Title of Invention

PROCESS OF RECOVERY OF PURE CURCUMINS FROM TURMERIC RHIZOMES

Abstract

A method for extraction of curcumins from turmeric rhizomes comprising of : a) Comminuting and drying of the wet turmeric rhizomes b) Extraction of curcumin from the dried rhizomes obtained in step (a) by suspending the rhizomes in aqueous alcohol solvent system under vigorously agitating conditions for a sufficient amount of time at a temperature in the range between 25-80° C. c) isolating the aqueous alcoholic solution of curcumins from the solid residue of turmeric from the suspension of step (b). d) Concentrating the isolated extract solution obtained in step (c) by 80-90 % evaporating the solvent and volatile oils of turmeric from the extract solution where the extent of evaporation is limited to 80-90 % of the original volume. t e) Crystallizing curcumins in purified form from the concentrated extract of step (d) by temperature induced solvent crystallization at a temperature in the range between 5-30°C. f) Separating the crystallized curcumin in pure form, from the remaining liquid solution.

Full Text

FORM 2 THE PATENTS ACT, 1970 (39 OF 1970) COMPLETE SPECIFICATION (See section 10; rule 13) Title:-Rhizomes." "Process of recovery of pure Curcumins from Turmeric Applicant:- THE GODAVARI SUGAR MILLS LIMITED, Fazalbhoy Building, 45/47, M.G. Road, Fort, Mumbai 400 001, Maharashtra, India An Indian Company. The following specifications particularly describes the nature of the invention in the manner in which it is to be performed. DESCRIPTION: The present invention relates to a single solvent system process for production of pure curcumin by extraction from turmeric rhizomes and by separating the curcumin from oleoresins, other volatile and nonvolatile oils of the turmeric rhizomes from the aqueous alcoholic extract by partial evaporation of the solvent and temperature induced crystallization. The present invention particularly relates to the single solvent system for extraction and isolation of curcumin using azeotropic ethanol. BACKGROUND OF THE INVENTION: Plants of the Curcuma genus and, especially, Curcuma longa are tropical plants known from ancient times that belong to the Zingiberaccae family and they originated in Asia. Dried Curcuma rhizomes are already used in Asia as a spice and textile dye. They are also used in popular medicines to treat stomach ailments. Curcuma longa (Family Zingiberaccae) or Turmeric is one of the oldest herbs in Ayurveda materia medica, and has been used in Ayurveda medicine internally as a stomach, tonic and blood purifier, and topically in the prevention and treatment of skin diseases. The significance of turmeric in medicine has changed considerably since the very recent discovery of the anti-oxidant properties of naturally occurring phenolic compounds. The same ground dried rhizome of Curcuma longa, which have been used for centuries as a spice, food preservative and a coloring agent, has been found to be a rich source of phenolic compounds or curcuminoids. Curcumin and turmeric have been used as anti-inflammatory drugs for many years. More recently, there has been much interest in possible chemopreventive effects of curcumin. Many of the anti-inflammatory and chemopreventive properties of curcumin may be related to the antioxidant properties of curcumin. In the last few years, new pharmacological applications have appeared in the scientific literature: antibacterial activity, anti-inflammatory activity, lipid per oxidation capacity, anti-hepatoxic capacity and anti-tumorogenic capacity. Curcumin and the curcuminoids present in the rhizomes of Curcuma, particularly Curcuma longa, and the Zingiberaceae families in general, have been used for the treatment of a large variety of diseases. Examples are U.S. Pat. No. 5,891,924 (inhibitor of NF kappa B activation), U.S. Pat. No. 5,336,496 (inhibitor of delta 5 desaturase), EP 256353 (treatment of bad absorption syndromes), EP 568001 (anti¬viral agent), U.S. Pat. No. 5,108,750 (hyperlipidaemia and platelet aggregation reducer), FR 2655054 (cell protector) and EP 550807 (antioxidant and anti¬inflammatory properties), EP440885 (anti-inflammatory), EP 319058 (against hair loss), U.S. Pat. No. 510,750, U.S. Pat. No. 4,906,471 and U.S. Pat. No. 4,842,859 (antiplatelet aggregation and anti-cholesterol agent), WO 88/05304 (treatment of neurological disorders), WO 96/03999 (lipidic peroxide reducer), ES 20103689 2. (modulates high and low density oxidised lipoproteins, protects keratinocytes against free radicals and increases cell proliferation in aged human tissue). It is obvious from this literature that use of curcumins in pharmaceutical and Food formulations has been gaining increasing interests. For both these formulations, a presence, even at p.p.m. levels, of toxic and carcinogenic organic solvents in the curcumin extract will not be acceptable, although many of the solvents in the multiple solvent systems, either extraction or purification of curcumin include solvents such as methanol, dichloromethane, acetone and petroleum ether. The solvent losses are also significant in handling highly volatile solvents such as acetone, methanol and dichloromethane. PRIOR ART OF THE INVENTION: Curcumin species are extracted using various solvents and examples are, a method for extracting curcumin from curcuma longa L.(JP 6009479), Method for obtaining apolar and polar extracts of curcuma and applications thereof (US 6,440,468) The extract of Curcuma longa can be obtained, according to Spanish Patent (ES 2103689), by the extraction of the Curcuma rhizomes by macerating with alcohol (methanol, ethanol). Supercritical C02 extraction and separation method of effective components of curcumae longae rhizome (CN 1319418). Majority of the extraction processes utilize at least two organic, highly volatile organic solvents in the extraction and purification of curcumins from turmeric rhizomes. For example, KR9205687 claims a method for extracting curcumins in Curcuma longa extract comprising of dissolving the whole extracts in a water content polar solvent (85-100 % methanol, 80-95 % ethanol or 75-90 % acetone) and precipitating curcumin by addition of excess amount of a non-polar solvent( n-hexane or petroleum ether (b.p. 40-60 deg.C)), agitating and leaving it to obtain a precipitate, and recrystallizing the precipitate from ethanol, methanol, acetone or a rnixture of these solvent. The whole extract has to be obtained from turmeric rhizomes before this purification method. Another patent WO9603999 also claims a similar process for extraction of apolar and polar extracts of turmeric. In most extraction processes the solvent in the primary extraction stages involving the solid rhizomes is removed completely before the purification. At this stage it is difficult to handle sticky mass containing oleoresins, other nonvolatile oils and curcumins. Recrystallizations using different solvent systems is a common practice. A United States Patent 6,440,468 claims such a process obtaining the apolar extract by extracting the rhizomes with an organic solvent, filtration and evaporation to dryness of the extract, dissolution of the oleoresin obtained in hot conditions, precipitation while allowing to cool down and filtration of the solid followed by drying and recrystallizing the solid in order to obtain a product having a purity in curcuminoids higher than 90%. 3 Use of supercritical C02 has been now most acceptable for getting natural products. JP6009479 claims obtaining an extract curcumin with specific aroma, bitter taste and strange smell from Curcuma longa L. contacting the rhizomes with carbon dioxide in its critical state at 100 to 300kgf/cm2 at 60 to 70 °C at a flow rate of 5 to 6 liters/min for 2 to 3 hours whereby the powder is separated into curcumin and essential oils. Then, the carbon dioxide containing essential oil is led into the carbon dioxide capturing vessel where the pressure of the carbon dioxide is reduced. The process requires expensive high pressure equipments with limited capacity of the process. Again the extraction of polar compounds such curcumin using supercritical C02 have been reported to be poor. Again the extract obtained has to be purified by solvent extraction/crystallization techniques and use of organic solvents cannot be completely eliminated. Since supercritical C02 has limited capacity for extraction of polar compounds, it is usually combined with organic polar solvents with sometime as much as 50% level and therefore the extract gets associated with the organic solvent on reduction of pressure whereby C02 is separated from the extract and the extract has to be processed in the same manner as the extract obtained from organic solvents. United States Patent 6,326,504 has reported a similar process for high pressure extraction of organic products from vegetable or animal matrices or extracts thereof wherein the process is carried out in the presence of one or more liquid solvents and one or more supercritical fluids wherein the proportion of the supercritical fluid is less than 50% by weight of the total weight of the solvent and the supercritical fluid. Another patent CN1319418 also uses a similar mixture of aq. alcohol with supercritical C02. In his United States Patent 4,138,212, Stransky suggested soap solutions for producing water and oil soluble curcumin coloring agents. The process, however, does not recover curcumin in pure form and the precipitate obtained by treatment of the extract solution with an acid is dispersed in an oil as a formulation for food colouration. Another aqueous solutions based process (US6224877) comprises of the steps of contacting the rhizome of Curcuma species with an aqueous hydrotrope solution at a temperature in the range of 0-100 C. for extraction of curcuminoids, separating the solution obtained from the solid residue, and recovering the curcuminoids from the solution by known methods. At higher temperatures, however, the starch from curcumins gets gelatinized and processing of the suspension becomes difficult DETAILED DESCRIPTION OF THE INVENTION The present invention refers to a process for extraction of and production of curcumins from turmeric rhizomes in purified form, free from the oleoresins and volatile and nonvolatile oils of the rhizomes, comprising the steps The Curcuma species for the extraction are selected from the group consisting of Curcuma longa, Curcuma aromatica, Curcuma amada, Curcuma zedoariai, Curcuma xanthorrhiza, Curcuma caesia, Curcuma aerugiosa, Curcuma angustifolia, Curcuma leucorrhiza, Curcuma pierreana, Curcuma domestica, and Curcuma mangga. 4 1. A method for extraction and production of curcumins from turmeric rhizomes, comprising the steps of: a) Comminuting and drying of the wet turmeric rhizomes b) Extraction of curcumin from the dried rhizomes obtained in step (a) by suspending the rhizomes in aqueous alcohol solvent system under vigorously agitating conditions for a sufficient amount of time at a temperature in the range between 25-80° C. c) isolating the aqueous alcoholic solution of curcumins from the solid residue of turmeric from the suspension of step (b). >> d) Concentrating the isolated extract solution obtained in step (c) by partially evaporating the solvent and volatile oils of turmeric from the extract solution. k e) Crystallizing curcumins in purified form from the concentrated extract of step (d) by temperature induced solvent crystallization at a temperature in the range between 5-30°C. f) Separating the crystallized curcumin in pure form, from the remaining liquid solution. Examples of suitable solvents used to extract the curcumin are, Ethanol isopropanol, n-propanol or aqueous solutions of these alcohols. The extraction procedure can be repeated several times and the individual extracts combined before concentration. The extracts can be filtered and concentrated by distillation. The novelty of this single solvent system based techniques lies in the use of environmentally friendly, food grade and naturally obtained ethanol for the extraction of curcumin from Curcuma longa as a natural product on one hand, while on the other hand this method reduces the number of process steps as well as the cost of extraction and avoids multiple, toxic and objectionable solvents , such as methanol, methylene dichloride, ethylene dichloride, acetone and ethyl acetate. This process increases the selectivity towards curcumin to obtain it in a highly purified form devoid of oleoresins and other turmeric oil. EMBODIMENTS OF THE INVENTION The present invention is additionally illustrated by the following Examples, which do not have the intention of limiting its scope. EXAMPLE 1 200g Dry turmeric powder and 1000ml (95%w/w) Ethanol were charged in to a stirred vessel. The suspension was stirred for 1 hr under refluxing conditions and then 6" by evaporation under stirring to 10% of its original volume and then subjected to cooling with stirring at 20 C for 6 hrs. Curcumin was obtained as pure crystals from the solution, which was filtered and dried with yield of 2.4g. The solid residue obtained from the first extract was again treated with 1000ml of ethanol (95%)and processed in the same manner to recover curcumin with the yield of 0.15g. EXAMPLE 2 200g Dry turmeric powder and 1000ml (90%w/w) Ethanol were charged in to a stirred vessel. The suspension was stirred for 1 hr under refluxing conditions and then filtered to remove solid residue from the extract solution. The extract was concentrated by evaporation under stirring to 10% of its original volume and then subjected to cooling with stirring at 20 C for 6 hrs. Curcumin was obtained as pure crystals from the solution, which was filtered and dried with yield of 1.09g. The solid residue obtained from the first extract was again treated with 1000ml of (90%) Ethanol and processed in the same manner to recover curcumin with the yield of 0 .443 g. EXAMPLE 3 200g Dry turmeric powder and 1000ml (95%w/w) isopropanol were charged in to a stirred vessel. The suspension was stirred for 1 hr under refluxing conditions and then filtered to remove solid residue from the extract solution. The extract was concentrated by evaporation under stirring to 10% of its original volume and then subjected to cooling with stirring at 20 C for 6 hrs. Curcumin was obtained as pure crystals from the solution, which was filtered and dried with yield of 2.13g. EXAMPLE-4 200g Dry turmeric powder and 1000ml (95%w/w) Isopropanol were charged in to a stirred vessel. The suspension was stirred for 15 minutes under refluxing conditions and then filtered to remove solid residue from the extract solution. The extract was concentrated by evaporation under stirring to 10% of its original volume and then subjected to cooling with stirring at 20 C for 6 hrs. Curcumin was obtained as pure crystals from the solution, which was filtered and dried with yield of 1.58g. United states patent 6440468 refers to a process wherein in the first step supercritical carbon dioxide modified with ethyl alcohol is used to extract oleoresins United states patent 6440468 also uses water in second step of the process which gives an extract devoid of Curcumins while the proposed invention uses aqueous alcoholic solution. The use of water in the process is an essential part of the invention as water is not used for extraction of curcuminoids ,the present invention recovers curcumin from aqueous alcoholic solution in single step. 6 We Claim: 1. A method for extraction of curcumins from turmeric rhizomes comprising of : a) Comminuting and drying of the wet turmeric rhizomes b) Extraction of curcumin from the dried rhizomes obtained in step (a) by suspending the rhizomes in aqueous alcohol solvent system under vigorously agitating conditions for a sufficient amount of time at a temperature in the range between 25-80° C. c) isolating the aqueous alcoholic solution of curcumins from the solid residue of turmeric from the suspension of step (b). d) Concentrating the isolated extract solution obtained in step (c) by 80-90 % evaporating the solvent and volatile oils of turmeric from the extract solution where the extent of evaporation is limited to 80-90 % of the original volume. t e) Crystallizing curcumins in purified form from the concentrated extract of step (d) by temperature induced solvent crystallization at a temperature in the range between 5-30°C. f) Separating the crystallized curcumin in pure form, from the remaining liquid solution. 2. A method for extraction and production of curcumin as in Claim 1, wherin the said solvent in step(b) is selected from a group consisting of aqueous solutions of Ethanol Isopropanol, n-Propanol, preferably, azeotropic ethanol consisting of 95% alcohol and remaining amount is water. 3. A method for extraction and production of curcumin as in Claim 1, wherein the turmeric rhizomes solid loading in the extraction stage, in step 1 (b) ,the suspension is 5 -50 % by weight. 4. A method for extraction and production of curcumin as in Claim 1, wherein the temperature of step 1 (b) is in the range of 25-80 °C, preferably at boiling point of aqueous alcohol solution. 5. A method for extraction and production of curcumin as in Claim 1, wherein the time of extraction of step 1 (b) is in the range of 15 minutes to 6 hours. 6. A method for extraction and production of curcumin as in Claim 1, where crystallizing curcumin from the concentrated extract in step (e) is conducted by reducing temperature of the concentrated extract solution in aqueous alcohol in the range of 5-30°C. 7. A method for extraction and production of curcumin as in claim 1, wherein the curcumin is obtained as a pure natural product using aqueous ethyl alcohol from fermentation route for extraction and production of curcumin suitable for direct application in food and pharmaceutical formulations. Dated this 23rd day of Sep 2005. Signature : Authorised signatory for Godavari Sugar Mills Ltd.

Documents:

971-mum-2004-cancelled pages(22-11-2005).pdf

971-mum-2004-claims(granted)-(22-11-2005).doc

971-mum-2004-claims(granted)-(22-11-2005).pdf

971-mum-2004-correspondence(18-4-2006).pdf

971-mum-2004-correspondence(ipo)-(25-1-2006).pdf

971-mum-2004-correspondence2(3-1-2005).pdf

971-mum-2004-form 1(10-9-2004).pdf

971-mum-2004-form 13(18-4-2006).pdf

971-mum-2004-form 19(10-9-2004).pdf

971-mum-2004-form 2(granted)-(22-11-2005).doc

971-mum-2004-form 2(granted)-(22-11-2005).pdf

971-mum-2004-form 3(10-7-2004).pdf

971-mum-2004-power of attorney(5-4-2006).pdf