Continuous preparation method of hydrogenated lecithin based on microreactor

Abstract

The invention belongs to the technical field of pharmaceutical chemicals, and provides a continuous preparation method of hydrogenated lecithin based on a microreactor. The method comprises the following steps: (1) dissolving lecithin in a solvent to obtain a lecithin solution; (2) continuously pumping the lecithin solution into a microreactor filled with a palladium-loaded catalyst, and simultaneously introducing hydrogen to carry out hydrogenation reaction; (3) after the reaction is finished, removing the solvent to obtain hydrogenated lecithin; the solvent is one or more of methanol, ethanol, normal hexane or normal heptane. The microchannel continuous flow technology is matched with the selection of the catalyst and the solvent, so that the lecithin is hydrogenated more thoroughly, and the stability, dispersity and emulsibility of the hydrogenated lecithin are improved; besides, an adopted solvent system is green and safe, reaction conditions are mild, a catalyst does not need to be separated, continuous operation, short reaction time and high production efficiency can be achieved, safety and economy are obviously improved, and the method is suitable for industrial application.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemical industry, and in particular relates to a continuous preparation method of hydrogenated lecithin based on a microreactor. Background Art

[0002] Hydrogenated lecithin is a product obtained by hydrogenating the unsaturated double bonds in the lecithin molecular structure through catalytic hydrogenation using lecithin such as soybean lecithin as raw materials. The hydrogenated lecithin has good chemical stability, dispersibility and emulsification properties, and is widely used in various industries such as food, pharmaceuticals, and cosmetics. Especially in cosmetics, hydrogenated lecithin has strong hydrophilicity and moisturizing properties, and has a strong affinity for the skin and mucous membranes. It can be used in cosmetic formulas to moisturize, emulsify and disperse, and have antioxidant effects. As a surfactant, it can also condition the skin to achieve a good oil-water balance and better absorb nutrients.

[0003] At present, most of the lecithin hydrogenation technologies adopt the kettle hydrogenation method. For example, Chinese invention patent CN103130829B discloses a method for preparing soybean lecithin by hydrogenation catalysis, and its specific process is as follows: soybean lecithin and a certain amount of catalyst are added to a reactor, and a solvent is added to dissolve it. The reactor is sealed and hydrogen is introduced to a certain pressure. The reaction is carried out at a constant temperature in a heat-collecting constant temperature heating magnetic stirrer for a certain time. After the reaction is completed, the product is separated from the catalyst, activated carbon is added for decolorization, filtered, the solvent is removed, and the hydrogenated lecithin product is purified by column chromatography. Chinese invention patent application CN108822146A discloses a method for producing high-purity hydrogenated soybean lecithin, (1) soybean lecithin, a catalyst and a solvent are added to a stainless steel reactor, and the reactor is sealed. Nitrogen is introduced to replace the air in the reactor, and then hydrogen is introduced to replace the nitrogen in the reactor, and finally a certain hydrogen pressure in the reactor is maintained for constant temperature reaction. (2) After the reaction is completed, the product is separated from the catalyst, activated carbon is added for decolorization, the solvent is removed after filtration, and high-purity hydrogenated soybean lecithin is obtained by recrystallization and pulping.

[0004] However, the traditional intermittent kettle hydrogenation method has low safety, and also has disadvantages such as high refrigerant energy consumption and long reaction residence time. In addition, the reactants, hydrogenation catalysts and reaction tail gases in the hydrogenation reaction are all highly explosive. In addition, in order to obtain higher quality hydrogenated lecithin, the above technologies all use activated carbon for decolorization, and the subsequent separation of decolorizers is also involved, which is relatively complicated. Microchannel continuous flow technology has the advantages of controllable reaction conditions and precise control of conditions such as temperature, pressure and flow rate. Microchannel reactors have the characteristics of large specific surface area, short raw material contact time, enhanced mass transfer and effective heat transfer, which can effectively improve conversion rate and selectivity. At present, microchannel continuous flow technology has been applied in many dangerous processes such as highly active reagents and has achieved excellent results. Therefore, the preparation of hydrogenated lecithin using microchannel continuous flow technology is a safe and efficient choice.

[0005] Chinese invention patent application CN119192227A discloses a continuous flow preparation process for hydrogenated lecithin with different phosphatidylcholine contents, which adopts a catalytic hydrogen transfer hydrogenation reaction, does not use exogenous hydrogen, and uses methanol as a hydrogen source. However, when hydrogen transfer occurs, methanol is also a methylation agent, and phosphatidylethanolamine PE is converted into phosphatidylcholine PC through a methylation reaction, which changes the ratio of phosphatidylethanolamine PE and phosphatidylcholine PC in lecithin itself, affecting the effect of hydrogenated lecithin in practical applications. In addition, the reaction temperature of this process is relatively high, which is not conducive to later scale-up and industrial production; the solvent uses a methanol-toluene mixed solvent, in which toluene has a high boiling point and is toxic, and the subsequent concentration and removal of the solvent and the mixed solvent recrystallization process are complicated in post-processing and the yield is relatively low, which is not conducive to scale-up industrial transformation.

[0006] In addition, there are many factors that affect the hydrogenation reaction rate, including the selection of catalysts and solvents, reaction temperature and pressure, etc. Based on this, it is necessary to conduct in-depth research on the process of preparing hydrogenated lecithin using microchannel continuous flow technology, and to systematically study its reaction system including the selection of catalysts and solvents, the regulation of reaction temperature and pressure, etc., to achieve green, safe and efficient preparation of hydrogenated lecithin. Summary of the invention

[0007] In view of the problems existing in the prior art, the present invention provides a continuous preparation method of hydrogenated lecithin based on a microreactor, which realizes catalytic hydrogenation of lecithin through microchannel continuous flow technology, so that the unsaturated double bonds in the molecule are hydrogenated more thoroughly, thereby significantly improving the stability, dispersibility and emulsification of the hydrogenated lecithin product and broadening its application range.

[0008] The purpose of the present invention is achieved through the following technical solutions: The present invention provides a continuous preparation method of hydrogenated lecithin based on a microreactor, comprising the following steps: (1) dissolving lecithin in a solvent to obtain a lecithin solution; (2) continuously pumping the lecithin solution into a microreactor filled with a palladium-loaded catalyst, while introducing hydrogen to carry out a hydrogenation reaction; (3) After the reaction is completed, the solvent is removed to obtain hydrogenated lecithin; The solvent is one or more of methanol, ethanol, n-hexane or n-heptane.

[0009] In the hydrogenated lecithin synthesis system of the present invention, the solvent used has the characteristics of being non-toxic and having a low boiling point, and is easy to separate after the reaction is completed. Moreover, compared with toluene and the like, it is not only safe but also has a better hydrogenation effect.

[0010] Preferably, the lecithin is any one of soybean lecithin, sunflower lecithin and egg yolk lecithin; and the content of phosphatidylcholine in the lecithin is greater than 20 wt%.

[0011] More preferably, the content of phosphatidylcholine in the lecithin is greater than 45 wt %.

[0012] Preferably, the concentration of the lecithin solution is 0.5-10 wt %.

[0013] More preferably, the concentration of the lecithin solution is 2.5-5 wt %.

[0014] Preferably, the volume flow rate ratio of the lecithin solution to hydrogen is 1:1-20.

[0015] More preferably, the volume flow rate ratio of the lecithin solution to hydrogen is 1:3-10.

[0016] Preferably, the carrier of the palladium-supported catalyst is C or γ-Al 2 O 3 .

[0017] More preferably, the carrier of the palladium-supported catalyst is γ-Al 2 O 3 .

[0018] Preferably, the palladium content in the palladium-supported catalyst is 0.5-10 wt%.

[0019] More preferably, the palladium content in the palladium-supported catalyst is 3-6 wt %.

[0020] Further preferably, the palladium content in the palladium-supported catalyst is 5 wt%.

[0021] Preferably, the diameter of the palladium-supported catalyst is 100-1000 μm.

[0022] More preferably, the diameter of the palladium-supported catalyst is 200-500 μm.

[0023] Preferably, the hydrogenation reaction temperature is 50-100°C; the hydrogenation reaction pressure is 1-5 MPa.

[0024] More preferably, the hydrogenation reaction temperature is 65-80°C; the hydrogenation reaction pressure is 1.5-3 MPa.

[0025] Preferably, the continuous preparation method of the present invention further comprises: before the lecithin solution is pumped into the microreactor, hydrogen and solvent are introduced into the equilibrium reaction system to make the microreactor reach the hydrogenation reaction temperature and pressure.

[0026] Compared with the prior art, the present invention has the following beneficial effects: 1. Compared with the traditional intermittent hydrogenation reaction, the present invention adopts microfluidic technology and a fixed bed microreactor with fast reaction heat transfer efficiency, so that the lecithin hydrogenation reaction is more thorough, the product hydrogenated lecithin has high saturation, and the stability, dispersibility and emulsification are greatly improved. In addition, the temperature is relatively mild, which can avoid the deactivation of the catalyst caused by intense heat release, and the safety is higher; at the same time, it can achieve continuous operation, short reaction time and precise controllability, which can reduce excessive hydrogenation and waste of hydrogen, and the yield is as high as 99% or more.

[0027] 2. In addition, the reaction product of the present invention is separated from the catalyst when leaving the reactor, and the catalyst will not be carried out by the reaction liquid, thus overcoming the problem of incomplete separation of the reaction product and the catalyst and great difficulty in recovery.

[0028] 3. The catalytically active component palladium in the metal-supported palladium catalyst of the present invention is mostly present in the form of microcrystals, which can be highly dispersed on the surface of the carrier, and has higher hydrogenation activity; and to a certain extent, it improves thermal stability, extends the service life of the catalyst, and reduces the cost of use; in addition, the solvent used in the present invention is non-toxic, has a low boiling point and is easy to separate, and has a better hydrogenation effect.

[0029] 4. Compared with the traditional intermittent hydrogenation reaction, the preparation of hydrogenated lecithin by the present invention does not change the structure of the natural phospholipids of lecithin, and keeps the proportion of components such as PC and PE in natural lecithin unchanged. Lecithin raw materials with corresponding PC and PE contents can be selected according to the PC and PE content requirements of the desired hydrogenated products. At the same time, only the unsaturated double bonds in the phospholipids are hydrogenated and reduced, so the color is whiter, the odor is lower, and the high-temperature thermal stability is higher.

[0030] 5. The continuous preparation method of the present invention has no scale-up effect and can be rapidly scaled up for production. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are 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.

[0032] 1. The material information used in the specific implementation of the present invention is as follows: Soybean lecithin (phosphatidylcholine PC content 92.1 wt %, phosphatidylethanolamine PE content 0) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd., product number SY-SO-231208; Soybean lecithin (phosphatidylcholine PC content 73.3 wt%, phosphatidylethanolamine PE content 8.7 wt%) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd., catalog number SD-240501; Egg yolk lecithin (phosphatidylcholine PC content 84.1 wt%, phosphatidylethanolamine PE content 7.9 wt%) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd., catalog number SY-EI80-240301; Sunflower lecithin (phosphatidylcholine PC content 71.3 wt%, phosphatidylethanolamine PE content 8.2 wt%) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd., catalog number SK-240301; Pd-γ-Al 2 O 3 Catalyst (Pd content 5 wt %, diameter 300 μm) Catalyst was purchased from Oushisheng (Beijing) Technology Co., Ltd., catalog number S-1103-5; Pd-γ-Al 2 O 3 The catalyst (Pd content 5 wt %, diameter 400 μm) was purchased from Zhejiang Weitong Catalytic New Materials Co., Ltd., catalog number MA00064; Pd-γ-Al 2 O 3 The catalyst (Pd content 2 wt %, diameter 200 μm) was purchased from Oushisheng (Beijing) Technology Co., Ltd., catalog number S-1104-2; Pd-γ-Al 2 O 3 The catalyst (Pd content 1 wt%, diameter 1000 μm) was purchased from Oushisheng (Beijing) Technology Co., Ltd., catalog number S-1100-1; Pd-γ-Al 2 O 3The catalyst (Pd content 0.5 wt %, diameter 100 μm) was purchased from Zhejiang Weitong Catalytic New Materials Co., Ltd., catalog number MA00051; The Pd-C catalyst (Pd content 5 wt%, diameter 400 μm) was purchased from Oushisheng (Beijing) Technology Co., Ltd., item number S-1300-5.

[0033] 2. The device information used in the specific implementation of the present invention is as follows: The microreactor was purchased from Oushisheng (Beijing) Technology Co., Ltd., model H-Flow-S10.

[0034] 3. The performance testing method of hydrogenated lecithin in the specific embodiment of the present invention is as follows: (1) Yield, calculated as follows: Yield = (W 1 / W 2 )×100%; Among them, W 1 is the mass of hydrogenated lecithin actually obtained; W 2 is the theoretical mass of hydrogenated lecithin.

[0035] (2) Iodine value: The iodine value of hydrogenated lecithin was tested in accordance with the national standard GB / T 5532-2022.

[0036] (3) Color: Observe with naked eye.

[0037] (4) PC and PE were detected by high performance liquid chromatography and quantified by external standard method. The specific chromatographic conditions are as follows: Evaporative light scattering detector (drift tube: 72 °C, jet flow rate: 2.0 L / min), chromatographic column: AlltimaSilica, 250 mm × 4.6 mm, 5 μm; Mobile phase: Mobile phase A is methanol-water-glacial acetic acid-triethylamine (volume ratio 85:15:0.45:0.05), and mobile phase B is n-hexane-isopropanol (volume ratio 5:12); The elution procedure is shown in Table 1 below: Table 1 HPLC elution program

[0038] The column temperature was 40°C; The flow rate was 1.0 mL / min.

[0039] Examples 1-8 A continuous preparation method of hydrogenated soybean lecithin based on a microreactor (the reaction conditions of each embodiment are shown in Table 2), the specific operation is as follows: 5 g of spherical Pd-γ-Al 2 O 3 Catalyst, according to the set temperature and pressure, first introduce hydrogen (purity 99.99%) for 10 min, then introduce the solvent for 30 min to balance the reaction system, and stop introducing the solvent after the temperature and pressure of the microreactor are stable; use the solvent to prepare a soybean lecithin (PC content 73.3 wt%, PE content 8.7wt%) solution with the corresponding mass concentration in Table 1, and introduce it into the microreactor at a volume flow rate ratio of 1:10 with hydrogen, and collect the reaction product at the outlet of the microreactor according to the set reaction temperature and pressure. After 2 h, the obtained reaction product is rotary evaporated to remove the solvent to obtain hydrogenated soybean lecithin. The yield, iodine value, color, and PC and PE content of the hydrogenated lecithin prepared in each embodiment are shown in Table 2.

[0040] Table 2 Reaction conditions and results of Examples 1-8

[0041] Example 9 A continuous preparation method of hydrogenated egg yolk lecithin based on a microreactor, the specific operation is as follows: 5 g of spherical Pd-C catalyst (Pd content 5 wt%, diameter 400 μm) was loaded into the microreactor, the temperature was set to 60 ℃, the pressure was set to 2.5 MPa, hydrogen (purity 99.99%) was introduced at a flow rate of 15 mL / min for 10 min, and methanol was introduced at a flow rate of 1 mL / min for 30 min. After the temperature and pressure of the microreactor were stable, the introduction of methanol was stopped. A 5 wt% egg yolk lecithin (PC content 84.1 wt%, PE content 7.9 wt%) solution was prepared with methanol and introduced into the microreactor at a flow rate of 1 mL / min. The reaction products were collected at the outlet of the microreactor. After 2 h, the reaction products were rotary evaporated to remove methanol to obtain white hydrogenated egg yolk lecithin with a yield of 98.6%, an iodine value of 8.9, a PC content of 83.8 wt%, and a PE content of 8.1 wt%.

[0042] Example 10 A continuous preparation method of hydrogenated sunflower lecithin based on a microreactor, the specific operation is as follows: The microreactor was loaded with 5 g of spherical Pd-γ-Al 2 O 3Catalyst (Pd content 5 wt%, diameter 300 μm), set temperature to 70 ℃, pressure to 2 MPa, hydrogen (purity 99.99%) was introduced at a flow rate of 5 mL / min for 10 min, and then methanol was introduced at a flow rate of 1 mL / min for 30 min. After the temperature and pressure of the microreactor were stable, the introduction of methanol was stopped. A 5 wt% sunflower lecithin solution (PC content 71.3 wt%, PE content 8.2wt%) was prepared with methanol and introduced into the microreactor at a flow rate of 1 mL / min. The reaction products were collected at the outlet of the microreactor. After 2 h, the obtained reaction products were rotary evaporated to remove methanol to obtain white hydrogenated sunflower lecithin with a yield of 99.2%, an iodine value of 4.2, a PC content of 71.6 wt%, and a PE content of 8.1wt%.

[0043] Embodiment 11 A continuous preparation method of hydrogenated soybean lecithin based on a microreactor, the specific operation is as follows: The microreactor was loaded with 5 g of spherical Pd-γ-Al 2 O 3 Catalyst (Pd content 5 wt%, diameter 300 μm), set temperature to 80 ℃, pressure to 2 MPa, hydrogen (purity 99.99%) was introduced at a flow rate of 10 mL / min for 10 min, and then methanol was introduced at a flow rate of 1 mL / min for 30 min. After the temperature and pressure of the microreactor were stable, the introduction of methanol was stopped; a 5 wt% soybean lecithin (PC 92.1 wt%, PE content 0) solution was prepared with methanol and introduced into the microreactor at a flow rate of 1 mL / min. The reaction products were collected at the outlet of the microreactor. After 2 h, the reaction products were rotary evaporated to remove methanol to obtain white hydrogenated soybean lecithin with a yield of 98.6%, an iodine value of 2.1, a PC content of 91.7 wt%, and a PE content of 0.

[0044] Example 12 A continuous preparation method of hydrogenated soybean lecithin based on a microreactor, the specific operation is as follows: The microreactor was loaded with 5 g of spherical Pd-γ-Al 2 O 3Catalyst (Pd content 5 wt%, diameter 300 μm), set temperature to 60 ℃, pressure to 2 MPa, hydrogen (purity 99.99%) was introduced at a flow rate of 10 mL / min for 10 min, and then methanol / n-hexane (volume ratio 7 / 3) was introduced at a flow rate of 1 mL / min for 30 min. After the temperature and pressure of the microreactor were stable, the introduction of methanol / n-hexane (volume ratio 7 / 3) was stopped. A 2.5 wt% soybean lecithin (PC content 73.3 wt%, PE content 8.7 wt%) solution was prepared with methanol / n-hexane (volume ratio 7 / 3) and introduced into the microreactor at a flow rate of 1 mL / min. The reaction product was collected at the outlet of the microreactor. After 2 h, the obtained reaction product was rotary evaporated to remove methanol / n-hexane to obtain off-white hydrogenated lecithin with a yield of 97.9%, an iodine value of 9.3, a PC content of 73.2 wt%, and a PE content of 8.8 wt%.

[0045] Comparative Example 1 Example 9 is changed into a method for preparing hydrogenated egg yolk lecithin in an intermittent manner, and the specific operations are as follows: To a 1L high-pressure hydrogenation reactor, 10 g of egg yolk lecithin and 200 mL of methanol were added in sequence. After stirring and dissolving, 5 g of spherical Pd-C catalyst (Pd content 5 wt%, diameter 400 μm) was added. The nitrogen was replaced three times. The reaction temperature was controlled at 60 °C, and hydrogen was slowly introduced until the hydrogen pressure reached 2.5 MPa. The reaction was continued for 6 h. After the reaction was completed, the Pd-C catalyst was filtered out at 60 °C. The filtrate was rotary evaporated to remove methanol to obtain light yellow hydrogenated egg yolk lecithin with a yield of 98.9% and an iodine value of 33.6.

[0046] Comparative Example 2 A continuous preparation method of hydrogenated lecithin based on a microreactor, the specific operation is as follows: On the basis of Example 10, methanol was replaced by methanol / toluene (volume ratio 1 / 1) to obtain light yellow hydrogenated sunflower lecithin, 98.9%, iodine value 24.2, PC content 71.2 wt%, PE content 8.3 wt%.

[0047] Comparative Example 3 A continuous preparation method of hydrogenated lecithin based on a microreactor, the specific operation is as follows: On the basis of Example 12, methanol / n-hexane (volume ratio of 7 / 3) was replaced by methanol / toluene (volume ratio of 7 / 3) to obtain light yellow hydrogenated soybean lecithin with a yield of 97.5%, an iodine value of 19.5, a PC content of 72.9 wt%, and a PE content of 8.1 wt%.

[0048] It can be seen from the above results that the iodination value of hydrogenated lecithin prepared by changing the type of solvent is greater than 10, and the yield of the mixed solvent of methanol and toluene is also reduced in the low-temperature hydrogenation reaction, indicating that the change of solvent will also affect the degree of hydrogenation of lecithin. The continuous hydrogenation process of the present invention makes the lecithin hydrogenated more thoroughly by selecting the solvent.

[0049] In addition, samples were taken from Example 10, Example 12, Comparative Example 2 and Comparative Example 3 at 2, 4, 6 and 8 hours during the continuous hydrogenation process to test their iodide values, and the reaction effects were analyzed. The results are shown in Table 3.

[0050] Table 3 Changes in iodine value of hydrogenated lecithin

[0051] Note: Since the color of Comparative Example 2 and Comparative Example 3 has changed from light yellow to yellow at 4 hours, and the color continues to darken as the reaction time increases, there is no need to test the iodine value later.

[0052] It can be seen from the above results that in the low-temperature continuous hydrogenation reaction of the present invention, the solvent containing toluene will cause the catalyst to be deactivated, thereby affecting the hydrogenation effect.

[0053] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A continuous preparation method of hydrogenated lecithin based on a microreactor, characterized in that: The following steps are involved: (1) dissolving lecithin in a solvent to obtain a lecithin solution; (2) continuously pumping the lecithin solution into a microreactor filled with a palladium-loaded catalyst, while introducing hydrogen to carry out a hydrogenation reaction; (3) After the reaction is completed, the solvent is removed to obtain hydrogenated lecithin; The solvent is one or more of methanol, ethanol, n-hexane or n-heptane.

2. The continuous preparation method according to claim 1, characterized in that The lecithin is any one of soybean lecithin, sunflower lecithin and egg yolk lecithin; the content of phosphatidylcholine in the lecithin is greater than 20 wt%.

3. The continuous preparation method according to claim 2, characterized in that The content of phosphatidylcholine in the lecithin is greater than 45 wt %.

4. The continuous preparation method according to claim 1, characterized in that The concentration of the lecithin solution is 0.5-10 wt %; the volume flow rate ratio of the lecithin solution to hydrogen is 1:1-20.

5. The continuous preparation method according to claim 4, characterized in that The concentration of the lecithin solution is 2.5-5wt%; the volume flow rate ratio of the lecithin solution to hydrogen is 1:3-10.

6. The continuous preparation method according to claim 1, characterized in that: The carrier of the palladium-supported catalyst is C or γ-Al2O3.

7. The continuous preparation method according to claim 1, characterized in that: The palladium content of the palladium-supported catalyst is 0.5-10 wt %; the diameter of the palladium-supported catalyst is 100-1000 μm.

8. The continuous preparation method according to claim 7, characterized in that: The palladium content of the palladium-supported catalyst is 3-6wt%; the diameter of the palladium-supported catalyst is 200-500 μm.

9. The continuous preparation method according to claim 1, characterized in that: The temperature of the hydrogenation reaction is 50-100° C.; the pressure of the hydrogenation reaction is 1-5 MPa.

10. The continuous preparation method according to claim 9, characterized in that The temperature of the hydrogenation reaction is 65-80°C; the pressure of the hydrogenation reaction is 1.5-3 MPa.

Images