A method for separating high purity d-delta-tocopherol from mixed tocopherols

Abstract

This invention discloses a method for separating and obtaining high-purity D-δ-tocopherol from mixed tocopherols. The method of this invention includes (1) mixing mixed tocopherols with a loading solvent and adsorbing them onto an anion exchange resin column, then eluting them with an eluent, collecting the D-δ-tocopherol enriched fraction and removing the solvent to obtain crude D-δ-tocopherol; wherein the mixed tocopherols contain D-δ-tocopherol and at least one selected from D-α-tocopherol, D-β-tocopherol, and D-γ-tocopherol; (2) mixing the crude D-δ-tocopherol with a raw material solvent to obtain a raw material solution; then fractionally extracting the raw material solution using an extractant containing an ionic liquid to obtain an extract rich in D-δ-tocopherol; (3) back-extracting the extract to obtain high-purity D-δ-tocopherol. The method of this invention couples adsorption and extraction processes, which can obtain high-purity D-δ-tocopherol from mixed tocopherols with low D-δ-tocopherol content, reducing the amount of extractant used, saving costs, and increasing efficiency.

Description

Technical Field

[0001] This application relates to a method for separating and obtaining high-purity D-δ-tocopherol from a mixture of tocopherols. Background Technology

[0002] D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol are the main components of natural vitamin E (also known as tocopherol). These four homologues have extremely similar molecular structures, differing only in the number and position of methyl groups on the benzene ring. This minute structural difference leads to differences in their physiological functions and physicochemical properties: in terms of biological activity, the generally accepted order is D-α- > D-β- > D-γ- > D-δ-tocopherol; however, in terms of in vitro antioxidant activity, this order is exactly reversed: D-δ- > D-γ- > D-β- > D-α-tocopherol. D-δ-tocopherol exhibits the highest in vitro antioxidant activity and is considered a highly safe natural antioxidant. Therefore, the efficient separation of highly antioxidant D-δ-tocopherol from mixtures has significant economic value and broad application prospects.

[0003] However, achieving efficient separation of D-δ-tocopherol presents significant technical challenges. First, as mentioned above, the four homologues exhibit extremely small structural differences, making separation highly challenging. Second, in natural tocopherols, D-β-tocopherol and D-γ-tocopherol are the most abundant, accounting for over 60%, while the content of D-δ-tocopherol is typically low (around 20%), and its separation is affected by numerous other components (especially D-β- and D-γ-tocopherol).

[0004] Various separation methods based on adsorption or chromatography principles have been disclosed in this field. For example, Chinese patent CN108675980A discloses a high-pressure preparative liquid chromatography method that can obtain D-δ-tocopherol monomers with extremely high purity, but this method is not suitable as an economical means for large-scale industrial production. Chinese patent CN108101877B discloses a rotating disk continuous chromatography method that uses a strong base anion exchange resin and attempts to achieve continuous separation in one step by setting up multiple complex elution units, but this method has a complex system design and huge equipment investment. A method disclosed in Chinese patent CN101445498A requires two ion exchange chromatography operations and can finally obtain D-δ-tocopherol products with a purity of over 80%, but the process is lengthy and the purity is limited. The "silica gel-resin coupled adsorption" method disclosed in Chinese patent CN104230872A proves that the idea of ​​"coarse enrichment + adsorption purification" is feasible. In addition, some literature has reported methods for separating D-δ-tocopherol by liquid-liquid extraction using strongly hydrogen-bonded basic ionic liquids. This extraction method features high separation efficiency, a simple process flow, and ease of scale-up, making it suitable for industrial production. It demonstrates high efficiency in processing D-δ-tocopherol feedstocks with concentrations greater than 70%, yielding high-purity products. However, when this method is directly applied to process low-concentration feedstocks, the significant interference from D-β and D-γ homologues drastically increases the number of extraction stages required for separation, resulting in substantial recycling volumes of extractant and solvent, and consequently, excessively high separation costs.

[0005] In summary, there is an urgent need to develop a new process route to solve the technical challenge of large-scale preparation of high-purity D-δ-tocopherol from mixed tocopherols with low D-δ-tocopherol content in an economical and efficient manner. Summary of the Invention

[0006] To address one of the aforementioned technical problems in the prior art, this invention provides a method for separating and obtaining high-purity D-δ-tocopherol from a mixture of tocopherols. Compared to using resin adsorption alone for separating D-δ-tocopherol, this method offers a larger processing capacity and a simpler process. Furthermore, it is more economical than using extraction alone when processing low-concentration raw materials.

[0007] The method of this invention couples resin adsorption with ionic liquid extraction. First, D-δ-tocopherol is efficiently enriched using anion exchange resin. Then, the enriched product is used as a raw material and extracted and purified using an extractant containing ionic liquid. This solves the technical problem of the existing process being unable to economically and efficiently prepare high-purity D-δ-tocopherol from low-content raw materials.

[0008] The technical solution of the present invention is as follows: A method for separating and obtaining high-purity D-δ-tocopherol from a mixture of tocopherols, comprising the following steps: (1) Mix the mixed tocopherols with the loading solvent and adsorb them onto an anion exchange resin column, then elute them with an eluent, collect the D-δ-tocopherol enriched fraction and remove the solvent to obtain crude D-δ-tocopherol; wherein the mixed tocopherols contain D-δ-tocopherol and at least one selected from D-α-tocopherol, D-β-tocopherol and D-γ-tocopherol; (2) The crude D-δ-tocopherol is mixed with a raw material solvent to obtain a raw material solution; then the raw material solution is fractionally extracted using an extractant containing ionic liquid to obtain an extract rich in D-δ-tocopherol. (3) The extract was back-extracted to obtain high-purity D-δ-tocopherol.

[0009] In some embodiments, the D-δ-tocopherol content in the mixed tocopherols is 1% to 70% by mass, for example, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or any value between therewith. In some embodiments, the D-δ-tocopherol content in the mixed tocopherols is 1% to 20% by mass.

[0010] In some embodiments, the loading solvent is selected from one or more of alcohols, ketones, esters, and ethers. In some embodiments, the loading solvent is selected from one or more of C1-C6 alcohols, C3-C6 ketones, C3-C6 esters, and C2-C6 ethers. In some preferred embodiments, the loading solvent is selected from one or more of methanol, ethanol, propanol, ethyl acetate, and petroleum ether. In some more preferred embodiments, the loading solvent is ethanol.

[0011] In some embodiments, the mass ratio of the mixed tocopherols to the volume of the loading solvent is 1 g: (5-15) mL, for example, 1 g: 5 mL, 1 g: 8 mL, 1 g: 10 mL, 1 g: 12 mL, 1 g: 15 mL, etc. In some embodiments, the mass ratio of the mixed tocopherols to the volume of the loading solvent is 1 g: (8-12) mL.

[0012] In some embodiments, the anion exchange resin is a basic anion exchange resin.

[0013] In some embodiments, the anion exchange resin is a type I or type II anion exchange resin. In some embodiments, the anion exchange resin is a macroporous or gel-type resin.

[0014] In some embodiments, the anion exchange resin is a weakly basic anion exchange resin, such as a macroporous weakly basic styrene-based anion exchange resin, including but not limited to D301.

[0015] In some preferred embodiments, the anion exchange resin is a strongly basic anion exchange resin.

[0016] In some embodiments, the strongly basic anion exchange resin is an anion exchange resin with quaternary ammonium groups on a styrene backbone.

[0017] The strong basic anion exchange resins described in this invention include, but are not limited to, one or more of the following: D201, D202, PA series (such as PA306S, PA308, PA312, PA316, PA400, PA418), HZ202, LS202, FPA40Cl, SA series (such as SA10A, SA12A, SA20A), HPA series (such as HPA25), and UBA series (such as UBA120P).

[0018] In some preferred embodiments, the anion exchange resin is pretreated before use to ensure that it is in a suitable ionic form. For example, it is treated sequentially with an acid solution and an alkaline solution, washed with deionized water until neutral, and finally swollen or replaced with a sample solvent.

[0019] In some embodiments, the adsorption operating temperature is 10°C to 50°C, for example, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 50°C, or any value between them. In some preferred embodiments, it is 20°C to 30°C.

[0020] In some embodiments, during adsorption, the flow rate of the loading solution is 0.5 to 3 BV / h, for example, 0.5 BV / h, 0.8 BV / h, 1.0 BV / h, 1.2 BV / h, 1.5 BV / h, 1.8 BV / h, 2.0 BV / h, 2.2 BV / h, 2.5 BV / h, 2.8 BV / h, 3.0 BV / h, etc., preferably 0.8 to 1.5 BV / h.

[0021] In some embodiments, the eluent is an acidic solution.

[0022] In some embodiments, the acidic solution is a solution formed by dissolving an organic acid in an organic solvent. In some preferred embodiments, the organic acid is selected from C1-C6 carboxylic acids, such as formic acid, acetic acid, and propionic acid, or one or more thereof. In some embodiments, the eluent has a mass concentration of 0.5% to 10%, for example, 0.5%, 0.8%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, etc., preferably 1% to 5%. In some preferred embodiments, the organic solvent is selected from one or more of alcohols, ketones, esters, and ethers. In some preferred embodiments, the organic solvent is selected from one or more of methanol, ethanol, propanol, ethyl acetate, and petroleum ether. In some preferred embodiments, the organic solvent is selected from at least one of ethanol and ethyl acetate. In some more preferred embodiments, the eluent is an acetic acid-ethanol solution.

[0023] In some embodiments, the loading solvent is the same solvent as the organic solvent in the acidic solution.

[0024] In some embodiments, the eluent flow rate during elution is 0.5 BV / h to 3 BV / h, for example, 0.5 BV / h, 0.8 BV / h, 1 BV / h, 1.5 BV / h, 2 BV / h, 2.5 BV / h, 3 BV / h, or any value between them. In some preferred embodiments, the eluent flow rate during elution is 0.8 to 1.5 BV / h.

[0025] In some embodiments, the elution method is isocratic elution.

[0026] In some embodiments, the elution method is gradient elution. In some embodiments, the gradient elution is a gradient elution of the acidic component from low to high concentration. In some embodiments, the eluent volume for each concentration gradient in the gradient elution is 0.1 BV to 10 BV, for example, 0.1 BV, 0.5 BV, 1 BV, 2 BV, 4 BV, 6 BV, 8 BV, 10 BV, or any value between them. In some preferred embodiments, the eluent volume for each concentration gradient in the gradient elution is 0.5 BV to 2 BV.

[0027] In some preferred embodiments, during elution, elution is performed sequentially with acetic acid-ethanol solutions of 0.8–1.5% acetic acid, 1.8–2.5% acetic acid, 2.8–3.5% acetic acid, 3.8–4.5% acetic acid, and 4.8–5.5% acetic acid.

[0028] In some preferred embodiments, during elution, elution is performed sequentially with acetic acid-ethanol solutions of 1%, 2%, 3%, 4%, and 5% concentrations, respectively.

[0029] In some embodiments, in step (1), the solvent removal includes removing the solvent by at least one of vacuum distillation, thin-film evaporation or rotary evaporation.

[0030] In some embodiments, the raw material solvent is a nonpolar organic solvent and / or a weakly polar organic solvent.

[0031] In some embodiments, the raw material solvent is selected from one or more of C6-C10 straight-chain alkanes, C6-C10 branched alkanes, C6-C10 cycloalkanes, C6-C10 alkenes, petroleum ethers, C2-C10 ethers, and C2-C10 ester solvents. In some preferred embodiments, the raw material solvent is selected from one or more of n-hexane, n-heptane, cycloalkanes, petroleum ethers, methyl tert-butyl ether, and butyl acetate. In some embodiments, the extraction raw material solvent is n-hexane.

[0032] In this invention, the hydrophilic ionic liquid is preferably an ionic liquid with strong hydrogen bond basicity.

[0033] In some embodiments, the hydrophilic ionic liquid is composed of both cations and anions. The cations are selected from at least one of the following: choline cations, betaine cations, amino acid cations, guanidinyl cations, imidazole cations, pyridine cations, piperidine cations, pyrrolidine cations, quinoline cations, indole cations, morpholine cations, piperazine cations, pyran cations, pyrazine cations, quaternary phosphonium cations, and quaternary ammonium cations. The anions of the hydrophilic ionic liquid are selected from at least one of the following: halogen anions, carboxyl anions, carbonate anions, nitrate anions, sulfate anions, sulfite anions, sulfonate anions, phosphate anions, phosphite anions, and amino acid anions.

[0034] In some embodiments, the hydrophilic ionic liquid is selected from at least one of choline lysine, 1-butyl-3-methylimidazolium bromide, 1-ethyl-1-methylpiperidine acetate, tetrabutylammonium chloride, 1-butyl-1-methylpyrrolidine nitrate, 1-hydroxyethyl-3-methylimidazolium sulfite, betaine alanine, and 1-butyl-2,3-dimethylimidazolium palmitate. In some embodiments, the hydrophilic ionic liquid is choline lysine or tetrabutylammonium chloride.

[0035] In some embodiments, the extractant further contains a polar solvent, which includes one or more of water, alcohols, nitriles, ketones, sulfones, sulfoxides, and amides. In some preferred embodiments, the polar solvent is one or more of water, methanol, ethylene glycol, glycerol, acetonitrile, acetone, dimethyl sulfoxide, N-methylformamide, and N,N-dimethylformamide. In some embodiments, the polar solvent is one or more of methanol, ethylene glycol, glycerol, and acetonitrile.

[0036] In some embodiments, the extractant is a hydrophilic ionic liquid. In some embodiments, the extractant is a mixture of a hydrophilic ionic liquid and a polar solvent.

[0037] In some embodiments, the extractant contains a hydrophilic ionic liquid at a mass fraction of 0.01% to 100%, for example, 0.01%, 0.05%, 0.1%, 0.5%, 0.8%, 1%, 2%, 5%, 10%, 12%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 100%, or any value between these values. In some preferred embodiments, the extractant contains a hydrophilic ionic liquid at a mass fraction of 0.1% to 20%. In some more preferred embodiments, the extractant contains a hydrophilic ionic liquid at a mass fraction of 0.1% to 10%. In some specific embodiments, the extractant contains a hydrophilic ionic liquid at a mass fraction of 5% to 10%. In some specific embodiments, the extractant contains a hydrophilic ionic liquid at a mass fraction of 0.1% to 5%.

[0038] In some embodiments, the total concentration of D-δ-tocopherol enriched products in the feed solution is 0.2 g / L to 200 g / L, for example, 0.2 g / L, 0.5 g / L, 1 g / L, 3 g / L, 5 g / L, 8 g / L, 10 g / L, 20 g / L, 30 g / L, 40 g / L, 50 g / L, 60 g / L, 70 g / L, 80 g / L, 90 g / L, 100 g / L, 120 g / L, 150 g / L, 180 g / L, 200 g / L, or any value between them. In some preferred embodiments, it is 5 g / L to 50 g / L.

[0039] In some embodiments, the flow ratio of extractant to feedstock in the multi-stage fractionation extraction is (0.1–20):1, for example, 0.1:1, 0.5:1, 1:1, 2:1, 4:1, 5:1, 6:1, 8:1, 10:1, 15:1, 20:1, or any value between them. In some preferred embodiments, the flow ratio is (1–15):1, for example, 1:1, 2:1, 3:1, 5:1, 8:1, 10:1, 12:1, 15:1, or any value between them. In some embodiments, the flow ratio is (5–15):1. In some embodiments, the flow ratio is (4–6):1.

[0040] In some embodiments, the fractionation extraction further utilizes a detergent with a detergent-to-feed liquid flow ratio of (0.05–10):1, for example, 0.05:1, 0.1:1, 0.5:1, 1:1, 2:1, 5:1, 10:1, or any value between them. In some preferred embodiments, the flow ratio is (0.1–5):1. In some preferred embodiments, the flow ratio is (0.1–1):1. Preferably, the detergent used in this invention is the same type as the feed solvent.

[0041] Unless otherwise specified, "flow ratio" in this invention refers to "volume ratio".

[0042] In some embodiments, the fractionation extraction is carried out at a temperature of 10–60°C, for example, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, or any value between them. In some preferred embodiments, the operating temperature is 20–50°C.

[0043] In some embodiments, the fractional extraction is a multi-stage fractional extraction. In some embodiments, the fractional extraction has 2 to 20 extraction stages, for example, 2, 3, 5, 8, 10, 12, 15, 18, 20 stages or any value between them. In some preferred embodiments, the extraction stages are 5 to 15 stages; in some specific embodiments, the washing stages of the fractional extraction are 2 to 20 stages, preferably 3 to 10 stages.

[0044] In some embodiments, the extraction solvent is selected from nonpolar organic solvents and / or weakly polar organic solvents. In some preferred embodiments, the extraction solvent is selected from one or more of C6-C10 straight-chain alkanes, C6-C10 branched alkanes, C6-C10 cycloalkanes, C6-C10 alkenes, petroleum ethers, C2-C10 ethers, and C2-C10 ester solvents. In some more preferred embodiments, the extraction solvent is of the same type as the extraction feed solvent.

[0045] In some embodiments, the back-extraction operation temperature is 10°C to 60°C, for example, 10°C, 20°C, 30°C, 40°C, 50°C, 60°C, or any value between them. In some embodiments, the back-extraction operation temperature is 20°C to 50°C.

[0046] In some embodiments, step (3) further includes: washing the back-extracted phase obtained after back-extraction with water and distilling under reduced pressure to obtain high-purity D-δ-tocopherol.

[0047] In some specific embodiments, the method includes the following steps: (1) Adsorption: Mixed tocopherols and loading solvent are mixed in a certain ratio to prepare a loading solution. The loading solution is passed into a pre-treated chromatographic column packed with strong basic anion exchange resin and adsorption is carried out at a certain temperature. Then, an acidic solution is used as the eluent for gradient elution. As the concentration of acid in the acidic solution increases, D-α-, D-β- and D-γ-, D-δ-tocopherols can be eluted sequentially, and the D-δ-tocopherol enriched fraction is collected. The collected D-δ-tocopherol enriched fraction is desolvated by vacuum distillation to obtain crude D-δ-tocopherol. (2) Extraction: The crude D-δ-tocopherol obtained in step (1) is dissolved in the raw material solvent to obtain the raw material liquid; a hydrophilic ionic liquid or a binary mixed solvent composed of a hydrophilic ionic liquid and a polar solvent is used as the extractant, and fractional extraction is carried out in a multi-stage extraction tower. The fractional extraction is divided into an extraction section and a washing section. The extractant enters the fractional extraction system from the first stage of the extraction section, the raw material liquid enters the fractional extraction system from the last stage of the extraction section, and the washing agent enters the fractional extraction system from the first stage of the washing section. The raw material liquid is combined and enters the extraction section together in the last stage of the washing section. The extraction phase and the washing phase are subjected to multi-stage countercurrent extraction. The extract rich in D-δ-tocopherol flows out from the first stage of the washing section, and the raffinate enriched with D-α-tocopherol, D-β-tocopherol and D-γ-tocopherol flows out from the first stage of the extraction section. (3) Back-extraction: The extract from step (2) is back-extracted using the same back-extraction solvent as the raw material solvent and detergent. The back-extracted phase is washed with water and distilled under reduced pressure to obtain D-δ-tocopherol. The extractant is recycled. Optionally, (4) The raffinate from step (2) is washed with water and distilled under reduced pressure to obtain D-α-tocopherol, D-β-tocopherol and D-γ-tocopherol.

[0048] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention employs a coupled process of "adsorption enrichment followed by extraction purification," which solves the technical bottleneck of the difficulty in economically processing low-content D-δ-tocopherol raw materials using ionic liquid extraction alone. The adsorption treatment step increases the D-δ-tocopherol content in low-concentration mixed tocopherol raw materials to over 70%, significantly reducing the number of extraction stages, extractant usage, and solvent circulation in subsequent extraction steps, thereby greatly improving the overall economic efficiency of the process.

[0049] 2. This invention combines anion exchange resin adsorption with ionic liquid extraction. The process route is reasonable and technically feasible, enabling the efficient preparation of high-purity D-δ-tocopherol products from low-content mixed tocopherol raw materials at low cost. Detailed Implementation

[0050] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The specific embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the invention in any way.

[0051] Unless otherwise specified, all reagents used in the following experiments of this invention are commercially available products or reagents prepared according to conventional methods. Unless otherwise specified, all methods used in the experiments are conventional experimental methods. Unless otherwise specified, all instruments used in the experiments are commercially available.

[0052] To overcome the shortcomings of existing technologies, such as low throughput and lengthy processes when using adsorption alone, or poor economic efficiency when using extraction alone to directly process low-concentration D-δ-tocopherol raw materials, this invention provides a high-throughput, simple, and efficient adsorption-extraction coupling method to separate high-purity D-δ-tocopherol from low-content mixed tocopherols.

[0053] The molecular structures of δ-tocopherol are very similar to those of other tocopherol homologues. The difference lies in the fact that D-δ-tocopherol has one methyl group substituting on the benzene ring, while other homologues have two to three methyl groups. Since the methyl group is an electron-donating group, it weakens the acidity of the phenolic hydroxyl group. Therefore, D-δ-tocopherol, which has the fewest methyl groups, has the strongest acidity of its phenolic hydroxyl group.

[0054] Building upon this foundation, the present invention first utilizes the strongest adsorption and binding force of anion exchange resin for D-δ-tocopherol. Through gradient elution, D-α-, D-β-, D-γ-, and D-δ-tocopherol are eluted sequentially, and the D-δ-tocopherol-enriched fraction is collected, increasing the D-δ-tocopherol content to a suitable extraction level, i.e., above 70%. Subsequently, purification is achieved using extraction, and the resulting D-δ-tocopherol-enriched product is introduced into a multi-stage fractionation extraction process. This step utilizes an ionic liquid with strong hydrogen-bonding basicity as the extractant, which strongly interacts with the phenolic hydroxyl groups of D-δ-tocopherol. Using a non-polar / weakly polar solvent as the raw material solvent, a liquid-liquid two-phase system is constructed for efficient extraction.

[0055] The adsorption-extraction coupling process of this invention can economically and efficiently prepare high-purity D-δ-tocopherol from low-content raw materials with lower equipment requirements and solvent consumption.

[0056] In the following examples and comparative examples, the concentrations of tocopherol homologues were analyzed using high-performance liquid chromatography (HPLC). The specific HPLC analytical conditions were as follows: Waters Sunfire C18 column (4.6 mm × 250 mm, particle size 5 μm), column temperature 30°C, mobile phase methanol:water = 96:4 (v / v), flow rate 1 mL / min. An ultraviolet detector was used with a detection wavelength of 292 nm.

[0057] The strongly basic anion exchange resin used in the following embodiments and comparative examples of this invention is DIAION from Mitsubishi Chemical Corporation. TM The series includes a type I strong base anion exchange resin, SA10A; the weak base anion exchange resin used is macroporous weak base styrene-based anion exchange resin D301.

[0058] In the following examples and comparative examples, "1% acetic acid-ethanol solution" refers to an acetic acid-ethanol solution with a mass concentration of 1%. Similarly, "2% acetic acid-ethanol solution" refers to an acetic acid-ethanol solution with a mass concentration of 2%.

[0059] In the following examples and comparative examples, the methods for calculating yield and purity are as follows: Yield (overall yield) = (mass of D-δ-tocopherol in the final product / mass of D-δ-tocopherol in the feedstock) × 100%; Purity (final product) = Mass of D-δ-tocopherol in the product / Total mass of the product × 100%.

[0060] Example 1

[0061] A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol (D-δ-tocopherol) enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 92.8%, and the yield (relative to the enriched product) was 94.6%.

[0062] Example 2 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 70% by mass, D-α-tocopherol accounts for 10% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 20%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 90.3%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 95.8%, and the yield (relative to the enriched product) was 96.2%.

[0063] Example 3 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 1% by mass, D-α-tocopherol accounts for 59% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 40%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. Fractionated elution was prepared (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 70%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 89.5%, and the yield (relative to the enriched product) was 90.1%.

[0064] Example 4 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% formic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 78.5%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 92.1%, and the yield (relative to the enriched product) was 94.2%.

[0065] Example 5 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethyl acetate solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. Fractionated elution was prepared (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 79.5%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 92.5%, and the yield (relative to the enriched product) was 94.3%.

[0066] Example 6 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a weakly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 70.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 89.8%, and the yield (relative to the enriched product) was 91%.

[0067] Example 7 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 3.0 BV / h using 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 75.6%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 91.8%, and the yield (relative to the enriched product) was 93.7%.

[0068] Example 8 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 10% acetic acid-ethanol solution. Fractionated elution was prepared (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 86.5%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 93.7%, and the yield (relative to the enriched product) was 95.2%.

[0069] Example 9 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 2 BV of 2% acetic acid-ethanol solution, 2 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 85.9%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 93.2%, and the yield (relative to the enriched product) was 95.3%.

[0070] Example 10 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 20%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 93.7%, and the yield (relative to the enriched product) was 95.2%.

[0071] Example 11 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enriched fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A tetrabutylammonium chloride ionic liquid-methanol mixed solvent was used as the extractant (choline lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 92.1%, and the yield (relative to the enriched product) was 94.3%.

[0072] Example 12 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-acetonitrile mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 91.8%, and the yield (relative to the enriched product) was 93.2%.

[0073] Example 13 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 50 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 90.1%, and the yield (relative to the enriched product) was 92.1%.

[0074] Example 14 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:1:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 91.4%, and the yield (relative to the enriched product) was 91.0%.

[0075] Example 15 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 15:5:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 95.5%, and the yield (relative to the enriched product) was 90.2%.

[0076] Example 16 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in petroleum ether to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times at 30°C with 1 / 2 volume of petroleum ether. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 90.1%, and the yield (relative to the enriched product) was 90.0%.

[0077] Example 17 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 50 °C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30 °C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 91.2%, and the yield (relative to the enriched product) was 93.4%.

[0078] Example 18 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (5 stages) and a washing stage (3 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 89.3%, and the yield (relative to the enriched product) was 90.2%.

[0079] Example 19 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (8 stages) and a washing stage (8 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 91.3%, and the yield (relative to the enriched product) was 93.4%.

[0080] Example 20 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixed solvent was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 50°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 91.5%, and the yield (relative to the enriched product) was 93.2%.

[0081] Comparative Example 1 A mixture of D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (with D-δ-tocopherol comprising 20% ​​by mass, D-α-tocopherol 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol 50%) was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixture was used as the extractant (choline-lysine ionic liquid comprising 5% by mass) and n-hexane as the washing agent. The flow ratio of extractant, washing agent, and feed solution was 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times at 30°C with half a volume of n-hexane. The combined n-hexane phases were washed with water and subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 69.2%, and the yield (relative to the enriched product) was 70.5%.

[0082] Comparative Example 2 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (with D-δ-tocopherol comprising 20% ​​by mass, D-α-tocopherol 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by elution with ethanol. The eluent was collected in fractions (100 mL each) at a flow rate of 1.0 BV / h and analyzed by HPLC. The enriched D-δ-tocopherol fraction was collected. The enriched fraction was then subjected to vacuum distillation to obtain a D-δ-tocopherol enriched product (purity increased to 30.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. A choline-lysine ionic liquid-methanol mixture was used as the extractant (choline-lysine ionic liquid mass fraction was 5%), and n-hexane was used as the washing agent. The flow ratio of extractant, washing agent, and feed liquid was 5:0.2:1 (v / v / v). Fractional extraction was carried out at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The combined n-hexane phases were washed with water and subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 72.1%, and the yield (relative to the enriched product) was 73.4%.

[0083] Comparative Example 3 A mixture of raw materials D-α-tocopherol, D-β-tocopherol, D-γ-tocopherol, and D-δ-tocopherol (of which D-δ-tocopherol accounts for 20% by mass, D-α-tocopherol accounts for 30% by mass, and the total mass percentage of D-β-tocopherol and D-γ-tocopherol is 50%) was dissolved in ethanol to prepare a 100 g / L loading solution. The loading solution was passed through a strongly basic anion exchange resin column at a flow rate of 1.0 BV / h for adsorption, followed by gradient elution. Elution was performed sequentially at a flow rate of 1.0 BV / h with 1 BV of 1% acetic acid-ethanol solution, 1 BV of 2% acetic acid-ethanol solution, 1 BV of 3% acetic acid-ethanol solution, 1 BV of 4% acetic acid-ethanol solution, and 1 BV of 5% acetic acid-ethanol solution. The eluent was fractionated (per 100 g / L). The D-δ-tocopherol enrichment fraction was detected by HPLC and collected. The enriched fraction was then subjected to vacuum distillation to obtain the D-δ-tocopherol enriched product (purity increased to 80.2%). The D-δ-tocopherol enriched product was dissolved in n-hexane to prepare an extraction feed solution with a total concentration of 20 g / L. Methanol was used as the extractant, and n-hexane as the washing agent, with a flow ratio of extractant, washing agent, and feed solution of 5:0.2:1 (v / v / v). Fractional extraction was performed at 30°C, consisting of an extraction stage (10 stages) and a washing stage (6 stages). The extract was back-extracted three times with 1 / 2 volume of n-hexane at 30°C. The n-hexane phases were combined, washed with water, and then subjected to vacuum distillation to obtain the product D-δ-tocopherol. The purity of D-δ-tocopherol in the product was 82.3%, and the yield (relative to the enriched product) was 82.9%.

[0084] It should be noted that the embodiments described above are only for explaining the present invention and do not constitute any limitation on the present invention. The present invention has been described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory terms, not limiting terms. Modifications can be made to the present invention within the scope of the claims, and revisions can be made to the present invention without departing from the scope and spirit of the present invention. Although the present invention described herein relates to specific methods, materials, and embodiments, it does not mean that the present invention is limited to the specific examples disclosed herein; on the contrary, the present invention can be extended to all other methods and applications with the same function.

Claims

1. A method for separating and obtaining high-purity D-δ-tocopherol from a mixture of tocopherols, comprising the following steps: (1) Mix the mixed tocopherols with the loading solvent and adsorb them onto an anion exchange resin column, then elute them with an eluent, collect the D-δ-tocopherol enriched fraction and remove the solvent to obtain crude D-δ-tocopherol; wherein the mixed tocopherols contain D-δ-tocopherol and at least one selected from D-α-tocopherol, D-β-tocopherol and D-γ-tocopherol; (2) The crude D-δ-tocopherol is mixed with a raw material solvent to obtain a raw material solution; then the raw material solution is fractionally extracted using an extractant containing ionic liquid to obtain an extract rich in D-δ-tocopherol. (3) The extract was back-extracted to obtain high-purity D-δ-tocopherol.

2. The method according to claim 1, characterized in that, In the mixed tocopherols, the mass percentage of D-δ-tocopherol is 1%–70%, or 1%–20%; and / or In step (1), the mass ratio of the mixed tocopherols to the volume of the loading solvent is 1 g : (5-15) mL.

3. The method according to claim 1 or 2, characterized in that, The loading solvent is selected from one or more of alcohols, ketones, esters, and ethers; preferably, the loading solvent is selected from one or more of methanol, ethanol, propanol, ethyl acetate, and petroleum ether, more preferably ethanol; and / or The anion exchange resin is a basic anion exchange resin, preferably a strongly basic anion exchange resin, more preferably a type I or type II strongly basic anion exchange resin; further preferably a macroporous or gel-type strongly basic anion exchange resin; and / or The adsorption operation temperature is 10℃~50℃, preferably 20℃~30℃; and / or During adsorption, the flow rate of the loading solution is 0.5–3 BV / h, preferably 0.8–1.5 BV / h.

4. The method according to any one of claims 1-3, characterized in that, The eluent is an acidic solution; preferably, it is a solution formed by dissolving an organic acid in an organic solvent; the organic acid is preferably selected from C1-C6 carboxylic acids, more preferably from one or more of formic acid, acetic acid, and propionic acid; the mass concentration of the organic acid in the eluent is preferably 0.5%-10%, more preferably 1%-5%; the organic solvent is preferably selected from one or more of alcohols, ketones, esters, and ethers, more preferably from one or more of methanol, ethanol, propanol, ethyl acetate, and petroleum ether, and even more preferably from at least one of ethanol and ethyl acetate; and / or The sample loading solvent is the same solvent as the organic solvent in the acidic solution; and / or During elution, the eluent flow rate is 0.5–3 BV / h, preferably 0.8–1.5 BV / h; and / or The elution is isocratic elution or gradient elution, preferably gradient elution; preferably, the volume of eluent for each concentration gradient in the gradient elution is 0.1 to 10 BV, more preferably 0.5 to 2 BV.

5. The method according to any one of claims 1-4, characterized in that, The raw material solvent is a nonpolar organic solvent and / or a weakly polar organic solvent; preferably, the raw material solvent is selected from one or more of C6-C10 straight-chain alkanes, C6-C10 branched alkanes, C6-C10 cycloalkanes, C6-C10 alkenes, petroleum ethers, C2-C10 ethers, and C2-C10 esters; more preferably, the raw material solvent is selected from one or more of n-hexane, n-heptane, cycloalkanes, petroleum ethers, methyl tert-butyl ether, and butyl acetate.

6. The method according to any one of claims 1-5, characterized in that, The extractant is a hydrophilic ionic liquid, or a mixture of a hydrophilic ionic liquid and a polar solvent; and / or, The hydrophilic ionic liquid has strong hydrogen-bonding basicity; and / or The hydrophilic ionic liquid is composed of cations and anions, wherein the cations are selected from at least one of choline cations, betaine cations, amino acid cations, guanidine cations, imidazole cations, pyridine cations, piperidine cations, pyrrolidine cations, quinoline cations, indole cations, morpholine cations, piperazine cations, pyran cations, pyrazine cations, quaternary phosphorus cations, and quaternary ammonium cations; and the anions are selected from at least one of halogen anions, borate anions, carboxylate anions, carbonate anions, nitrate or nitrite anions, sulfate anions, sulfite anions, sulfonate anions, phosphate anions, phosphite anions, and amino acid anions; and / or The hydrophilic ionic liquid is selected from at least one of choline lysine, 1-butyl-3-methylimidazolium bromide, 1-ethyl-1-methylpiperidine acetate, tetrabutylammonium chloride, 1-butyl-1-methylpyrrolidine nitrate, 1-hydroxyethyl-3-methylimidazolium sulfite, betaine alanine, and 1-butyl-2,3-dimethylimidazolium palmitate, preferably choline lysine or tetrabutylammonium chloride; and / or The extractant also contains a polar solvent, which includes one or more of water, alcohol, nitriles, ketones, sulfones, sulfoxides, and amides; preferably, the polar solvent is one or more of water, methanol, ethylene glycol, glycerol, acetonitrile, acetone, dimethyl sulfoxide, N-methylformamide, and N,N-dimethylformamide, more preferably one or more of methanol, ethylene glycol, glycerol, and acetonitrile.

7. The method according to any one of claims 1-6, characterized in that, The extractant contains a hydrophilic ionic liquid with a mass fraction of 0.01% to 100%, preferably 0.1% to 20%, more preferably 0.1% to 10%, and even more preferably 5% to 10%.

8. The method according to any one of claims 1-7, characterized in that, The concentration of D-δ-tocopherol in the feed solution is 0.2 g / L to 200 g / L, preferably 5 g / L to 50 g / L; and / or In the fractional extraction, the flow ratio of extractant to feed liquid is (0.1–20):1; preferably (1–15):1, more preferably (4–6):1; and / or The fractionation extraction also uses a detergent, and the flow ratio of the detergent to the feed liquid is (0.05-10):1, preferably (0.1-1):1; preferably, the detergent and the feed solvent are of the same type.

9. The method according to any one of claims 1-8, characterized in that, The fractionation extraction is performed at a temperature of 10–60°C, preferably 20–50°C; and / or The fractional extraction is a multi-stage fractional extraction, wherein the extraction stage has 2 to 20 stages, preferably 5 to 15 stages; the washing stage has 2 to 20 stages, preferably 3 to 10 stages; and / or The back-extraction operation temperature is 10–60°C, preferably 20–50°C; and / or The back-extraction solvent used is selected from non-polar organic solvents and / or weakly polar organic solvents, preferably from one or more of C6-C10 straight-chain alkanes, C6-C10 branched alkanes, C6-C10 cycloalkanes, C6-C10 alkenes, petroleum ethers, C2-C10 ethers, and C2-C10 esters; preferably, the back-extraction solvent is the same type as the raw material solvent.

10. The method according to any one of claims 1-9, characterized in that, Step (3) also includes: washing the back-extracted phase obtained after back-extraction with water and distilling under reduced pressure to obtain high-purity D-δ-tocopherol.