CN111116643B - Synthetic method of hydrogenated soybean phosphatidylcholine - Google Patents
Synthetic method of hydrogenated soybean phosphatidylcholine Download PDFInfo
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- CN111116643B CN111116643B CN201911273964.2A CN201911273964A CN111116643B CN 111116643 B CN111116643 B CN 111116643B CN 201911273964 A CN201911273964 A CN 201911273964A CN 111116643 B CN111116643 B CN 111116643B
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- JLPULHDHAOZNQI-JLOPVYAASA-N [(2r)-3-hexadecanoyloxy-2-[(9e,12e)-octadeca-9,12-dienoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC JLPULHDHAOZNQI-JLOPVYAASA-N 0.000 title claims abstract description 38
- 238000010189 synthetic method Methods 0.000 title description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 72
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000005406 washing Methods 0.000 claims abstract description 29
- 238000001914 filtration Methods 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 239000003208 petroleum Substances 0.000 claims abstract description 21
- 239000000047 product Substances 0.000 claims abstract description 21
- 238000001035 drying Methods 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 17
- 238000001953 recrystallisation Methods 0.000 claims abstract description 15
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 11
- 239000000706 filtrate Substances 0.000 claims abstract description 10
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 10
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 238000002425 crystallisation Methods 0.000 claims abstract description 6
- 230000008025 crystallization Effects 0.000 claims abstract description 6
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 229940083466 soybean lecithin Drugs 0.000 claims abstract description 5
- 239000008215 water for injection Substances 0.000 claims abstract description 5
- 239000012043 crude product Substances 0.000 claims abstract description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 56
- 238000003756 stirring Methods 0.000 claims description 26
- 239000003960 organic solvent Substances 0.000 claims description 18
- 239000012528 membrane Substances 0.000 claims description 17
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 17
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- 239000012065 filter cake Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 238000007599 discharging Methods 0.000 claims description 4
- 238000013019 agitation Methods 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 abstract description 4
- 238000001291 vacuum drying Methods 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 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 11
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- -1 10% in content Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000008347 soybean phospholipid Substances 0.000 description 2
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 210000003486 adipose tissue brown Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000010999 medical injection Methods 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003248 quinolines Chemical group 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000005303 weighing 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
- C07F9/10—Phosphatides, e.g. lecithin
- C07F9/103—Extraction or purification by physical or chemical treatment of natural phosphatides; Preparation of compositions containing phosphatides of unknown structure
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses a method for synthesizing hydrogenated soybean phosphatidylcholine, which comprises the following steps: (1) hydrogenation reaction: adding soybean lecithin, palladium carbon, toluene, water for injection and methanol into a reaction kettle, then completing hydrogenation reaction in a hydrogen environment, and filtering to obtain filtrate; (2) concentration and crystallization: firstly concentrating the filtrate for the first time, and then adding toluene for secondary concentration; refluxing, filtering and drying to obtain a crude product of the hydrogenated soybean phosphatidylcholine; (3) washing with petroleum ether and vacuum drying; (4) recrystallizing; (5) drying to obtain white powdered hydrogenated soybean phosphatidylcholine. According to the invention, through reasonable formula design, the target carbon is used as a catalyst for catalytic hydrogenation, the catalytic condition is mild, the energy consumption is low, the cost is controllable, and the obtained product is purified for three times through concentration crystallization, petroleum ether washing and recrystallization, so that the obtained hydrogenated soybean phosphatidylcholine product has high purity, high yield and excellent performance, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of preparation of phosphatidylcholine, and particularly relates to a synthetic method of hydrogenated soybean phosphatidylcholine.
Background
Phosphatidylcholine (1, 2-diacyl-sn-glycerol-3-phosphatidylcholine) is an amphiphilic molecule consisting of a hydrophilic head and a hydrophobic tail, which is a phospholipid with a choline group inserted in the head. Phosphatidylcholine is an important component of biological membranes and can be easily extracted from a variety of sources, such as egg yolk and soybean, and hexane is a commonly used agent for extraction. Phosphatidylcholine is also an important constituent of brown fat in animal and plant tissues. Phosphatidylcholine is an important component of cell membrane and pulmonary surfactant, and is more common on the outer lobes of the phospholipid bilayer. Phosphatidylcholine transferase is a carrier that transports phosphatidylcholine from membrane to membrane.
Since phospholipid is a surfactant and has good emulsifying properties, it is widely used in the fields of foods, medicines and cosmetics. Because the phosphatidyl choline has strong hydrophilicity, the phosphatidyl choline is suitable for being used as an oil-in-water (O/W) emulsifier, the application is wide, the domestic demand is increased year by year, but the yield and the quality of the high-purity phosphatidyl choline in China are low, and most of the high-purity phosphatidyl choline depend on import, especially the phosphatidyl choline for medical injection. The soybean phospholipids have the problems of peculiar smell, dark color, easy oxidation, instability and the like in application, so that the chemical modification is carried out on the soybean phospholipids, and catalytic hydrogenation is one of the chemical modification methods.
In the literature, nickel or platinum is used as a catalyst for catalytic hydrogenation earlier, but the nickel or platinum has the disadvantages of low activity, difficult regeneration, high reaction temperature and pressure, high requirement on equipment, high energy consumption and no contribution to industrial production; the latter is relatively expensive and increases the production costs.
Disclosure of Invention
The invention mainly solves the technical problem of providing a method for synthesizing hydrogenated soybean phosphatidylcholine.
In order to solve the technical problems, the invention adopts a technical scheme that: the synthesis method of the hydrogenated soybean phosphatidylcholine comprises the following steps:
(1) hydrogenation reaction: adding soybean lecithin, palladium carbon, toluene, water for injection and methanol into a reaction kettle, then completing hydrogenation reaction in a hydrogen environment, discharging, filtering reaction liquid to remove the palladium carbon, and washing obtained filtrate with a first organic solvent;
(2) concentration and crystallization: firstly concentrating the filtrate washed in the step (1), and then adding toluene for secondary concentration; slowly adding acetone into the concentrated solution, stirring uniformly, performing reflux reaction, performing hot filtration on the mixture after the reaction is finished, and washing and drying the obtained filter cake by using a second organic solvent to obtain a crude product of the hydrogenated soybean phosphatidylcholine;
(3) washing with petroleum ether: adding the product dried in the step (2) into petroleum ether, stirring and washing, then removing the petroleum ether by filtration, washing the obtained filter cake with the petroleum ether, and drying in vacuum;
(4) and (3) recrystallization: dissolving the hydrogenated soybean phosphatidylcholine dried in the step (3) in a recrystallization solvent, slowly stirring and cooling to recrystallize the hydrogenated soybean phosphatidylcholine, then performing filtration, and washing with acetone;
(5) and (3) drying: and (4) drying the product washed in the step (4) in vacuum to obtain white powdered hydrogenated soybean phosphatidylcholine.
In a preferred embodiment of the present invention, in the step (1), the hydrogenation reaction conditions are: the pressure is 0.8-1.3 MPa, the temperature is 30-55 ℃, and the stirring speed is 280-300 rpm.
In a preferred embodiment of the present invention, in the step (1), the method for removing palladium on carbon by filtration comprises: the mixture was filtered through a filter paper and then through a 0.2 μm PTFE filter.
In a preferred embodiment of the present invention, in the step (2), the temperature of the primary concentration and the secondary concentration is 45 ℃; the liquid-solid mass ratio after the primary concentration is below 1.2; the liquid-solid mass ratio after secondary concentration is 1.2-1.4; the adding time of the acetone is more than 1 h; the conditions of the reflux reaction are as follows: the temperature is 56-60 ℃, the time is 60-90 min, and the stirring speed is 90-130 rpm.
In a preferred embodiment of the present invention, in the step (3), the conditions of the agitation washing are as follows: the temperature is 35 +/-5 ℃, the stirring speed is below 180rpm, and the time is 1 h.
In a preferred embodiment of the present invention, in the step (4), the recrystallization method is: at the stirring speed of 100-150 r/min, firstly cooling to 36-40 ℃, keeping the temperature for 30min, and then cooling to below 20 ℃ until the precipitated solid becomes uniform powder.
In a preferred embodiment of the present invention, the first organic solvent, the second organic solvent, toluene, methanol, acetone, petroleum ether and the recrystallization solvent are filtered through a 0.2 μm PTFE membrane and used.
In a preferred embodiment of the present invention, the first organic solvent is a mixed solution of toluene and methanol in a volume ratio of 1.2: 1.
In a preferred embodiment of the present invention, the second organic solvent is a mixed solution of acetone and methanol in a volume ratio of 10: 1.
In a preferred embodiment of the present invention, the recrystallization solvent includes acetone and methanol, wherein the amount of acetone is 6.5 times the mass of the hydrogenated soybean phosphatidylcholine, and the amount of methanol is 1.4 times the mass of the hydrogenated soybean phosphatidylcholine.
The invention has the beneficial effects that: the synthetic method of the hydrogenated soybean phosphatidylcholine adopts the target carbon as the catalyst for catalytic hydrogenation through reasonable formula design, has mild catalytic conditions, low energy consumption and controllable cost, and purifies the obtained product by three times of concentration crystallization, petroleum ether washing and recrystallization, so that the obtained hydrogenated soybean phosphatidylcholine product has high purity, high yield and excellent performance, and is suitable for industrial production.
Detailed Description
The following detailed description of the preferred embodiments of the present invention is provided to enable those skilled in the art to more readily understand the advantages and features of the present invention, and to clearly and unequivocally define the scope of the present invention.
The embodiment of the invention comprises the following steps:
the invention discloses a method for synthesizing hydrogenated soybean phosphatidylcholine, which comprises the following steps:
(1) hydrogenation reaction: adding soybean lecithin, palladium carbon, toluene, water for injection and methanol into a reaction kettle, then completing hydrogenation reaction under the hydrogen environment at the stirring speed of 280-300 rpm at the temperature of 30-55 ℃ and under the pressure of 0.8-1.3 MPa, discharging, filtering the reaction solution by using filter paper, then filtering by using a 0.2 mu m PTFE filter membrane to remove the palladium carbon, washing the obtained filtrate by using a first organic solvent, wherein the first organic solvent is a mixed solution of toluene and methanol with the volume ratio of 1.2:1, and filtering by using a 0.2 mu m PTFE filter membrane before use;
(2) concentration and crystallization: firstly, carrying out primary concentration on the filtrate washed in the step (1) at 45 ℃ to ensure that the liquid-solid mass ratio after primary concentration is below 1.2; adding toluene, and performing secondary concentration at 45 ℃ to ensure that the liquid-solid mass ratio after secondary concentration is 1.2-1.4; slowly adding acetone into the concentrated solution, controlling the adding time to be more than 1h, uniformly stirring, carrying out reflux reaction for 60-90 min under the conditions of 56-60 ℃ and the stirring speed of 90-130 rpm, carrying out hot filtration on the mixture after the reaction is finished, washing and drying the obtained filter cake by using a second organic solvent which is more than 40 ℃ and filtered by a 0.2-micron PTFE filter membrane to obtain a crude product of the hydrogenated soybean phosphatidylcholine; the second organic solvent is a mixed solution of acetone and methanol in a volume ratio of 10: 1;
(3) washing with petroleum ether: adding the product dried in the step (2) into petroleum ether filtered by a PTFE filter membrane of 0.2 mu m, stirring and washing for 1h at the stirring speed of below 180rpm at the temperature of 35 +/-5 ℃, then removing the petroleum ether by filtration, washing the obtained filter cake with the petroleum ether, and drying in vacuum;
(4) and (3) recrystallization: dissolving the hydrogenated soybean phosphatidylcholine dried in the step (3) in a recrystallization solvent, wherein the recrystallization solvent comprises acetone and methanol, the amount of the acetone is 6.5 times of the mass of the hydrogenated soybean phosphatidylcholine, and the amount of the methanol is 1.4 times of the mass of the hydrogenated soybean phosphatidylcholine; or adding all methanol and a small amount of acetone until the product is completely dissolved, and then adding the rest acetone, so that the dissolving speed can be increased; after completely dissolving, slowly stirring and cooling to recrystallize the hydrogenated soybean phosphatidylcholine, specifically, under the stirring speed of 100-150 r/min, firstly cooling to 36-40 ℃, keeping the temperature for 30min, then cooling to below 20 ℃ until the precipitated solid becomes uniform powder, then carrying out filtration, and washing with acetone which is 0.8 times of the weight of the powder and is filtered by a 0.2 mu m PTFE filter membrane;
(5) and (3) drying: and (4) drying the product washed in the step (4) in vacuum to obtain white powdered hydrogenated soybean phosphatidylcholine.
Example 1
To a 10L reactor were added 1250 g of soybean lecithin (EPIKURON 200), 50 g of Pd/C (palladium on carbon, 10% in content, water content: about 60%), 3500 ml of toluene, 325 ml of water for injection (or purified water) and 2400 ml of methanol in this order. The autoclave was replaced three times with nitrogen and then three times with hydrogen. The initial set temperature of the reaction kettle is 30 ℃ (the reaction releases heat, the temperature rises to 50 +/-5 ℃ within 1 hour), the stirring speed is 290 rpm, the initial pressure is 1.0 MPa, and the pressure is controlled within the range of 0.8-1.3 MPa in the reaction process. And after reacting for 3 hours, reducing the pressure by 17-19 kg, stopping the reaction, discharging, filtering the reaction solution to remove palladium carbon, specifically, filtering once with common filter paper, filtering the filtrate once with a 0.2-micron PTFE membrane, washing the obtained filter cake with a first organic solvent, wherein the first organic solvent is a mixed solution of 265 ml of toluene and 220 ml of methanol.
Transferring the washed filtrate into a round bottom flask, distilling at 45 ℃ under reduced pressure, concentrating to be less than 2900 g, adding 2.4L of toluene (the toluene is filtered by a 0.2um PTFE membrane), and performing rotary evaporation on the mixture at 45 ℃ until the mass is 2750-3000 g. If the mass of the mixture is less than 2750 g, toluene may be added thereto to adjust the mass to fall within this range. Transferring the concentrated solution to a 20L glass kettle, setting the temperature to be 50 ℃, slowly adding 10.6L of acetone (0.2 um PTFE membrane for filtration), controlling the dropping time to be more than 1h, then stirring at the reflux temperature of 56-60 ℃ for at least 60 minutes, filtering the mixture while the mixture is hot by throwing, washing a filter cake by using a mixed solution of 4.7L of acetone and 0.47L of methanol (0.2 um PTFE membrane for filtration) at the temperature of more than 40 ℃ to obtain a white powdery product, and then placing the white powdery product into a vacuum drying oven for drying at room temperature overnight.
After drying, transferring the product into a glass reaction kettle, adding 4.5L of petroleum ether for washing, stirring at low speed of about 35 ℃ for about 1h, rotating at the speed of below 180rpm, removing the petroleum ether by spin filtration, washing a filter cake with 1.5L of petroleum ether, and drying the product in a vacuum drying oven; the petroleum ether was filtered through a 0.2um PTFE membrane prior to use.
Weighing the dried product, adding acetone (filtered by 0.2um PTFE membrane) accounting for 6.5 times of the product mass and methanol (filtered by 0.2um PTFE membrane) accounting for 1.4 times of the product mass, heating to about 50 ℃ for dissolution (all methanol and a small amount of acetone can be added at first, and the rest acetone is added after the product is completely dissolved, so that the dissolution speed can be accelerated); after complete dissolution, slowly stirring and gradually cooling until a small amount of solid appears, keeping the temperature within the range of 36-40 ℃ for about 30 minutes, separating out a large amount of white solid in the process, then cooling to below 20 ℃, slowly stirring to form uniform powder, and washing the powder with 0.8 time of acetone (0.2 um PTFE membrane filtration) by weight after filtration.
And (4) putting the product obtained by washing into a vacuum drying oven, drying at room temperature overnight, and then filling into a polyethylene bag for low-temperature storage.
The yield of the reaction is 82-85%, and the product is white powdery solid.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (8)
1. A method for synthesizing hydrogenated soybean phosphatidylcholine is characterized by comprising the following steps:
(1) hydrogenation reaction: adding soybean lecithin, palladium carbon, toluene, water for injection and methanol into a reaction kettle, then completing hydrogenation reaction in a hydrogen environment, discharging, filtering reaction liquid to remove the palladium carbon, and washing obtained filtrate with a first organic solvent; the conditions of the hydrogenation reaction are as follows: the pressure is 0.8-1.3 MPa, the temperature is 30-55 ℃, and the stirring speed is 280-300 rpm;
(2) concentration and crystallization: firstly concentrating the filtrate washed in the step (1), and then adding toluene for secondary concentration; slowly adding acetone into the concentrated solution, stirring uniformly, performing reflux reaction, performing hot filtration on the mixture after the reaction is finished, and washing and drying the obtained filter cake by using a second organic solvent to obtain a crude product of the hydrogenated soybean phosphatidylcholine;
(3) washing with petroleum ether: adding the product dried in the step (2) into petroleum ether, stirring and washing, then removing the petroleum ether by filtration, washing the obtained filter cake with the petroleum ether, and drying in vacuum;
(4) and (3) recrystallization: dissolving the hydrogenated soybean phosphatidylcholine dried in the step (3) in a recrystallization solvent, slowly stirring and cooling to recrystallize the hydrogenated soybean phosphatidylcholine, then performing filtration, and washing with acetone; the recrystallization method comprises the following steps: under the stirring speed of 100-150 r/min, firstly cooling to 36-40 ℃, keeping the temperature for 30min, and then cooling to below 20 ℃ until the precipitated solid becomes uniform powder;
(5) and (3) drying: and (4) drying the product washed in the step (4) in vacuum to obtain white powdered hydrogenated soybean phosphatidylcholine.
2. The method for synthesizing hydrogenated soybean phosphatidylcholine according to claim 1, wherein in the step (1), the method for removing palladium on carbon by filtration is: the mixture was filtered through a filter paper and then through a 0.2 μm PTFE filter.
3. The method for synthesizing hydrogenated soybean phosphatidylcholine according to claim 1, wherein in the step (2), the temperature of the first and second concentration is 45 ℃; the liquid-solid mass ratio after the primary concentration is below 1.2; the liquid-solid mass ratio after secondary concentration is 1.2-1.4; the adding time of the acetone is more than 1 h; the conditions of the reflux reaction are as follows: the temperature is 56-60 ℃, the time is 60-90 min, and the stirring speed is 90-130 rpm.
4. The method for synthesizing hydrogenated soybean phosphatidylcholine according to claim 1, wherein in the step (3), the conditions of the agitation washing are: the temperature is 35 +/-5 ℃, the stirring speed is below 180rpm, and the time is 1 h.
5. The method for synthesizing hydrogenated soybean phosphatidylcholine according to claim 1, wherein the first organic solvent, the second organic solvent, toluene, methanol, acetone, petroleum ether and recrystallization solvent are all filtered with 0.2 μm PTFE filter membrane and used.
6. The method of synthesizing hydrogenated soybean phosphatidylcholine according to claim 5, wherein said first organic solvent is a mixed solution of toluene and methanol at a volume ratio of 1.2: 1.
7. The method for synthesizing hydrogenated soybean phosphatidylcholine according to claim 5, wherein the second organic solvent is a mixed solution of acetone and methanol at a volume ratio of 10: 1.
8. The method of synthesizing hydrogenated soybean phosphatidylcholine according to claim 5, wherein said recrystallization solvent comprises acetone and methanol, wherein said acetone is used in an amount of 6.5 times the mass of said hydrogenated soybean phosphatidylcholine, and said methanol is used in an amount of 1.4 times the mass of said hydrogenated soybean phosphatidylcholine.
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| CN105732702A (en) * | 2016-03-16 | 2016-07-06 | 苏州东南药业股份有限公司 | Hydrogenated soybean lecithin and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105732702A (en) * | 2016-03-16 | 2016-07-06 | 苏州东南药业股份有限公司 | Hydrogenated soybean lecithin and preparation method and application thereof |
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| CN111116643A (en) | 2020-05-08 |
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