implementations, Ar has the formula:

[0029] In certain implementations, R¹ can be Ci.₄alkyl or OCi^alkyl, for example R¹ can be methyl, methoxy, ethyl, ethoxy, n-propyl, n-propoxy, isopropyl, isopropoxy, n-butyl, n- butoxy, isobutyl, isobutoxy, sec-butyl, sec-butoxy, tert-butyl, or tert-butoxy. In further implementations, R¹ is isopropyl.

[0030] In some implementations, the compound can have the formula:

[0031] In some implementations, the compound is a compound of Formula (la):

[Formula (la)], wherein X, R, and L have the meanings given above.

[0032] In some implementations of the compound of Formula (la), R is methyl, ethyl, n- propyl, isopropyl, isobutyl, or n-butyl, L is CH₂ or CH₂CH₂, preferably CH₂, and X is CH₂. In certain implementations of the compound of Formula (la) R is methyl, ethyl, n-propyl, isopropyl, isobutyl, or n-butyl, L is CH₂ or CH₂CH₂, preferably CH₂, X is CH₂, and Ar has the formula:

wherein R¹ is OCi-4alkyl, preferably methoxy, ethoxy, n-propoxy, isopropoxy, isobutoxy, or n- butoxy.

[0033] In some implementations, the compound is a compound of Formula (lb) or Formula

(lc):

or a combination thereof. In some implementations of the compound of Formula (lb), R^v is H. In some implementations of the compound of Formula (lc), R* is H.

[0034] In some implementations of the compound of Formula (lb) and/or (lc), R is methyl, ethyl, n-propyl, isopropyl, isobutyl, or n-butyl, L is CH₂ or CH₂CH₂, preferably CH₂, and X is CH₂. In certain implementations of the compound of Formula (lb) and/or (lc) R is methyl, ethyl, n-propyl, isopropyl, isobutyl, or n-butyl, L is CH₂ or CH₂CH₂, preferably CH₂, X is CH₂, and Ar has the formula:

wherein R¹ is OCi.₄alkyl, preferably methoxy, ethoxy, n-propoxy, isopropoxy, isobutoxy, or n- butoxy.

[0035] In some implementations, the composition can include a mixture of the compound of Formula (la) and either the compound of Formula (lb) or Formula (lc), or a mixture of all three compounds. In other implementations, the composition can include the compound of Formula (la) and none of the compound of Formula (lb) or Formula (lc).

[0036] Also provided herein are edible articles containing one or more compounds of Formula (1). In certain implementations, the edible article is free of curcumin. In certain implementations, the edible article includes the compound(s) of Formula (1) in an amount of 0.01-100 mg/kg relative to the edible article, preferably 0.01-10 mg/kg, 0.01-1 mg/kg, 0.01.- 0.1 mg/kg, 0.1-1 mg/kg, 1-10 mg/kg, or 10-100 mg/kg.

[0037] In some implementations, the edible article includes a broth, a soup, a meatcontaining product, a fish-containing product, a poultry-containing product, a dairycontaining product, a fruit-containing product, a vegetable-containing product a graincontaining product, a potato-containing product. It is to be understood that designating a product under one of the aforementioned categories does not exclude other products from the edible article. For example, an edible article that contains meat-containing product can also contain a dairy-containing product.

[0038] In some implementations, the food product is a potato-based products, for example a chip or French fry. [0039] Also disclosed herein are methods of providing edible articles with improved salt flavor and reduced sodium content. In certain implementations the method includes the step of adding one or more compounds of Formula (1) to an edible article, or to a component used to make an edible article. The compound(s) of Formula (1) may be added to the edible article (or component) in an amount of 0.01-100 mg/kg relative to the edible article (or component), preferably 0.01-10 mg/kg, 0.01-1 mg/kg, 0.01. -0.1 mg/kg, 0.1-1 mg/kg, 1-10 mg/kg, or 10-100 mg/kg.

EXAMPLES

[0040] The following examples are for the purpose of illustration of the invention only and are not intended to limit the scope of the present invention in any manner whatsoever.

[0041] Example 1 - Evaluation of salt enhancement

[0042] Ten trained panelists evaluated the impact of 3-hydroxy-l-(4- isopropylbenzyl)piperidine-2, 6-dione on saltiness enhancement, in duplicate using the 2-AFC followed by the intensity rating procedure described above. In each session, panelists were presented with one pair of chicken broth samples (low-sodium chicken broth, College Inn Brand), which was the "control" sample and the other was the "treatment" sample consisting of the control sample with 3-hydroxy-l-(4-isopropylbenzyl)piperidine-2, 6-dione at a concentration of 1.03mg/L. Each sample was served in 8 mL aliquots in black loz portion cups maintained at 35°C. Panelists were asked to swirl each sample in their mouths for 10 seconds and rinse with water between samples. Following this, they were asked to select the saltier sample within the pair. All paired samples were presented in a blinded and randomized manner, and sample order was counterbalanced across the panelists over two sessions. Water was provided as a palate cleanser between samples. All evaluations were conducted using Compusense Cloud software (Compusense Inc., Guelph, Canada) and the data was analyzed using a binomial probability (one-side) test. The spiked sample was significantly saltier than the control (selected 15/20; p-value = 0.02).

[0043] The compositions and methods of the appended claims are not limited in scope by the specific compositions and methods described herein, which are intended as illustrations of a few aspects of the claims and any compositions and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the compositions and methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative compositions and method steps disclosed herein are specifically described, other combinations of the compositions and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein or less, however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated. The term "comprising" and variations thereof as used herein is used synonymously with the term "including" and variations thereof and are open, nonlimiting terms. Although the terms "comprising" and "including" have been used herein to describe various embodiments, the terms "consisting essentially of" and "consisting of" can be used in place of "comprising" and "including" to provide for more specific embodiments of the invention and are also disclosed. Other than in the examples, or where otherwise noted, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood at the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, to be construed in light of the number of significant digits and ordinary rounding approaches

Claims

CLAIMS What is claimed is:

1. A salty taste enhancing compound or composition, comprising a compound of Formula (1):

[Formula (1)], or a salt thereof, wherein

X is null, CH₂, or CH₂CH₂;

L is null, CH₂, or CH₂CH₂;

R is H, Ci-₃alkyl, or C(=O)Ci.₃alkyl;

Ar optionally substituted C₆-ioaryl or Ci-i₀heteroaryl;

Z¹ and Z² are either both null, or Z¹ is OR^Z or N(R^Z)₂ and Z² is H, wherein R^z is in each case independently selected from H and Ci-₃alkyl;

Y¹ and Y² are either both null, or Y¹ is OR^y or N( R^y)₂ and Y² is H, wherein R^y is in each case independently selected from H and Ci-₃a Ikyl; providing that Z² and Y² are not both H.

2. The compound or composition according to claim 1, wherein the composition is free of cuminaldehyde.

3. The compound or composition according to claim 1, wherein the compound of Formula 1 is present in the composition in an amount of at least 90% by weight, at least 95% by weight, at least 98% by weight, or at least 99% by weight.

4. The compound or composition according to claim 1, wherein the composition consists essentially of the compound of Formula 1.

5. The compound or composition according to claim 1, wherein the composition consists essentially of the compound of Formula 1 and water, and optionally a buffer and/or preservative.

6. The compound or composition according to claim 1, wherein the compound has the formula:

7. The compound or composition according to claim 6, wherein the composition comprises a compound of Formula (la), Formula (lb), or Formula (lc):

or a combination thereof.

8. The compound or composition according to claim 1, 6 or 7, wherein X is CH₂.

9. The compound or composition according to claim 1, 6 or 7, wherein R is H.

10. The compound or composition according to claim 1, 6 or 7, wherein L is CH₂.

11. The compound or composition according to claim 1, 6 or 7, wherein Ar is an unsubstituted phenyl ring, a monosubstituted phenyl ring, a disubstituted phenyl ring, or a trisubstituted phenyl ring.

12. The compound or composition according to claim 1, 6 or 7, wherein Ar has the formula:

wherein R¹ is selected from R¹*, OR¹*, COOR¹*, wherein R¹* is selected from H and Ci-4a Ikyl; and

R² is selected from R²*, OR²*, COOR²*, wherein R²* is selected from H and Ci-₄a Ikyl.

13. The compound or composition according to claim 1, 6, or 7, wherein Ar has the formula:

14. The compound or composition according to claim 1, 6, or 7, wherein Ar has the formula:

15. The compound or composition according to claim 1, 6, or 7, wherein R¹ is Ci.₄a Ikyl or OCi. 4alkyl.

16. The compound or composition according to claim 1, 6, or 7, wherein R¹ is methyl, methoxy, ethyl, ethoxy, n-propyl, n-propoxy, isopropyl, isopropoxy, n-butyl, n-butoxy, isobutyl, isobutoxy, sec-butyl, sec-butoxy, tert-butyl, or tert-butoxy.

17. The compound or composition according to claim 1, 6, or 7, wherein R¹ is isopropyl.

18. A method for enhancing the salty flavor of an edible article, comprising adding to the edible article the compound or composition according to any preceding claim.

19. The method according to any preceding claim, wherein the edible article comprises a food, a drink, a medication.

20. The method according to any preceding claim, wherein the edible article comprises a broth, a soup, a meat-containing product, a fish-containing product, a poultry-containing product, a dairy-containing product, a fruit-containing product, a vegetable-containing product a graincontaining product, a potato-containing product, or a combination thereof.

21. The method according to claim 18, wherein the compound or composition is added to the edible article in an amount to provide the compound of Formula (1) at concentration of 0.01-100 mg/kg relative to the edible article, preferably 0.01-10 mg/kg, 0.01-1 mg/kg, 0.01.- 0.1 mg/kg, 0.1-1 mg/kg, 1-10 mg/kg, or 10-100 mg/kg.

22. An edible article comprising the compound or composition according to any of claims 1 or 6- 17, wherein the edible article is free of cuminaldehyde.

23. The edible article according to claim 21 or 22 , wherein the edible article comprises a broth, a soup, a meat-containing product, a fish-containing product, a poultry-containing product, a dairy-containing product, a fruit-containing product, a vegetable-containing product a graincontaining product, a potato-containing product, or a combination thereof.