CROSS-REFERENCE TO RELATED APPLICATIONS

This patent document claims priority to U.S. Provisional Patent Application No. 63/003,756, filed April 1, 2020, and U.S. Provisional Patent Application No. 63/012,773, filed April 20, 2020, each of which is incorporated by reference in its entirety.

BACKGROUND

Curcumin is the major bioactive molecule of turmeric, which is an ingredient and dietary supplement. Curcumin is known to be effective at treating cancer and inflammation. Numerous attempts to develop curcumin pharmaceuticals nevertheless failed in part because curcumin has limited solubility and limited bioavailability and because curcumin is thought to have limited chemical stability. Curcumin formulations with improved solubility, bioavailability, and stability are desirable.

SUMMARY

Various aspects of this disclosure relate to anionic forms of structural isomers of curcumin.

Without limiting this disclosure or any patent claim that matures from this document, anionic forms of curcumin and its structural isomers display improved solubility in water relative to molecular forms because anionic forms carry negative charges, which favors hydrogen bonding to water; charge-charge repulsion maximizes surface area in liquid formulations, which generally improves bioavailability and pharmacokinetics; the administration of anionic forms of curcumin and its structural isomers to subjects converts the anionic forms to molecular forms; the molecular forms partition out of liquid formulations and into the epithelial lining of a subject for rapid absorption, which improves bioavailability and pharmacokinetics; and the molecular forms avoid first-pass metabolism, for example, when the molecular forms partition into the epithelial lining of the mouth or esophagus, which improves bioavailability and pharmacokinetics.

Without limiting this disclosure or any patent claim that matures from this document, those skilled in the relevant arts generally believed that liquid formulations comprising curcumin generally, and the anionic forms of curcumin specifically, lacked sufficient stability to be pharmaceutically relevant; the perceived instability of curcumin generally, and the anionic forms of curcumin specifically, arose in part from the conversion of curcumin into one or more structural isomers of curcumin, which decreases measured curcumin concentrations in curcumin formulations.

This patent document discloses anionic forms of structural isomers of curcumin that can be manufactured from curcumin using acid-base chemistry. The anionic forms of structural isomers of curcumin display improved solubility, bioavailability, and pharmacokinetics relative to known curcumin formulations, and they are expected to display comparable or improved efficacy at treating the health conditions that curcumin is known to treat.

Curcuma longa (turmeric) biosynthetically produces curcumin, which is a tautomer that exists as 3-hydroxy-l,7-bis(4-hydroxy-3-methoxyphenyl)hepta-l,3,6-trie n-5-one (Compound I) and 1,7- bis(4-hydroxy-3-methoxyphenyl)hepta-l,6-dien-3,5-dione (Compound II).

The molecule of Compound I can be deprotonated to produce the anion 2-methoxy-4-[3-hydroxy- 5-oxo-7-(4-hydroxy-3-methoxyphenyl)hepta-l,3,6-trienyl]pheno late (Compound III) and the anion 2-methoxy-4-[5-hydroxy-3-oxo-7-(4-hydroxy-3-methoxyphenyl)he pta-l,4,6-trienyl]phenolate (Compound IV).

The molecule of Compound II can be deprotonated to produce the anion 2-methoxy-4-[3,5-dioxo- 7-(4-hydroxy-3-methoxyphenyl)hepta-l,6-dienyl]phenolate (Compound V).

The anion of Compound III has resonance structures 5-hydroxy-3-oxo-l-(4-hydroxy-3- methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l,4-dien-6-ide (Compound VI), 5 -hy droxy-3 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(3 -methoxy-4-oxocy clohexa-2, 5 - dienylidene)hepta-l,5-dien-4-ide (Compound VII), and 5-hydroxy-l-(4-hydroxy-3- methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l,3,5-triene-3-oxide (Compound VIII), each of which is an anion. The anion of Compound VI can be reprotonated to produce the molecule 5 -hydroxy-3 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(3 -methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l, 4-diene (Compound IX). The anion of Compound VII can be reprotonated to produce the molecule 5 -hydroxy-3 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(3 - methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l, 5-diene (Compound X). The anion of Compound VIII can be reprotonated to produce the molecule 3,5-dihydroxy-l-(4-hydroxy-3-methoxyphenyl)- 7-(3 -methoxy-4-oxocy cl ohexa-2, 5 -di enylidene)hepta- 1 , 3 , 5 -triene (Compound XI).

“3-methoxy-4-oxocyclohexa-2,5-dienylidene” refers to Substituent 1; “-ide” refers to a carbanion; and “oxide” refers to -O ¹ .

Substituent 1

The anion of Compound IV has resonance structure 3-hydroxy-5-oxo-l-(4-hydroxy-3- methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l,3-dien-6-ide (Compound XII), which is an anion. The anion of Compound XII can be reprotonated to produce the molecule 3 -hy droxy-5 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(3 -methoxy-4-oxocy clohexa-2, 5 - dienylidene)hepta- 1,3 -diene (Compound XIII).

The anion of Compound V has resonance structure 3,5-dioxo-l-(4-hydroxy-3-methoxyphenyl)-7- (3-methoxy-4-oxocyclohexa-2,5-dienylidene)hept-l-en-6-ide (Compound XIV), which is an anion. The anion of Compound XIV can be reprotonated to produce the molecule 3,5-dioxo-l-(4-hydroxy- 3-methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene )hept-l-ene (Compound XV).

The molecule of Compound IX can be deprotonated to produce the anion 2-methoxy-4-[5- hydroxy-3-oxo-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)he pta-l,4-dienyl]phenolate (Compound XVI). The anion of Compound XVI has resonance structures 3-hydroxy-5-oxo-l,7- bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hept-3-en-6-ide (Compound XVII) and 5-hydroxy-

1.7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-2, 4-diene-3-oxide (Compound XVIII), each of which is an anion. The anion of Compound XVII can be reprotonated to produce the molecule 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienyli dene)hept-3-ene (Compound XIX). The anion of Compound XVIII can be reprotonated to produce the molecule 3,5- dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-2, 4-diene (Compound XX).

The molecule of Compound X can be deprotonated to produce the anion 2-methoxy-4-[5- hydroxy-3-oxo-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)he pta-l,5-dienyl]phenolate (Compound XXI). The anion of Compound XXI has resonance structures 3-hydroxy-5-oxo-l,7- bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hept-2-en-6-ide (Compound XXII) and 5-hydroxy-

1.7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-2, 5-diene-3-oxide (Compound XXIII), each of which is an anion. The anion of Compound XXII can be reprotonated to produce the molecule 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienyli dene)hept-2-ene (Compound XXIV). The anion of Compound XXIII can be reprotonated to produce the molecule 3, 5-dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene )hepta-2, 5-diene (Compound XXV).

The molecule of Compound XV can be deprotonated to produce the anion 2-methoxy-4-[3,5- dioxo-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hept-l-eny l]phenolate (Compound XXVI). The anion of Compound XXVI has the resonance structure 3,5-dioxo-l,7-bis(3-methoxy-4- oxocyclohexa-2,5-dienylidene)heptan-2-ide (Compound XXVII), which is an anion. The anion of Compound XXVII can be reprotonated to produce the molecule 3,5-dioxo-l,7-bis(3-methoxy-4- oxocyclohexa-2,5-dienylidene)heptane (Compound XXVIII). Compounds IX, X, XI, XIII, XV, XIX, XX, XXIV, XXV, and XXVIII are molecules that are structural isomers of curcumin and that can be produced from curcumin using acid-base chemistry in a protic polar solvent such as ethanol. Compounds III, IV, V, VI, VII, VIII, XII, XIV, XVI,

XVII, XVIII, XXI, XXII, XXIII, XXVI, and XXVII are anions that can be produced from curcumin using acid-base chemistry in a protic polar solvent. Additional anions are described in the detailed description that follows, and these anions can be produced from curcumin using a strategy similar to the strategy described above.

DETAILED DESCRIPTION

Various aspects of this disclosure relate to a composition, comprising an anion.

“Comprise” and “comprising” refer to open sets such that a composition comprising an anion can also comprise additional anions, a cation, and a solvent.

In some embodiments, the anion is 5-hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-2,4-diene-3-oxide.

In some embodiments, the anion is 5-hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-3,5-diene-3-oxide.

In some embodiments, the anion is 3,5-dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-2,4-dien-6-ide.

In some embodiments, the anion is 5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-2-ene-3 -oxide.

In some embodiments, the anion is 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-2-en-4-ide.

In some embodiments, the anion is 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- di eny li dene)hept-2 -en-6-i de .

In some embodiments, the anion is 5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-3 -ene-3 -oxide.

In some embodiments, the anion is 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-3 -en-2-ide.

In some embodiments, the anion is 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-3 -en-6-ide.

In some embodiments, the anion is 5-hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-2,5-diene-3-oxide.

In some embodiments, the anion is 3,5-dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-2,5-dien-4-ide.

In some embodiments, the anion is 3,5-dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- di eny li dene)heptan-2-i de .

In some embodiments, the anion is 3,5-dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- di eny li dene)heptan-4-i de .

In some embodiments, the anion is 2-methoxy-4-[3-hydroxy-5-oxo-7-(3-methoxy-4- oxocy cl ohexa-2, 5 -di eny 1 idene)hepta- 1 , 3 -di eny 1 ] phenol ate .

In some embodiments, the anion is 5-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l,3-diene-3-oxide.

In some embodiments, the anion is 3-hydroxy-5-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,3-dien-6-ide.

In some embodiments, the anion is 2-methoxy-4-[5-hydroxy-3-oxo-7-(3-methoxy-4- oxocy cl ohexa-2, 5 -di eny 1 idene)hepta- 1,4-di eny 1 ] phenol ate .

In some embodiments, the anion is 3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l,4-diene-5-oxide.

In some embodiments, the anion is 5-hydroxy-3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,4-dien-6-ide.

In some embodiments, the anion is 2-methoxy-4-[5-hydroxy-3-oxo-7-(3-methoxy-4- oxocy cl ohexa-2, 5 -di eny 1 idene)hepta- 1 , 5 -di eny 1 ] phenol ate .

In some embodiments, the anion is 3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l,5-diene-5-oxide.

In some embodiments, the anion is 5-hydroxy-3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,5-dien-4-ide.

In some embodiments, the anion is 2-methoxy-4-[3,5-dioxo-7-(3-methoxy-4-oxocyclohexa-2,5- di eny li dene)hept- 1 -eny 1 ] phenol ate .

In some embodiments, the anion is 3,5-dioxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4- oxocy cl ohexa-2, 5 -di eny 1 idene)hept- 1 -en-4 -i de .

In some embodiments, the anion is 3,5-dioxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hept-l-en-6-ide.

In some embodiments, the anion is 2-methoxy-4-[3,5-dihydroxy-7-(3-methoxy-4-oxocyclohexa- 2, 5 -di eny li dene)hepta- 1,3,5 -tri eny 1 ] phenol ate .

In some embodiments, the anion is 5 -hydroxy- l-(4-hydroxy-3-methoxyphenyl)-7-(3-m ethoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l,3,5-triene-3-oxide.

In some embodiments, the anion is 3 -hydroxy- l-(4-hydroxy-3 -methoxyphenyl)-7-(3 -methoxy-4- oxocy cl ohexa-2, 5 -di eny 1 idene)hepta- 1 , 3 , 5 -tri ene- 5 -oxi de .

In some embodiments, the anion is 2-methoxy-4-[3-hydroxy-5-oxo-7-(4-hydroxy-3- methoxyphenyl)hepta-l,3,6-trienyl]phenolate.

In some embodiments, the anion is 2-methoxy-4-[5-hydroxy-3-oxo-7-(4-hydroxy-3- methoxyphenyl)hepta-l,4,6-trienyl]phenolate.

In some embodiments, the anion is 2-methoxy-4-[3,5-dioxo-7-(4-hydroxy-3- methoxyphenyl)hepta-l,6-dienyl]phenolate. In some embodiments, the anion has the chemical formula C21H19O6 ; the anion has the chemical structure set forth in General Structure 1; General Structure 1 contains exactly 10 double bonds; R1 is hydroxy, oxide, or oxo; R2 is hydroxy or oxo; and the 4 dotted lines in General Structure 1 depict 0, 1, or 2 double bonds. Each “hydroxy” and each “oxide” contributes exactly 0 double bonds by definition. Each “oxo” contributes exactly 1 double bond by definition. Each of the 21 carbon atoms participates in either exactly 0 or exactly 1 double bond. The carbon atom that is covalently bound to R1 participates in exactly 1 double bond. The carbon atom that is covalently bound to R2 participates in exactly 1 double bond. In some embodiments, the anion has the chemical formula C21H19O6 ; the anion has the chemical structure set forth in General Structure 2; General Structure 2 contains exactly 10 double bonds; R1 is hydroxy, oxide, or oxo; R2 is hydroxy, oxide, or oxo; R3 is hydroxy or oxide; and the 3 dotted lines in General Structure 2 depict 0, 1, or 2 double bonds. Various aspects of this disclosure relate to a composition, comprising a plurality of anions, which comprises an anion.

In some embodiments, the plurality of anions consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or each of 5-hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-2,4-diene-3-oxide; 5- hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hep ta-3,5-diene-3-oxide; 3,5- dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-2,4-dien-6-ide; 5-oxo-l,7- bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hept-2-ene-3-ox ide; 3 -hydroxy-5 -oxo- l,7-bis(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hept-2-en-4-ide; 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hept-2-en-6-ide; 5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-3-ene-3 -oxide; 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-3-en-2-ide; 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-3-en-6-ide; 5-hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta- 2,5-diene-3-oxide; 3,5-dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylide ne)hepta-2,5- dien-4-ide; 3,5-dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h eptan-2-ide; and 3,5- dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hepta n-4-ide. In some specific embodiments, the plurality of anions consists of 5 anions. In some very specific preferred embodiments, the plurality of anions consists of 5 different anions; the plurality of anions consists of oxides and phenolates; and the plurality of anions lacks carbanions.

“Consist” and “consisting” refer to closed sets such that a plurality of anions that consists of 5- hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hep ta-2,4-diene-3-oxide cannot comprise any other anion; a composition that comprises a plurality of anions that consists of 5- hydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hep ta-2,4-diene-3-oxide can nevertheless comprise additional anions that are not included in the plurality of anions.

In some embodiments, the plurality of anions consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or each of 2-methoxy-4-[3-hydroxy-5-oxo-7-(3-methoxy-4-oxocyclohexa-2,5 -dienylidene)hepta-l,3- dienyljphenolate; 5-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocycloh exa-2,5- dienylidene)hepta- 1,3 -diene-3 -oxide; 3-hydroxy-5-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,3-dien-6-ide; 2-methoxy-4-[5-hydroxy-3-oxo-7- (3 -methoxy-4-oxocyclohexa-2,5-dienylidene)hepta- 1 ,4-dienyl]phenolate; 3 -oxo- 1 -(4-hydroxy-3 - methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l,4-diene-5-oxide; 5- hy droxy-3 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)-7 -(3 -methoxy-4-oxocy clohexa-2, 5 - dienylidene)hepta-l,4-dien-6-ide; 2-methoxy-4-[5-hydroxy-3-oxo-7-(3-methoxy-4-oxocyclohexa- 2,5-dienylidene)hepta-l,5-dienyl]phenolate; 3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy- 4-oxocyclohexa-2,5-dienylidene)hepta-l,5-diene-5-oxide; 5 -hydroxy-3 -oxo-l-(4-hydroxy-3- methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l,5-dien-4-ide; 2-methoxy- 4-[3,5-dioxo-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hep t-l-enyl]phenolate; 3,5-dioxo-l-(4- hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-die nylidene)hept-l-en-4-ide; 3,5- di oxo-1 -(4-hydroxy-3-m ethoxyphenyl)-7-(3-methoxy-4-oxocy cl ohexa-2,5-di enylidene)hept-l -en-6- ide; 2-methoxy-4-[3,5-dihydroxy-7-(3-methoxy-4-oxocyclohexa-2,5-d ienylidene)hepta-l,3,5- trienyljphenolate; 5-hydroxy-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocy clohexa-2,5- dienylidene)hepta-l,3,5-triene-3-oxide; and 3-hydroxy-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,3,5-triene-5- oxide. In some specific embodiments, the plurality of anions consists of 10 anions. In some very specific preferred embodiments, the plurality of anions consists of 10 different anions; the plurality of anions consists of oxides and phenolates; and the plurality of anions lacks carbanions.

In some embodiments, the plurality of anions consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,

15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or each of 5-hydroxy-l,7-bis(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-2,4-diene-3-oxide; 5 -hydroxy- l,7-bis(3-m ethoxy-4- oxocyclohexa-2,5-dienylidene)hepta-3,5-diene-3-oxide; 3,5-dihydroxy-l,7-bis(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-2,4-dien-6-ide; 5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-2-ene-3 -oxide; 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-2-en-4-ide; 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-2-en-6-ide; 5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hept- 3-ene-

3-oxide; 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienyli dene)hept-3-en-2-ide; 3- hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylide ne)hept-3-en-6-ide; 5-hydroxy- l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-2,5-d iene-3-oxide; 3,5-dihydroxy-l,7- bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-2,5-dien- 4-ide; 3,5-dioxo-l,7-bis(3-methoxy-

4-oxocyclohexa-2,5-dienylidene)heptan-2-ide; 3,5-dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)heptan-4-ide; 2-methoxy-4-[3-hydroxy-5-oxo-7-(3-methoxy-4-oxocyclohexa-2,5 - dienylidene)hepta- 1 ,3 -dienyljphenolate; 5-oxo- 1 -(4-hydroxy-3 -methoxyphenyl)-7-(3 -methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l,3-diene-3-oxide; 3-hydroxy-5-oxo-l-(4-hydroxy-3- methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l,3-dien-6-ide; 2-methoxy- 4-[5-hydroxy-3-oxo-7-(3-methoxy-4-oxocyclohexa-2,5-dienylide ne)hepta-l,4-dienyl]phenolate; 3- oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocyclohex a-2,5-dienylidene)hepta-l,4- diene-5-oxide; 5-hydroxy-3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4 -oxocyclohexa- 2,5-dienylidene)hepta-l,4-dien-6-ide; 2-methoxy-4-[5-hydroxy-3-oxo-7-(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l,5-dienyl]phenolate; 3-oxo-l-(4-hydroxy-3-methoxyphenyl)- 7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,5-diene- 5-oxide; 5 -hydroxy-3 -oxo-1 -(4- hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-die nylidene)hepta-l,5-dien-4-ide; 2- methoxy-4-[3,5-dioxo-7-(3-methoxy-4-oxocyclohexa-2,5-dienyli dene)hept-l-enyl]phenolate; 3,5- dioxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocycloh exa-2,5-dienylidene)hept-l-en-4- ide; 3,5-dioxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocy clohexa-2,5- dienylidene)hept-l-en-6-ide; 2-methoxy-4-[3,5-dihydroxy-7-(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-l,3,5-trienyl]phenolate; 5-hydroxy-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,3,5-triene-3- oxide; and 3 -hydroxy- 1 -(4-hydroxy - 3-methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene )hepta-l,3,5-triene-5-oxide. In some specific embodiments, the plurality of anions consists of 15 anions. In some very specific preferred embodiments, the plurality of anions consists of 15 different anions; the plurality of anions consists of oxides and phenolates; and the plurality of anions lacks carbanions.

In some embodiments, the composition comprises a molecule. In some specific embodiments, the anion has a conjugate acid; and the molecule is the conjugate acid of the anion.

In some embodiments, the molecule is 3,5-dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-2, 4-diene.

In some embodiments, the molecule is 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- di eny li dene)hept-2 -ene .

In some embodiments, the molecule is 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hept-3 -ene.

In some embodiments, the molecule is 3,5-dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- di eny li dene)hepta-2, 5 -di ene .

In some embodiments, the molecule is 3,5-dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- di eny li denejheptane .

In some embodiments, the molecule is 3-hydroxy-5-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l, 3-diene.

In some embodiments, the molecule is 5-hydroxy-3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l, 4-diene.

In some embodiments, the molecule is 5-hydroxy-3-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l, 5-diene.

In some embodiments, the molecule is 3,5-dioxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy- 4-oxocyclohexa-2,5-dienylidene)hept-l-ene.

In some embodiments, the molecule is 3, 5 -dihydroxy-1 -(4-hy droxy-3 -methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-l,3,5-triene.

In some embodiments, the molecule is 2-methoxy-4-[3-hydroxy-5-oxo-7-(4-hydroxy-3- methoxyphenyl)hepta- 1 , 3 , 6-trienyl]phenol .

In some embodiments, the molecule is 2-methoxy-4-[5-hydroxy-3-oxo-7-(4-hydroxy-3- methoxyphenyl)hepta-l,4,6-trienyl]phenol.

In some embodiments, the molecule is 2-methoxy-4-[3,5-dioxo-7-(4-hydroxy-3- methoxyphenyl)hepta-l,6-dienyl]phenol.

In some embodiments, the molecule has the chemical formula C21H20O6; the molecule has the chemical structure set forth in General Structure 1; General Structure 1 contains exactly 10 double bonds; R1 is hydroxy or oxo; R2 is hydroxy or oxo; and the 4 dotted lines in General Structure 1 depict 0, 1, or 2 double bonds.

In some embodiments, the molecule has the chemical formula C21H20O6; the molecule has the chemical structure set forth in General Structure 2; General Structure 2 contains exactly 10 double bonds; R1 is hydroxy or oxo; R2 is hydroxy or oxo; R3 is hydroxy; and the 3 dotted lines in General Structure 2 depict 0, 1, or 2 double bonds.

In some embodiments, the composition comprises a plurality of molecules, which comprises a molecule.

In some embodiments, the plurality of molecules consists of 2, 3, 4, or each of 3, 5 -dihydroxy- 1,7- bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hepta-2, 4-diene; 3-hydroxy-5-oxo-l,7-bis(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hept-2-ene; 3-hydroxy-5-oxo-l,7-bis(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hept-3-ene; 3,5-dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)hepta-2, 5-diene; and 3,5-dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)heptane. In some very specific preferred embodiments, the plurality of molecules consists of 5 molecules.

In some embodiments, the plurality of molecules consists of 2, 3, 4, or each of 3-hydroxy-5-oxo- l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2, 5-dienylidene)hepta-l,3-diene; 5- hy droxy-3 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)-7 -(3 -methoxy-4-oxocy clohexa-2, 5 - dienylidene)hepta- 1 ,4-diene; 5-hydroxy-3 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(3 -m ethoxy-4- oxocyclohexa-2,5-dienylidene)hepta-l, 5-diene; 3,5-dioxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hept-l-ene; and 3,5-dihydroxy-l-(4-hydroxy-3- methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l,3,5-triene. In some very specific preferred embodiments, the plurality of molecules consists of 5 molecules.

In some embodiments, the plurality of molecules consists of 2, 3, 4, 5, 6, 7, 8, 9, or each of 3,5- dihydroxy-l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-2, 4-diene; 3-hydroxy-5-oxo- l,7-bis(3-methoxy-4-oxocyclohexa-2,5-dienylidene)hept-2-ene; 3-hydroxy-5-oxo-l,7-bis(3- methoxy-4-oxocyclohexa-2,5-dienylidene)hept-3-ene; 3, 5-dihydroxy- 1, 7-bis(3-methoxy-4- oxocyclohexa-2,5-dienylidene)hepta-2, 5-diene; 3,5-dioxo-l,7-bis(3-methoxy-4-oxocyclohexa-2,5- dienylidene)heptane; 3-hydroxy-5-oxo-l-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4 - oxocy clohexa-2, 5 -dienylidene)hepta- 1 , 3 -diene; 5 -hydroxy-3 -oxo- 1 -(4-hy droxy-3 -methoxyphenyl)- 7-(3-methoxy -4-oxocy cl ohexa-2,5-dienylidene)hepta-l, 4-diene; 5 -hydroxy-3 -oxo-1 -(4-hy droxy-3 - methoxyphenyl)-7-(3-methoxy-4-oxocyclohexa-2,5-dienylidene)h epta-l, 5-diene; 3,5-dioxo-l-(4- hy droxy-3 -methoxyphenyl)-7-(3 -methoxy-4-oxocy clohexa-2, 5 -dienylidene)hept- 1 -ene; and 3,5- dihydroxy-1 -(4-hy droxy-3-methoxyphenyl)-7-(3-methoxy -4-oxocy clohexa-2, 5-di enylidene)hepta- 1,3,5-triene. In some very specific preferred embodiments, the plurality of molecules consists of 10 molecules.

In some embodiments, the composition comprises the molecule and the anion at a molar ratio of at least 1:100,000 and no greater than 10:1. In some specific embodiments, the composition comprises the molecule and the anion at a molar ratio of at least 1 : 10,000 and no greater than 1:1. In some very specific embodiments, the composition comprises the molecule and the anion at a molar ratio of at least 1 : 100 and no greater than 1:1.

In some embodiments, the composition comprises a cation.

In some embodiments, the cation is ammonium (“NH4+”); protonated ethanolamine; choline; protonated sphingosine; protonated lysine; protonated arginine; sodium cation (“Na+”); potassium cation (“K+”); magnesium cation (“Mg++”); calcium cation (“Ca++”); zinc cation (“Zn++”); manganese cation (“Mn++”); iron(II) cation (“Fe++”); iron(III) cation (“Fe+++”); copper(I) cation (“Cu+”); or copper(II) cation (“Cu++”). In some specific embodiments, the cation is sodium cation. In some specific embodiments, the cation is potassium cation.

In some embodiments, the cation has a molar concentration; the anion has a molar concentration; the cation has a net charge; the cation has an equivalent concentration, which is equal to the molar concentration of the cation multiplied by the net charge of the cation; and the composition has a ratio of the molar concentration of the anion to the equivalent concentration of the cation that is at least 1 :2 and no greater than 10:9. In some specific embodiments, the cation has a molar concentration; the anion has a molar concentration; the cation has a net charge; the cation has an equivalent concentration, which is equal to the molar concentration of the cation multiplied by the net charge of the cation; and the composition has a ratio of the molar concentration of the anion to the equivalent concentration of the cation that is at least 9:10 and no greater than 10:9.

In some embodiments, the cation has a molar concentration; the anion has a molar concentration; the cation has a net charge; the cation has an equivalent concentration, which is equal to the molar concentration of the cation multiplied by the net charge of the cation; and the equivalent concentration of the cation is greater than the molar concentration of the anion. In some specific embodiments, the cation has a molar concentration; the anion has a molar concentration; the cation has a net charge; the cation has an equivalent concentration, which is equal to the molar concentration of the cation multiplied by the net charge of the cation; and the equivalent concentration of the cation is at least 2 percent greater than the molar concentration of the anion.

In some embodiments, the composition comprises the cation at a concentration of at least 10 nanomolar and no greater than 1 molar. In some specific embodiments, the composition comprises the cation at a concentration of at least 10 micromolar and no greater than 100 millimolar.

In some embodiments, the composition comprises a salt that consists of the cation and the anion.

In some embodiments, the composition comprises a protic polar solvent and a Bronsted base; wherein the protic polar solvent has an acid dissociation constant of no greater than 100 femtomolar for conversion of the protic polar solvent into the Bronsted base; and the anion, the cation, and the Bronsted base are solutes that are dissolved in the protic polar solvent.

“Bronsted base” refers to a proton acceptor.

“Dissolved” refers to a solute that is solvated in a liquid phase; a chemical species that is present within a phase that is dispersed within a liquid phase, such as the dispersed phase of an emulsion, is not dissolved in the liquid phase; a chemical species that is non-covalently bound to any chemical species that is a solid in the absence of a solvent, such as a cyclodextrin, is not dissolved in a liquid phase.

In some embodiments, the composition comprises a protic polar solvent and a Bronsted base; wherein the protic polar solvent has an acid dissociation constant of no greater than 100 femtomolar for conversion of the protic polar solvent into the Bronsted base; and the anion and the Bronsted base are solutes that are dissolved in the protic polar solvent. In some embodiments, the composition comprises the protic polar solvent at a concentration of at least 5 molar and no greater than 55.5 molar. In some specific embodiments, the composition comprises the protic polar solvent at a concentration of at least 10 molar and no greater than 14 molar.

In some embodiments, the protic polar solvent is 1-butanol, 2-butanol, 1,3-butanediol, ethanol, isoamyl alcohol, isobutanol, 1-pentanol, 1-propanol, 2-propanol, propane- 1,2-diol, propane-1, 3- diol, or propane- 1,2, 3 -triol.

In some embodiments, the protic polar solvent is water; the composition comprises the water at a concentration of at least 25 molar and no greater than 55.5 molar; and the Bronsted base is hydroxide.

In some embodiments, the protic polar solvent is ethanol; the composition comprises the ethanol at a concentration of at least 5 molar and no greater than 17.2 molar; and the Bronsted base is ethoxide.

In some embodiments, the protic polar solvent is propane-1, 2-diol; the composition comprises the propane- 1,2-diol at a concentration of at least 5 molar and no greater than 13.7 molar; and the Bronsted base is l-hydroxypropane-2-oxide or 2-hydroxypropane-l -oxide.

In some embodiments, the protic polar solvent is propane-1, 2, 3-triol; the composition comprises the propane- 1,2, 3 -triol at a concentration of at least 5 molar and no greater than 13.7 molar; and the Bronsted base is l,3-dihydroxypropane-2-oxide or 2,3 -dihydroxypropane-1 -oxide.

In some embodiments, the composition comprises the Bronsted base and the protic polar solvent at a molar ratio of at least 1 : 1,000,000,000 and no greater than 1:10. In some specific embodiments, the composition comprises the Bronsted base and the protic polar solvent at a molar ratio of at least 1 : 100,000,000 and no greater than 1 : 1,000. In some very specific embodiments, the composition comprises the Bronsted base and the protic polar solvent at a molar ratio of at least 1 : 10,000,000 and no greater than 1 : 10,000.

In some embodiments, the composition comprises water and hydroxide.

In some embodiments, the composition comprises ethanol and ethoxide.

In some embodiments, the composition comprises propane- 1,2-diol and one or both of 1- hydroxypropane-2-oxide and 2-hydroxypropane-l -oxide.

In some embodiments, the composition comprises propane-1, 2, 3-triol and one or both of 1,3- dihydroxypropane-2-oxide and 2,3-dihydroxypropane-l-oxide.

In some embodiments, the composition comprises the anion at a concentration of at least 1 micromolar and no greater than 1 molar. In some specific embodiments, the composition comprises the anion at a concentration of at least 100 micromolar and no greater than 1 molar. In some very specific embodiments, the composition comprises the anion at a concentration of at least 100 micromolar and no greater than 100 millimolar.

In some embodiments, the composition comprises the anion at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter. In some specific embodiments, the composition comprises the anion at a concentration of at least 100 milligrams per liter and no greater than 100 grams per liter. In some very specific embodiments, the composition comprises the anion at a concentration of at least 500 milligrams per liter and no greater than 50 grams per liter.

In some embodiments, the composition is a beverage that is suitable for human consumption.

Various aspects of this disclosure relate to a composition described anywhere in the disclosure, for use as a medicament.

Various aspects of this disclosure relate to a composition described anywhere in the disclosure, for use to treat a health condition.

“Treat” refers to at least one of: to cure a health condition; to increase the probability that a health condition will be cured; to shorten the time over which a health condition is cured; to increase the probability that the time necessary to cure a health condition will be shortened; to decrease the severity of a health condition; to increase the probability that the severity of a health condition will decrease; to shorten the time over which the severity of a health condition is decreased; to increase the probability that the time necessary to decrease the severity of a health condition will be shortened; to inhibit a health condition from worsening; to increase the probability that a health condition will not worsen; to delay the worsening of a health condition; to increase the probability that the worsening of a health condition will be delayed; to inhibit the occurrence or recurrence of a health condition; to decrease the probability that a health condition will occur or reoccur; to delay the onset of a health condition; to increase the probability that the onset of a health condition will be delayed; to alleviate at least one symptom of a health condition; to increase the probability that at least one symptom of a health condition will be alleviated; to shorten the time over which at least one symptom of a health condition is alleviated; to increase the probability that the time necessary to alleviate at least one symptom of a health condition will be shortened; to decrease the severity of at least one symptom of a health condition; to increase the probability that the severity of at least one symptom of a health condition will be decreased; to shorten the time over which the severity of at least one symptom of a health condition is decreased; to increase the probability that the time necessary to decrease the severity of at least one symptom of a health condition will be shortened; to inhibit at least one symptom of a health condition from worsening; to increase the probability that at least one symptom of a health condition will not worsen; to delay the worsening of at least one symptom of a health condition; to increase the probability that the worsening of at least one symptom of a health condition will be delayed; to inhibit at least one symptom of a health condition from occurring or reoccurring; to decrease the probability that at least one symptom of a health condition will occur or reoccur; to delay the onset of at least one symptom of a health condition; and to increase the probability that the onset of at least one symptom of a health condition will be delayed.

Various aspects of this disclosure relate to a composition described anywhere in the disclosure, for use in manufacturing a medicament.

Various aspects of this disclosure relate to a method to change the color of a liquid, comprising providing a composition described anywhere in the disclosure, wherein the composition has an initial color; and contacting the composition with a Bronsted acid to change the initial color to a final color.

“Bronsted acid” refers to a proton donor.

Various aspects of this disclosure relate to a method to market a consumer product, comprising providing a composition described anywhere in the disclosure, wherein the composition has an initial color; and contacting the composition with a Bronsted acid to change the initial color to a final color.

In some embodiments, the method comprises recording a first image of the composition prior to contacting the composition with the Bronsted acid; and recording a second image of the composition after contacting the composition with the Bronsted acid.

In some embodiments, the method comprises recording video of the composition while the composition is contacted with the Bronsted acid.

In some embodiments, the initial color is maroon or a shade of red. In some embodiments, the final color is gold or a shade of yellow. The constitutional isomers of curcumin absorb violet light with a k ax of approximately 425 nanometers and transmit wavelengths that produce a golden color. The anions of the constitutional isomers of curcumin red-shift the absorption spectrum relative to molecular forms and transmit wavelengths that produce a maroon color.

In some embodiments, the Bronsted acid is hydronium, citric acid, or carbonic acid.

In some embodiments, the method comprises consuming a portion of the composition after contacting the composition with the Bronsted acid, wherein a human consumes the portion of the composition by drinking it or otherwise orally administering it.

Various aspects of this disclosure relate to a method to administer a composition described anywhere in the disclosure, comprising orally administering the composition to a subject. In some embodiments, the subject is a human.

Various aspects of this disclosure relate to a method to treat a health condition, comprising providing a composition described anywhere in the disclosure; and consuming a therapeutically effective amount of the composition, wherein a human subject consumes the therapeutically effective amount of the composition by either swallowing or otherwise orally administering it.

In some embodiments, the composition is formulated to allow the conversion of the anion into one or more structural isomers of curcumin before the anion reaches the stomach of the human subject; and the composition is formulated to allow absorption of the one or more structural isomers of curcumin by the epithelial lining of the gastrointestinal tract between the lips and the stomach, excluding the stomach and the outer surfaces of the lips, and including the esophagus and the inner surfaces of the lips.

“One or more structural isomers of curcumin” consists of one or more molecules disclosed in this patent document that have the chemical formula C21H20O6.

In some embodiments, the administering produces a Tmax, which is the time it takes to achieve a maximum blood concentration of the one or more structural isomers of curcumin following the administering; and the Tmax is no greater than 60 minutes. In some specific embodiments, the Tmax is no greater than 30 minutes. In some very specific embodiments, the Tmax is no greater than 10 minutes.

In some embodiments, the composition that is administered comprises a combined amount of the anion and one or more structural isomers of curcumin; the composition has an oral bioavailability, which is the total amount of the one or more structural isomers of curcumin that enter the blood of the human subject following the administering divided by the combined amount; and the oral bioavailability is at least 5 percent. In some specific embodiments, the oral bioavailability is at least 10 percent. In some very specific embodiments, the oral bioavailability is at least 25 percent. In some embodiments, the health condition is cancer. In some specific embodiments, the health condition is a carcinoma, a sarcoma, a lymphoma, a leukemia, a germ cell tumor, or a blastoma. In some very specific embodiments, the health condition is brain cancer; ovarian cancer; breast cancer; vaginal cancer; vulvar cancer; uterine cancer; cervical cancer; endometrial cancer; prostate cancer; testicular cancer; penile cancer; liver cancer; intrahepatic bile duct cancer; lung cancer; small cell lung cancer; non-small cell lung cancer; bronchial cancer; mesothelioma; pancreatic cancer; gall bladder cancer; non-melanoma skin cancer; melanoma; Kaposi sarcoma; thyroid cancer; head and neck cancer; nasopharyngeal cancer; oropharyngeal cancer; hypopharyngeal cancer; laryngeal cancer; oral cavity cancer; tongue cancer; mouth cancer; salivary gland cancer; esophageal cancer; gastric cancer; colorectal cancer; colon cancer; rectal cancer; anal cancer; kidney cancer; renal cell cancer; renal pelvis cancer; bladder cancer; urethral cancer; Hodgkin lymphoma; non-Hodgkin’s lymphoma; myeloma; multiple myeloma; acute lymphocytic leukemia; chronic lymphocytic leukemia; acute myeloid leukemia; chronic myeloid leukemia; osteosarcoma; or a soft tissue cancer.

In some embodiments, the health condition is a viral infection or a bacterial infection. In some specific embodiments, the health condition is a viral infection caused by an enveloped virus; an influenza virus infection; a coronavirus infection; a pneumococcal infection; a human immunodeficiency virus infection; a hepatitis delta virus infection; a Zika virus infection; an Ebola virus infection; a bacterial infection; a Clostridium difficile infection; a Staphylococcus aureus infection; a Mycobacterium tuberculosis infection; an Enterococcus faecalis infection; or a Salmonella infection.

In some embodiments, the health condition is an autoimmune disease. In some specific embodiments, the health condition is arthritis; inflammatory bowel disease; psoriasis; lupus; or multiple sclerosis.

In some embodiments, the health condition is a neurodegenerative disease. In some specific embodiments, the health condition has a progression that correlates with increasing amyloid. In some very specific embodiments, the health condition is Alzheimer’s Disease; Parkinson’s Disease; transmissible spongiform encephalopathy; tauopathy; Huntington’s Disease; or amyloidosis.

In some embodiments, the health condition is type II diabetes.

In some embodiments, the health condition is myocardial infarction.

In some embodiments, the health condition is ischemic stroke.

In some embodiments, the health condition is cell disease.

In some embodiments, the health condition is hyperlipidemia.

In some embodiments, the health condition is hypercholesterolemia.

All combinations of features set forth in the preceding detailed description are combinable provided that each specific combination is grammatically and scientifically consistent. Selected combinations of features are set forth in the following claims.