WO2009019712A1 - Nouvelle composition à base de xanthophylles contenant de la (trans, méso)-zéaxanthine, et son procédé de préparation - Google Patents

Nouvelle composition à base de xanthophylles contenant de la (trans, méso)-zéaxanthine, et son procédé de préparation Download PDF

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WO2009019712A1
WO2009019712A1 PCT/IN2007/000327 IN2007000327W WO2009019712A1 WO 2009019712 A1 WO2009019712 A1 WO 2009019712A1 IN 2007000327 W IN2007000327 W IN 2007000327W WO 2009019712 A1 WO2009019712 A1 WO 2009019712A1
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trans
zeaxanthin
lutein
meso
composition
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PCT/IN2007/000327
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Thattarupambil Krishnadas Sunil Kumar
Padinjarevattam Abdulkadir Sherena
Madapura Lingappiah Shankaranarayana
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Omniactive Health Technologies Pvt Ltd.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/179—Colouring agents, e.g. pigmenting or dyeing agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/80—Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A23L33/155—Vitamins A or D
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to xanthophyll composition containing( trans, meso)- zeaxanthin) , (trans, R,R) - zeaxanthin and (trans, R,R)- lutein useful for nutrition and health care and a process for its preparation. More particularly , the invention relates to a xanthophylls composition containing at least 80 % by weight of total xanthophylls , out of which the (trans,3R,3'S, meso )-zeaxanthin content is at least 80 %, the remaining being( trans, R,R )-zeaxanthin , ( trans, R,R)-lutein and trace amounts of other carotenoids .
  • This invention further provides a xanthophyll composition containing at least 80 % by weight of total xanthophylls , out of which at least 50% being( trans, R,R)- zeaxanthin, the remaining being ( trans,3R,3'S, meso) -zeaxanthin , ( trans, R,R)- lutein and trace amounts of other carotenoids .
  • This invention further provides a xanthophyll composition containing at least 80% by weight of total xanthophylls , out of which at least 50% being( trans, R,R)- lutein, the remaining being( trans,3R,3'S, meso) -zeaxanthin , ( trans, R 7 R)- zeaxanthin and trace amounts of other carotenoids .
  • the xanthophyll composition containing (trans ,3R,3'S, meso) - zeaxanthin , (trans, R,R ) -zeaxanthin and (trans, R,R ) -lutein of the present invention is particularly useful for nutrition and health care .
  • Carotenoids are yellow, red and orange pigments and are widely distributed in nature. •Although specific carotenoids have been identified in various fruits and vegetables , bird feathers, egg-yolk, poultry skin, crustaceans and macular eye region , they are especially abundant in marigoldvpetals, corn and leafy vegetables. The correlation between dietary carotenoids and carotenoids found in human serum and plasma indicate that only selected groups of carotenoids make their entry into the human blood stream to exert their effect. Each carotenoid shows an individual pattern of absorption, plasma transport and metabolism.
  • Carotenoids absorb light in the 400-500 ran region of the visible spectrum. This physical property imparts the characteristic yellow / red color to the pigments.
  • Carotenoids contain a conjugated backbone composed of isoprerie units, which are usually inverted at the center of the molecule, imparting symmetry. Changes in geometrical configuration about the double bonds result in the existence of many cis- and trans- isomers. Mammalian species do not synthesize carotenoids and therefore these have to be obtained from dietary sources such as fruits , vegetables and egg yolks. In the recent years , carotenoids have been reported to have several health benefits , which include prevention anti or protection against serious health disorders.
  • Carotenoids are non-polar compounds classified into two sub-classes, namely , polar compounds called xanthophylls or oxy-carotenoids and non-polar hydrocarbon carotenes like ⁇ -carotene, lycopene, etc. Both the sub-classes have atleast nine conjugated double bonds responsible for the characteristic colors of the carotenoids.
  • Xanthophylls have ring structures at the end of the conjugated double bond chain with polar functions like hydroxyl or keto group.
  • the examples for xanthophylls include lutein, zeaxanthin, capsanthin, canthaxanthin, ⁇ -cryptoxanthin, astaxanthin, etc.
  • xanthophylls like lutein and zeaxanthin have attracted the renewed attention of scientists and researchers in the biomedical, chemical and nutritional field in recent years.
  • Lutein and zeaxanthin contribute to yellow and orange - yellow colours respectively.
  • Lutein and zeaxanthin can be present in plant material in the free form and also in ester form.
  • Lutein is present in green leafy vegetables like spinach, kale and broccoli in the free form; fruits like mango, orange and papaya; red paprika, algae, yellow corn, contain lutein in the form of its esters. It is, also present in the blood stream and various tissues in human body and particularly in the macula , lens and retina of the eye.
  • Lutein is chemically designated as ⁇ , ⁇ -carotene 3,3'-diol.
  • Zeaxanthin is formed by the addition of two hydroxy groups to ⁇ -carotene .
  • zeaxanthin Since the hydroxy positions are in 3 and J-, the chemical name for zeaxanthin is ⁇ / ⁇ -carotene-S ⁇ '-diol.
  • the common name of zeaxanthin is derived from zea mays because this carotenoid was first identified in corn ( zea mays).
  • lutein is not symmetrical as the position of double bond in the left ring is not identical with the double bond position in the right ring.
  • Zeaxanthin is completely symmetrical with regards to left and right rings due to an extra conjugated double bond compared to lutein .
  • Xanthophylls can show both optical ( R-and S- stereo isomers ) and geometrical isomers ( trans,E- and cis,Z- ) .
  • the conformation of R- and S- stereo isomers is based on CD spectral and chiral column HPLC studies while the conformation of cis- and trans- isomers is based on electronic , infrared , NMR , HPLC-MS and HPLC-KMR on-line spectroscopy studies. It is well known that when an organic molecule has a carbon atom with four different types of atoms or groups attached to it , that carbon atom is designated as chiral carbon atom.
  • trans-zeaxanthin The chiral carbon atom is responsible for two different spatial arrangements leading to formation of optical isomers while the number of double bonds of the polyene chain and the presence of a methyl group and the absence of steric hindrance decide the number of trans- and cis- isomers. .
  • the carbon atoms at 3 and 3' positions in the two end rings are both chiral atoms.
  • trans-zeaxanthin has two chiral centers at the carbon atoms C3 and C3', based on the positions of the secondary hydroxy groups attached to them .
  • the isomer causing rotation of polarized light in a right handed manner is called R-stereo isomer
  • conjugated double bonds of lutein and zeaxanthin contribute to the distinctive colours of each pigment, and also influence the ability of these to quench singlet oxygen. Due to the extra conjugated double bond, zeaxanthin is believed to be a stronger antioxidant compared to lutein.
  • the macular pigment of the eye is composed primarily of three xanthophylls pigments , namely ( R,R)- ⁇ lutein , (R,R) ⁇ zeaxanthin and (R,S)-zeaxanthin in the order 36, 18 and 18% of the total carotenoid content of the retina along with the remaining 20% consisting of minor carotenoids like oxo-lutein , epi-lutein and ⁇ , ⁇ -carotene 3,3'-dione (J.T.Landrum and RA-Bone/Arch-Biochem Biophys,385,28(2001)).
  • xanthophyll pigments are found throughout the tissues of the eye, the highest concentration is seen in the macula lutea region of the retina, including a central depression in the retina called the fovea.
  • the concentration of xanthophylls pigments increases progressively towards the center of the macula and in the fovea , the concentration of these xanthophylls pigments are approximately thousand fold higher than in other human tissues.
  • the fovea is a relatively small area within the macula, in which the cone photoreceptors reach their maximal concentration. About 50% of the total amounts of the xanthophylls is concentrated in the macula where zeaxanthin dominates over lutein by ratio of 2:1 ( Handelman et al. , Measurements of carotenoids in human and monkey -retinas., in Methods in Enzymology, LPacker (editor)213A,220- 230, Academic press , NY, 1992; Billsten et al . , Photochemistry and photobiology, 78, 138-145, 2003 ) .
  • zeaxanthin is 50 :50 mixture of (trans- 3R,3'R)-zeaxar ⁇ thin and (trans-3R,3'S)- zeaxanthin along with small quantity of (3S,3'S)- zeaxanthin (J.T.Landrum and R.A.Bone, Arch.Biochem.Biophy., 385, 28 , 2001) .
  • the fovea is particularly important for proper visual function (e.g. > acuity) and disease and damage to this area is known to result in legal blindness.
  • age-related macular degeneration AMD is characterized by pathological changes in the retina, retinal pigment epithelium (RPE) and/ or the choroid and preferentially affects the macular region of the retina.
  • RPE retinal pigment epithelium
  • This is the leading cause of irreversible vision loss in the United States among those ⁇ £ ⁇ y old and there is no established treatment available for most patients .
  • the loss of central vision results in the possible inability to recognize faces. , to read or drive a car and therefore has a significant effect on an individual's ability to live independently.
  • xanthophylls binding protein XBP
  • the XBP is suggested to be involved in the uptake of lutein and zeaxanthin from the blood stream and stabilization of the same in the retina.
  • the complex may be a better antioxidant than the free xanthophylls, facilitating improved protection of ocular tissue from oxidative damages .
  • Lutein is a common carotenoid found in most fruits and vegetables, while zeaxanthin in the (R,R)- isomer form is present only in minute quantities in most fruits and vegetables. Dietary sources of zeaxanthin are limited to greens, certain yellow/ orange fruits and vegetables such as corn, nectarines, oranges, papaya, persimons and squash. Capsicum annum is another most common spice widely used which is a good source of zeaxanthin.
  • Wolfberry (Lycium barbarum , fructus lyc ⁇ or Gou Qi Zi) plant has small red berries which are commonly used in Chinese home cooking and has been shown to have a high content of zeaxanthin (mainly as zeaxanthin dipalmitate) but negligible amounts of lutein.
  • the dried fruit of wolfberry is prescribed by Chinese herbalists as a therapeutic agent for a number of eye diseases.
  • lutein dipalmitate ( Helenien ) isolated from the blossom leafs of Helenium autumnale is reported to be used for the treatment of the visual disorders.
  • the dietary source of meso-zeaxanthin is mainly from seafoods like shrimps, fish, turtle, etc, thereby the vegetarian population is deprived of meso - zeaxanthin.
  • pharmaceuticals composition containing meso - zeaxanthin for treatment of retinal disorders like increasing the deposition of macular pigments in the human eye and therapeutic treatment or prophylaxis of AMD (Howard et al. , US patent No.6, 329, 432 , 2001 ) . Lutein and zeaxanthin occur naturally in trans-isomeric form in fruits , vegetables and flowers (marigold).
  • the preferred bio- available form is trans-isomeric as evidenced from the data of geometric isomers compositional analysis of human plasma. ( Khachik et al. , Isolation and structure elucidation of geometric isomers of lutein , zeaxanthin in extracts of human plasma , J.Chrom.582, 153-156 , 1992) . In view of this, it is desirable to use the trans-isomeric form of meso- zeaxanthin in dietary supplements.
  • trans-xanthophylls occur naturally in foods with good stability and in greater bio- vailability compared to corresponding cis-isomers, it would be useful for industry and nutritional product formulators to have (trans,3R,3'S,meso) - zeaxanthin from a commercial scale process, made from natural source material same as that which is already accepted by the market for lutein and zeaxanthin products , namely marigold.
  • meso-zeaxanthin product should be made from safe solvents (GRAS solvents) for producing dietary supplements suitable for human consumption , with minimal solvent residues and specific ratios of ; lutein and zeaxanthin isomers keeping in mind market requirements .
  • GRAS solvents safe solvents
  • zeaxanthin and meso-zeaxanthin as an antioxidant and also their role in the prevention of eye diseases have stimulated the R&D efforts for finding ) commercially viable process for production of zeaxanthin and meso-zeaxanthin-rich products which can be used as safe sources of nutritional supplements for human consumption.
  • meso-zeaxanthin While so far meso-zeaxanthin has not been as well recognized as a dietary supplementation ingredient compared to (3R,3'R)— zeaxanthin, it has attracted the attention of health practitioners and pharmacologists who have evinced interest for use of meso-zeaxanthin in formulations for increasing macular pigment density in the human eye and for therapeutic treatment or prophylaxis of diseases and disorders of macula in particular AMD (Howard et al . , US Patent No. 6, 218, 436 , 2001 ; 6, 329, 432 , 2001) .
  • a pharmaceutical composition containing an effective dose of meso- zeaxanthin and a carrier or diluent is disclosed.
  • the carrier or diluent may be selected from a earotenoid such as lutein, an isomer of zeaxanthin .
  • the composition may contain at least one compound selected from the group consisting of lutein , (3R,3'R)- zeaxanthin and (3S,3'S)- zeaxanthin.
  • the use of trans, meso-zeaxanthin has not been disclosed
  • Rodriguez has described a method of isomerising lutein to yield a mixture of zeaxanthin epimers by employing non aqueous media and heating a mixture of alkali and propylene glycol. Though the circular dichroism spectrum indicated the formation of meso-isomer of zeaxanthin , no attempts were made to quantify the meso-zeaxanthin content and also provide the composition of the isomerised products.( US patent No. 5, 973, 211, 1999) .
  • xanthophyll composition containing (trans, 3R,3'S,meso)- zeaxanthin, , (trans, R 5 R)- zeaxanthin and (trans, R 7 R)- lutein is not hitherto reported .
  • Such a composition will be useful for nutrition and health care and as colorants for foods and feeds.
  • the main objective of the present invention is to provide a xanthophyll composition containing ( trans 7 3R,3'S,meso)-zeaxanthin , (trans, R 7 R)- zeaxanthin and (trans, R,R)- lutein and trace amounts of other carotenoids which is safe for human consumption and useful for nutrition and health care.
  • Another objective of the present invention is to provide a xanthophyll composition containing at least 50 % by weight of total xanthophylls out of which at least 80% is (trans,3R,3'S,meso) - zeaxanthin , the remaining being (trans, R,R)-zeaxanthin and (trans, R,R)- lutein and trace amounts of other carotenoids .
  • a xanthophyll composition containing at least 80 % by weight of total xanthophylls , out of which at least 80 % is (trans,3R,3'S, meso)-zeaxanthin, the remaining being (trans, R,R)- lutein, ( trans, R,R) - zeaxanthin and trace amounts of other carotenoids .
  • a xanthophyll composition wherein the composition contains at least 80 % by weight of total xanthophylls , out of which at least 50% being (trans, R,R)- zeaxanthin , the remaining being (trans, 3R,3'S, meso) -zeaxanthin , (trans, R,R)— lutein and trace amounts of other carotenoids .
  • a xanthophyll composition wherein the composition contains at least 80 % by weight of total xanthophylls , out of which at least . 50% being (trans, R 7 R)- lutein , the remaining being (trans,3R,3'S, meso) -zeaxanthin , (trans, R,R)-- zeaxanthin and trace amounts of other carotenoids .
  • Still another objective of the present invention is to provide a process for the preparation of xanthophyll composition containing( trans,3R,3'S,meso)- zeaxanthin (trans, R,R)- zeaxanthin and (trans, R,R)- lutein and trace amounts of other carotenoids which is safe for human consumption and useful for nutrition and health care .
  • the present invention provides a xanthophyll composition containing (trans;3R,3'S, meso)- zeaxanthin , ( trans, R,R)- lutein and (trans, R,R)- zeaxanthin and trace amounts of other carotenoids which is useful for nutrition and health care .
  • a xanthophyll composition wherein the composition contains at least 50 % by weight of. total xanthophylls , out of which 80 % being (trans ⁇ R ⁇ 'S, meso) -zeaxanthin ⁇ , the remaining being (trans, R,R)-, lutein, (trans, R,R,)- zeaxanthin and trace amounts of other carotenoids which is useful for nutrition and health care .
  • a xanthophyll composition wherein the composition contains at least 80 % by weight of total xanthophylls , out of which 80 % being (trans,3R,3'S, meso) -zeaxanthin , the remaining being (trans, R,R)- lutein, (trans, R,R,)- zeaxanthin and trace amounts of other carotenoids which is useful for nutrition and health care .
  • a xanthophyll composition wherein the composition contains at least 80 % by weight of total xanthophylls , out of which 45 % being (trans,3R,3'S, meso) -zeaxanthin , 50 % by weight being (trans, R,R)- zeaxanthin , 5 to 7 % being (trans, R,R)- lutein and trace amounts of other carotenoids which is useful for nutrition and health care .
  • a xanthophyll composition wherein the composition contains at least 80 % by weight of total xanthophylls , out of which the (trans,3R,3'S, meso) -zeaxanthin being is at least 80 % , the amount of (trans, R, R)- lutein being in the range of 5 to 15% and the amount of (trans, R, R) - zeaxanthin being in the range of 5 to 7 % and trace amounts of other carotenoids which is useful for nutrition and health care .
  • a xanthophyll composition containing at least 80 % by weight of total xanthophylls , out of which at least 50% being (trans, R,R)- zeaxanthin r, x the remaining being (trans, 3R,3'S,meso) - zeaxanthin , (trans, R,R)- lutein and trace amounts of other carotenoids which is useful for nutrition and health care .
  • the other carotenoids present in the composition may be those selected from beta- carotene , lycopene , beta-cryptoxanthin , astaxanthin or their mixtures .
  • composition of the present invention may be in the form selected from the group of beadlets , micro-encapsulated powders , oil suspensions , liquid dispersions , capsules , pellets , ointments , soft gel capsules , tablets , chewable tablets or lotions / liquid preparations.
  • the composition of the present invention may be provided with a coating which helps preserve the original quality characteristics .
  • a process for the preparation of a xanthophyll composition containing (trans,3R,3'S,meso)- zeaxanthin, (trans, R 7 R)- lutein & (trans, R,R)- zeaxanthin which is useful for nutrition and health care as dietary supplements which comprises
  • the composition containing the desired amount of r(trans,R,S, meso)-zeaxanthin and trans-lutein can be obtained .
  • the composition prepared as described above has to be mixed with appropriate amount of (trans, R R)- zeaxanthin .
  • the suitable solvent medium in step (i) While selecting the suitable solvent medium in step (i) a variety of criteria are to be taken into consideration . Accordingly, the major criteria to be considered in solvent selection are (i) it should be water immiscible ( ⁇ ) the solvent should be non- halogenated (i ⁇ ) the solvent should have GRAS status (iv) the solubility of zeaxanthin in the solvent should be high (v) boiling point of the solvent should be in the range of 80 o 2OO.degree.C and (vi) stability of zeaxanthin isomers in the solvent used should be high.
  • * ⁇ e solvent which can be employed may be selected from aromatic primary alcohols , especially phenyl carbinol and also p-isobenzyl alcohol .
  • the solvents in which zeaxanthin is highly soluble such as - chloroform , benzene , DMSO , etc. cannot be used in the process of the present invention because such solvents even in trace amounts are prohibited for human consumption . Hence , the solvent used should fall under GRAS status . It is also to be noted that the stage where the solvent is to be used contains large amounts of water . Therefore , the solvent to be used in the process of invention should be water immiscible so as to facilitate phase separation . Accordingly , many of the solvents which fall under GRAS status and in which lutein-containing material or zeaxanthin is highly soluble cannot be used as such .
  • the amount of alkali which is used in step (i) may be in the range of 0.5 parts to 1 part of lutein containing material.
  • the alkali used may be selected from sodium /potassium hydroxide and preferably potassium hydroxide.
  • the step ( i ) may be carried out tinder an inert atmosphere , using inert gases such as nitrogen , helium , preferably nitrogen under reduced pressure.
  • the polar solvent used in step (vi ) may be selected from methanol, ethanol .
  • the ratio of alcohol and water used is 0.7 : 0.3 to 0.8 : 0.2.
  • the ratio of non-polar solvent and aliphatic alcohol used may be about 0.5 :0.5 to 0.8 : 0.2.
  • the non-polar solvent used may be selected from hexane , heptane , preferably hexane .
  • the alcohol used may be selected from aliphatic alcohols like ethanol, methanol , isopropyl alcohol and mixtures thereof .
  • the process consists of mixing lutein or an extract containing lutein ester with the solvent such as phenyl carbinol and an alkali such as potassium hydroxide in a three necked vessel fitted with a water condenser and heating the mixture under stirring for a period of 3 to 36 hrs and maintaining the temperature at around 80-200 degree C , It is necessary that sufficient excess alkali is to be used for accelerating the isomerisation reaction.
  • the amount of alkali can be in the range of 0.5 parts to 1 part of the plant extract(oleoresin) or more preferably from 0.5 to 1 part of alkali to one part of saponified oleoresin containing lutein .
  • the reaction time may be 3 to 36 hrs and depends on the temperature used , which may be in the range of 80-200 degree C and with continuous stirring of the reaction mixture.
  • the material is taken out and washed with a mixture of alcohol-water preferably 70 : 30 to remove the excess alkali and other impurities.
  • the crude xanthophyll composition is further washed with non polar hydrocarbon solvent - alcohol mixture , preferably 80:20 filtered and vacuum dried to obtain orange red composition containing (trans,3R,3'S, meso)-zeaxanthin / (trans, R,R)-lutein, (trans, R,R)- zeaxanthin and trace amounts of other carotenoids .
  • the column used was a ChiralPak AD , packed with silicagel (10 um) , coated with amylose tris-(3,5- dimethylphenylcarbamate) as selector .
  • the reference standards like ( trans,3R,3'S,:meso)- zeaxnthin , (trans / 3R / 3'R,6'R)-lutein and ( tranS / SR / S'RJ-zeaxanthin were sourced form Carotenature ( Lupsingen, Switzerland) .
  • LC-ApcI-MS was run on a Micromass VG platform II quadrapole mass spectrometer equipped with an Apcl interface , operating in the positive mode ( Breiftier et al . , BritJ.Nutri , 91, 707-713 , 2004)) .
  • the spectrophotometric analysis of the xanthophyll composition prepared by the process of the present invention as explained above showed that the total xanthophyll content in the composition is in the range 50 to 90% by weight ( 452 nm El % 2348).
  • the chiral column HPLC analysis of the composition prepared showed that the composition contains >90% by weight of (tranS / SR / S'S / ineso)- zeaxanthin and the remaining comprising of (trans,R,R) -zeaxanthin and (trans,R,R)- lutein based on HPLC peak areas.
  • Figs 1-3 show the chiral HPLC chromatograms of a xanthophylls composition containing (tranS / SR ⁇ 'S, meso)-zeaxanthin , (trans,3R,3'R)-zeaxanthin and (trans-3R / 3'R,6'R)-lutein and the added reference compounds.
  • the oleoresin ( 100 g ) containing 11.2 g total xanthophylls (measured by spectrophotometric method) and (trans,R,R)-lutein and (trans, R,R)-zeaxanthin 69.5 and 5.34 % AUC respectively by HPLC analysis was transferred into a three necked RB flask ( 500 ml capacity) followed by addition of 50g phenyl carbinol and 5Og potassium hydroxide.
  • a water condenser was fixed passing water and through the other neck nitrogen gas was bubbled and through the central neck a stirrer was fixed for uniform mixing.
  • the flask was fixed in an oil bath maintaining the temperature of the oil between 100-110 degree.
  • the oleoresin ( 100 g ) containing 8.5 g total xanthophylls (measured by spectrophotometric method) and trans-lutein and trans, zeaxanthin 67 and 5.80% AUC respectively by HPLC was transferred into a three necked RB flask ( 500 ml capacity) followed by addition of 50g phenyl carbinol and 5Og potassium hydroxide.
  • a water condenser was fixed and through the other neck nitrogen gas was bubbled and through the central neck a stirrer was fixed for uniform mixing.
  • the flask was fixed in an oil bath maintaining the temperature of the oil between 100-110 degree. C .
  • composition when analysed by chiral column HPLC and LC-ApcI-MS to have (trans,3R,3'S, meso) zeaxanthin in an amount of > 90% of the total xanthophyll content and the amount of (trans,R,R)- zeaxanthin to be 5 % and the amount of (trans,R,R)-lutein to be 3% AUC .
  • Oleoresin 100 g containing 10.2. g total xanthophylls (measured by spectrophotometric method) and trans-lutein and trans, zeaxanthin 69.52 and 4.80% AUC respectively by HPLC was transferred into a three necked RB flask ( 500 ml capacity) followed by addition of '5Og phenyl carbinol and 3Og potassium hydroxide.
  • a water condenser was fixed and through the other neck nitrogen gas was bubbled and through the central neck a stirrer was fixed for uniform mixing.
  • the flask was fixed in an oil bath maintaining the temperature of the oil between 100-110 degree. C .
  • composition when analysedjby chiral HPLC and LC-ApcI-MS was found to have (trans, R,R)-rutein in an amount of > 50 % of the total xanthophyll content and the amount of (trans,R,S,meso)- zeaxanthin to be 45 % and the amount of (tfans,R,R)-zeaxanthin to be 5% AUC.
  • the isomeric reaction was continued for 18 hrs after which the resulting red colored product (200 g) was removed and subjected to two stage purification steps .
  • the composition was washed with 2 liters of ethanol /water( 70/30 )to obtain 30 g of crude xanthophyll composition.
  • the composition was further )washed with 620 ml of hexane/IPA mixture of (80/20 ) and dried under vacuum to yield a final xanthophylls composition showing total xanthophylls . content 76.52% by weight.
  • composition was analysed by chiral column HPLC and LC-ApcI-MS and found that it contained (trans,R,S,meso)-- zeaxanthin in amount of >90% based on the total xanthophylls content , the amount of (trans,R,R- zeaxanthin was found to be >5% and the amount of (trans,-R,R)-lutein >3% AUC .
  • the marigold oleoresin ( 100 g ) containing 10.5 g total xanthophylls (measured by spectrophotometric method) and trans -lutein and trans,zeaxanfhin 67.34 and 5.14 % AUC respectively by HPLC was transferred into a three necked RB flask ( 500 ml capacity) followed by addition of 50g phenyl carbinol and 50g potassium hydroxide.
  • the flask was fixed in an oil bath maintaining the temperature of the oil between 108-110 degree. C .
  • composition when analysed by chiral column HPLC and LC-ApcI-MS showed that the composition consisted of 92 % (trans,3R,3'S,meso)-zeaxanthin out of the total xanthophyll content .
  • the amount of (trans, R,R)- zeaxanthin was found to be 4 %and the amount of (trans, R,R)- lutein was found to be 4% based on peak areas .
  • composition has all the essential macular xanthophylls including (tranS / SR/S'S/mesoJ-zeaxanthin , (tranS / R / R ⁇ zeaxanthin and ( trans,R,R) - lutein and provision for obtaining varying contents of the individual xanthophylls.
  • the xanthophylls composition meets safety considerations because of the use of GRAS reagents and hence is useful for nutrition and dietary supplements for eye health.
  • Both retinyl lutein and lutein in the present case are derived from plant source and both of them under go a common allylic isomeric rearrangement to form trans,meso- zeaxanthin , thereby establishing similarity and superiority over the one prepared completely by synthetic route.
  • Naturally occurring lutein can be sourced in plenty from marigold flowers , a widely cultivated commercial crop and also the processed products like oleoresin,free lutein and lutein ester.
  • composition is useful for nutrition and health care and as colorants for food and feeds and is safe for human consumption

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Abstract

Cette invention a trait à une nouvelle composition à base de xanthophylles contenant des formes trans-isomériques de méso-zéaxanthine, de zéaxanthine et de lutéine, ladite composition étant utilisée en nutrition et dans les soins de santé ; l'invention concerne par ailleurs un procédé de préparation de cette composition. Le procédé implique le chauffage d'un mélange constitué d'un matériau contenant de la lutéine en même temps qu'un alcool aromatique et un hydrure alcalin, suivi d'une purification.
PCT/IN2007/000327 2007-08-03 2007-08-03 Nouvelle composition à base de xanthophylles contenant de la (trans, méso)-zéaxanthine, et son procédé de préparation WO2009019712A1 (fr)

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Cited By (4)

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Publication number Priority date Publication date Assignee Title
EP2473065A1 (fr) * 2009-09-02 2012-07-11 Omniactive Health Technologies Ltd. Composition à base de xanthophylles contenant des pigments maculaires et son procédé de préparation
GB2492881A (en) * 2011-07-07 2013-01-16 Howard Foundation Holdings Ltd Composition comprising meso-zeaxanthin for improving visual performance
US20180280266A1 (en) * 2015-09-28 2018-10-04 Omniactive Health Technologies Limited Xanthophyll compositions for skin lightening
CN114098070A (zh) * 2021-12-14 2022-03-01 宁夏宸溪健康生物工程有限公司 一种枸杞原汁复合型护眼口服液及其制备方法

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2473065A1 (fr) * 2009-09-02 2012-07-11 Omniactive Health Technologies Ltd. Composition à base de xanthophylles contenant des pigments maculaires et son procédé de préparation
EP2473065B1 (fr) * 2009-09-02 2016-04-13 OmniActive Health Technologies Ltd. Composition de xanthophiles comprenant des pigments de la macula et procede de preparation
US10485833B2 (en) 2009-09-02 2019-11-26 Omniactive Health Technologies Limited Xanthophyll composition containing macular pigments and a process for its preparation
GB2492881A (en) * 2011-07-07 2013-01-16 Howard Foundation Holdings Ltd Composition comprising meso-zeaxanthin for improving visual performance
GB2503608A (en) * 2011-07-07 2014-01-01 Howard Foundation Holdings Ltd Meso-zeaxanthin, lutein and zeaxanthin composition for improving contrast sensitivity in age-related macular degeneration
US8623428B2 (en) 2011-07-07 2014-01-07 Howard Foundation Holdings Limited Visual performance and/or macular pigmentation
US8962043B2 (en) 2011-07-07 2015-02-24 Howard Foundation Holdings Limited Visual performance and/or macular pigmentation
US9463167B2 (en) 2011-07-07 2016-10-11 Howard Foundation Holdings Limited Visual performance and/or macular pigmentation
US9603813B2 (en) 2011-07-07 2017-03-28 Howard Foundation Holdings Limited Visual performance and/or macular pigmentation
US20180280266A1 (en) * 2015-09-28 2018-10-04 Omniactive Health Technologies Limited Xanthophyll compositions for skin lightening
CN114098070A (zh) * 2021-12-14 2022-03-01 宁夏宸溪健康生物工程有限公司 一种枸杞原汁复合型护眼口服液及其制备方法

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