MONOMERIC BIMETAL HYDROXYCITRIC ACID COMPOUNDS AND METHODS OF MAKING AND USING THE SAME
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.
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.