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WO2012023146A1 - Composition pharmaceutique d'extrait de curcuma reformulé et son procédé de préparation - Google Patents

Composition pharmaceutique d'extrait de curcuma reformulé et son procédé de préparation Download PDF

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Publication number
WO2012023146A1
WO2012023146A1 PCT/IN2011/000543 IN2011000543W WO2012023146A1 WO 2012023146 A1 WO2012023146 A1 WO 2012023146A1 IN 2011000543 W IN2011000543 W IN 2011000543W WO 2012023146 A1 WO2012023146 A1 WO 2012023146A1
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Prior art keywords
turmeric
extract
reformulated
hexane
ethanol
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PCT/IN2011/000543
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English (en)
Inventor
Benny Antony
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Benny Antony
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Publication of WO2012023146A1 publication Critical patent/WO2012023146A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/028—Flow sheets
    • B01D11/0284—Multistage extraction
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0288—Applications, solvents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0292—Treatment of the solvent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps

Definitions

  • the present invention relates to a pharmaceutical composition of reformulated turmeric extract comprising curcumin, demethoxycurcumin, bisdemethoxycurcumin, Ar-turmerone and other constituents of essential oil of turmeric which increase the absorption and blood level concentration of curcumin, retention of curcumin in the plasma up to 14 hours and increase the area under curve (AUC) of concentration time plots of curcumin following oral administration, and a method of preparing said pharmaceutical composition.
  • curcumin demethoxycurcumin, bisdemethoxycurcumin, Ar-turmerone and other constituents of essential oil of turmeric which increase the absorption and blood level concentration of curcumin, retention of curcumin in the plasma up to 14 hours and increase the area under curve (AUC) of concentration time plots of curcumin following oral administration
  • Turmeric is the rhizome or underground stem of a ginger-like plant. It is an ancient spice, a native of South East Asia, used from antiquity as dye and a condiment, said to have been originated in the eastern parts of India. Interest in turmeric probably originated as a textile dye, and later as a food colorant and substitute for the costly saffron. Its use dates back nearly 4000 years, to the Vedic culture in India where it was used as a culinary spice and had some religious significance.
  • Ayurveda, Unani, Siddha and Chinese medicine recommend turmeric for a large number of disorders and diseases.
  • Traditional Indian medicine use the turmeric powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorders, rheumatic disorders, sprains and swellings caused by injury and sinusitis.
  • the dried rhizome has been applied to fresh wounds and to insect stings and to help the healing process in chickenpox and smallpox. It is also applied topically for ulcers, wounds, eczema and inflammations.
  • turmeric paste is used topically to treat ulcers and scabies. Since the Ayurvedic times, numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary and gastrointestinal systems, aches, pains, wounds, sprains and liver disorders. Modern research has confirmed and provided a scientific basis for these various health claims, unlike many other traditional medicines. Since the isolation of curcumin as the main active constituent of turmeric about two centuries ago, much of the scientific interest has shifted to this molecule rather than on turmeric.
  • curcumin acts at multiple targets and at multiple levels.
  • the number of transcription factors and signaling pathways modulated by curcumin is, indeed, bewildering 1 ' 2 .
  • curcumin is fast emerging as a cure-all, for valid reasons.
  • Curcumin has demonstrated benefit for most, if not all, chronic diseases afflicting civilization. It is an antioxidant several times more potent than alpha tocopherol and can effectively scavenge oxygen and nitrogen free radicals.
  • Curcumin is a complete anti-inflammatory modulating all the agents involved in the complex process of inflammation including cytokines, chemokines, adhesion molecules, growth factors and transcription factors such as NF-KB and AP-1 and a large number of kinases, notably the MAP kinases p38 and JNK.
  • curcumin can affect all the steps believed to be involved in the pathologic process of atherosclerosis.
  • curcumin can potentially reverse insulin resistance, the first clinically relevant stage of the disease.
  • curcumin can sensitize insulin by inducing the transcription factor PPAR, similar to the thiazolidinediones currently used for the purpose.
  • Turmeric may contain well over a hundred chemical compounds, most of these originating from the essential oil part of turmeric. A complete analysis of all these constituents has not so far been undertaken. However, the major and characteristic components of turmeric are the three curcuminoids and sequiterpenoids. Curcuminoids includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Major sesqiterpenoids include Ar-Turmerone, aTurmerone, . ⁇ -Turmerone, Curcumene, Zingiberene etc.
  • Compounds other than the three curcuminoids are constituents of the volatile oil fraction, the major components of which are the turmerones, notably Ar- turmerone 5 ' 6 ' 7 ' 8 .
  • the yield and composition are apparently influenced by the agro climatic conditions where turmeric is grown and also by the method of extraction 6 ⁇ 7 ' 8,9 .
  • the curcuminoids usually range about 4-5%, but up to 8% has been reported .
  • curcumin has shown cancer chemo preventive, antineoplastic and antiinflammatory properties 10 . Especially interesting is its ability to prevent the formation of carcinogen-induced intestinal premalignant lesions and malignancies in rats' 1 12 and in the multiple neoplasia 13 , a genetic model of the human disease familial adenomatous polyposis. Curcumin acts as a scavenger of oxygen species such as hydroxyl radical, super oxide anion and singlet oxygen 14 15 ' 16 , and interferes with lipid per oxidation 17 ' 18 .Curcumin suppresses a number of key elements in cellular signal induction pathways pertinent to growth, differentiation and malignant transformations.
  • Curcumin directly inhibit the cyclooxygenase-2 and also inhibits the transcription of the gene responsible for its production.
  • Cyclooxygenases COX catalyze the synthesis of prostaglandins (PGs) from arachidonic acid.
  • Curcumin is among the few agents to block both the COX and LOX (lipoxygenase) pathways of inflammation and carcinogenesis by directly modulating arachidonic acid metabolism.
  • COX Cyclooxygenases
  • LOX lipoxygenase
  • curcumin demonstrates poor levels in blood after oral dosing 21 which may be related to its inadequate absorption and fast metabolism. Curcumin absorption and retention may also be poor in humans as seen from the results of a recent pilot study of a standardized turmeric extract in colorectal cancer patients 22 . Indirect evidence suggests that curcumin is metabolized in the intestinal tract. It has been suggested that the intestinal tract plays an important role in the metabolic disposition of curcumin.
  • Intestinal mucosa as well as liver and kidney tissue from the rat can glucuronidate and sulfate curcumin, as judged by the analysis of differential amounts of curcumin present before and after treatment of tissue extracts with conjugate-hydrolyzing enzymes 23 .
  • gut metabolism contributes substantially to the overall metabolic yield generated from curcumin in vivo.
  • Curcumin when given orally or intraperitoneally to rats is mostly excreted in the feces and only a little in the urine. Only traces of curcumin are found in the blood from the heart, liver and kidney. Curcumin, when added to isolated hepatocytes is quickly metabolized and the major biliary metabolites are glucuronides of tetrahydrocurcumin and hexahydrocurcumin. Curcumin, after metabolism in the liver, is mainly excreted through bile.
  • curcumin was given at doses of 0.45 and 3.6 g daily for four months. Only in patients taking 3.6gm per day, curcumin was detected from plasma and it was only at a single time point showing 1 1 .1 ⁇ 0.6 nmol/L. Curcumin was not detected in the plasma of patients taking lower doses 2S .
  • oral administration of 440 to 2200 mg curcuma extract per day corresponding to 36 to 180 mg curcumin failed to get curcumin or its metabolites detected in plasma or urine even after 29 days 26 .
  • curcumin must be absorbed from its oral route of administration at a suitable rate, be distributed in adequate concentration in the blood and remain in the system for a sufficient period at an effective concentration level.
  • One measure of drug absorption is its blood serum concentration at various time intervals after administration.
  • curcumin Certain drugs have a correlation between blood serum concentration and the presence of drug effects.
  • the mere administration of curcumin does not bring about its medicinal properties, rather it has to be absorbed and present in the blood and retained in detectable amounts.
  • a recent study in rats by 26 showed that, up-regulation of Glutathione S Transferase activity in the liver and decrease of MiG levels in colon mucosa after oral administration of curcumin were accompanied by measurable tissue levels of curcumin. It is conceivable that higher doses of curcumin, which furnish measurable plasma curcumin concentrations, are required to elicit a therapeutic effect in vivo.
  • Drug concentrations in the blood can be determined and graphed against time to obtain a drug blood level curve.
  • the time course of a drug's concentration in the plasma correlates well with the onset, intensity and duration of the pharmacologic effect.
  • the measurement of sequential plasma concentration of drugs after their administration is used to establish dosage regimens that are likely to produce the desired therapeutic levels for appropriate period of time, without the risk of drug failure or toxicity.
  • a drug When a drug is administered by an oral route, it usually appears in the plasma within a short time, and its concentration rises steadily until it peaks. Once absorbed into the circulation, it is subjected simultaneously to distribution, biotransformation, and excretion. During the initial period, the rate of absorption and distribution exceeds the rate of elimination (positive slope of the curve). The peak plasma concentration is reached when absorption and elimination rates are equal (C max ). Thereafter, the elimination rate exceeds the rate of absorption because fewer drugs remain available at the site of administration and plasma drug levels begin to fall (negative slope of the curve). So the rate and extent of absorption of a drug, usually from the GI tract after administration by oral route is very important.
  • FIG 2 provides a comparative graph of curcumin content in blood (nM/L) following administration of reformulated turmeric extract, regular turmeric extract powder, raw turmeric powder,essential oil of turmeric having 10-15% Ar-turmerone, curcuminoid mxture alone, ethanol extract concentrate of oleoresin or ethanol extract concentrate of essential oil of turmeric.
  • One embodiment provides a reformulated turmeric extract having a 1 : 1 ratio of ethanol extract concentrate of oleoresin and ethanol extract concentrate of essential oil.
  • the ethanol extract concentrate of oleoresin includes curcumin, demethoxycurcumin and bisdemethoxycurcumin.
  • the ethanol extract concentrate of essential oil includes essential oil of turmeric having of Ar-turmerone.
  • An embodiment of the present invention provides a pharmaceutical composition of reformulated turmeric extract wherein, the curcumin content ranges, by weight, from about 290 mg to about 375 mg; demethoxy. curcumin content ranges, by weight, from about 84 mg to about 125 mg; bisdemethoxy curcumin content ranges, by weight, from about 8 mg to about 40 mg; Ar-turmerone content ranges, by weight, from about 16 mg to about 33 mg; and other sesqiterpenoids of essential oil of turmeric content ranges, by weight, from about 13 mg to about 30 mg.
  • An embodiment of the present invention discloses a pharmaceutical composition of reformulated turmeric extract wherein, the peak blood curcumin level, Cmax of the reformulated turmeric composition is 3-14 fold higher compared to regular turmeric extract capsules containing 95% curcuminoid.
  • An embodiment of the present invention discloses a pharmaceutical composition of reformulated turmeric extract wherein, the absorption of curcumin from the disclosed composition is 60- 98% compared to regular turmeric extract capsules.
  • An embodiment of the present invention discloses a pharmaceutical composition of reformulated turmeric extract wherein, curcumin is retained in the blood after oral administration of a reformulated turmeric extract up to 14 hours post drug compared to regular turmeric extract capsules.
  • an embodiment of the present invention discloses a pharmaceutical composition of reformulated turmeric extract wherein, the AUC of curcumin from reformulated turmeric extract is 3-14 times greater than from composition of regular turmeric extract capsules.
  • the ethanol extract concentrate of oleoresin is prepared by the process including powdering dried rhizomes of turmeric to form turmeric powder.
  • the turmeric powder is extracted with n-hexane by adding n-hexane to the turmeric powder in a ratio of 4: 1 of n-hexane to turmeric powder to obtain a first residue and n-hexane extract.
  • the first residue and the n-hexane extract are separated.
  • the first residue is dried to obtain a second dried residue.
  • the second dried residue is extracted with ethanol to obtain an ethanol extract and a third residue.
  • the ethanol extract is concentrated to obtain the ethanol extract concentrate of oleoresin.
  • the ethanol extract concentrate of essential oil is prepared by the process including powdering dried rhizomes of turmeric to form turmeric powder.
  • the turmeric powder is extracted with n-hexane by adding n-hexane to the turmeric powder in a ratio of 4: 1 of n-hexane to turmeric powder to obtain a residue and n-hexane extract.
  • the residue and the n-hexane extract are separated.
  • the n-hexane extract is concentrated to form a concentrated hexane extract.
  • the concentrated hexane extract is mixed with ethanol in the presence of silica to obtain an ethanol extract.
  • the ethanol extract is concentrated to obtain the ethanol extract concentrate of essential oil.
  • One embodiment discloses a method of preparing a reformulated turmeric extract comprising a 1 : 1 ratio of ethanol extract concentrate of oleoresin and ethanol extract concentrate of essential oil.
  • the method discloses mixing the ethanol extract concentrate of oleOresin and the ethanol extract concentrate of essential oil in a 1 : 1 ratio to obtain a blend. Ethanol is added to the blend in 2: 1 ratio and kept for 4 days at 27°C to obtain a residue and a filtrate. The resulting residue and the filtrate are separated. The residue is dried and powdered to obtain the reformulated turmeric extract.
  • An embodiment of the present invention discloses a method of preparing a reformulated turmeric extract wherein, the peak blood curcumin levels Cmax of the reformulated composition was 3-14 fold higher compared to regular turmeric extract capsules.
  • An embodiment of the present invention discloses a method of preparing a reformulated turmeric extract wherein, the absorption of curcumin from the disclosed composition is 60- 98% compared to regular turmeric extract capsules.
  • An embodiment of the present invention discloses a method of preparing a capsule containing the above composition for oral administration to mammals, especially humans.
  • An embodiment of the present invention relates to a pharmaceutical composition of reformulated turmeric extract to increase the absorption and blood level concentration of curcumin, retention of curcumin in the plasma up to 14 hours and increase the area under curve (AUC) of concentration time plots of curcumin comprising of curcumin, demethoxycurcumin, bisdemethoxycurcumin, Ar turmerone and other components of essential oil of turmeric.
  • AUC area under curve
  • reformulated turmeric extract is a mixture of curcumin, demethoxycurcumin, bisdemethoxy curcumin, Ar-turmerone and other components of essential oil of turmeric.
  • essential oil of turmeric is also referred to as “volatile oil” or “volatile oil of turmeric.”
  • volatile oil is also referred to as “volatile oil” or “volatile oil of turmeric.”
  • other constituents of essential oil of turmeric includes sesquiterpenoids
  • the reformulated turmeric extract of the preferred embodiment of the present invention is made from turmeric by a process comprising of: Dried rhizomes of turmeric is powdered in a pulverisor to obtain turmeric powder. " Next n-hexane in the amount of four times the quantity of turmeric powder is added to the turmeric powder for hexane extraction. The extraction is performed using an extractor with reflux condenser. The bottom of the extractor is fitted with a polypropylene (100 microns) filter cloth. The mixture is refluxed at the boiling temperature (50-70°C) of hexane for one hour to obtain a residue (Yield 92.5% and moisture content 6%) and a hexane extract (yield 6%).
  • the residue is further extracted two more times with four times the quantity of n-hexane.
  • the residue and hexane extracts are separated by draining out the hexane extract from the extractor bottom through the polypropylene filter cloth using a centrifugal pump.
  • the residue is dried in a rotary vacuum drier.
  • the dried residue is extracted with 3 times the quantity of ethanol.
  • the ethanol extraction of the residue is performed at 60-70 °C temperature for 1 hour using an extractor with reflux condenser.
  • the extractor is fitted with polypropylene (100 microns) filter cloth at the bottom of extractor to separate the ethanol extract and the residue.
  • the ethanol extract is concentrated at 60-70°C under vacuum (550mm Hg) to form ethanol extract concentrate containing Oleoresin (yield 20%).
  • the oleoresin includes curcuminoids.
  • the hexane extract is concentrated at 50-70°C under vacuum (500mm Hg) to form concentrated hexane extract.
  • 2 times the quantity of silica 200-400mesh size is mixed with the concentrated hexane extract in a sigma mixer for one hour and is refluxed with 2 times the quantity of 90% ethanol for 1 hour by using extractor with reflux condenser and fitted with polypropylene (l OOmicrons) filter cloth at the bottom of extractor.
  • Silica is removed by draining out the ethanol extract from the extractor bottom through the polypropylene filter cloth using a centrifugal pump.
  • the ethanol extract is concentrated at 60-70°C under vacuum (550mm Hg) to form ethanol extract concentrate (yield 10%).
  • the ethanol extract concentrate includes the essential oil of turmeric. " Next, a 1 : 1 ratio of ethanol extract concentrate of oleoresin and ethanol extract concentrate of essential oil is blended in a double cone blender to obtain blend. Then, ethanol is added to the blend at a ratio of 2: 1 of the ethanol to the blend to obtain a mixture. The mixture is kept for 4 days in a stainless steel (SS-316) holding vessel with conical bottom with jacket for circulating cooling water at 27°C.
  • SS-316 stainless steel
  • the mixture is transferred to a plate & frame filter press by using a stainless steel screw pump. This transfer separates the mixture into a residue (yield 4%) and a filtrate.
  • the filtrate has the resin and fat.
  • the residue is dried by using rotary vacuum drier (700mm Hg) to obtain a dried residue.
  • the dried residue is powdered in a pulverisor to form a fine powder of reformulated turmeric extract containing of curcumin, demethoxycurcumin, bisdemethoxycurcumin, Ar turmerone and other components of essential oil of turmeric.
  • One embodiment provides a reformulated turmeric extract having a 1 : 1 ratio of ethanol extract concentrate of oleoresin and ethanol extract concentrate of essential oil.
  • the ethanol extract concentrate of oleoresin includes curcumin, demethoxycurcumin and bisdemethoxycurcumin.
  • the ethanol extract concentrate of essential oil includes essential oil of turmeric having of Ar-turmerone.
  • An embodiment of the present invention provides a composition of reformulated turmeric extract which when given orally, significantly increase the absorption and blood level concentration of curcumin, retention of curcumin in the plasma up to 14 hours and increase the area under curve (AUC) of concentration time plots of curcumin.
  • Another embodiment of the present invention provides a method of preparing the reformulated turmeric extract which when given orally, significantly increase the absorption and blood level concentration of curcumin, retention of curcumin in the plasma up to 14 hours and increase the area under curve (AUC) of concentration time plots of curcumin.
  • composition of a reformulated turmeric extract wherein, the curcumin content ranges, by weight, from about 290 mg to about 375mg, demethoxy curcumin content ranges, by weight, from about 60 mg to about 125 mg bisdemethoxy curcumin content ranges, by weight, from about 8 mg to about 40 mg, Ar- turmerone content ranges, by weight, from about 6 mg to about 36 mg and other sesqiterpenoids of essential oil of turmeric content ranges, by weight, from about 10 mg to about 30 mg
  • the composition of reformulated turmeric extracts the curcumin ranges, by weight, from about 325 mg to about 360 mg.
  • the demethoxycurcumin ranges, by weight, from about 84 mg to about 93 mg.
  • the bisdemethoxy curcumin ranges, by weight, from about 9 mg to about 40 mg.
  • the Ar turmerone ranges, by weight, from about 16 mg to about 33 mg and other sesqiterpenoids of essential oil of turmeric content ranges, by weight, from about 13 mg to about 25 mg.
  • curcumin ranges from about 58 % to about 75 %. In some embodiments of the reformulated turmeric extract, demethoxycurcumin ranges from about 12 % to about 25 %. In some embodiments of the reformulated turmeric extract, bisdemethoxycurcumin ranges from about 1 .6 % to about 8 %. In some embodiments, of the reformulated turmeric extract Ar-turmerone ranges from about 1.2 % to about 7.2 %. In some embodiments of the reformulated turmeric extract, curcumin ranges from about 290 mg to about 375 mg. In some embodiments of the reformulated turmeric extract, demethoxycurcumin ranges from about 60 mg to about 125 mg. In some embodiments of the reformulated turmeric extract, bisdemethoxycurcumin ranges from about 8 mg to about 40 mg. In some embodiments of the reformulated turmeric extract of claim 1 , Ar-turmerone ranges from about 6 mg to about 36 mg.
  • curcuminoids Ar- turmerone and other sesqiterpenoids of essential oil of turmeric.
  • Curcumin 60.4% demethoxycurcumin 22.6%, bisdemethoxycurcumin 7.7%,Ar- turmerone 4.2% and other sesqiterpenoids of essential oil of turmeric 4.9 %.
  • the present invention is the optimal composition among different composition, which showed maximum absorption of curcumin, increase the blood level concentration of curcumin, retention of curcumin in the plasma up to 14 hours and increase the area under curve (AUC).
  • absorption of curcumin from the reformulated turmeric extract composition ranges from 60% to 98%. In one embodiment of the present invention, the increases in the blood level concentration of curcumin from the reformulated turmeric extract ranges from 3 times to 14 times.
  • oral administration of the reformulated turmeric extract resulted in about a 10-fold increase in blood level of curcumin compared to oral administration of regular turmeric extract.
  • the regular turmeric extract includes curcumin, demethoxycurcumin and bisdemethoxycurcumin.
  • oral administration of the reformulated turmeric extract resulted in retention of curcumin in blood for 10 hours.
  • the retention of curcumin from the reformulated turmeric extract in blood ranges from 5 hrs to 14hrs.
  • Reformulated turmeric extract pharmaceutical composition is encapsulated into hard gelatin capsules.
  • the disclosure provides a method of preparing a hard gelatin capsule with the composition. Dried rhizomes of turmeric are powdered in a pulverisor to obtain turmeric powder. Next n-hexane in the amount of four times the quantity of turmeric powder was added to the turmeric powder for hexane extraction. The extraction is performed using an extractor with reflux condenser. The bottom of the extractor is fitted with a polypropylene (100 microns) filter cloth. The mixture was refJuxed at the boiling temperature (50-70°C) of hexane for one hour to obtain a residue and a hexane extract.
  • the residue is further extracted two more times with four times the quantity of n-hexane.
  • the residue and hexane extracts are separated by draining out the hexane extract from the extractor bottom through the polypropylene filter cloth using a centrifugal pump.
  • the residue is dried in a rotary vacuum drier.
  • the dried residue is extracted with 3 times the quantity of ethanol.
  • the ethanol extraction of the residue is performed at 60-70 °C temperature for 1 hour using an extractor with reflux condenser.
  • the extractor is fitted with polypropylene (100 microns) filter cloth at the bottom of extractor to separate the ethanol extract and the residue.
  • the ethanol extract is concentrated at 60-70°C under vacuum (550mm Hg) to form ethanol extract concentrate containing Oleoresin
  • the oleo resin includes curcuminoids.
  • the hexane extract is concentrated at 50-70°C under vacuum (500mm Hg) to form concentrated hexane extract. Then 2 times the quantity of silica (200-400mesh size) is mixed with the concentrated hexane extract in a sigma mixer for one hour and is refluxed with 2 times the quantity of 90% ethanol for 1 hour by using extractor with reflux condenser and fitted with polypropylene (l OOmicrons) filter cloth at the bottom of extractor. Silica is removed by draining out the ethanol extract from the extractor bottom through the polypropylene filter cloth using a centrifugal pump. The ethanol extract is concentrated at 60-70°C under vacuum (550mm Hg) to form ethanol extract concentrate.
  • the ethanol extract concentrate includes the essential oil of turmeric.
  • a 1 : 1 ratio of ethanol extract concentrate of oleoresin and ethanol extract concentrate of essential oil are blended in a double cone blender to obtain blend.
  • ethanol is added to the blend at a ratio of 2: 1 of the ethanol to the blend to obtain a mixture.
  • the mixture is kept for 4 days in a stainless steel (SS-316) holding vessel with conical bottom with jacket for circulating cooling water at 27°C. After 4 days, the mixture is transferred to a plate & frame filter press by using a stainless steel screw pump. This transfer separates the mixture into a residue and a filtrate.
  • the filtrate has the resin and fat.
  • the residue is dried by using rotary vacuum drier (700mm Hg) to obtain a dried residue.
  • the dried residue is powdered in a pulverisor to form a fine powder of reformulated turmeric extract.
  • the powder is charged into a hopper of a semiautomatic capsule filling machine in an air-conditioned and de-humidified room.
  • a '0' size hard gelatin capsule shell is loaded into the tray of the capsule filling machine.
  • the powder of the reformulated turmeric extract is filled into the capsule shell and is compressed into hard gelatin capsule shell of '0' size.
  • the filled capsules are sorted by a sorting machine and polished with the help of a polishing machine to obtain the reformulated turmeric extract in capsule form.
  • the ethanol extract concentrate of oleoresin is prepared by the process including powdering dried rhizomes of turmeric to form turmeric powder.
  • the turmeric powder is extracted with n-hexane by adding n-hexane to the turmeric powder in a ratio of 4: 1 of n-hexane to turmeric powder to obtain a first residue and n-hexane extract.
  • the first residue and the n-hexane extract are separated.
  • the first residue is dried to obtain a second dried residue.
  • the second dried residue is extracted with ethanol to obtain an ethanol extract and a third residue.
  • the ethanol extract is concentrated to obtain the ethanol extract concentrate of oleoresin.
  • the ethanol extract concentrate of essential oil is prepared by the process including powdering dried rhizomes of turmeric to form turmeric powder.
  • the turmeric powder is extracted with n-hexane by adding n-hexane to the turmeric powder in a ratio of 4: 1 of n-hexane to turmeric powder to obtain a residue and n-hexane extract.
  • the residue and the n-hexane extract are separated.
  • the n-hexane extract is concentrated to form a concentrated hexane extract.
  • the hexane extract is mixed with ethanol in the presence of silica to obtain an ethanol extract.
  • the ethanol extract is concentrated to obtain the ethanol extract concentrate of essential oil.
  • One embodiment discloses a method of preparing a reformulated turmeric extract comprising a 1 : 1 ratio of ethanol extract concentrate of oleoresin and ethanol extract concentrate of essential oil.
  • the method discloses mixing the ethanol extract concentrate of oleoresin and the ethanol extract concentrate of essential oil in a 1 : 1 ratio to obtain a blend.
  • Ethanol is added to the blend in 2: 1 ratio and kept for 4 days at 27°C to obtain a residue and a filtrate.
  • the residue and the filtrate are separated.
  • the residue is dried and powdered the residue to obtain the reformulated turmeric extract.
  • One embodiment provides a method of increasing absorption of curcumin in blood by administering the reformulated turmeric extract.
  • One embodiment provides a method of increasing blood level concentration of curcumin by administering the reformulated turmeric extract.
  • One embodiment provides a method of increasing the retention time of curcumin in blood by administering the reformulated turmeric extract.
  • One embodiment provides a method of increasing the area under the curve of curcumin in blood by administering the reformulated turmeric extract.
  • the disclosed pharmaceutical composition of reformulated turmeric extract can be used for attaining a therapeutically significant level of curcumin in the human body for the treatment of various disease conditions.
  • the residue and hexane extract were separated by draining out the hexane extract from the extractor bottom through the polypropylene filter cloth using a centrifugal pump. After first extraction, the residue was further extracted two more times with four times the quantity of n-hexane. The residue was dried by rotary vacuum drier to obtain 231 Kg dried material. The dried residue was extracted with 3 times the quantity of ethanol. The ethanol extraction of the residue was performed at 60-70 °C temperature for 1 hour using an extractor with reflux condenser. The extractor was fitted with polypropylene (100 microns) filter cloth at the bottom of extractor to separate the ethanol extract and the residue.
  • the ethanol extract was concentrated at 60-70°C under vacuum (550mm Hg) to form ethanol extract concentrate containing Oleoresin (46 Kg).
  • the oleo resin includes curcuminoids.
  • the hexane extract was concentrated at 50-70°C under vacuum (500mm Hg) to form concentrated hexane extract 15Kg.
  • Silica 30Kg (200-400mesh size) was mixed with the concentrated hexane extract (1 Kg) in a Sigma Mixer-l OOkg (GMP) (manufacturer: Pharma fab industries, Mumbai, volume capacity: 300LTS, Working capacity: lOOKg) for One hour and the mixture was extracted with 30L 90% ethanol for 1 hour by using extractor with reflux condenser and fitted with polypropylene (l OOmicrons) filter cloth of bottom of extractor.
  • the silica was separated from the ethanol extract by draining out the ethanol extract from the extractor bottom through polypropylene filter cloth using a centrifugal pump.
  • the ethanol extract was concentrated at 60-70°C under vacuum (550mm Hg) to form ethanol extract concentrate containing essential oil of turmeric (1 .5 Kg).
  • the ethanol extract concentrate containing oleoresin and ethanol extract concentrate containing essential oil of turmeric was blended in 1 : 1 ratio (1.5 Kg Ethanol extract concentrate of essential oil and 1 .5 Kg ethanol extract concentrate of Oleoresin) by using Double Cone Blender (stainless steel SS-31 6, capacity 2000 litre, manufacturer: Zebra Pharma, Mumbai) for 1 hour. Ethanol (2: 1 ) was added to the blend and kept at 27° for four days.
  • 500mg of the reformulated turmeric extract powder had a curcumin content of 31 8 mg, demethoxycurcumin content of 104 mg, bisdemethoxycurcumin content of 32mg, Ar-turmerone content in the composition was 21 mg and other sesqiterpenoids of the essential oil in the composition was 25mg.
  • a 500 mg capsule containing reformulated turmeric extract was prepared by encapsulating the reformulated turmeric extract powder from Example 1 into hard gelatin capsules. The encapsulation was done in a 21 °C air-conditioned and de- humidified room. 0.1 kg of powdered reformulated turmeric extract was charged into the hopper of a semi- automatic capsule filling machine. '0' size hard gelatin capsule shell was loaded to the tray and the powder was filled into the shell. The filled weight of capsules was checked simultaneously and these capsules were sorted by a sorting machine and polished with the help of a polishing machine to obtain 200 capsules of 500 mg of reformulated turmeric extract powder per capsule.
  • the rhizomes of turmeric (300Kg) were dried.
  • the dried turmeric rhizomes were powdered to form powdered turmeric.
  • the powdered turmeric was treated with ethyl acetate (900 L) to form a solution.
  • the extraction was carried out at 78°C temperature for 1 hr. After initial extraction, the extraction process was repeated 4 more times and the resultant solution was filtered and the solvent was stripped from the filtered solution to form an extract.
  • This extract was cooled to about 4° C to obtain crystals of curcuminoid (12Kg) and a liquid.
  • the crystals of curcuminoid were isolated from the liquid by filtration.
  • the crystals were powdered to form powdered curcuminoid mixture having 95% curcuminoids.
  • the powdered curcuminoid mixture was referred to as regular turmeric extract.
  • a 500 mg capsule containing regular turmeric extract was prepared by encapsulating the powdered curcuminoid mixture having 95% curcuminoids from Example 3 into hard gelatin capsules. The encapsulation was done in a 21 °C air-conditioned and dehumidified room. 3kg of powdered curcuminoid mixture having 95% curcuminoids was charged into the hopper of a semi- automatic capsule filling machine. '0' size hard gelatin capsule shell was loaded to the tray and the powder was filled into the shell. The filled weight of capsules was checked simultaneously and these capsules were sorted by a sorting machine and polished with the help of a polishing machine to obtain 6000 capsules of 500 mg each.
  • the raw turmeric rhizomes (l OKg) were collected and cleaned. The rhizomes were dried and pulverized to get turmeric powder (2.5Kg). The turmeric powder was sieved through 20 meshes to obtain the raw turmeric powder. The raw turmeric powder had 5% curcuminoids
  • a 500 mg capsule with raw turmeric powder (curcuminoids 5%) was prepared by encapsulating the raw turmeric powder from Example 5 into hard gelatin capsules. The encapsulation was done in an air-conditioned (21 °C) and de- humidified room. 2.5 kg of raw turmeric powder was charged into the hopper of a semi- automatic capsule filling machine. '0' size hard gelatin capsule shell was loaded to the tray and the raw turmeric powder was filled into the shell. The filled weight of capsules were checked simultaneously and these capsules were sorted by a sorting machine and polished with the help of a polishing machine to obtain 5000 capsules of 500 mg of raw turmeric powder per capsule.
  • the rhizomes of turmeric (50Kg) were dried.
  • the dried turmeric rhizomes were powdered to form powdered turmeric.
  • the powdered turmeric was treated with ethyl acetate (1 0 L) to form a solution.
  • the extraction was carried out at 78°C temperature for 1 hr. After initial extraction, the extraction process was repeated 4 more times on the powdered turmeric and the resultant solution was filtered.
  • the solvent was stripped from the filtered solution to form an extract.
  • This extract was cooled to about 4° C to obtain crystals of curcuminoid mixture (2Kg) and a liquid.
  • the crystals of curcuminoid mixture were isolated from the liquid by filtration.
  • the filtered liquid had essential oil of turmeric and a resin.
  • the filtered liquid was then steam distilled to obtain 2.5 Kg of essentia] oil of turmeric.
  • the essential oil of turmeric had 10- 1 %Ar- turmerone.
  • a 500 mg capsule with essential oil of turmeric containing 10-15% Ar- turmerone was prepared by encapsulating the essential oil of turmeric from Example 7 in soft gelatin capsules. The encapsulation was done in an air-conditioned (24°C) and relative humidity 40-60%. 2.5 kg essential oil of turmeric having 10-15 % Ar-turmerone was charged into the hopper of a semi- automatic capsule filling machine. '0' size soft gelatin capsule shell was loaded to the tray and the blended extract powder was filled into the shell. The filled weight of capsules was checked simultaneously and these capsules were sorted by a sorting machine and polished with the help of a polishing machine to obtain 5000 capsules of 500 mg essential oil of turmeric per capsule.
  • the rhizomes of turmeric (300Kg) were dried.
  • the dried turmeric rhizomes were powdered to form powdered turmeric.
  • the powdered turmeric was treated with ethyl acetate (900 L) to form a solution.
  • the extraction was carried out at 78°C temperature for 1 hr. After initial extraction, the extraction process was repeated 4 more times and the resultant solution was filtered and the solvent was stripped from the filtered solution to form an extract.
  • This extract was cooled to about 4° C to obtain crystals of curcuminoid mixture (12Kg) and a liquid.
  • the crystals of curcuminoid mixture were isolated from the liquid by filtration.
  • the crystals obtained were recrystallised in ethanol.
  • the turmeric rhizomes (500Kg) were dried to obtain 125Kg and powdered by using pulverisor (stainless steel SS-304).
  • the powdered turmeric of 10-20 mesh 125Kg was extracted with four times with 500L of n-hexane.
  • the extraction was carried out by refluxing at boiling temperatures of hexane of about 50° C to 70°C for one hour to obtain residue 1 15 Kg and hexane extract 7.5Kg.
  • the residue and hexane extract were separated. After first extraction, the residue was further extracted two more times with four times the quantity of n-hexane.
  • the residue was dried by rotary vacuum drier to obtain 1 15 Kg dried material.
  • the dried residue was extracted with 3 times the quantity of ethanol.
  • a 500 mg capsule containing ethanol extract concentrate of Oleoresin was prepared by encapsulating the powdered ethanol extract concentrate of Oleoresin having 94% curcuminoids from Example 1 1 into hard gelatin capsules. The encapsulation was done in a 21 °C air-conditioned and de- humidified room. 3 kg of powdered ethanol extract concentrate of Oleoresin having 94% curcuminoids was charged into the hopper of a semi- automatic capsule filling machine. '0' size hard gelatin capsule shell was loaded to the tray and the powder was filled into the shell. The filled weight of capsules was checked simultaneously and these capsules were sorted by a sorting machine and polished with the help of a polishing machine to obtain 6000 capsules of 500 mg each.
  • the turmeric rhizomes (l OOOKg) were dried to obtain 250Kg and powdered by using pulverisor (stainless steel SS-304).
  • the powdered turmeric of 10-20 mesh 250Kg was extracted with four times with 1000L of n-hexane.
  • the extraction was carried out by refluxing at boiling temperatures of hexane of about 50° C to 70°C for one hour to obtain residue 231 Kg and hexane extract 15Kg.
  • the residue and hexane extract were separated. After first extraction, the residue was further extracted two more times with four times the quantity of n-hexane.
  • the hexane extract was concentrated at 50-70°C under vacuum (500mm Hg) to form concentrated hexane extract 15Kg.
  • Silica 30Kg 200-400mesh size
  • GMP Sigma Mixer-l OOkg
  • the silica was separated from the ethanol extract by draining out the ethanol extract from the extractor bottom through polypropylene filter cloth using a centrifugal pump.
  • the ethanol extract was concentrated at 60-70°C under vacuum (550mm Hg) to form ethanol extract concentrate containing essential oil (1 .5 Kg).
  • a 500 mg capsule containing ethanol extract concentrate of essential oil of turmeric was prepared by encapsulating the powdered ethanol extract concentrate of essential oil of turmeric from Example 13 into soft gelatin capsules. The encapsulation was done in an air-conditioned (24°C) and relative humidity 40-60%. 1 kg ethanol extract concentrate of essential oil of turmeric was charged into the hopper of a semi- automatic capsule filling machine. '0' size soft gelatin capsule shell was loaded to the tray and the blended extract powder was filled into the shell. The filled weight of capsules was checked simultaneously and these capsules were sorted by a sorting machine and polished with the help of a polishing machine to obtain 2000 capsules of 500 mg essential oil of turmeric per capsule.
  • Albino rats weighing 150 - 200 gm of both sexes were used for the study.
  • the rats were kept individually in polypropylene cages and maintained in well ventilated room under normal and uniform conditions like 12 hours light and dark cycle and at 26 + 2°C. Water and feed were given ad-libitum.
  • the animals were divided into 8 groups and 3 animals were used for each group. The animals were divided as shown in table 1.
  • Table 1 Segregation of rats for experimental study.
  • turmeric extract having Curcumin 63.6%(318mg), Demethoxycurcumin 20.8%(104mg), Bisdemethoxy Curcumin 6.4%(32mg), Ar-turmerone 4.2% (21mg) and other sesqiterpenoids of essential oil of turmeric 5% (25mg) (compound 2) was solubilized in DMSO and fed.
  • Raw turmeric powder with 5% curcuminoids of which Curcumin 2.5% (12.5 mg), Demethoxycurcumin 1.6% (8mg)and bisdemethoxycurcuminO.9% (4.5mg) (compound 3) was mixed with DMSO and fed to group 4 animals.
  • curcuminoid mixture having 97% curcuminoid mixture of which curcumin 75% (375mg), Demethoxy curcumin 17.2% (86mg) and Bisdemethoxycurcumin 4.8% (24mg) (compound 4) solubilized in DMSO was given.
  • essential oil of turmeric with 10- 15% Ar-turmerone (compound 5) in DMSO was given.
  • ethanol extract concentrate of oleoresin having 94%curcuminoid mixture of which curcumin 72.3% (361.5mg), Demethoxy curcumin 17.2% ( 86mg) and Bisdemethoxy curcumin4.5% (22.5mg) (compound 6) solubilized in DMSO was given.
  • ethanol extract concentrate of essential oil of turmeric (compound 7) solubilized in DMSO was fed.
  • the animals were able to access drinking water freely.
  • the study drugs were given by oral route.
  • Two hours post drug the blood was collected for analysis of curcumin levels in the blood by HPLC method.
  • the blood was extracted exhaustively with ethyl acetate to recover curcumin.
  • the ethyl acetate extract was analyzed by HPLC on a RP-C18 column (25x4.5mm) using methanol as solvent and UV detection at 420nm.
  • the eluent flow rate was lml/min.
  • Fig: 1 shows the results of blood levels of curcumin in albino rats.
  • Fig. 1 The results as shown in Fig. 1 indicates that the level of curcumin in the blood was higher in albino rats fed with reformulated turmeric extract compared to rats fed with regular turmeric, curcuminoid mixture alone and ethanol extract concentrate of oleoresin.
  • the blood level concentration of curcumin was very low for animals fed with raw turmeric powder.
  • the curcumin content in the blood in animals fed with essential oil of turmeric with 10 -15% Ar-turmerone and ethanol extract concentrate of essential oil of turmeric were not detectable.
  • Albino rats weighing 150 - 200 gm of both sexes were used for the study.
  • the rats were kept individually in polypropylene cages and maintained in well ventilated room under normal and uniform conditions like 12 hours light and dark cycle and at 26 + 2°C. Water and feed were given ad-libitum.
  • the animals were divided into 8 groups and 2 animals were used for each group. The animals were divided as shown in table 2.
  • Ethanol extract concentrate of essential oil of turmeric prepared as per example 13 in DMSO.
  • Group 1 animals consisted of animals which were given vehicle, DMSO. Regular turmeric extract with 95% curcuminoids of which curcumin 73%(365 mg),Demethoxy curcumin 16.2%(81 mg) and Bisdemethoxy curcumin 5.8%(29 mg)(compound 1 ) was solubilized in DMSO and fed to group 2 animals as shown in table 2. This was the curcumin control.
  • turmeric extract with having Curcumin 63.6%(31 8mg),demethoxycurcumin 20.8%(104mg),Bisdemethoxy Curcumin 6.4%(32mg),Ar-turmerone 4.2%(21 mg) and other sesqiterpenoids of essential oil of turmeric 5%(25mg) (compound 2) was solubilized in DMSO and fed.
  • Raw turmeric powder with 5% curcuminoids of which Curcumin 2.5%(12.5mg), Demethoxycurcuminl .6%(8mg) and Bisdemethoxycurcumin 0.9% (4.5mg)(compound 3) was mixed with DMSO and fed to group 4 animals.
  • curcuminoid mixture having 97% curcuminoid mixture of which curcumin 75% (375mg), Demethoxycurcumin 17.2% (86mg) and Bisdemethoxycurcumin 4.8% (24mg) (compound 4) solubilized in DMSO was given.
  • curcumin 75% 375mg
  • Demethoxycurcumin 17.2% 86mg
  • Bisdemethoxycurcumin 4.8% 24mg
  • Group B Subjects given four 500mg capsules of the disclosed composition of reformulated turmeric extract prepared as per Example 2 (Compound 2).
  • Group C Subjects given four 500mg capsules of raw turmeric powder containing 5% curcuminoids prepared as per Example 6 (Compound 3).
  • Group E Subjects given four 500mg capsules of curcuminoid mixture alone with 97% curcuminoids prepared as per Example 10(Compound 5)
  • Group F Subjects given four 500mg capsules of ethanol extract concentrate of oleoresin having 94% curcuminoids prepared as per Example 12 (Compound 6)
  • Group G Subjects given four 500mg capsules of ethanol extract concentrate of essential oil of turmeric prepared as per Example 14 (compound 7)
  • the blood samples of patients at different time points were taken during the cross over study and the curcumin content in blood was analyzed in a HPLC.
  • the blood was extracted exhaustively with ethyl acetate to recover curcumin.
  • the ethyl acetate extract was analyzed by HPLC on a RP-C18 column (25x4.5mm) using methanol as solvent and UV detection at 420nm.
  • the eluent flow rate was l ml/min.
  • the level of curcumin in blood was plotted in y axis and the time period in hours is plotted in x axis and given in Fig: 2.
  • the curcumin content in the blood of volunteers given the reformulated turmeric extract, regular turmeric extract powder, raw turmeric powder, essential oil of turmeric with 10-15% Ar-turmerone, curcuminoid mixture alone, ethanol extract concentrate of oleoresin and ethanol extract concentrate of essential oil of turmeric at given time point was taken and the average values of all such time points were taken and plotted on a graph as shown in Fig: 2.

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Abstract

L'invention concerne un extrait de curcuma reformulé ayant un rapport 1:1 de concentré d'extrait à l'éthanol d'oléorésine et de concentré d'extrait à l'éthanol d'huile essentielle. Le concentré d'extrait à l'éthanol d'oléorésine comprend de la curcumine, de la déméthoxycurcumine et de la bisdéméthoxycurcumine. Le concentré de l'extrait à l'éthanol d'huile essentielle comprend de l'huile essentielle de curcuma ayant de l'Ar-turmérone. L'invention concerne également un procédé de préparation d'un extrait de curcuma reformulé ayant un rapport de 1:1 de concentré d'extrait à l'éthanol d'oléorésine et de concentré d'extrait à l'éthanol d'huile essentielle.
PCT/IN2011/000543 2010-08-16 2011-08-12 Composition pharmaceutique d'extrait de curcuma reformulé et son procédé de préparation WO2012023146A1 (fr)

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WO2014068597A2 (fr) * 2012-11-03 2014-05-08 Benny Antony Formulation de curcumine ayant une biodisponibilité accrue de curcumine et procédé de préparation et de traitement associé
WO2014111956A2 (fr) * 2013-01-17 2014-07-24 Benny Antony Formulations à libération prolongée de curcuminoïdes et leur procédé de préparation
WO2016185488A1 (fr) 2015-05-15 2016-11-24 Parachur Vivek Anand Composition oléorésineuse en poudre hautement concentrée et procédé de préparation de cette composition
CN106866397A (zh) * 2017-03-29 2017-06-20 广州市科虎生物技术研究开发中心 一种低本高效的姜黄素提取方法
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WO2020089944A1 (fr) 2018-11-03 2020-05-07 Olene Life Sciences Private Limited Procédé de préparation d'un extrait d'herbes et compositions de ce dernier
CN111991376A (zh) * 2020-08-26 2020-11-27 广东工业大学 芳姜黄酮在制备防治溃疡性结肠炎及调节肠道菌群的产品中的应用
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CN115894203A (zh) * 2022-12-29 2023-04-04 晨光生物科技集团股份有限公司 一种姜黄素的提取方法与应用

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WO2014068597A3 (fr) * 2012-11-03 2014-09-04 Benny Antony Formulation de curcumine ayant une biodisponibilité accrue de curcumine et procédé de préparation et de traitement associé
WO2014068597A2 (fr) * 2012-11-03 2014-05-08 Benny Antony Formulation de curcumine ayant une biodisponibilité accrue de curcumine et procédé de préparation et de traitement associé
WO2014111956A2 (fr) * 2013-01-17 2014-07-24 Benny Antony Formulations à libération prolongée de curcuminoïdes et leur procédé de préparation
WO2014111956A3 (fr) * 2013-01-17 2014-12-04 Benny Antony Formulations à libération prolongée de curcuminoïdes et leur procédé de préparation
AU2016263309B2 (en) * 2015-05-15 2021-09-02 Vivek Anand PARACHUR A highly concentrated powdered oleoresin composition and process for preparation thereof
WO2016185488A1 (fr) 2015-05-15 2016-11-24 Parachur Vivek Anand Composition oléorésineuse en poudre hautement concentrée et procédé de préparation de cette composition
EP3294310A4 (fr) * 2015-05-15 2019-02-06 Parachur, Vivek Anand Composition oléorésineuse en poudre hautement concentrée et procédé de préparation de cette composition
WO2018020302A1 (fr) * 2016-07-29 2018-02-01 Synthite Industries Limited Procédé d'extraction et d'isolement de curcuminoïdes
CN106866397A (zh) * 2017-03-29 2017-06-20 广州市科虎生物技术研究开发中心 一种低本高效的姜黄素提取方法
WO2020089944A1 (fr) 2018-11-03 2020-05-07 Olene Life Sciences Private Limited Procédé de préparation d'un extrait d'herbes et compositions de ce dernier
CN113727723A (zh) * 2018-11-03 2021-11-30 奥莱妮生命科学私人有限公司 制备草药提取物及其组合物的方法
EP3856217A4 (fr) * 2018-11-03 2021-12-01 Olene Life Sciences Private Limited Procédé de préparation d'un extrait d'herbes et compositions de ce dernier
JP2022512960A (ja) * 2018-11-03 2022-02-07 オレーヌ ライフ サイエンシズ プライベート リミテッド ハーブ抽出物の調製方法及びハーブ抽出物の組成物
WO2021110915A1 (fr) * 2019-12-04 2021-06-10 Pranarôm International S.A. Procede de transformation d'une huile essentielle
BE1027762B1 (fr) * 2019-12-04 2021-10-11 Univ Grenoble Alpes Procede de transformation d’une huile essentielle
CN111991376A (zh) * 2020-08-26 2020-11-27 广东工业大学 芳姜黄酮在制备防治溃疡性结肠炎及调节肠道菌群的产品中的应用
CN111991376B (zh) * 2020-08-26 2022-12-16 广东工业大学 芳姜黄酮在制备防治溃疡性结肠炎及调节肠道菌群的产品中的应用
CN115894203A (zh) * 2022-12-29 2023-04-04 晨光生物科技集团股份有限公司 一种姜黄素的提取方法与应用
CN115894203B (zh) * 2022-12-29 2024-08-23 晨光生物科技集团股份有限公司 一种姜黄素的提取方法与应用

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