CN110128467A - A kind of process of purification of glycerol phosphatidyl choline crude product and its obtained glycerolphosphocholine - Google Patents
A kind of process of purification of glycerol phosphatidyl choline crude product and its obtained glycerolphosphocholine Download PDFInfo
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- CN110128467A CN110128467A CN201910376147.3A CN201910376147A CN110128467A CN 110128467 A CN110128467 A CN 110128467A CN 201910376147 A CN201910376147 A CN 201910376147A CN 110128467 A CN110128467 A CN 110128467A
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 title claims abstract description 89
- 238000000034 method Methods 0.000 title claims abstract description 64
- 230000008569 process Effects 0.000 title claims abstract description 48
- 239000012043 crude product Substances 0.000 title claims abstract description 38
- 238000000746 purification Methods 0.000 title claims abstract description 30
- 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 29
- 239000000243 solution Substances 0.000 claims abstract description 71
- 238000010612 desalination reaction Methods 0.000 claims abstract description 13
- 239000012141 concentrate Substances 0.000 claims abstract description 12
- 238000002425 crystallisation Methods 0.000 claims abstract description 11
- 230000008025 crystallization Effects 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 238000000638 solvent extraction Methods 0.000 claims abstract description 10
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 238000004090 dissolution Methods 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 7
- 239000011347 resin Substances 0.000 claims description 25
- 229920005989 resin Polymers 0.000 claims description 25
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000010828 elution Methods 0.000 claims description 15
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical group C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000003456 ion exchange resin Substances 0.000 claims description 14
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 14
- 238000001179 sorption measurement Methods 0.000 claims description 13
- 238000004061 bleaching Methods 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 239000008367 deionised water Substances 0.000 claims description 10
- 229910021641 deionized water Inorganic materials 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 9
- 238000005292 vacuum distillation Methods 0.000 claims description 9
- 230000002378 acidificating effect Effects 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 150000002148 esters Chemical group 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 239000003610 charcoal Substances 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 18
- 239000012535 impurity Substances 0.000 abstract description 13
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 4
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 235000011187 glycerol Nutrition 0.000 description 27
- 239000002253 acid Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 229960000935 dehydrated alcohol Drugs 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 4
- 229960004756 ethanol Drugs 0.000 description 3
- 238000001914 filtration 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
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- XENVCRGQTABGKY-ZHACJKMWSA-N chlorohydrin Chemical compound CC#CC#CC#CC#C\C=C\C(Cl)CO XENVCRGQTABGKY-ZHACJKMWSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- -1 Time 2h Substances 0.000 description 1
- OMEBXAYMRCYOTB-UHFFFAOYSA-N [P].OCC(O)CO Chemical compound [P].OCC(O)CO OMEBXAYMRCYOTB-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 150000001768 cations Chemical class 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
- 230000003930 cognitive ability Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000001924 fatty-acyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 239000000049 pigment Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 239000002351 wastewater 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of processes of purification of glycerol phosphatidyl choline crude product, belong to pharmaceutical compound finishing technology field.The process the following steps are included: (a) by glycerolphosphocholine crude product aqueous solution successively through solvent extraction twice and decoloration, obtain solution M1；(b) solution M1 is obtained into concentrate G successively through desalination and concentration；(c) concentrate G is obtained into glycerolphosphocholine successively through dissolution, crystallization and drying.Its key points of the technical solution are that glycerolphosphocholine crude product aqueous solution is removed remaining solvent and reaction raw materials through solvent extraction twice, the color of product is adjusted through decoloration, process through purifying such as desalination removal salt impurity is used cooperatively, with the impurity content for significantly reducing product, the advantages of improving the purity of product.The invention also discloses the glycerolphosphocholines being prepared using above-mentioned purification process.
Description
Technical field
The present invention relates to pharmaceutical compound finishing technology field, in particular to a kind of purification of glycerol phosphatidyl choline crude product
Process and its obtained glycerolphosphocholine.
Background technique
Choline glycerophosphatide (GPC) is the production that two fatty acyl groups on phosphatidyl choline (PC) molecule are hydrolyzed completely
Object is a kind of important neurotransmitter and phospholipid precursor, can be used for pharmaceuticals industry, to improve the cognitive ability and raising of the elderly
Teen-age memory.But partial pigment and non polar impurities may be contained in the lower GPC of purity, property is not under normal temperature and pressure
Stablize, not only pharmacological action is weak, it is also possible to generate the toxin being harmful to the human body.However preparation, purifying and the detection of country GPC
Technology is relatively not mature enough, it is more difficult to meet the needs of market is to high quality, high-purity GPC.
Existing application No. is the Chinese patent applications of 201810794573 .4, and it discloses a kind of Purifing of Glycerol phosphatide
The method of phatidylcholine, will ethyl alcohol, methanol and toluene mix after mixed again with crude glycerol phosphatidyl choline, then sequentially mistake
Silicagel column, aluminum oxide column, ion exchange resin column, then ethyl alcohol mixing is added thereto and is placed on the decentralization of certain temperature condition
It sets, makes its crystallization, the glycerolphosphocholine being then evaporated above-mentioned crystal after being concentrated to get purification.The purification process
Using as eluant, eluent, being mixed with silicic acid in products obtained therefrom using ethyl alcohol, methanol and toluene Mixed Solvent, and silica gel column chromatography at
This is higher, and the rate of recovery is lower, and the method for purification can generate a large amount of waste water, is unfavorable for producing on a large scale.
Therefore it provides a kind of product purity is high, at low cost, the method for the few purification of glycerol phosphatidyl choline of the three wastes is to need
It solves the problems, such as.
Summary of the invention
In view of the shortcomings of the prior art, the purpose of the present invention one is to provide a kind of work of purification of glycerol phosphatidyl choline crude product
Process, the process can significantly reduce the impurity content of product, improve the purity of product
The second object of the present invention is to provide a kind of glycerolphosphocholine have the advantages that purity is high.
In order to realize above-mentioned first purpose, the present invention provides the following technical scheme that
A kind of process of purification of glycerol phosphatidyl choline crude product, the process the following steps are included:
(a) glycerolphosphocholine crude product aqueous solution is obtained into solution M1 successively through solvent extraction twice and decoloration；
(b) solution M1 is obtained into concentrate G successively through desalination and concentration；
(c) concentrate G is obtained into glycerolphosphocholine successively through dissolution, crystallization and drying.
By using above-mentioned technical proposal, glycerolphosphocholine crude product aqueous solution is removed through solvent extraction twice and is remained
Solvent and reaction raw materials, the color of product is adjusted through decoloration, the technique through the desalination removal purifying such as salt impurity is used cooperatively,
The impurity content that product can be significantly reduced improves the purity of product.
Further, the solvent that solvent extraction uses in the step (a) includes organic solvent；The organic solvent includes
Acetone.
R- glycerin chlorohydrin, preferable organic solvent third would generally be used in the raw material of the preparation method of glycerolphosphocholine at present
The ketone solvent used as extraction, can preferably remove remaining R- glycerin chlorohydrin.
Further, decoloration process uses activated carbon adsorption in the step (a)；The process conditions of the activated carbon adsorption
It include: 40-50 DEG C of bleaching temperature, bleaching time 20-40min.
The color of the adjustable crude product GPC of adsorption bleaching makes the color of GPC closer to white, also adsorbable some particles
Impurity avoids the color of impurity effect GPC, GPC is made more easily to be used for field of medicine preparation.
Activated carbon raw material source is wide, cheap, preferably the technique of activated carbon adsorption and its decoloration, and it is de- can to increase absorption
The effect of color reduces production cost.
Further, desalinating process is exchanged using ion exchange resin in the step (b)；
The adsorption column that the ion exchange resin exchange uses is highly acidic resin and basic resin mixed bed column；
The mass ratio of the highly acidic resin and basic resin is 1:2 ~ 1:5.
Desalinating process can remove the salts impurity such as PC-K for including in glycerolphosphocholine crude product and KCL.It is preferred that adopting
With ion exchange resin exchange process, resin column can regenerate recycling, reduce production cost.
It is preferred that adsorption column is the mixed proportion of highly acidic resin and basic resin mixed bed column and two kinds of resins, it can be simultaneously
Remove anion and cation, hence it is evident that the effect for promoting desalination, the effect for removing ionic impurity are good.
Further, ion exchange resin exchange technique the following steps are included:
(I) solution M1 is eluted, flow velocity 300-500L/h, time 20-40min obtains solution M2；
(II) solution M1 remaining after step (I) is eluted, flow velocity 300-500L/h obtains solution M3；
(III) it is eluted after mixing solution M2 and solution M3, flow velocity 600-800L/h, time 1-3h obtain solution M4；
(IV) de-, flow velocity 600-800L/h, time 1-3h is washed with deionized water, solution and solution M4 are mixed to get solution after elution
M5。
In above-mentioned ion exchange resin technique, solution M1 a part is first carried out elution, and be kept separately again will be remaining molten
Liquid M1 all carries out solution merging after elution is kept separately elution twice and is eluted again, and solution M1 is washed twice
It is de-, de-, reduction loss of product is finally washed with deionized water.
Further, concentration uses vacuum distillation concentration and vacuum and low temperature concentration in the step (b)；The vacuum distillation
Solid content after concentration is 30-50%；The condition of the vacuum and low temperature concentration includes: vacuum degree -0.08 ~ -0.12Mpa, and temperature is small
In 60 DEG C；Moisture content after the vacuum and low temperature concentration is less than 15%.
Glycerolphosphocholine after desalination is first subjected to vacuum distillation concentration, removes most of solvent, then carry out vacuum
Low temperature concentration, it is possible to reduce the time of concentration promotes the effect of concentration.
It is preferred that the solid content after vacuum distillation concentration, can control the process of vacuum distillation concentration, reduce entire concentrated
The time cost of journey.It is preferred that the condition of vacuum and low temperature concentration can prevent long-time high temperature concentration bring material from decomposing, cause
The problem of material pH is reduced.It is preferred that the moisture content after vacuum and low temperature concentration, can control the effect being finally concentrated, prevents from being concentrated
Object agglomeration is not easy to subsequent technique and carries out.
Further, the solvent dissolved in the step (c) includes dehydrated alcohol；The condition of dissolution includes: temperature 50-70
DEG C, time 1-3h.
Preferred solvent is dehydrated alcohol and the condition preferably dissolved, and solute effect is good, and dehydrated alcohol low pollution, price is just
Preferably.
Further, temperature -5 ~ 0 DEG C crystallized in the step (c), time 20-35h；Drying in the step (c)
50-70 DEG C of temperature, time 6-10h.
Product GPC crystallization is precipitated by cooling after glycerolphosphocholine dissolution, impurity component stays in a solvent, improves
Product purity.
It is preferred that dry temperature and time, avoids the too low influence drying effect of temperature or temperature is excessively high that product is caused to decompose
The problems such as, drying time is rationally controlled according to drying temperature, saves the process time, reduces energy consumption.
In order to realize above-mentioned second purpose, the present invention provides the following technical scheme that using above-mentioned purification of glycerol phosphatide
The process of phatidylcholine crude product is made.
Compared with prior art, the invention has the following advantages:
1, the process of purification of glycerol phosphatidyl choline crude product provided by the invention, by glycerolphosphocholine crude product aqueous solution
Remaining solvent and reaction raw materials are removed through solvent extraction, the color of product is adjusted through decoloration, through desalination removal salt impurity etc.
The technique of purifying is used cooperatively, and can significantly reduce the impurity content of product, improves the purity of product.
2, the process of purification of glycerol phosphatidyl choline crude product provided by the invention, few, the at low cost, technique with the three wastes
The advantages that simple.
Specific embodiment
Invention is further described in detail with reference to embodiments.Wherein, the purity of glycerolphosphocholine crude product
It is 65%.
Embodiment 1
A kind of process of purification of glycerol phosphatidyl choline crude product, comprising the following steps:
(1) take lower layer's water phase stand-by with acetone extract 2 times GPC crude product aqueous solution；
(2) add deionized water to be uniformly mixed the water phase that step (1) obtains, add active carbon to decolourize, 40 DEG C of bleaching temperature, stir
Bleaching time 20min is mixed, filtering removal active carbon obtains solution M1；
(3) by solution M1 through ion exchange resin desalination, adsorption column is D001 macropore strong acid resin and 711 macroporous strong basic trees
Rouge mixed bed column is eluted, and the mass ratio of D001 macropore strong acid resin and 711 macroporous strong basic resins is 1:2；
The technique of ion exchange resin exchange: solution M1 elution, flow velocity 300L/h, time 40min obtain solution M2；Surplus solution M1
Elution, flow velocity 300L/h obtain solution M3；It is eluted after solution M2 and solution M3 mixing, flow velocity 600L/h, time 3h are obtained molten
Liquid M4；De-, flow velocity 600L/h, time 3h is washed with deionized water, solution and solution M4 are mixed to get solution M5 after elution；
(4) vacuum distillation is used to be concentrated into solid content as 30%, then vacuum and low temperature concentration, vacuum degree -0.08Mpa, temperature solution M5
50 DEG C of degree obtains concentrate G until moisture content is 10%；
(5) dehydrated alcohol is added into concentrate G, is warming up to 50 DEG C, stirring 3h to uniform dissolution；It is cooled to -5 DEG C of holding 20h
It is crystallized；It is centrifuged after the completion of crystallization and dry, dry temperature 50 C, time 10h obtains glycerolphosphocholine.
The purity of glycerolphosphocholine obtained is 99 %.
Embodiment 2
A kind of process of purification of glycerol phosphatidyl choline crude product, comprising the following steps:
(1) take lower layer's water phase stand-by with acetone extract 2 times GPC crude product aqueous solution；
(2) add deionized water to be uniformly mixed the water phase that step (1) obtains, add active carbon to decolourize, 50 DEG C of bleaching temperature, stir
Bleaching time 40min is mixed, filtering removal active carbon obtains solution M1；
(3) by solution M1 through ion exchange resin desalination, adsorption column is D001 macropore strong acid resin and 711 macroporous strong basic trees
Rouge mixed bed column is eluted, and the mass ratio of D001 macropore strong acid resin and 711 macroporous strong basic resins is 1:5；
The technique of ion exchange resin exchange: solution M1 elution, flow velocity 500L/h, time 20min obtain solution M2；Surplus solution M1
Elution, flow velocity 500L/h obtain solution M3；It is eluted after solution M2 and solution M3 mixing, flow velocity 800L/h, time 1h are obtained molten
Liquid M4；De-, flow velocity 800L/h, time 1h is washed with deionized water, solution and solution M4 are mixed to get solution M5 after elution；
(4) vacuum distillation is used to be concentrated into solid content as 50%, then vacuum and low temperature concentration, vacuum degree -0.12Mpa, temperature solution M5
50 DEG C of degree obtains concentrate G until moisture content is 10%；
(5) dehydrated alcohol is added into concentrate G, is warming up to 70 DEG C, stirring 1h to uniform dissolution；Be cooled to 0 DEG C of holding 35h into
Row crystallization；It is centrifuged after the completion of crystallization and dry, dry temperature 70 C, time 6h obtains glycerolphosphocholine.
The purity of glycerolphosphocholine obtained is 98.8 %.
Embodiment 3
A kind of process of purification of glycerol phosphatidyl choline crude product, comprising the following steps:
(1) take lower layer's water phase stand-by with acetone extract 2 times GPC crude product aqueous solution；
(2) add deionized water to be uniformly mixed the water phase that step (1) obtains, add active carbon to decolourize, 45 DEG C of bleaching temperature, stir
Bleaching time 30min is mixed, filtering removal active carbon obtains solution M1；
(3) by solution M1 through ion exchange resin desalination, adsorption column is D001 macropore strong acid resin and 711 macroporous strong basic trees
Rouge mixed bed column is eluted, and the mass ratio of D001 macropore strong acid resin and 711 macroporous strong basic resins is 1:3；
The technique of ion exchange resin exchange: solution M1 elution, flow velocity 400L/h, time 30min obtain solution M2；Surplus solution M1
Elution, flow velocity 400L/h obtain solution M3；It is eluted after solution M2 and solution M3 mixing, flow velocity 700L/h, time 2h are obtained molten
Liquid M4；De-, flow velocity 700L/h, time 2h is washed with deionized water, solution and solution M4 are mixed to get solution M5 after elution；
(4) vacuum distillation is used to be concentrated into solid content as 40%, then vacuum and low temperature concentration, vacuum degree -0.1Mpa, temperature solution M5
50 DEG C of degree obtains concentrate G until moisture content is 10%；
(5) dehydrated alcohol is added into concentrate G, is warming up to 55 DEG C, stirring 2h to uniform dissolution；It is cooled to -3 DEG C of holding 30h
It is crystallized；It is centrifuged after the completion of crystallization and dry, 55 DEG C of dry temperature, time 8h obtains glycerolphosphocholine.It is obtained
The purity of glycerolphosphocholine is 99.8%.
Embodiment 4
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 are that decoloration is warm in step (2)
50 DEG C of degree, bleaching time 40min.
The purity of glycerolphosphocholine obtained is 99.6%.
Embodiment 5
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 be, adsorption column in step (3)
For D001 macropore strong acid resin.
The purity of glycerolphosphocholine obtained is 98%.
Embodiment 6
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 be, adsorption column in step (3)
For 711 macroporous strong basic resins.
The purity of glycerolphosphocholine obtained is 98.1%.
Embodiment 7
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 are that D001 is big in step (3)
The mass ratio of hole highly acidic resin and 711 macroporous strong basic resins is 1:5.
The purity of glycerolphosphocholine obtained is 98.3%
Embodiment 8
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 be, step (3) intermediate ion tree
The technique of Ester exchange: solution M1 is all eluted, and flow velocity 400L/h obtains solution M4；De-, flow velocity 700L/h is washed with deionized water,
Time 2h, solution and solution M4 are mixed to get solution M5 after elution.
The purity of glycerolphosphocholine obtained is 98.6%
Embodiment 9
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 are that vacuum is low in step (4)
59 DEG C of temperature of temperature concentration.
The purity of glycerolphosphocholine obtained is 99.4%.
Embodiment 10
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 be, crystallization time 20h.
The purity of glycerolphosphocholine obtained is 99.3%.
Comparative example 1
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 is, without solvent extraction.
The purity of glycerolphosphocholine obtained is 73.6%.
Comparative example 2
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 are, only carry out a solvent extraction
It takes.
The purity of glycerolphosphocholine obtained is 90.5%.
Comparative example 3
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 is, without desalination.
The purity of glycerolphosphocholine obtained is 88.7%.
Comparative example 4
A kind of process of purification of glycerol phosphatidyl choline crude product, the difference with embodiment 3 are, without crystallization.
The purity of glycerolphosphocholine obtained is 93.2%.
The purity of glycerolphosphocholine made from embodiment 1-10 is not less than 98% in the scope of the present invention, bright
The aobvious purity 65% higher than glycerolphosphocholine crude product.Glycerol phosphorus made from comparative example 1-4 not outside the scope of the present invention
The purity of phosphatidylcholine is significantly lower than the product purity of embodiment 1-10.
Above-mentioned specific embodiment is only explanation of the invention, is not limitation of the present invention, art technology
Personnel can according to need the modification that not creative contribution is made to the present embodiment after reading this specification, but as long as
All by the protection of Patent Law in scope of the presently claimed invention.
Claims (10)
1. a kind of process of purification of glycerol phosphatidyl choline crude product, which is characterized in that the process includes following step
It is rapid:
(a) glycerolphosphocholine crude product aqueous solution is obtained into solution M1 successively through solvent extraction twice and decoloration；
(b) solution M1 is obtained into concentrate G successively through desalination and concentration；
(c) concentrate G is obtained into glycerolphosphocholine successively through dissolution, crystallization and drying.
2. process according to claim 1, which is characterized in that the solvent that solvent extraction uses in the step (a)
Including organic solvent；The organic solvent includes acetone.
3. process according to claim 1 or 2, which is characterized in that decoloration process is using activity in the step (a)
Charcoal absorption；The process conditions of the activated carbon adsorption include: 40-50 DEG C of bleaching temperature, bleaching time 20-40min.
4. process according to claim 1, which is characterized in that desalinating process uses ion tree in the step (b)
Ester exchange；
The adsorption column that the ion exchange resin exchange uses is highly acidic resin and basic resin mixed bed column；
The mass ratio of the highly acidic resin and basic resin is 1:2 ~ 1:5.
5. process according to claim 4, which is characterized in that the technique of the ion exchange resin exchange includes following step
It is rapid:
(I) solution M1 is eluted, flow velocity 300-500L/h, time 20-40min obtains solution M2；
(II) solution M1 remaining after step (I) is eluted, flow velocity 300-500L/h obtains solution M3；
(III) it is eluted after mixing solution M2 and solution M3, flow velocity 600-800L/h, time 1-3h obtain solution M4；
(IV) de-, flow velocity 600-800L/h, time 1-3h is washed with deionized water, solution and solution M4 are mixed to get solution after elution
M5。
6. process according to claim 1, which is characterized in that the step (b) further includes adjusting pH value after desalination
The step of being concentrated again；The pH value is 5-7.
7. process according to claim 1, which is characterized in that concentration is dense using being evaporated under reduced pressure in the step (b)
Contracting and vacuum and low temperature concentration；
Solid content after the vacuum distillation concentration is 30-50%；
The condition of the vacuum and low temperature concentration includes: vacuum degree -0.08 ~ -0.12Mpa, and temperature is less than 60 DEG C；
Moisture content after the vacuum and low temperature concentration is less than 15%.
8. process according to claim 1, which is characterized in that the solvent dissolved in the step (c) includes anhydrous
Ethyl alcohol；The condition of the dissolution includes: 50-70 DEG C of temperature, time 1-3h.
9. according to the described in any item processes of claim 6-8, which is characterized in that the temperature-crystallized in the step (c)
5 ~ 0 DEG C, time 20-35h；
Dry 50-70 DEG C of temperature in the step (c), time 6-10h.
10. a kind of glycerolphosphocholine, which is characterized in that use the described in any item purification of glycerol phosphatide of claim 1-9
The process of phatidylcholine crude product is made.
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| CN114100194A (en) * | 2021-11-16 | 2022-03-01 | 杨凌萃健生物工程技术有限公司 | Device and method for removing chloromycerol from glycerophosphatidylcholine |
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