CN109694384A - A kind of preparation method of anticholinesterase - Google Patents
A kind of preparation method of anticholinesterase Download PDFInfo
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- CN109694384A CN109694384A CN201710995464.4A CN201710995464A CN109694384A CN 109694384 A CN109694384 A CN 109694384A CN 201710995464 A CN201710995464 A CN 201710995464A CN 109694384 A CN109694384 A CN 109694384A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000000544 cholinesterase inhibitor Substances 0.000 title claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000006136 alcoholysis reaction Methods 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 19
- 150000002327 glycerophospholipids Chemical class 0.000 claims abstract description 16
- 229910001868 water Inorganic materials 0.000 claims abstract description 16
- 239000011347 resin Substances 0.000 claims abstract description 15
- 229920005989 resin Polymers 0.000 claims abstract description 15
- KXGFMDJXCMQABM-UHFFFAOYSA-N 2-methoxy-6-methylphenol Chemical compound [CH]OC1=CC=CC([CH])=C1O KXGFMDJXCMQABM-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000005011 phenolic resin Substances 0.000 claims abstract description 12
- 229920001568 phenolic resin Polymers 0.000 claims abstract description 12
- 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 claims abstract description 10
- 239000003729 cation exchange resin Substances 0.000 claims abstract description 10
- 239000011148 porous material Substances 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 238000007598 dipping method Methods 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 4
- 238000010828 elution Methods 0.000 claims abstract description 4
- 239000012535 impurity Substances 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- 229960000583 acetic acid Drugs 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000001179 sorption measurement Methods 0.000 claims description 3
- 239000012071 phase Substances 0.000 claims description 2
- 239000008367 deionised water Substances 0.000 abstract description 7
- 229910021641 deionized water Inorganic materials 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 238000011084 recovery Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 230000003287 optical effect Effects 0.000 abstract description 2
- 238000004061 bleaching Methods 0.000 abstract 1
- 239000007844 bleaching agent Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 235000019441 ethanol Nutrition 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 238000000034 method Methods 0.000 description 9
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical class OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 3
- 238000007654 immersion Methods 0.000 description 3
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 3
- BQPIGGFYSBELGY-UHFFFAOYSA-N mercury(2+) Chemical compound [Hg+2] BQPIGGFYSBELGY-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000008719 thickening Effects 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000005341 cation exchange Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 239000008777 Glycerylphosphorylcholine Substances 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 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
- 230000003321 amplification Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- AYJRCSIUFZENHW-DEQYMQKBSA-L barium(2+);oxomethanediolate Chemical compound [Ba+2].[O-][14C]([O-])=O AYJRCSIUFZENHW-DEQYMQKBSA-L 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- SUHOQUVVVLNYQR-MRVPVSSYSA-N choline alfoscerate Chemical compound C[N+](C)(C)CCOP([O-])(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-N 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 229960004956 glycerylphosphorylcholine Drugs 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005406 washing Methods 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A kind of preparation method of anticholinesterase belongs to natural drug separating and purifying technology field.Step: first large pores cation exchange resin is impregnated with acid solution, acid solution is drained and is rinsed with water, then with dipping by lye, be rinsed with water, then with acid soak, rinsed with deionized water, then replaced with low-carbon alcohols；Phosphoglyceride is added in low-carbon alcohols, filters after adding alkali to react, is washed with low-carbon alcohols, adjusts pH to alkalescent, is concentrated under reduced pressure and is transferred in separatory funnel after cooling down, stand, separate lower layer's low-carbon alcohol phase；Phosphoglyceride and phenolic resin are filled into column, alcoholysis mixed liquor upper prop is adsorbed, resin removal of impurities is washed with low-carbon alcohols, elution is referred to tree with pure water；With bleaching agent bleaching, it is concentrated under reduced pressure, obtains finished product.Advantage: processing step is brief, meets industrialization production requirements；It economizes on resources, reduces cost；The total recovery of finished product is obtained up to 65.47-86.08%, external standard content up to 99% or more, optical purity is up to 99%.
Description
Technical field
The invention belongs to natural drug separating and purifying technology fields, and in particular to a kind of preparation side of anticholinesterase
Method.
Background technique
Glycerolphosphocholine (English name are as follows: novel glycerophosphorylCholine is abbreviated as novel GPC)
For people's naturally occurring aqueous phospholipid metabolite in vivo, while before being also synthesis acetylcholine and phosphatidyl choline (PC)
Body, structure are made of choline, glycerol and phosphatidyl.Novel GPC belongs to anticholinesterase, can effectively prevent and
Cerebral infarction is treated, the memory and cognitive ability of patient can be not only improved, treats Alzheimer disease and cranial nerve
The effects of the effects of injured, and be also act against muscular atrophy, resists hyperlipidemia and artery sclerosis, protects blood vessel, therefore quilt
It is widely used in the industries such as medicine and health care product.
The preparation method of novel GPC has solvent extraction (referred to as purifying extraction), the precipitation method, recrystallization method and chromatographic column
Chromatography etc..Earliest purifying extraction be from Pancreas Bovis seu Bubali abstraction purification obtain novel GPC sterling (GSchmidt,
J.Biochem, 1945,161-523).1954, United States Patent (USP) US2864848 disclosed the mercury salt precipitation method, and this method is with mercury
The form of salt precipitates by-product, and removes excessive mercury ion by hydrogen sulfide and barium carbonate, it can be difficult to mercury ion is filled
Divide and remove, due to remaining unreacted PC, it is therefore desirable to add the novel GPC of calcium precipitation and remove mercury ion, finally with tree
Rouge removes calcium salt.It can be seen that this method efficiency is lower, process is more complex, and final yield is also unsatisfactory.Then, Brockerhoff
Novel GPC sterling is prepared with recrystallization method, but needs to remove catalyst, and recrystallization purifying, entire mistake are carried out to product
Journey is more complicated, and cost is relatively high, is not suitable for commercial-scale production.
Summary of the invention
Task of the invention lies in provide one kind facilitate simplify processing step and operate it is convenient and use satisfaction industry
Change amplification production requirement, be conducive to will to isolate and purify material recycling and uses and economize on resources and reduce preparation cost and beneficial
In the preparation method for the anticholinesterase for obtaining ideal purity.
The task of the present invention is in this way to complete, a kind of preparation method of anticholinesterase, comprising the following steps:
A phenolic resin) is produced, first large pores cation exchange resin is impregnated with acid solution, acid solution is drained and uses water
It rinses, then uses dipping by lye, drain lye and be rinsed with water again, then, again with acid soak, drain acid solution and in turn
It is rinsed with deionized water, drains water, finally replaced with low-carbon alcohols, obtain phenolic resin；
B phosphoglyceride is added in low-carbon alcohols) alcoholysis reaction, and at room temperature plus alkali is stirred to react, and is taken out after reaction
Filter, obtains alcoholysis reaction organic phase, is washed with low-carbon alcohols, filtrate vinegar acid for adjusting pH to alkalescent, after being concentrated under reduced pressure and cooling down
It is transferred in separatory funnel, stands, separate lower layer's low-carbon alcohol phase, obtain alcoholysis mixed liquor；
C) resin adsorption purifies, and phosphoglyceride and phenolic resin are filled column, alcoholysis mixed liquor upper prop is adsorbed, and controls
Alcoholysis mixed liquor processed flows through the flow of resin column, washs resin removal of impurities with low-carbon alcohols, finally refers to elution to tree with pure water, contained
There is the aqueous solution of novel GPC；
D) decoloration concentration at room temperature decolourizes to the aqueous solution containing novel GPC with decolorising agent, colourless liquid is obtained by filtration
Body, then be concentrated under reduced pressure, novel GPC is obtained, low-carbon alcohols recycle and are re-used in step A).
In a specific embodiment of the invention, step A) described in acid solution and macroporous type cation exchange tree
The weight ratio of rouge is 3-5: 1, and the acid solution is the hydrochloric acid solution or sulfuric acid solution that mass percent concentration is 3-5%, institute
The time impregnated to large pores cation exchange resin stated is 150-210min, it is described be rinsed with water water used be go from
Sub- water, and rinse to pH5-7；The weight ratio of the lye and large pores cation exchange resin is 3-5: 1, the lye
The sodium hydroxide solution or potassium hydroxide solution for being 3-5% for mass percent concentration, the time of the dipping by lye are 150-
210min, it is described to be rinsed with water water used again as deionized water, and rinse to pH7-10；The acid solution and macroporous type
The weight ratio of cation exchange resin is 3-5: 1, and the acid solution is the hydrochloric acid solution or sulphur that mass percent concentration is 3-5%
Acid solution, time of acid soak are 150-210min, described and then to be rinsed with water water used be deionized water, and are rinsed
It is neutrality to pH value.
In another specific embodiment of the invention, the large pores cation exchange resin is that acrylic acid series is big
Pass cation exchange resin.
In another specific embodiment of the invention, step B) described in phosphoglyceride and low-carbon alcohols weight
Than being 1: 1-8；The reaction time for adding alkali to be stirred to react at room temperature is 2-18h；The alkali and phosphoglyceride
Molar ratio is 1-3: 2；The filtrate is adjusted to pH6.0-7.5 with acetic acid；The reduced pressure is by the filter of pH6.0-7.5
Liquid is concentrated into 1.2~1.8 times of phosphoglyceride weight；The time of the standing is 40-80min.
In another specific embodiment of the invention, step B) described in alcoholysis reaction organic phase be novel GPC,
The mixture of novel GPE, Novel GPS and other by-products.
Of the invention there are one in specific embodiment, step C) described in phosphoglyceride and phenolic resin
W/v is 1: 1-5；The control alcoholysis mixed liquor flow through resin column flow be by flow control be 50-80ml/
h。
In a still more specific embodiment of the invention, step D) described in decolorising agent be active carbon, active carbon
Weight ratio with the aqueous solution containing novel GPC is 0.05~0.2: 1,；The thickening temperature of the reduced pressure is 45-70
DEG C, decompressed pressure is -0.09~-0.1MPa.
In a specific embodiment in turn of the invention, the low-carbon alcohols are methanol, ethyl alcohol, normal propyl alcohol.
In yet a further embodiment of the present invention it is characterized in that described adds alkali stirring anti-at room temperature
The reaction time answered is 4h, it is characterised in that the alkali is sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide.
Of the invention again and then in a specific embodiment, the phosphoglyceride and phenolic resin body by weight
Product is than being 1: 2；The control alcoholysis mixed liquor flow through resin column flow be by flow control be 80ml/h.
Technical solution provided by the invention relative to prior art there is processing step to be briefly satisfied industrialization and put
Mass production requirement；Due to can be by step D) in low-carbon alcohols recycle and be re-used in step A), thus can economize on resources and
Reduce preparation cost；The total recovery of obtained anticholinesterase up to 65.47-86.08%, external standard content up to 99% or more,
Optical purity is up to 99%.
Specific embodiment
Below with reference to embodiment, the present invention will be further described
Embodiment
A) produce phenolic resin, first with mass percent concentration be 3% hydrochloric acid solution to acrylic acid series macroporous type sun from
Sub-exchange resin impregnates, the hydrochloric acid solution and acrylic acid series macroporous type cation exchange tree that wherein mass percent concentration is 3%
The weight ratio of rouge is 5: 1, and the time of immersion is 150min, and hydrochloric acid solution is drained after immersion and drains acid solution and spends
Ionized water is rinsed to pH7, then is used the sodium hydroxide solution (i.e. lye) that mass percent concentration is 3% instead and impregnated, the hydroxide
The weight ratio of sodium solution and acrylic acid series large pores cation exchange resin is 4: 1, and the time of dipping by lye is 150min, lye
Sodium hydroxide solution is drained after immersion and drains lye, and is rinsed again with deionized water to pH10, is then used again
The hydrochloric acid solution that mass percent concentration is 3% impregnates 150min, which exchanges with acrylic acid series macroporous type cation
The weight ratio of resin is 5: 1, drains acid solution after impregnating again and drains hydrochloric acid solution and rinsed in turn with deionized water,
Water is drained after flushing, finally uses ethanol replacement, the moisture content in resin is replaced as ethanol solution, obtains phenolic resin, this
It is preferable to use raw by Chinese Shanghai Hua Zhen Science and Technology Ltd. for acrylic acid series large pores cation exchange resin described in step
The trade mark that is producing and widely selling before present patent application proposition in market is HD-2, DK110, D152 or D113 etc.；
B phosphoglyceride is added in ethyl alcohol) alcoholysis reaction, and the weight ratio of phosphoglyceride and ethyl alcohol is 1:8, in room
Temperature is lower to be added sodium methoxide, is stirred to react 4h, and the mol ratio of sodium methoxide and phosphoglyceride is 1: 2, filters, obtains after reaction
Alcoholysis reaction organic phase, the alcoholysis reaction organic phase are the mixing of novel GPC, novel GPE, Novel GPS and other by-products
Object washs alcoholysis reaction organic phase with ethyl alcohol, and filtrate is adjusted to pH7 with acetic acid, and it is 20 DEG C that thickening temperature, which is then concentrated under reduced pressure,
Decompressed pressure is -0.1MPa.Stop concentration when being concentrated into 1.5 times of phosphoglyceride weight, is transferred to separatory funnel after cooling
In, 60min is stood, alcoholysis mixed liquor is obtained；
C) resin adsorption purifies, and phosphoglyceride is filled with the phenolic resin volume ratio 1: 5 by weight obtained by step A)
Column, and will be adsorbed by the alcoholysis mixed liquor upper prop that step B) is obtained, it is by the flow control that alcoholysis mixed liquor flows through resin column
80ml/h is cleaned with ethanol washing resin, finally refers to elution to tree with deionized water, obtain the aqueous solution containing novel GPC；
D) decoloration concentration at room temperature lives to the aqueous solution decoloration containing novel GPC obtained by step C) with active carbon
Property charcoal with containing novel GPC aqueous solution weight ratio be 0.05: 1, colourless liquid is obtained by filtration, to colourless liquid depressurize
Concentration, thickening temperature are 70 DEG C, and decompressed pressure is -0.1MPa, obtains novel GPC, low-carbon alcohols, that is, ethyl alcohol is recycled and reused
In the displacement of step A).
The total recovery of the present embodiment is 86.08%, is detected through HPLC-ELSD, external standard content 99.2%, chemical purity ee is
99%, [α]20 D=-2.6 ° of (C=10, H2O, pH=5.5).
Claims (1)
1. a kind of preparation method of anticholinesterase, it is characterised in that the following steps are included:
A phenolic resin) is produced, first large pores cation exchange resin is impregnated with acid solution, acid solution is drained and is rinsed with water,
Dipping by lye is used again, lye is drained and is rinsed with water again, then, is used acid soak again, is drained acid solution and spend in turn
Ionized water rinses, and drains water, is finally replaced with low-carbon alcohols, obtains phenolic resin；
B phosphoglyceride is added in low-carbon alcohols) alcoholysis reaction, and at room temperature plus alkali is stirred to react, and filters after reaction,
Alcoholysis reaction organic phase is obtained, is washed with low-carbon alcohols, filtrate vinegar acid for adjusting pH to alkalescent is concentrated under reduced pressure and is transferred to after cooling down
In separatory funnel, stands, separate lower layer's low-carbon alcohol phase, obtain alcoholysis mixed liquor；
C) resin adsorption purifies, and phosphoglyceride and phenolic resin are filled column, alcoholysis mixed liquor upper prop is adsorbed, and control alcohol
Solution mixed liquor flows through the flow of resin column, washs resin removal of impurities with low-carbon alcohols, finally refers to elution to tree with pure water, obtain containing new
The aqueous solution of type GPC；
D) decoloration concentration at room temperature decolourizes to the aqueous solution containing novel GPC with decolorising agent, through colourless liquid is obtained by filtration,
It is concentrated under reduced pressure again, obtains novel GPC, low-carbon alcohols recycle and are re-used in step A).
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710995464.4A CN109694384A (en) | 2017-10-23 | 2017-10-23 | A kind of preparation method of anticholinesterase |
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| CN201710995464.4A CN109694384A (en) | 2017-10-23 | 2017-10-23 | A kind of preparation method of anticholinesterase |
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| CN109694384A true CN109694384A (en) | 2019-04-30 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128467A (en) * | 2019-05-07 | 2019-08-16 | 天津康巢生物医药股份有限公司 | A kind of process of purification of glycerol phosphatidyl choline crude product and its obtained glycerolphosphocholine |
-
2017
- 2017-10-23 CN CN201710995464.4A patent/CN109694384A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128467A (en) * | 2019-05-07 | 2019-08-16 | 天津康巢生物医药股份有限公司 | A kind of process of purification of glycerol phosphatidyl choline crude product and its obtained glycerolphosphocholine |
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