WO2018020302A1

WO2018020302A1 - A process for extraction and isolation of curcuminoids

Info

Publication number: WO2018020302A1
Application number: PCT/IB2016/055794
Authority: WO
Inventors: Aju JACOB; Vishal MENON; Jose PAUL; Sunilkumar Olluara GOVINDAN; Anju V MATHEW
Original assignee: Synthite Industries Limited
Priority date: 2016-07-29
Filing date: 2016-09-28
Publication date: 2018-02-01
Also published as: EP3490576A1

Abstract

The present disclosure relates to the field of organic chemistry in general, and isolation of curcuminoids from turmeric in particular. The present disclosure relates to a simple, economical and energy efficient process for extraction and isolation of curcuminoids. The said process comprises extraction of turmeric using solvents, removal of solvent to obtain oleoresin and further extraction of the oleoresin using solvents, followed by crystallization of curcuminoids. The curcuminoids obtained by the instant process can be used in the field of therapeutics due to their anti-oxidant activity, anti-inflammatory activity and chemotherapeutic activity.

Description

"A PROCESS FOR EXTRACTION AND ISOLATION OF CURCUMINOIDS"

TECHNICAL FIELD

The present disclosure relates to the field of organic chemistry in general. Particularly, it relates to a process of isolation and purification of curcuminoids from Curcuma longa. The present disclosure provides for extraction of turmeric using solvents, not limiting to polar and/or non-polar solvents, removal of solvent to obtain oleoresin, further extraction/enrichment of the oleoresin using solvents, isolation of the enriched curcuminoid oleoresin and crystallization to obtain curcuminoids.

BACKGROUND OF THE DISCLOSURE

Turmeric {Curcuma longa) is well known and commonly used as a home remedy for bacterial contamination (as antibacterial) and as a food preservative (as antioxidant). The turmeric paste is used in different applications, for glowing skin, antibacterial and for healing wounds.

Turmeric has been used for many ailments, particularly as an anti-inflammatory agent, and curcumin has been identified as the active ingredient of turmeric. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial and anticarcinogenic activities. Additionally, the hepato- and nephro-protective [liver- and kidney-protective], thrombosis- suppressing, myocardial infarction-protective, hypoglycemic, and antirheumatic effects of curcumin are also well established.

The Curcuminoids extracted from turmeric include Curcumin, which is the principal active ingredient in turmeric, and it shares its therapeutic role with two closely related compounds called demethoxycurcumin and bis(demethoxy)curcumin. The Curcumin pigment imparts a reddish orange hue, demethoxy curcumin gives an orange yellow shade and bis-demethoxy curcumin produces yellow color.

Isolation of curcuminoids from Curcuma longa and related species have been carried out in the past. Although processes for such extraction and crystallization of curcuminoids from Curcuma longa are available, they use extreme process conditions, and have other limitations such as, poor yield, low recovery from the initial extract and low purity/quality of curcuminoids obtained. Further, said processes do not efficiently extract/isolate all the ingredients including curcumin, demethoxycurcumin and bis(demethoxy)curcumin in the final product. Also, in the present scenario, the crop yields are decreasing and the curcumin content in the turmeric crop is also varying and decreasing. Hence, it is important to achieve better curcuminoids recovery from the raw materials available.

Accordingly, there is a need for an improved and economically feasible process for the extraction and crystallization of curcuminoids with good yield and consistent quality. The present disclosure aims at overcoming the drawbacks of prior art to provide an improved and energy efficient process for the extraction and crystallization of curcuminoids to obtain maximum recovery of curcuminoids with high yield and consistent quality.

STATEMENT OF THE DISCLOSURE

Accordingly, the present disclosure relates to a process for extraction and isolation of curcuminoid from turmeric comprising steps of- extracting turmeric flakes with a solvent mixture, distilling the extracted solvent mixture to obtain oleoresin, extracting the oleoresin with a solvent mixture to obtain enriched curcuminoid oleoresin, and crystallizing the enriched curcuminoid oleoresin using a solvent mixture to isolate the curcuminoids.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure relates to a process for extraction and isolation of curcuminoid from turmeric comprising steps of:

extracting turmeric flakes with a solvent mixture;

distilling the extracted solvent mixture to obtain oleoresin;

extracting the oleoresin with a solvent mixture to obtain enriched curcuminoid oleoresin; and crystallizing the enriched curcuminoid oleoresin using a solvent mixture to isolate the curcuminoids.

In an embodiment of the present disclosure, the extraction of turmeric flakes is carried out in the presence of solvent mixture selected from a group comprising polar solvent, non-polar solvent and a combination thereof, preferably a mixture of polar solvents or a combination of polar and non-polar solvent.

In another embodiment of the present disclosure, the polar solvent is selected from a group comprising water, ethyl acetate, isopropanol, methyl acetate, methanol and ethanol; and the non-polar solvent is selected from a group comprising hexane and heptane. In yet another embodiment of the present disclosure, the solvent extraction of turmeric flakes is performed with a solvent mixture selected from a group comprising ethyl acetate and water; ethyl acetate and hexane; ethyl alcohol and water.

In still another embodiment of the present disclosure, the ethyl acetate and water is at a ratio ranging from about 92:8 to about 98:2; preferably 95:5; the ethyl alcohol and water is at a ratio ranging from about 85: 15 to 95:5; preferably 90: 10; the ethyl acetate and hexane is at a ratio 95:5; and the solvent extraction of turmeric flakes is at a temperature ranging from about 60° C to about 85° C, preferably 65° C, for a time period ranging from about 2 hours to about 6 hours, preferably 2 hours.

In still another embodiment of the present disclosure, the distillation of extracted solvent is carried out at a temperature ranging from about 70° C to about 90° C, preferably 80° C, for a time period ranging from about 6 hours to about 10 hours, preferably 8 hours, under vacuum.

In still another embodiment of the present disclosure, the oleoresin is extracted to obtain enriched curcuminoid oleoresin using solvent mixture selected from a group comprising of polar solvent, non-polar solvent and a combination thereof, preferably a combination of polar and non-polar solvents; wherein the polar solvent is selected from a group comprising water, ethyl acetate, isopropanol, methyl acetate, methanol, ethanol and combinations thereof, and the non-polar solvent is selected from a group comprising hexane, heptane and a combination thereof; and wherein said step is carried out at a temperature ranging from about 50° C to about 80° C, preferably 65° C, for a time period ranging from about 2 hours to about 6 hours, preferably 2 hours.

In still another embodiment of the present disclosure, the solvent mixture is a combination selected from a group comprising ethyl acetate and hexane; hexane, isopropyl alcohol and water; heptane, isopropanol and water; hexane, ethanol and water.

In still another embodiment of the present disclosure, hexane, isopropyl alcohol and water is at a ratio ranging from about 60:37:3 to about 90:8:2, preferably 85: 12:3; heptane, isopropanol and water is at a ratio of about 85: 12:3; hexane, ethanol and water is at a ratio ranging from about 75:23 :2 to about, 85: 12:3, preferably 80: 18:2; and ethyl acetate, hexane is employed at a ratio ranging from about 30 to about 70. In still another embodiment of the present disclosure, the step of extracting turmeric flakes with a solvent, the step of extracting the oleoresin with a solvent to obtain enriched curcuminoid oleoresin, or a combination thereof is repeated, and said repetition ranges from about one time to about three times.

In still another embodiment of the present disclosure, crystallizing the enriched curcuminoid oleoresin to isolate the curcuminoid is carried out using solvent mixture selected from a group comprising polar solvent, non-polar solvent and a combination thereof, preferably a combination of polar and non-polar solvents; and wherein the step is carried out under heating conditions at a temperature ranging from about 70° C to about 85° C, preferably80° C followed by cooling at a temperature ranging from about 25° C to about 35° C, preferably 30° C, for a time period ranging from about 6 hours to about 12 hours, preferably 10 hours, and wherein, the isolated curcuminoid is subjected to filtration, washing, drying and combination of acts thereof.

In still another embodiment of the present disclosure, the polar solvent is selected from a group comprising water, ethyl acetate, isopropanol, methyl acetate, methanol, ethanol and combinations thereof; and the non-polar solvent is selected from a group comprising hexane, heptane and a combination thereof.

In still another embodiment of the present disclosure, the solvent mixture is a combination selected from a group comprising hexane, isopropyl alcohol and water; ethyl acetate, hexane; heptane, isopropanol and water ; hexane, ethanol and water; and wherein the combination of hexane, isopropyl alcohol and water is at a ratio ranging from about 20:55:25 to about 2:96:2, preferably 5:85: 10; or wherein, ethyl acetate and hexane is at a ratio ranging from about from about 70:30 to 50:50, preferably about 65:35 to about 55:45, more preferably about 60:40; or wherein a combination of heptane, isopropanol and water is at a ratio of about 5:80: 15, preferably about 7:87:6, more preferably about 6:86:8; or wherein, a combination of hexane, ethanol and water are used at a ratio ranging from about 5:80: 15 to 10:85:5, preferably about 7:85:8.

In still another embodiment of the present disclosure, the process for extraction and isolation of curcuminoid from turmeric comprises recycling of solvents. In still another embodiment of the present disclosure, the extraction efficiency of curcuminoids from turmeric ranges from about 98% to about 99.5%; wherein, the recovery of curcuminoid ranges from about 60% to about 70%; wherein, the purity of recovered curcuminoids ranges from 95% to 98%; and wherein the curcuminoid distribution comprises of curcumin ranging from about 75% to about 80%, demethoxy curcumin ranging from about 10%) to about 15%) and bisdemethoxy curcumin ranging from about 5% to about 10%.

The present disclosure is addressed to the aforementioned needs of the art and provides an improved process for the extraction and crystallization of curcuminoids from C. longa with high recovery, enhanced yield and purity.

The present disclosure provides an improved process for the extraction and crystallization of curcuminoids; curcumin, demethoxycurcumin and bis (Demethoxy) curcumin (curcuminoids) from C. longa, the structures of which are provided below.

Bis~Dernethoxy curcumin

The present disclosure relates to a process for the extraction and crystallization of curcuminoids, wherein the process comprises steps of:

a. extraction of a sample containing curcuminoids by solvent mixture ,

b. distillation of extracted solvent to obtain 'oleoresin',

c. extraction of oleoresin by solvent mixture to obtain enriched curcuminoid oleoresin, d. crystallization of enriched curcuminoid oleoresin using solvent mixture to obtain the final crystallized curcuminoid product. In a non-limiting embodiment, the sample is obtained from C. longa (turmeric).

In a non-limiting embodiment, the sample is turmeric rhizome.

In a preferred embodiment, the sample is turmeric flakes obtained from turmeric rhizome. In an embodiment, turmeric powder with about 10-15% moisture is made into flakes (sample).

In another non-limiting embodiment, a combination of polar solvents, or a combination of polar and non-polar solvents are employed for the solvent extraction of step (a).

In a non-limiting embodiment of step (a), the polar solvent is selected from a group comprising water, isopropanol, ethyl acetate, methyl acetate, methanol, ethanol, acetone and combinations thereof.

In a non-limiting embodiment of step (a), the non-polar solvent is selected from a group comprising hexane, heptane, and a combination thereof.

In an exemplary embodiment of step (a), the process is carried out in presence of a combination of polar and non-polar solvents.

In a preferred embodiment of step (a), a solvent mixture comprising two or more solvents is employed for the solvent extraction.

In a preferred embodiment, the water content of the polar solvents is optimized below 10%. In a preferred embodiment, the extraction volume of the solvent ranges from 3 times to 10 times with respect to the Curcuma longal turmeric flakes.

In non-limiting embodiments, a solvent mixture selected from a group comprising combination of ethyl acetate and water, combination of ethyl acetate and hexane, combination of ethyl alcohol and water is employed for the solvent extraction in step (a).

In a preferred embodiment, ethyl acetate and water is employed as the solvent mixture for solvent extraction of turmeric in step (a). In another embodiment, the ethyl acetate and water are used at a ratio ranging from about 92:8 to about 98:2.

In a preferred embodiment, the ethyl acetate and water are used at a ratio ranging from about 94:6 to about 96:4.

In a more preferred embodiment, the ethyl acetate and water are used at a ratio of about 95:5.

In another embodiment, the ethyl alcohol and water are used at a ratio ranging from about 80:20 to about 95:5.

In a preferred embodiment, the ethyl alcohol and water are used at a ratio ranging from about 85: 15 to 95:5.

In a more preferred embodiment, the ethyl alcohol and water are used at a ratio of about 90: 10.

In another embodiment, the ethyl acetate and hexane are used at a ratio of about 80:20.

In a preferred embodiment, the ethyl acetate and hexane are used at a ratio of about 90: 10.

In a more preferred embodiment, the ethyl acetate and hexane are used at a ratio of about 95:5.

In another non-limiting embodiment, the process of solvent extraction in step (a) is carried out under heating conditions.

In yet another non-limiting embodiment, said process of solvent extraction is carried out at a temperature ranging from about 60° C to about 85° C.

In a preferred embodiment, the process of solvent extraction in step (a) is carried out at a temperature of about 65° C. In a non-limiting embodiment, the process of solvent extraction in step (a) is carried out for a time period ranging from about 2 hours to about 6 hours.

In a preferred embodiment, the process of solvent extraction of turmeric in step (a) is carried out for a time period of about 2 hours.

In still another non-limiting embodiment, the process of solvent extraction of turmeric in step (a) is carried out under pressure.

In a preferred embodiment, said process of solvent extraction of turmeric is carried out under atmospheric pressure conditions.

In a preferred embodiment, the solvent extraction of turmeric in step (a) is repeated multiple times. In an embodiment, the solvent extraction of step (a) is repeated for about 3 to 6 times.

In a preferred embodiment, the solvent extraction of turmeric in step (a) comprises recycling/reuse of solvents after solvent extraction.

In a non-limiting embodiment, the solvent extraction of step (a) comprises recycling of solvents with water.

In a preferred embodiment of step (a), polar solvents extract polar compounds, and water extracts water soluble compounds.

In a non-limiting embodiment, the solvent extraction of step (a) provides curcuminoid extraction efficiency of 98% to 99.5% from the sample.

The process step (b) of the present disclosure includes desolventisation involving distillation of the extracted solvent to obtain oleoresin.

In an embodiment, the process of distillation of extracted solvent in step (b) is carried out at a temperature ranging from about 70° C to about 90° C. In a preferred embodiment, the process of distillation of extracted solvent in step (b) is carried out at a temperature of about 80° C.

In another embodiment, the process of distillation of extracted solvent in step (b) is carried out for a time period ranging from about 6 hours to about 10 hours.

In a preferred embodiment, the process of distillation of extracted solvent is carried out for a time period of about 8 hours.

In still another non-limiting embodiment, the process of distillation of extracted solvent of step (b) is carried out under vacuum.

In a preferred embodiment, the process of distillation of extracted solvent is carried out under 600-700 mm vacuum.

In an exemplary embodiment of step (b), distillation of the extracted solvent yields oleoresin.

In a preferred embodiment of step (b), the temperature and pressure of distillation/desolventization are selected to get maximum solvent recovery and minimum degradation of curcuminoids.

The process step (c) of the present disclosure includes extraction of oleoresin obtained from the solvent extraction of Curcuma longa to obtain enriched curcuminoid oleoresin.

In a non-limiting embodiment, the extraction of oleoresin in step (c) is done using solvent(s).

In another non-limiting embodiment, a combination of polar solvents, a combination of non- polar solvent(s), or a combination of polar and non-polar solvents are employed for the solvent extraction of step (c).

In a non-limiting embodiment of step (c), the polar solvent is selected from a group comprising water, isopropanol, ethyl acetate, methyl acetate, methanol, ethanol and combinations thereof. In a non-limiting embodiment of step (c), the non-polar solvent is selected from a group comprising hexane, heptane and a combination thereof.

In an exemplary embodiment of step (c), the process is carried out in presence of a combination of polar and non-polar solvents.

In a preferred embodiment of step (c), a solvent mixture comprising two or more solvents is employed for the solvent extraction.

In a non-limiting embodiment, the oleoresin is extracted in step (c) using organic solvents, water and combinations thereof.

In non-limiting embodiments, a solvent mixture selected from a group comprising combination of ethyl acetate and hexane, combination of hexane, isopropyl alcohol and water, combination of heptane, isopropanol and water and combination of hexane, ethanol and water are employed for the solvent extraction in step (c).

In a preferred embodiment, a combination of hexane, isopropyl alcohol and water is employed as the solvent mixture for solvent extraction of oleoresin in step (c).

In another embodiment, a combination of hexane, isopropyl alcohol and water is used at a ratio ranging from about 60:37:3 to about 90:8:2.

In a preferred embodiment, a combination of hexane, isopropyl alcohol and water is used at a ratio ranging from about 80: 17:3 to about 86: 12:2.

In embodiment, the combination of hexane, isopropyl alcohol and water is used at a ratio of about 85: 12:3.

In a preferred embodiment, a combination of heptane, isopropanol and water are used at a ratio of about 85: 12:3.

In a preferred embodiment, a combination of ethyl acetate and hexane is employed as the solvent mixture for solvent extraction of oleoresin in step (c). In a preferred embodiment, a combination of ethyl acetate and hexane is used at a ratio ranging from about 30 to about 70.

In a preferred embodiment, a combination of hexane, ethanol and water is used at a ratio ranging from about 75:23 :2 to about, 85: 12:3.

In a preferred embodiment, a combination of hexane, ethanol and water is used at a ratio of about 80: 18:2.

In another non-limiting embodiment, the process of solvent extraction in step (c) is carried out under heating conditions.

In yet another non-limiting embodiment, said process of solvent extraction is carried out at a temperature ranging from about 50° C to about 80° C.

In a preferred embodiment, the process of solvent extraction in step (c) is carried out at a temperature of about 65° C.

In a non-limiting embodiment, the process of solvent extraction in step (c) is carried out for a time period ranging from about 2 hours to about 6 hours.

In a preferred embodiment, the process of solvent extraction in step (c) is carried out for a time period of about 2 hours.

In still another non-limiting embodiment, the process of solvent extraction in step (c) is carried out under pressure.

In a preferred embodiment, said process of solvent extraction is carried out under atmospheric pressure conditions.

In a preferred embodiment, the solvent extraction in step (c) is repeated multiple times. In an embodiment, the solvent extraction of step (c) is repeated for about 2 to 4 times. In a preferred embodiment, the solvent extraction of step (c) is repeated two times.

In a preferred embodiment, the solvent extraction in step (c) comprises recycling/reuse of solvents after solvent extraction.

In a non-limiting embodiment, the solvent extraction of step (c) comprises recycling of solvent mixture.

In a preferred embodiment, the oleoresin is extracted with solvent mixture to remove non- curcuminoids from the oleoresin.

In an embodiment, the non-curcuminoids include volatile oils, fixed oils, carbohydrates and other compounds which are removed by the employment of solvent mixtures of the present process.

In a preferred embodiment of step (c), the solvent mixture enriches curcuminoids in the oleoresin.

In a non-limiting embodiment, the enrichment of the curcuminoids ranges from 45-65% from the initial curcuminoids content in the oleoresin.

The process step (d) includes crystallization of the enriched curcuminoid oleoresin to obtain curcuminoids.

In a non-limiting embodiment, the process of crystallization of step (d) is carried out by addition of solvent mixture under heating conditions followed by cooling. The said crystallization is followed by filtration, washing, drying to obtain the final product.

In another non-limiting embodiment, a combination of polar solvents, or a combination of polar and non-polar solvents are employed for the crystallization step (d).

In a non-limiting embodiment of step (d), the polar solvent is selected from a group comprising water, isopropanol, ethyl acetate, methyl acetate, methanol, ethanol and combinations thereof. In a non-limiting embodiment of step (d), the non-polar solvent is selected from a group comprising hexane, heptane and a combination thereof.

In an exemplary embodiment of step (d), the process is carried out in presence of a combination of polar and non-polar solvents.

In a preferred embodiment of step (d), a solvent mixture comprising of two or more solvents are employed in the crystallization.

In non-limiting embodiments, a solvent mixture selected from a group comprising combination of hexane, isopropyl alcohol and water, combination of ethyl acetate and hexane, combination of isopropanol, heptane and water and combination of ethanol, hexane and water are employed in the crystallization step (d).

In a preferred embodiment, a combination of hexane, isopropyl alcohol and water is employed as the solvent mixture for crystallisation of enriched curcuminoid oleoresin in step (d).

In another embodiment, a combination of hexane, isopropyl alcohol and water are used at a ratio ranging from about 20:55:25 to about 2:96:2.

In a preferred embodiment, a combination of hexane, isopropyl alcohol and water is used at a ratio ranging from about 10:70:20 to 3 :90:7.

In a more preferred embodiment, a combination of hexane, isopropyl alcohol and water is used at a ratio of about 5:85: 10.

In a preferred embodiment, a combination of ethyl acetate and hexane is employed as the solvent mixture for crystallisation of enriched curcuminoid oleoresin in step (d).

In another embodiment, a combination of ethyl acetate and hexane is used at a ratio ranging from about 70:30 to 50:50. In a preferred embodiment, a combination of ethyl acetate and hexane is used at a ratio ranging from about 65:35 to 55:45.

In a more preferred embodiment, a combination of ethyl acetate and hexane is used at a ratio of about 60:40.

In a preferred embodiment, a combination of heptane, isopropanol and water is employed as the solvent mixture for crystallization of enriched curcuminoid oleoresin in step (d).

In another embodiment, a combination of heptane, isopropanol and water are used at a ratio of about 5:80: 15.

In a preferred embodiment, a combination of heptane, isopropanol and water is used at a ratio of about 7:87:6.

In a more preferred embodiment, a combination of heptane, isopropanol and water is used at a ratio of about 6:86:8.

In a preferred embodiment, a combination of hexane, ethanol and water is employed as the solvent mixture for crystallization of enriched curcuminoid oleoresin in step (d).

In another embodiment, a combination of hexane, ethanol and water are used at a ratio of about 5:80: 15 to 10:85:5.

In a preferred embodiment, a combination of hexane, ethanol and water is used at a ratio of about 7:85:8.

In another non-limiting embodiment, the process of crystallization of step (d) is carried out under heating conditions.

In yet another non-limiting embodiment, said process of crystallization of step (d) is carried out at a temperature ranging from about 70° C to about 85° C. In a preferred embodiment, the process of crystallization of step (d) is carried out at a temperature of about 80° C.

In another non-limiting embodiment, the process of crystallization of step (d) is followed by cooling.

In yet another non-limiting embodiment, said cooling in crystallization of step (d) is carried out at a temperature ranging from about 25° C to about 35° C.

In a preferred embodiment, the cooling in crystallization of step (d) is carried out at a temperature of about 30° C.

In a non-limiting embodiment, the process of crystallization of step (d) is carried out for a time period ranging from about 6 hours to about 12 hours.

In a preferred embodiment, the process of crystallization of step (d) is carried out for a time period of about 10 hours.

In still another non-limiting embodiment, the process of crystallization of step (d) is carried out under pressure.

In a preferred embodiment, said process of crystallization of step (d) is carried out under atmospheric pressure conditions.

In still another non-limiting embodiment, the process of crystallization is followed by filtration, washing and drying the product.

In a preferred embodiment, the filtration of crystallized product in step (d) is carried out by techniques selected from a group comprising of centrifugation, pressure filtration and vacuum filtration.

In a preferred embodiment, the filtration of crystallized product in step (d) is carried out by rotary pressure filtration. In an embodiment, the washing of the filtered crystallized product in step (d) is carried out in the presence of solvent(s).

In a non-limiting embodiment, a combination of polar solvents, a combination of non-polar solvent(s), or a combination of polar and non-polar solvents are employed for washing the crystallized product in step (d).

In another non-limiting embodiment, the polar solvent is selected from a group comprising water, isopropanol, ethyl acetate, methyl acetate, methanol, ethanol and combinations thereof. In another non-limiting embodiment, the non-polar solvent is selected from a group comprising hexane, heptane and a combination thereof.

In an exemplary embodiment, the washing of the filtered crystallized product is carried out in presence of a combination of polar and non-polar solvents.

In a non-limiting embodiment, the solvent selected from a group comprising combination of ethyl acetate and hexane; combination of isopropanol and water; combination of isopropanol, hexane, water; and combination of ethyl acetate, hexane, and water is employed for washing.

In a non-limiting embodiment, the washing of the filtered crystallized product is carried out by a combination of ethyl acetate and hexane.

In a preferred embodiment, a combination of ethyl acetate and hexane is used at a ratio ranging from about 70:30 to 50:50.

In a non-limiting embodiment, the washing of the filtered crystallized product is carried out by isopropanol: water mixture (80:20) ranging from about 0.5 to 2 times of the oleoresin charged for crystallisation. In a more preferred embodiment, isopropanol: water mixture (80:20) about one time of the oleoresin is used for crystallisation. In a non-limiting embodiment, the drying of the washed crystallized product in step (d) is carried out under heating conditions.

In another non-limiting embodiment, the drying of the washed crystallized product in step (d) is carried out at a temperature ranging from about 60° C to about 100° C.

In a preferred embodiment, the drying of the washed crystallized product in step (d) is carried out at a temperature of about 85° C.

In still another non-limiting embodiment, the drying of the washed crystallized product in step (d) is carried out under reduced pressure.

In a preferred embodiment, the drying of the washed crystallized product in step (d) is carried out under reduced pressure conditions, preferably 700-730 mm of mercury.

The process of the present disclosure provides an extraction efficiency of curcuminoids from Curcuma longa ranging from about 98% to about 99.5%.

The process of the present disclosure provides a recovery of curcuminoids ranging from about 60%) to about 70%. The said recovery is based on the curcuminoid content present and extracted from the turmeric sample.

In an embodiment, the distribution of ingredients in the recovered curcuminoids is about 75% to about 80%) of Curcumin, about 10%> to about 15%> of demethoxy curcumin and about 5% to about 10%) of bisdemethoxy curcumin.

In the process of the present disclosure, the purity of curcuminoids obtained ranges from about 95% to about 98%.

The present disclosure describes a process of extraction and isolation of curcuminoids from C. longa, said process comprising steps of:

a. extraction of turmeric flakes containing curcuminoids by solvents, wherein the solvent extraction is carried out in presence of a combination of polar or combination of polar/ non- polar solvents. b. desolventization involving distillation of the extracted solvent to obtain oleoresin.

c. extraction of the obtained oleoresin to obtain enriched curcuminoid oleoresin, wherein said step is carried out in presence of a combination of polar and non-polar solvents.

d. crystallization of enriched curcuminoid oleoresin using solvents to obtain the crystallized curcuminoid product, wherein the crystallization of enriched curcuminoid oleoresin is carried out in presence of a combination of polar and non-polar solvents.

The present disclosure further describes a process of extraction and isolation of curcuminoids from C. longa, said process comprising steps of:

a. extraction of turmeric flakes containing curcuminoids by solvent extraction, wherein the solvent extraction is carried out in presence of a combination of ethyl acetate and water, or a combination of ethyl acetate and hexane or a combination of ethyl alcohol and water.

b. desolventization involving distillation of the extracted solvent to obtain oleoresin.

c. extraction of the obtained oleoresin to obtain enriched curcuminoid oleoresin, wherein said step is carried out in presence of a combination of hexane, isopropyl alcohol and water, or a combination of heptane, isopropanol and water, or a combination of ethyl acetate and hexane, or a combination hexane, ethanol and water.

d. crystallization of enriched curcuminoid oleoresin using solvents to obtain the crystallized curcuminoid product, wherein the crystallization of enriched curcuminoid oleoresin is carried out in presence of a combination of hexane, isopropyl alcohol and water, or a combination of ethyl acetate and hexane, or a combination of heptane, isopropanol and water, or a combination of ethanol, hexane and water.

a. extraction of turmeric flakes containing curcuminoids by solvent extraction, wherein the solvent extraction is carried out in presence of a combination of ethyl acetate and water, or ethyl acetate and hexane, or ethyl alcohol and water ; wherein, the ethyl acetate and water are used at a ratio ranging from about 92:8 to about 98:2, preferably about 94:6 to 96:4, more preferably about 95:5; or wherein, the ethyl acetate and hexane are used in a ratio ranging from about 80:20 to about 90: 10, preferably about 95:5; or wherein, the ethyl alcohol and water are used in the ratio ranging from about 80:20 to about 95:5 preferably about 85: 15 to about 95:5, more preferably about 90: 10; and wherein, the solvent extraction is carried out at a temperature ranging from about 60° C to about 70°C, preferably about65° C for a time period ranging from about 2 hours to about 6 hours, preferably about 2 hours under pressure, preferably atmospheric pressure conditions.

b. desolventization involving distillation of the extracted solvent to obtain oleoresin; wherein, distillation of extracted solvent is carried out at a temperature ranging from about 70° C to about 90° C, preferably about 80° C; wherein, distillation of extracted solvent is carried out for a time period ranging from about 6 hours to about 10 hours, preferably, about 8 hours under vacuum, preferably 600-700mm vacuum.

c. extraction of the oleoresin to obtain enriched curcuminoid oleoresin, wherein said step is carried out in presence of a combination of hexane, isopropyl alcohol and water, or combination of heptane, isopropanol and water, or combination of ethyl acetate and hexane, or a combination hexane, ethanol and water; wherein, a combination of hexane, isopropyl alcohol and water are used in a ratio ranging from about 60:37:3 to about 90:8:2, preferably about 80: 17:3 to about 86: 12:2, more preferably about 85: 12:3; or wherein combination of heptane, isopropanol and water are used at a ratio of about 85: 12:3 ,or wherein, a combination of ethyl acetate and hexane is used at a ratio ranging from about 30 to about 70; or wherein, a combination hexane, ethanol and water are used at a ratio ranging from about 75:23 :2 to about, 85: 12:3, preferably 80: 18:2; wherein, solvent extraction is carried out at a temperature ranging from about 50° C to about 80° C, preferably, 65° C for a time period ranging from about 2 hours to about 6 hours, preferably 2 hours; under pressure, preferably atmospheric pressure.

d. crystallization of enriched curcuminoid oleoresin using solvent to obtain the crystallized curcuminoid product, wherein the crystallization of enriched curcuminoid oleoresin is carried out in presence of a combination of hexane, isopropyl alcohol and water, or combination of ethyl acetate and hexane, or combination of isopropanol, heptane and water, or combination of ethanol, hexane and water; wherein, a combination of hexane, isopropyl alcohol and water is used in a ratio ranging from about from about 20:55:25 to about 2:96:2, preferably about 10:70:20 to about 3 :90:7, more preferably 5:85: 10; or wherein, ethyl acetate and hexane is used in a ratio ranging from about from about 70:30 to 50:50, preferably about 65:35 to about 55:45, more preferably about 60:40; or wherein a combination of heptane, isopropanol and water are used at a ratio of about 5:80: 15, preferably about 7:87:6, more preferably about 6:86:8; or wherein, a combination of hexane, ethanol and water are used at a ratio ranging of about 5:80: 15, preferably about 10:85:5, more preferably about 7:85:8; wherein the crystallization is carried out at a temperature ranging from about 70° C to about 85°C, preferably about 80°C; wherein, the process of heating during the crystallization is followed by cooling at a temperature ranging from about 25° C to about 35° C, preferably 30°C, for a time period ranging from about 6 hours to about 12 hours, preferably 10 hours under atmospheric pressure conditions; wherein, crystallization is followed by filtration by rotary pressure filter; wherein, the filtration is followed by washing the crystallized product in the presence of solvent(s); wherein, a combination of isopropanol and water in the ratio 80:20 and ethyl acetate and hexane; wherein, ethyl acetate and hexane are used at a ratio ranging from about 60 to 40 preferably ; wherein, the washing of the filtered crystallized product is followed by drying the product at a temperature ranging from about 60°C to about 100° C, preferably 85°C under reduced pressure, preferably 700-730 mm of mercury.

Thus, the present disclosure provides an efficient process for the extraction and crystallization of curcuminoids with high yield and quality. The process of the present disclosure is a simple, economical and energy efficient process for the isolation and crystallization of curcuminoids. The process of the present disclosure further provides for maximum recovery of curcuminoids from the oleoresin, thus, reducing the cost. Furthermore, the specific solvent mixtures employed in the various steps to crystallize the curcuminoids from the enriched oleoresin by cooling to ambient temperature resulting in a cost effective and efficient process, unlike prior art processes which involves crystallisation at low temperatures for longer time.

In an aspect of the present disclosure, a curcuminoid product containing curcumin ranging from about 75% to about 80%, demethoxy curcumin ranging from about 10% to about 15% and bisdemethoxy curcumin ranging from about 5% to about 10% is provided, wherein said product with the specified concentrations of each component is a requisite/standard for pharmaceutical and nutraceutical applications. Further, it is the process of the present disclosure which is improved and efficient in achieving said curcuminoid product comprising curcumin ranging from about 75% to about 80%, demethoxy curcumin ranging from about 10%) to about 15%) and bisdemethoxy curcumin ranging from about 5% to about 10%>.

The turmeric (C.longa) used in the present disclosure was procured from the following places; Gundalpettu-Karnataka (T G variety), Aleppey (finger and mother variety), Myanmar -Burma (finger and mother variety), Ethiopia (finger and mother variety), Vietnam (finger and mother variety) and Indonesia (finger and mother variety). Additional embodiments and features of the present disclosure will be apparent to one of ordinary skill in the art based upon description and examples provided herein. However, the examples below should not be construed to limit the scope of the present disclosure.

Examples

Example 1: Solvent Extraction of Turmeric (C. longa) and distillation of oleoresin

About 500 gms of Curcuma longa flakes are mixed with about 2500 ml of ethyl acetate containing water (ethyl acetate: water = 95(v): 5(v)) and heated to 65°C. The temperature is maintained for about 2 hours under stirring. The mixture is then cooled to about 50°C and settled for half an hour. The solvent is separated by decantation and the residue is treated with about 1500 ml of the above aqueous ethyl acetate and the above step is repeated. The solvent is separated from the solid. This process of extracting turmeric flakes is repeated two more times with about 2500 ml solvent mixture and the combined solvent mixture extracted is finally distilled under reduced pressure at temperature less than of about 85°C to yield the oleoresin.

Weight of oleoresin obtained = 70 gms.

The curcuminoids are analyzed by HPLC as per USP.

Total curcuminoid content value was 32%.

Example 2: Solvent Extraction of Turmeric (C. longa) and distillation of oleoresin

About 500 gms of Curcuma longa flakes are mixed with about 2500 ml of ethyl acetate: hexane solution (ethyl acetate: Hexane = 95: 5) and heated to about 65°C. The temperature is maintained for about 2 hours under stirring. The mixture is then cooled to about 50°C and settled for half an hour. The solvent is separated by decantation and the residue is treated with about 1500 ml of the above solvent mixture and the above step is repeated. The solvent is separated from the solid. This process of extracting turmeric flakes is repeated two more times with about 2500 ml solvent mixture and the combined solvent mixture extracted is finally distilled under reduced pressure at temperature less than 85°C to yield the oleoresin. Weight of oleoresin obtained = 60 gms.

The curcuminoids are analyzed by HPLC as per USP.

Total curcuminoid content value reported is 36%. Example 3: Solvent Extraction of Turmeric (C. longa) and distillation of oleoresin

About 500 gms of Curcuma longa flakes are mixed with about 2500 ml of ethyl alcohol : water solution (ethyl alcohol : water = 90: 10) and heated to about 70°C. The temperature is maintained for about 2 hours under stirring. The mixture is then cooled to about 50°C and settled for half an hour. The solvent is separated by decantation and the residue is treated with about 1500 ml of the above solvent mixture and the above step is repeated. The solvent is separated from the solid. This process of extracting turmeric flakes is repeated two more times with about 2500 ml solvent mixture and the combined solvent mixture extracted is finally distilled under reduced pressure at temperature less than 85°C to yield the oleoresin.

Weight of oleoresin obtained = 50 gms.

The curcuminoids are analyzed by HPLC as per USP.

Total curcuminoid content value reported is 38%.

Example 4: Obtaining enriched curcuminoid oleoresin

About 100 gm of turmeric oleoresin obtained in Example 1 with curcuminoids content 32% is mixed with about 500 ml hexane, about 70.5 ml isopropanol and about 17.5 ml water and heated to about 65°C under mechanical stirring. The temperature is maintained for about 2 hours and cooled to ambient temperature of about 30°C. The solid is separated by decantation and the residue is analyzed for curcuminoids.

Weight of the curcuminoids = 60 gms.

Curcuminoids content by HPLC = 50%.

Example 5: Obtaining enriched curcuminoid oleoresin

About 100 gm of turmeric oleoresin obtained in Example 2 with curcuminoids content 36% is mixed with about 500 ml hexane, about 70.5 ml isopropanol and about 17.5 ml water and heated to about 65°C under mechanical stirring. The temperature is maintained for about 2 hours and cooled to ambient temperature of about 30°C. The solid is separated by decantation and the residue is analyzed for curcuminoids.

Weight of the curcuminoids = 60 gn

Curcuminoids content by HPLC = 50 Example 6: Obtaining enriched curcuminoid oleoresin

About 100 gm of turmeric oleoresin obtained in Example 1 with curcuminoids content 32% is mixed with about 500 ml heptane, about 70.5 ml isopropanol and about 17.5 ml water and heated to about 65°C under mechanical stirring. The temperature is maintained for about 2 hours and cooled to ambient temperature of about 30°C. The solid is separated by decantation and the residue is analyzed for curcuminoids.

Weight of the curcuminoids = 58 gms.

Curcuminoids content by HPLC = 51%.

Example 7: Obtaining enriched curcuminoid oleoresin

About 100 gm of turmeric oleoresin obtained in Example 3 with curcuminoids content 38% is mixed with about 500 ml hexane, about 113 ml ethanol and about 13 ml water and heated to about 65°C under mechanical stirring. The temperature is maintained for about 2 hours and cooled to ambient temperature of about 30°C. The solid is separated by decantation and the residue is analyzed for curcuminoids.

Weight of the curcuminoids = 60 gms.

Curcuminoids content by HPLC = 50%.

Example 8: Crystallisation and isolation of enriched curcuminoids oleoresin

About 100 gms of turmeric oleoresin with 50% curcuminoids is heated to about 80°C with about 255 ml of isopropanol, about 15 ml hexane and about 30 ml water under mechanical stirring. The temperature is maintained for about 2 hours under the mechanical stirring. The mixture is cooled to about 30°C and stirred for about 6 hours. The mixture is filtered and the residue is washed with about 40 ml of isopropanol two times and dried at 85°C under 700 mm vacuum.

Weight of the product = 35 gms.

Curcuminoids content by HPLC = 95.8%

Curcumin = 78%, Demethoxy curcumin = 15%, bis demethoxy curcumin = 2.8%.

Color value by UV = 15000

Further, the color value in the present examples is determined by UV as follows: Method of analysis for color value determination

0.2gm of powder product is weighed into a 100 ml volumetric flask, and volume is made up with alcohol (95%). 1.00 ml of this solution is pipetted into a second 100 ml flask and volume is made up with alcohol. In presence of a tungsten lamp source and UV visible spectrophotometer, the value is set to zero in spectrophotometer using alcohol as blank. The absorbance of 0.01% solution of oleoresin at the peak maximum is taken, which is approximately 425 nm. This value multiplied by 1000 gives the colour value. If the reading is too high, a 0.005%> solution is used and the absorbance is multiplied by 2000.

Calculation: Color value = Absorbance of 0.01% solution at 425 nm x 1000

Example 9: Crystallization and Isolation of enriched curcuminoid oleoresin

About 100 gms of turmeric oleoresin with 50%> curcuminoids is heated to about 80°C with about 180 ml ethyl acetate and about 120 ml hexane and the temperature is maintained for about one hour under stirring. The mixture is then cooled to about 30°C and stirred for about 5 hours.

The crystallised product is filtered and washed with about 60 ml of the ethyl acetate and hexane mixture two times and dried at about 85°C under reduced pressure of 700 mm Hg.

Weight of the curcuminoids = 25 gms.

Color value by UV = 15000

Total curcuminoids content by HPLC = 96.5%

Curcumin = 79%, Demethoxy curcumin = 15%, bis demethoxy curcumin = 2.5%.

Example 10: Crystallization and Isolation of enriched curcuminoid oleoresin

About 100 gms of turmeric oleoresin with 50% curcuminoids is heated to about 80°C with about 22 ml hexane, 266 ml ethanol and about 26 ml water and the temperature is maintained for about one hour under stirring. The mixture is then cooled to about 30°C and stirred for about 5 hours.

The crystallized product is filtered and washed with about 60 ml of the ethanol and water mixture two times and dried at about 85°C under reduced pressure of 700 mm Hg.

Weight of the curcuminoids Color value by UV = 15000

Total curcuminoids content by HPLC = 96.5%

Curcumin = 79%, Demethoxy curcumin = 15%, bis demethoxy curcumin = 2.5%. Example 11: Obtaining enriched curcuminoid oleoresin

About 100 gm of turmeric oleoresin with curcuminoids content 28% is mixed with 500ml of hexane and ethyl acetate in the ration of 70:30 and heated to about 65°C. The mixture is stirred with mechanical stirrer and the temperature is maintained for about one hour. The mixture is then cooled to about 30°C and stirred for about 4 hours. The mixture is filtered and the wet cake is washed with the hexane and ethyl acetate mixture 100 ml for about two times. The product is dried at temperature below 85°C under reduced pressure.

Weight of the product = 48 gms.

Curcuminoids content by HPLC = 50%

The enrichment content varies with quality of turmeric. Certain quality of turmeric will have less quantity of curcuminoids.

Example 12: Crystallization and Isolation of curcuminoids.

About 100 gms of turmeric oleoresin with 50% curcuminoids is heated to about 80°C with about 300 ml of isopropanol, about 20 ml heptane and about 30 ml water under mechanical stirring. The temperature is maintained for about 2 hours under the mechanical stirring. The mixture is cooled to about 30°C and stirred for about 6 hours. The mixture is filtered and the residue is washed with about 40 ml of isopropanol for about two times and dried at about 85°C under about 700 mm vacuum.

Weight of the product = 34gms

Color value by UV = 15000

Curcuminoids content by HPLC = 95.5%

Curcumin = 77.2%, Demethoxy curcumin = 14.5%, bis demethoxy curcumin = 3.8%

Claims

WE CLAIM:

1. A process for extraction and isolation of curcuminoid from turmeric comprising steps of:

extracting turmeric flakes with a solvent mixture;

distilling the extracted solvent mixture to obtain oleoresin;

extracting the oleoresin with a solvent mixture to obtain enriched curcuminoid oleoresin; and

crystallizing the enriched curcuminoid oleoresin using a solvent mixture to isolate the curcuminoids.

2. The process as claimed in claim 1, wherein the extraction of turmeric flakes is carried out in the presence of solvent mixture selected from a group comprising polar solvent, non-polar solvent and a combination thereof, preferably a mixture of polar solvents or a combination of polar and non-polar solvent.

3. The process as claimed in claim 2, wherein the polar solvent is selected from a group comprising water, ethyl acetate, isopropanol, methyl acetate, methanol and ethanol; and the non-polar solvent is selected from a group comprising hexane and heptane.

4. The process as claimed in claim 2 or claim 3, wherein the solvent extraction of turmeric flakes is performed with a solvent mixture selected from a group comprising ethyl acetate and water; ethyl acetate and hexane; ethyl alcohol and water.

5. The process as claimed in claim 4, wherein the ethyl acetate and water is at a ratio ranging from about 92:8 to about 98:2; preferably 95:5; the ethyl alcohol and water is at a ratio ranging from about 85: 15 to 95:5; preferably 90: 10; the ethyl acetate and hexane is at a ratio 95:5; and the solvent extraction of turmeric flakes is at a temperature ranging from about 60° C to about 85° C, preferably 65° C, for a time period ranging from about 2 hours to about 6 hours, preferably 2 hours.

6. The process as claimed in claim 1, wherein the distillation of extracted solvent is carried out at a temperature ranging from about 70° C to about 90° C, preferably 80° C, for a time period ranging from about 6 hours to about 10 hours, preferably 8 hours, under vacuum.

7. The process as claimed in claim 1, wherein the oleoresin is extracted to obtain enriched curcuminoid oleoresin using solvent mixture selected from a group comprising of polar solvent, non-polar solvent and a combination thereof, preferably a combination of polar and non-polar solvents; wherein the polar solvent is selected from a group comprising water, ethyl acetate, isopropanol, methyl acetate, methanol, ethanol and combinations thereof, and the non-polar solvent is selected from a group comprising hexane, heptane and a combination thereof; and wherein said step is carried out at a temperature ranging from about 50° C to about 80° C, preferably 65° C, for a time period ranging from about 2 hours to about 6 hours, preferably 2 hours.

8. The process as claimed in claim 7, wherein the solvent mixture is a combination selected from a group comprising ethyl acetate and hexane; hexane, isopropyl alcohol and water; heptane, isopropanol and water; hexane, ethanol and water.

9. The process as claimed in claim 8, wherein hexane, isopropyl alcohol and water is at a ratio ranging from about 60:37:3 to about 90:8:2, preferably 85: 12:3; heptane, isopropanol and water is at a ratio of about 85: 12:3; hexane, ethanol and water is at a ratio ranging from about 75:23 :2 to about, 85: 12:3, preferably 80: 18:2; and ethyl acetate, hexane is employed at a ratio ranging from about 30 to about 70.

10. The process as claimed in claim 1, wherein the step of extracting turmeric flakes with a solvent, the step of extracting the oleoresin with a solvent to obtain enriched curcuminoid oleoresin, or a combination thereof is repeated, and said repetition ranges from about one time to about three times.

11. The process as claimed in claim 1, wherein crystallizing the enriched curcuminoid oleoresin to isolate the curcuminoid is carried out using solvent mixture selected from a group comprising polar solvent, non-polar solvent and a combination thereof, preferably a combination of polar and non-polar solvents; and wherein the step is carried out under heating conditions at a temperature ranging from about 70° C to about 85° C, preferably80° C followed by cooling at a temperature ranging from about 25° C to about 35° C, preferably 30° C, for a time period ranging from about 6 hours to about 12 hours, preferably 10 hours, and wherein, the isolated curcuminoid is subjected to filtration, washing, drying and combination of acts thereof.

12. The process as claimed in claim 11, wherein the polar solvent is selected from a group comprising water, ethyl acetate, isopropanol, methyl acetate, methanol, ethanol and combinations thereof; and the non-polar solvent is selected from a group comprising hexane, heptane and a combination thereof.

13. The process as claimed in claim 11 or claim 12, wherein the solvent mixture is a combination selected from a group comprising hexane, isopropyl alcohol and water; ethyl acetate, hexane; heptane, isopropanol and water ; hexane, ethanol and water; and wherein the combination of hexane, isopropyl alcohol and water is at a ratio ranging from about 20:55:25 to about 2:96:2, preferably 5:85: 10; or wherein, ethyl acetate and hexane is at a ratio ranging from about from about 70:30 to 50:50, preferably about 65:35 to about 55:45, more preferably about 60:40; or wherein a combination of heptane, isopropanol and water is at a ratio of about 5:80: 15, preferably about 7:87:6, more preferably about 6:86:8; or wherein, a combination of hexane, ethanol and water are used at a ratio ranging from about 5:80: 15 to 10:85:5, preferably about 7:85:8.

14. The process as claimed in any of claims 1 to 13, wherein said process comprises recycling of solvents.

15. The process as claimed in claim 1, wherein the extraction efficiency of curcuminoids from turmeric ranges from about 98% to about 99.5%; wherein, the recovery of curcuminoid ranges from about 60% to about 70%; wherein, the purity of recovered curcuminoids ranges from 95% to 98%; and wherein the curcuminoid distribution comprises of curcumin ranging from about 75% to about 80%, demethoxy curcumin ranging from about 10% to about 15% and bisdemethoxy curcumin ranging from about 5% to about 10%.