Methods of making and using compositions comprising flavonoids

Abstract

The subject invention relates to novel micoparticulate and soluble forms of flavonoids, and their synthesis. The invention also includes novel formulations of such 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 composition comprising:
 a flavonoid, preferably apigenin, and   a heat stable flavonoid solubilizing compound, preferably a nonionic surfactant,   wherein said composition is formed by mixing the flavonoid and said heat stable flavonoid solubilizing compound to a temperature where said flavonoid is dissolved in said surfactant, and wherein the composition is preferably in the form of a food supplement, dietary supplement or medical food.   
     
     
         2 . A composition as in  claim 1  further comprising an alcohol. 
     
     
         3 . A patch for application of a flavonoid transdermally comprising a substrate having two sides, a first side having the composition of  claim 1  and an adhesive, and a second side with a material which is impermeable to the composition and adhesive on the first side. 
     
     
         4 . A method of producing a hydrated flavonoid, comprising:
 mixing a flavone with an alkali metal hydroxide to form an aqueous solution of an alkali metal flavone salt;   acidifying the aqueous solution of an alkaline metal flavonoid salt with an acidic agent to a pH level of less than 7 to form a hydrated flavonoid precipitate,   wherein the acidifying step is done under conditions producing flavonoid nanofibers having an average size of 50-1000 nanometers.   
     
     
         5 . A method as in  claim 4  wherein after the acidifying step is the step of filtering the precipitate, wherein the filtering step preferably comprises adjusting the product of the acidifying step to a pH less than 7 and filtering the material using a filter greater than 2 microns. 
     
     
         6 . A method of producing a hydrated flavonoid, preferably hydrated apigenin or hydrated luteolin, comprising:
 dissolving a flavonoid in a non-toxic organic solvent to form a mixture, wherein the dissolving step is preferably done at a temperature of about 20° C. to below the boiling point of the organic solvent; and   adding water to the mixture to form a hydrated flavonoid precipitate;   wherein the adding water step is done under conditions producing flavonoid nanofibers having an average size of 50-1000 nanometers.   
     
     
         7 . (canceled) 
     
     
         8 . A method of preparing a topical formulation of a hydrated flavonoid comprising:
 solubilizing a flavonoid in an alcohol;   adding the alcohol solubilized flavonoid to a dermatologically acceptable carrier,   adjusting the pH of the formulation to a dermatologically acceptable pH, preferably 4 to 8,   wherein the adjusting the pH step is done under conditions producing flavonoid nanofibers having an average size of 50-1000 nanometers.   
     
     
         9 . A method of preparing a topical formulation of a flavonoid comprising:
 adding a flavonoid to an emulsion carrier, preferably an oil in water, or water in oil emulsion carrier, to form a mixture;   heating the mixture until it has the approximate viscosity of water, wherein the mixture is preferably heated to about 120° F.-170° F., and forming a dispersion of microparticles in the mixture using cavitational forces.   
     
     
         10 . A method as in  claim 9  wherein the forming a dispersion step is accomplished using sonication or high pressure homogenization. 
     
     
         11 . A method as in  claim 9  wherein the emulsion includes an agent to inhibit microparticle agglomeration. 
     
     
         12 . A method of preparing a solubilized flavonoid composition comprising:
 mixing flavonoid particles with a heat stable flavonoid solubilizing compound, preferably a nonionic surfactant, more preferably a polysorbate when said flavonoid is apigenin, to form a mixture,   heating the mixture to a temperature where the flavonoid particles are solubilized to form a solution, and
 cooling the solution. 
   
     
     
         13 . A method as in  claim 12  further comprising adding a small chain alcohol to the solution to form a solution with a reduced viscosity. 
     
     
         14 . A method of reducing and/or preventing the effects of sun exposure comprising applying a therapeutically effective amount of a sunscreen formulation to the skin comprising the composition of  claim 1 , or a method of treating the effects of sun exposure comprising applying a therapeutically effective amount of a formulation to sun damaged skin comprising the composition of  claim 1 . 
     
     
         15 . A method of treating cancer in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a formulation comprising the composition of  claim 1 , or a method of reducing the likelihood of cancer occurring in a mammal comprising administering to a mammal a prophylactic amount of a formulation comprising the composition of  claim 1 . 
     
     
         16 . A method of treating acne, alopecia, dermal sensitization and irritation, dry skin (xerosis, ichthyosis), fungal infections, and rosacea, contact dermatosis, in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a formulation comprising the composition of  claim 1 . 
     
     
         17 . A method of treating autoimmune disease preferably psoriasis, lupus, or arthritis, in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a formulation comprising the composition of  claim 1 . 
     
     
         18 . A method of treating a TNFα related disease in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a flavonoid formulation comprising the composition of  claim 1 , or a method of reducing the likelihood of a TNFα related disease occurring in a mammal comprising administering to a mammal a prophylactic amount of a flavonoid formulation comprising the composition of  claim 1 . 
     
     
         19 . A method of treating an IL-1β related disease in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a flavonoid formulation comprising the composition of  claim 1 , or a method of reducing the likelihood of a IL-1β related disease occurring in a mammal comprising administering to a mammal a prophylactic amount of a flavonoid formulation comprising the composition of  claim 1 .