WO2016028235A1 - A system and method for extracting and/or concentrating vitamin e - Google Patents

A system and method for extracting and/or concentrating vitamin e Download PDF

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WO2016028235A1
WO2016028235A1 PCT/TH2014/000039 TH2014000039W WO2016028235A1 WO 2016028235 A1 WO2016028235 A1 WO 2016028235A1 TH 2014000039 W TH2014000039 W TH 2014000039W WO 2016028235 A1 WO2016028235 A1 WO 2016028235A1
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temperature
vitamin
heated mixture
determined
fatty acid
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PCT/TH2014/000039
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French (fr)
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Thailand Research Fund The
Patcharin Raviyan
Nanthina DUMRONGWATTANAKOOL
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Chiang Mai University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
    • C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present disclosure generally relates to the extraction and concentration of vitamin E from vitamin E containing materials and/or vitamin E containing compounds. More particularly, the present disclosure relates to a system and method for extracting and/or concentrating vitamin E from vitamin E containing materials and/or vitamin E containing compounds.

Description

T TH2014/000039
1
A SYSTEM AND METHOD FOR EXTRACTING AND/OR CONCENTRATING
VITAMIN E
TECHNICAL FIELD
The present disclosure generally relates to the extracting and concentrating of vitamin E from vitamin E containing materials and/or vitamin E containing compounds. More particularly, the present disclosure relates to a system and method for extracting and/or concentrating vitamin E from vitamin E containing materials and/or vitamin E containing compounds. BACKGROUND
Several methods have been developed to extract and concentrate vitamin E from vitamin E containing materials and/or vitamin E containing compounds. Such methods include supercritical fluid extraction (SFE), saponification, trans-esterification, acid catalyzed hydrolysis, enzymatic hydrolysis, molecular distillation, solvent fractionation, urea inclusion compound formation, membrane filtration and liquid chromatography. Typically, two or more of the above mentioned methods can be used in combination to increase the concentration of Vitamin E in an intermediate product or final product.
Supercritical fluid extraction (SFE) is the most commonly used method for extracting and concentrating vitamin E from vitamin E containing materials and/or vitamin E containing compounds. SFE typically involves low processing temperatures, minimal thermal degradation of sensitive bioactive components (e.g., vitamin E) and minimal oxidation of sensitive bioactive components (e.g, vitamin E). However, SFE is a relatively complicated method that typically requires high capital costs and high operating costs. Further, a large and expensive SFE apparatus is typically required to provide for a high production volume of purified vitamin E. Moreover, in the case of a feed sample containing a low concentration of vitamin E, a substantial number of sequential extraction cycles are typically required to extract and concentrate vitamin E from the feed sample. Therefore, there is a need to provide a system and method for extracting and/or concentrating vitamin E from a vitamin E containing material(s) and/or vitamin E containing compound(s) that avoid or at least ameliorate one or more of the disadvantages described above. BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram of a supercritical fluid extractor in accordance with an embodiment of the present disclosure, where P indicates High Pressure Pump, HE indicates Heat Exchanger, MV indicates Valve, V indicates Extractor Vessel, BPR indicates Back Pressure Regulator, CS indicates Cyclone Separator and PG indicates Pressure Gauge
FIG. 2A is a microscopic image of a urea crystal obtained via urea-fatty acid ester complexation wherein the cooling temperature is kept constant. FIG. 2B is a microscopic image of a urea crystal obtained via a urea-fatty acid ester complexation step in accordance with an embodiment of the present disclosure, wherein the urea-fatty acid ester complexation step comprises sequentially reducing the cooling temperature to a series of pre-determined temperatures. SUMMARY
In certain embodiments, the present disclosure provides a method of concentrating vitamin E in a vitamin E containing sample, comprising esterifying the vitamin E containing sample to form an esterified sample comprising vitamin E molecules and fatty acid esters; contacting the esterified sample with a first solvent and urea to form a first mixture; heating the first mixture to form a heated mixture; sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures; thereby forming a solid phase comprising a urea-fatty acid ester complex and a liquid phase comprising the first solvent and vitamin E; separating the liquid phase from the solid phase; and removing the first solvent from the liquid phase thereby forming a concentrated sample of vitamin E.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to at least two distinct pre-determined temperatures. In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises pre-determined temperatures between about 50°C to about -25 °C. 9
3
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about 20°C and about 50°C. In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about 0°C and about 30°C.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the then temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 25°C.
In certain embodiments, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about -20°C and about 10°C.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about 20°C and about 50°C for a period of time greater than 5 minutes.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about 0°C and about 30°C for a period of time greater than 5 minutes.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about - 10°C and about 20°C for a period of time greater than 5 minutes. In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 1 hour.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures further comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about 0°C and about 30°C for a period of time greater than 5 minutes.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures further comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 5 minutes.
In certain embodiments, the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures further comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 1 hour.
In certain embodiments, the step of heating the mixture comprises heating the mixture to a temperature of about 40°C to about 100°C.
In certain embodiments, the first solvent is an alcohol.
In certain embodiments, the present disclosure provides a method of concentrating vitamin E in a vitamin E containing sample comprising esterifying the vitamin E containing sample to form an esterified sample comprising vitamin E molecules and fatty acid esters; contacting the esterified sample with a first solvent and urea to form a first mixture; heating the first mixture at a temperature of about 40°C to about 100°C to form a heated mixture; sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing and then maintaining the temperature of the 00039
5 heated mixture at a pre-determined temperature of between about 20°C and about 50°C for a period of time greater than 5 minutes, reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about 0°C and about 30°C for a period of time greater than 5 minutes, reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about - 10°C and about 20°C for a period of time greater than 5 minutes, and reducing the temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 1 hour; thereby forming a solid phase comprising a urea-fatty acid ester complex and a liquid phase comprising the first solvent and vitamin E; separating the liquid phase from the solid phase; and removing the first solvent from the liquid phase thereby forming a concentrated sample of vitamin E.
In certain embodiments, the methods disclosed herein further comprise the step of further purifying the concentrated sample of vitamin E.
In certain embodiments, the step of further purifying the concentrated sample of vitamin E comprises supercritical fluid extraction, saponification, transesterification, acid catalysed hydrolysis, enzymatic hydrolysis, molecular distillation, solvent fractionation, membrane filtration, liquid chromatography, or a combination of two or more thereof.
In certain embodiments, the step of further purifying the concentrated sample of vitamin E comprises supercritical fluid extraction.
In certain embodiments, the vitamin E containing sample comprises a fatty acid distillate selected from the group consisting of a fatty acid distillate of palm oil, a fatty acid distillate of soybean oil, a fatty acid distillate of avocado oil, a fatty acid distillate of wheat germ oil, a fatty acid distillate of olive oil, a fatty acid distillate of grape seed oil, a fatty acid distillate of vegetable oil or a combination of two or more thereof. DETAILED DESCRIPTION
In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments can be utilized, and other changes can be made, without departing from the spirit or scope of the subject matter presented herein. Unless specified otherwise, the terms "comprising" and "comprise" as used herein, and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, un-recited elements.
As used herein, the term "about", in the context of measurement values, conditions, concentrations of components, etc., means +/- 5% of the stated value, or +/- 4% of the stated value, or +/- 3% of the stated value, or +/- 2% of the stated value, or +/- 1% of the stated value, or +/- 0.5% of the stated value, or +/- 0% of the stated value.
Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range.
For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1 ,
2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.
As used herein, the phrase "sequential cooling urea-fatty acid ester complexation" refers to the urea-fatty acid ester complexation step of the present disclosure, wherein the urea-fatty acid ester complexation step comprises sequentially reducing the cooling temperature to a series of pre-determined temperatures.
As used herein, the phrase "maintaining the temperature" when used in connection with the sequential cooling step as described herein means keeping the temperature within ±10°C, ±9°C, ±8°C, ±7°C, ±6°C, ±5°C, ±4°C, ±3°C, ±2°C, ±1 °C, ±0.9°C, ±0.8°C, ±0.7°C, ±0.6°C, ±0.5°C, ±0.4°C, ±0.3 °C, ±0.2°C, or ±0.1°C of the pre-determined temperature for the allotted period of time. As used herein, the term "sample" means "vitamin E containing sample" unless specified otherwise.
As used herein, the term "vitamin E" can refer to any of the eight naturally occurring forms of vitamin E and combinations thereof. In some embodiments, vitamin E can include alpha- tocopherol, beta-tocopherol, gamma- tocopherol, delta-tocopherol, alpha-tocotrienol, beta- tocotrienol, gamma-tocotrienol, and delta-tocotrienol, and combinations thereof. In some embodiments, the term "vitamin E" can include all stereoisomeric forms of any one or more of the aforementioned vitamin E compounds and combinations thereof.
The present disclosure relates to a system and method for extracting and/or concentrating vitamin E from a vitamin E containing sample(s), vitamin E containing material(s) and/or vitamin E containing compound(s). The system and/or method of the present disclosure for extracting and/or concentrating vitamin E can be used to concentrate vitamin E in a vitamin E containing sample via a urea- fatty acid complexation step that comprises sequentially reducing the cooling temperature to a series of pre-determined temperatures. The system and/or method of the present disclosure for extracting and/or concentrating vitamin E can be used to pre-concentrate vitamin E in a vitamin E containing sample via a urea-fatty acid complexation step prior to the final purification of the vitamin E in the sample by SFE, wherein the urea-fatty acid complexation step comprises sequentially reducing the cooling temperature to a series of pre-determined temperatures.
In accordance with the present disclosure, the urea-fatty acid complexation step that comprises sequentially reducing the cooling temperature to a series of pre-determined temperatures (also referred to as "sequential cooling urea-fatty acid complexation") can be used to effectively remove fatty acids from a vitamin E containing sample and, thus, significantly increase the quantity of vitamin E in the sample.
In some embodiments, the vitamin E containing sample can comprise a vitamin E containing material, a vitamin E containing food, a vitamin E containing oil, a vitamin E containing compound, a vitamin E containing fatty acid distillate, or a combination of one or more thereof.
In some embodiments, the Vitamin E containing oil can comprise palm oil, soybean oil, avocado oil, wheat germ oil, rice oil, rice bran oil, olive oil, grape seed oil, vegetable oil, or a combination of one or more thereof.
In some embodiments, the vitamin E containing fatty acid distillate can comprise a fatty acid distillate of palm oil, a fatty acid distillate of soybean oil, a fatty acid distillate of avocado oil, a fatty acid distillate of wheat germ oil, a fatty acid distillate of olive oil, a fatty acid distillate of grape seed oil, a fatty acid distillate of vegetable oil, or a combination of one or more thereof.
In some embodiments, fatty acid by-products obtained from the sequential cooling urea-fatty acid complexation of the present disclosure can be easily separated from the vitamin E containing sample and subsequently used for other purposes including commercial purposes.
For example, fatty acid by-products can be used in the production of biodiesel. Palmitic acid can be used in the manufacture of pharmaceuticals, cosmetics, lube oils and food additives.
Oleic acid can be used in the manufacture of synthetic dairy products, while linoleic acid can be used in the manufacture of animal feeds, nutrient supplements, additives and medicine.
In a surprising and unexpected finding, the inventors found that sequentially reducing the cooling temperature to a series of pre-determined temperatures during the urea-fatty acid ester complexation step can significantly increase the concentration of vitamin E in a vitamin E containing sample in comparison to keeping the cooling temperature constant during the urea- fatty acid ester complexation step.
In a surprising and unexpected finding, the inventors found that sequentially reducing the cooling temperature to a series of pre-determined temperatures during the urea-fatty acid ester complexation step can result in an increase and/or improvement in the removal the majority of fatty acids from a vitamin E containing sample in comparison to keeping the cooling temperature constant during the urea-fatty acid ester complexation step. In some embodiments, the sequential cooling urea-fatty acid ester complexation of the present disclosure can be used for small-scale extracting and/or concentrating of vitamin E.
In some embodiments, the sequential cooling urea-fatty acid ester complexation of the present disclosure can be used for small-scale extracting and/or pre-concentrating of vitamin E.
In some embodiments, the sequential cooling urea-fatty acid ester complexation of the present disclosure uses inexpensive, renewable, and/or reusable materials including urea and ethanol and/or methanol as a solvent.
In some embodiments, the sequential cooling urea-fatty acid ester complexation of the present disclosure can be utilized for large scale extraction and/or concentration of vitamin E from a sample. The present disclosure offers many benefits over existing vitamin E extraction and/or concentration methods due in part to the lower temperatures utilized during the urea-fatty acid ester complexation step, the use of recyclable, economic solvents/reagents, and greatly improved yields and purity of the isolated and/or concentrated vitamin E.
Large scale extraction and/or concentration of vitamin E as described herein can result in major energy savings as compared with known methods. For example, known methods for molecular distillation of vitamin E from palm fatty acid distillate can require extraction temperatures of around 120°C. On large scale, this method would require a much higher energy expenditure as compared with the present disclosure, which in some embodiments calls for temperatures ranging from 75 to -5°C. Both the cost and environmental impact of the present disclosure can be further minimized by the use of reusable reagents and solvents, such as urea, ethanol, and carbon dioxide, and the utilization of a closed system, which can further decrease environmental impact.
In some embodiments, the sequential cooling urea-fatty acid ester complexation of the present disclosure can be used as a robust pre-concentrating step for increasing the concentration of vitamin E in a vitamin E containing sample because of the low temperature employed and environmentally friendly operating conditions. In some embodiments, the system and method of the present disclosure for extracting and/or concentrating vitamin E provides can be a safe and/or affordable system and method for concentrating vitamin E in a vitamin E containing sample. In some embodiments, the system and method of the present disclosure for extracting and/or concentrating vitamin E provides can be a safe and/or affordable system and method for extracting vitamin E from a vitamin E containing sample.
In some embodiments, the system and method of the present disclosure for extracting and/or concentrating vitamin E provides can be a safe and/or affordable system and method for producing a final vitamin E product.
One or more of the disadvantages of the Supercritical Fluid Extraction (SFE) method described above can be avoided and/or ameliorated by utilizing the system and/or method of the present disclosure for extracting and/or concentrating vitamin E. In particular, one or more of the disadvantages of SFE can be avoided and/or ameliorated by preparing a pre- concentrated vitamin E feed sample by using the sequential cooling urea-fatty acid ester complexation step of the present disclosure. In accordance with the present disclosure, the sequential cooling urea-fatty acid ester complexation can be used to effectively separate and remove fatty acids from a vitamin E containing sample, which can significantly increase the quantity of vitamin E in the sample. The step of pre-concentrating the vitamin E in the sample via the sequential cooling urea- fatty acid ester complexation prior to the final purification of the vitamin E via SFE can result in a considerable or significant reduction in the amount of sample that is fed to or loaded in the SFE apparatus in comparison to the amount of sample fed to or loaded when the sequential cooling urea-acid complexation is not performed.
In some embodiments, the step of pre-concentrating the vitamin E sample using the sequential cooling urea-fatty acid ester complexation step reduces the amount of sample fed to the SFE apparatus by about 50 times, about 40 times, about 30 times, about 20 times, about 10 times, or about 5 times less than when the step of pre-concentrating the vitamin E sample using the sequential cooling urea-fatty acid ester complexation is not employed. Additionally, the pre-concentrating of the vitamin E in the sample via the sequential cooling urea-fatty acid ester complexation prior to the final purification of the vitamin E via SFE can result in a decrease in the overall operation time of the SFE apparatus in comparison to the overall operation time when the sequential cooling urea-fatty acid ester complexation is not performed.
For example, in some embodiments, when the vitamin E sample is pre-concentrated using the sequential cooling urea-fatty acid ester complexation step prior to SFE purification, vitamin E in the sample can be concentrated from 0.5% (w/w) to 33% (w/w) (using 2 cycles of SFE purification of 60 minutes/cycle), whereas when no pre-concentration sequential cooling urea- fatty acid ester complexation step is used on the vitamin E sample prior to SFE purification, vitamin E in the sample can be concentrated from 0.5% (w/w) to 2% (w/w) ) (using 2 cycles of SFE purification of 60 minutes/cycle). Furthermore, in some embodiments, the vitamin E in a pre-concentrated sample can be further concentrated using SFE from 0.5% (w/w) to 80% (w/w) by employing five cycles of SFE (60 minutes/cycle).
In some embodiments, pre-concentrating a vitamin E sample using sequential cooling urea- fatty acid ester complexation can reduce SFE operation time by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90% as compared with SFE operation time of a vitamin E sample that has not been subjected to sequential cooling urea-fatty acid ester complexation.
Thus, the pre-concentrating of the vitamin E in the sample via the sequential cooling urea- fatty acid ester complexation prior to the final purification of the vitamin E via SFE can result in a considerable or significant reduction in the size of the SFE apparatus required in comparison to the size of the SFE apparatus required when the sequential cooling urea-fatty acid ester complexation is not performed. In some embodiments, employing sequential cooling urea-fatty acid ester complexation prior to SFE purification can result in up to a 50 fold decrease in the size of the SFE apparatus required to further concentrate the vitamin E sample.
Further, the pre-concentrating of the vitamin E in the sample via the sequential cooling urea- fatty acid ester complexation prior to the final purification of the vitamin E via SFE can result in a considerable or significant reduction in the operational costs for performing the SFE in comparison to the operation costs for performing the SFE when the sequential cooling urea- acid complexation is not performed. In some embodiments, the combination of the sequential cooling urea-fatty acid ester complexation of the present disclosure with a final SFE purification step can provide for both time efficient and cost efficient concentrating of vitamin E in comparison to the concentrating of vitamin E using only SFE. As further discussed in the examples below, when a vitamin E sample is first subjected to sequential cooling urea-fatty acid ester complexation the concentration of vitamin E in the sample increased from 0.5% (w/w) to 25% (w/w). This pre-concentrated sample could then be further concentrated using SFE, which further increased the concentration of vitamin E in the sample from 25% (w/w) to 33% (w/w) (using 2 x 60 minute SFE cycles). When a vitamin E sample is not pre-concentrated using sequential cooling urea-fatty acid ester complexation, SFE purification of the sample only increased the concentration of vitamin E in the sample from 0.5% (w/w) to 2 % (w/w) (using 2 x 60 minute SFE cycles).
In some embodiments, the final vitamin E product produced by the system and method of the present disclosure can have high purity and excellent biological activity. In some embodiments, the final vitamin E product produced by the combination of the sequential cooling urea-fatty acid ester complexation of the present disclosure with a final SFE purification step (e.g., utilizing one, two, three, four, five, six seven, or eight cycles of SFE) can have a concentration of vitamin E in the purified product of about 10% (w/w) to about 95% (w/w); about 10% (w/w) to about 85% (w/w); about 10% (w/w) to about 80% (w/w); about 10% (w/w) to about 70% (w/w); about 10% (w/w) to about 60% (w/w); about 10% (w/w) to about 50% (w/w); about 10% (w/w) to about 40% (w/w); or about 20% (w/w) to about 40% (w/w). It is well known that esters of fatty acids have an improved tendency to form urea complexes, which in turn can improve the efficiency of the sequential cooling urea fatty acid (ester) complexation step. Thus, in some embodiments, the vitamin E sample is first reacted with an alcohol under esterification conditions to convert at least some or substantially all of the fatty acids present in the vitamin E into aliphatic fatty acid esters.
In some embodiments, the alcohol used in the esterification reaction is a C1-C8 straight or branched chain alcohol. In some embodiments, the alcohol used in the esterification reaction is a C1 -C6 straight or branched chain alcohol. In some embodiments, the alcohol used in the esterification reaction is a C1-C2 alcohol.
In some embodiments, the alcohol used in the esterification reaction is methyl alcohol, ethyl alcohol, o-propyl alcohol, /'-propyl alcohol, a butyl alcohol, a pentyl alcohol, or a hexyl alcohol.
In some embodiments, the alcohol is used as the solvent for the esterification reaction. In some embodiments, the alcohol is present in a volume ratio of (alcohol: vitamin E containing sample) 1-10:1 (v.v). In some embodiments, the alcohol is present in a volume ratio of (alcohol: vitamin E containing sample): about 1 -9: 1 (v.v); about 1-8:1 (v:v); about 1- 7: l(v:v); about l-6:l(v:v); about 2-6:l(v:v); about 3-6: 1 (v.v); or about 3.5-3.5:1 (v.v). In some embodiments, the esterification reaction is conducted in the presence of an acid catalyst. The acid catalyst can be heterogeneous acid catalyst or a homogenous acid catalyst. Suitable homogenous acid catalysts that can be used include, but are not limited to hydrochloric acid, sulfuric acid, p-toluene sulfonic acid, benzene sulfonic acid, methanesulfonic acid, phosphoric acid, and other such homogenous acid catalysts known to those skilled in the art. Suitable heterogeneous acid catalysts can be used include, but are not limited to polymeric aryl sulfonic acids, such as Amberlyst® resins.
In some embodiments, the acid catalyst can be present in the esterification reaction at a concentration of about 1% (v/v), about 2% (v/v), about 3% (v/v), about 4% (v/v), about 5% (v/v), about 6% (v/v), about 7% (v/v), about 8% (v/v), about 9% (v/v), or about 10% (v/v). In some embodiments, the acid catalyst can be present in the esterification reaction at a concentration of about 1-4% (v/v). The esterification reaction can be conducted at a temperature of from about 0°C to about 120°C. In some embodiments, the esterification reaction is conducted between about 20°C to about 80°C. In some embodiments, the esterification reaction is conducted between about 50 to about 80°C.
The esterification reaction can be allowed to react until some or substantially all of the fatty acids present in the vitamin E sample are consumed, e.g., converted in to fatty acid esters or side products. In some embodiments, the esterification is allowed to react for about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 8 hours, or about 10 hours. In some embodiments, the esterification reaction is allowed to react for about 1 to about 4 hours.
Upon consumption of some or substantially all of the fatty acids present in the vitamin E sample, the temperature of the vitamin E sample can be brought to room temperature and the crude product of the esterification reaction can optionally be purified using liquid-liquid extraction.
For example, the crude reaction mixture can be partitioned between water and a non-polar volatile organic solvent in a liquid-liquid extraction step. Any non-polar volatile organic solvent can be used. Suitable non-polar volatile organic solvents include, but are not limited to aliphatic hydrocarbons, such as pentanes, hexanes, and petroleum ether, and aromatic solvents, such as benzene and toluene. The organic layer can then be collected and the water layer can optionally be re-extracted one or more times with additional portions of the same or different non-polar volatile organic solvent. The organic extracts can then be combined and concentrated, e.g., under reduced pressure, to afford the esterified sample comprising vitamin E molecules and fatty acid esters.
The esterification reaction can convert at least some or substantially all of the fatty acids present in the sample to fatty acid esters. In some embodiments, the esterified vitamin E sample contains less than about 20% (w/w), less than about 18% (w/w), less than about 16% (w/w), less than about 14% (w/w), less than about 12% (w/w), less than about 10% (w/w), less than about 9% (w/w), less than about 8% (w/w), less than about 7% (w/w), less than about 6% (w/w), less than about 5% (w/w), less than about 4% (w/w), less than about 3% (w/w), less than about 2% (w/w), less than about 1% (w/w), or less than about 0.5% (w/w) of fatty acid.
The resulting fatty acid ester sample can optionally be further purified or can be used directly in the urea-fatty acid ester complexation step.
Vitamin E can be extracted and/or concentrated using the principle of urea-fatty acid ester complexation or urea inclusion. While not wishing to be bound by theory, it is believed that urea can form an inclusion complex with C6 to C22 straight-chain fatty acids and/or fatty acid esters without entrapping bulky molecules such as vitamin E.
Urea crystallizes in a tightly packed tetragonal structure via hydrogen bonding. In the presence of guest molecules and at crystallization temperatures for urea, urea crystallizes by intermolecular attractions, such as van der Waals interaction and hydrogen bonding interactions, between the urea molecules and/or the guest molecules to form a hexagonal structure with the guest molecules within the hexagonal crystals. The developed channels of the hexagon crystals can be large enough to accommodate aliphatic chains having seven or more carbon atoms. Double bonds in a carbon chain increase the bulk of the molecule and reduce the likelihood of its inclusion with urea.
As a result, urea-fatty acid ester complexation is dependent on the number of double bonds in the fatty acid moieties. For example, monoenes are more likely to be complexed with urea as compared with dienes. Dienes, in turn, are more likely to be complexed with urea as compared to trienes.
When the target molecule is vitamin E, the bulky vitamin E molecule can be separated from other fatty acids esters and/or fatty acids using the principle of urea-fatty acid ester complexation. The fatty acids esters and/or fatty acids can be trapped inside the urea crystals while the bulky vitamin E molecule cannot be incorporated inside the urea crystals. The bulky vitamin E molecule outside the urea crystal can separated from the urea-fatty acid ester complex. Meanwhile, the fatty acid esters can be collected by decomposition of the urea structure. The esterified vitamin E sample described herein can be further concentrated by using the urea-fatty acid ester complexation process as described herein, wherein the temperature is sequentially reduced during the urea-fatty acid co-crystallization process to a series of predetermined temperatures, which can result in an increase in the removal of fatty acid esters and fatty acids present in the esterified vitamin E sample.
The urea-fatty acid ester complexation reaction is conducted in a first solvent. The selection of suitable first solvents for the urea-fatty acid ester complexation reaction is well within the skill of a person of ordinary skill in the art.
Suitable first solvents can include, but are not limited to saturated and unsaturated hydrocarbons, aromatic solvents, halogenated solvents, aliphatic alcohols, aliphatic ethers, aliphatic esters, aliphatic ketones, aliphatic amides, and mixtures thereof. Suitable first solvents can include, but are not limited to methylene chloride, chloroform, 1 ,2- dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, tetrahydropyran, 1 ,4- dioxane, ethyl acetate, acetone, 2-butanone, N,N-dimethylformamide, N,N- dimethylacetamide, methanol, ethanol, propanols, butanols, pentanols, hexanols, ethylene glycol, and mixtures thereof.
In the examples below, ethanol is used as the first solvent in the urea-fatty acid ester complexation.
The esterified vitamin E sample can be brought into contact with the first solvent and urea to form a first mixture. The amount of esterified vitamin E, urea, and first solvent used to form the first mixture is well within the skill of a person of ordinary skill in the art. In some embodiments the urea, esterified vitamin E sample, and first solvent (e.g., ethanol) are used in a ratio of about 2-8 to about 1 to about 2-8 weight:weight:volume (w:w:v) to form the first mixture.
In some embodiments the urea, esterified vitamin E sample, and first solvent are used in a ratio of about 2-8 to about 1 to about 2-7 (w:w:v); about 2-8 to about 1 to about 2-6 (w:w:v); about 2-8 to about 1 to about 3-6 (w:w:v); or about 2-8 to about 1 to about 4-5 (w:w:v) to form the first mixture.
In some embodiments the urea, esterified vitamin E sample, and first solvent are used in a ratio of about 2-7 to about 1 to about 2-8 (w:w:v); about 2-6 to about 1 to about 2-8 (w:w:v); about 3-6 to about 1 to about 2-8 (w:w:v); or about 4-6 to about 1 to about 2-8 (w:w:v) to form the first mixture.
In some embodiments, the urea, esterified vitamin E sample, and first solvent are used in a ratio of about 2-7 to about 1 to about 2-7 (w:w:v); about 2-6 to about 1 to about 2-6 (w:w:v); about 3-6 to about 1 to about 3-6 (w:w:v); about 4-6 to about 1 to about 4-6 (w:w:v); or about 4-6 to about 1 to about 5-7 (w:w:v) to form the first mixture.
In the examples below, embodiments the urea, esterified vitamin E sample, and first solvent are used in a ratio of 5: 1 :5.64 (w:w:v) to form the first mixture.
The urea, esterified vitamin E sample, and first solvent can be brought into contact sequentially or simultaneous and in any order to form the first mixture. In some embodiments, the urea, esterified vitamin E sample, and first solvent can be brought into contact under an inert atmosphere. Suitable inert atmospheres include nitrogen and argon.
The first solvent can be heated to the desired temperature before it is brought into contact with the esterified vitamin E sample and urea and/or after it is brought into contact with the esterified vitamin E sample and urea.
In the examples below, the first mixture is formed by adding the esterified vitamin E to a solution of ethanol at room temperature. Urea is then added and the resulting mixture is heated.
In some embodiments, the first mixture is formed at room temperature and then heated until some or substantially all of the urea is dissolved into the first solvent. The selection of time that the first mixture is heated is well within the skill of a person of ordinary skill in the art. In some embodiments, the length of time that the first mixture is heated is about 5 minutes to about 60 minutes, about 5 minutes to about 50 minutes, about 5 minutes to about 40 minutes, about 5 minutes to about 30 minutes, about 10 minutes to about 30 minutes, or about 10 minutes to about 20 minutes.
The selection of temperature that the first mixture is heated is well within the skill of a person of ordinary skill in the art. In some embodiments, the first mixture is heated at about 40- 210°C.
In some embodiments, the first mixture is heated at about 40-200°C, about 40-180°C, about 40-160°C, about 50-140°C, about 50-120°C, about 40-1 10°C, about 40-90°C, 50-90°C, or about 60-80°C.
The first mixture can be agitated by shaking or stirring while heat is applied.
In some embodiments, the temperature of the heated mixture is sequentially cooled to a series of pre-determined temperatures under an inert atmosphere. Suitable inert atmospheres include nitrogen and argon.
Once some or substantially all of the urea in the heated first mixture is dissolved into the first solvent, the temperature of the heated first mixture can be sequentially reduced to a series of pre-determined temperatures. In some embodiments, the temperature of the heated first mixture is reduced to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more distinct pre-determined temperatures.
In some embodiments, the temperature of the heated first mixture is reduced to 2-8, 2-7, 2-6, 3-6, 3-5, or 3-4 distinct pre-determined temperatures. In some embodiments, the temperature of the heated first mixture is reduced to 1, 2, 3, or 4 distinct pre-determined temperatures.
In some embodiments, each consecutive pre-determined temperature in the pre-determined temperature is progressively lowered until the final pre-determined temperature in the predetermined temperature sequence is reached. The temperature difference between any one of the pre-determined temperatures to the next pre-determined temperature in the pre-determined temperature sequence can differ by any amount. In some embodiments, the temperature any one of the pre-determined temperatures to the next pre-determined temperature in the pre-determined temperature sequence can differ by about 5°C, about 10°C, about 15°C, about 20°C, about 25°C, or about 30°C lower in temperature.
In some embodiments, the temperature of any one of the pre-determined temperatures to the next pre-determined temperature in the pre-determined temperature sequence can differ by about 5°C to about 25°C, about 5°C to about 20°C, or about 5°C to about 15°C lower in temperature.
In some embodiments, the first pre-determined temperature is about 25°C to about 60°C, about 25°C to about 55°C, about 25°C to about 50°C, about 20°C to about 50°C, about 25°C to about 45°C, about 25°C to about 40°C, or about 30°C to about 40°C.
In some embodiments, the second pre-determined temperature is about 0°C to about 40°C, about 0°C to about 35°C, about 0°C to about 30°C, about 0°C to about 25°C , about 5°C to about 25°C, about 5°C to about 20°C, or about 10°C to about 40°C.
In some embodiments, the third pre-determined temperature is about -15°C to about 20°C, - 15°C to about 15°C, -15°C to about 10°C, -10°C to about 10°C, -5°C to about 10°C, or 0°C to about 10°C. In some embodiments, the fourth pre-determined temperature is about -25°C to about 10°C, about -20°C to about 10°C, about -15°C to about 10°C, about -15°C to about 5°C, about - 15°C to about 0°C, or about -10°C to about 5°C.
Once the temperature of the heated first mixture reaches any one of the first distinct pre- determined temperature through to the penultimate distinct pre-determined temperature, the temperature of the heated mixture can be maintained at the pre-determined temperature for a period of from about 1 minute to about 120 minutes; about 5 minutes to about 120 minutes; about 5 minutes to about 110 minutes; about 5 minutes to about 100 minutes; about 5 minutes to about 90 minutes; about 5 minutes to about 80 minutes; about 5 minutes to about 70 minutes; about 5 minutes to about 60 minutes; about 5 minutes to about 50 minutes; or about 10 minutes to about 50 minutes. Once the temperature of the heated first mixture reaches any one of the first distinct predetermined temperature through to the penultimate distinct pre-determined temperature, the temperature of the heated mixture can be maintained at the distinct pre-determined temperature for a period greater than about 1 minute, greater than about 5 minutes, greater than about 10 minutes, greater than about 15 minutes, greater than about 20 minutes, greater than about 25 minutes, greater than about 30 minutes, greater than about 35 minutes, greater than about 40 minutes, greater than about 45 minutes, greater than about 50 minutes, greater than about 55 minutes, or greater than about 60 minutes.
In some embodiments, the temperature of the first pre-determined distinct temperature is maintained for about 1 minute to about 60 minutes, about 1 minute to about 50 minutes, about 1 minute to about 40 minutes, about 1 minute to about 30 minutes, about 5 minutes to about 30 minutes, about 10 minutes to about 30 minutes, or about 10 minutes to about 20 minutes.
In some embodiments, the temperature of the first pre-determined distinct temperature is maintained for a period greater than about 1 minute, greater than about 5 minutes, greater than about 10 minutes, or greater than about 12 minutes.
In some embodiments, the temperature of the second pre-determined distinct temperature is maintained for about 1 minute to about 60 minutes, about 10 minutes to about 60 minutes, about 20 minutes to about 60 minutes, about 20 minutes to about 50 minutes, or about 20 minutes to about 40 minutes.
In some embodiments, the temperature of the second pre-determined distinct temperature is maintained for greater than about 1 minute, greater than about 5 minutes, greater than about 10 minutes, greater than about 15 minutes, greater than about 20 minutes, greater than about 25 minutes, or greater than about 27 minutes. In some embodiments, the temperature of the third pre-determined distinct temperature is maintained for about 10 minutes to about 90 minutes, about 10 minutes to about 80 minutes, about 10 minutes to about 70 minutes, about 10 minutes to about 60 minutes, about 20 minutes to about 60 minutes, about 30 minutes to about 60 minutes, about 35 minutes to about 60 minutes, about 35 minutes to about 55 minutes, about 35 minutes to about 50 minutes, or about 35 minutes to about 45 minutes.
In some embodiments, the temperature of the third pre-determined distinct temperature is maintained for a period greater than about 1 minute, greater than about 5 minutes, greater than about 10 minutes, greater than about 15 minutes, greater than about 20 minutes, greater than about 25 minutes, greater than about 30 minutes, greater than about 35 minutes, greater than about 40 minutes, or greater than about 42 minutes.
In some embodiments, in which there are more than four pre-determined distinct temperatures in the pre-determined temperature sequence, the temperature of the fourth pre-determined distinct temperature through the penultimate distinct temperature is maintained for about 10 minutes to about 90 minutes, about 10 minutes to about 80 minutes, about 10 minutes to about 70 minutes, about 10 minutes to about 60 minutes, about 20 minutes to about 60 minutes, about 30 minutes to about 60 minutes, about 35 minutes to about 60 minutes, about 35 minutes to about 55 minutes, about 35 minutes to about 50 minutes, or about 35 minutes to about 45 minutes.
Once the temperature of the heated first mixture reaches the final distinct pre-determined temperature, the temperature of the final pre-determined temperature can be maintained long enough for some or substantially all of the fatty acids and/or fatty acid esters present in the heated first mixture to co-crystallize with the urea. In some embodiments, the temperature of the heated first mixture is maintained at the final pre-determined temperature for a period of about 1 hour to about 20 hours; about 2 hours to about 20 hours; about 3 hours to about 20 hours; about 4 hours to about 20 hours; about 5 hours to about 20 hours; about 6 hours to about 20 hours; about 7 hours to about 20 hours; about 7 hours to about 19 hours; about 7 hours to about 18 hours; about 7 hours to about 17 hours; about 7 hours to about 16 hours; about 8 hours to about 16 hours; about 9 hours to about 16 hours; about 9 hours to about 15 hours; about 9 hours to about 14 hours; or about 10 hours to about 14 hours. In some embodiments, the heated mixture is agitated by shaking or stirring during the period of time that the temperature of the heated mixture is maintained at any of the pre-determined temperatures. In some embodiments, the heated mixture is agitated by shaking or stirring every 1 -5, 2-5, 2- 4, or 2-3 minutes during the period of time that the temperature of the heated mixture is maintained at any of the pre-determined temperatures.
After the heated mixture is allowed to remain at the final temperature of the pre-determined temperature sequence for the allotted period of time, the liquid phase is separated from the precipitated urea-fatty acid ester and/or urea-fatty acid complex.
The precipitated urea-fatty acid ester and/or urea-fatty acid complex can optionally be washed with additional portions of organic solvent to increase the amount of vitamin E recovered. Suitable organic solvents useful for washing the precipitated urea-fatty acid ester and/or urea- fatty acid complex include aliphatic hydrocarbons, aromatic solvents, and alcohols.
Suitable organic solvents useful for washing the precipitated urea-fatty acid ester and/or urea- fatty acid complex include methanol, ethanol, propanols, butanols, pentanols, hexanols, and mixtures thereof.
The recovered organic solvent used to wash the precipitated urea-fatty acid ester and/or urea- fatty acid complex can then be combined with the liquid phase recovered from the heated mixture to give a combined liquid phase containing vitamin E.
The combined liquid phase containing vitamin E can optionally be further purified. In some embodiments, the combined liquid phase containing vitamin E is further purified by liquid- liquid extraction. In such embodiments, the combined liquid phase containing vitamin E can be partitioned between water and an organic extraction solvent. The organic extraction solvent containing the vitamin E is then collected and the water layer can be re-extracted one or more times using additional portions of the same or different organic extraction solvent. Suitable organic extraction solvents include, but are not limited to aliphatic hydrocarbons, aromatic solvents, ethers, acetates, and haloalkanes.
In some embodiments, the organic extraction solvent is a C4-C20 branched or unbranched hydrocarbon or mixtures thereof. In some embodiments the organic extraction solvent is pentanes, hexanes, or peteroleum ether.
After the liquid-liquid extraction purification of the esterified sample of vitamin E has been completed, all of the organic extraction solvent fractions containing vitamin E can be combined.
The combined organic extraction solvent fractions containing vitamin E can then be optionally washed with one or more portions of distilled water and then the organic extraction solvent can be separated from the vitamin E thereby forming pre-concentrated vitamin E.
Suitable methods for removing the organic extraction solvent include, but are not limited to atmospheric distillation and distillation under reduced pressure.
The pre-concentrated vitamin E can then be further purified using supercritical fluid extraction.
A supercritical fluid is a material that can be either liquid or gas used in a state above the critical temperature and critical pressure where gases and liquids can coexist. A supercritical fluid has a low viscosity and has better transport properties than liquids. As such, a supercritical fluid can diffuse easily through solid materials and, thus, provide for faster extraction yields. Importantly, the density of the supercritical fluid can be modified by altering the pressure and/or temperature of the supercritical fluid.
Many types of solvents can be used for supercritical extraction. The most applicable - supercritical fluid solvent for extraction of natural products for foods and medicines is supercritical carbon dioxide (C02). Supercritical carbon dioxide (SC-C02) is inactive, relatively non-toxic, relatively inexpensive, easily obtainable, odourless, tasteless, nonflammable and environmentally friendly. SC-C02 is a Generally Recognized As Safe (GRAS) solvent and can be recycled. SC-C02 has a convenient critical temperature (i.e., 31.3°C) and pressure (i.e., 7.38 MPa). SC-C02 is a gas at room temperature; thus, once the extraction is completed and the system is decompressed, a substantial exclusion of SC-C02 is achieved without residues thereby yielding a solvent-free product.
In some embodiments, the supercritical fluid extraction step of the present disclosure utilizes carbon dioxide as the supercritical fluid.
The general process of supercritical fluid extraction can be divided into two steps: (1) exclusion of the target molecule from the matrix to the surface of the matrix particle; and (2) solvation of the target molecule in the supercritical fluid and transport of the target molecule in the supercritical fluid to the collection device. The first step can be regarded as an irreversible desorption/diffusion process and the second step can be regarded as a chromatographic or reversible elution process. The second step is mainly governed by the solubility of the target molecule in the supercritical fluid. Both the first step and second step affect the rate of extraction.
SC-C02 can be used to extract and enrich vitamin E from plants, vegetable oils, palm oil, crude palm oil, rice oil, rice bran oil, wheat germ oil, olive oil ,grape seed oil, soy bean oil, avocado oil, soybean oil deodorizer distillate, wheat germ, and by-products thereof. The operating conditions for extracting vitamin E can be modified based on the type of the sample fed or loaded into the supercritical fluid extraction apparatus.
In some embodiments, the fluid used in the supercritical fluid extraction can be carbon dioxide.
EXAMPLES
Urea-fatty acid ester complexation process in accordance with
an embodiment of the present disclosure
In accordance with an embodiment of the present disclosure, the overall process of urea-fatty acid ester complexation comprises three steps. Treatment of Vitamin E Sample to Form Esterified Vitamin E Sample
Palm fatty acid distillate (20 g) was added to anhydrous ethanol (95% v/v) under a nitrogen atmosphere. Concentrated H2S04 (2 mL) was then added to the reaction mixture. A reflux condenser is attached to the reaction vessel and the reaction mixture was heated to reflux (70°C) under nitrogen and stirring.
After two hours, the reaction mixture was cooled to room temperature and then was transferred to a light-proof separately funnel containing distilled water (100 mL) and hexanes (100 mL). The separatory funnel was shaken several times. The two layers were allowed to settle and the organic layer was collected. The organic layer was washed with distilled water (100 mL). The aqueous layer was extracted with an additional portion of hexanes (50 mL).
The organic fractions were combined and the hexanes was evaporated at 60°C under reduced pressure (335 mbar). Ethanol (10 mL, 95% (v/v)) was then added to the concentrated sample and the sample was dried by azeotropic drying at 60°C under reduced pressure (72 mbar) to yield 13.03 grams of an esterified fatty acid ethyl ester vitamin E sample. The concentration of vitamin E in the esterified sample was 8428 ppm.
Urea-Fatty Acid Ester Complexation
The esterified fatty acid ethyl ester (20 g) produced above was added to ethanol (95% v/v) under a nitrogen atmosphere. Urea (100 g) was added and the resulting reaction mixture was heated to 70°C under a nitrogen atmosphere with shaking for 15 minutes. During which time substantially all of the urea dissolved into solution.
The reaction vessel was then flushed with nitrogen and the temperature of the reaction mixture was reduced to 35°C during which time the reaction mixture was shaken every 2-3 minutes.
Upon reaching 35°C, the temperature of the reaction mixture was maintained at 35°C for 15 minutes. Every 2-3 minute over the 15 minute interval, the reaction mixture was shaken.
The temperature of the reaction mixture was then reduced to 25°C and the temperature was maintained at 25°C for 30 minutes. Every 2-3 minute over this 30 minute interval, the reaction mixture was shaken. The temperature of the reaction mixture was then reduced to 15°C and the temperature was maintained at 15°C for 60 minutes. Every 2-3 minute over this 60 minute interval, the reaction mixture was shaken. The temperature of the reaction mixture was then reduced to 5°C and the temperature was maintained at 5°C for 90 minutes. Every 2-3 minute over this 90 minute interval, the reaction mixture was shaken.
The temperature of the reaction mixture was then reduced to -5°C and the temperature was maintained at -5°C for 720 minutes. During this 720 minute interval, the reaction mixture was not shaken.
The precipitate was filtered off and the filtrate collected. The precipitate was then washed with 100 mL of ethanol (95% v/v) at -20°C.
The combined filtrate was then added to a separatory funnel under nitrogen and partitioned between hexanes (50 mL) and distilled water (50 mL). The separatory funnel was gently shaken with venting. The separatory funnel was allowed to sit until the two phases separated. The organic layer was collected and the aqueous layer was extracted with hexanes (2 X 50 mL). The organic layers were combined and washed with distilled water (50 mL).
The organic layer was then concentrated at 60°C under reduced pressure (335 mbar). Ethanol (10 mL, 95% v/v) was added to the concentrated and the resulting solution was dried using azeotropic drying at 60°C under reduced pressure (72 mbar) to yield 0.64 g of the urea-fatty acid ester complexation pre-concentrated vitamin E sample. The concentration of each of the vitamin E isomers present in the pre-concentrated vitamin E sample obtained using sequential reduction of the cooling temperature are presented in the table below. Concentration of Vitamin E Isomers in Pre-Concentrated Vitamin E Sample Obtained Using Sequential Reduction of the Cooling Temperature
Vitamin E isomers Concentration (ppm)
Alpha-tocopherol
92450±1724
Alpha-tocotrienol 43512+516
Beta-tocopherol 1885±39
Beta-tocotrienol 7783±155
Gamma-tocopherol 8518±395
Gamma-tocotrienol 71986±787
Delta-tocopherol 3326±1 19
Delta-tocotrienol 22136±528
Total tocopherol* 106181+2278 (42.20 %w/w)
Total tocotrienol* 145419±1987 ( 57.80%w/w)
Total vitamin E** 251600±4266 (25.16 %w/w)
Remark: * The percentage of total- tocopherol and total- tocotrienol calculated from total vitamin E
** The percentage of total vitamin E calculated from vitamin E derivatives in 100 g of sample
The pre-concentrated vitamin E sample obtained using sequential reduction of the cooling temperature was analysed using high-performance liquid chromatography (SHIMADZU- HPLC model HPLC LC-10Avp™), which utilized a low pressure gradient consisting of a CBM-IOA™ System controller, DGU-12A™ In-Line Degasser, LC-10AD Pump™, CTO- 10A™ Oven using silica column contained with 0.5 μιη Pinnacle II silica™. The column had measured 250 X 4.6 mm (RESTEK Serial No. 10070775M) assembled with a guard column and the sample was injected into the column manually. The sample was measured using a RF-10AXL fluorescence detector and all functions were controlled by the program of CLASS-LC10 version 1.64™ software.
The following analytical conditions were used for HPLC analysis of the vitamin E sample. Analytical conditions
Mobile phase Hexane:Isopropanol, 99:1
Injection volume 20 μηιΐ
Flow rate 1.7 ml/min
Analysis time 20 min
Column temperature 30° C
Detector Fluorescence Detector (Excitation 290 rim/Emission 330 nm)
Calibration External standard calibration The pre-concentrated vitamin E sample obtained using sequential reduction of the cooling temperature was determined to have a vitamin E concentration of 143,319 ppm (14.33% w/w).
COMPARATIVE EXAMPLE
As a Comparative Example, urea-fatty acid ester complexation was also performed with a Vitamin E containing sample (Sample 2) using a constant cooling method.
Treatment of Vitamin E Sample to Form Esterified Vitamin E Sample
The esterified vitamin E sample was prepared in the same fashion as described above.
Urea-Fatty Acid Ester Complexation
The esterified fatty acid ethyl ester (20 g) was added to ethanol (95% v/v) under a nitrogen atmosphere. Urea (100 g) was added and the resulting reaction mixture was heated to 70°C under a nitrogen atmosphere with shaking for 15 minutes. During which time substantially all of the urea dissolved into solution.
The reaction vessel was then flushed with nitrogen and the temperature of the reaction mixture was reduced to -5°C and maintained at this temperature for 12 hours. The precipitate was filtered off and the filtrate collected. The precipitate was then washed with 100 mL of ethanol (95% v/v) at -20°C.
The combined filtrate was then added to a separatory funnel under nitrogen and partitioned between hexanes (50 mL) and distilled water (50 mL). The separatory funnel was gently shaken with venting. The separatory funnel was allowed to sit until the two phases separated. The organic layer was collected and the aqueous layer was extracted with hexanes (2 X 50 mL). The organic layers were combined and washed with distilled water (50 mL). The organic layer was then concentrated at 60°C under reduced pressure (335 mbar). Ethanol (10 mL, 95% v/v) was added to the concentrated and the resulting solution was dried using azeotropic drying at 60°C under reduced pressure (72 mbar) to yield 0.39 g of the pre- concentrated vitamin E sample. The pre-concetrated vitamin E sample was analysed using high-performance liquid chromatography (HPLC). The pre-concentrated vitamin E sample prepared using the constant cooling method was determined to have a vitamin E concentration of 88,499 ppm (8.85% w/w). The concentration of each of the vitamin E isomers present in the pre-concentrated vitamin E sample obtained using conventional coolingare as summarized in the table below.
Concentration of Vitamin E Isomers in Pre-Concentrated Sample Obtained Using Conventional Cooling
Vitamin E Concentration (ppm) isomers
Alpha-tocopherol 35716±157
Alpha-tocotrienol 20109±257
Beta-tocopherol 250±21
Beta-tocotrienol 370±6
Gamma-tocopherol 2824+359
Gamma-tocotrienol 23330+101 1
Delta-tocopherol 162±20
Delta-tocotrienol 5735+330
Total tocopherol* 38954±203 (44.02% w/w)
Total tocotrienol* 49545 +1091 (55.98% w/w)
Total vitamin E** 88499+1294 (8.85% w/w) * The percentage of total- tocopherol and total- tocotrienol calculated from total vitamin E
**The percentage of total vitamin E calculated from vitamin E derivatives in 100 g of sample
RESULTS OF UREA-FATTY ACID ESTER COMPLEXATION FOR THE
EXAMPLE AND COMPARATIVE EXAMPLE
The results of the Inventive Example and Comparative Example illustrated that the efficacy of urea-fatty acid ester complexation was indeed affected by the cooling pattern. The use of sequential reduction of the cooling temperature (e.g., crystallization temperature of urea) to the series of predetermined temperatures provided an increase in the quantity or concentration of vitamin E in the resulting sample when compared to using a constant cooling temperature.
For Sample 1 of the Inventive Example, the sequential reduction of the cooling temperature (e.g., crystallization temperature of urea) resulted in a residue having a vitamin E concentration of 251,600 ppm, while for Sample 2 of the Comparative Example the constant cooling method resulted in a residue having a vitamin E concentration of 88,499 ppm. Thus, the quantity or concentration of vitamin E increased from 8.85% under the constant cooling method to 25.16% w/w under the sequential reduction of the cooling temperature of the present disclosure. Sequentially reducing the cooling temperature to a series of predetermined temperatures resulted in a 75% increase in vitamin E quantity or concentration when compared to using the constant cooling method.
Further, the percent recovery of vitamin E was elevated from 21.62% under the constant cooling method to 32.04% under the sequential reduction of the cooling temperature. As can be seen, the cooling patterns had an influence on urea-fatty acid ester complexation. While not wishing to be bound by theory, it is believed that the sequential reduction of the cooling temperature altered the structure of urea crystals to favor fatty acid inclusion to a greater degree than the constant cooling method.
The ratio of urea to the esterified sample, the ratio of 95% ethyl alcohol to the esterified sample, and the reaction temperature showed a typical effect on vitamin E concentration, vitamin E recovery and vitamin E production yield. The effect of reaction temperature on the concentration of vitamin E and recovery of vitamin E was relatively high compared to the effect of the ratio of urea to the esterified sample. Out of the three variables mentioned here, the ratio of 95% ethyl alcohol to the esterified sample was the most significant variable affecting the degree of vitamin E production yield.
A study of the optimal conditions for urea-fatty acid ester complexation by sequential reduction of the cooling temperature showed that the concentration of total vitamin E tended to increase when the ratio of urea to vitamin E mixture is increased and the reaction temperature is increased.
Our experiments indicated that the interaction between the ratio of urea to vitamin E mixture and the ratio of ethanol (95% v/v) to vitamin E mixture resulted in the increasing of concentration of total vitamin E isolated, when the ratio of urea to vitamin E mixture was increased and proportion of urea to ethanol (95% v/v) was 1 : 1. The proportion of urea to ethanol (95% v/v) is related to the concentration of urea solution, which related to the reaction temperature. The concentration of total vitamin E was increased by increasing concentration of urea solution and reaction temperature. However, increasing the concentration of urea solution showed greater effect on increasing concentration of total vitamin E than the reaction temperature.
Conditions for the urea-fatty acid ester complexation by sequential reduction of the included the following: a ratio of urea to the esterified sample of 5: 1 (weight: weight); a ratio of ethanol (95% v/v) to the esterified sample of 5.64: 1 (volume:weight); and a reaction temperature of 70°C for 15 minutes under an atmosphere of nitrogen. The cooling temperature (e.g., the crystallization temperature of urea) can be reduced sequentially according to the following series of pre-determined temperatures and for the following series of pre-determined times: 25°C for 15 minutes, 15°C for 30 minutes, 5°C for 45 minutes, and finally -5°C for 12 hours. The Sample 1 can be shaken for 2-3 minutes at each predetermined cooling temperature. Purification methods, which included sequential reduction in cooling temperature yielded a pre-concentrated vitamin E with a purity of 25.16% total vitamin E (w/w) and an 85.93%) recovery of Vitamin E from the vitamin E sample. Referring to FIG. 2, microscopic images were taken of the urea crystals formed in Sample 2 of the Comparative Example (see FIG. 2A) and the urea crystals formed in Sample 1 of the Example (see FIG. 2B). The microscopic images at 40X magnification demonstrated that a urea crystal formed from urea-fatty acid ester complexation under a constant cooling temperature was larger than the urea crystal formed from urea-fatty acid ester complexation under sequential reduction of the cooling temperature. While not wishing to be bound by theory, it is believed that different sizes of the observed urea crystals could be due, in part, to the shaking interval used for Sample 1 of the Example. The Sample 1 of the Example, which underwent urea-fatty acid complexation sequential reduction of the cooling temperature, required shaking for 2-3 minutes at each predetermined cooling temperature. The repeated shaking may enhance the collision between urea molecules and fatty acid molecules. The collisions may increase the van der Waals attractions that assist in developing the small urea crystals. As a result of the smaller size, the concentration of total vitamin E outside the crystals could be increased.
Supercritical Fluid Extraction
Referring to Figure 1 , a commercial supercritical fluid extraction apparatus (TharTechnologies™ Model SFE-100-2-Base™) was used to further concentrate and/or extract vitamin E from the residue (Sample 1 residue) formed from the third step of the sequential cooling urea-fatty acid ester complexation. The optimal conditions used for the vitamin E extraction included: a SC-C02 flow rate of 10 g/min; an extraction time of 60 min; a pressure of 325 bar; and an extraction temperature of 33.18°C. 60.03 g of Sample 1 residue was subjected to the aforementioned supercritical fluid extraction protocol five times. The results of each extraction are summarized below.
Amount of Sample Obtained Total Concentration of
SCF Extraction Run (Cycle)
After Extraction (g) Vitamin E (ppm)
Amount of Sample Before
60.03 255,600
SCF Extraction
First SCF Extraction 51.13 294,933
Second SCF Extraction 43.31 330,207
Third SCF Extraction 41.31 358,937
Fourth SCF Extraction 35.87 412,735
Fifth SCF Extraction 13.57 797,691 RESULTS OF UREA-FATTY ACID ESTER COMPLEXATION AND
SUPER-CRITICAL FLUID EXTRACTION
The SC-C0 extraction under the optimal conditions described above for 5 cycles of SC-C02 extraction combined with the sequential cooling urea-fatty acid ester complexation enriched the concentration of vitamin E from 25.16 wt. % to 79.77 wt. %. The impurities present in the 79.77 wt. % vitamin E included squalene (72.81 wt. % relative to the weight of impurities in the sample), oleic acid (12.59 wt. % relative to the weight of impurities in the sample), linoleic acid (10.00 wt. % relative to the weight of impurities in the sample), linoleic acid ethyl ester (2.98 wt. % relative to the weight of impurities in the sample) and oleic acid ethyl ester (1.62 wt. % relative to the weight of impurities in the sample).
ANTIOXIDANT ACTIVTY OF THE CONCENTRATED VITAMIN E
The biological activity of vitamin E can be determined by the scavenging activity and the antioxidant activity of the sample.
Vitamin E concentrated by the combined processes of sequential cooling urea-fatty acid ester complexation with SC-C02 extraction provided a l ,l-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging effect of 88.37%, which is greater than the DPPH scavenging effect obtained from commercial natural mixed tocopherol (87.85%) and synthetic alpha-tocopherol (87.19%).
Vitamin E concentrated by the combined processes of sequential cooling urea-fatty acid ester complexation with SC-C02 extraction demonstrated a superoxide radical scavenging ability of 53.19. Whereas commercial vitamin E demonstrated a superoxide radical scavenging ability of 43.56%.
APPLICATION
The system and/or method of the present disclosure can be used to concentrate vitamin E extracted from fatty acid distillates of palm oil, soybean oil, avocado oil, wheat germ oil, rice oil, rice bran oil, olive oil, grape seed oil, crude palm oil, and/or vegetable oil. Other potential applications include the extracting and/or concentrating of vitamin E from other vitamin E containing materials, vitamin E containing foods, or vitamin E containing compounds. The system and/or method of the present disclosure for extracting and/or concentrating vitamin E can be used to pre-concentrate vitamin E in a sample prior to the final purification of the vitamin E in the sample by SFE. The system and/or method of the present disclosure for extracting and/or concentrating vitamin E can be used to provide a high purity vitamin E product.
While various aspects and embodiments have been disclosed herein, it will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit of the invention being indicated by the appended claims.

Claims

1. A method of concentrating vitamin E in a vitamin E containing sample, comprising: esterifying the vitamin E containing sample to form an esterified sample comprising vitamin E molecules and fatty acid esters;
contacting the esterified sample with a first solvent and urea to form a first mixture; heating the first mixture to form a heated mixture;
sequentially reducing the temperature of the heated mixture to a series of predetermined temperatures;
thereby forming a solid phase comprising a urea-fatty acid ester complex and a liquid phase comprising the first solvent and vitamin E;
separating the liquid phase from the solid phase; and removing the first solvent from the liquid phase thereby forming a concentrated sample of vitamin E.
2. The method of claim 1 , wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to at least two distinct pre-determined temperatures.
3. The method of claim 1 or 2, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises pre-determined temperatures between about 50°C to about -25°C.
4. The method of any one of claims 1-3, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about 20°C and about 50°C.
5. The method of any one of claims 1-3, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about 0°C and about 30°C.
6. The method of any one of claims 1-3, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the then temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 25°C.
7. The method of any one of claims 1-3, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about -20°C and about 10°C.
8. The method of claim 4, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about 20°C and about 50°C for a period of time greater than 5 minutes.
9. The method of claim 5, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about 0°C and about 30°C for a period of time greater than 5 minutes.
10. The method of claim 6, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 5 minutes.
1 1. The method of claim 7, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 1 hour.
12. The method of claim 8, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures further comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about 0°C and about 30°C for a period of time greater than 5 minutes.
13. The method of claim 12, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures further comprises reducing and then maintaining the temperature of the heated mixture at a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 5 minutes.
14. The method of claim 13, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures further comprises reducing the temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 1 hour.
15. The method of claim 1 , wherein the step of heating the mixture comprises heating the mixture to a temperature of about 40°C to about 100°C.
16. The method of claim 1 , wherein the first solvent is an alcohol.
17. A method of concentrating vitamin E in a vitamin E containing sample comprising: esterifying the vitamin E containing sample to form an esterified sample comprising vitamin E molecules and fatty acid esters;
contacting the esterified sample with a first solvent and urea to form a first mixture; heating the first mixture at a temperature of about 40°C to about 100°C to form a heated mixture;
sequentially reducing the temperature of the heated mixture to a series of predetermined temperatures, wherein the step of sequentially reducing the temperature of the heated mixture to a series of pre-determined temperatures comprises:
reducing and then maintaining the temperature of the heated mixture at a predetermined temperature of between about 20°C and about 50°C for a period of time greater than 5 minutes, reducing and then maintaining the temperature of the heated mixture at a predetermined temperature of between about 0°C and about 30°C for a period of time greater than 5 minutes,
reducing and then maintaining the temperature of the heated mixture at a pre- determined temperature of between about -10°C and about 20°C for a period of time greater than 5 minutes, and
reducing the temperature of the heated mixture to a pre-determined temperature of between about -10°C and about 20°C for a period of time greater than 1 hour;
thereby forming a solid phase comprising a urea-fatty acid ester complex and a liquid phase comprising the first solvent and vitamin E;
separating the liquid phase from the solid phase; and removing the first solvent from the liquid phase thereby forming a concentrated sample of vitamin E.
18. The method of any one of claims 1 -17, further comprising the step of further purifying the concentrated sample of vitamin E.
19. The method of claim 18, wherein the step of further purifying the concentrated sample of vitamin E comprises supercritical fluid extraction, saponification, transesterification, acid catalysed hydrolysis, enzymatic hydrolysis, molecular distillation, solvent fractionation, membrane filtration, liquid chromatography, or a combination of two or more thereof.
20. The method of claim 19, wherein the step of further purifying the concentrated sample of vitamin E comprises supercritical fluid extraction.
21. The method of claim 1 or 17, wherein the vitamin E containing sample comprises a fatty acid distillate selected from the group consisting of a fatty acid distillate of palm oil, a fatty acid distillate of soybean oil, a fatty acid distillate of avocado oil, a fatty acid distillate of wheat germ oil, a fatty acid distillate of olive oil, a fatty acid distillate of grape seed oil, a fatty acid distillate of vegetable oil or a combination of two or more thereof.
PCT/TH2014/000039 2014-08-18 2014-08-18 A system and method for extracting and/or concentrating vitamin e WO2016028235A1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108299373A (en) * 2018-05-07 2018-07-20 宜春大海龟生命科学有限公司 The method that natural VE is extracted from rice bran oil deodorization distillate
CN111530122A (en) * 2020-06-02 2020-08-14 中国科学技术大学先进技术研究院 Supercritical extraction-molecular distillation combined device

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4594437A (en) * 1985-02-21 1986-06-10 Uc Unitas Corporation Process for recovering tocopherols from deodorizer sludge
EP0255824B1 (en) * 1985-12-19 1990-01-24 Norsk Hydro A/S A process for the production of refined fish oil concentrate
US5670669A (en) * 1993-08-06 1997-09-23 Henkel Corporation Recovery of tocopherols
US6414166B1 (en) * 1999-12-29 2002-07-02 National Science Council Process for preparing tocopherol concentrates
US20060189815A1 (en) * 2005-02-17 2006-08-24 Tou Gee P Quality of crude oils and fats and recovery of minor components

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4594437A (en) * 1985-02-21 1986-06-10 Uc Unitas Corporation Process for recovering tocopherols from deodorizer sludge
EP0255824B1 (en) * 1985-12-19 1990-01-24 Norsk Hydro A/S A process for the production of refined fish oil concentrate
US5670669A (en) * 1993-08-06 1997-09-23 Henkel Corporation Recovery of tocopherols
US6414166B1 (en) * 1999-12-29 2002-07-02 National Science Council Process for preparing tocopherol concentrates
US20060189815A1 (en) * 2005-02-17 2006-08-24 Tou Gee P Quality of crude oils and fats and recovery of minor components

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108299373A (en) * 2018-05-07 2018-07-20 宜春大海龟生命科学有限公司 The method that natural VE is extracted from rice bran oil deodorization distillate
CN108299373B (en) * 2018-05-07 2021-01-12 宜春大海龟生命科学有限公司 Method for extracting natural vitamin E from rice bran oil deodorizer distillate
CN111530122A (en) * 2020-06-02 2020-08-14 中国科学技术大学先进技术研究院 Supercritical extraction-molecular distillation combined device

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