Preparation method of distearoyl phosphatidylcholine

Abstract

The invention discloses a preparation method of distearoyl phosphatidylcholine, which comprises the following steps: dropwise adding N, N '-dicyclohexylcarbodiimide into glyceryl phosphatidylcholine and stearic acid at a low temperature under the action of 4-dimethylaminopyridine and a phase transfer catalyst, and reacting to obtain a crude product of distearoyl phosphatidylcholine; in the purification process, filtration is performed firstly, then a solvent is removed from filtrate, the product is purified through mixed solvent pulping and mixed solvent recrystallization, impurities in a crude product are removed, high-purity distearoyl phosphatidylcholine is obtained, raw materials are cheap, reaction conditions are mild, operation is safe, the yield is high, the process is simple, and the method is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of phospholipid synthesis, in particular to a method for preparing distearoylphosphatidylcholine. Background Art

[0002] Phospholipids are a class of lipids containing phosphoric acid, which are widely present in various biological membrane structures. The polar end containing the phosphate group in the phospholipid structure is hydrophilic, and the two longer hydrocarbon chain non-polar ends are lipophilic. This unique amphiphilic structure makes phospholipids tend to be oriented in water, and spontaneously form a double-layer membrane structure driven by hydrophobic effects, becoming the skeleton of biological membranes and regulating the transport of substances and signal transmission inside and outside cells. Phospholipids not only play a key role in living organisms, but are also widely used in the fields of medicine, food and cosmetics, especially in liposome technology. However, because natural phospholipid molecules contain unsaturated fatty acid chains, they are susceptible to oxidation, resulting in a short life and poor stability of liposome materials, limiting their application in certain high-demand pharmaceutical preparations.

[0003] Diethyl phosphatidylcholine (DSPC) is an important class of synthetic phospholipids with two stearic acid groups and one phosphatidylcholine head group. Due to its strong antioxidant capacity and good physical stability, DSPC is widely used in the preparation of liposomes, nano drug carriers and vaccine preparations, especially in long-acting release and targeted drug delivery systems.

[0004] The common method for preparing distearoylphosphatidylcholine in the prior art has multiple, "Total Synthesis of Phosphatidylcholine, Phosphatidylethanolamine and Phosphatidylglycerol" (Chen Guangyou, Northwest University, Master's Degree Thesis, 2006) discloses the synthetic method of distearoylphosphatidylcholine, using glycerol as raw material, successively through reduction, chlorination, condensation, dihydroxyl and monohydroxyl protection and deprotection, acylation, phosphorylation, head group protection, coupling and deprotection steps, prepare distearoylphosphatidylcholine. The method relates to multiple protection and deprotection steps, which not only increases the complexity of the reaction, but also prolongs the reaction time, and may cause the reduction of product yield. In addition, the required multiple reagents and separation and purification steps make the overall cost of the reaction higher, which is unfavorable for industrialized production.

[0005] Ichihara et al. (Chem.Phys.Lipids, 2005,137,94-99) load glycerylphosphatidylcholine on diatomite, then suspend the obtained solid mixture in a suitable organic solvent, add fatty acid and condensing agent, and carry out esterification to obtain difatty acylphosphatidylcholine. This method avoids the drawback of increasing the solubility of glycerylphosphatidylcholine with highly polluted and highly toxic cadmium chloride traditionally. However, when using glass instruments to prepare diatomite-loaded glycerylphosphatidylcholine, the sample easily adheres to the container wall. To avoid the occurrence of this situation, it is necessary to use expensive polytetrafluoroethylene containers, which increases production costs. In addition, the method also relates to the use of solid-phase loading and organic solvents, and the process is complicated and difficult for large-scale production.

[0006] Chinese patent document CN110563758A discloses a method for preparing difatty acylphosphatidylcholine by solid phase reaction, wherein fatty acid is dissolved in an organic solvent, a condensation coupling agent is added, the temperature is raised and refluxed, active esters of fatty acid are prepared, solid phase (preferably alumina) is added to load glycerol phosphatidylcholine, and difatty acylphosphatidylcholine is prepared by continuous reflux; high-activity solid adsorbent is recovered by filtration, mother liquor is desolventized, crude product is pulped with organic solvent and recrystallized to obtain high-purity difatty acylphosphatidylcholine. The yield of this method is only 67%, and the lower yield means that a large amount of raw materials are wasted, which is not conducive to large-scale production. In addition, the method involves multi-step reflux and the use of organic solvents, and the process is relatively complicated and the operation is difficult.

[0007] Chinese patent document CN114014889A discloses a method for synthesizing phosphatidylcholine using a solid phase carrier, in which the phosphatidylcholine is first melted and then uniformly adsorbed with activated carbon, and then acylated with fatty acid chloride, and the resulting product is filtered and recrystallized to obtain high-purity phosphatidylcholine. Activated carbon is used as a solid phase carrier in this method, but the process involves the melting and uniform adsorption of phosphatidylcholine, which may cause fluctuations in product purity. Although the yield is high (85%), the use of activated carbon and the subsequent recrystallization step still increase the complexity and cost of production. In addition, the regeneration and treatment of activated carbon may also bring additional environmental and economic costs.

[0008] In the method of the document "Wang Yubing, Zhu Shanliang, Liu Fei / Synthesis of 1,2-distearoylphosphatidylcholine (2016, 43 (22), 73-74)", stearic acid is used as a raw material to prepare stearic anhydride through condensation of N, N'-dicyclohexylcarbodiimide; lecithin is used as a raw material, and hydrolyzed under the action of tetrabutylammonium hydroxide to obtain glycerophosphatidylcholine, and glycerophosphatidylcholine is then synthesized with stearic anhydride under the catalysis of triethylamine to synthesize 1,2-distearoylphosphatidylcholine. This method requires that stearic acid be first prepared as stearic anhydride, which increases the complexity and time cost of the synthesis process. In addition, stearic anhydride itself may not be stable enough and is easily hydrolyzed or degraded, affecting the subsequent reaction efficiency with glycerophosphatidylcholine. In addition, tetrabutylammonium hydroxide is a relatively strong base, which easily leads to increased corrosiveness of the reaction system, requires higher reactor materials, and may have an adverse effect on the environment. In addition, since the acylation reaction is difficult to complete, the actual yield may be lower than expected, especially when the scale is scaled up.

[0009] In summary, although the preparation methods of distearoylphosphatidylcholine in the prior art have their own advantages, they generally have problems such as complex operation, high cost, low yield, and harsh reaction conditions, and are difficult to meet the requirements of large-scale industrial production. Summary of the invention

[0010] The invention provides a method for preparing distearoylphosphatidylcholine, so as to at least solve one of the defects of the prior art in preparing distearoylphosphatidylcholine, such as complex operation, high cost, low yield and harsh reaction conditions.

[0011] In view of this, the scheme of the present invention is:

[0012] The preparation method of distearoylphosphatidylcholine comprises the following steps:

[0013] S1. N, N'-dicyclohexylcarbodiimide is added dropwise to a mixed system of glycerophosphatidylcholine (GPC), stearic acid, 4-dimethylaminopyridine and a phase transfer catalyst, and the mixture is fully reacted to obtain a crude solution;

[0014] S2. Filter the crude product solution obtained in step S1, and purify the filtrate to obtain distearoylphosphatidylcholine.

[0015] The reaction formula of the preparation method of the distearoylphosphatidylcholine is as follows:

[0016]

[0017] Furthermore, the phase transfer catalyst includes at least one of tetrabutylammonium bromide, tetraethylammonium bromide, benzyltriethylammonium chloride, tetrabutylphosphine bromide, tetramethylammonium chloride, 18-crown-6-polyether, and 15-crown-6-polyether.

[0018] Furthermore, the molar ratio of the glycerophosphatidylcholine, stearic acid, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide is 1:(2-6):(2-6):(2-6).

[0019] Furthermore, the molar ratio of the glycerol phosphatidylcholine to the phase transfer catalyst is 1:(0.05-0.5).

[0020] Furthermore, in step S1, the dropping temperature of the N,N'-dicyclohexylcarbodiimide is 5 to 20°C, and the dropping time is 2 to 6 hours.

[0021] Furthermore, in step S1, the reaction temperature is 20 to 60° C., and the reaction time is 24 to 48 hours.

[0022] Furthermore, in step S1, the solvent used in the mixed system and / or N,N'-dicyclohexylcarbodiimide is chloroform.

[0023] Further, in step S2, the purification step comprises:

[0024] a) removing the solvent from the filtrate;

[0025] b) adding solvent I to the material obtained in step a) and stirring evenly, adding solvent II to slurry, filtering, collecting solids, and drying to obtain a slurry product;

[0026] c) the pulped product is dissolved in solvent I again, filtered, and solvent II is added to the filtrate to precipitate solids, which are filtered, and the filter cake is collected and dried to obtain pure distearoylphosphatidylcholine.

[0027] The solvent I is selected from at least one of methanol, ethanol, isopropanol, tetrahydrofuran, ethyl acetate, butyl acetate, dichloromethane, chloroform, benzene, acetonitrile, DMF and DMSO;

[0028] The solvent II is selected from at least one of cyclohexane, n-hexane, petroleum ether, ethyl ether, acetone, butanone, methyl ethyl ketone, methyl isopropyl ketone, dioxane and methyl tert-butyl ether.

[0029] Preferably, in step c), the dissolution temperature of the pulped product is 30-55°C, and the solid precipitation temperature is 0-40°C.

[0030] Preferably, the content of the pure distearoylphosphatidylcholine is greater than 99%.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] The preparation method of the invention comprises the following steps: glycerol phosphatidylcholine and stearic acid are reacted under the action of 4-dimethylaminopyridine and a phase transfer catalyst, and N,N'-dicyclohexylcarbodiimide is added dropwise at low temperature to obtain distearoyl phosphatidylcholine. The raw materials are cheap, the reaction conditions are mild, the operation is safe, the yield is high, and the method is suitable for industrial production.

[0033] In the purification process of the preparation method of the present invention, the filtrate is firstly desolventized, and the product is purified by mixed solvent beating and mixed solvent recrystallization to remove impurities in the crude product to obtain high-purity distearoylphosphatidylcholine. The process is simple and suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The figure is the hydrogen nuclear magnetic spectrum of distearoylphosphatidylcholine obtained by the preparation method of the present invention.

[0035] Figure 2 The infrared spectrum of distearoylphosphatidylcholine obtained by the preparation method of the present invention.

[0036] Figure 3 The HPLC detection spectrum of distearoylphosphatidylcholine obtained by the preparation method of the present invention is shown. DETAILED DESCRIPTION

[0037] The technical solution of the present invention will be clearly and completely described below in conjunction with the preferred embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] In one embodiment, a method for preparing distearoylphosphatidylcholine is provided, comprising the steps of:

[0039] S1. N, N'-dicyclohexylcarbodiimide is added dropwise to a mixed system of glycerophosphatidylcholine (GPC), stearic acid, 4-dimethylaminopyridine and a phase transfer catalyst, the dropping temperature is 5-20°C, and the dropping time is 2-6 hours; then the mixture is reacted at 20-60°C for 24-48 hours to obtain a crude product solution; the molar ratio of the glycerophosphatidylcholine, stearic acid, 4-dimethylaminopyridine, phase transfer catalyst and N, N'-dicyclohexylcarbodiimide is 1: (2-6): (2-6): (2-6): (0.05-0.5);

[0040] S2. The crude product solution obtained in step S1 is filtered, and the filtrate is purified to obtain distearoylphosphatidylcholine; the purification step comprises:

[0041] a) removing the solvent from the filtrate;

[0042] b) adding solvent I to the material obtained in step a) and stirring evenly, adding solvent II to slurry, filtering, collecting solids, and drying to obtain a slurry product;

[0043] c) dissolving the pulped product in solvent I, filtering, adding solvent II to the filtrate, precipitating solid, filtering, collecting the filter cake, and drying to obtain pure distearoylphosphatidylcholine.

[0044] In the above embodiments, the phase transfer catalyst is selected from at least one of tetrabutylammonium bromide, tetraethylammonium bromide, benzyltriethylammonium chloride, tetrabutylphosphine bromide, tetramethylammonium chloride, 18-crown-6-polyether, and 15-crown-6-polyether.

[0045] In a preferred embodiment, the phase transfer catalyst is tetrabutylammonium bromide, and the molar ratio of glycerophosphatidylcholine to tetrabutylammonium bromide is 1:(0.05-0.5); preferably 1:(0.2-0.5); more preferably 1:(0.4-0.5).

[0046] In the above embodiments, the solvent I is selected from at least one of methanol, ethanol, isopropanol, tetrahydrofuran, ethyl acetate, butyl acetate, dichloromethane, chloroform, benzene, acetonitrile, DMF and DMSO; the solvent II is selected from at least one of cyclohexane, n-hexane, petroleum ether, ether, acetone, butanone, methyl ethyl ketone, methyl isopropyl ketone, dioxane and methyl tert-butyl ether.

[0047] In a preferred embodiment, in step S1, the mixed system and N,N'-dicyclohexylcarbodiimide can be selected from commonly used solvents in the art, such as commonly used chloroform.

[0048] In the above embodiment, the preparation method is to obtain distearoylphosphatidylcholine by reacting glycerol phosphatidylcholine and stearic acid in 4-dimethylaminopyridine under the action of a phase transfer catalyst, by dropwise adding N,N'-dicyclohexylcarbodiimide, with cheap raw materials, mild reaction conditions, safe operation, and high yield, which can reach more than 90%; in the purification process, the filtrate is first desolventized, and the product is purified by mixed solvent beating and mixed solvent recrystallization to remove impurities in the crude product, so as to obtain distearoylphosphatidylcholine with a content greater than 99%.

[0049] In some preparation examples, an appropriate amount of the obtained distearoylphosphatidylcholine sample was taken, dissolved in CDCl3, and subjected to nuclear magnetic resonance hydrogen spectrum measurement. The nuclear magnetic hydrogen spectrum is shown in Figure 1 , the results are shown in Table 1.

[0050] Table 1: Summary of H NMR spectrum analysis data of distearoylphosphatidylcholine samples

[0051] serial number Actual displacement structure Theoretical hydrogen number A 0.85~0.88(t,6H) <![CDATA[CH3,-C]]> 6 B 1.24(m,56H) <![CDATA[CH2,-C / -C]]> 56 C 1.56(br,4H) <![CDATA[CH2,-C / -C]]> 4 D 2.24~2.29(m,4H) <![CDATA[CH2,-C(=O)O-C / -C]]> 4 E 3.35(s,9H) <![CDATA[CH3,-Np(C)(C)C]]> 9 F 3.79(m,2H) <![CDATA[CH2,-Np(C) / C-O-P(=O)]]> 2 G 3.89~3.92(m,2H) <![CDATA[CH2,-O-P(=O)(O) / -C-O-C(=O)]]> 2 H 4.11~4.13(dd,1H) <![CDATA[CH2,-C-Np(C)C / -O-P(=O)(O)]]> 1 I 4.25~4.27(br,2H) <![CDATA[CH2,-O-P(=O)(O)(O) / -C-O-C(=O)]]> 2 J 4.37~4.39(dd,1H) <![CDATA[CH2,-C-Np(C)C / -O-P(=O)(O)]]> 1 K 5.15~5.20(m,1H) CH,-COP(=O) / -COC(=O) / -OC(=O) 1

[0052] Take an appropriate amount of the obtained distearoylphosphatidylcholine sample, and use the Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0402, potassium bromide tablet method to determine the infrared spectrum of the sample. The infrared detection diagram is shown in Figure 2 The results are shown in Table 2.

[0053] Table 2: Infrared spectrum analysis of distearoylphosphatidylcholine sample

[0054] <![CDATA[Wavenumber (cm -1 )]]> Characteristic Group Vibration Type 2955.83 <![CDATA[—CH3]]> Asymmetric stretching vibration 2917.42 <![CDATA[—CH2—]]> Asymmetric stretching vibration 2849.72 <![CDATA[—CH2—]]> Symmetrical stretching vibration 1727.48 C=O Stretching vibration 1469.87 <![CDATA[—CH2—]]> Bending vibration 1261.96 C—O—C Asymmetric stretching vibration 1094.86、1078.12、1053.95 C—O or P—O Stretching vibration 966.73 C—O—C Bending vibration

[0055] The obtained distearoylphosphatidylcholine was analyzed. Octadecyl bonded silica gel was used as a filler (chromatographic column 150 mm × 4.6 mm, 3.5 μm), 0.5% triethylamine acetate buffered aqueous solution was used as mobile phase A (triethylamine acetate buffer: 15% triethylamine aqueous solution, pH value adjusted to about 5.5 with acetic acid), 0.5% triethylamine acetate buffered ethanol solution was used as mobile phase B; gradient elution was performed according to Table 3; column temperature was 50°C; flow rate was 0.4 ml per minute; injection volume was 5 μl; the detector was an electrospray detector, the nebulizer temperature was 50°C, filtering: 3.6s; frequency was 5 Hz, and the chromatogram obtained under these conditions was as follows Figure 3 As shown, through Figure 3 It can be seen that the purity of distearoylphosphatidylcholine prepared by the method described in the example is >99%.

[0056] Table 3: Mobile phase gradient for HPLC detection

[0057] Time (minutes) Mobile phase A (%) Mobile phase B (%) 0 80 20 5 20 80 21 5 95 34 5 95 35 80 20 40 80 20

[0058] The following are preferred implementation examples. If the manufacturer of the reagent or instrument is not specified in the examples, conventional products can be purchased from the market. If the specific conditions are not specified, conventional conditions or conditions recommended by the manufacturer can be used.

[0059] Example 1

[0060] Weigh 50g of glycerophosphatidylcholine, 220g of stearic acid, 95g of 4-dimethylaminopyridine and 29.3g of tetrabutylammonium bromide in a 2000mL three-necked flask, add 1000mL of chloroform, and stir evenly at 10°C. Dissolve 160g of N, N'-dicyclohexylcarbodiimide in 500mL of chloroform, and add dropwise to the reaction system at 10°C within 4 hours. After the addition is complete, heat to 40°C and react for 36 hours. After the reaction is completed, cool, filter, collect the filtrate, and concentrate to dryness to obtain a yellow viscous substance. Add 100mL of dichloromethane to the yellow viscous substance, stir evenly, add 1000mL of acetone to pulp, filter and collect the solid, and dry in vacuo. 1000 mL of dichloromethane was added to the solid, the temperature was raised to 45 ° C, stirred and dissolved, filtered while hot, the filtrate was collected, 1000 mL of methyl tert-butyl ether was added to the filtrate at 45 ° C, and the temperature was slowly reduced to 35 ° C, a large amount of white solid was precipitated, the solid was collected by filtration, and vacuum dried to obtain 142.60 g of white powdered distearoylphosphatidylcholine with a yield of 92.84%. The product was identified as distearoylphosphatidylcholine by nuclear magnetic hydrogen spectrum analysis and infrared detection, and the purity detected by HPLC was 99.5%.

[0061] Example 2

[0062] Weigh 50g of glycerophosphatidylcholine, 115g of stearic acid, 50g of 4-dimethylaminopyridine and 29.3g of tetrabutylammonium bromide in a 2000mL three-necked flask, add 1000mL of chloroform, and stir evenly at 5°C. Dissolve 80g of N, N'-dicyclohexylcarbodiimide in 500mL of chloroform and add dropwise to the reaction system at 5°C within 2 hours. After the addition is complete, heat to 50°C and react for 30 hours. After the reaction is completed, cool, filter, collect the filtrate, and concentrate to dryness to obtain a yellow viscous substance. Add 100mL of DMF to the yellow viscous substance, stir evenly, add 1000mL of petroleum ether to pulp, filter and collect the solid, and dry in vacuo. 1000mL DMF was added to the solid, the temperature was raised to 50°C, stirred and dissolved, filtered while hot, the filtrate was collected, 1000mL methyl isopropyl ketone was added to the filtrate at 50°C, the temperature was slowly lowered to 30°C, a large amount of white solid was precipitated, the solid was collected by filtration, and vacuum dried to obtain 142.54g of white powdery distearoylphosphatidylcholine with a yield of 92.80%. The product was identified as distearoylphosphatidylcholine by nuclear magnetic hydrogen spectrum analysis and infrared detection, and the purity detected by HPLC was 99.4%.

[0063] Example 3

[0064] Weigh 50g of glycerophosphatidylcholine, 275g of stearic acid, 118g of 4-dimethylaminopyridine and 29.3 of tetrabutylammonium bromide in a 2000mL three-necked flask, add 1000mL of chloroform, and stir evenly at 20°C. Dissolve 200g of N, N'-dicyclohexylcarbodiimide in 500mL of chloroform, and add dropwise to the reaction system at 20°C within 6 hours. After the addition is complete, heat to 30°C and react for 45 hours. After the reaction is completed, cool, filter, collect the filtrate, and concentrate to dryness to obtain a yellow viscous substance. Add 100mL of tetrahydrofuran to the yellow viscous substance, stir evenly, add 1000mL of n-hexane for pulping, filter and collect the solid, and dry in vacuo. 1000mL DMSO was added to the solid, the temperature was raised to 35°C, stirred and dissolved, filtered while hot, the filtrate was collected, 1000mL dioxane was added to the filtrate at 35°C, the temperature was slowly lowered to 10°C, a large amount of white solid was precipitated, the solid was collected by filtration, and vacuum dried to obtain 142.69g of white powdery distearoylphosphatidylcholine with a yield of 92.90%. The product was identified as distearoylphosphatidylcholine by nuclear magnetic hydrogen spectrum analysis and infrared detection, and the purity detected by HPLC was 99.6%.

[0065] Example 4

[0066] The effects of different phase transfer catalysts on the yield of distearoylphosphatidylcholine were compared. Other conditions and steps were the same as in Example 1. The results are shown in Table 4.

[0067] Table 4: Comparison of the effects of different phase transfer catalysts

[0068] Phase transfer catalyst Yield (%) Tetrabutylammonium bromide 92.84 Tetraethylammonium bromide 89.11 Benzyltriethylammonium chloride 85.83 Tetrabutylphosphonium bromide 87.97 Tetramethylammonium chloride 90.07 18-Crown-6-polyether 85.69 15-Crown-6-polyether 86.56

[0069] Example 5

[0070] The effects of different amounts of phase transfer catalyst tetrabutylammonium bromide (TBAB) on the yield and content of distearoylphosphatidylcholine were compared. Other conditions and steps were the same as in Example 1. The results are shown in Table 5:

[0071] Table 5: Comparison of the effects of using different amounts of tetrabutylammonium bromide

[0072]

[0073]

[0074] Comparative Example 1

[0075] The difference from Example 1 is that during the reaction of distearoylphosphatidylcholine, N,N'-dicyclohexylcarbodiimide is not added, and the other conditions and steps are the same as those of Example 1. Finally, 66.47 g of white powder is obtained, with a yield of 43.28%.

[0076] Comparative Example 2

[0077] The difference from Example 1 is that N,N'-dicyclohexylcarbodiimide is directly added in the preparation reaction of distearoylphosphatidylcholine, and the other conditions and steps are the same as those in Example 1. Finally, 110.35 g of white powder is obtained, with a yield of 71.85%.

[0078] Comparative Example 3

[0079] The difference from Example 1 is that in the preparation reaction of distearoylphosphatidylcholine, N,N'-dicyclohexylcarbodiimide is added dropwise at 30°C, and the other conditions and steps are the same as those in Example 1. Finally, 122.14 g of white powder is obtained, with a yield of 79.52%.

[0080] Conclusion: It is not difficult to see from the above examples and comparative examples that adding a phase transfer catalyst during the reaction process can significantly improve the reaction conversion rate, especially tetrabutylammonium bromide has the best effect. In addition, it can be seen from the comparative example that the conversion rate can be synergistically improved by dropping N,N'-dicyclohexylcarbodiimide at low temperature.

[0081] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing distearoylphosphatidylcholine, characterized in that the steps include: S1. N, N'-dicyclohexylcarbodiimide is added dropwise to a mixed system of glycerophosphatidylcholine, stearic acid, 4-dimethylaminopyridine and a phase transfer catalyst, and the reaction is sufficient to obtain a crude solution; S2. Filter the crude product solution obtained in step S1, and purify the filtrate to obtain distearoylphosphatidylcholine.

2. The preparation method according to claim 1, characterized in that: The phase transfer catalyst includes at least one of tetrabutylammonium bromide, tetraethylammonium bromide, benzyltriethylammonium chloride, tetrabutylphosphine bromide, tetramethylammonium chloride, 18-crown-6-polyether, and 15-crown-6-polyether.

3. The preparation method according to claim 1, characterized in that: The molar ratio of the glycerol phosphatidylcholine, stearic acid, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide is 1:(2-6):(2-6):(2-6).

4. The preparation method according to claim 1, characterized in that: The molar ratio of the glycerol phosphatidylcholine to the phase transfer catalyst is 1:(0.05-0.5).

5. The preparation method according to claim 1, characterized in that: In step S1, the dropping temperature of the N,N'-dicyclohexylcarbodiimide is 5 to 20°C, and the dropping time is 2 to 6 hours.

6. The preparation method according to claim 1, characterized in that: In step S1, the reaction temperature is 20 to 60° C., and the reaction time is 24 to 48 hours.

7. The preparation method according to claim 1, characterized in that: In step S1, the solvent used in the mixed system and / or N,N'-dicyclohexylcarbodiimide is chloroform.

8. The preparation method according to claim 1, characterized in that: In step S2, the purification step comprises: a) removing the solvent from the filtrate; b) adding solvent I to the material obtained in step a) and stirring evenly, adding solvent II to slurry, filtering, collecting solids, and drying to obtain a slurry product; c) re-dissolving the pulped product in solvent I, filtering, adding solvent II to the filtrate, precipitating solids, filtering, collecting the filter cake, and drying to obtain pure distearoylphosphatidylcholine; The solvent I is selected from at least one of methanol, ethanol, isopropanol, tetrahydrofuran, ethyl acetate, butyl acetate, dichloromethane, chloroform, benzene, acetonitrile, DMF and DMSO; The solvent II is selected from at least one of cyclohexane, n-hexane, petroleum ether, ethyl ether, acetone, butanone, methyl ethyl ketone, methyl isopropyl ketone, dioxane and methyl tert-butyl ether.

9. The preparation method according to claim 8, characterized in that: In step c), the dissolution temperature of the pulped product is 30-55°C, and the solid precipitation temperature is 0-40°C.

10. The preparation method according to claim 8, characterized in that: The content of the pure distearoylphosphatidylcholine is greater than 99%.

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