Preparation method and purification method of medium / long-chain fatty acid triglyceride

Abstract

The invention relates to the technical field of chemical engineering separation, in particular to a preparation method and a corresponding purification method of medium / long-chain fatty acid triglyceride. According to the preparation method of the medium / long-chain fatty acid triglyceride, provided by the invention, the medium / long-chain fatty acid is used as a raw material as well as a catalyst and is subjected to esterification reaction at high temperature. No extra catalyst is added in the reaction, the subsequent purification process is simplified, the synthesis process is efficient, operation is simple, and large-scale production is easy. According to the purification method of the medium / long-chain fatty acid triglyceride, separation of the medium / long-chain fatty acid triglyceride from other by-products with similar structures can be achieved through simple crystallization, and the triglyceride is high in purity and has good industrial potential. The purification method provided by the invention is simple to operate, does not need complex equipment, is low in cost and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the field of chemical engineering separation technology, and in particular to a preparation method and a purification method of medium / long-chain fatty acid triglycerides. Background Art

[0002] Triglycerides are formed by the molecular esterification reaction of three hydroxyl groups of glycerol molecules with three fatty acids, and are the main components of lipids. According to the carbon chain length of the fatty acids on the glycerol skeleton, they are divided into short-chain (C2-C5), medium-chain (C6-C12) and long-chain (C13-C24) fatty acid triglycerides. Among them, medium / long-chain fatty acid triglycerides have a wide range of application values, such as the treatment of fat malabsorption, celiac disease and hyperlipidemia. In addition, medium / long-chain fatty acid triglycerides can be used as stabilizers, emulsifiers and lubricants, and can also be used as raw materials and auxiliary materials for the production of food, pharmaceuticals and cosmetics, and have broad application prospects in the fields of functional food, medicine, daily chemical industry, etc. Natural medium / long-chain fatty acid triglycerides mainly come from animals and plants, with limited supply from the source, and it is difficult to meet the requirements of product purity and other indicators in the pharmaceutical and daily chemical products industries. Therefore, it is necessary to prepare medium / long-chain fatty acid triglycerides through artificial synthesis.

[0003] At present, the synthesis method of medium / long-chain fatty acid triglycerides is mainly the catalytic esterification reaction of medium / long-chain fatty acids and glycerol. The products contain impurities such as monoglycerides, diglycerides and free fatty acids, resulting in low product purity and poor stability. In order to obtain higher purity medium / long-chain fatty acid triglyceride raw materials, the subsequent separation and purification route is crucial. At present, the main purification methods of triglycerides include chromatography, molecular distillation and simulated moving bed chromatography. Among them, chromatography consumes a large amount of organic solvents, and the filling capacity of silica gel columns is limited, which limits the scale-up production of the separation process; molecular distillation has problems such as high distillation temperature, high equipment cost and high parameter requirements; although simulated moving bed chromatography can obtain triglycerides with a purity close to 100%, the simulated moving bed equipment is complex and the investment cost is high. Summary of the invention

[0004] The object of the present invention is to provide a method for preparing and purifying medium / long chain fatty acid triglycerides. The purification method provided by the present invention is simple to operate, does not require complex equipment, has low cost, and is suitable for industrial production.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a method for preparing medium / long chain fatty acid triglycerides, comprising the following steps:

[0007] Glycerol, excess medium / long-chain fatty acids and an alkane solvent are mixed, and no additional catalyst is added. An esterification reaction is carried out under an inert atmosphere and reflux conditions of the alkane solvent to obtain a crude medium / long-chain fatty acid triglyceride product; the temperature of the esterification reaction is 120-200°C.

[0008] Preferably, the alkane solvent includes one or more of C6-C10 straight-chain or branched alkanes;

[0009] The inert atmosphere includes at least one of a nitrogen atmosphere and a rare gas atmosphere.

[0010] Preferably, the esterification reaction time is 2 to 20 hours.

[0011] Preferably, after the esterification reaction is completed, the process further comprises removing the alkane solvent and the generated water in the obtained esterification reaction liquid.

[0012] The present invention provides a method for purifying medium / long-chain fatty acid triglycerides, comprising the following steps: dissolving a crude medium / long-chain fatty acid triglyceride product in a polar organic solvent to obtain a glyceride solution; impurities in the crude medium / long-chain fatty acid triglyceride product include one or more of monoglyceride, diglyceride, medium / long-chain fatty acid and glycerol;

[0013] The glyceride solution is subjected to a primary crystallization to precipitate medium / long chain fatty acid triglycerides, and solid-liquid separation is performed to obtain pure medium / long chain fatty acid triglycerides; the crystallization temperature of the primary crystallization is -10 to 25°C.

[0014] Preferably, the initial temperature of the primary crystallization is 30-70°C.

[0015] Preferably, the polar organic solvent includes one or more of a polar alcohol solvent and acetonitrile.

[0016] Preferably, the concentration of the crude medium / long-chain fatty acid triglyceride product in the glyceride solution is 20 to 200 mg / mL.

[0017] Preferably, after the solid-liquid separation, the obtained solid is dissolved again in a polar organic solvent for secondary crystallization.

[0018] Preferably, the crystallization time of the primary crystallization is 0.5 to 16 hours.

[0019] The present invention provides a method for preparing medium / long-chain fatty acid triglycerides. The present invention does not add a catalyst additionally, uses the medium / long-chain fatty acids themselves as both raw materials and catalysts, and performs an esterification reaction at a high temperature (120-200° C.). Compared with the existing esterification reaction, the catalyst is omitted, and there is no need to separate the catalyst subsequently. The synthesis process is green and efficient, the operation is simple, and it is easy to scale up production.

[0020] In addition, the present invention uses inert gas as protective gas and alkane solvent as medium for reflux reaction, which greatly avoids the formation of oxidation products during the reaction and reduces the generation of impurities.

[0021] The present invention provides a method for purifying medium / long-chain fatty acid triglycerides, which utilizes the fact that the solubility of medium / long-chain fatty acid triglycerides in polar solvents under low temperature conditions is lower than that of impurities, and can separate medium / long-chain fatty acid triglycerides from other byproducts with similar structures through simple crystallization, and the triglycerides have high purity and good industrialization potential. The purification method provided by the present invention is simple to operate, does not require complex equipment, is low in cost, and is suitable for industrial production.

[0022] Furthermore, the present invention further improves the purity of medium / long-chain fatty acid triglycerides through secondary crystallization. When the mass content of medium / long-chain fatty acid triglycerides in the crude medium / long-chain fatty acid triglycerides is above 15%, the purity of the product reaches above 95% after secondary crystallization purification. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The undecanoic acid triglyceride product purified in Example 1 1 H-NMR spectrum;

[0024] Figure 2 The undecanoic acid triglyceride product purified in Example 1 13 C-NMR spectrum;

[0025] Figure 3 The product of 15-hydroxy-1-pentadecanoic acid triglyceride obtained by purification in Example 7 1 H-NMR spectrum;

[0026] Figure 4 The product of 15-hydroxy-1-pentadecanoic acid triglyceride obtained by purification in Example 7 13 C-NMR spectrum. DETAILED DESCRIPTION

[0027] The present invention provides a method for preparing medium / long chain fatty acid triglycerides, comprising the following steps:

[0028] Glycerol, excess medium / long-chain fatty acids and an alkane solvent are mixed, and no additional catalyst is added. An esterification reaction is carried out under an inert atmosphere and reflux conditions of the alkane solvent to obtain a crude medium / long-chain fatty acid triglyceride product; the temperature of the esterification reaction is 120-200°C.

[0029] In the present invention, unless otherwise specified, the raw materials used are commercially available products well known in the art.

[0030] In the present invention, the medium / long-chain fatty acids refer to medium-chain (C6-C12) fatty acids and / or long-chain (C13-C24) fatty acids. The present invention does not make special requirements on the specific types of the medium-chain fatty acids and long-chain fatty acids. The medium-chain fatty acids and long-chain fatty acids well known in the art can be used. Specifically, the medium-chain fatty acids can be undecanoic acid, n-octanoic acid, and lauric acid; the long-chain fatty acids can be tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, and tetracosanoic acid, which are not listed here.

[0031] In the present invention, the medium / long-chain fatty acids are in excess relative to glycerol (that is, the molar ratio of medium / long-chain fatty acids to glycerol is greater than 3). Preferably, the molar ratio of medium / long-chain fatty acids to glycerol is preferably (3.1-6.0):1.

[0032] In the present invention, the medium / long chain fatty acid not only participates in the esterification reaction as a raw material, but also acts as a catalyst to catalyze the esterification reaction.

[0033] In the present invention, the alkane solvent preferably includes one or more of C6-C10 straight-chain or branched alkanes, more preferably one or more of n-hexane, n-octane and n-decane. In the present invention, the amount of the alkane solvent is preferably 4 to 15 times the molar number of the medium / long chain fatty acid.

[0034] In the present invention, the inert atmosphere preferably includes at least one of a nitrogen atmosphere and a rare gas atmosphere; the rare gas preferably includes one or more of helium, neon, argon, krypton and xenon.

[0035] In the present invention, the temperature of the esterification reaction is 120-200°C. In a specific embodiment of the present invention, the temperature of the esterification reaction may be 120°C, 140°C, 160°C, 180°C or 200°C. The time of the esterification reaction is preferably 2-20h. In a specific embodiment of the present invention, the time of the esterification reaction may be 2h, 4h, 6h, 8h, 10h, 12h, 15h, 18h or 20h.

[0036] The present invention generates medium / long-chain fatty acid triglycerides through esterification reaction, accompanied by the generation of a small amount of monoglycerides and diglycerides, and residual unreacted medium / long-chain fatty acids; the monoglycerides, diglycerides and residual unreacted medium / long-chain fatty acids are mixed in the medium / long-chain fatty acid triglycerides as impurities.

[0037] After the esterification reaction is completed, the present invention preferably further comprises removing the alkane solvent and the generated water in the obtained esterification reaction liquid.

[0038] The present invention has no special requirements on the removal method of the alkane solvent and water, and any removal method known in the art may be used, such as rotary evaporation and flash evaporation.

[0039] The present invention does not add any additional catalyst, but uses the medium / long-chain fatty acid itself as both a raw material and a catalyst, and performs an esterification reaction at a high temperature (120-200° C.). Compared with the existing esterification reaction, the catalyst is omitted, and there is no need to separate the catalyst subsequently. The synthesis process is green and efficient, the operation is simple, and it is easy to scale up production.

[0040] In addition, the present invention uses inert gas as protective gas and alkane solvent as medium for reflux reaction, which greatly avoids the formation of oxidation products during the reaction and reduces the generation of impurities.

[0041] In the present invention, the mass content of medium / long-chain fatty acid triglycerides in the crude medium / long-chain fatty acid triglycerides product obtained through the above reaction reaches more than 15%.

[0042] The present invention provides a method for purifying medium / long-chain fatty acid triglycerides, comprising the following steps: dissolving a crude medium / long-chain fatty acid triglyceride product in a polar organic solvent to obtain a glyceride solution;

[0043] The glyceride solution is subjected to a primary crystallization to precipitate medium / long chain fatty acid triglycerides, and solid-liquid separation is performed to obtain pure medium / long chain fatty acid triglycerides; the temperature of the primary crystallization is -10 to 25°C.

[0044] The invention dissolves the crude product of medium / long chain fatty acid triglyceride in a polar organic solvent to obtain a glyceride solution.

[0045] The present invention has no special requirements on the source of the crude medium / long-chain fatty acid triglyceride product. It can be prepared by the preparation method provided by the present invention (see above), or by a conventional catalytic esterification reaction (additional catalyst needs to be added), as long as the impurities in the crude medium / long-chain fatty acid triglyceride product include one or more of monoglyceride, diglyceride, medium / long-chain fatty acid and glycerol.

[0046] In the present invention, the mass content of medium / long-chain fatty acid triglycerides in the crude medium / long-chain fatty acid triglycerides is preferably 15% or more, more preferably 30% or more. When the mass content of medium / long-chain fatty acid triglycerides in the crude medium / long-chain fatty acid triglycerides is lower than 15%, the purity of the purified triglycerides will be lower than 95%.

[0047] In the present invention, the polar organic solvent preferably includes one or more of a polar alcohol solvent and acetonitrile; the polar alcohol solvent preferably includes one or more of methanol, ethanol and isopropanol.

[0048] In the present invention, the concentration of the crude medium / long-chain fatty acid triglyceride product in the glyceride solution is preferably 20 to 200 mg / mL. In a specific embodiment of the present invention, the concentration of the crude medium / long-chain fatty acid triglyceride product in the glyceride solution may be 20 mg / mL, 50 mg / mL, 80 mg / mL, 120 mg / mL, 150 mg / mL, 170 mg / mL or 200 mg / mL.

[0049] After obtaining the glyceride solution, the present invention performs a primary crystallization on the glyceride solution to precipitate medium / long-chain fatty acid triglycerides, and performs solid-liquid separation to obtain pure medium / long-chain fatty acid triglycerides.

[0050] In the present invention, the initial temperature of the primary crystallization is 30-70°C. In a specific embodiment of the present invention, the initial temperature of the primary crystallization may be 30°C, 40°C, 50°C, 60°C or 70°C.

[0051] In the present invention, the cooling rate of the primary crystallization is preferably 2 to 20°C / h. In a specific embodiment of the present invention, the cooling rate of the primary crystallization may be 2°C / h, 5°C / h, 10°C / h, 15°C / h or 20°C / h. In the present invention, the crystallization temperature of the primary crystallization is -10 to 25°C. In a specific embodiment of the present invention, the crystallization temperature of the primary crystallization may be -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C or 25°C.

[0052] In the present invention, the crystallization time of the primary crystallization is preferably 0.5 to 16 h. In a specific embodiment of the present invention, the crystallization time of the primary crystallization can be 0.5 h, 2 h, 5 h, 10 h, 12 h or 16 h.

[0053] At -10 to 25°C, the solubility of impurities such as monoglycerides, diglycerides, medium / long-chain fatty acids and glycerol in polar solvents is higher than that of triglycerides. The present invention utilizes the difference in solubility to crystallize medium / long-chain fatty acid triglycerides.

[0054] The present invention has no special requirements for the solid-liquid separation method, and any solid-liquid separation method known in the art may be used, such as filtration or filter pressing.

[0055] After solid-liquid separation, the present invention preferably dissolves the obtained solid again in a polar organic solvent for secondary crystallization.

[0056] Before being dissolved in the polar organic solvent again, the solid may be washed or not washed in the present invention. When washing is performed, the washing liquid used for washing is preferably a polar organic solvent with a temperature of 0 to 10°C.

[0057] In the present invention, the conditions for the secondary crystallization are the same as those for the primary crystallization and will not be described in detail here.

[0058] After the secondary crystallization, the present invention preferably performs solid-liquid separation, washing and drying on the obtained crystal system to obtain a pure product of medium / long chain fatty acid triglycerides.

[0059] In the present invention, the solid-liquid separation and washing have been discussed above and will not be repeated here.

[0060] The present invention has no special requirements for the drying process, and a drying process well known in the art can be used.

[0061] In the present invention, the purity of the pure medium / long chain fatty acid triglyceride obtained by secondary crystallization reaches more than 97%.

[0062] The preparation method and purification method of the medium / long-chain fatty acid triglyceride provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0063] In the following examples and comparative examples, the high performance liquid chromatography (HPLC) analysis conditions of medium / long chain fatty acid triglyceride are: chromatographic column is C18 column (4.6mm ID×250mm, particle diameter 5μm), column oven 30°C, UV detector, wavelength 205nm, mobile phase is water / acetonitrile / isopropanol, gradient elution is adopted, flow velocity 1.0mL / min. According to the alkyl chain length of triglyceride to be analyzed, the ratio of acetonitrile and isopropanol is slightly adjusted. The shorter the alkyl chain, the higher the acetonitrile ratio, the longer the alkyl chain, the higher the isopropanol ratio, which is a conventional technical means in this area. Table 1 has listed the HPLC gradient elution conditions of pentadecanoic acid triglyceride in Example 7.

[0064] Table 1. HPLC gradient elution conditions of pentadecanoic acid triglyceride (volume percentage)

[0065] Time / min Acetonitrile / % Isopropyl alcohol / % water / % 0 57 38 5 8 57 38 5 10 40 60 0 22 40 60 0 22.01 57 38 5 30 57 38 5

[0066] Example 1

[0067] Undecanoic acid and glycerol were dissolved in n-hexane at a molar ratio of 4:1, and refluxed under a nitrogen atmosphere, with a reaction temperature of 120°C and a reaction time of 6h. After the reaction was completed, the reaction solution was subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product was analyzed by HPLC, and the area normalization method was used to calculate that the product contained 18.36% fatty acids, 3.24% monoglycerides, 12.45% diglycerides, and 65.95% triglycerides (Note: the area percentage can be equivalent to the mass percentage). The undecanoic acid glyceride mixture was dissolved in anhydrous ethanol at 40°C to prepare a 100 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10h for slow crystallization, filtered, and the resulting crystalline product was washed with 4°C anhydrous ethanol, dried, and the HPLC purity of the undecanoic acid triglyceride primary crystallization product obtained by liquid chromatography analysis was 83.54%. The product of the first crystallization was recrystallized again by repeating the above process. The obtained crystal product was filtered, and the solid was washed with 4°C anhydrous ethanol and dried. The HPLC purity of the obtained undecanoic acid triglyceride product was 99.08% (product 1 H-NMR and 13 C-NMR diagrams are Figure 1 and Figure 2 As shown, it is proved to be undecanoic acid triglyceride).

[0068] Example 2

[0069] This embodiment is similar to embodiment 1, except that the molar ratio of undecanoic acid to glycerol is different. The specific implementation method is: undecanoic acid and glycerol are dissolved in n-hexane at a molar ratio of 6:1, and reflux reaction is carried out under a nitrogen atmosphere, the reaction temperature is 120°C, and the reaction time is 6 hours. After the reaction is completed, the reaction solution is subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product is analyzed by high performance liquid chromatography (HPLC), and the area normalization method is used to calculate that the product contains 73.22% fatty acids, 0.15% monoglycerides, 7.45% diglycerides, and 19.18% triglycerides. The undecanoic acid glyceride mixture was dissolved in anhydrous ethanol at 40°C to prepare a 100 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10 hours for slow crystallization, filtered, and the obtained crystalline product was washed with 4°C anhydrous ethanol. The washed crystals were repeated with the above process for secondary recrystallization, the obtained crystalline product was filtered, the solid was washed with 4°C anhydrous ethanol and dried, and the HPLC purity of the undecanoic acid triglyceride product obtained by liquid phase analysis was 95.01%.

[0070] Example 3

[0071] This embodiment is similar to embodiment 1, except that the reaction time is different. The specific implementation method is as follows: undecanoic acid and glycerol are dissolved in n-hexane at a molar ratio of 4:1, and reflux reaction is carried out under a nitrogen atmosphere, the reaction temperature is 120°C, and the reaction time is 12h. After the reaction is completed, the reaction solution is subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product is analyzed by high performance liquid chromatography (HPLC), and the area normalization method is used to calculate that the product contains 15.56% fatty acids, 0.02% monoglycerides, 10.21% diglycerides, and 74.21% triglycerides. The undecanoic acid glyceride mixture was dissolved in anhydrous ethanol at 40°C to prepare a 100 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10 hours for slow crystallization, filtered, and the obtained crystalline product was washed with 4°C anhydrous ethanol. The washed crystals were repeated with the above process for secondary recrystallization, the obtained crystalline product was filtered, the solid was washed with 4°C anhydrous ethanol and dried, and the HPLC purity of the undecanoic acid triglyceride product obtained by liquid phase analysis was 96.46%.

[0072] Example 4

[0073] This embodiment is similar to embodiment 1, except that the reaction temperature is different. The specific implementation method is as follows: undecanoic acid and glycerol are dissolved in n-hexane at a molar ratio of 4:1, and reflux reaction is carried out under a nitrogen atmosphere, the reaction temperature is 180°C, and the reaction time is 6 hours. After the reaction is completed, the reaction solution is subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product is analyzed by high performance liquid chromatography (HPLC), and the area normalization method is used to calculate that the product contains 14.01% fatty acids, 0.24% monoglycerides, 9.08% diglycerides, and 76.67% triglycerides. The undecanoic acid glyceride mixture was dissolved in anhydrous ethanol at 40°C to prepare a 100 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10 hours for slow crystallization, filtered, and the obtained crystalline product was washed with 4°C anhydrous ethanol. The washed crystals were repeated with the above process for secondary recrystallization, the obtained crystalline product was filtered, the solid was washed with 4°C anhydrous ethanol and dried, and the HPLC purity of the undecanoic acid triglyceride product obtained by liquid phase analysis was 96.97%.

[0074] Example 5

[0075] This embodiment is similar to Example 1, except that the inert gas atmosphere is different. The specific implementation method is: undecanoic acid and glycerol are dissolved in n-hexane at a molar ratio of 4:1, and reflux reaction is carried out under a helium atmosphere, the reaction temperature is 120°C, and the reaction time is 6 hours. After the reaction is completed, the reaction solution is rotary evaporated to remove the n-hexane solvent and the water generated by the reaction. The reaction product is analyzed by high performance liquid chromatography (HPLC), and the area normalization method is used to calculate that the product contains 15.22% fatty acids, 1.53% monoglycerides, 9.86% diglycerides, and 73.39% triglycerides. The undecanoic acid glyceride mixture was dissolved in anhydrous ethanol at 40°C to prepare a 100 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10 hours for slow crystallization, filtered, and the obtained crystalline product was washed with 4°C anhydrous ethanol. The washed crystals were repeated with the above process for secondary recrystallization, the obtained crystalline product was filtered, the solid was washed with 4°C anhydrous ethanol and dried, and the HPLC purity of the undecanoic acid triglyceride product obtained by liquid phase analysis was 98.43%.

[0076] Example 6

[0077] This embodiment is similar to embodiment 1, and the main difference is that the crystallization solvent is different. The specific implementation method is: undecanoic acid and glycerol are dissolved in n-hexane at a molar ratio of 4:1, and reflux reaction is carried out under a nitrogen atmosphere, the reaction temperature is 120°C, and the reaction time is 6 hours. After the reaction is completed, the reaction solution is rotary evaporated to remove the n-hexane solvent and the water generated by the reaction. The reaction product is analyzed by HPLC, and the area normalization method is used to calculate that the product contains 18.36% fatty acids, 3.24% monoglycerides, 12.45% diglycerides, and 65.95% triglycerides. The undecanoic acid glyceride mixture was dissolved in acetonitrile at 40°C to prepare a 40 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10 hours for slow crystallization, filtered, and the obtained crystalline product was washed with 4°C acetonitrile. The washed crystals were repeated with the above process for secondary recrystallization, the obtained crystalline product was filtered, the solid was washed with 4°C acetonitrile and dried, and the HPLC purity of the undecanoic acid triglyceride product obtained by liquid phase analysis was 95.01%.

[0078] Example 7

[0079] Dissolve pentadecanoic acid and glycerol in n-hexane at a molar ratio of 3.5:1, and perform reflux reaction under nitrogen atmosphere, the reaction temperature is 180°C, and the reaction time is 14h. After the reaction is completed, the reaction solution is subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product was analyzed by HPLC, and the area normalization method was used to calculate that the product contained 38.52% fatty acids, 1.53% monoglycerides, 9.01% diglycerides, and 50.94% triglycerides. The pentadecanoic acid glyceride mixture was dissolved in 60°C isopropanol to prepare a 100mg / mL solution, cooled to 25°C at a cooling rate of 5°C / h, and then kept warm for 6h for slow crystallization, filtered, and the obtained crystalline product was washed with 0°C isopropanol, and the washed crystals were repeated for secondary recrystallization. The obtained crystalline product was washed with 0°C isopropanol and dried. The HPLC purity of the pentadecanoic acid triglyceride product obtained by liquid phase analysis was 98.5% (product 1 H-NMR and 13 C-NMR diagrams are Figure 3 and Figure 4 As shown, it is proved to be pentadecanoic acid triglyceride).

[0080] Example 8

[0081] Caprylic acid and glycerol were dissolved in n-hexane at a molar ratio of 3.1:1, and refluxed under a nitrogen atmosphere, with a reaction temperature of 120°C and a reaction time of 2h. After the reaction, the reaction solution was subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product was analyzed by HPLC, and the area normalization method was used to calculate that the product contained 21.50% fatty acids, 12.44% monoglycerides, 10.40% diglycerides, and 68.10% triglycerides. The caprylic acid glyceride mixture was dissolved in methanol at 40°C to prepare a 200 mg / mL solution, cooled to 0°C at a cooling rate of 5°C / h, and then kept warm for 3h for slow crystallization, filtered, and the obtained crystalline product was washed with anhydrous ethanol, and the washed crystals were repeated for secondary recrystallization. The obtained crystalline product was washed with methanol and dried, and the HPLC purity of the caprylic acid triglyceride product obtained by liquid phase analysis was 99.04%.

[0082] Example 9

[0083] Dodecanoic acid (lauric acid) and glycerol were dissolved in n-octane at a molar ratio of 5:1, and n-hexane reflux reaction was carried out under nitrogen atmosphere, the reaction temperature was 190°C, and the reaction time was 10h. After the reaction was completed, the reaction solution was subjected to rotary evaporation to remove the n-octane solvent and the water generated by the reaction. Subsequently, HPLC analysis and area normalization method were used to obtain 59.59% fatty acids, 0.14 monoglycerides, 8.21% diglycerides, and 32.06% triglycerides. The undecanoic acid glyceride mixture was dissolved in n-butanol at 50°C to prepare a 20mg / mL lauric acid glyceride solution, cooled to 0°C at a cooling rate of 10°C / h, and then kept warm for 2h for slow crystallization, filtered, and the obtained crystal product was washed with anhydrous ethanol, and the washed crystals were repeated for secondary recrystallization. The obtained crystal product was washed with acetonitrile and dried, and the HPLC purity of the obtained lauric acid triglyceride product was 97.50% by liquid phase analysis.

[0084] Example 10

[0085] The tetradecanoic acid (lignoceric acid) and glycerol were dissolved in n-decane at a molar ratio of 4:1, and the n-decane reflux reaction was carried out under a nitrogen atmosphere, the reaction temperature was 200°C, and the reaction time was 20h. After the reaction was completed, the reaction solution was subjected to rotary evaporation to remove the n-decane solvent and the water generated by the reaction. Subsequently, the product was analyzed by high performance liquid chromatography (HPLC) and the area normalization method was obtained to contain 12.40% fatty acids, no obvious monoglyceride, 12.45% diglyceride, and 65.95% triglyceride. The undecanoic acid glyceride mixture was dissolved in anhydrous n-butanol at 60°C to prepare a 50mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 4.5h for slow crystallization, filtered, and the resulting crystalline product was washed with 7°C anhydrous n-butanol, and the washed crystals were repeated for secondary recrystallization. The obtained crystalline product was filtered, and the solid was washed with 7°C anhydrous n-butanol and dried in vacuo. The HPLC purity of the obtained tetracosyl triglyceride product was 96.63% after liquid phase analysis.

[0086] Embodiment 11

[0087] The myristic acid and glycerol were subjected to n-octane reflux reaction in a nitrogen atmosphere at a molar ratio of 4:1, the reaction temperature was 170°C, and the reaction time was 20h. After the reaction was completed, the reaction solution was subjected to rotary evaporation to remove the n-octane solvent and the water generated by the reaction. Subsequently, the product was analyzed by high performance liquid chromatography (HPLC) and the area normalization method was obtained to contain 11.91% fatty acids, 3.22% monoglycerides, 10.83% diglycerides, and 74.04% triglycerides. The myristic acid glyceride mixture was dissolved in anhydrous ethanol at 55°C to prepare a myristic acid glyceride solution of 110mg / mL, cooled to -5°C at a cooling rate of 20°C / h, and then kept warm for 2h for slow crystallization, filtered, and the obtained crystal product was washed with 0°C anhydrous ethanol, and the washed crystals were repeated for secondary recrystallization. The obtained crystal product was filtered, the solid was washed and dried with 0°C anhydrous ethanol, and the HPLC purity of the obtained myristic acid triglyceride product was 98.79% by liquid phase analysis.

[0088] Comparative Example 1

[0089] This embodiment is similar to Example 1, except that the reaction gas atmosphere is different. The specific implementation method is as follows: undecanoic acid and glycerol are dissolved in n-hexane at a molar ratio of 4:1, and a reflux reaction is carried out in air at a reaction temperature of 120°C and a reaction time of 6 hours. After the reaction is completed, the reaction solution is subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product is analyzed by high performance liquid chromatography (HPLC), and the area normalization method is used to calculate that the product contains 19.32% fatty acids, 2.41% monoglycerides, 10.57% diglycerides, 46.87% triglycerides, and 20.83% other impurities. The undecanoic acid glyceride mixture was dissolved in anhydrous ethanol at 40°C to prepare a 100 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10 hours for slow crystallization, filtered, and the obtained crystalline product was washed with 4°C anhydrous ethanol. The washed crystals were repeated with the above process for secondary recrystallization, the obtained crystalline product was filtered, the solid was washed with 4°C anhydrous ethanol and dried, and the HPLC purity of the undecanoic acid triglyceride product obtained by liquid phase analysis was 82.51%.

[0090] Comparative Example 2

[0091] This embodiment is similar to embodiment 1, except that the reaction time is different. The specific implementation method is as follows: undecanoic acid and glycerol are dissolved in n-hexane at a molar ratio of 4:1, and a reflux reaction is carried out in air at a reaction temperature of 120°C and a reaction time of 0.5h. After the reaction is completed, the reaction solution is subjected to rotary evaporation to remove the n-hexane solvent and the water generated by the reaction. The reaction product is analyzed by high performance liquid chromatography (HPLC), and the area normalization method is used to calculate that the product contains 39.32% fatty acids, 7.69% monoglycerides, 38.77% diglycerides, and 5.78% triglycerides. The undecanoic acid glyceride mixture was dissolved in anhydrous ethanol at 40°C to prepare a 100 mg / mL solution, cooled to 5°C at a cooling rate of 10°C / h, and then kept warm for 10 hours for slow crystallization, filtered, and the obtained crystalline product was washed with 4°C anhydrous ethanol. The washed crystals were repeated with the above process for secondary recrystallization, the obtained crystalline product was filtered, the solid was washed with 4°C anhydrous ethanol and dried, and the HPLC purity of the undecanoic acid triglyceride product obtained by liquid phase analysis was 89.73%.

[0092] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing medium / long chain fatty acid triglycerides, characterized in that: The following steps are involved: Glycerol, excess medium / long-chain fatty acids and an alkane solvent are mixed, and no additional catalyst is added. An esterification reaction is carried out under an inert atmosphere and reflux conditions of the alkane solvent to obtain a crude medium / long-chain fatty acid triglyceride product; the temperature of the esterification reaction is 120-200°C.

2. The preparation method according to claim 1, characterized in that: The alkane solvent includes one or more of C6-C10 straight-chain or branched alkanes; The inert atmosphere includes at least one of a nitrogen atmosphere and a rare gas atmosphere.

3. The preparation method according to claim 1, characterized in that: The esterification reaction time is 2 to 20 hours.

4. The preparation method according to any one of claims 1 to 3, characterized in that: After the esterification reaction is completed, the method further includes removing the alkane solvent and the generated water in the obtained esterification reaction liquid.

5. A method for purifying medium / long chain fatty acid triglycerides, characterized in that: The following steps are involved: Dissolving a crude medium / long-chain fatty acid triglyceride product in a polar organic solvent to obtain a glyceride solution; impurities in the crude medium / long-chain fatty acid triglyceride product include one or more of monoglyceride, diglyceride, medium / long-chain fatty acid and glycerol; The glyceride solution is subjected to a primary crystallization to precipitate medium / long chain fatty acid triglycerides, and solid-liquid separation is performed to obtain pure medium / long chain fatty acid triglycerides; the crystallization temperature of the primary crystallization is -10 to 25°C.

6. The purification method according to claim 5, characterized in that The initial temperature of the primary crystallization is 30-70°C.

7. The purification method according to claim 5, characterized in that The polar organic solvent includes one or more of a polar alcohol solvent and acetonitrile.

8. The purification method according to claim 5 or 7, characterized in that: The concentration of the crude medium / long-chain fatty acid triglyceride product in the glyceride solution is 20 to 200 mg / mL.

9. The purification method according to claim 5, characterized in that After the solid-liquid separation, the obtained solid is dissolved again in a polar organic solvent for secondary crystallization.

10. The purification method according to claim 5 or 6, characterized in that: The crystallization time of the primary crystallization is 0.5 to 16 hours.

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