WATER-SOLUBLE LIPOPHILIC NATURAL COMPOUND FORMULATIONS

Abstract

Methods and formulations for increasing the water solubility and/or bioavailability of lipophilic natural compounds are disclosed. The formulations may be employed to make liquid filled capsules or clear and stable beverages containing therapeutic amounts of the active ingredients, for example.

Claims

1. A water-soluble lipophilic natural compound formulation, comprising: at least 0.01 wt % curcumin extract; and a non-ionic surfactant.

2. The formulation of claim 1, wherein the curcumin extract and the non-ionic surfactant are present in the formulation at a weight ratio from 1:5 to 1:200.

3. The formulation of claim 1, wherein the curcumin extract is present at least at 0.1 wt %.

4. The formulation of claim 1, wherein the curcumin extract is present at from 1 wt % to 80 wt %.

5. The formulation of claim 1, wherein the curcumin extract is present at from 0.1 wt % to 30 wt %.

6. The formulation of claim 1, consisting essentially of the curcumin extract and the non-ionic surfactant, and optionally pH adjusting agents, excipients, or combinations thereof

7. The formulation of claim 1, wherein said non-ionic surfactant is a non-ionic water soluble mono-, di-, or tri-glyceride; non-ionic water soluble mono- or di-fatty acid ester of polyethyelene glycol; non-ionic water soluble sorbitan fatty acid ester; polyglycolyzed glyceride; non-ionic water soluble triblock copolymers; or derivative thereof.

8. The formulation of claim 1, wherein said non-ionic surfactant is a non-ionic water soluble mono-, di-, or tri-glyceride.

9. The formulation of claim 1, wherein said non-ionic surfactant is a polyoxyl castor oil.

10. The formulation of claim 1, wherein said formulation is a non-alcoholic formulation and a non-aprotic solvated formulation.

11. The formulation of claim 1, comprising from 1 mg to 50 mg of the curcumin extract.

12. The formulation of claim 1, wherein said formulation is in a soft gel capsule.

13. The formulation of claim 1, wherein said formulation is solubilized in water and is in the form of beverage.

14. The formulation of claim 1, further comprising water.

15. The formulation of claim 15, wherein the water is added at greater than 50 wt % and the formulation is clear with no visible particles or micelles to the naked eye.

16. A method for enhancing the bioavailability of a lipophilic natural compound in a subject, comprising administering to the subject a formulation comprising a curcumin extract and a non-ionic surfactant.

17. The method of claim 16, wherein the formulation is in the form of a liquid consumable.

18. The method of claim 17, wherein the liquid consumable further comprises at least 50 wt % water and the curcumin extract is solubilized or finely dispersed in the water to form a clear solution.

19. The method of claim 17, wherein the liquid consumable is contained with a soft gel tablet.

20. The method of claim 16, wherein the curcumin extract and the non-ionic surfactant are present in the formulation at a weight ratio from 1:5 to 1:200.

Description

EXAMPLES

[0074] The following examples below are meant to illustrate certain embodiments of the present disclosure, and are not intended to limit the scope of the disclosure.

Example 1

[0075] Water soluble compositions of co-enzyme Q-10 were formulated containing the non-ionic surfactant macrogolglycerol hydroxystearate (polyoxyl 40 castor oil). The polyoxyl castor oil (non-ionic surfactant) was heated and stirred to a temperature of about 100 F., then the powdered co-enzyme Q-10 (Co-Q-10) was added slowly and mixed until a clear viscous emulsion phase formulation was formed containing dissolved Co-Q-10. The emulsion phase formulation included macrogolglycerol hydroxystearate 40 and powdered Co-Q-10. The Co-Q-10/surfactant mixture was then slowly added to warm water (100 F.) until a crystal clear solution was formed. The formulation also included other pH modifiers, preservatives, etc., in minor amounts. Table 1 below sets forth the formulation.

TABLE-US-00001 TABLE 1 Co-Q-10 WS Ingredients Wt % Co-Enzyme Q-10 5.25% Water 64.25% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%
The aqueous Co-Enzyme A-10 formulation was analyzed by HPLC and found to contain 0.5%, or 50 mg/ml co-enzyme Q-10 (ubidecarenone).

Example 2

[0076] A water soluble formulation of lycopene was prepared by mixing a lycopene extract (Lyc-O-Mato, Lycored corporation) containing 15% lycopene with polyoxyl castor oil. First, the polyoxyl castor oil was warmed about 100-110 F. and mixed with the liquid lycopene formulation until a clear red emulsion was formed. This emulsion was then very slowly added to water that has been heated to about 100-110 F. until a clear water soluble lycopene concentrate was obtained. The formulation also included other pH modifiers, preservatives, etc., in minor amounts. The water soluble concentrate was a deep red color and was added to additional water at room temperature to make a water soluble beverage. Table 2 below sets forth the formulation.

TABLE-US-00002 TABLE 2 Lycopene WS Ingredients Wt % Lycopene 3.3% Water 66.2% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 3

[0077] A water soluble formulation of lutein was prepared by mixing a lutein extract (Xangold, Cognis Corporation) containing 80% lutein with polyoxyl castor oil. First, the polyoxyl castor oil was warmed to about 100-110 F. and then mixed with a powdered lutein formulation until a clear red emulsion was formed. This emulsion was then very slowly added to water that has been heated to about 100-110 F. until a clear water soluble lutein concentrate was obtained. The water soluble concentrate was a deep yellow/orange color and was added to additional water at room temperature to make a water soluble beverage. The formulation also included other pH modifiers, preservatives, etc., in minor amounts. Table 3 below sets forth the formulation.

TABLE-US-00003 TABLE 3 Lutein WS Ingredients Wt % Lutein 3.3% Water 66.2% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 4

[0078] A water soluble formulation of quercetin was prepared with quercetin dihydrate. First, polyoxyl castor oil was heated to about 100-110 F. and stirred. The powdered quercetin dehydrate was added until a clear, slightly yellow emulsion was formed. This emulsion was then very slowly added to water that has been heated to about 100-110 F. until a clear water soluble quercetin concentrate was obtained. The water soluble concentrate was clear and free of visible particles, and was added to additional water at room temperature to make a clear water soluble beverage. The formulation also included other pH modifiers, preservatives, etc., in minor amounts. Table 4 below sets forth the formulation.

TABLE-US-00004 TABLE 4 Quercetin WS Ingredients Wt % Quercetin dihydrate 1.4% Water 68.1% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 5

[0079] A water soluble formulation of a green tea extract containing EGCG was made by mixing a green tea extract containing 94% EGCG in warm polyoxyl castor (about 100-110 F.) until a clear emulsion was formed. This emulsion was then very slowly added to water that had been heated to about 100-110 F. until a clear water soluble EGCG green tea extract concentrate was obtained. The water soluble concentrate was added to additional water at room temperature to make a water soluble beverage. The formulation also included other pH modifiers, preservatives, etc., in minor amounts. Table 5 below sets forth the formulation.

TABLE-US-00005 TABLE 5 EGCG Green Tea WS Ingredients Wt % EGCG 94% 3.3% Water 66.2% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 6

[0080] Water soluble compositions of lemon oil were formulated containing the non-ionic surfactant macrogolglycerol hydroxystearate (polyoxyl 40 castor oil). The polyoxyl castor oil (non-ionic surfactant) was heated and stirred to a temperature of about 100 F., then the lemon oil was added slowly and mixed until a clear viscous solution was formed containing dissolved lemon oil. The dissolved lemon oil emulsion was then slowly added to warm water (100 F.) until a crystal clear solution was formed. The water soluble concentrate was added to additional water at room temperature to make a crystal clear, water soluble beverage. The same formulation of example 6 was replicated with D-limonene. The formulation also included other pH modifiers, preservatives, etc., in minor amounts. Table 6 below sets forth the formulation.

TABLE-US-00006 TABLE 6 Lemon Oil WS Ingredients Wt % Lemon Oil 6.25% Water 65.25% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 7

[0081] Water soluble compositions of grapefruit seed extract were formulated containing macrogolglycerol hydroxystearate (polyoxyl 40 castor oil). Grapefruit seed extract is a natural preservative and is effective against both gram positive and gram negative bacteria. The polyoxyl castor oil was heated and stirred to a temperature of about 100 F., and then the grapefruit seed oil was added slowly and mixed until a clear viscous solution was formed containing dissolved grapefruit seed extract. The dissolved grapefruit seed extract emulsion was then slowly added to warm water (100-110 F.) until a crystal clear solution was formed. The water soluble concentrate may be added to beverages or other emulsions to make a crystal clear, water soluble preservative system that is effective against both gram positive and gram negative bacteria. The formulation included pH modifiers, preservatives, etc., in minor amounts. Table 7 below sets forth the formulation.

TABLE-US-00007 TABLE 7 Grapefruit seed WS Ingredients Wt % Grapefruit seed 2% Extract Water 67.70% Macrogolglycerol 30% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 8

[0082] Water soluble compositions of essential flavor oils were formulated containing macrogolglycerol hydroxystearate (polyoxyl 40 castor oil) and an essential flavor oil. Most essential oil flavors contain 20-45% alcohol to make them soluble. The polyoxyl castor oil (non-ionic surfactant) was heated and stirred to a temperature of about 100 F., and a pure orange essential oil containing no alcohol was slowly mixed with the polyoxyl castor oil until a clear viscous solution was formed containing dissolved essential orange oil. The orange essential oil emulsion was then slowly added to warm water (100-110 F.) until a crystal clear solution was formed. The water soluble concentrate can be added to beverages to impart flavor without the need of an alcohol containing essential oil extract. The formulation also included other pH modifiers, preservatives, etc., in minor amounts. Table 8 below sets forth the formulation.

TABLE-US-00008 TABLE 8 Orange Essential Oil WS Ingredients Wt % Orange Oil Flavor 1.25% Water 68.25% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 9

[0083] Water soluble compositions of curcumin were formulated containing macrogolglycerol hydroxystearate (polyoxyl 40 castor oil) and curcumin extract that is 99% pure 1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione by HPLC. The polyoxyl castor oil (non-ionic surfactant) was heated and stirred to a temperature of about 125 F., and the curcumin powder was slowly mixed with the polyoxyl castor oil until a clear viscous solution was formed containing dissolved curcumin powder. The curcumin emulsion was then slowly added to warm water (100-125 F.) until a crystal clear solution was formed. The water soluble concentrate can be added to beverages to make a curcumin supplement.

The formulation also included other pH modifiers, preservatives, etc., in minor amounts. Table 9 below sets forth the formulation.

TABLE-US-00009 TABLE 9 Curcumin WS Ingredients Wt % Curcumin 99% 1.25% Water 68.25% Macrogolglycerol 30.20% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 10

[0084] A water soluble formulation of lutein is prepared by mixing a lutein extract (Xangold, Cognis Corporation) containing 80% lutein with polyoxyl castor oil. First, the polyoxyl castor oil is warmed to about 100-110 F. and then mixed with a powdered lutein formulation until a clear red emulsion is formed. This emulsion is then very slowly added to water that has been heated to about 100-110 F. until a clear water soluble lutein concentrate is obtained. The water soluble concentrate is a deep yellow/orange color and is added to additional water at room temperature to make a water soluble beverage. The formulation also can include other pH modifiers, preservatives, etc., in minor amounts. Table 10 below sets forth the formulation.

TABLE-US-00010 TABLE 10 Lutein WS Ingredients Wt % Lutein 3.3% Water 86.4% Macrogolglycerol 10% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%

Example 11

[0085] A water soluble formulation of lycopene is prepared by mixing a lycopene extract (Lyc-O-Mato, Lycored corporation) containing 15% lycopene with polyoxyl castor oil. First, the polyoxyl castor oil is warmed to about 100-110 F. and mixed with the liquid lycopene formulation until a clear red emulsion is formed. This emulsion is then very slowly added to water that is heated to about 100-110 F. until a clear water soluble lycopene concentrate is obtained. The formulation also may include other pH modifiers, preservatives, etc., in minor amounts. The water soluble concentrate is deep red color and can be added to additional water at room temperature to make a water soluble beverage. Table 11 below sets forth the formulation.

TABLE-US-00011 TABLE 11 Lycopene WS Ingredients Wt % Lycopene 3.3% Water 56.4% Macrogolglycerol 40% hydroxystearate 40 Sodium Benzoate 0.06% Potassium Sorbate 0.04% Citric Acid 0.20% Total 100.00%