Monomeric bimetal hydroxycitric acid compounds and methods of making and using the same

Abstract

Monomeric bimetal hydroxycitric acid (HCA) compounds are provided. The subject compounds include a divalent metal (X) bonded to the carboxylic acids of C2 and C3 and a monovalent metal (Y) bonded to the carboxylic acid of C1. Also provided are methods of preparing the subject compounds from a dimeric starting material (e.g., X 3 (HCA) 2 ) which include acidifying the dimer to produce a monomeric intermediate which is subsequently neutralized with YOH base. Methods of alleviating at least one symptom associated with a target disease or condition in a subject are provided. Also provided are compositions including the subject monomeric bimetal HCA compounds which find use in a variety of therapeutic applications.

What is claimed is: 
     
         1 . A monomeric hydroxycitric acid (HCA) compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         X is a divalent metal selected from Group IIA metals, Group IIB metals and Group VIIA metals; and 
         Y is a monovalent metal; 
         or a hydrate thereof. 
       
     
     
         2 . The monomeric HCA compound of  claim 1 , wherein X is a Group IIA group metal. 
     
     
         3 . The monomeric HCA compound of  claim 2 , wherein X is selected from Mg, Ca, Sr, Ba and Ra. 
     
     
         4 . The monomeric HCA compound of  claim 1 , wherein X is a Group IIB group metal. 
     
     
         5 . The monomeric HCA compound of  claim 4 , wherein X is Zn. 
     
     
         6 . The monomeric HCA compound of  claim 1 , wherein X is a Group VIIA group metal. 
     
     
         7 . The monomeric HCA compound of  claim 6 , wherein X is Mn. 
     
     
         8 . The monomeric HCA compound of  claim 1 , wherein Y is a Group IA metal. 
     
     
         9 . The monomeric HCA compound of  claim 8 , wherein Y is selected from Li, Na and K. 
     
     
         10 . The monomeric HCA compound of any one of  claims 1 - 9 , wherein the HCA is (−)-hydroxycitric acid. 
     
     
         11 . A method of alleviating at least one symptom associated with a target disease or condition in a subject, the method comprising:
 administering to a subject in need thereof an amount of a compound of  claim 1  effective to alleviate at least one symptom associated with a target disease or condition;   wherein the target disease or condition is selected from an obesity-related condition, diabetes, an inflammatory condition, osteoarthritis, hypertension, osteoporosis, wound healing, immunomodulation, metabolic dysfunction and cardiovascular disease.   
     
     
         12 . The method of  claim 11 , wherein the target disease or condition is an obesity-related condition. 
     
     
         13 . The method of  claim 12 , wherein the subject is obese and achieves a weight loss of 5% or more following administration of the monomeric HCA compound. 
     
     
         14 . The method of  claim 11 , wherein the target disease or condition is an inflammatory condition. 
     
     
         15 . The method of  claim 11 , wherein the target disease or condition is osteoarthritis or osteoporosis. 
     
     
         16 . The method of  claim 15 , wherein the at least one symptom is selected from pain, joint inflammation, loss of joint fluid, immobility of joints, legs or fingers, decreased bone density and calcification. 
     
     
         17 . The method of  claim 11 , wherein the monomeric HCA compound is selected from LiMgHCA, NaMgHCA, KMgHCA, LiCaHCA, NaCaHCA, KCaHCA, LiSrHCA, NaSrHCA, KSrHCA, LiZnHCA, NaZnHCA, KZnHCA, LiMnHCA, NaMnHCA and KMnHCA. 
     
     
         18 . A method of preparing a monomeric hydroxycitric acid (HCA) compound, the method comprising: 
       a) acidifying dimeric X 3 (HCA) 2  with an acidic solution under conditions sufficient to produce a monomeric HX(HCA) compound of the formula: 
       
         
           
           
               
               
           
         
         wherein X is a divalent metal; 
       
       b) neutralizing the monomeric HX(HCA) compound with a YOH solution under conditions sufficient to produce a monomeric hydroxycitric acid (HCA) compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein X is a divalent metal and Y is a monovalent metal; and 
       
       c) isolating the monomeric hydroxycitric acid (HCA) compound. 
     
     
         19 . The method of  claim 18 , further comprising, prior to step b), isolating and drying the monomeric HX(HCA) compound. 
     
     
         20 . The method of  claim 18 , wherein:
 X is selected from Mg, Ca, Sr, Zn and Mn; and   Y is selected from Li, Na and K.