CN108997412A - The method of purification of crude glycerol phosphatidyl choline - Google Patents
The method of purification of crude glycerol phosphatidyl choline Download PDFInfo
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- CN108997412A CN108997412A CN201810794600.8A CN201810794600A CN108997412A CN 108997412 A CN108997412 A CN 108997412A CN 201810794600 A CN201810794600 A CN 201810794600A CN 108997412 A CN108997412 A CN 108997412A
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- CN
- China
- Prior art keywords
- mixed liquor
- purification
- phosphatidyl choline
- aqueous solution
- column
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 238000000034 method Methods 0.000 title claims abstract description 29
- 238000000746 purification Methods 0.000 title claims abstract description 22
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 title claims abstract description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 42
- 239000007864 aqueous solution Substances 0.000 claims abstract description 20
- 238000001035 drying Methods 0.000 claims abstract description 19
- 238000001704 evaporation Methods 0.000 claims abstract description 19
- 239000003513 alkali Substances 0.000 claims abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 17
- 230000008020 evaporation Effects 0.000 claims abstract description 16
- 239000004519 grease Substances 0.000 claims abstract description 14
- 238000002156 mixing Methods 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000001450 anions Chemical class 0.000 claims abstract description 10
- 150000001768 cations Chemical class 0.000 claims abstract description 9
- 238000005374 membrane filtration Methods 0.000 claims abstract description 9
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 239000010409 thin film Substances 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 6
- 239000010408 film Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000003930 cognitive ability Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses a kind of methods of purification of crude glycerol phosphatidyl choline, wherein the method for purification includes: to dry after the aqueous solution mixing of alkali 1) is added into crude glycerol phosphatidyl choline, and material drying M1 is made；2) methanol is added in material drying M1 to mix, mixed liquor M2 is made；3) mixed liquor M2 is crossed into aluminum oxide column, mixed liquor M3 is made；4) mixed liquor M3 is concentrated by evaporation, grease M4 is made；5) after adding water to mix grease M4 sequentially after cation seperation column and anion column, through membrane filtration, mixed liquor M5 is made；6) dry, the glycerolphosphocholine after being purified after being concentrated by evaporation mixed liquor M5.It realizes without using a large amount of various types of organic solvents, inorganic solution is introduced, further increase it and prepare safety, and can preferably guarantee the effect of the purity of its purification.
Description
Technical field
The present invention relates to the finishing passes of glycerolphosphocholine, and in particular, to crude glycerol phosphatidyl choline
Method of purification.
Background technique
Glycerolphosphocholine is the product by generating after two fatty acid chain hydrolysis on phospholipid molecule, is lecithin in human body
The catabolite of rouge.It plays particularly important effect in the synthesis and metabolism of phosphatide, for human body cognitive ability
Raising, maintenance of hormone level etc. have particularly important meaning.The study found that it is for reducing hyperlipidemia, improving always
Year man memory and cognitive ability, treatment alzheimer's disease etc. have certain effect.
Glycerophosphatide is prepared generally by modes such as chemical synthesis, chemical hydrolysis or biological enzyme hydrolysis in the prior art
Phatidylcholine, so that wherein often containing certain impurity, the purity of glycerolphosphocholine obtained also tends to lower.It is right
It also tend to be eluted by the way that a large amount of various organic solvents are added in the method for its purification, so as to cause the big of organic solvent
Amount introduces.
Therefore it provides it is a kind of without using a large amount of various types of organic solvents, inorganic solution is introduced, is further increased
It prepares safety, and can preferably guarantee that the method for purification of the crude glycerol phosphatidyl choline of the purity of its purification is the present invention
The problem of urgent need to resolve.
Summary of the invention
For the above-mentioned prior art, the purpose of the present invention is to provide one kind without using a large amount of various types of organic molten
Agent introduces inorganic solution, further increases it and prepares safety, and can preferably guarantee the crude sweet of the purity that it is purified
The method of purification of oily phosphatidyl choline.
To achieve the goals above, the present invention provides a kind of methods of purification of crude glycerol phosphatidyl choline, wherein institute
Stating method of purification includes:
1) it is dried after the aqueous solution mixing of alkali is added into crude glycerol phosphatidyl choline, material drying M1 is made；
2) methanol is added in material drying M1 to mix, mixed liquor M2 is made；
3) mixed liquor M2 is crossed into aluminum oxide column, mixed liquor M3 is made；
4) mixed liquor M3 is concentrated by evaporation, grease M4 is made；
5) after adding water to mix grease M4 sequentially after cation seperation column and anion column, through membrane filtration, mixing is made
Liquid M5；
6) dry, the glycerolphosphocholine after being purified after being concentrated by evaporation mixed liquor M5.
Preferably, in step 1), the aqueous solution of the alkali is selected from sodium hydrate aqueous solution and/or potassium hydroxide aqueous solution.
Preferably, in step 1), the concentration of alkali is 3-5mol/L in the aqueous solution of the alkali.
Preferably, mixed process is to be stirred, and stirring rate is 100-300r/min in step 1), and mixing time is
10-15min。
Preferably, in step 2), relative to the material drying M1 of 10g, the dosage of the methanol is 10-20mL.
Preferably, in step 5), the filter opening of film is 0.2-0.5 μm.
Preferably, step 4) and evaporating concentration process in step 6) are to be placed in thin film evaporator to be evaporated concentration.
Through the above technical solutions, the present invention dries after the aqueous solution mixing of alkali is added in crude glycerol phosphatidyl choline
It is dry, methanol mixing is then added thereto, and cross the elution of aluminum oxide column, after being further concentrated by evaporation plus water is sequentially through sun
Ion column and anion column, and after be evaporated concentration and drying again through membrane filtration so that be used only methanol this have
Solvent can be purified preferably crude sweet in conjunction with the aqueous solution of alkali, and then under the premise of largely not introducing various organic solvents
Oily phosphatidyl choline improves its safety used.
Other features and advantages of the present invention will the following detailed description will be given in the detailed implementation section.
Specific embodiment
Detailed description of the preferred embodiments below.It should be understood that described herein specific
Embodiment is merely to illustrate and explain the present invention, and is not intended to restrict the invention.
The endpoint of disclosed range and any value are not limited to the accurate range or value herein, these ranges or
Value should be understood as comprising the value close to these ranges or value.For numberical range, between the endpoint value of each range, respectively
It can be combined with each other between the endpoint value of a range and individual point value, and individually between point value and obtain one or more
New numberical range, these numberical ranges should be considered as specific open herein.
The present invention provides a kind of methods of purification of crude glycerol phosphatidyl choline, wherein the method for purification includes:
1) it is dried after the aqueous solution mixing of alkali is added into crude glycerol phosphatidyl choline, material drying M1 is made；
2) methanol is added in material drying M1 to mix, mixed liquor M2 is made；
3) mixed liquor M2 is crossed into aluminum oxide column, mixed liquor M3 is made；
4) mixed liquor M3 is concentrated by evaporation, grease M4 is made；
5) after adding water to mix grease M4 sequentially after cation seperation column and anion column, through membrane filtration, mixing is made
Liquid M5；
6) dry, the glycerolphosphocholine after being purified after being concentrated by evaporation mixed liquor M5.
The present invention is dried after the aqueous solution mixing of alkali is added in crude glycerol phosphatidyl choline, and first is then added thereto
Alcohol mixing, and the elution of aluminum oxide column is crossed, after being further concentrated by evaporation plus water is sequentially through cation seperation column and anion column, and
Concentration and drying are evaporated again by membrane filtration, so that this organic solvent of methanol is used only, in conjunction with the water-soluble of alkali
Liquid, and then under the premise of largely not introducing various organic solvents, crude glycerolphosphocholine can be preferably purified, it is improved
The safety used.
In a preferred embodiment of the invention, in step 1), the aqueous solution of the alkali is selected from sodium hydroxide water
Solution and/or potassium hydroxide aqueous solution.
In further preferred embodiment, in step 1), the concentration of alkali is 3-5mol/L in the aqueous solution of the alkali.
In one kind more preferably embodiment, mixed process is to be stirred, and stirring rate is 100- in step 1)
300r/min, mixing time 10-15min.
More preferably in embodiment, in step 2), relative to the material drying M1 of 10g, the use of the methanol
Amount is 10-20mL.
In one kind more preferably embodiment, in step 5), the filter opening of film is 0.2-0.5 μm.
In further preferred embodiment, evaporating concentration process is to be placed in thin film evaporator in step 4) and step 6)
It is evaporated concentration.
The present invention will be described in detail by way of examples below.Wherein, the purity of crude glycerol phosphatidyl choline is
63.6%.
Embodiment 1
1) it is the sodium hydrate aqueous solution of 4mol/L with 100r/min's that concentration is added into crude glycerol phosphatidyl choline
Stirring rate is dried after being stirred 10min, and material drying M1 is made；
2) 10mL methanol is added in 10g material drying M1 to mix, mixed liquor M2 is made；
3) mixed liquor M2 is crossed into aluminum oxide column, mixed liquor M3 is made；
4) mixed liquor M3 is placed in thin film evaporator and is concentrated by evaporation, grease M4 is made；
5) after adding water to mix grease M4 sequentially after cation seperation column and anion column, through 0.3 μm of membrane filtration, system
Obtain mixed liquor M5；
6) mixed liquor M5 is placed in thin film evaporator to dry after being concentrated by evaporation, the glycerolphosphocholine after being purified
A1.(purity of glycerolphosphocholine A1 obtained is 95.2%)
Embodiment 2
1) it is the sodium hydrate aqueous solution of 4mol/L with 300r/min's that concentration is added into crude glycerol phosphatidyl choline
Stirring rate is dried after being stirred 15min, and material drying M1 is made；
2) 20mL methanol is added in 10g material drying M1 to mix, mixed liquor M2 is made；
3) mixed liquor M2 is crossed into aluminum oxide column, mixed liquor M3 is made；
4) mixed liquor M3 is placed in thin film evaporator and is concentrated by evaporation, grease M4 is made；
5) after adding water to mix grease M4 sequentially after cation seperation column and anion column, through 0.3 μm of membrane filtration, system
Obtain mixed liquor M5；
6) mixed liquor M5 is placed in thin film evaporator to dry after being concentrated by evaporation, the glycerolphosphocholine after being purified
A2.(purity of glycerolphosphocholine A2 obtained is 94.8%)
Embodiment 3
1) it is the sodium hydrate aqueous solution of 4mol/L with 200r/min's that concentration is added into crude glycerol phosphatidyl choline
Stirring rate is dried after being stirred 12min, and material drying M1 is made；
2) 15mL methanol is added in 10g material drying M1 to mix, mixed liquor M2 is made；
3) mixed liquor M2 is crossed into aluminum oxide column, mixed liquor M3 is made；
4) mixed liquor M3 is placed in thin film evaporator and is concentrated by evaporation, grease M4 is made；
5) after adding water to mix grease M4 sequentially after cation seperation column and anion column, through 0.3 μm of membrane filtration, system
Obtain mixed liquor M5；
6) mixed liquor M5 is placed in thin film evaporator to dry after being concentrated by evaporation, the glycerolphosphocholine after being purified
A3.(purity of glycerolphosphocholine A3 obtained is 96.5%)
Comparative example 1
It is operated according to the method for embodiment 1, unlike, without step 1), directly by crude glycerol phosphatidyl
Choline and methanol mixing, the glycerolphosphocholine D1 after being purified.(purity of glycerolphosphocholine D1 obtained is
76.9%)
Comparative example 2
It is operated according to the method for embodiment 2, unlike, without cation seperation column and anion column, directly filter,
Glycerolphosphocholine D2 after being purified.(purity of glycerolphosphocholine D2 obtained is 73.1%)
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above
Detail within the scope of the technical concept of the present invention can be with various simple variants of the technical solution of the present invention are made, this
A little simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case where shield, can be combined in any appropriate way, in order to avoid unnecessary repetition, the present invention to it is various can
No further explanation will be given for the combination of energy.
In addition, various embodiments of the present invention can be combined randomly, as long as it is without prejudice to originally
The thought of invention, it should also be regarded as the disclosure of the present invention.
Claims (7)
1. a kind of method of purification of crude glycerol phosphatidyl choline, which is characterized in that the method for purification includes:
1) it is dried after the aqueous solution mixing of alkali is added into crude glycerol phosphatidyl choline, material drying M1 is made；
2) methanol is added in material drying M1 to mix, mixed liquor M2 is made；
3) mixed liquor M2 is crossed into aluminum oxide column, mixed liquor M3 is made；
4) mixed liquor M3 is concentrated by evaporation, grease M4 is made；
5) after adding water to mix grease M4 sequentially after cation seperation column and anion column, through membrane filtration, mixed liquor M5 is made；
6) dry, the glycerolphosphocholine after being purified after being concentrated by evaporation mixed liquor M5.
2. method of purification according to claim 1, wherein in step 1), the aqueous solution of the alkali is selected from sodium hydroxide water
Solution and/or potassium hydroxide aqueous solution.
3. method of purification according to claim 1 or 2, wherein in step 1), the concentration of alkali is in the aqueous solution of the alkali
3-5mol/L。
4. method of purification according to claim 1 or 2, wherein mixed process is to be stirred, and stir speed in step 1)
Rate is 100-300r/min, mixing time 10-15min.
5. method of purification according to claim 1 or 2, wherein in step 2), relative to the material drying M1 of 10g,
The dosage of the methanol is 10-20mL.
6. method of purification according to claim 1 or 2, wherein in step 5), the filter opening of film is 0.2-0.5 μm.
7. method of purification according to claim 1 or 2, wherein evaporating concentration process is to be placed in step 4) and step 6)
Concentration is evaporated in thin film evaporator.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810794600.8A CN108997412A (en) | 2018-07-19 | 2018-07-19 | The method of purification of crude glycerol phosphatidyl choline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810794600.8A CN108997412A (en) | 2018-07-19 | 2018-07-19 | The method of purification of crude glycerol phosphatidyl choline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108997412A true CN108997412A (en) | 2018-12-14 |
Family
ID=64599909
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|---|---|---|---|
| CN201810794600.8A Pending CN108997412A (en) | 2018-07-19 | 2018-07-19 | The method of purification of crude glycerol phosphatidyl choline |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093410A (en) * | 2011-01-11 | 2011-06-15 | 江南大学 | Method for separating and purifying L-alpha-glycerophosphorylcholine (L-alpha-GPC) by silica gel column chromatography |
| CN102875592A (en) * | 2012-09-29 | 2013-01-16 | 常熟富士莱医药化工有限公司 | Natural L-alpha-glycero-phosphatidylcholine preparation method |
| CN103172659A (en) * | 2013-03-29 | 2013-06-26 | 山东罗欣药业股份有限公司 | L-alpha-glyceryl phosphoryl choline crystal form compound |
| CN105017307A (en) * | 2015-07-22 | 2015-11-04 | 沈阳天峰生物制药有限公司 | Method for preparing high-purity natural L-alpha-glycerylphosphorylcholine |
| CN106083916A (en) * | 2016-06-08 | 2016-11-09 | 芜湖福民生物药业有限公司 | The preparation method of choline alfoscerate crystal |
-
2018
- 2018-07-19 CN CN201810794600.8A patent/CN108997412A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093410A (en) * | 2011-01-11 | 2011-06-15 | 江南大学 | Method for separating and purifying L-alpha-glycerophosphorylcholine (L-alpha-GPC) by silica gel column chromatography |
| CN102875592A (en) * | 2012-09-29 | 2013-01-16 | 常熟富士莱医药化工有限公司 | Natural L-alpha-glycero-phosphatidylcholine preparation method |
| CN103172659A (en) * | 2013-03-29 | 2013-06-26 | 山东罗欣药业股份有限公司 | L-alpha-glyceryl phosphoryl choline crystal form compound |
| CN105017307A (en) * | 2015-07-22 | 2015-11-04 | 沈阳天峰生物制药有限公司 | Method for preparing high-purity natural L-alpha-glycerylphosphorylcholine |
| CN106083916A (en) * | 2016-06-08 | 2016-11-09 | 芜湖福民生物药业有限公司 | The preparation method of choline alfoscerate crystal |
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