Methods of increasing solubility of poorly soluble compounds and methods of making and using formulations of such compounds
The subject invention relates to novel soluble forms of planar ring structured organic compounds including flavonoids, and their production. The invention also includes the use of these novel formulations of planar ring structured organic compounds in the preparation of formulations and products. The invention also relates to a wide variety of applications of the formulations of the invention. The subject invention includes novel soluble forms and various formulations of flavonoids. Further, the invention includes novel methods of manufacturing the flavonoid formulations. The invention also relates to a wide variety of applications of the flavonoid formulations.
1. A method of preparing a solubilized flavonoid concentrate comprising:
i) mixing said flavonoid in the absence of a carrier with a heat stable solubilizing compound, wherein said heat stable solubilizing compound is not said carrier, to form a mixture,
ii) heating said mixture resulting from step (i) to a temperature of greater than 150° C. such that said flavonoid is solubilized to form a concentrate, and
iii) cooling said concentrate resulting from step (ii).
2. The method as is claim 1 wherein step i) and step ii) are performed simultaneously.
3. The method as in claim 1 wherein said heat stable solubilizing compound is a surfactant.
4. The method as in claim 3 wherein said surfactant is a nonionic surfactant.
5. The method as in claim 4 wherein said nonionic surfactant is polysorbate-80, polyoxyl 20 cetostearyl ether, or polyoxyl 40 hydrogenated castor oil.
6. The method as in claim 1 wherein said mixture is heated to greater than 170° C.
7. The method as in claim 1 wherein said heat stable solubilizing compound is polysorbate 80 or polyoxyl 40 hydrogenated castor oil, said flavonoid is apigenin and said mixture is heated to a temperature greater than 170° C.
8. The method as in claim 1 further comprising, after step ii) or step iii), adding a carrier.
9. The method as in claim 8 wherein said carrier is a water based carrier.
10. The method as in claim 8 wherein said carrier comprises dimethyl sulfoxide and water.
11. The method as in claim 8 wherein said carrier comprises dimethyl sulfoxide, hydroxypropyl cellulose and water.
12. The method as in claim 8 wherein said carrier comprises ethanol, propylene glycol and water.
13. The method as in claim 1 wherein said heat stable solubilizing compound is a polysorbate and said flavonoid is apigenin.
14. The method as in claim 1 further comprising, after step ii) or step iii), adding a small chain alcohol to said mixture to reduce the viscosity of said mixture.
15. The method as in claim 1 wherein said flavonoid is apigenin, luteolin, quercetin, rutin an epicatechin or hesperiden.
16. The method as in claim 15 wherein said flavonoid is apigenin.
17. The method as in claim 1 wherein said heat stable solubilizing compound is a polysorbate or polyoxyl 40 hydrogenated castor oil, said flavonoid is apigenin, and said mixture is heated to greater than 170° C.
18. The method as in claim 1 wherein the flavonoid is a flavone.
19. The method as in claim 1 wherein the flavonoid is a flavonol.
20. The method as in claim 1 wherein the flavonoid is a flavanone.
21. The method as in claim 1 wherein the flavonoid is a flavanol.
22. The method as in claim 1 wherein the flavonoid is an isoflavone.
23. A method of increasing the solubility of a flavonoid in an aqueous carrier, wherein said flavonoid has a solubility in water of less than 1 mg/ml, comprising:
i) mixing said flavonoid in the absence of a carrier with a heat stable solubilizing compound wherein said heat stable solubilizing sound is not said carrier, to form a mixture,
ii) heating said mixture resulting from step (i) to a temperature of greater than 150° C. such that said flavonoid is solubilized to form a concentrate,
iii) cooling said concentrate resulting from step (ii), and
iv) adding said cooled concentrate resulting from step iii) to an aqueous carrier.
24. The method as in claim 23 wherein said flavonoid has a solubility in water of less than 0.1 mg/ml.
25. The method as in claim 23 wherein said heat stable solubilizing compound is a surfactant.
26. The method as in claim 25 wherein said surfactant is a nonionic surfactant.
27. The method according to claim 26 wherein said nonionic surfactant is polysorbate-80, polyoxyl 20 cetostearyl ether, or polyoxyl 40 hydrogenated castor oil.
28. The method as in claim 23 wherein said mixture is heated to greater than 170° C.
29. The method as in claim 23 wherein said heat stable solubilizing compound is polysorbate 80 or polyoxyl 40 hydrogenated castor oil, said flavonoid is apigenin, and said mixture is heated to greater than 170° C.
30. The method as in claim 23 wherein said heat stable solubilizing compound is a polysorbate and said flavonoid is apigenin.
31. The method as in claim 23 wherein said carrier comprises dimethyl sulfoxide and water.
32. The method as in claim 23 wherein said carrier comprises dimethyl sulfoxide, hydroxypropyl cellulose and water.
33. The method as in claim 23 wherein said carrier comprises ethanol, propylene glycol and water.
34. The method as in claim 23 wherein the flavonoid is a flavone.
35. The method as in claim 23 wherein the flavonoid is a flavonol.
36. The method as in claim 23 wherein the flavonoid is a flavanone.
37. The method as in claim 23 wherein the flavonoid is a flavanol.
38. The method as in claim 23 wherein the flavonoid is an isoflavone.
39. A method of preparing a solubilized polyphenol concentrate comprising:
i) mixing said polyphenol in the absence of a carrier with a heat stable solubilizing compound, wherein said heat stable solubilizing compound is not said carrier, to form a mixture,
ii) heating said mixture resulting from step (i) to a temperature of greater than 150° C. so that said polyphenol is solubilized to form a concentrate, and
iii) cooling said concentrate resulting from step (ii).
40. The method as in claim 39 wherein the molar ratio of said polyphenol to said heat stable solubilizing compound is 1:2 to 1:20.
41. The method as in claim 39 wherein the molar ratio of said polyphenol to said heat stable solubilizing compound is 1:2 to 1:5.
42. The method as in claim 39 wherein said polyphenol is resveratrol.
43. The method as in claim 39 wherein said heat stable solubilizing compound is a surfactant.
44. The method as in claim 43 wherein said surfactant is nonionic.
45. The method as in claim 44 wherein said nonionic surfactant is polysorbate-80, polyoxyl 20 cetostearyl ether, or polyoxyl 40 hydrogenated castor oil.