Method and System for Measuring the Pharmacokinetics of Liposomal Curcumin and its Metabolite Tetrahydrocurcumin

Abstract

The present invention includes a stabilized curcumin composition. The composition includes a curcumin composition and a phosphate composition, wherein the phosphate composition is non-buffering and is provided in an amount sufficient to stabilize and/or prevent the degradation of curcumin and/or a curcuminoid in a biological sample.

What is claimed is: 
     
         1 . A method of determining a curcumin level in a sample comprising the steps of:
 providing the sample suspected of comprising a curcuminoid;   adding a strong acid to the sample, wherein the strong acid composition is non-buffering; and   detecting the amount of curcuminoid in the sample, wherein the non-buffering strong acid reduces the degradation of the curcuminoid in the sample.   
     
     
         2 . The method of  claim 1 , wherein the sample is an in vitro sample. 
     
     
         3 . The method of  claim 1 , wherein the sample is an aqueous sample, a supernatant sample, a tears sample, a sputum sample, a blood sample or a bile sample. 
     
     
         4 . The method of  claim 1 , wherein the curcuminoid composition comprises curcumin and analogues and derivatives selected from curcumin; tetrahydrocurcumin; hexahydrocurcumin and hexahydrocurcuminol; curcumin glucuronide; and curcumin sulfate. 
     
     
         5 . The method of  claim 1 , wherein the strong acid is selected from at least one of a phosphoric acid; an orthophosphoric acid; a phosphate salt; or a Na-phosphate. 
     
     
         6 . The method of  claim 1 , wherein the curcuminoid composition further comprises a liposome, a phospholipid or a polymer composition to form an encapsulated curcuminoid composition. 
     
     
         7 . The composition of  claim 6 , wherein the liposome, the phospholipid or the polymer composition is selected from the group consisting of phosphatidylcholine (lecithin), lysolecithin, lysophosphatidylethanol-amine, phosphatidylserine, phosphatidylinositol, sphingomyelin, phosphatidylethanolamine (cephalin), cardiolipin, phosphatidic acid, cerebrosides, dicetylphosphate, phosphatidylcholine, and dipalmitoyl-phosphatidylglycerol, stearylamine, dodecylamine, hexadecyl-amine, acetyl palmitate, glycerol ricinoleate, hexadecyl sterate, isopropyl myristate, amphoteric acrylic polymers, fatty acid, fatty acid amides, cholesterol, cholesterol ester, diacylglycerol, and diacylglycerolsuccinate; or wherein the polymer composition is selected from the group consisting of polyesters, polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyorthoesters, polyphosphoesters, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids), copolymers, terpolymers, and combinations or mixtures thereof. 
     
     
         8 . The composition of  claim 6 , wherein the encapsulated curcuminoid composition has a size of about 10-900 nm. 
     
     
         9 . A kit for detecting curcumin comprising:
 a first vial for a biological sample, and   a second vial with an amount of a strong acid that is a non-buffering sufficient to stabilize a curcuminoid in a biological sample; and   a set of instructions for stabilizing a curcumin sample using the non-buffering phosphate composition, wherein the non-buffering phosphate composition comprises a phosphoric acid; an orthophosphoric acid; a phosphate salt; or a Na-phosphate to stabilize curcumin; tetrahydrocurcumin; hexahydrocurcumin and hexahydrocurcuminol; curcumin glucuronide; and curcumin sulfate.   
     
     
         10 . A method of stabilizing stabilizing a curcumin composition in plasma sample or a bile sample against degradation during an analytical processes comprising the steps of:
 providing a sample comprising a curcumin composition, wherein the sample is a bile sample or a blood sample and the curcumin composition is selected from curcumin; tetrahydrocurcumin; hexahydrocurcumin and hexahydrocurcuminol; curcumin glucuronide; and curcumin sulfate;   adding a phosphate composition to the sample, wherein the phosphate composition is non-buffering and is selected from a phosphoric acid; an orthophosphoric acid; a phosphate salt; or a Na-phosphate; and   detecting the amount of curcuminoid in the sample, wherein the non-buffering phosphate composition reduces the degradation of the curcuminoid in the sample.   
     
     
         11 . A stabilized curcumin composition comprising:
 a curcumin composition and a phosphate composition, wherein the phosphate composition is non-buffering and is provided in an amount sufficient to at least one of reduce the degradation or stabilize the curcumin in a sample.   
     
     
         12 . The stabilized curcumin composition of  claim 14 , wherein the curcumin composition selected from Curcumin; tetrahydrocurcumin; hexahydrocurcumin and hexahydrocurcuminol; curcumin glucuronide; and curcumin sulfate. 
     
     
         13 . The stabilized curcumin composition of  claim 14 , wherein the phosphate composition is selected from at least one of a phosphoric acid, a orthophosphoric acid, a phosphate salt, or a Na-phosphate. 
     
     
         14 . The stabilized curcumin composition of  claim 14 , further comprising a liposome to form a liposomal curcumin composition. 
     
     
         15 . The stabilized curcumin composition of  claim 14 , wherein the stabilized curcumin composition comprises a solution dosage form. 
     
     
         16 . A method of performing a clinical trial to evaluate a candidate drug comprising a curcumin or curcuminoid believed to be useful in treating a medical condition, the method comprising:
 (a) obtaining a first tissue samples prior to providing the candidate substance from tissue suspected from a set of patients;   (b) administering the candidate drug to a first subset of the patients, and a placebo to a second subset of the patients;   (c) repeating step (a) after the administration of the candidate drug or the placebo; and   (d) obtaining a second tissue sample from the first and second set of patients and stabilizing the curcumin or curcuminoids in the second tissue samples by adding an effective amount of a non-buffering phosphate; and   (e) determining of there is a statistically significant difference in the amount of curcumin or curcuminoids in the second tissue samples between the first and second subset of patients, wherein a statistically significant reduction indicates that the candidate drug is useful in treating said disease state.   
     
     
         17 . The stabilized curcumin composition of claim  19 , wherein the curcumin composition selected from at least one of curcumin; tetrahydrocurcumin; hexahydrocurcumin and hexahydrocurcuminol; curcumin glucuronide; or curcumin sulfate.