Nutraceutical co-crystal compositions
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.
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-am inopyridine, 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-am inopyridine, 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 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-am inopyridine, 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.
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.