A method for extracting cholesterol by reactive extrusion from fish oil residue and co-producing calcium fatty acid

Abstract

The present invention discloses a method for extracting cholesterol by reactive extrusion from fish oil residue and co-producing calcium fatty acid, belonging to the technical field of cholesterol extraction, which comprises the following steps: preheating the feeding section of a screw reactive extrusion integrated machine to 50-80 °C, pumping fish oil residue into the upper opening of the first section of the barrel by a metering pump, feeding calcium oxide or calcium hydroxide and a phase transfer catalyst into the side of the first section of the barrel for saponification reaction, and simultaneously starting a vacuum pumping unit to remove low-boiling substances; extruding the saponified material through a cylindrical die into a homogenizer, adding a lower alcohol for extraction at 60 °C, and centrifuging to separate the liquid and solid phases; drying and pulverizing the solid phase to obtain calcium fatty acid, subjecting the liquid phase to vacuum distillation to recover the solvent, recrystallizing the residue with ethanol-formic acid after a small amount of water washing to obtain cholesterol, collecting the washing water, and removing water by vacuum distillation to obtain crude glycerol. The present invention adopts a solid-liquid phase transfer catalytic continuous reactive extrusion saponification process, which does not require the use of a large amount of flammable solvents and does not produce salty wastewater, and is suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of cholesterol extraction, and particularly relates to a method for reacting and extruding to extract cholesterol from fish oil residue and co-producing calcium fatty acid salt. Background Art

[0002] Cholesterol is an important pharmaceutical intermediate, mainly used in the production of vitamin D2, D3, artificial bezoar, synthetic hormones, anticancer drugs, liquid crystal materials, etc., and can also be used as the molting hormone of shrimp and an additive for aquaculture feed. At present, there are mainly two ways to produce cholesterol: one is to extract it from the brainstem and spinal cord of animals. For example, CN201110050728.1 discloses a method for extracting cholesterol from animal brain dry powder by ultrasonic extraction; the other is to extract it from lanolin. For example, CN111171098B discloses a method for preparing cholesterol from lanolin. The brainstem and spinal cord of cattle and sheep are clearly listed as dangerous raw materials in the "Prohibition on the Use of Raw Materials That May Cause Transmissible Spongiform Encephalopathy" (EU Directive 97 / 534 / EC) and are prohibited from use; the content of impurities such as 24-dehydrocholesterol, 7-dehydrocholesterol, and dihydrocholesterol in cholesterol prepared by lanolin extraction is relatively high, and the purification process is complex, with large investment and high cost.

[0003] Fish oil residue is the residue after extracting fish oil from fatty fish. The main component is glycerol fatty acid ester, containing 4-15% cholesterol. Patent WO2016 / 096989A1 reports that fish oil residue is first saponified with an aqueous solution of NaOH or KOH and then extracted with hydrophobic solvents such as hexane and heptane to obtain cholesterol. This method uses a large amount of flammable solvents and generates a large amount of high-concentration organic wastewater containing salt. Summary of the Invention

[0004] The present invention provides a method for reacting and extruding to extract cholesterol from fish oil residue and co-producing calcium fatty acid salt, which solves the problems in the prior art that a large amount of flammable solvents need to be used and a large amount of high-concentration organic wastewater containing salt is generated when extracting cholesterol from fish oil residue.

[0005] To solve the above technical problems, the technical solution adopted by the present invention is:

[0006] A method for reacting and extruding to extract cholesterol from fish oil residue and co-producing calcium fatty acid salt, comprising the following steps:

[0007] (A) Preheat the feeding section of the screw reaction extrusion machine to 50-80 °C. The liquid material, fish oil residue, is pumped into the upper opening of the first section of the barrel by a metering pump. The solid materials, calcium oxide or calcium hydroxide, and the phase transfer catalyst, are fed and sampled from the side of the first section of the barrel. Control the screw speed at 20-50 rpm to make the materials enter the kneading reaction section and stay for 4-10 min, and carry out the saponification reaction at 130-180 °C. At the same time, turn on the vacuum pumping unit to remove low-boiling substances;

[0008] (B) Control the temperature of the extrusion section at 60 - 100 °C, extrude the saponified material through a cylindrical die into a homogenizer, add a lower alcohol for extraction at 60 °C for 3 - 5 times, and centrifuge to separate the liquid and solid phases.

[0009] (C) Dry and crush the solid phase to obtain calcium fatty acid, distill the liquid phase under reduced pressure to recover the solvent, wash the residue with a small amount of water, and then recrystallize it with ethanol - formic acid to obtain cholesterol. Collect the washing water, and distill off the water under reduced pressure to obtain crude glycerol.

[0010] Among them, in step (A), the screw reaction extrusion machine is a co - rotating twin - screw extruder with a screw length - to - diameter ratio of 44 - 60:1; the dosage of calcium oxide or calcium hydroxide is 1.0 - 1.5 times the amount required according to the saponification value of the fish oil residue; the phase - transfer catalyst is one or more of benzyltriethylammonium chloride, benzyltriethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, tetrabutylammonium bromide, tetramethylammonium hydroxide, betaine, dodecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, and hexadecyltrimethylammonium bromide, and the addition amount of the phase - transfer catalyst is 0.5 - 2% of the weight percentage of the fish oil residue.

[0011] Among them, in step (B), the lower alcohol is one or more of C1 - C4 monohydric alcohols; the weight ratio of the lower alcohol to the saponified material is 1 - 2:1.

[0012] Among them, in step (C), the recrystallization method after washing with water is as follows: the residue after distillation under reduced pressure of the liquid phase is washed with a small amount of water 2 - 3 times, add an ethanol / formic acid mixed solvent 5 - 10 times its mass, heat to the reflux state for 1 - 2 h, and cool and crystallize at 0 - 10 °C to obtain cholesterol; the weight content of ethanol in the ethanol / formic acid mixed solvent is 70 - 90%.

[0013] The technical solution provided by the present invention has the following beneficial effects compared with the prior art:

[0014] 1. The present invention uses the residue from fish oil production as a raw material to extract cholesterol, with by - products of calcium fatty acid and crude glycerol. Calcium fatty acid can be used as a high - energy feed additive for ruminants, realizing the full utilization of fish oil waste liquid.

[0015] 2. The present invention adopts a solid - liquid phase - transfer catalytic continuous reaction extrusion saponification process, which does not require the use of a large amount of flammable solvents and does not produce salty wastewater, and is suitable for industrial production. Brief Description of the Drawings

[0016] Figure 1 It is a process flow chart for the reaction extrusion extraction of cholesterol and co - production of calcium fatty acid from fish oil residue in the present invention. Detailed Embodiments

[0017] The technical solution of the present invention will be clearly and completely described below in conjunction with specific embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0018] Example 1

[0019] This example provides a method for reacting and extruding to extract cholesterol from fish oil residue and co-producing calcium fatty acid. The process flow chart is as Figure 1 shown, including the following steps:

[0020] (1) Preheat the feeding section of the screw reaction extrusion machine (parallel co-rotating twin screws, screw length-diameter ratio 44:1) to 50 °C. Pump 6000 g of fish oil residue (cholesterol content 9.8% determined according to GB5009.128-2016, saponification value swaaa 2.60 mmol KOH / g, viscosity 95 mPa·s) into the first opening of the barrel with a metering pump. Add 30 g of phase transfer catalyst tetrabutylammonium bromide and 580 g of calcium hydroxide at the solid-side feeding inlet. Control the screw speed at 20 rpm to make the material enter the kneading reaction section and stay for 10 min. Carry out saponification reaction at 130 °C, and at the same time, turn on the vacuum unit to remove low-boiling substances.

[0021] (2) Control the temperature of the extrusion section at 60 °C. Extrude the saponified material through a cylindrical die to a homogenizer. Add ethanol at 60 °C, which is 2 times the weight of the saponified material, and extract 5 times. Centrifuge to separate the liquid and solid phases.

[0022] (3) Dry and crush the solid obtained by centrifugal separation to obtain 5408 g of calcium fatty acid, with a crude fat content of 83.0% and a Ca content of 6.52%. Recover the solvent by vacuum distillation of the liquid phase. Wash the residue with a small amount of water 3 times, add a mixed solvent of ethanol-formic acid (weight ratio 7:3) that is 5 times its weight, heat to the reflux state for 1 h, and cool and crystallize at 0 °C to obtain 412 g of cholesterol. Analyze the cholesterol purity by gas chromatography according to the method specified in the 41st edition of the United States Pharmacopoeia, and the purity is 96.0%, and the yield is 67.3%. Collect the washing water, remove water by vacuum distillation to obtain 320 g of crude glycerol, and detect the glycerol content by titration method according to GB / T13216-2008, which is 73.1%.

[0023] Example 2

[0024] This example provides a method for reacting and extruding to extract cholesterol from fish oil residue and co-producing calcium fatty acid, including the following steps:

[0025] (1) Preheat the feeding section of the twin-screw reactive extruder (parallel co-rotating twin-screw, screw length-diameter ratio 60:1) to 80 °C. Pump 6000 g of fish oil residue (cholesterol content 9.8% determined according to GB5009.128-2016, saponification value swaaa 2.60 mmol KOH / g, viscosity 95 mPa·s) into the first opening of the barrel with a metering pump. Add 120 g of phase transfer catalyst trioctylmethylammonium chloride and 870 g of calcium hydroxide through the solid side feeding inlet. Control the screw speed at 50 rpm to make the material enter the kneading reaction section and stay for 4 min. Conduct the saponification reaction at 180 °C, and at the same time, turn on the vacuum extraction unit to remove low-boiling substances.

[0026] (2) Control the temperature of the extrusion section at 100 °C. Extrude the saponified material through a cylindrical die into a homogenizer, add ethanol with a weight 1 time that of the saponified material, and extract 3 times at 60 °C. Centrifuge to separate the liquid and solid phases.

[0027] (3) Dry and crush the solid obtained by centrifugation to obtain 5802 g of calcium fatty acid, with a crude fat content of 75.3% and a Ca content of 8.32%. Recover the solvent by vacuum distillation of the liquid phase. Wash the residue with a small amount of water 2 times, add a mixed solvent of ethanol-formic acid (weight ratio 9:1) with a weight 10 times that of the residue, heat to the reflux state for 1 h, and cool and crystallize at 10 °C to obtain 403 g of cholesterol. Analyze the cholesterol purity by gas chromatography according to the method specified in the 41st edition of the United States Pharmacopoeia, and the purity is 96.2% with a yield of 65.9%. Collect the washing water, remove the water by vacuum distillation to obtain 345 g of crude glycerol, and detect the glycerol content by titration according to GB / T13216-2008, and the glycerol content is 72.4%.

[0028] Example 3-4

[0029] Compared with Example 1, change the type of fish oil residue, and the rest is the same as Example 1. Detect the cholesterol and calcium fatty acid of the obtained products, and the following data are obtained (Table 1).

[0030] Table 1. Influence of fish oil residue type on the reaction

[0031]

[0032] Examples 5-16

[0033] Compared with Example 1, change the type and dosage of the phase transfer catalyst, and the dosages of calcium hydroxide and calcium oxide, and the rest is the same as Example 1. Detect the cholesterol and calcium fatty acid of the obtained products, and the following data are obtained (Table 2).

[0034] Table 2-1. Influence of the ratio of each raw material on the reaction

[0035]

[0036]

[0037] Table 2-2, the influence of each raw material ratio on the reaction

[0038]

[0039] Examples 18-23

[0040] Relative to Example 1, by changing the screw aspect ratio, rotation speed, feeding section, kneading reaction section, extrusion section and other section temperatures of the screw reaction extruder, the residence time of the material in the kneading reaction section is controlled, and the rest is the same as Example 1. The obtained products cholesterol and fatty acid calcium are tested to obtain the following data (Table 3).

[0041] Table 3. Effect of screw aspect ratio and temperature of each section on reaction

[0042]

[0043]

[0044] Examples 24-28

[0045] Compared with Example 1, the amount of the lower alcohol used in step (2) and the number of extractions, and the recrystallization method in step (3) were changed, and the rest were the same as Example 1. The obtained products, cholesterol and fatty acid calcium, were tested and the following data were obtained (Table 4).

[0046] Table 4. Effect of post-treatment on the reaction

[0047]

[0048]

[0049] The above examples are only some specific embodiments of the present invention, and the present invention is not limited to the above examples, and many variations are possible. All variations that can be directly derived or associated with the contents disclosed by a person skilled in the art should be considered as the protection scope of the present invention.

Claims

1. A method for extracting cholesterol by reactive extrusion from fish oil residue and co-producing calcium fatty acid, characterized in that It includes the following steps: (A) Preheat the feeding section of the screw reactive extrusion machine to 50 - 80 °C. The liquid material, fish oil residue liquid, is pumped into the upper opening of the first section of the barrel by a metering pump. The solid materials, calcium oxide or calcium hydroxide, and phase transfer catalyst, are fed into the sample through side feeding of the first section of the barrel. Control the screw rotation speed at 20 - 50 rpm to make the materials enter the kneading reaction section and stay for 4 - 10 min, and carry out saponification reaction at 130 - 180 °C. At the same time, turn on the vacuum pumping unit to remove low-boiling substances; the phase transfer catalyst is one or more of benzyltriethylammonium chloride, benzyltriethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, tetrabutylammonium bromide, tetramethylammonium hydroxide, betaine, dodecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, and hexadecyltrimethylammonium bromide; (B) Control the temperature of the extrusion section at 60 - 100 °C. Extrude the saponified material through a cylindrical die into a homogenizer, add a lower alcohol and extract 3 - 5 times at 60 °C, and centrifuge to separate the liquid and solid phases; the lower alcohol is one or more of C1 - C4 monohydric alcohols; (C) Dry and crush the solid phase to obtain calcium fatty acid. Distill the liquid phase under reduced pressure to recover the solvent. After washing the residue with a small amount of water, recrystallize it with ethanol - formic acid to obtain cholesterol. Collect the washing water, and distill off the water under reduced pressure to obtain crude glycerol.

2. A method for extracting cholesterol by reactive extrusion from fish oil residue and co-producing calcium fatty acid according to claim 1, characterized in that: In step (A), the screw reactive extrusion machine is a co-rotating parallel twin-screw extruder, and the screw length-diameter ratio is 44 - 60:1; the dosage of calcium oxide or calcium hydroxide is 1.0 - 1.5 times the amount required according to the saponification value of the fish oil residue liquid; the addition amount of the phase transfer catalyst is 0.5 - 2% of the weight percentage of the fish oil residue liquid.

3. The method for reacting and extruding to extract cholesterol and co-produce calcium fatty acid from fish oil residue according to claim 1, characterized in that: In step (B), the weight ratio of the lower alcohol to the saponified material is 1 - 2:

1.

4. The method for the reactive extrusion extraction of cholesterol from fish oil residue and co-production of calcium fatty acid according to claim 1, characterized in that: In step (C), the recrystallization method after washing with water is as follows: The residue from the liquid phase distillation under reduced pressure is washed with a small amount of water 2 - 3 times, add an ethanol / formic acid mixed solvent 5 - 10 times its mass, heat to the reflux state for 1 - 2 h, and cool and crystallize at 0 - 10 °C to obtain cholesterol; the weight content of ethanol in the ethanol / formic acid mixed solvent is 70 - 90%.

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