CN106083916A - The preparation method of choline alfoscerate crystal - Google Patents
The preparation method of choline alfoscerate crystal Download PDFInfo
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- CN106083916A CN106083916A CN201610403610.5A CN201610403610A CN106083916A CN 106083916 A CN106083916 A CN 106083916A CN 201610403610 A CN201610403610 A CN 201610403610A CN 106083916 A CN106083916 A CN 106083916A
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- preparation
- choline alfoscerate
- crystal
- ethanol
- choline
- Prior art date
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Links
- 239000008777 Glycerylphosphorylcholine Substances 0.000 title claims abstract description 56
- 229960004788 choline alfoscerate Drugs 0.000 title claims abstract description 56
- SUHOQUVVVLNYQR-MRVPVSSYSA-O glycerylphosphorylcholine Chemical compound C[N+](C)(C)CCO[P@](O)(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-O 0.000 title claims abstract description 56
- 239000013078 crystal Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 58
- 239000011347 resin Substances 0.000 claims abstract description 28
- 229920005989 resin Polymers 0.000 claims abstract description 28
- 239000012043 crude product Substances 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 12
- 125000002091 cationic group Chemical group 0.000 claims abstract description 11
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000001450 anions Chemical class 0.000 claims abstract description 10
- 239000005457 ice water Substances 0.000 claims abstract description 8
- 238000001035 drying Methods 0.000 claims description 15
- 239000012528 membrane Substances 0.000 claims description 9
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 abstract description 7
- 229960001231 choline Drugs 0.000 abstract description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- 235000009508 confectionery Nutrition 0.000 description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- 210000000232 gallbladder Anatomy 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010029216 Nervousness Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical compound OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 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 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002243 precursor 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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the preparation method of a kind of choline alfoscerate crystal, wherein, described preparation method includes: choline alfoscerate and ethanol is mixed, forms mixed liquor M；Described mixed liquor M is crossed successively aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column, is then concentrated in vacuo, dries, obtain choline alfoscerate crude product N；Choline alfoscerate crude product N and ethanol are mixed, and heated and stirred, carry out ice-water bath process afterwards, described choline alfoscerate crystal is obtained after standing, the preparation method solving traditional choline glycerophosphatide crystal is relatively complicated, the crystal mass and the purity that obtain are the highest, the problem that the yield of preparation method is low.
Description
Technical field
The present invention relates to the preparation field of choline alfoscerate, in particular it relates to the preparation method of choline alfoscerate crystal.
Background technology
Choline glycerophosphatide is the product that in phosphatidylcholine molecules, two fatty acid chains are hydrolyzed completely, comprise choline,
Glycerol, phosphate, be one of product of phospholipid metabolism in body, is also the biological conjunction of important neurotransmitter acetylcholine
Become precursor, brain can be helped to carry out learning, the activity such as memory, even repair what senile dementia early stage patient had been partially damaged
Cognitive competence, it has critical treatment effect for nervousness and the abalienation of brain.Traditional choline glycerophosphatide crystal
Preparation method is relatively complicated, and the crystal mass and the purity that obtain are the highest, and the yield of preparation method is low.
Summary of the invention
It is an object of the invention to provide the preparation method of a kind of choline alfoscerate crystal, solve traditional phosphoglycerol gallbladder
The preparation method of alkali crystal is relatively complicated, and the crystal mass and the purity that obtain are the highest, the problem that the yield of preparation method is low.
To achieve these goals, the invention provides the preparation method of a kind of choline alfoscerate crystal, wherein, described system
Preparation Method includes:
(1) choline alfoscerate and ethanol are mixed, form mixed liquor M；
(2) described mixed liquor M is crossed successively aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column, then vacuum
Concentrate, dry, obtain choline alfoscerate crude product N；
(3) choline alfoscerate crude product N and ethanol are mixed, and heated and stirred, carry out ice-water bath process afterwards, after standing
To described choline alfoscerate crystal.
By technique scheme, the invention provides the preparation method of a kind of choline alfoscerate crystal, wherein, described system
Preparation Method includes: choline alfoscerate and ethanol is mixed, forms mixed liquor M；Described mixed liquor M is crossed successively aluminium sesquioxide
Post, resin anion (R.A.) post, cationic resin column, be then concentrated in vacuo, dry, and obtains choline alfoscerate crude product N；By sweet phosphoric acid gallbladder
Alkali crude product N and ethanol mixing, and heated and stirred, carry out ice-water bath process afterwards, obtain described choline alfoscerate crystal after standing,
Purity and the quality of the crystal obtained are higher, and preparation method is simple, yield is high, raw material is easy to get.
Other features and advantages of the present invention will be described in detail in detailed description of the invention part subsequently.
Detailed description of the invention
Hereinafter the detailed description of the invention of the present invention is described in detail.It should be appreciated that described herein specifically
Embodiment is merely to illustrate and explains the present invention, is not limited to the present invention.
The invention provides the preparation method of a kind of choline alfoscerate crystal, wherein, described preparation method includes: by sweet phosphorus
Acid choline and ethanol mixing, form mixed liquor M；Described mixed liquor M is crossed successively aluminium sesquioxide post, resin anion (R.A.) post, sun
Ion exchange resin post, is then concentrated in vacuo, dries, and obtains choline alfoscerate crude product N；Choline alfoscerate crude product N and ethanol are mixed,
And heated and stirred, carry out ice-water bath process afterwards, after standing, obtain described choline alfoscerate crystal.The purity of the crystal obtained and
Quality is higher, and preparation method is simple, yield is high, raw material is easy to get.
The present invention one preferred embodiment in so that choline alfoscerate can fully be dissolved into ethanol
In, in described mixed liquor M, the mass ratio of choline alfoscerate and ethanol is 1:1-2.5.
The present invention one preferred embodiment in so that the crystal prepared possesses higher quality and pure
Degree, described drying temperature is 55-65 DEG C, and drying time is 20-25min.
The present invention one preferred embodiment in so that the crystal prepared possesses higher quality and pure
Degree, described preparation method also includes: after described mixed liquor M crosses cationic resin column, after hybrid ionic resin column.
The present invention one preferred embodiment in, in order to improve the purity of prepared crystal further, described preparation
After method also includes heated and stirred, organic membrane is utilized to filter, it is preferred that the aperture of described organic membrane is 0.2-0.3 μm.
The present invention one preferred embodiment in so that choline alfoscerate crude product N can be the most molten
Entering in ethanol, in described heated and stirred, heating-up temperature is 65-70 DEG C.
Hereinafter will be described the present invention by embodiment.Choline alfoscerate uses the limited duty of Jinan greatization industry
The commercially available product that Ren company provides.
Embodiment 1
Choline alfoscerate and ethanol are mixed (mass ratio of choline alfoscerate and ethanol is 1:1), forms mixed liquor M；Will
Described mixed liquor M crosses aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column and hybrid ionic resin column successively, then
It is concentrated in vacuo, dries (drying temperature is 55 DEG C, and drying time is 20min), obtain choline alfoscerate crude product N；By sweet phosphoric acid gallbladder
Alkali crude product N and ethanol mixing, and heated and stirred (heating-up temperature is 65 DEG C), carry out ice-water bath after utilizing organic membrane to filter
Process, after standing, obtain choline alfoscerate crystal A1.
Embodiment 2
Choline alfoscerate and ethanol are mixed (mass ratio of choline alfoscerate and ethanol is 1:2.5), forms mixed liquor M；
Described mixed liquor M is crossed successively aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column and hybrid ionic resin column, so
Final vacuum concentrates, dries (drying temperature is 65 DEG C, and drying time is 25min), obtains choline alfoscerate crude product N；By sweet phosphoric acid
Choline crude product N and ethanol mixing, and heated and stirred (heating-up temperature is 70 DEG C), carry out frozen water after utilizing organic membrane to filter
Bath processes, and obtains choline alfoscerate crystal A2 after standing.
Embodiment 3
Choline alfoscerate and ethanol are mixed (mass ratio of choline alfoscerate and ethanol is 1:2), forms mixed liquor M；Will
Described mixed liquor M crosses aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column and hybrid ionic resin column successively, then
It is concentrated in vacuo, dries (drying temperature is 60 DEG C, and drying time is 22min), obtain choline alfoscerate crude product N；By sweet phosphoric acid gallbladder
Alkali crude product N and ethanol mixing, and heated and stirred (heating-up temperature is 68 DEG C), carry out ice-water bath after utilizing organic membrane to filter
Process, after standing, obtain choline alfoscerate crystal A3.
Comparative example 1
Choline alfoscerate and ethanol are mixed (mass ratio of choline alfoscerate and ethanol is 1:0.5), forms mixed liquor M；
Described mixed liquor M is crossed successively aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column and hybrid ionic resin column, so
Final vacuum concentrates, dries (drying temperature is 50 DEG C, and drying time is 15min), obtains choline alfoscerate crude product N；By sweet phosphoric acid
Choline crude product N and ethanol mixing, and heated and stirred (heating-up temperature is 55 DEG C), carry out frozen water after utilizing organic membrane to filter
Bath processes, and obtains choline alfoscerate crystal D1 after standing.
Comparative example 2
Choline alfoscerate and ethanol are mixed (mass ratio of choline alfoscerate and ethanol is 1:3), forms mixed liquor M；Will
Described mixed liquor M crosses aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column and hybrid ionic resin column successively, then
It is concentrated in vacuo, dries (drying temperature is 75 DEG C, and drying time is 30min), obtain choline alfoscerate crude product N；By sweet phosphoric acid gallbladder
Alkali crude product N and ethanol mixing, and heated and stirred (heating-up temperature is 75 DEG C), carry out ice-water bath after utilizing organic membrane to filter
Process, after standing, obtain choline alfoscerate crystal D2.
Table 1
By above table it can be seen that the choline alfoscerate crystal A1-A3 prepared within the scope of the present invention, its purity is relatively
Height, and the purity of choline alfoscerate crystal D1 and D2 prepared outside the scope of the invention is relatively low, therefore, utilizes system of the present invention
Purity height, quality for the choline alfoscerate crystal gone out are good.
The preferred embodiment of the present invention described in detail above, but, the present invention is not limited in above-mentioned embodiment
Detail, in the technology concept of the present invention, technical scheme can be carried out multiple simple variant, this
A little simple variant belong to protection scope of the present invention.
It is further to note that each the concrete technical characteristic described in above-mentioned detailed description of the invention, at not lance
In the case of shield, can be combined by any suitable means, in order to avoid unnecessary repetition, the present invention to various can
The compound mode of energy illustrates the most separately.
Additionally, combination in any can also be carried out between the various different embodiment of the present invention, as long as it is without prejudice to this
The thought of invention, it should be considered as content disclosed in this invention equally.
Claims (7)
1. the preparation method of a choline alfoscerate crystal, it is characterised in that described preparation method includes:
(1) choline alfoscerate and ethanol are mixed, form mixed liquor M；
(2) described mixed liquor M crossing aluminium sesquioxide post, resin anion (R.A.) post, cationic resin column successively, then vacuum is dense
Contracting, drying, obtain choline alfoscerate crude product N；
(3) choline alfoscerate crude product N and ethanol are mixed, and heated and stirred, carry out ice-water bath process afterwards, after standing, obtain institute
State choline alfoscerate crystal.
Preparation method the most according to claim 1, it is characterised in that in described mixed liquor M, choline alfoscerate and ethanol
Mass ratio is 1:1-2.5.
Preparation method the most according to claim 1, it is characterised in that described drying temperature is 55-65 DEG C, drying time is
20-25min。
Preparation method the most according to claim 1, it is characterised in that described preparation method also includes: described mixed liquor M mistake
After cationic resin column, after hybrid ionic resin column.
Preparation method the most according to claim 1, it is characterised in that after described preparation method also includes heated and stirred, profit
Filter with organic membrane.
Preparation method the most according to claim 5, it is characterised in that the aperture of described organic membrane is 0.2-0.3 μm.
Preparation method the most according to claim 5, it is characterised in that in described heated and stirred, heating-up temperature is 65-70
℃。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610403610.5A CN106083916A (en) | 2016-06-08 | 2016-06-08 | The preparation method of choline alfoscerate crystal |
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| CN201610403610.5A CN106083916A (en) | 2016-06-08 | 2016-06-08 | The preparation method of choline alfoscerate crystal |
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| CN106083916A true CN106083916A (en) | 2016-11-09 |
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| CN201610403610.5A Pending CN106083916A (en) | 2016-06-08 | 2016-06-08 | The preparation method of choline alfoscerate crystal |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997412A (en) * | 2018-07-19 | 2018-12-14 | 芜湖福民生物药业股份有限公司 | The method of purification of crude glycerol phosphatidyl choline |
| CN108997411A (en) * | 2018-07-19 | 2018-12-14 | 芜湖福民生物药业股份有限公司 | The purification process of glycerolphosphocholine |
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| 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 |
| CN103304594A (en) * | 2013-06-18 | 2013-09-18 | 上海科利生物医药有限公司 | Preparation method of L-alpha-glycerophosphoryl choline |
| US20130345464A1 (en) * | 2011-03-14 | 2013-12-26 | Hanseochem co., ltd | I-and ii-type crystals of l-a-glyceryl phosphoryl choline, and method for preparing same |
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| US20130345464A1 (en) * | 2011-03-14 | 2013-12-26 | Hanseochem co., ltd | I-and ii-type crystals of l-a-glyceryl phosphoryl choline, and method for preparing same |
| 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 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997412A (en) * | 2018-07-19 | 2018-12-14 | 芜湖福民生物药业股份有限公司 | The method of purification of crude glycerol phosphatidyl choline |
| CN108997411A (en) * | 2018-07-19 | 2018-12-14 | 芜湖福民生物药业股份有限公司 | The purification process of glycerolphosphocholine |
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Application publication date: 20161109 |