Preparation method of L-alpha-choline glycerophosphate

Abstract

The invention belongs to the field of biological medicine, and provides a preparation method of L-alpha-choline alfoscerate, which comprises the steps of esterification reaction, neutralization reaction, spray drying, condensation reaction, filtration, concentration, crystallization, redissolution and decoloration, resin impurity removal, secondary filtration and concentration, secondary crystallization, drying and packaging according to a process route. The esterification reaction adopts polyphosphoric acid and choline chloride for esterification reaction, the neutralization reaction takes a reaction product after esterification reaction, pure water is added for dilution, and then alkali is added for neutralization; drying the neutralization solution in a spray drying tower to obtain an intermediate product; an intermediate product obtained through spray drying is put into a condensation kettle, ethyl alcohol is added, and R-3-chloro-1, 2-propylene glycol is dropwise added till L-alpha-choline alfoscerate, metal chloride salt and metal phosphate salt are generated. The method is reasonable in design, the process difficulty between esterification reaction and condensation reaction is reduced, the process period can be shortened, the consumption of R-3-chloro-1, 2-propylene glycol can be reduced, the product purity can be guaranteed, and the method is suitable for large-scale popularization.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and in particular relates to a method for preparing L-α-glyceophosphocholine. Background Art

[0002] Glycerolphosphocholine (GPC) is a water-soluble small molecule normally present in the human body and serves as a biosynthetic precursor for the important neurotransmitter acetylcholine. The most important function of GPC is the choline it produces, a water-soluble B vitamin that plays a vital role in the brain and nervous system. Studies have shown that GPC plays a crucial role in the production of certain hormones and neurotransmitters, such as acetylcholine and human growth hormone, thereby supporting brain and nervous system function. L-α-Glycerolphosphocholine has important applications in many fields, including medicine and healthcare, food and nutrition, cosmetics, and biological science research.

[0003] The traditional synthesis process route is a multi-step complex synthesis path, such as "esterification reaction to produce phosphorylcholine chloride → synthesis and purification to produce phosphorylcholine chloride calcium salt → synthesis and purification to produce phosphorylcholine chloride potassium salt → synthesis of L-α-phosphocholine". The purification of different salts in this path requires complex processing steps, such as "phosphorylcholine chloride calcium salt reacts with potassium carbonate or potassium hydroxide to produce phosphorylcholine chloride crude potassium salt → filtration to remove calcium carbonate → refining → drying to obtain phosphorylcholine chloride pure potassium salt" and "phosphorylcholine chloride calcium salt reacts with potassium carbonate or potassium hydroxide to produce phosphorylcholine chloride crude potassium salt → filtration to remove calcium carbonate → refining → drying to obtain phosphorylcholine chloride pure potassium salt". In addition, the process cycle is long.

[0004] The R-3-chloro-1,2-propanediol used in traditional synthesis processes consumes large amounts and has multiple disadvantages, such as certain toxicity and difficulty in degradation in the environment. It may remain and accumulate in environmental media such as soil and water, causing long-term potential harm to the ecological environment and affecting ecological balance and biodiversity.

[0005] In traditional processes, the esterification reaction uses phosphoric acid and choline chloride for synthesis. This method has some disadvantages, such as harsh reaction conditions, complex product separation and purification process, and the potential generation of a large amount of waste. It is necessary to control the reaction conditions and perform effective product separation and purification to obtain high-purity choline phosphate. Summary of the Invention

[0006] The present invention addresses the technical problems existing in the conventional synthesis process of L-α-glycine choline and proposes a method for preparing L-α-glycine choline that has a reasonable design, is conducive to shortening the process cycle, can reduce the consumption of R-3-chloro-1,2-propanediol, and is conducive to ensuring the purity of the product.

[0007] In order to achieve the above-mentioned object, the technical solution adopted by the present invention is as follows: a preparation method of L-α-glycetocholine provided by the present invention comprises an esterification reaction, a condensation reaction, filtration, concentration, crystallization, redissolution and decolorization, resin impurity removal, secondary crystallization, drying and packaging according to the process route, wherein the esterification reaction and the condensation reaction further comprise a neutralization reaction and spray drying, and the resin impurity removal and the secondary crystallization further comprise a secondary filtration and concentration;

[0008] Esterification reaction: Polyphosphoric acid and choline chloride are used for esterification reaction. The feed ratio of polyphosphoric acid to choline chloride is 400kg:320kg~450kg by mass. The optimal reaction temperature range is 120℃~145℃.

[0009] Neutralization reaction: dilute the reaction product after the esterification reaction with pure water, then add alkali to neutralize it to a pH of 8.5-11.5; after the reaction is complete, add 1.5 times the molar amount of calcium chloride as inorganic phosphate, fully react for 4 hours, and then send the reaction filtrate to the spray drying process;

[0010] Spray drying: drying the neutralized solution in a spray drying tower to obtain an intermediate product, which is a mixture of phosphorylcholine chloride metal salt, phosphorylcholine phosphate metal salt and phosphate metal salt;

[0011] Condensation reaction: The intermediate obtained by spray drying is placed in a condensation kettle, 4000 L of ethanol is added as the reaction solvent medium, and R-3-chloro-1,2-propanediol is added dropwise to the reactor. The reaction temperature is 75°C to 85°C, and the reaction is refluxed for 50 to 65 hours. The reaction endpoint is confirmed by thin layer chromatography until L-α-phosphoglycerate choline, metal chloride salt, and metal phosphate salt are generated;

[0012] Crystallization: The concentrated liquid is cooled to -0°C to -15°C, stirred and crystallized for 6 to 8 hours, and then centrifuged to obtain crude L-α-glycerophosphorylcholine.

[0013] Preferably, the filtering process specifically includes: separating the insoluble substances phosphate metal salt and chloride metal salt in ethanol in the form of filter cake by plate filtration; and transferring the ethanol solution containing L-α-glycerophosphorylcholine to a concentration process.

[0014] Preferably, the concentration step specifically includes: concentrating the ethanol solution of L-α-glycerophosphorylcholine under vacuum at a temperature of 80° C. to 95° C.; and distilling for 4 to 6 hours to distill out 3000 L of ethanol.

[0015] Preferably, the resin impurity removal process specifically includes: removing ionizable impurities in the feed solution through anion and cation exchange resins, and the conductivity is: ≤50μs / cm.

[0016] Preferably, the secondary filtration and concentration process specifically includes: filtering the filtrate after resin impurities removal through a precision filter, concentrating the filtrate under reduced pressure, controlling the temperature to 90°C to 98°C, and achieving a maximum concentrated water output of 1850L to 1950L.

[0017] Preferably, the secondary crystallization process specifically includes: transferring the 90°C feed liquid after secondary filtration and concentration to a crystallization kettle, adding 4000-5000L of ethanol, cooling to the range of 8°C to -15°C, and crystallizing for 3-4 hours under stirring.

[0018] Preferably, the drying process specifically includes adopting vacuum drying at a temperature of 90° C. to 120° C. and drying to a moisture content of ≤1.0%.

[0019] Preferably, the exhaust gas generated by the spray drying tower is used to preheat the filtrate to be introduced into the spray drying tower. The spray drying tower comprises an exhaust pipe, a preheater is provided at the discharge end of the exhaust pipe, and a preheating chamber is provided inside the preheater for the filtrate to pass through.

[0020] Preferably, the spray drying tower includes a hot air distributor and an atomizer arranged at the top thereof, the hot air distributor includes a hot air duct, the end of the hot air duct is spiral and rotating blades and fixed blades are arranged on its inner side, the atomizer is arranged at the spiral center of the hot air duct, the atomizer includes an outer cone and an inner cone, the top of the outer cone is provided with a filtrate feed port, the bottom of the inner cone is provided with a rotating member, the top of the rotating member is provided with a power source connected to the transmission thereof, and the side and bottom of the rotating member are provided with spray holes for spraying toward the air outlet side of the hot air distributor.

[0021] Preferably, the rotating member includes a rotating shaft, a rotating body is provided on the side of the rotating shaft, a plurality of spiral guide blades are provided on the rotating body, and the rotating body is provided with a plurality of guide channels corresponding to the guide blades one by one, the guide channels are spiral and their side and bottom surfaces are open, the cross-section of the guide channels is trapezoidal and the small bottom end of the trapezoid is distributed on the side of the rotating body, an atomizing plate is provided in the guide channel, the atomizing plate includes a spiral section and a bottom plate section, and the spray holes are distributed on the spiral section and the bottom plate section.

[0022] Preferably, the rotating body includes a first-level inverted cone section that rotates with the bottom of the inner cone, and the side surface of the first-level inverted cone section is located on the same inverted cone surface as the side surface of the inner cone. The bottom of the first-level inverted cone section is provided with a second-level inverted cone section that rotates with the bottom of the outer cone, and the side surface of the second-level inverted cone section is located on the same inverted cone surface as the side surface of the outer cone. The top surface of the second-level inverted cone section is an inclined surface, and the top surface of the second-level inverted cone section and the bottom surface of the first-level inverted cone section are in a rounded transition.

[0023] Compared with the prior art, the advantages and positive effects of the present invention are:

[0024] 1. The present invention provides a method for preparing L-α-glycerophosphorylcholine, which realizes "esterification reaction to generate phosphorylcholine chloride → synthesis of phosphorylcholine chloride alkali metal salt → synthesis of L-α-glycerophosphorylcholine", simplifies the production process, and is conducive to shortening the process cycle.

[0025] 2. The present invention provides a method for preparing L-α-glycerophosphorylcholine, which adopts an innovative spray drying process to obtain a solid crude product of phosphorylcholine chloride alkali metal salt. This technical route realizes the synthesis of L-α-glycerophosphorylcholine by a direct condensation reaction of the solid crude product of phosphorylcholine chloride alkali metal salt, which is beneficial to shortening the process cycle and reducing the consumption of R-3-chloro-1,2-propylene glycol, which is beneficial to ensuring product quality.

[0026] 3. The present invention provides a method for preparing L-α-glycerophosphorylcholine. By adopting a preheater, the waste gas heat generated in the spray drying tower can be recovered, saving energy. In addition, the atomizer provided by the present invention has a good atomization effect and can fully contact with the hot air in the hot air duct to ensure product quality.

[0027] 4. The present invention has a reasonable design, is conducive to shortening the process cycle, can reduce the consumption of R-3-chloro-1,2-propylene glycol and is conducive to ensuring product purity, and is suitable for large-scale promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following is a brief introduction to the drawings required for use in the description of the embodiments. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0029] Figure 1 A process diagram of a method for preparing L-α-glycerocholine provided in an embodiment;

[0030] Figure 2 A schematic diagram of the working of the preheater and the exhaust pipe provided in the embodiment;

[0031] Figure 3 A working axonometric view of the hot air distributor and atomizer provided in the embodiment;

[0032] Figure 4 A front view of the hot air distributor and atomizer provided in the embodiment;

[0033] Figure 5 A front view of an atomizer provided in an embodiment;

[0034] Figure 6 A cross-sectional view of the atomizer provided in the embodiment taken along the BB direction;

[0035] Figure 7 A bottom view of the rotating member, atomizing plate and nozzle holes provided in the embodiment;

[0036] Figure 8 An exploded view of a rotating member, atomizing plate, and a nozzle hole provided in an embodiment;

[0037] Figure 9 A cross-sectional view of a hot air distributor provided in an embodiment;

[0038] In the above figures, 1. preheater; 2. exhaust pipe; 3. hot air distributor; 31. hot air duct; 32. rotating blades; 33. fixed blades; 4. atomizer; 41. outer cone; 42. inner cone; 43. filtrate feed port; 44. rotating part; 441. rotating shaft; 442. rotating body; 4421. first-stage inverted cone section; 4422. second-stage inverted cone section; 443. guide blades; 444. guide duct; 45. power source; 46. spray hole; 47. atomizing plate; 471. spiral section; 472. bottom plate section. DETAILED DESCRIPTION

[0039] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described below with reference to the accompanying drawings and embodiments. It should be noted that the embodiments of the present application and the features therein can be combined with each other unless they conflict. For the convenience of description, the words "upper", "lower", "left", and "right" appearing below only indicate the upper, lower, left, and right directions consistent with the drawings themselves and do not limit the structure.

[0040] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways than those described herein. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0041] Examples, such as Figure 1 As shown, the present invention provides a method for preparing L-α-glycerophosphocholine, which includes an esterification reaction, a condensation reaction, filtration, concentration, crystallization, redissolution and decolorization, resin impurity removal, secondary crystallization, drying and packaging according to the process route. A neutralization reaction and spray drying are also included between the esterification reaction and the condensation reaction. A secondary filtration and concentration is also included between the resin impurity removal and the secondary crystallization. The specific contents of some of the steps such as the esterification reaction, neutralization reaction, spray drying and condensation reaction are as follows:

[0042] Esterification reaction: Polyphosphoric acid and choline chloride are used for esterification reaction. The feed ratio of polyphosphoric acid to choline chloride is 400kg:320kg~450kg by mass. The optimal reaction temperature range is 120℃~145℃.

[0043] Neutralization reaction: The reaction product after the esterification reaction is diluted with pure water and then neutralized with alkali to a pH of 8.5-11.5. After the reaction is complete, calcium chloride 1.5 times the molar amount of inorganic phosphate is added and fully reacted for 4 hours. The reaction filtrate is then spray-dried. The neutralizing agent is any one of the alkali metal alkaline substances such as potassium hydroxide, sodium hydroxide, sodium carbonate, and potassium carbonate.

[0044] Spray drying: drying the neutralized solution in a spray drying tower to obtain an intermediate product, which is a mixture of phosphorylcholine chloride metal salt, phosphorylcholine phosphate metal salt and phosphate metal salt;

[0045] Condensation reaction: The intermediate obtained by spray drying is placed in a condensation kettle, 4000 L of ethanol is added as the reaction solvent medium, and R-3-chloro-1,2-propanediol is added dropwise to the reactor. The reaction temperature is 75°C to 85°C, and the reaction is refluxed for 50 to 65 hours. The reaction endpoint is confirmed by thin layer chromatography until L-α-phosphoglycerate choline, metal chloride salt, and metal phosphate salt are generated;

[0046] Crystallization: Cool the concentrated liquid to -0°C to -15°C, crystallize for 6 to 8 hours under stirring, and then centrifuge to obtain crude L-α-glycerophosphorylcholine;

[0047] Redissolution and decolorization: The hydrogen chloride gas produced by the esterification reaction can be absorbed by pure water during the redissolution and filtration steps, and can react with calcium carbonate, calcium oxide, or calcium hydroxide to produce a calcium chloride aqueous solution;

[0048] The present invention breaks through the traditional multi-step complex synthesis path of "esterification reaction to generate phosphorylcholine chloride → synthesis and purification to produce phosphorylcholine chloride calcium salt → synthesis and purification to produce phosphorylcholine chloride potassium salt → synthesis of L-α-phosphocholine", and realizes "esterification reaction to generate phosphorylcholine chloride → synthesis of phosphorylcholine chloride alkali metal salt → synthesis of L-α-phosphocholine", effectively simplifying the production process.

[0049] More specifically: first, there is no need to synthesize pure phosphorylcholine chloride potassium salt, and L-α-phosphoglycerate choline can be directly synthesized from crude phosphorylcholine chloride alkali metal salt; second, a large number of process steps of first synthesizing crude phosphorylcholine chloride calcium salt, then filtering and separating calcium phosphate, ceramic filtration, concentration, crystallization, filtering and separating crystals, drying, and pulverizing to obtain pure phosphorylcholine chloride calcium salt are omitted; third, a large number of steps of synthesizing and purifying pure phosphorylcholine chloride potassium salt from pure phosphorylcholine chloride calcium salt are omitted, such as "chlorination" Phosphorylcholine calcium salt reacts with potassium carbonate or potassium hydroxide to produce a crude product of phosphorylcholine potassium chloride → removes the calcium carbonate by filtration → purifies → dries to obtain a pure product of phosphorylcholine potassium chloride." Fourth, after the esterification reaction, an alkali metal is used to neutralize the product to obtain an aqueous solution of phosphorylcholine alkali metal chloride. A spray drying process is used to quickly and efficiently obtain a crude solid product of phosphorylcholine alkali metal chloride. This technical route is conducive to the direct condensation reaction of the crude solid product of phosphorylcholine metal chloride to synthesize L-α-phosphocholine. In this way, in addition to the subsequent purification step, the process chain is effectively shortened in the synthesis route of L-α-phosphocholine, which is conducive to shortening the process cycle.

[0050] The invention directly synthesizes L-α-glycophosphocholine from crude phosphorylcholine chloride alkali metal salt; the phosphorylcholine chloride alkali metal salt includes any one of phosphorylcholine chloride sodium salt, phosphorylcholine chloride potassium salt and the like.

[0051] Furthermore, determining the reaction endpoint using thin-layer chromatography offers the following advantages: It is simple and quick to operate, and TLC is relatively straightforward, requiring no complex instrumentation. Simply spot the sample on a thin-layer plate, place it in a developing agent, and then develop the color using an appropriate method to visualize the separation of the sample's components. The entire process is typically completed in a relatively short time, significantly improving experimental efficiency. Furthermore, the separation is effective and intuitive, making it easy to compare multiple samples simultaneously, particularly suitable for the simultaneous identification of L-α-phosphoglycerate choline, metal chloride, and metal phosphate required in this process.

[0052] In order to improve the quality of the final product of the preparation method of the present invention, the present invention also makes corresponding designs in the processes of filtration, concentration, resin impurity removal, secondary filtration and concentration, and secondary crystallization, as follows:

[0053] The filtration process specifically includes: separating the insoluble substances phosphate metal salts and chloride metal salts in ethanol in the form of filter cakes through plate filtration, and the separated filter cakes can be sold as by-products; the ethanol solution containing L-α-glycerophosphorylcholine is transferred to the concentration process for corresponding concentration treatment.

[0054] The concentration process specifically includes: concentrating the ethanol solution of L-α-glycerophosphorylcholine under vacuum pressure at a temperature of 80° C. to 95° C.; and distilling for 4 to 6 hours to distill out 3000 L of ethanol.

[0055] The resin impurity removal process specifically includes: removing ionizable impurities in the feed solution through anion and cation exchange resin, with a conductivity of: ≤50μs / cm. Under this conductivity, metal cations in the solution, such as calcium, sodium ions, etc., can be removed to achieve the purpose of separation and purification.

[0056] The secondary filtration and concentration process specifically includes: filtering the filtrate after the resin is impurities removed through a precision filter, and concentrating the filtrate under reduced pressure, controlling the temperature to 90° C. to 98° C., and the maximum concentrated water output to 1850 L to 1950 L.

[0057] The secondary crystallization process specifically includes: transferring the 90°C feed liquid after secondary filtration and concentration to a crystallization kettle, adding 4000-5000L of ethanol, cooling to a range of 8°C to -15°C, and crystallizing for 3-4 hours under stirring.

[0058] The drying process specifically includes adopting vacuum drying at a temperature of 90° C. to 120° C. and drying to a moisture content of ≤1.0%.

[0059] The purity of L-α-glycetocholine can be effectively improved through plate filtration, concentration, crystallization, resin impurity removal, secondary filtration and concentration, and secondary crystallization. In particular, the temperature of the secondary filtration and concentration is higher than that in the filtration and concentration processes, the temperature of the secondary crystallization also shows a step-by-step change compared to the first crystallization, and the stirring time is correspondingly extended. Finally, after vacuum drying, the yield can be controlled to 70-78%, meeting the requirements of industrial production.

[0060] like Figure 2 As shown, considering the problem of heat utilization in the spray drying tower, in order to improve the heat utilization rate, the exhaust gas generated by the spray drying tower provided by the present invention is used to preheat the filtrate to be entered into the spray drying tower. Specifically, the spray drying tower includes a waste pipe 2, and the discharge end of the waste pipe 2 is provided with a preheater 1. The interior of the preheater 1 is provided with a preheating chamber for the filtrate to pass through. The filtrate generated in the filtration step in the preparation process of the present invention is pumped upward into the preheating chamber of the preheater 1. The waste pipe 2 can preheat the filtrate to a certain extent during the process of passing through the preheater 1. The preheated filtrate then flows to the atomizer 4 of the spray drying tower. In this way, heat can be recycled and utilized, and the efficiency of rapid evaporation of the atomized filtrate after contact with hot air can be improved, thereby improving the quality of the intermediate product.

[0061] like Figure 3-Figure 9As shown, in order to improve the atomization and drying performance of the spray drying tower for the filtrate, the spray drying tower provided by the present invention includes a hot air distributor 3 and an atomizer 4 arranged at the top thereof, the hot air distributor 3 includes a hot air duct 31, the end of the hot air duct 31 is spiral and a rotating blade 32 and a fixed blade 33 are arranged on its inner side, the end of the hot air duct 31 is provided with an exhaust port, the exhaust port faces the rotating blade 32, the rotating blade 32 and the fixed blade 33 are staggered up and down, inside and outside, and a hollow bracket is provided at the bottom of the fixed blade 33, the bracket is connected to the bottom surface of the hot air duct 31 by a support rod, and the rotating blade 32 is first grasped and matched with the bracket through the support bushing at its bottom. In this way, the rotating blade 32 can be driven by the hot air to perform continuous rotation relative to the fixed blade 33, and the hot air can flow to the bottom of the atomizer 4 through the uniform distribution of the fixed blade 33 and the rotating blade 32.

[0062] Furthermore, the atomizer 4 is disposed at the spiral center of the hot air duct 31 and includes an outer cone 41 and an inner cone 42. A filtrate feed port 43 is disposed at the top of the outer cone 41, and a rotating member 44 is disposed at the bottom of the inner cone 42. A power source 45 is disposed at the top of the rotating member 44 in transmission connection therewith. Spray holes 46 are disposed on the sides and bottom of the rotating member 44, which spray toward the air outlet side of the hot air distributor 3. The outer cone 41 and the inner cone 42 remain stationary, and the filtrate is continuously pumped from the filtrate feed port 43 into the space between the outer cone 41 and the inner cone 42. The rotating member 44, driven by the power source 45, guides the filtrate at high speed to the spray holes 46. The high-speed centrifugal action of the filtrate and the rapid reduction in the aperture of the spray holes 46 generate spray on both the sides and bottom of the rotating member 44. The spray can fully contact the hot air with a tendency to move, thereby achieving rapid drying. The exhaust gas generated during this process enters the heat recovery path and is discharged separately.

[0063] In order to improve the atomization effect of the rotating member 44 in the atomizer 4, the rotating member 44 provided by the present invention includes a rotating shaft 441, a rotating body 442 is provided on the side of the rotating shaft 441, a plurality of spiral guide blades 443 are provided on the rotating body 442, and a plurality of guide channels 444 corresponding to the guide blades 443 are provided on the rotating body 442. The guide channels 444 are spiral and their side and bottom surfaces are open. The cross-section of the guide channels 444 is trapezoidal and the small bottom end of the trapezoid is distributed on the side of the rotating body 442. An atomizing plate 47 is provided in the guide channel 444. The atomizing plate 47 includes a spiral section 471 and a bottom plate section 472, and the spray holes 46 are distributed on the spiral section 471 and the bottom plate section 472. Among them, the guide blades 443 can make the high-speed rotating filtrate form a continuous water flow toward the guide channel 444. The guide channel 444 uses the spatial distribution characteristics of the centrifugal filtrate to compress the centrifugal filtrate in the centrifugal direction. In particular, the space of the spray holes 46 on the atomizing plate 47 changes sharply compared with the cross-section of the guide channel 444, thereby realizing high-pressure centrifugal atomization. In addition, the spiral section 471 and the bottom plate section 472 have spray holes 46 for controlling the direction and distribution uniformity of the spray. Therefore, this spray drying tower has good atomization performance and drying performance.

[0064] In order to improve the matching performance between the rotating body 442 and the outer cone 41 and the inner cone 42, the rotating body 442 provided by the present invention includes a first-level inverted cone section 4421 that rotates with the bottom of the inner cone 42, and the side of the first-level inverted cone section 4421 is located on the same inverted cone surface as the side of the inner cone 42. The bottom of the first-level inverted cone section 4421 is provided with a second-level inverted cone section 4422 that rotates with the bottom of the outer cone 41, and the side of the second-level inverted cone section 4422 is located on the same inverted cone surface as the side of the outer cone 41. The top surface of the second-level inverted cone section 4422 is a slope, and the top surface of the second-level inverted cone section 4422 and the bottom surface of the first-level inverted cone section 4421 are in a rounded transition. On the one hand, the first-stage inverted cone section 4421 and the inner cone cylinder 42, and the second-stage inverted cone section 4422 and the outer cone cylinder 41 can maintain good rotational sealing. On the other hand, the filtrate can quickly enter the centrifugal path, and the second-stage inverted cone section 4422 has a bevel and rounded transition between it and the first-stage inverted cone section 4421. This design allows the filtrate to more effectively enter different guide channels 444 during the centrifugal process, which is conducive to ensuring the formation of a continuous supply route and ensuring the uniformity and sufficiency of the atomization of the atomizer 4.

[0065] The above description is merely a preferred embodiment of the present invention and does not constitute any other form of limitation to the present invention. Any person skilled in the art may utilize the technical contents disclosed above to change or modify them into equivalent embodiments with equivalent changes for application in other fields. However, any simple modification, equivalent change, and modification of the above embodiments made in accordance with the technical essence of the present invention without departing from the technical solution of the present invention shall still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A method for preparing L-α-glycerocholine, comprising, according to a process route, esterification reaction, condensation reaction, filtration, concentration, crystallization, redissolution and decolorization, resin impurity removal, secondary crystallization, drying and packaging, characterized in that: The steps between the esterification reaction and the condensation reaction include a neutralization reaction and spray drying, and the steps between the resin impurity removal and the secondary crystallization include secondary filtration and concentration. Esterification reaction: Polyphosphoric acid and choline chloride are used for esterification reaction. The feed ratio of polyphosphoric acid to choline chloride is 400kg:320kg~450kg by mass. The optimal reaction temperature range is 120℃~145℃. Neutralization reaction: dilute the reaction product after the esterification reaction with pure water, then add alkali to neutralize it to a pH of 8.5-11.5; after the reaction is complete, add 1.5 times the molar amount of calcium chloride as inorganic phosphate, fully react for 4 hours, and then send the reaction filtrate to the spray drying process; Spray drying: drying the neutralized solution in a spray drying tower to obtain an intermediate product, which is a mixture of phosphorylcholine chloride metal salt, phosphorylcholine phosphate metal salt and phosphate metal salt; Condensation reaction: The intermediate obtained by spray drying is placed in a condensation kettle, 4000 L of ethanol is added as the reaction solvent medium, and R-3-chloro-1,2-propanediol is added dropwise to the reactor. The reaction temperature is 75°C to 85°C, and the reaction is refluxed for 50 to 65 hours. The reaction endpoint is confirmed by thin layer chromatography until L-α-phosphoglycerate choline, metal chloride salt, and metal phosphate salt are generated; Crystallization: The concentrated liquid is cooled to -0°C to -15°C, stirred and crystallized for 6 to 8 hours, and then centrifuged to obtain crude L-α-glycerophosphorylcholine.

2. The method for preparing L-α-glycerocholine according to claim 1, wherein: The filtering process specifically includes: separating the insoluble substances phosphate metal salt and chloride metal salt in ethanol in the form of filter cake by plate filtering; and transferring the ethanol solution containing L-α-glycerophosphocholine to a concentration process.

3. The method for preparing L-α-glycerocholine according to claim 2, wherein: The concentration process specifically includes: concentrating the ethanol solution of L-α-glycerophosphorylcholine under vacuum pressure at a temperature of 80° C. to 95° C.; and distilling for 4 to 6 hours to distill out 3000 L of ethanol.

4. The method for preparing L-α-glycerocholine according to claim 3, wherein: The secondary filtration and concentration process specifically includes: filtering the filtrate after the resin is impurities removed through a precision filter, and concentrating the filtrate under reduced pressure, controlling the temperature to 90° C. to 98° C., and the maximum concentrated water output to 1850 L to 1950 L.

5. The method for preparing L-α-glycerocholine according to claim 4, wherein: The secondary crystallization process specifically includes: transferring the 90°C feed liquid after secondary filtration and concentration to a crystallization kettle, adding 4000-5000L of ethanol, cooling to a range of 8°C to -15°C, and crystallizing for 3-4 hours under stirring.

6. The method for preparing L-α-glycerocholine according to claim 5, wherein: The drying process specifically includes adopting vacuum drying at a temperature of 90° C. to 120° C. and drying to a moisture content of ≤1.0%.

7. The method for preparing L-α-glycerocholine according to claim 1, wherein: The waste gas generated by the spray drying tower is used to preheat the filtrate to be introduced into the spray drying tower. The spray drying tower includes a waste pipe, a preheater is provided at the discharge end of the waste pipe, and a preheating chamber is provided inside the preheater for the filtrate to pass through.

8. The method for preparing L-α-glycerophosphocholine according to claim 1 or 7, wherein: The spray drying tower includes a hot air distributor and an atomizer arranged at the top thereof, the hot air distributor includes a hot air duct, the end of the hot air duct is spiral and is provided with rotating blades and fixed blades on the inner side thereof, the atomizer is arranged at the spiral center of the hot air duct, the atomizer includes an outer cone and an inner cone, the top of the outer cone is provided with a filtrate feed port, the bottom of the inner cone is provided with a rotating member, the top of the rotating member is provided with a power source connected to the rotating member, and the side and bottom of the rotating member are provided with spray holes that spray toward the air outlet side of the hot air distributor.

9. The method for preparing L-α-glycerocholine according to claim 8, wherein: The rotating member includes a rotating shaft, a rotating body is provided on the side of the rotating shaft, a plurality of spiral guide blades are provided on the rotating body, and the rotating body is provided with a plurality of guide channels corresponding to the guide blades one by one. The guide channels are spiral and their side and bottom surfaces are open. The cross-section of the guide channels is trapezoidal and the small bottom end of the trapezoid is distributed on the side of the rotating body. An atomizing plate is provided in the guide channel, and the atomizing plate includes a spiral section and a bottom plate section. The spray holes are distributed on the spiral section and the bottom plate section.

10. The method for preparing L-α-glycerocholine according to claim 9, wherein: The rotating body includes a first-level inverted cone section that rotates with the bottom of the inner cone, and the side surface of the first-level inverted cone section is located on the same inverted cone surface as the side surface of the inner cone. The bottom of the first-level inverted cone section is provided with a second-level inverted cone section that rotates with the bottom of the outer cone, and the side surface of the second-level inverted cone section is located on the same inverted cone surface as the side surface of the outer cone. The top surface of the second-level inverted cone section is an inclined surface, and the top surface of the second-level inverted cone section and the bottom surface of the first-level inverted cone section are in a rounded transition.

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