COMPOSITIONS COMPRISING 2-[(1R,6R)-6-ISOPROPENYL-3-METHYLCYCLOHEX-2-EN-1-YL]-3-HYDROXY-5-PENTYLPHENOLATE

Abstract

Various aspects of the disclosure relate to 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and compositions comprising 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

Claims

1-21. (canceled)

22. A composition, comprising one or both of sodium ion (“Na+”) and potassium ion (“K+”); one or more of caffeine, thiamine, niacin, nicotinamide, riboflavin, pantothenate, sucrose, fructose, glucose, acesulfame, saccharin, stevioside, rebaudioside A, sucralose, tagatose, erythritol, maltitol, xylitol, mannitol, isomalt, and a mogroside; 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate; and 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol, wherein the composition comprises the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2- en-1-yl]-5-pentylbenzene-1,3-diol at a molar ratio of at least 1:10 and no greater than 10,000:1.

23. The composition of claim 22, comprising the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol at a molar ratio of at least 1:1 and no greater than 100:1.

24. The composition of claim 22, comprising xylitol.

25. The composition of claim 22, comprising ethanol.

26. The composition of claim 22, water.

27. The composition of claim 22, comprising water at a concentration by weight of at least 50 percent and no greater than 99.99 percent.

28. A composition, comprising potassium ion (“K+”); xylitol; 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate; and 2-[(1R, 6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol.

29. The composition of claim 28, comprising the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol at a molar ratio of at least 1:10 and no greater than 10,000:1.

30. The composition of claim 28, comprising the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol at a molar ratio of at least 1:1 and no greater than 100:1.

31. The composition of claim 28, comprising a solid phase, wherein the solid phase comprises a salt, and the salt comprises the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the potassium ion.

32. The composition of claim 28, comprising ethanol.

33. The composition of claim 28, comprising water.

34. The composition of claim 28, comprising water at a concentration by weight of at least 50 percent and no greater than 99.99 percent.

35. A composition, comprising sodium ion (“Na+”); xylitol; 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate; and 2-[(1R, 6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol.

36. The composition of claim 35, comprising the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol at a molar ratio of at least 1:10 and no greater than 10,000:1.

37. The composition of claim 35, comprising the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol at a molar ratio of at least 1:1 and no greater than 100:1.

38. The composition of claim 35, comprising a solid phase, wherein the solid phase comprises a salt, and the salt comprises the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and the sodium ion.

39. The composition of claim 35, comprising ethanol.

40. The composition of claim 35, comprising water.

41. The composition of claim 35, comprising water at a concentration by weight of at least 50 percent and no greater than 99.99 percent.

Description

DETAILED DESCRIPTION

[0013] Various aspects of the disclosure relate to 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and compositions comprising 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

##STR00001##

[0014] 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

[0015] In some embodiments, a composition comprises a salt of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate. The salt can be, for example, a sodium, potassium, calcium, zinc, magnesium, manganese, iron(II), iron(III), copper, choline, citicoline, thiamine, lysine, or arginine salt.

[0016] In some embodiments, a composition comprises 1R,6R CBD.

[0017] In some embodiments, a composition comprises water, ethanol, or both water and ethanol.

[0018] In some embodiments, a composition comprises sodium ion at a concentration of at least 10 parts per billion (“ppb”) by weight. A composition can optionally comprise sodium ion at a concentration of 10 ppb to 10% by weight.

[0019] In some embodiments, a composition comprises potassium ion at a concentration of at least 10 ppb by weight. A composition can optionally comprise potassium ion at a concentration of 10 ppb to 10% by weight.

Exemplification

[0020] The examples disclose specific embodiments that do not limit this disclosure or any patent claim that matures from this disclosure.

Example 1. Determining pH stability of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate in Water

[0021] 1 gram of 1R,6R CBD was dissolved in 6.6 milliliters of 0.5 molar potassium hydroxide (0.5 M KOH) in ethanol to produce 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate. The solution was then diluted with 100 millimolar sodium carbonate (100 mM Na.sub.2CO.sub.3) in water to a final volume of 50 milliliters and a 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5- pentylphenolate concentration of approximately 20 grams per liter. 0.5 milliliters of the 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate solution was added to each of 25 test tubes containing 9.5 milliliters of 0.1 molar carbonate/bicarbonate (CO.sub.3.sup.2−/HCO.sub.3.sup.−) buffer according to Table 1. Each test tube contained approximately 10 milligrams of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate at a concentration of approximately 1 gram per liter, approximately 0.66% ethanol by weight, trace potassium ion, and variable sodium ion, carbonate ion, and bicarbonate ion. pH's were confirmed by multiple different measurements.

TABLE-US-00001 TABLE 1 Aqueous compositions comprising 2-[(1R,6R)- 6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3- hydroxy-5-pentylphenolate at variable pH 0.1M 0.1M Sample pH Na.sub.2CO.sub.3* NaHCO.sub.3 1 9.1 0.06 mL 8.94 mL 2 9.2 0.20 mL 8.80 mL 3 9.3 0.36 mL 8.64 mL 4 9.4 0.56 mL 8.44 mL 5 9.5 0.80 mL 8.20 mL 6 9.6 1.08 mL 7.92 mL 7 9.7 1.41 mL 7.59 mL 8 9.8 1.78 mL 7.22 mL 9 9.9 2.21 mL 6.79 mL 10 10.0 2.67 mL 6.33 mL 11 10.3 4.25 mL 4.75 mL 12 10.3 4.25 mL 4.75 mL 13 10.3 4.25 mL 4.75 mL 14 10.4 4.79 mL 4.21 mL 15 10.4 4.79 mL 4.21 mL 16 10.4 4.79 mL 4.21 mL 17 10.5 5.32 mL 3.68 mL 18 10.5 5.32 mL 3.68 mL 19 10.5 5.32 mL 3.68 mL 20 11.0 7.42 mL 1.58 mL 21 11.0 7.42 mL 1.58 mL 22 11.0 7.42 mL 1.58 mL 23 11.5 8.44 mL 0.56 mL 24 11.5 8.44 mL 0.56 mL 25 11.5 8.44 mL 0.56 mL

[0022] The amount of Na.sub.2CO.sub.3 in Table 1 does not include the ˜0.5 mL of 0.1 M Na.sub.2CO.sub.3 that was added with the 0.5 mL of 20 gram-per-liter solution of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

[0023] It was expected that 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate would form 1R,6R CBD at pH's below a threshold pH as evidenced by an expected color change from purple (indicative of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate) to yellow-brown (indicative of 1R,6R CBD). No color change occurred at pH's of 9.1 and above. This finding suggested that either the pK.sub.a of 1R,6R CBD is less than 9.1, at least in dilute aqueous solutions, or that it may be possible to kinetically trap 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate in an aqueous solution at a pH below the pK.sub.a of 1R,6R CBD.

[0024] Example 2. Determining the approximate pK.sub.a of IR, 6R CBD 0.5 milliliters of the 20 gram-per-liter solution of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate described in Example 1 was diluted with 9.5 milliliters of distilled water comprising varying concentrations of sodium bicarbonate, and color was monitored as shown in Table 2. pH's were confirmed by multiple different measurements.

TABLE-US-00002 TABLE 2 Samples used to determine an approximate pK.sub.a for 1R,6R CBD NaHCO.sub.3 concentration Sample pH in millimolar color 26 8.0 1000 faint purple 27 8.3 500 light purple 28 8.6 250 purple 29 8.9 125 purple 30 9.2 62 purple
A color change was visually apparent at a pH of 8.0, and a subtle color change was visually apparent at pH of 8.3. These findings suggest that the pK.sub.a of 1R,6R CBD was between 8.0 and 8.5 under the test conditions. This result is surprising given that previously reported pK.sub.a's for 1R,6R CBD range from 9.13 to 9.64 and because the chemically-related molecule resorcinol has a pK.sub.a of 9.15. Further, even though sample 26, which had a pH of 8.0, displayed a color change indicative of conversion from 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate to 1R,6R CBD, no lipid phase formed, which suggests that the interconversion between 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and 1R,6R CBD in aqueous solution can kinetically trap 1R,6R CBD in the aqueous phase and inhibit the production of a lipid phase. These findings suggest that 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate, the conjugate base of 1R,6R CBD, is suitable for use in beverages for human consumption.

Example 3. Confirming Commercial Viability of Beverages Comprising 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

[0025] 20 milliliters of water was removed from a 1 liter bottle of ESSENTIA® OVERACHIEVING H.sub.2O®. ESSENTIA® OVERACHIEVING H.sub.2O® contains purified water, sodium bicarbonate, dipotassium phosphate, magnesium sulfate, and calcium chloride, and its pH was determined to be about 9.5. The 20 milliliters of removed water was replaced with 20 milliliters of the 20 gram-per-liter solution of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate, which is described in Example 1, and the bottle was hermetically sealed using the screw cap top of the bottle to produce a hermetically-sealed container comprising approximately 400 milligrams of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate. The pH of the liquid was measured and determined to be about 10. The liquid was purple and transparent. 5 milliliters of water was removed from a 500 milliliter bottle of DASANI® purified water.

[0026] DANSANI® purified water contains purified water, magnesium sulfate, potassium chloride, and sodium chloride, and its pH was determined to be about 7.0. The 5 milliliters of removed water was replaced with 5 milliliters of the 20 gram-per-liter solution of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate, which is described in Example 1, and the bottle was hermetically sealed using the screw cap top of the bottle to produce a hermetically-sealed container comprising approximately 100 milligrams of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate. The pH of the liquid was measured and determined to be about 9.5. The liquid was transparent and purple.

[0027] 0.5 milliliters of water was removed from a 500 milliliter bottle of DASANI® purified water. DANSANI® purified water contains purified water, magnesium sulfate, potassium chloride, and sodium chloride, and its pH was determined to be about 7.0. The 0.5 milliliters of removed water was replaced with 0.5 milliliters of the 20 gram-per-liter solution of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5- pentylphenolate, which is described in Example 1, and the bottle was hermetically sealed using the screw cap top of the bottle to produce hermetically-sealed container comprising approximately 10 milligrams of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate. The pH of the liquid was measured and determined to be about 8.5. The liquid was transparent and lacked discernable color.

[0028] The preceding experiments confirm that 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate is suitable for use in beverages.