Title of Invention

"A PROCESS FOR PREPARING HIGHLY WATER SOLUBLE ALKELINE EARCH AND ALKELI METAL DOUBLE SALTS OF HYDROXYCITRIC ACID

Abstract This invention relates to a novel process for preparing higjily water soluble alkaline earth metal and alkali metal double salts of hydroxycitric acid. These salts are practically odourless and has negligible taste and are therefor useful as nutraceuticals. Aqueous extract of the fruits belonging to Garcinia species are treated to precipitate its alkaline earth metal salts such as the calcium salt This sparingly soluble product is dissolved in alkali hydroxide and the pH of the solution is adjusted by adding purified extract of the fruit rind. Ca/Na or Ca/K double salts are particularly useful.
Full Text

This invention relates to a process for preparing highly water soluble double salts of hydroxycitric acid particularly alkali and alkaline earth metal double salts.
Fruits, particularly the rind of fiuits, of the plant belonging to Garcinia species are a rich naturally occuring source of hydroxycitric acid. Garcinia species grow abundantly in India and in the south East Asian countries. *Kdajm' an extract of Garcinia fiuits is used in in^iarting tart flavour to dishes, particularly meat and fish dishes. Ayurveda, the traditional hatal medicinal system, considers Garcinia as om of the herbs that k beneficial to heart Garcinia or malabar tamarind has also received considerable attention in recent times as a nutraceutical for effective obesity c(»itrol.
Hydroxycitric acid has been known to be baieficial for the control and reduction of mammalian body wei^ In particular, the (-) hydroxycitric acid isomer and derivatives thereof are found to inhibit fatty acid and cholesterol synthesis. These con^unds also function as a natural anorectic agent in mammals. This particular stereois Naturally occuring hydroxycitric acid and its derivatives may be obtained by known methods of extraction of the fruits of the species Garcinia. One such method has be^ disclosed by Lewis Y.S., Methods in enzymology (J.M. Lowenstein, Ed, vol.13, p.613, Academic Press NY 1969).

Certain physical prq>erties of hydroxycitric acid and its derivatives are not ideally suited for their use as nutraceuticals. For instance, hydroxycitric acid exhibits very strong scwir taste while its calcium sak thougjb not very pungent in taste is poorly soluble in water thereby reducing its bioavailability; the trip(Aassium salt of this acid is highly hygroscopic and is alkaline in nature. These undesirable diaract^stics such as taste and solubility affect the bioavailability or biological use of these compc^nds. It has been found that the double salt of Ca/K or Ca/Na of (-) - hydroxycitric acid are ideal for biological use, particularly, because of their ideal physical characteristics. Further, desirable properties of these double salts are their low sodium content in Ca/K double salt and balanced pH.
These double salts are hi^y water soluble, have no strong or undesirable taste and are practically odouriess. These sahs are therefore ideal for a variety of applications inclu^ng^beverages. Preparation of these double salts are disclosed in PCT WO 0015051 published on 23 March 2000 having priority in US patent application no.892414 filed on 14 July 1997; US patent no,6160172 dat^ 12 December 2000 and US patent no.6395296 dated 28 May 2002.
The processes of preparingjhe-double sah disclosed in the jwrior art are tedius and the final {u-oduct obtaified may cont^n harmful ccmtaminants, thus limiting its utility value. For instance, me-prtJcedure disclosed in PCT WO 0015051 consists of converting calcium salt of (-) - HC A into free HCA and the free (-) HC A is partially neutralized by the addition of Ca (OH)2 followed by con^lete neutralization with KOH. Removal of calcium phoi^hate and unreacted {^oi^horic acid from the reaction mixture is a cumbersome procedure. Indian patent no. 182487 involves conv^^ion of the calcium sah of (-) HCA into free HCA with oxalic acid. Hie

liberated HCA is treated with sodium hydroxide followed by partial replaceni^nt of sodium by calcium by treating with calcium chloride. Removal of calcium oxalate and excess oxalic acid fix>m the reaction mixture limits the utility of this method. US patent no.5656314 discloses cotiv^sion of calcium salt of hydroxycitric acid and into free acid with sulj^uric acid. Purification of the final product obtained by this process also involves tedious procedure.
Thus, the object of this invention is to conv^ calcium salt of hydroxycitric acid into a hi^y water soluble calcium, potassium o£ calcium, sodium dcmble salt using a simple cost effective process. Inorganic or organic acids are not used in this process of conversion ccmsequ^tly, removal of undesired by-products and excess acid from the reaction mixture is avoided. Surprisingly, it is observed that the Ca/K double salt is largely free of the lactone form of hydroxycitric add and when dissolved in water, the salt does not equilibrate between the free form and the lactone tbrm. Further, desirable properties of the Ca/K double salt i& its balanced pH and a low ( Fmits of Garcinia atrovindis, Garcina cambogia or Garcinia indica are extracted with water, jweferably at room temperature. The rind of the fruits are preferred for extracticm as it contains a very hi^ percentage of HCA. Tt^ aqueous extract is treated with calcium hydroxide to precipitate sparingly soluble calcium salt of hydroxycitric acid. The precipitated calcium salt is dissolved by adding aqueous potassium hydroxide. The desired calcium potassium double salt is obtained frcmi this solution by adjusting its pH with purified aqueous extract of Garcinia rind.
Purified Garcina fruit rind extract may be obtained by treating the aqueous extract of the fruit rind with acetone, filtering the said treated extract to separate suspended solids therefrom and concentrating the filtrate wiiich is used to adjust the pH of the alkaline solution in the process of preparing the double salts of HCA.

Calcium salt of HC A may also be prepared by neutralizing the aqueous extract of the fruits with sodium hydroxide followed by treatment with calcium chloride.
This invention relates to a jwocess for preparing highly water soluble alkali metal/alkaline earth metal double sah of hydroxycitric acid which comprises the steps of fM-ecipitating sparingly soluble alkaline earth metal salt of hydroxycitric acid from an aqueous extract of the plants belonging to Garcinia species, dissolving said alkaline earth metal salt in aqueous alkali, adjusting the pH of said alkaline solution by adding an extract of Garcinia fruit thereto, purifying and drying the same thereafter to obtain higjily water soluble double salts of hydroxycitric acid.
Garcinia fruits and fruit rinds are particularly preferred because of their high hydroxycitric acid content. The description herein is limited to the prq)aration of Ca/K or Ca/Na double salts, though the same procedure is applicable fc^ the preparation of any alkali metal/alkaline earth metal double salts. The first step in the process is the preparation of calcium salt of hydroxycitric acid from the aqueous plant extract. This may be carried out by neutralization of the extract with an alkali. Calcium hydroxide and sodium hydroxide are preferred when calcium hydroxide is added to the aqueous plant extract, sparingly soluble calcium salt of hydroxycitric acid gets precipitated. Howev^, if sodium hydroxide is used for neutralization, calcium chloride must be added for converting the sodium salt to the calcium salt This precipitate is washed, with wat^ and the resulting calcium salt is converted into the double sah by dissolving the same in aqueous potassium or sodium hydroxide followed by adjustment of its pH by adding purified Garcinia fruit extract thereto.

Accordingly the present invention provides a process for preparing highly water soluble alkaline earth and alkali metal double salts of hydroxycitric acid comprising the steps of precipitating sparingly soluble alkaline earth metal salts of hydroxycitric acid from an aqueous extract of the plants belonging to Garcinia species, dissolving said alkaline earth metal salts in aqueous alkali, adjusting the pH of said alkaline solution by adding an extract of purified Garcinia fruit extract thereto, purifying and drying the same thereafter to obtain highly soluble double salts of hydroxycitric acid.

TTie following examples are particularly described the jwreferred embodiinent of this inventioa
Exan^le I:
Step 1: Prec>afati About 12.5 k^ of aqueous extract of Garcinia fruit ccmtaining about 9% of total solids was treated with 400 g of Ca(OH)2 at room temperature. The resulting precipitate of calcium salt of HCA was filtered and dried in vacuum fw about 4 hours. Product yield was about 560 g.
In another variation about 10 kg of Garcinia fruit extract containing about 9% of total solids was treated with 1.7 L of 20% NaOH solution under stirring for 2 hours. pH of this solution was adjusted to 7 by adding 200 ml of 50% HCl Subsequently 4L of 20% solution of calcium chlc^de was added to this to precipitate the calcium salt of HCA Ttiis precipitate was filtered and washed with wat^ and dried under vacuum at 80*^C for a period of 4 hours to yield 550 g of the salt
Step 2: Conversion of calcium sah of HCA to calcium potassiimi (fcmble isah of HCA
About 280 g of the calcium salt prepared by tl^step aboj^^as susp^ded in 2.8 L of water and about 2 L of 10% KOH solution wST^^d to it under stirring. The pH of the resulting solution was adjusted to 8.0 by adding purified Garcinia fruit rind extract. The solution thus obtained was treated with 150 g of activated charcoal atah
Example 11:
Step 1: Calcium salt of hydroxy citric acid was prepared according to example I. Step 2: CcMiversion of calcium salt of HCA to calcium potassium double salt.
About 20 g of the calcium salt prep^ed above was suspended in 200 ml of water and the pH was adjusted to 13 by adding 10% solution of KOH under stirring. The pll of this solution was then adjusted to pH 8 by purified Garcinia finit rind extract. The solution thus obtained was treated with activated diarcoal (10 g) at SO°C for one hour and then filtered. The filtrate was concentrated and then spray dried to yield 30 g of calcium potassium double salt
Example III:
Step 1: Preparation of calcium sah of HCA was carried out as per example L Step 2: Conversion of calcium sah into Ca-Na double salt of HCA
About 280 g the calcium sah obtained in step 1 was suspended in 2.8 L of water and about 1.4 L of 10% NaOH was added thereto under stirring. The pH of the resulting solution was adjusted to 8 by adding purified Garcinia fruit rind extract The solution was treated with 150 g of activated charcoal at 80**C for an hour and then filtered. The filtrate was concentrated and spray dried to give calcium sodiimi double salt of hydroxycitric acid. Approximate yield 540 g.
In all the above exanq>les the purified Garcinia extract used is obtained by tieating an aqueous extract of the fiuit rind with acetone. Settled mass firom the extract has been filtered off and the filtrate has been used for adjusting the pH.
invention also includes calcium potassium or calcium sodium double salts of hydroxycitric acid.



WE CLAIM:
1. A process fc^* preparing highly water soluble alkaline earth and alkali metal double salts of hydroxycitric acid; comprising the steps of precipitating sparingly soluble alkaline earth metal salts of hydroxycitric acid from an aqueous extract of the plants belonging to Garcinia species, dissolving said alkaline earth metal salts in aqueous alkali, adjusting the pH of said alkaline solution by adding an extract of purified Garcinia fruit extract thereto, purifying and drying the same thereafter to obtain highly soluble double salts of hydroxycitric acid.
2. The {M-ocess as claimed in claim 1, v^erein calciimi sah of hydroxycitric acid is precipitated from the aqueous extract of Garcinia plant by adding calciimi hydroxide thereto.
3. The process as claimed in claim 1, \^ereiti calcium salt of hydroxycitric acid is precipitated from the aqueous extract of Garcinia plant by adding a solution of sodium hydroxide thereto followed by adding a solution of calcium chloride.
4. The process as claimed in claims 1 to 3, wherein the Garcinia plant is Garcinia atroviridis, Garcinia cambogia or Garcinia indica.
5. The process as claimed in claims 1 to 4, wherein the fruit rind of Garcinia species is subjected to aqueous extraction.
6. The process as claimed in claims 1 to 5, wherein said calcium salt is treated
. with KOH solution having a concentration of 5 to 50%, preferably 5 to 15%
weight/volume.

The process as claimed in claims 1 to 6, wherein said purified Garcinia fruit extract is obtained by treating the aqueous extract thereof with acetone, and separating the insolubles therefrom.
The process as claimed in claims 1 to 7, wherein said aqueous extract containing the double salt is purified by treatment with activated charcoal, filtered and then spray dried.
The process as claimed in claim 8, wherein the filtrate is concentrated and dried under vacuum.
A process for preparing highly water soluble alkali and alkaline earth metal double salts of hydroxycitric acid substantially as herein described and exemplified.


Documents:

402-che-2003-abstract.pdf

402-che-2003-claims.pdf

402-che-2003-correspondnece-others.pdf

402-che-2003-correspondnece-po.pdf

402-che-2003-description(complete).pdf

402-che-2003-form 1.pdf

402-che-2003-form 19.pdf

402-che-2003-form 26.pdf

402-che-2003-form 3.pdf


Patent Number 197910
Indian Patent Application Number 402/CHE/2003
PG Journal Number 30/2009
Publication Date 24-Jul-2009
Grant Date
Date of Filing 12-May-2003
Name of Patentee LAILA IMPEX
Applicant Address 40-15-14, BRINDAVAN COLONY, VIJAYAWADA-520010, ANDHRA PRADESH, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 GOTTUMUKKALA VENKATA SUBBARAJU LAKSMISURYA, A-16 NALANDA NAGAR, TIRUPATI-517502.
2 PRATHA SRIDHAR 54-16-3/6A (II FLOOR), ADITYA BUILDINGS, LOYOLA GARDENS, VIJAYAWADA-520008, ANDHRA PRADESH, INDIA.
3 GOKARAJU GANGA RAJU 40-15-14, BRINDAVAN COLONY, VIJAYAWADA-520010, ANDHRA PRADESH, INDIA.
4 GOKARAJU RAMA RAJU 40-15-14, BRINDAVAN COLONY, VIJAYAWADA-520010, ANDHRA PRADESH, INDIA.
PCT International Classification Number C07C59/265
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA