CN101519396B - Method for purifying d-Alpha tocopherol succinate - Google Patents
Method for purifying d-Alpha tocopherol succinate Download PDFInfo
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- CN101519396B CN101519396B CN2009100964650A CN200910096465A CN101519396B CN 101519396 B CN101519396 B CN 101519396B CN 2009100964650 A CN2009100964650 A CN 2009100964650A CN 200910096465 A CN200910096465 A CN 200910096465A CN 101519396 B CN101519396 B CN 101519396B
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- tocopherol succinate
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Abstract
The invention relates to a method for purifying d-Alpha tocopherol succinate, which uses the resin column chromatography as a main method and comprises the following steps: adopting macroporous absorbent resin as an immobile phase, the crude product of the d-Alpha tocopherol succinate as solute, and latent organic solvent as solvent; mixing by a certain sample number and sample concentration; controlling the sample flow, sampling at the column temperature of 20-50 DEG C, eluting by eluent and collecting, and at last rotatably evaporating the collected eluent to dryness. The quality of the product of the d-Alpha tocopherol succinate treated by the method reaches the standard established by developed countries in Europe and America; and meanwhile, the method has simple process, low cost, andno pollution to the environment, thereby being a more ideal treating method.
Description
Technical field
The present invention relates to field of fine chemical, be specifically related to the method for d-alpha-tocopherol succinate purification.
Background technology
D-alpha-tocopherol succinate be the d-alpha-tocopherol one of derived product, it has continued the biological activity of d-alpha-tocopherol, and on the original basis, because the effect of succsinic acid group, making it have anticancer effect, is a kind of very promising effectively auxiliary cancer therapy drug.In addition, it is good galactogogue hormone and secretion of growth hormone promotor.Except as a kind of natural vitamin E product, d-alpha-tocopherol succinate can also be as the intermediate of synthesizing water-soluble vitamin E.American-European countries is very harsh to the requirement of d-alpha-tocopherol succinate at present, the d-alpha-tocopherol succinate product of producing and purifying of the same trade now detects the content of d-alpha-tocopherol succinate generally in 70% (production) and 78%～84% (back of purifying) by HPLC (high performance liquid chromatography), and product the polynuclear aromatics and the content of benzopyrene higher, do not meet the requirement of American-European countries, and reach more than 99.5% by the product content that present method obtains, and polynuclear aromatics content is less than 25ppb (1ppb is part per billion), benzopyrene meets the specification of quality of American-European countries less than 0.5ppb.
Summary of the invention
The purpose of this invention is to provide a kind of products obtained therefrom content very high is the method for the d-alpha-tocopherol succinate purification of main method with the resin column chromatography.
For achieving the above object, the processing method of the present invention's employing is:
With the resin column chromatography is main method, the employing macroporous adsorbent resin is a stationary phase, the thick product of d-alpha-tocopherol succinate is a solute, inert organic solvents is a solvent, with certain applied sample amount, upward sample concentration mixing, sample on the flow of sample in the control, 20 ℃～50 ℃ the column temperature carries out wash-out with eluent afterwards and collects, and at last the elutriant collected is steamed evaporate to dryness and gets final product through revolving.
Its concrete steps are as follows:
(1) prepares: be ready to chromatography column;
(2) dress post: get a certain amount of macroporous adsorbent resin, with the inert organic solvents washing resin and adorn post as stationary phase;
(3) mix: get the thick product of d-alpha-tocopherol succinate with certain applied sample amount, mix the last sample concentration that reaches certain with inert organic solvents;
(4) go up sample: the flow in the control during sample, with 20 ℃～50 ℃ column temperatures with mixing solutions along tube wall adding stationary phase surface;
(5) wash-out: add the d-alpha-tocopherol succinate on the eluent wash-out resin after upper prop finishes;
(6) collect: collect elutriant, revolve the steaming evaporate to dryness and promptly obtain product.
Above-mentioned steps (2), (3) described inert organic solvents be meant in normal hexane, chloroform, anhydrous methanol, ethanol, the Virahol any or plant arbitrarily and mix with arbitrary proportion.
Preferable inert organic solvents is meant any in anhydrous methanol, ethanol, the Virahol.
Resin in above-mentioned be in D-101 type macroporous adsorbent resin, AB-8 type macroporous adsorbent resin, DA-201 type macroporous adsorbent resin, X-5 type macroporous adsorbent resin, DM130 macroporous adsorbent resin, the DM-301 type macroporous adsorbent resin any.
The described applied sample amount of above-mentioned steps (3) is that every 100mL resin adds 1g～thick product of 6gd-alpha-tocopherol succinate (content is about 70%), and last sample concentration is 0.1g/mL～0.35g/mL.
The described flow of above-mentioned steps (4) is 1%～5% of a resin volume for the per minute add-on.
Above-mentioned eluent be in normal hexane, chloroform, anhydrous methanol, ethanol, the Virahol any or plant arbitrarily and mix with arbitrary proportion.
Preferable eluent is meant any in anhydrous methanol, ethanol, the Virahol.
The method of d-alpha-tocopherol succinate purification of the present invention, products obtained therefrom content height, d-alpha-tocopherol succinate recovery rate height after it is handled, good product quality, the content that detects d-alpha-tocopherol succinate by HPLC (high performance liquid chromatography) reaches more than 99.5%, polynuclear aromatics content is less than 25ppb (1ppb is part per billion), benzopyrene is less than 0.5ppb, and quality product can reach the standard that American-European developed country formulates, and technology is simple, cost is low, environmentally safe.
Embodiment
The present invention is further illustrated below in conjunction with embodiment, and following each embodiment only is used to illustrate the present invention, but to the present invention without limits.
Embodiment one
Be ready to chromatography column, as stationary phase, with the anhydrous methanol washing, recharging chromatography column to bed volume is 100mL earlier X-5 type macroporous adsorbent resin.Applied sample amount with 3g is mixed into the solution that 0.25g/mL goes up sample concentration with the thick product of d-alpha-tocopherol succinate (content is about 70%, down together) with anhydrous methanol, and the flow of control 2mL/min, 30 ℃ column temperature add the stationary phase surface with mixing solutions.Use anhydrous methanol as the eluent wash-out after upper prop finishes, collect elutriant, revolve the steaming evaporate to dryness.Product content is 99.8% after testing, and polynuclear aromatics content is 18ppb, and benzopyrene is less than 0.5ppb.
Embodiment two
Be ready to chromatography column, D-101 type macroporous adsorbent resin as stationary phase, is used washing with alcohol earlier, recharging chromatography column to bed volume is 200mL.Applied sample amount with 8g is mixed into the solution that 0.15g/mL goes up sample concentration with thick product of d-alpha-tocopherol succinate and ethanol, and the flow of control 6mL/min, 40 ℃ column temperature add the stationary phase surface with mixing solutions.Use Virahol as the eluent wash-out after upper prop finishes, collect elutriant, revolve the steaming evaporate to dryness.Product content is 99.6% after testing, and polynuclear aromatics content is 20ppb, and benzopyrene is less than 0.5ppb.
Embodiment three
Be ready to chromatography column, as stationary phase, with the anhydrous methanol washing, recharging chromatography column to bed volume is 200mL earlier D-101 type macroporous adsorbent resin.Applied sample amount with 6g is mixed into the solution that 0.1g/mL goes up sample concentration with thick product of d-alpha-tocopherol succinate and anhydrous methanol, and the flow of control 4mL/min, 45 ℃ column temperature add the stationary phase surface with mixing solutions.Use ethanol as the eluent wash-out after upper prop finishes, collect elutriant, revolve the steaming evaporate to dryness.Product content is 99.7% after testing, and polynuclear aromatics content is 16ppb, and benzopyrene is less than 0.5ppb.
Embodiment four
Be ready to chromatography column, AB-8 type macroporous adsorbent resin as stationary phase, is used washed with isopropyl alcohol earlier, recharging chromatography column to bed volume is 100mL.Applied sample amount with 4g is mixed into the solution that 0.2g/mL goes up sample concentration with thick product of d-alpha-tocopherol succinate and Virahol, and the flow of control 5mL/min, 20 ℃ column temperature add the stationary phase surface with mixing solutions.Use anhydrous methanol as the eluent wash-out after upper prop finishes, collect elutriant, revolve the steaming evaporate to dryness.Product content is 99.6% after testing, and polynuclear aromatics content is 19ppb, and benzopyrene is less than 0.5ppb.
Embodiment five
Be ready to chromatography column, DA-201 type macroporous adsorbent resin as stationary phase, is used washing with alcohol earlier, recharging chromatography column to bed volume is 300mL.Applied sample amount with 10g is mixed into the solution that 0.14g/mL goes up sample concentration with thick product of d-alpha-tocopherol succinate and ethanol, and the flow of control 12mL/min, 31 ℃ column temperature add the stationary phase surface with mixing solutions.Use Virahol as the eluent wash-out after upper prop finishes, collect elutriant, revolve the steaming evaporate to dryness.Product content is 99.7% after testing, and polynuclear aromatics content is 21ppb, and benzopyrene is less than 0.5ppb.
Embodiment six
Be ready to chromatography column, as stationary phase, with ethanol, anhydrous methanol (1: 1 volume ratio) washing, recharging chromatography column to bed volume is 200mL earlier DM130 type macroporous adsorbent resin.Applied sample amount with 9g is mixed into the solution that 0.23g/mL goes up sample concentration with the thick product of d-alpha-tocopherol succinate and ethanol, anhydrous methanol (1: 1 volume ratio of volume ratio), and the flow of control 7mL/min, 36 ℃ column temperature add the stationary phase surface with mixing solutions.Use Virahol as the eluent wash-out after upper prop finishes, collect elutriant, revolve the steaming evaporate to dryness.Product content is 99.7% after testing, and polynuclear aromatics content is 19ppb, and benzopyrene is less than 0.5ppb.
Embodiment seven
Be ready to chromatography column, as stationary phase, with Virahol, anhydrous methanol (1: 1 volume ratio) washing, recharging chromatography column to bed volume is 150mL earlier DM-301 type macroporous adsorbent resin.Applied sample amount with 7g is mixed into the solution that 0.18g/mL goes up sample concentration with the thick product of d-alpha-tocopherol succinate and Virahol, anhydrous methanol (volume ratio 1: 1), and the flow of control 4.5mL/min, 34 ℃ column temperature add the stationary phase surface with mixing solutions.Upper prop finishes back ethanol, anhydrous methanol (volume ratio 1: 1) as the eluent wash-out, collects elutriant, revolves the steaming evaporate to dryness.Product content is 99.8% after testing, and polynuclear aromatics content is 18ppb, and benzopyrene is less than 0.5ppb.
Embodiment eight
Be ready to chromatography column, as stationary phase, with normal hexane, chloroform, anhydrous methanol, ethanol, Virahol (volume ratio 1: 1: 1: 1: 1) washing, recharging chromatography column to bed volume is 200mL earlier DM130 type macroporous adsorbent resin.Applied sample amount with 11g is mixed into the solution that 0.27g/mL goes up sample concentration with the thick product of d-alpha-tocopherol succinate and normal hexane, chloroform, anhydrous methanol, ethanol, Virahol (volume ratio 1: 1: 1: 1: 1), and the flow of control 9mL/min, 47 ℃ column temperature add the stationary phase surface with mixing solutions.Upper prop finishes back chloroform, anhydrous methanol, ethanol (volume ratio 1: 1: 1) as the eluent wash-out, collects elutriant, revolves the steaming evaporate to dryness.Product content is 99.6% after testing, and polynuclear aromatics content is 21ppb, and benzopyrene is less than 0.5ppb.
Embodiment nine
Be ready to chromatography column, as stationary phase, with the anhydrous methanol washing, recharging chromatography column to bed volume is 100mL earlier D-101 type macroporous adsorbent resin.With the applied sample amount of 4g thick product of d-alpha-tocopherol succinate and anhydrous methanol are mixed into the solution that 0.2g/mL goes up sample concentration, mixing solutions are added the stationary phase surface with the column temperature of 28 ℃ of flow, the controls of 3mL/min.Upper prop finishes back anhydrous methanol, ethanol (volume ratio 1: 1) as the eluent wash-out, collects elutriant, revolves the steaming evaporate to dryness.Product content is 99.7% after testing, and polynuclear aromatics content is 18ppb, and benzopyrene is less than 0.5ppb.
Embodiment ten
Be ready to chromatography column, as stationary phase, with ethanol, Virahol (volume ratio 1: 1) washing, recharging chromatography column to bed volume is 200mL earlier AB-8 type macroporous adsorbent resin.Applied sample amount with 11g is mixed into the solution that 0.17g/mL goes up sample concentration with the thick product of d-alpha-tocopherol succinate and ethanol, Virahol (volume ratio 1: 1), and the flow of control 6mL/min, 29 ℃ column temperature add the stationary phase surface with mixing solutions.Upper prop finishes back ethanol, anhydrous methanol (volume ratio 1: 1) as the eluent wash-out, collects elutriant, revolves the steaming evaporate to dryness.Product content is 99.6% after testing, and polynuclear aromatics content is 21ppb, and benzopyrene is less than 0.5ppb.
The coupling that need to prove inert organic solvents in the foregoing description, resinous type, flow, applied sample amount in addition, go up sample concentration, column temperature, eluent can also have multiple combination.
Claims (5)
1. the method for a d-alpha-tocopherol succinate purification is characterized in that comprising the following steps:
(1) prepares: be ready to chromatography column;
(2) dress post: get a certain amount of macroporous adsorbent resin, with in anhydrous methanol, ethanol, the Virahol any as the organic solvent washing resin and adorn post as stationary phase;
(3) mix: get the thick product of d-alpha-tocopherol succinate with certain applied sample amount, mix the last sample concentration that reaches certain with above-mentioned organic solvent;
(4) go up sample: the flow in the control during sample, with 20 ℃～50 ℃ column temperatures with mixing solutions along tube wall adding stationary phase surface;
(5) wash-out: add the d-alpha-tocopherol succinate on any wash-out resin in anhydrous methanol, ethanol, the Virahol;
(6) collect: collect elutriant, revolve the steaming evaporate to dryness.
2. the method for d-alpha-tocopherol succinate purification as claimed in claim 1 is characterized in that: described resin is any in D-101 type macroporous adsorbent resin, AB-8 type macroporous adsorbent resin, DA-201 type macroporous adsorbent resin, X-5 type macroporous adsorbent resin, DM130 macroporous adsorbent resin, the DM-301 type macroporous adsorbent resin.
3. the method for d-alpha-tocopherol succinate purification as claimed in claim 1 is characterized in that: the described applied sample amount of step (3) is that every 100mL resin adds 1g～thick product of 6gd-alpha-tocopherol succinate.
4. the method for d-alpha-tocopherol succinate purification as claimed in claim 1 is characterized in that: the described upward sample concentration of step (3) is 0.1g/mL～0.35g/mL.
5. the method for d-alpha-tocopherol succinate purification as claimed in claim 1 is characterized in that: the described flow of step (4) is 1%～5% of a resin volume for the per minute add-on.
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| CN2009100964650A CN101519396B (en) | 2009-03-09 | 2009-03-09 | Method for purifying d-Alpha tocopherol succinate |
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| CN2009100964650A CN101519396B (en) | 2009-03-09 | 2009-03-09 | Method for purifying d-Alpha tocopherol succinate |
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| CN101519396B true CN101519396B (en) | 2011-10-26 |
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| CN102432583A (en) * | 2011-10-25 | 2012-05-02 | 浙江华源制药科技开发有限公司 | Method for preparing low-benzopyrene high-purity d-alpha tocopherol acetate |
| CN112899322B (en) * | 2021-02-03 | 2022-11-18 | 山东新元素生物科技有限公司 | Method for recovering high-content natural d-alpha-tocopherol succinate from leftovers |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001019383A1 (en) * | 1999-09-17 | 2001-03-22 | Alcon, Inc. | Stable carotene-xanthophyll beadlet compositions and methods of use |
| WO2005017134A2 (en) * | 2003-08-19 | 2005-02-24 | Council Of Scientific And Industrial Research | Isozyme of autoclavable superoxide dismutase (sod) derived from curcuma longa l |
| CN100432066C (en) * | 2006-03-10 | 2008-11-12 | 浙江华源制药科技开发有限公司 | Method for removing micro polynary arene in natural vitamine E |
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2009
- 2009-03-09 CN CN2009100964650A patent/CN101519396B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001019383A1 (en) * | 1999-09-17 | 2001-03-22 | Alcon, Inc. | Stable carotene-xanthophyll beadlet compositions and methods of use |
| WO2005017134A2 (en) * | 2003-08-19 | 2005-02-24 | Council Of Scientific And Industrial Research | Isozyme of autoclavable superoxide dismutase (sod) derived from curcuma longa l |
| CN100432066C (en) * | 2006-03-10 | 2008-11-12 | 浙江华源制药科技开发有限公司 | Method for removing micro polynary arene in natural vitamine E |
Non-Patent Citations (2)
| Title |
|---|
| 孙倩.d-α-生育酚琥珀酸酯制备精制工艺研究.《浙江大学硕士学位论文》.2007,40-56. * |
| 张倩 等.生育酚琥珀酸酯的研究进展.《中国食物与营养》.2008,(第6期),31-32. * |
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Owner name: ZHEJIANG YIBAOXIN BIOTECHNOLOGY CO., LTD. Free format text: FORMER NAME: ZHEJIANG WORLDBEST PHARMACEUTICALS SCIENCE TECHNIC DEVELOPMENT CO., LTD. |
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Address after: 321100 Zhejiang city of Lanxi Province River Street No. 158 bridge mountain Patentee after: Zhejiang Worldbest Pharmaceuticals Science & Technic Development Co., Ltd. Address before: 321100 Zhejiang city of Lanxi Province River Street No. 158 bridge mountain Patentee before: Zhejiang Worldbest Pharmaceuticals Science Technic Development Co., Ltd. |