CN104926862A - Preparation method for glycerophosphatidylcholine - Google Patents
Preparation method for glycerophosphatidylcholine Download PDFInfo
- Publication number
- CN104926862A CN104926862A CN201510229848.6A CN201510229848A CN104926862A CN 104926862 A CN104926862 A CN 104926862A CN 201510229848 A CN201510229848 A CN 201510229848A CN 104926862 A CN104926862 A CN 104926862A
- Authority
- CN
- China
- Prior art keywords
- mixture
- preparation
- exchange resin
- ion exchange
- glycerolphosphocholine
- 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.)
- Granted
Links
Abstract
The invention discloses a preparation method for glycerophosphatidylcholine. The preparation method comprises the steps: mixing a compound shown in the formula (I) with anhydrous sodium carbonate to prepare a mixture M1; putting the mixture M1 and (R)-(-)-3-chloro-1,2-propylene glycol in anhydrous ethanol for reflux to obtain a mixture M2; after diluting the mixture M2 by 5-10 times, flowing the mixture M2 through first ion exchange resin to obtain a mixture M3; after diluting the mixture M3 by 2-4 times, flowing the mixture M3 through second ion exchange resin to obtain a mixture M4; washing the mixture M4 by 70-90wt% ethanol to obtain a mixture M5; washing the mixture M5 by distilled water to obtain a mixture M6; after flowing the mixture M6 through third ion exchange resin, filtering the mixture M6 to obtain a filtrate so as to obtain the glycerophosphatidylcholine. The formula (I) is as shown in the description, wherein R is Ca2<+> or Mg2<+>. The effects of simple preparation method, high synthetic ratio and great reduction of production cost are achieved.
Description
Technical field
The present invention relates to the preparation field of glycerolphosphocholine, particularly, relate to a kind of preparation method of glycerolphosphocholine.
Background technology
Phosphatide is the general name of the lipoid cpd of phosphorous acid group, is distributed widely in occurring in nature.All contain phosphatide in nearly all cell, it is the ultimate constituent of cytolemma, is important living matter.At present, commodity phosphatide generally extracts from soybean, and wherein the composition of phosphatide mainly contains phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositols (PI), phosphatidylserine (PS), phosphatidic acid (PA) etc.Soybean phospholipid, except having physiologically active, also has the characteristics such as emulsification, instant, wetting, dispersion, anti-oxidant, solubilising, is widely used in the fields such as food, medicine, makeup, weaving, process hides, feed.Due to the relation of molecular structure, phosphatide application in some aspects has limitation.In order to improve the performance of phosphatide, widening the Application Areas of phosphatide, the phospholipid prod of production special requirement, needing to carry out processing modified to natural phospholipid product.
Glycerolphosphocholine is the product that two fatty acyl groups on phosphatidylcholine (PC) molecule are hydrolyzed completely; it has the effect of stablizing brain cognitive ability significantly, even can repair the cognitive ability that early stage old dementia patient part is in damaged condition.Unlike the medicine that those suppress vagusstoff to decompose, GPC stimulates body to produce new phosphatidylcholine.Zooscopy shows, and GPC can prevent the forfeiture of memory.The control group controlled at experiment condition relatively after find, by the mouse that feeding GPC mouse age is larger, its brain is specially taken charge of in the hippocampus of memory and learning capacity, and the loss of neural connection is less.The review comment that scientist Kidd PM reports for 13 clinical experiments according to one section, conclusion draws: for 4,054 old memory loss, or apoplexy or mini strokes, caused vascular loses in the sufferer of intelligence, GPC can the memory of continuative improvement brain and attention, even if at multiple experiment test environment, it still can improve the clinical symptom of patient significantly.
In addition, GPC, by the effect to nerve growth factor, can protect and promote interneural conduction.Nerve growth factor susceptor can reduce because of aging, and GPC can promote that it grows, repair, and the performance of nerve growth factor susceptor in cerebellar cortex (Cerebellar Cortex, it is the region that in brain, control action is coordinated) can be increased.GPC excites the release of neurotransmitter GABA (γ-aminobutyric acid, gamma amino butyric acid) by different mechanism, makes brain cell obtain more GABA.And the decline of the GABA content of the elderly's brain, cognitive ability can be caused impaired, cause dementia, dysthymia disorders, and the generation of the common brain degenerations such as psychosis, as Alzheimer's disease and Heng Dingdun chorea.
At present, the domestic report to the visible document of GPC is few, and external giving the research of GPC is shown great attention to, and has carried out large quantifier elimination to the application of its Clinical Basis.The research such as Canal N shows, young healthy people takes GPC and has the effect improving its attention, memory and cognitive ability.ParnettiL etc. (2001) research shows, for brain environmental degradation and the patient suffering from Alzheimer's disease, to have the effect that significant Improving memory power goes down after taking GPC.(1993), Tomasina C etc. (1994) researchs such as Aguglia E etc. (1993), BarbagalloSangiorgi G show to take unique curative effect for cerebral apoplexy and brain injury patients.Ceda GP etc. (1994) research shows, GPC has the effect of recovery the elderly hormone function.The research that Sannita WG (1993) has carried out one " age is with hypomnesis " in age crowd over fifty years old shows, takes GPC and has the function improving memory.(1991), the Sicurella L etc. (1990) such as Abbati C etc. (1993), Sicurella L are showing the clinical study of 65 years old crowd, and GPC has the raising choline connection neural reaction times and visual cortex shows relevant Dopamine approach.(1991), the Ban TA etc. such as (1992), the Muratorio A etc. (1993), Paciaroni E (1992), Palleschi M etc. (1993) etc. such as (1991), the Frattola L etc. (1991) such as Di Perri R in succession conduct a research and show that GPC improves overall clinical symptom, comprise cognitive ability, emotional symptoms and external symptom such as tired, dizzy.(1992), the Schettini G etc. (1993), Parnetti L etc. (1993) such as Ban TA etc. (1991), Palleschi M in succession conduct a research and show that GPC has important improvement result for treatment Alzheimer's disease.(1994), the Tomasina C etc. (1996), GambiD etc. (1993) such as Aguglia E etc. (1993), Barbagallo Sangiorgi G, Consoli D (1994) in succession conduct a research and show that GPC has important improvement result for treatment cerebral apoplexy.The oral GPC of (1993) young volunteers to health such as de Moliner P are studied, and after ten hours, find that GPC can be good at the ion concentration being absorbed and significantly increase choline.Tserng K-Y etc. (2004) research thinks that GPC is the precursor substance that in body, synthesis PC is very important.Ferraro L etc. (1996) research thinks that GPC also supports other signal scheme such as Dopamine HCL, nor-epinephrine and GABA function.
Glycerolphosphocholine (GPC) is Choline Sources, has good Improving memory and cognitive function, and it can pass hemato encephalic barrier, is the choline source of ethyl ester phatidylcholine and phosphatidylcholine synthesis.Multinomial research shows, GPC can improve cognitive function, and has good tolerance and improving mental functioning, neural system idea and memory important role.It is a kind of important neurotransmitter and phospholipid precursor, has provide protection to the cerebrovascular.One to 55-65 year the random same dosage glycerolphosphocholine of 12 weeks by a definite date that carries out of the male sex old organic brain syndrome patient and oxiracetam curative effect comparative studies in, show both there is good tolerance, occur because of untoward reaction the phenomenon stopping treatment without patient.Oxiracetam curative effect in maintaining treatment is rapid-action, but along with treatment stopping drug effect failing fast; Glycerolphosphocholine onset is slow, but curative effect is more lasting, stops treatment consistent with the clinical efficacy of 8 weeks treatments period after 8 weeks.From external clinical efficacy for many years, glycerolphosphocholine injures in senile dementia at treatment head trauma good curative effect, and side effect is little.
In Europe, the medicine " Gliation " for the treatment of Alzheimer's disease, its main active ingredient is exactly GPC.The drug effect of GPC, more easily by sufferer is accepted, and side effect is less.
The domestic research report about this product is little, and main syntheti c route has following several:
1, natural extract
Be raw material with phospholipid of natural soybean, after hydrolysis, cross that post is refining obtains product.This route technique is simple, abundance, but due to phosphatidylcholine content in phosphatide on the low side, cause final cost higher, and easily cause chiral structure racemization in hydrolytic process, cause product specific rotation defective.
2, complete synthesis route
Route one (three-step reaction):
Route two (two step reactions):
Above route complex process, chiral intermediate high expensive, in chiral intermediate ring opening process, also easily produces racemization.
Therefore, provide a kind of preparation method simple, synthetic ratio is high, and the preparation method greatly reducing the glycerolphosphocholine of production cost is the problem that the present invention needs solution badly.
Summary of the invention
For above-mentioned prior art, the object of the invention is to overcome when in prior art, glycerolphosphocholine extracts from crude substance often because phosphatidylcholine content in phosphatide is on the low side, cause final cost higher, and easily cause chiral structure racemization in hydrolytic process, the problem such as cause product specific rotation defective, simultaneously traditional synthetic method craft is complicated, the problem that cost is higher, thus provide a kind of preparation method simple, synthetic ratio is high, greatly reduces the preparation method of the glycerolphosphocholine of production cost.
To achieve these goals, the invention provides a kind of preparation method of glycerolphosphocholine, wherein, described preparation method comprises:
1) will such as formula the compound shown in (I) and anhydrous sodium carbonate mixing, obtained mixture M 1;
2) mixture M 1 and (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through the first ion exchange resin after mixture M 2 being diluted 5-10 times, obtain mixture M 3;
4) flow through the second ion exchange resin after mixture M 3 being diluted 2-4 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 70-90 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) leaching filtrate is crossed after mixture M 6 being flowed through the 3rd ion exchange resin, obtained glycerolphosphocholine;
Wherein, R is Ca
2+or Mg
2+.
Pass through technique scheme, obtained mixture M 1 after the present invention will mix with anhydrous sodium carbonate such as formula the compound shown in (I), then by mixture M 1 and (R)-(-)-3-chloro-1, 2-propylene glycol is placed in dehydrated alcohol and refluxes, the mixture M 2 obtained after backflow is flowed through the first ion exchange resin after dilution certain multiple, then flow through the second ion exchange resin after another multiple of redilution, last again with flowing through the 3rd ion exchange resin after ethanol and distilled water wash again, and then make the preparation method of the glycerolphosphocholine obtained in this way not only simple, and the product purity obtained is high, greatly save production cost, improve production efficiency.
Other features and advantages of the present invention are described in detail in embodiment part subsequently.
Accompanying drawing explanation
Accompanying drawing is used to provide a further understanding of the present invention, and forms a part for specification sheets, is used from explanation the present invention, but is not construed as limiting the invention with embodiment one below.In the accompanying drawings:
Fig. 1 is a kind of reaction principle figure provided by the invention.
Embodiment
Below the specific embodiment of the present invention is described in detail.Should be understood that, embodiment described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
The invention provides a kind of preparation method of glycerolphosphocholine, wherein, described preparation method comprises:
1) will such as formula the compound shown in (I) and anhydrous sodium carbonate mixing, obtained mixture M 1;
2) mixture M 1 and (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through the first ion exchange resin after mixture M 2 being diluted 5-10 times, obtain mixture M 3;
4) flow through the second ion exchange resin after mixture M 3 being diluted 2-4 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 70-90 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) leaching filtrate is crossed after mixture M 6 being flowed through the 3rd ion exchange resin, obtained glycerolphosphocholine;
Wherein, R is Ca
2+or Mg
2+.
Above-mentioned design obtains mixture M 1 after mixing with anhydrous sodium carbonate such as formula the compound shown in (I), then by mixture M 1 and (R)-(-)-3-chloro-1, 2-propylene glycol is placed in dehydrated alcohol and refluxes, the mixture M 2 obtained after backflow is flowed through the first ion exchange resin after dilution certain multiple, then flow through the second ion exchange resin after another multiple of redilution, last again with flowing through the 3rd ion exchange resin after ethanol and distilled water wash again, and then make the preparation method of the glycerolphosphocholine obtained in this way not only simple, and the product purity obtained is high, greatly save production cost, improve production efficiency.
Compound shown in described formula (I) and described (R)-(-)-3-chloro-1, consumption between 2-propylene glycol can add according to any amount, certainly, in order to make reaction complete as far as possible, further saving cost, one of the present invention preferred embodiment in, relative to 100 weight parts described formula (I) shown in compound, the consumption of described (R)-(-)-3-chlorine-1,2-propylene glycol is 30-80 weight part.
Certainly, because can contamination precipitation be produced in reaction process, thus, in order to increase the purity of obtained product further, and reduce the difficulty of follow-up removal of impurities as far as possible, one of the present invention preferred embodiment in, step 1) in can also be included in mixing after carry out centrifugal and cross leaching supernatant liquor, and supernatant liquor is distilled to dry, obtain mixture M 1.
The mode that described still-process can adopt according to this area routine operates, and such as, can be air distillation, certainly, higher in order to make to distill the purity of after product, one of the present invention more preferred embodiment in, described still-process can be chosen as underpressure distillation.
Step 2) in reflux operation can according to this area routine use reflux type operate, return time can be not construed as limiting, certainly, react completely as far as possible to make reaction in cost-effective situation, one of the present invention preferred embodiment in, step 2) in return time can be further defined to 20-30h.
Step 3) and step 4) in flow through ion exchange resin operation can only operate once, certainly, in order to make its filtration more complete, one of the present invention preferred embodiment in, step 3) and step 4) can recirculation operation 2-3 time.Namely calculate as cyclical operation 1 time through first ion exchange resin and the second ion exchange resin.
Similarly, step 5) and step 6) can recirculation operate 2-3 time.
In order to make the purity of the glycerolphosphocholine obtained higher, one of the present invention more preferred embodiment in, step 7) in can also comprise filtrate distillation and concentration.
Described first ion exchange resin and described second ion exchange resin can be the ion exchange resin that this area routine uses, can be such as anionite-exchange resin, certainly, one of the present invention preferred embodiment in, consider the type of impurity, described first ion exchange resin and described second ion exchange resin can be chosen as Zeo-karb further.
Similarly, of the present invention another preferred embodiment in, described 3rd ion exchange resin can be chosen as Zeo-karb and anionite-exchange resin.
Compound shown in formula (I) can provide in any form, certainly, in reaction process, reaction is easier in order to make it as far as possible, one of the present invention preferred embodiment in, the compound shown in formula (I) can be selected to be provided by the aqueous solution of concentration for 15-30 % by weight.
Below will be described the present invention by embodiment.In following examples, the compound shown in formula (I) is phosphoryl chloride choline calcium salt four hydrate, and its preparation method is as shown in preparation example 1; (R) preparation method of-3-chlorine-1,2-propylene glycol is as shown in preparation example 2; Described anhydrous sodium carbonate, described dehydrated alcohol, described Zeo-karb and affiliated anionite-exchange resin are conventional commercial product.
Preparation example 1
1) under 25 DEG C and-0.09MPa, 140g phosphoric acid is slowly dripped (rate of addition is 10/s) in the thick product of 100g choline chloride 60 (choline chloride 60 containing 70%), be warming up to 70 DEG C after dropwising and carry out underpressure distillation until without distilled water, then be warming up to 120 DEG C and control pressure reacts 6h under-0.09MPa, then add 50g water termination reaction with obtained phosphoryl chloride choline base mixture;
2) at 25 DEG C, above-mentioned for 100g phosphoryl chloride choline base mixture is mixed 10min until the pH to 8 of system is with obtained metathesis mixture with 3000g calcium hydroxide aqueous solution (massfraction of calcium hydroxide is 15%);
3) under 25 DEG C and 35Pa, above-mentioned metathesis mixture is carried out underpressure distillation until obtain solidliquid mixture to solid precipitation;
4) above-mentioned solidliquid mixture is cooled to-5 DEG C and carries out crystallization 40min, then filter and at 100 DEG C dry 2h obtain 100g phosphoryl chloride choline calcium salt four hydrate (purity is 100%);
5) by the filtrate of above-mentioned filtration recrystallization 40min at-5 DEG C, then filter and at 100 DEG C dry 2h obtain phosphoryl chloride choline calcium salt four hydrate.
Preparation example 2
1) at 108 DEG C, (S)-epichlorohydrin 100g, water 60g and sulfuric acid 1.5g are carried out ring-opening reaction 6h with obtained open loop mixture;
2) at 25 DEG C, 15g aqueous sodium hydroxide solution (massfraction of sodium hydroxide is 5%) and 100g open loop mixture are carried out neutralization reaction 15min to obtain neutralise mixt (pH is for 7.0);
3) by underpressure distillation, the water in neutralise mixt is removed (after dewatering, the water ratio of mixture is 0.3%), then filter to obtain filtrate;
4) filtrate is carried out at 33pa and 126 DEG C fractionation with obtained (R)-3-chlorine-1,2-propylene glycol.
Embodiment 1
1) 10g phosphoryl chloride choline calcium salt four hydrate is added in 35g deionized water, the aqueous solution of obtained phosphoryl chloride choline calcium salt, centrifugal and cross leaching supernatant liquor after the above-mentioned aqueous solution is mixed with 25g anhydrous sodium carbonate, by supernatant liquor underpressure distillation to dry, obtained mixture M 1;
2) mixture M 1 and 3g (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through Zeo-karb after mixture M 2 being diluted 5 times, obtain mixture M 3;
4) flow through Zeo-karb after mixture M 3 being diluted 2 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 70 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) cross leaching filtrate after mixture M 6 being flowed through respectively Zeo-karb and anionite-exchange resin, filtrate decompression is distilled, obtained glycerolphosphocholine A1.(amount of product is 7.7g, and purity is 98.7%, and pH value is 5.5, and specific rotation is-2.4 °)
Embodiment 2
1) 10g phosphoryl chloride choline calcium salt four hydrate is added in 65g deionized water, the aqueous solution of obtained phosphoryl chloride choline calcium salt, centrifugal and cross leaching supernatant liquor after the above-mentioned aqueous solution is mixed with 40g anhydrous sodium carbonate, by supernatant liquor underpressure distillation to dry, obtained mixture M 1;
2) mixture M 1 and 8g (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through Zeo-karb after mixture M 2 being diluted 10 times, obtain mixture M 3;
4) flow through Zeo-karb after mixture M 3 being diluted 4 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 90 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) cross leaching filtrate after mixture M 6 being flowed through respectively Zeo-karb and anionite-exchange resin, filtrate decompression is distilled, obtained glycerolphosphocholine A2.(amount of product is 7.8g, and purity is 100%, and pH value is 6.5, and specific rotation is-2.8 °)
Embodiment 3
1) 10g phosphoryl chloride choline calcium salt four hydrate is added in 40g deionized water, the aqueous solution of obtained phosphoryl chloride choline calcium salt, centrifugal and cross leaching supernatant liquor after the above-mentioned aqueous solution is mixed with 30g anhydrous sodium carbonate, by supernatant liquor underpressure distillation to dry, obtained mixture M 1;
2) mixture M 1 and 5g (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through Zeo-karb after mixture M 2 being diluted 8 times, obtain mixture M 3;
4) flow through Zeo-karb after mixture M 3 being diluted 3 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 85 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) cross leaching filtrate after mixture M 6 being flowed through respectively Zeo-karb and anionite-exchange resin, filtrate decompression is distilled, obtained glycerolphosphocholine A3.(amount of product is 7.75g, and purity is 99.3%, and pH value is 6.2, and specific rotation is-2.7 °)
Embodiment 4
1) 10g phosphoryl chloride choline calcium salt four hydrate is added in 35g deionized water, the aqueous solution of obtained phosphoryl chloride choline calcium salt, by the above-mentioned aqueous solution and the mixing of 15g anhydrous sodium carbonate, obtained mixture M 1;
2) mixture M 1 and 3g (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through Zeo-karb after mixture M 2 being diluted 5 times, obtain mixture M 3;
4) flow through Zeo-karb after mixture M 3 being diluted 2 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 70 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) leaching filtrate is crossed after mixture M 6 being flowed through respectively Zeo-karb and anionite-exchange resin, obtained glycerolphosphocholine A4.(amount of product is 7.2g, and purity is 92.3%, and pH value is 4.5, and specific rotation is-2.2 °)
Embodiment 5
1) 10g phosphoryl chloride choline calcium salt four hydrate is added in 65g deionized water, the aqueous solution of obtained phosphoryl chloride choline calcium salt, by the above-mentioned aqueous solution and the mixing of 60g anhydrous sodium carbonate, obtained mixture M 1;
2) mixture M 1 and 8g (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through Zeo-karb after mixture M 2 being diluted 10 times, obtain mixture M 3;
4) flow through Zeo-karb after mixture M 3 being diluted 4 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 90 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) leaching filtrate is crossed after mixture M 6 being flowed through respectively Zeo-karb and anionite-exchange resin, obtained glycerolphosphocholine A5.(amount of product is 7.15g, and purity is 91.7%, and pH value is 6.5, and specific rotation is-2.4 °)
Embodiment 6
Be prepared according to the preparation method of embodiment 1, unlike, the consumption of described anhydrous sodium carbonate is 15g, and the consumption of described (R)-(-)-3-chlorine-1,2-propylene glycol is 2g, obtained glycerolphosphocholine A6.(amount of product is 7.21g, and purity is 92.4%, and pH value is 4.5, and specific rotation is-2.2 °)
Embodiment 7
Be prepared according to the preparation method of embodiment 3, unlike, the consumption of described anhydrous sodium carbonate is 50g, and the consumption of described (R)-(-)-3-chlorine-1,2-propylene glycol is 12g, obtained glycerolphosphocholine A7.(amount of product is 7.8g, and purity is 100%, and pH value is 6.5, and specific rotation is-2.9 °)
Comparative example 1
Be prepared according to the preparation method of embodiment 3, unlike, without step 3) and step 4), obtained glycerolphosphocholine D1.(amount of product is 5.2g, and purity is 66.7%, and pH value is 4.5, and specific rotation is 2.1 °)
Comparative example 2
Be prepared according to the preparation method of embodiment 3, unlike, step 1) in anhydrous sodium carbonate be the saturated aqueous solution of sodium carbonate, obtained glycerolphosphocholine D2.(amount of product is 6.1g, and purity is 78.2%, and pH value is 6.5, and specific rotation is 1.8 °)
Comparative example 3
Be prepared according to the preparation method of embodiment 3, unlike, step 5) in the concentration of ethanol be 50 % by weight, obtained glycerolphosphocholine D3.(amount of product is 5.9g, and purity is 75.6%, and pH value is 4.5, and specific rotation is-2.5 °)
Can be found out by above-mentioned data, the working method being prepared glycerolphosphocholine by the present invention is simple, and when obtaining glycerolphosphocholine by method of the present invention, the purity of the glycerolphosphocholine obtained is all higher than 90%, and the cost used is lower, the glycerolphosphocholine obtained outward in the scope of the invention or purity not high, or cost is higher, or specific rotation has obvious difference, and purity when preparing glycerolphosphocholine in preferable range of the present invention is higher, and cost performance is also higher.
More than describe the preferred embodiment of the present invention in detail; but the present invention is not limited to the detail in above-mentioned embodiment, within the scope of technical conceive of the present invention; can carry out multiple simple variant to technical scheme of the present invention, these simple variant all belong to protection scope of the present invention.
It should be noted that in addition, each concrete technical characteristic described in above-mentioned embodiment, in reconcilable situation, can be combined by any suitable mode, in order to avoid unnecessary repetition, the present invention illustrates no longer separately to various possible array mode.
In addition, also can carry out arbitrary combination between various different embodiment of the present invention, as long as it is without prejudice to thought of the present invention, it should be considered as content disclosed in this invention equally.
Claims (10)
1. a preparation method for glycerolphosphocholine, is characterized in that, described preparation method comprises:
1) will such as formula the compound shown in (I) and anhydrous sodium carbonate mixing, obtained mixture M 1;
2) mixture M 1 and (R)-(-)-3-chlorine-1,2-propylene glycol are placed in dehydrated alcohol to reflux, obtain mixture M 2;
3) flow through the first ion exchange resin after mixture M 2 being diluted 5-10 times, obtain mixture M 3;
4) flow through the second ion exchange resin after mixture M 3 being diluted 2-4 times, obtain mixture M 4;
5) by mixture M 4 by concentration be 70-90 % by weight washing with alcohol after obtain mixture M 5;
6) by mixture M 5 with obtaining mixture M 6 after distilled water wash;
7) leaching filtrate is crossed after mixture M 6 being flowed through the 3rd ion exchange resin, obtained glycerolphosphocholine;
Wherein, R is Ca
2+or Mg
2+.
2. preparation method according to claim 1, wherein, relative to 100 weight parts described formula (I) shown in compound, the consumption of described (R)-(-)-3-chlorine-1,2-propylene glycol is 30-80 weight part.
3. preparation method according to claim 1, wherein, step 1) in be also included in mixing after carry out centrifugal and cross leaching supernatant liquor, and supernatant liquor is distilled to dry, obtains mixture M 1.
4. preparation method according to claim 3, wherein, described still-process is underpressure distillation.
5. preparation method according to claim 1, wherein, step 2) in return time be 20-30h.
6. preparation method according to claim 1, wherein, step 3) and step 4) recirculation operation 2-3 time.
7. preparation method according to claim 1, wherein, step 5) and step 6) recirculation operation 2-3 time.
8. preparation method according to claim 1, wherein, step 7) in also comprise filtrate distillation and concentration.
9. preparation method according to claim 1, wherein, described first ion exchange resin and described second ion exchange resin are Zeo-karb;
Preferably, described 3rd ion exchange resin is Zeo-karb and anionite-exchange resin.
10. preparation method according to claim 1, wherein, the compound shown in formula (I) is provided by the aqueous solution of concentration for 15-30 % by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510229848.6A CN104926862B (en) | 2015-05-07 | 2015-05-07 | The preparation method of glycerolphosphocholine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510229848.6A CN104926862B (en) | 2015-05-07 | 2015-05-07 | The preparation method of glycerolphosphocholine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104926862A true CN104926862A (en) | 2015-09-23 |
| CN104926862B CN104926862B (en) | 2017-12-01 |
Family
ID=54114308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510229848.6A Active CN104926862B (en) | 2015-05-07 | 2015-05-07 | The preparation method of glycerolphosphocholine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104926862B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106083918A (en) * | 2016-06-08 | 2016-11-09 | 芜湖福民生物药业有限公司 | The preparation method of phosphoryl chloride choline calcium salt four hydrate |
| CN108101937A (en) * | 2017-11-13 | 2018-06-01 | 湖南华纳大药厂手性药物有限公司 | A kind of method for preparing L- α-glycerolphosphocholine |
| CN108516987A (en) * | 2018-04-19 | 2018-09-11 | 厦门大学 | A kind of glycerolphosphocholine and its aqueous synthesis method |
| CN110028524A (en) * | 2019-05-07 | 2019-07-19 | 天津康巢生物医药股份有限公司 | A kind of process preparing glycerolphosphocholine and its glycerolphosphocholine obtained |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101967160A (en) * | 2010-09-09 | 2011-02-09 | 常熟富士莱医药化工有限公司 | One-step method for preparing raceme DL, D or L-a-glycerin phosphorus acyl choline |
| CN104513267A (en) * | 2014-01-11 | 2015-04-15 | 芜湖福民生物药业有限公司 | Glycerophosphorylcholine preparation method |
-
2015
- 2015-05-07 CN CN201510229848.6A patent/CN104926862B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101967160A (en) * | 2010-09-09 | 2011-02-09 | 常熟富士莱医药化工有限公司 | One-step method for preparing raceme DL, D or L-a-glycerin phosphorus acyl choline |
| CN104513267A (en) * | 2014-01-11 | 2015-04-15 | 芜湖福民生物药业有限公司 | Glycerophosphorylcholine preparation method |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106083918A (en) * | 2016-06-08 | 2016-11-09 | 芜湖福民生物药业有限公司 | The preparation method of phosphoryl chloride choline calcium salt four hydrate |
| CN106083918B (en) * | 2016-06-08 | 2018-07-06 | 芜湖福民生物药业有限公司 | The preparation method of four hydrate of phosphoryl chloride choline calcium salt |
| CN108101937A (en) * | 2017-11-13 | 2018-06-01 | 湖南华纳大药厂手性药物有限公司 | A kind of method for preparing L- α-glycerolphosphocholine |
| CN108101937B (en) * | 2017-11-13 | 2020-03-10 | 湖南华纳大药厂手性药物有限公司 | Method for preparing L- α -glycerophosphatidylcholine |
| CN108516987A (en) * | 2018-04-19 | 2018-09-11 | 厦门大学 | A kind of glycerolphosphocholine and its aqueous synthesis method |
| CN110028524A (en) * | 2019-05-07 | 2019-07-19 | 天津康巢生物医药股份有限公司 | A kind of process preparing glycerolphosphocholine and its glycerolphosphocholine obtained |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104926862B (en) | 2017-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104844647A (en) | Preparation method of glycerinum phosphatidylcholine | |
| CN104926862A (en) | Preparation method for glycerophosphatidylcholine | |
| DE69624768T2 (en) | nutritional composition | |
| US10076530B2 (en) | Lipid compositions with high DHA content | |
| FI72118B (en) | FRAMEWORK FOR THERAPEUTIC ADJUSTMENT OF THERAPEUTIC ORGANIC EQUIPMENT | |
| CN105287666B (en) | A kind of preparation method of Seabuckthorm Seed Oil | |
| CN105497093B (en) | A kind of composition with auxiliary improvement of memory power function, preparation method and the capsule containing the composition | |
| US11576935B2 (en) | Non-winterized, standardized marine source oil products and methods of making thereof | |
| CN106755228A (en) | The technique for preparing the oligomeric Gly-His-Lys of selenium yeast using Se-enriched yeast | |
| CN104513267A (en) | Glycerophosphorylcholine preparation method | |
| CN102286561B (en) | Method for extracting active ingredients of fresh pilos antler through enzymatic degradation | |
| CN106174494A (en) | A kind of compositions and the application in the product preparing nourishing the brain and improving intelligence thereof | |
| CN102578391B (en) | Compound propolis feed additive capable of promoting growth and improving immunity of poultry and method for preparing same | |
| FR3040881A1 (en) | PROCESS FOR OBTAINING A CONCENTRATE OF MARINE MINERALS | |
| CN108329344A (en) | A kind of purification process of glycerophosphonolipid phatidylcholine | |
| CN105456049A (en) | Coenzyme Q10 massage balm with functions of diminishing inflammation, relieving pain and protecting skin | |
| US20160243061A1 (en) | Compositions comprising choline and derivatives thereof, uses thereof and processes for their preparation | |
| CN109097190B (en) | Method for enriching phospholipid from krill oil | |
| CN108175808A (en) | A kind of pharmaceutical composition and its application | |
| CN103040869B (en) | Artificial bear gall powder and preparation method thereof | |
| KR20010069433A (en) | Hernacium Erinaceum use health assistance food | |
| EP0073173A1 (en) | Products extracted from invertebrate sea-animals, their preparation and their uses in dietetics,pharmaceutics and cosmetology | |
| CN102151285B (en) | Neutral calcium supplement preparation | |
| CN105985859A (en) | Cod liver oil extract and preparation method thereof | |
| KR101768029B1 (en) | Cosmetic Composition For Moisturizing Skin Comprising Perna Canaliculus as Active Ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address |
Address after: 241000 No. 3 factory building, spark fire Industrial Park, Yijiang District, Wuhu, Anhui Patentee after: Wuhu Fumin pharmaceutical Limited by Share Ltd Address before: 241000 the 3 factory building of Spark Industrial Park, high tech Development Zone, Wuhu, Anhui. Patentee before: WUHU FOMAN BIOPHARMA CO., LTD. |
|
| CP03 | Change of name, title or address |