Granted Patent B2

US 12,497,381 · App. 18/807,086 · Granted Dec 16, 2025

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

Assignee: Ready Mix Naturals, LLC

C07D401/04A61K9/007A61K47/12A61K47/18C07D213/72C07D401/14C07D413/14

Abstract

Claims (100)

1 . A vaporizable alkaloid 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;

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 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;

at least one solvent, and

at least one flavoring agent selected from the group comprising geraniol, geranial, valeric acid, ethyl maltol, ethyl butyrate, ethyl acetate, maltol, ethyl 3-methyl-3-phenylglycidate, furaneol, methyl cyclopentenolone, ethyl cyclopentenolone, δ-decalactone, γ-decalactone, α-nonalactone, β-nonalactone, cis-3-hexanol, iso-amyl acetate, ethyl-2-methyl butyrate, butyric acid, ethyl butyrate, 2-methylbutyric acid, benzyl alcohol, ethyl hexanoate, benzaldehyde, iso-amyl isovalerate, hexanoic acid, ethyl propionate, γ-undecalactone, acetyl propionyl, raspberry ketone, furfural, 5-methylfurfural, maltol, 2-acetylpyrazine, 2,3,5-trimethylpyrazine, 2-acetylpyrrole, 2-isopropyl-4-methylthiazole, 2-isobutylthiazole, furfuryl mercaptan, thiomenthone, p-menthene-8-thiol, tropathiane, hexyl acetate and mixtures thereof, wherein the vaporizable alkaloid composition is entirely devoid of (R) or (S) nicotine.

2 . The vaporizable alkaloid 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 has a structure according to Formula (IA-1):

or a salt, or mixed salt thereof; or has a structure according to Formula (IA-2):

or a salt, or mixed salt thereof; or has a structure according to Formula (IA-3):

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

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

or a salt, or mixed salt thereof.

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

or a salt, or mixed salt thereof.

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

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

or a salt, or mixed salt thereof; or has a structure 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.

5 . The vaporizable alkaloid 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.

6 . The vaporizable alkaloid composition of claim 1 , further comprising an organic acid selected from the group consisting 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, valeric acid, and mixtures thereof.

7 . The vaporizable alkaloid composition of claim 6 , wherein the organic acid is selected from the group consisting of citric acid, acetic acid, benzoic acid, tartaric acid, lactic acid, salicylic acid, malic acid, levulinic acid, and mixtures thereof.

8 . The vaporizable alkaloid composition of claim 6 , wherein the molar ratio of total substituted pyridine compound to total organic acid is about 25:1 to about 75:1.

9 . The vaporizable alkaloid composition of claim 1 , wherein the solvent is selected from the group consisting of propylene glycol, water, ethanol, glycerin, and mixtures thereof.

10 . The vaporizable alkaloid composition of claim 1 , further comprising at least one chemosensory irritant.

11 . The vaporizable alkaloid composition of claim 10 , wherein the chemosensory irritant is selected from the group consisting 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, anandamide, cannabidiol, Δ 9 -tetrahydrocannabinol, baicalein, baicalin, wogonin, norwogonin, oroxylin A, β-sitosterol and mixtures thereof.

12 . The vaporizable alkaloid composition of claim 10 , wherein the chemosensory irritant is a spice additive exhibiting a spiciness of from about 1,000 to about 20,000,000 Scoville Heat Units (SHU).

13 . The vaporizable alkaloid composition of claim 12 , wherein the spice additive is selected from the group consisting of capsaicin, dihydrocapsaicin, norcapsaicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, gingerol, piperine, Shogaol, isopiperine, chavicine, isochavicine, 2-piperamine, piperanine (4,5-dihydropiperine), piperamide, 4-pipericide, piperyline, piperlonguminine, piperettine, 6,7-dihydropiperettine, 5-sarmentodine, 6-sarmentine, 7-trichostachine, and mixtures thereof.

14 . The vaporizable alkaloid composition of claim 12 , wherein the spice additive is capsaicin or a mixture of capsaicinoids.

15 . A vaporizable alkaloid composition comprising:

(a) from about 1 wt. % to about 80 wt. % of a 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;

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 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;

(b) from about 0.05 wt. % to about 1.5 wt. % in total of at least one organic acid; and

(c) remainder solvent,

wherein the weight percentages are based on the total weight of the vaporizable alkaloid composition; and

wherein the molar ratio of moles of substituted pyridine compound to total moles of organic acid is from about 25:1 to about 75:1.

16 . The vaporizable alkaloid composition of claim 15 , wherein the substituted pyridine compound is selected from (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.

17 . The vaporizable composition of claim 15 , wherein the molar ratio of moles substituted pyridine compound to total moles of organic acid is about 50:1.

18 . A method for promoting smoking cessation in an individual desirous of cessation, the method comprising:

administering to the individual, over a time period determined for cessation, a series of vaporizable alkaloid compositions for the individual to inhale by vaping, each vaporizable alkaloid composition in the series comprising at least one vaporizable alkaloid composition according to claim 1 .

19 . The method of claim 18 , wherein the vaporizable alkaloid composition in the series of vaporizable alkaloid compositions having the highest level (w/v) of said substituted pyridine compound of Formula (I), or salt, or mixed salt thereof comprises about 100 mg/mL of said substituted pyridine compound of Formula (I), or salt, or mixed salt thereof.

20 . The method of claim 18 , wherein the vaporizable alkaloid composition in the series of vaporizable alkaloid compositions having the lowest level (w/v) of substituted pyridine compound of Formula (I), or salt, or mixed salt thereof comprises no more than about 1 mg/mL of said substituted pyridine compound of Formula (I), or salt, or mixed salt thereof.

21 . A vaporizable alkaloid 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;

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 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;

at least one solvent, and at least one organic acid wherein the organic acid is selected from the group consisting of formic acid, acetic acid, trifluoroacetic acid, aspartic acid, butanoic acid, butyric acid, 2-methylbutyric acid, 3-methylbutyric acid, benzoic acid, caprylic acid, crotonic acid, ethylenediaminetetraacetic acid, fumaric acid, gluconic acid, glutamic acid, glyceric acid, glycolic acid, lactic acid, lauric acid, levulinic acid, maleic acid, malonic acid, mandelic acid, methane sulfonic acid, oxalic acid, phenylacetic acid, phthalic acid, picric acid, propionic acid, pyruvic acid, salicylic acid, stearic acid, tannic acid, tartronic acid, valeric acid, and mixtures thereof, and wherein the vaporizable alkaloid composition is entirely devoid of (R) or (S) nicotine.

22 . A vaporizable alkaloid 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;

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 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; at least one chemosensory irritant; and

at least one solvent, wherein the vaporizable alkaloid composition is entirely devoid of (R) or (S) nicotine.

23 . A vaporizable alkaloid 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;

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 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;

at least one solvent; and at least one organic acid,

wherein the vaporizable alkaloid composition is entirely devoid of (R) or (S) nicotine and the molar ratio of substituted pyridine compound to organic acid is about 25:1 to about 75:1.

Assignments (1)

Continuity (4)

References Cited (53)