NUTRACEUTICAL CO-CRYSTAL COMPOSITIONS

• US 20100204204A1
• Filed: 06/06/2008
• Published: 08/12/2010
• Est. Priority Date: 06/06/2007
• Status: Abandoned Application

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Pujari, Twarita, Shytle, Roland Douglas, Clarke, Heather, Marshall, Lissette, Kapildev, Arora, Ong, Tien Teng, Kavuru, Padmini, Zaworotko, Michael
• Application Number:
  US12/663,212
• Publication Number:
  US 20100204204A1
• Time in Patent Office: Days
• US Class Current: 514/212.30
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: C07D 401/14 containing three or more hetero rings

Abstract

Co-crystals comprising at least one nutraceutical compound and at least one co-crystal former with or without impurities. These co-crystals may be included in compositions (optionally also including other components such as pharmaceutically acceptable excipients, other nutritional supplements, etc.) having utility as pharmaceuticals, nutraceuticals, nutritional supplements, and foodstuffs.

Claims

1. A composition comprising a co-crystal of a nutraceutical and a co-crystal former, the co-crystal with or without impurities wherein

(i) the nutraceutical and the co-crystal former are hydrogen bonded to each other,

(ii) the nutraceutical is selected from the group consisting of vitamin B2 (riboflavin), glucosamine HCl, chlorogenic acid, lipoic acid, catechin hydrate, creatine, acetyl-L-carnitine HCl, vitamin B6, pyridoxine, caffeic acid, naringenin, vitamin B1 (thiamine HCl), baicalein, luteolin, hesperedin, rosmarinic acid, epicatechin gallate, epigallocatechin, vitamin B9 (folic), genistein, methylvanillin, ethylvanillin, silibinin, diadzein, melatonin, rutin hydrate, vitamin A, retinol, vitamin D2 (ergocalciferol), vitamin E (tocopherol), diosmin, menadione (K3), vitamin D3 (caholecalciferol), phloretin, indole-3-carbinol, fisetin, glycitein, chrysin, gallocatechin, vitamin B4 (adenine), vitamin B5 (pantothenic acid), vitamin B7 (biotin), theobromine, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid, and

(iii) a co-crystal former selected from the group consisting of pharmaceutically acceptable carbohydrates, amines, amides, sulfonamides, carboxylic acids, sulfonic acids, phenols, polyphenols, aromatic heterocycles, xanthines and alcohols.

2. The composition of claim 1 wherein the nutraceutical is selected from the group consisting of resveratrol, EGCG, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

3. The composition of claim 2 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

4. The composition of claim 1 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

5. The composition of claim 1 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

6. The composition of claim 2 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

7. The composition of claim 5 wherein the nutraceutical is selected from the group consisting of EGCG, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

8. A co-crystal composition comprising EGCG and a co-crystal former wherein EGCG and the co-crystal former are hydrogen bonded to each other, the co-crystal being with or without impurities.

9. The co-crystal composition of claim 8 wherein the co-crystal former is selected from the group consisting of pharmaceutically acceptable carbohydrates, amines, amides, sulfonamides, carboxylic acids, sulfonic acids, phenols, polyphenols, aromatic heterocycles, xanthines and alcohols.

10. The composition of claim 8 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

11. The composition of claim 8 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

12. A co-crystal comprising at least one nutraceutical compound and L-ascorbic acid wherein the nutraceutical compound and L-ascorbic acid are hydrogen bonded.

13. The co-crystal of claim 12 wherein the nutraceutical is selected from the group consisting of vitamin B2 (riboflavin), glucosamine HCl, chlorogenic acid, lipoic acid, catechin hydrate, creatine, acetyl-L-carnitine HCl, vitamin B6, pyridoxine, caffeic acid, naringenin, vitamin B1 (thiamine HCl), baicalein, luteolin, hesperedin, rosmarinic acid, epicatechin gallate, epigallocatechin, vitamin B9 (folic), genistein, methylvanillin, ethylvanillin, silibinin, diadzein, melatonin, rutin hydrate, vitamin A, retinol, vitamin D2 (ergocalciferol), vitamin E (tocopherol), diosmin, menadione (K3), vitamin D3 (caholecalciferol), phloretin, indole-3-carbinol, fisetin, glycitein, chrysin, gallocatechin, vitamin B4 (adenine), vitamin B5 (pantothenic acid), vitamin B7 (biotin), theobromine, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

14. The composition of claim 12 wherein the nutraceutical is selected from the group consisting of resveratrol, EGCG, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

15. The composition of claim 12 wherein the nutraceutical is selected from the group consisting of EGCG, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

56. The co-crystal of claim 12 wherein the nutraceutical compound is a zwitterion and/or has at least one carboxylate group.

57. The co-crystal of claim 12 wherein the nutraceutical compound is a vitamin, amino acid or derivative thereof, alkaloid, peptide, flavonoid, steroidal, terpenoid, pharmaceutical, hormone or prohormone.

58. The cocrystal of claim 12 wherein the nutraceutical is nicotinic acid or sarcosine.

59. The cocrystal of claim 12 wherein the molar ratio of the nutraceutical to L-ascorbic acid is about 1:

1.

60. The cocrystal of claim 58 wherein the molar ratio of the nutraceutical to L-ascorbic acid is about 1:

1.

16. A co-crystal comprising:

a nutraceutical and a co-crystal former, wherein the nutraceutical is a flavonoid and the co-crystal former is a xanthine.

17. The co-crystal of claim 16 wherein the flavonoid is epigallocatechin-3-gallate, quercetin, or hesperitin.

18. A co-crystal, comprising:

a nutraceutical and a co-crystal former, wherein the nutraceutical is epigallocatechin-3-gallate, quercetin, or hesperitin, and the co-crystal former is caffeine, theobromine, or theophylline

19. A process for the preparation of a nutraceutical co-crystal, the process comprising combining at least one nutraceutical and at least one co-crystal former and inducing the nutraceutical(s) and the co-crystal former(s) to hydrogen bond with each other wherein:

(i) the nutraceutical is selected from the group consisting of vitamin B2 (riboflavin), glucosamine HCl, chlorogenic acid, lipoic acid, catechin hydrate, creatine, acetyl-L-carnitine HCl, vitamin B6, pyridoxine, caffeic acid, naringenin, vitamin B1 (thiamine HCl), baicalein, luteolin, hesperedin, rosmarinic acid, epicatechin gallate, epigallocatechin, vitamin B9 (folic), genistein, methylvanillin, ethylvanillin, silibinin, diadzein, melatonin, rutin hydrate, vitamin A, retinol, vitamin D2 (ergocalciferol), vitamin E (tocopherol), diosmin, menadione (K3), vitamin D3

(caholecalciferol), phloretin, indole-3-carbinol, fisetin, glycitein, chrysin, gallocatechin, vitamin B4 (adenine), vitamin B5 (pantothenic acid), vitamin B7

(biotin), theobromine, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid, and

(ii) a co-crystal former selected from the group consisting of pharmaceutically acceptable carbohydrates, amines, amides, sulfonamides, carboxylic acids, sulfonic acids, phenols, polyphenols, aromatic heterocycles, xanthines and alcohols.

20. The process of claim 19 wherein the nutraceutical is selected from the group consisting of resveratrol, EGCG, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

21. The process of claim 20 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

22. The process of claim 19 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

23. The process of claim 19 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

24. The process of claim 20 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

25. The process of claim 23 wherein the nutraceutical is selected from the group consisting of EGCG, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

26. A process for the preparation of a nutraceutical co-crystal, the process comprising combining at least one nutraceutical and at least one co-crystal former and inducing the nutraceutical(s) and the co-crystal former(s) to hydrogen bond with each other wherein the nutraceutical comprises EGCG.

27. The process of claim 26 wherein the co-crystal former selected from the group consisting of pharmaceutically acceptable carbohydrates, amines, amides, sulfonamides, carboxylic acids, sulfonic acids, phenols, polyphenols, aromatic heterocycles, xanthines and alcohols.

28. The process of claim 26 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

29. The process of claim 26 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

30. A process for the preparation of a nutraceutical co-crystal, the process comprising combining at least one nutraceutical compound and L-ascorbic acid and inducing the nutraceutical compound(s) and L-ascorbic acid to hydrogen bond with each other.

31. The process of claim 30 wherein the nutraceutical is selected from the group consisting of vitamin B2 (riboflavin), glucosamine HCl, chlorogenic acid, lipoic acid, catechin hydrate, creatine, acetyl-L-carnitine HCl, vitamin B6, pyridoxine, caffeic acid, naringenin, vitamin B1 (thiamine HCl), baicalein, luteolin, hesperedin, rosmarinic acid, epicatechin gallate, epigallocatechin, vitamin B9 (folic), genistein, methylvanillin, ethylvanillin, silibinin, diadzein, melatonin, rutin hydrate, vitamin A, retinol, vitamin D2 (ergocalciferol), vitamin E (tocopherol), diosmin, menadione (K3), vitamin D3 (caholecalciferol), phloretin, indole-3-carbinol, fisetin, glycitein, chrysin, gallocatechin, vitamin B4 (adenine), vitamin B5 (pantothenic acid), vitamin B7 (biotin), theobromine, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

32. The process of claim 30 wherein the nutraceutical is selected from the group consisting of resveratrol, EGCG, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

33. The process of claim 30 wherein the nutraceutical is selected from the group consisting of EGCG, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

34. A process for the preparation of a nutraceutical co-crystal comprising a flavonoid and a xanthine, the process comprising combining the flavonoid and the xanthine and inducing the flavonoid and the xanthine to hydrogen bond with each other.

35. The process of claim 34 wherein the flavonoid is epigallocatechin-3-gallate, quercetin, or hesperitin.

36. The process of claim 34 wherein the flavonoid is epigallocatechin-3-gallate, quercetin, or hesperitin, and the xanthine is caffeine, theobromine, or theophylline

37. A process for improving animal health or nutrition, the process comprising administering to the animal a composition comprising a nutraceutical co-crystal wherein

(i) the nutraceutical co-crystal comprises a nutraceutical and a co-crystal former hydrogen bonded to each other, the nutraceutical co-crystal with or without impurities

(ii) the nutraceutical is selected from the group consisting of vitamin B2 (riboflavin), glucosamine HCl, chlorogenic acid, lipoic acid, catechin hydrate, creatine, acetyl-L-carnitine HCl, vitamin B6, pyridoxine, caffeic acid, naringenin, vitamin B1 (thiamine HCl), baicalein, luteolin, hesperedin, rosmarinic acid, epicatechin gallate, epigallocatechin, vitamin B9 (folic), genistein, methylvanillin, ethylvanillin, silibinin, diadzein, melatonin, rutin hydrate, vitamin A, retinol, vitamin D2 (ergocalciferol), vitamin E (tocopherol), diosmin, menadione (K3), vitamin D3 (caholecalciferol), phloretin, indole-3-carbinol, fisetin, glycitein, chrysin, gallocatechin, vitamin B4 (adenine), vitamin B5 (pantothenic acid), vitamin B7 (biotin), theobromine, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid, and

(iii) the co-crystal former selected from the group consisting of pharmaceutically acceptable carbohydrates, amines, amides, sulfonamides, carboxylic acids, sulfonic acids, phenols, polyphenols, aromatic heterocycles, xanthines and alcohols.form of epigallocatechin-3-gallate to a person or animal having or predisposed to having a condition resulting from oxidative stress.

38. The process of claim 37 wherein the nutraceutical is selected from the group consisting of resveratrol, EGCG, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

39. The process of claim 37 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

40. The process of claim 37 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

41. The process of claim 37 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

42. The process of claim 38 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

43. The process of claim 41 wherein the nutraceutical is selected from the group consisting of EGCG, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

44. A process for improving animal health or nutrition, the process comprising administering to the animal a composition comprising a nutraceutical co-crystal comprising EGCG and a co-crystal former.

45. The process of claim 44 wherein the co-crystal former selected from the group consisting of pharmaceutically acceptable carbohydrates, amines, amides, sulfonamides, carboxylic acids, sulfonic acids, phenols, polyphenols, aromatic heterocycles, xanthines and alcohols.

46. The process of claim 44 wherein the co-crystal former is selected from the group consisting of 1,5-napthalene-disulfonic acid, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, 4-aminopyridine, 4-chlorobenzene-sulfonic acid, 4-ethoxyphenyl urea, 7-oxo-DHEA, acesulfame, acetohydroxamic acid, adenine, adipic acid, alanine, allopurinaol, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, caffeine, camphoric acid, capric acid, chrysin, cinnamic acid, citric acid, clemizole, cyclamic acid, cysteine, dimethylglycine, D-ribose, fumaric acid, galactaric acid, genistein, gentisic acid, glucamine N-methyl, gluconic acid, glucosamine, glucuronic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hippuric acid, histidine, hydroquinone, imidazole, ipriflavone, isoleucine, lactobionic acid, lauric acid, leucine, lysine, maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinamide, nicotinic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, piperazine, procaine, proline, p-toluenesulfonic acid, pyridoxamine, pyridoxine (4-pyridoxic acid), pyroglutamic acid, quercetin, resveratrol, saccharin, salicylic acid, salicylic acid 4-amino, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, threonine, TRIS, tryptophan, tyrosine, urea, valine, Vitamin K5, xylitol, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

47. The process of claim 44 wherein the co-crystal former is selected from the group consisting of L-ascorbic acid (vitamin C), salicylic acid, citric acid, gallic acid, maleic acid, malic acid, tartaric acid, nicotinamide, iso-nicotinamide, nicotinic acid, iso-nicotinic acid, caffeine, paraxanthine, theobromine, theophylline, caprolactam, lactose, glucose and sucrose.

48. A process for improving animal health or nutrition, the process comprising administering to the animal a composition comprising a nutraceutical co-crystal comprising at least one nutraceutical compound and L-ascorbic acid.

49. The process of claim 48 wherein the nutraceutical is selected from the group consisting of vitamin B2 (riboflavin), glucosamine HCl, chlorogenic acid, lipoic acid, catechin hydrate, creatine, acetyl-L-carnitine HCl, vitamin B6, pyridoxine, caffeic acid, naringenin, vitamin B1 (thiamine HCl), baicalein, luteolin, hesperedin, rosmarinic acid, epicatechin gallate, epigallocatechin, vitamin B9 (folic), genistein, methylvanillin, ethylvanillin, silibinin, diadzein, melatonin, rutin hydrate, vitamin A, retinol, vitamin D2 (ergocalciferol), vitamin E (tocopherol), diosmin, menadione (K3), vitamin D3 (caholecalciferol), phloretin, indole-3-carbinol, fisetin, glycitein, chrysin, gallocatechin, vitamin B4 (adenine), vitamin B5 (pantothenic acid), vitamin B7 (biotin), theobromine, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

50. The process of claim 48 wherein the nutraceutical is selected from the group consisting of resveratrol, EGCG, quercetin, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

51. The process of claim 48 wherein the nutraceutical is selected from the group consisting of EGCG, ferulic acid, ellagic acid, hesperitin, and protocatechuic acid.

52. A process for improving animal health or nutrition, the process comprising administering to the animal a composition comprising a nutraceutical co-crystal comprising a flavonoid and a xanthine.

53. The process of claim 52 wherein the flavonoid is epigallocatechin-3-gallate, quercetin, or hesperitin.

54. The process of claim 52 wherein the flavonoid is epigallocatechin-3-gallate, quercetin, or hesperitin, and the xanthine is caffeine, theobromine, or theophylline.

55. (canceled)

61. A pharmaceutical composition comprising a co-crystal comprising at least one nutraceutical compound and L-ascorbic acid wherein the nutraceutical compound and L-ascorbic acid are hydrogen bonded.

62. The pharmaceutical composition of claim 61 wherein the nutraceutical compound is a zwitterion and/or has at least one carboxylate group.

63. The pharmaceutical composition of claim 62 wherein the nutraceutical compound is a vitamin, amino acid or derivative thereof, alkaloid, peptide, flavonoid, steroidal, terpenoid, pharmaceutical, hormone or prohormone.

64. The pharmaceutical composition of claim 61 wherein the nutraceutical is nicotinic acid or sarcosine.

65. The pharmaceutical composition of claim 61 wherein the molar ratio of the nutraceutical to L-ascorbic acid is about 1:

1.

66. (canceled)

67. A method of making a co-crystal, the method comprising:

combining a nutraceutical compound and a first solvent to form a nutraceutical admixture;

combining L-ascorbic acid and a second solvent to form an L-ascorbic acid admixture;

combining the nutraceutical admixture and the L-ascorbic acid admixture under crystallization conditions to form a co-crystal in a solid phase, the co-crystal comprising the nutraceutical and L-ascorbic acid wherein the nutraceutical compound and L-ascorbic acid are hydrogen bonded; and

optionally isolating the co-crystal.

68. The method of claim 67 wherein the first and second solvents are independently selected from water, alcohols, and mixtures thereof.

69-81. -81. (canceled)