Granted Patent B2

US 12,478,091 · App. 18/926,671 · Granted Nov 25, 2025

Inventors: Charlotte L. Owen (Seguin, TX); Richard Avila, Jr. (Prescott Valley, AZ); Geoff W. Habicht (Phoenix, AZ)

Assignee: Ready Mix Naturals, LLC

A24B15/167A24B15/303A24B15/38

Abstract

Claims (58)

1 . A composition, comprising:

at least one substituted pyridine compound of Formula (I):

or a salt, or mixed salt thereof, wherein:

A is selected from:

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, and

R 6 and R 7 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl and substituted alkenyl, or R 6 and R 7 together are ═O;

R 8 , R 9 , R 10 , R 11 , and R 12 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, and substituted alkenyl;

R 13 and R 14 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, and substituted alkenyl, or R 13 and R 14 together are ═O;

n is an integer from 1 to 10; and

R 15 and R 16 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl and substituted alkenyl, or R 15 and R 16 together with the N atom to which they are bonded form a 3-8 membered optionally substituted heterocyclic ring,

with the proviso that if A is

and R 5 is methyl, then R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 cannot all be H; and

at least one chemosensory irritant, wherein the chemosensory irritant comprises at least one of oleocanthal, 4-hydroxy-2-nonenal, 4-oxo-2-nonenal, allicin, allyl isothiocyanate, icilin, polygodial, cinnamaldehyde, trans-p-methoxycinnamaldehyde, methyl syringate, 2-chlorobenzylidene malononitrile, 1-chloroacetophenone, ethyl bromoacetate, 4-hydroxyhexenal, toluene diisocyanate, p-benzoquinone, methyl p-hydroxybenzoate, flufenamic acid, niflumic acid, mefenamic acid, diclofenac, hydroxy-α-sanshool, 6-paradol, carvacrol, eugenol, thymol, methyl eugenol, 2,6-dimethylphenol, 2,5-dimethylphenol, 3,4-dimethylphenol, 2,6-diisopropylphenol, farnesyl thiosalicylic acid, 4-allylanisole, curcumin, niacin, camphor, olvanil, arvanil, baicalein, baicalin, wogonin, norwogonin, oroxylin A, β-sitosterol, dihydrocapsaicin, norcapsaicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, shogaol, 6-shogaol, isopiperine, chavicine, isochavicine, 2-piperamine, piperanine (4,5-dihydropiperine), piperamide, 4-pipericide, piperyline, piperlonguminine, piperettine, piperdardine, 6,7-dihydropiperettine, 5-sarmentodine, 6-sarmentine, or 7-trichostachine,

wherein the composition is entirely devoid of (R) or (S) nicotine.

2 . The composition of claim 1 , wherein the at least one substituted pyridine compound has a structure according to Formula (IA):

or a salt, or mixed salt thereof; or

according to Formula (IA-1):

or a salt, or mixed salt thereof; or

according to Formula (IA-2):

or a salt, or mixed salt thereof; or

according to Formula (IA-3):

or a salt, or mixed salt thereof; or according to Formula (IA-4):

or a salt, or mixed salt thereof; or according to Formula (IA-5):

or a salt, or mixed salt thereof; or according to Formula (IB):

or a salt, or mixed salt thereof; or according to Formula (IC):

or a salt, or mixed salt thereof, or according to Formula (ID):

or a salt, or mixed salt thereof; or according to Formula (IE):

or a salt, or mixed salt thereof; or according to Formula (IAA):

or a salt, or mixed salt thereof, with the proviso that if R 5 is CH 3 , then R 1 , R 2 , R 3 , and R 4 cannot all be H.

3 . The composition of claim 1 , wherein the at least one substituted pyridine compound is selected from (R) or (S)-3-(pyrrolidin-2-yl)pyridine, (R) or (S)-2-methyl-3-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-4-methyl-3-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-3-methyl-5-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-2-methyl-5-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-2,6-dimethyl-3-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-2,4-dimethyl-5-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-2,3-dimethyl-5-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-2,4-dimethyl-3-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-2,5-dimethyl-3-(1-methylpyrrolidin-2-yl)pyridine, (R) or (S)-3,4-dimethyl-5-(1-methylpyrrolidin-2-yl)pyridine,

or a salt, or a mixed salt thereof.

4 . The composition of claim 1 , further comprising an organic acid or a salt thereof.

5 . The composition of claim 4 , wherein the organic acid or salt thereof comprises at least one of formic acid, acetic acid, trifluoroacetic acid, aspartic acid, butanoic acid, butyric acid, 2-methylbutyric acid, 3-methylbutyric acid, benzoic acid, caprylic acid, citric acid, crotonic acid, ethylenediaminetetraacetic acid, fumaric acid, gluconic acid, glutamic acid, glyceric acid, glycolic acid, lactic acid, lauric acid, levulinic acid, maleic acid, malic acid, malonic acid, mandelic acid, methane sulfonic acid, oxalic acid, phenylacetic acid, phthalic acid, picric acid, propionic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, tannic acid, tartaric acid, tartronic acid, or valeric acid, or a salt thereof.

6 . The composition of claim 1 , wherein the chemosensory irritant further comprises a cannabinoid, wherein the cannabinoid comprises at least one of anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-arachidonoyl dopamine (NADA), N-oleoyldopamine (OLDA), palmitoylethanolamide (PEA), N-acyl GABA (NGABA), N-acyl glycine (NGly), N-arachidonoyl glycine (NAGly), N-acyl aspartic acid (NAsp), N-acyl serine (NSer), Δ9-tetrahydrocannabinol (Δ9-THC), Δ9-tetrahydrocannabinolic acid (Δ9-THCA), Δ9-tetrahydrocannabivarin (THCV), Δ9-THCVA, cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabinol (CBN), cannabichromene (CBC), or a synthetic cannabinoid.

7 . The composition of claim 6 , wherein the synthetic cannabinoid comprises at least one of WIN55,212-2, 6-Iodopravadoline (AM630), (R)-AM1241, (S)-AM1241, SR141716A, Gp-1a, AM251, SR144528, JWH133, HU308, HU910, CP55, 940, or nabilone.

8 . The composition of claim 1 , wherein the chemosensory irritant further comprises at least one of capsaicin, piperine, gingerol, linalool, vanillin, or caffeine.

9 . The composition of claim 1 , wherein the chemosensory irritant further comprises a phytochemical, wherein the phytochemical comprises at least one of a resiniferanoid, a ginsenoside, zingerone, paradol, an evodia compound, an unsaturated 1,4-dialdehyde sesquiterpene, a 1,4-dialdehyde terpene, or warburganal.

10 . The composition of claim 9 , wherein the unsaturated 1,4-dialdehyde sesquiterpene comprises at least one of polygodial, isovelleral, or drimanial.

11 . The composition of claim 9 , wherein the 1,4-dialdehyde terpene comprises at least one of cinnamodial, cinnamosmolide, or cinnamolide.

12 . The composition of claim 1 , wherein the chemosensory irritant further comprises a phytochemical, wherein the phytochemical comprises a phytochemical from at least one of capsicum annuum, zingiber officiale, piper nigrum , euphorbia reinifera, euenia carophyllata, ocimum gratissiumum, panax, aframomum melgueta, evodia rutaecarpa , drymis winteri, cinnamosma fragrans, warburgia, scutellaria baicalensis, vitex agnus, pterodon pubescens, croton macrostachyus , angelicae pubescentis, ephedra sinica, amphilophium crucigerum , bosewellia carterii, commiphora myrrha, echinophora platyloba, nypa fruticans, corydalis saxicola, coptis chinensis, ononis spinosa, parkia platycephala , or cymbopogon citratus.

13 . A composition, comprising:

at least one substituted pyridine compound of Formula (I):

or a salt, or mixed salt thereof, wherein:

A is selected from:

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, and

R 6 and R 7 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl and substituted alkenyl, or R 6 and R 7 together are ═O;

R 8 , R 9 , R 10 , R 11 , and R 12 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, and substituted alkenyl;

R 13 and R 14 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, and substituted alkenyl, or R 13 and R 14 together are ═O;

n is an integer from 1 to 10; and

R 15 and R 16 are independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl and substituted alkenyl, or R 15 and R 16 together with the N atom to which they are bonded form a 3-8 membered optionally substituted heterocyclic ring,

with the proviso that if A is

and R 5 is methyl, then R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 cannot all be H; and

an organic acid comprising acetic acid and citric acid or salts thereof,

wherein the composition is entirely devoid of (R) or(S) nicotine.

14 . The composition of claim 13 , wherein the substituted pyridine compound is selected from nicotinamide, (S)-N,N-dimethyl-3-(5-(1-methylpyrrolidin-2-yl)pyridin-2-yl) propan-1-amine, (S)-N,N-dimethyl-2-(2-(pyridin-3-yl)pyrrolidin-1-yl)ethan-1-amine, (S)-N,N-dimethyl-3-(2-(pyridin-3-yl)pyrrolidin-1-yl)propan-1-amine, N,N-dimethyl-1-(pyridin-3-yl)methanamine, and N-methyl-N-(pyridin-3-ylmethyl)ethanamine.

15 . The composition of claim 13 , further comprising a chemosensory irritant comprising at least one of oleocanthal, 4-hydroxy-2-nonenal, 4-oxo-2-nonenal, allicin, allyl isothiocyanate, icilin, polygodial, cinnamaldehyde, trans-p-methoxycinnamaldehyde, methyl syringate, 2-chlorobenzylidene malononitrile, 1-chloroacetophenone, ethyl bromoacetate, 4-hydroxyhexenal, toluene diisocyanate, p-benzoquinone, methyl p-hydroxybenzoate, flufenamic acid, niflumic acid, mefenamic acid, diclofenac, hydroxy-α-sanshool, 6-paradol, linalool, carvacrol, eugenol, thymol, vanillin, methyl eugenol, 2,6-dimethylphenol, 2,5-dimethylphenol, 3,4-dimethylphenol, 2,6-diisopropylphenol, caffeine, farnesyl thiosalicylic acid, 4-allylanisole, curcumin, niacin, camphor, olvanil, arvanil, baicalein, baicalin, wogonin, norwogonin, oroxylin A, β-sitosterol, dihydrocapsaicin, norcapsaicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, shogaol, 6-shogaol, isopiperine, chavicine, isochavicine, 2-piperamine, piperanine (4,5-dihydropiperine), piperamide, 4-pipericide, piperyline, piperlonguminine, piperettine, piperdardine, 6,7-dihydropiperettine, 5-sarmentodine, 6-sarmentine, 7-trichostachine, a cannabinoid, or a phytochemical.

16 . The composition of claim 13 , wherein the cannabinoid comprises at least one of anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-arachidonoyl dopamine (NADA), N-oleoyldopamine (OLDA), palmitoylethanolamide (PEA), N-acyl GABA (NGABA), N-acyl glycine (NGly), N-arachidonoyl glycine (NAGly), N-acyl aspartic acid (NAsp), N-acyl serine (NSer), Δ9-tetrahydrocannabinol (Δ9-THC), Δ9-tetrahydrocannabinolic acid (Δ9-THCA), Δ9-tetrahydrocannabivarin (THCV), Δ9-THCVA, cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabinol (CBN), cannabichromene (CBC), or a synthetic cannabinoid.

17 . The composition of claim 16 , further comprising at least one flavoring agent.

Assignments (1)

Continuity (4)

References Cited (51)