Methods for extracting cholesterol

Abstract

This invention relates to a method for separating compounds, specifically a method for extracting cholesterol. The method includes the following steps: a) mixing cholesterol-containing raw materials, an alkali source, a catalyst, and a solvent in a first mixture; adding an inorganic salt to the resulting reaction solution for a second mixture; b) adding an extractant to the mixture for continuous extraction, separating and obtaining an extract; c) concentrating the extract to obtain crude cholesterol, and recrystallizing to obtain cholesterol. This invention lowers the saponification reaction energy barrier, promotes the reaction of cholesterol-containing raw materials under milder conditions, does not pollute the environment, and ensures a thorough reaction. The addition of an inorganic salt to the reaction solution, preferably using a continuous extraction column, improves the purity and yield of cholesterol in the extracted layer, resulting in high extraction efficiency, low energy consumption, safe and stable operation, and suitability for industrial production.

Description

Technical Field

[0001] This invention relates to methods for separating compounds, and more specifically to a method for extracting cholesterol. Background Technology

[0002] Cholesterol, also known as cholesterol ester, is a derivative of cyclopentanoperhydrophenanthrene and an essential substance for animal tissue cells, participating in cell membrane formation. Cholesterol is also an important pharmaceutical intermediate, primarily used as a raw material for the production of vitamin D3, bile acids, and steroid hormones. It can also be used as an emulsifier in W / O emulsions in cosmetics and pharmaceutical preparations, an additive in animal feed, and in electronic liquid crystal materials. Because cholesterol contains multiple chiral carbon atoms, its chemical synthesis is difficult. Currently, the main methods for preparing cholesterol are extraction from lanolin and animal brainstem and viscera, which are limited by raw material sources and high costs. Extracting cholesterol from fish oil to achieve efficient resource utilization has attracted considerable attention.

[0003] CN113348160A discloses fish oil cholesterol, but the method requires high-temperature saponification reaction and high-vacuum short-path distillation, resulting in high energy consumption and difficulty in controlling process stability.

[0004] WO2019 / 053744A1 discloses a method for extracting cholesterol from fish oil waste residue. In this method, the fish oil waste residue is saponified with NaOH using 4-dimethylaminopyridine (DMAP) as a catalyst. DMAP is highly toxic and particularly dangerous because it can be absorbed through the skin.

[0005] CN109705184B discloses a continuous method for extracting high-purity cholesterol from fish oil residue. The extractant is a mixed solvent of n-heptane and ethyl acetate. The saponified liquid is countercurrently extracted in a multi-stage series continuous centrifuge to obtain an extract. The extract is then countercurrently washed in a multi-stage series continuous centrifuge with a mixed solvent of water, methanol, and ethanol. The speed of the multi-stage series continuous centrifuge can reach 2100-2800 rpm. The high speed brings safety risks.

[0006] In summary, existing fish oil cholesterol extraction processes are unstable, involve high reaction temperatures, and pose safety hazards, making them unsuitable for industrial production. Therefore, there is a need to find a method that is mild, environmentally friendly, energy-efficient, and capable of efficiently extracting high-purity cholesterol, suitable for industrial production. Summary of the Invention

[0007] The purpose of this invention is to overcome the problems of unstable cholesterol extraction processes, high reaction temperatures, and safety hazards in existing technologies, which are not conducive to industrial production. This invention provides a cholesterol extraction method that features mild reaction conditions, safety and environmental friendliness, low energy consumption, and the ability to efficiently extract high-purity cholesterol, making it suitable for industrial production.

[0008] To achieve the above objectives, the first aspect of the present invention provides a method for extracting cholesterol, the method comprising: a) mixing cholesterol-containing raw materials, an alkaline source, a catalyst and a solvent in a first mixture, and adding an inorganic salt to the obtained reaction solution for a second mixture to obtain a mixed solution; b) adding an extractant to the mixed solution for continuous extraction, and separating to obtain an extract; c) concentrating the extract to obtain crude cholesterol, and recrystallizing to obtain cholesterol.

[0009] A second aspect of the present invention provides a method for extracting cholesterol, the method comprising the following steps:

[0010] a. Mix cholesterol-containing raw materials, alkali source, catalyst and solvent in the first mixture, add inorganic salt to the obtained reaction solution for the second mixture, and obtain a mixed solution;

[0011] b. In a continuous extraction column, the mixture is countercurrently contacted with a mixture of polar and nonpolar organic solvents to perform continuous extraction and separate the extract.

[0012] c. After concentrating the extract to obtain crude cholesterol, mix it with a mixed solvent of C1-C3 organic acids and C1-C4 alcohols, and recrystallize to obtain cholesterol.

[0013] Through the above technical solution, the present invention has the following beneficial effects:

[0014] The method of this invention can reduce the energy barrier of saponification reaction, promote the reaction of cholesterol-containing raw materials under milder conditions, is environmentally friendly, has low energy consumption, is safe and stable in operation, improves the purity and yield of cholesterol in the extraction layer, has high extraction efficiency, and is suitable for industrial production. Attached Figure Description

[0015] Figure 1 This is an extraction column structure and extraction flow chart according to a preferred embodiment of the present invention. Detailed Implementation

[0016] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0017] This invention provides a method for extracting cholesterol, comprising: a) mixing cholesterol-containing raw materials, an alkaline source, a catalyst, and a solvent in a first mixture, and adding an inorganic salt to the resulting reaction solution for a second mixture to obtain a mixed solution; b) adding an extractant to the mixed solution for continuous extraction, and separating to obtain an extract; c) concentrating the extract to obtain crude cholesterol, and recrystallizing to obtain cholesterol.

[0018] The method of the present invention can lower the saponification reaction energy barrier, promote the reaction of cholesterol-containing raw materials under milder conditions, and ensure a thorough reaction. The addition of inorganic salts to the reaction solution in the method of the present invention increases the specific gravity of the reaction solution and reduces extraction and emulsification.

[0019] In this invention, as long as the purpose of this invention can be achieved, there is no particular limitation on the saponification value of the cholesterol-containing raw material. According to a preferred embodiment of this invention, the saponification value of the cholesterol-containing raw material is 80-180 mgKOH / g.

[0020] In this invention, as long as the purpose of this invention can be achieved, there is no particular limitation on the cholesterol content in the cholesterol-containing raw material. According to a preferred embodiment of this invention, the cholesterol content in the cholesterol-containing raw material is 8-12% by mass.

[0021] According to a preferred embodiment of the present invention, the cholesterol-containing raw material is selected from fish oil residue and / or fish oil, preferably fish oil residue.

[0022] In this invention, the range of alkaline sources is relatively wide. According to a preferred embodiment of this invention, the alkaline source is selected from at least one of potassium hydroxide, sodium hydroxide, and lithium hydroxide.

[0023] During the research process, the inventors discovered that the phase transfer catalyst described in step (a) serves to lower the energy barrier of the saponification reaction, promote the reaction under mild conditions, and improve production safety.

[0024] In this invention, the range of catalysts is relatively wide. According to a preferred embodiment of this invention, the catalyst is selected from at least one of tetrabutylammonium chloride, tetrabutylammonium bromide, dodecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, benzyltriethylammonium bromide, and benzyltriethylammonium chloride.

[0025] In this invention, the range of solvents that can be selected is relatively wide. According to a preferred embodiment of this invention, the solvent is selected from at least one of water, methanol, and ethanol.

[0026] In this invention, the addition of inorganic salts to the reaction solution in step (a) increases the specific gravity of the mixture, reduces extraction emulsification, reduces stratification time, and improves product quality and extraction efficiency.

[0027] In this invention, the range of inorganic salts that can be selected is relatively wide. According to a preferred embodiment of this invention, the inorganic salt is selected from at least one of potassium acetate, sodium acetate, sodium sulfate, sodium chloride, potassium chloride, calcium chloride, and lithium chloride.

[0028] In this invention, as long as the purpose of this invention can be achieved, there is no particular limitation on the weight ratio of the cholesterol-containing raw material, solvent and catalyst. According to a preferred embodiment of this invention, the weight ratio of the cholesterol-containing raw material, solvent and catalyst is 1:(0.5-5):(0.01-0.15), preferably 1:(0.5-1):(0.01-0.12).

[0029] In this invention, as long as the purpose of this invention can be achieved, there is no particular limitation on the weight ratio of the reaction solution to the inorganic salt. According to a preferred embodiment of this invention, the weight ratio of the reaction solution to the inorganic salt is 1:(0.05-0.5), preferably 1:(0.05-0.25).

[0030] In this invention, the conditions for the first mixing can be conventional choices in the art. According to a preferred embodiment of the invention, the conditions for the first mixing include: pH value ≥ 11.

[0031] According to a preferred embodiment of the present invention, the conditions for the first mixing include a temperature of 30-100°C, preferably 35-75°C.

[0032] According to a preferred embodiment of the present invention, the conditions for the first mixing include: a time of 1-12 hours, preferably 2-5 hours.

[0033] According to a preferred embodiment of the present invention, the conditions for the second mixing include a temperature of 20-90°C, preferably 30-75°C.

[0034] According to a preferred embodiment of the present invention, the extraction conditions include an extraction temperature of 20-90°C, preferably 30-50°C.

[0035] According to a preferred embodiment of the present invention, the extraction conditions include a stirring speed of 60-90 rpm.

[0036] In this invention, the range of selectable extractants is relatively wide. According to a preferred embodiment of this invention, the extractant is a polar and non-polar mixed system. Because cholesterol has multiple hydrophobic ring structures, a hydroxyl group, and a saturated hydrocarbon chain containing eight carbons, its solubility is poor in individual polar or non-polar solvents, but it has good solubility in mixed solvents, thus improving extraction efficiency.

[0037] According to a preferred embodiment of the present invention, the polar solvent content in the extractant is 5-45% by weight, preferably 15-35% by weight.

[0038] In this invention, the range of nonpolar solvents is relatively wide. According to a preferred embodiment of this invention, the nonpolar solvent is selected from at least one of toluene, xylene, petroleum ether, and C6-C8 alkanes.

[0039] In this invention, the range of polar solvents is relatively wide. According to a preferred embodiment of this invention, the polar solvent is selected from at least one of the monohydric alcohols of C1-C8.

[0040] According to a preferred embodiment of the present invention, the extraction is carried out in a continuous extraction column, in which the extractant and the mixture are subjected to multi-stage countercurrent extraction. The resulting extract is then further separated from impurities in a settling zone, thereby improving the purity and yield of cholesterol in the extract layer. The extraction efficiency is high, the energy consumption is low, and the operation is safe and stable.

[0041] According to a preferred embodiment of the present invention, at least two semi-partitions are staggered along the axial direction of the cavity of the continuous extraction column. The semi-partitions at both ends form two settling zones with the inner wall of the extraction column, and the semi-partitions at both ends form an extraction zone with the inner wall of the extraction column. The continuous extraction column is provided with a mixing device, a temperature control device disposed on the outer wall of the extraction column, and at least one mixed liquid inlet, at least one extractant inlet, at least one extractant outlet, and at least one raffinate outlet.

[0042] According to a preferred embodiment of the present invention, the ratio of the mixed liquid feed volume flow rate to the extractant feed volume flow rate in the continuous extraction column is 1:(3-12), preferably 1:(4-8).

[0043] like Figure 1 The temperature control device is a hot water insulated jacket, which is provided with a hot water inlet and a hot water outlet; the mixing device includes a stirring paddle located inside the extraction column cavity and a drive motor outside the extraction column.

[0044] like Figure 1 The extraction process shown is as follows: circulate hot water to keep warm, start stirring, introduce the mixed liquid into inlet #3, introduce the extractant into inlet #2, exit the residual extract from outlet #1, and overflow the extract from outlet #4.

[0045] use Figure 1The extraction apparatus shown is used for cholesterol extraction. The method includes: a) mixing cholesterol-containing raw materials, an alkaline source, a catalyst, and a solvent in a first mixture, and adding inorganic salts to the resulting reaction solution for a second mixture; b) pumping the mixture into a continuous extraction column through port 3, and pumping the extractant into a continuous extractant column through port 2 for continuous extraction, separating the overflow from port 4 to obtain the extract; c) concentrating the extract to obtain crude cholesterol, and recrystallizing to obtain cholesterol.

[0046] In this invention, there are no particular restrictions on the concentration method. According to a preferred embodiment of the invention, the concentration method is evaporation concentration.

[0047] In this invention, as long as the purpose of this invention can be achieved, there are no special requirements for the recrystallization method. According to a preferred embodiment of this invention, the recrystallization is carried out in a mixed solution of C1-C4 alcohols and C1-C3 organic acids.

[0048] According to a preferred embodiment of the present invention, the content of C1-C4 alcohols in the mixed solution is 20-40% by weight.

[0049] According to a preferred embodiment of the present invention, the organic acids of C1-C3 are formic acid and / or acetic acid.

[0050] According to a preferred embodiment of the present invention, the recrystallization conditions include a weight ratio of the mixed solution to crude cholesterol of (4:12):1.

[0051] According to a preferred embodiment of the present invention, the recrystallization conditions include: mixing the crude cholesterol product with a mixed solution of C1-C4 alcohols and C1-C3 organic acids, heating to 60-65°C, stirring until the solution is clear, cooling to 20-25°C, and allowing cholesterol crystals to precipitate for 3-4 hours, followed by solid-liquid separation, and drying the resulting solid phase at 60-70°C for 5-6 hours.

[0052] This invention provides a method for extracting cholesterol, the method comprising the following steps:

[0053] a. Mix cholesterol-containing raw materials, alkali source, catalyst and solvent in the first mixture, add inorganic salt to the obtained reaction solution for the second mixture, and obtain a mixed solution;

[0054] b. In a continuous extraction column, the mixture is countercurrently contacted with a mixture of polar and nonpolar organic solvents to perform continuous extraction and separate the extract.

[0055] c. After concentrating the extract to obtain crude cholesterol, mix it with a mixed solvent of C1-C3 organic acids and C1-C4 alcohols, and recrystallize to obtain cholesterol.

[0056] The aforementioned optimized scheme can further improve cholesterol extraction efficiency.

[0057] The present invention will be described in detail below through examples. In the following examples, the cholesterol mass percentage was determined according to the high performance liquid chromatography method for cholesterol detection in the National Pharmacopoeia.

[0058] Example 1

[0059] Weigh 10 kg of fish oil residue (cholesterol content 9.5%, saponification value 140 mg KOH / g), add 7.20 kg of 15% sodium hydroxide aqueous solution, add 150 g of phase transfer catalyst tetrabutylammonium chloride, heat to 60℃ and saponification reaction for 3 h. Saponification is complete when the pH value is >11. Add 4.44 kg of 25% sodium chloride aqueous solution and stir well to prepare a mixture. Maintain the mixture at 50℃ for later use.

[0060] A continuous extraction column with a volume of 2L was used, with a jacket containing 50℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1L / h, and the petroleum ether extraction solution containing 18% n-octanol was introduced through inlet #2 at a flow rate of 6L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 1147g of crude cholesterol.

[0061] 5390g of formic acid solution with a mass content of 20% methanol was added to the crude cholesterol and recrystallized to obtain 807g of cholesterol (cholesterol mass content ≥97%).

[0062] Example 2

[0063] Weigh 10 kg of fish oil residue (cholesterol content 8%, saponification value 140 mg KOH / g), add 7.15 kg of 15% sodium hydroxide methanol solution, add 120 g of phase transfer catalyst tetrabutylammonium bromide, heat to 60℃ and saponification reaction for 3 h. Saponification is complete when the pH value is >11. Add 4.33 kg of 25% sodium chloride aqueous solution and stir well to prepare a mixed solution. Maintain the mixed solution at 50℃ for later use.

[0064] A continuous extraction column with a volume of 2L was used, with the jacket containing 50℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1L / h, and the petroleum ether extraction solution containing 18% n-octanol was introduced through inlet #2 at a flow rate of 6L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 965g of crude cholesterol.

[0065] 4850g of butyric acid solution containing 40% n-butanol was added to crude cholesterol and recrystallized to obtain 675g of cholesterol (cholesterol content ≥97%).

[0066] Example 3

[0067] Weigh 10 kg of fish oil residue (cholesterol content 11%, saponification value 140 mg KOH / g), add 7.20 kg of 40% sodium hydroxide aqueous solution, add 100 g of dodecyltrimethylammonium chloride phase transfer catalyst, heat to 60℃ and saponification reaction for 3 h. Saponification is complete when the pH value is >11. Add 3.43 kg of 25% sodium chloride aqueous solution and stir well to prepare a mixture. Maintain the mixture at 50℃ for later use.

[0068] A continuous extraction column with a volume of 2L was used, with the jacket containing 50℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1L / h, and the petroleum ether extraction solution containing 18% n-octanol was introduced through inlet #2 at a flow rate of 6L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 1331g of crude cholesterol.

[0069] Crude cholesterol was recrystallized from 6000g of acetic acid solution containing 20% ​​methanol to obtain 935g of cholesterol (cholesterol content 96.9%).

[0070] Example 4

[0071] Weigh 10 kg of fish oil residue (cholesterol content 9.5%, saponification value 180 mg KOH / g), add 7.50 kg of 20% potassium hydroxide ethanol solution, add 100 g of phase transfer catalyst tetradecyltrimethylammonium bromide, heat to 50℃ and saponify for 4 hours. Saponification is complete when the pH value is >11. Add 6.45 kg of 70% potassium acetate aqueous solution and stir well to prepare a mixture. Maintain the mixture at 40℃ for later use.

[0072] A continuous extraction column with a volume of 2L was used, with the jacket containing 50℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1.5L / h, and the hexane extraction mixture containing 20% ​​n-pentanol was introduced through inlet #2 at a flow rate of 10L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 1135g of crude cholesterol.

[0073] Crude cholesterol was recrystallized by adding 4600g of acetic acid solution with a mass content of 30% ethanol to obtain 798g of cholesterol (cholesterol mass content ≥97%).

[0074] Example 5

[0075] Weigh 10 kg of fish oil residue (cholesterol content 9.5%, saponification value 80 mg KOH / g), add 6.43 kg of 10% lithium hydroxide aqueous solution, add 1000 g of phase transfer catalyst benzyltriethylammonium chloride, heat to 70℃ and saponification reaction for 3 h. Saponification is complete when the pH value is >11. Add 2.52 kg of 40% sodium acetate aqueous solution and stir well to prepare a mixture. Maintain the mixture at 70℃ for later use.

[0076] A continuous extraction column with a volume of 2L was used, with the jacket containing 70℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1L / h, and the n-octane extraction mixture containing 23% n-butanol was introduced through inlet #2 at a flow rate of 7L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 1116g of crude cholesterol.

[0077] 5050g of a propionic acid solution containing 40% isopropanol was added to the crude cholesterol and recrystallized to obtain 774g of cholesterol (cholesterol content ≥97.0%).

[0078] Example 6

[0079] Weigh 10 kg of fish oil residue (cholesterol content 9.5%, saponification value 140 mg KOH / g), add 7.50 kg of 20% potassium hydroxide aqueous solution, add 100 g of phase transfer catalyst benzyltriethylammonium bromide, heat to 90℃ and saponification reaction for 3 h. Saponification is complete when the pH value is >11. Add 2.73 kg of 40% calcium chloride aqueous solution and stir well to prepare a mixed solution. Maintain the mixed solution at 80℃ for later use.

[0080] A continuous extraction column with a volume of 2L was used, with the jacket containing 50℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1L / h, and the heptane extraction solution containing 25% isopropanol was introduced through inlet #2 at a flow rate of 8L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 1130g of crude cholesterol.

[0081] 5600g of butyric acid solution containing 40% n-butanol was added to crude cholesterol and recrystallized to obtain 790g of cholesterol (cholesterol content ≥97%).

[0082] Example 7

[0083] Weigh 10 kg of fish oil residue (cholesterol content 9.5%, saponification value 140 mg KOH / g), add 7.50 kg of 20% potassium hydroxide aqueous solution, add 100 g of phase transfer catalyst dodecyltrimethylammonium bromide, heat to 90℃ and saponify for 3.5 h. Saponification is complete when the pH value is >11. Add 4.00 kg of 30% potassium chloride aqueous solution and stir well to prepare a mixture. Maintain the mixture at 80℃ for later use.

[0084] A continuous extraction column with a volume of 2L was used, with the jacket containing 80℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1L / h, and the toluene extraction mixture containing 30% ethanol was introduced through inlet #2 at a flow rate of 8L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 1129g of crude cholesterol.

[0085] Crude cholesterol was recrystallized from 6000g of acetic acid solution containing 20% ​​methanol to obtain 749g of cholesterol (cholesterol content ≥97.0%).

[0086] Example 8

[0087] Weigh 10 kg of fish oil residue (cholesterol content 9.5%, saponification value 140 mg KOH / g), add 7.50 kg of 20% potassium hydroxide aqueous solution, add 100 g of phase transfer catalyst tetradecyltrimethylammonium chloride, heat to 60℃ and saponify for 5 hours. Saponification is complete when the pH value is >11. Add 1.45 kg of 70% potassium acetate aqueous solution and stir well to prepare a mixture. Maintain the mixture at 50℃ for later use.

[0088] A continuous extraction column with a volume of 2L was used, with the jacket containing 50℃ circulating hot water for insulation. The stirring speed was 60-90 rpm. The mixed solution was introduced through inlet #3 at a flow rate of 1L / h, and the xylene extraction mixture containing 45% methanol was introduced through inlet #2 at a flow rate of 7L / h. The raffinate was discharged through outlet #1, and the extract overflowed through outlet #4. The flow rate of the raffinate at outlet #1 was controlled to ensure no stratification in the upper and lower settling zones. The extract was collected and evaporated to dryness to obtain 1168g of crude cholesterol.

[0089] Crude cholesterol was recrystallized from 8000g of acetic acid solution containing 20% ​​methanol to obtain 813g of cholesterol (cholesterol content 96.5%).

[0090] Comparative Example 1

[0091] Same as Example 1, except that continuous extraction column extraction was not used. Instead, 50 L of a petroleum ether extraction mixture containing 18% n-octanol was used for the first extraction and layering, followed by a second extraction and layering with another 50 L of the extraction mixture, and a third extraction and layering with yet another 50 L of the extraction mixture. The extract was collected and evaporated to dryness to obtain 1123 g of crude cholesterol.

[0092] Crude cholesterol was recrystallized by adding 5270g of a formic acid solution with a mass content of 20% methanol to obtain 790g of cholesterol (cholesterol mass content 96.1%).

[0093] Comparative Example 2

[0094] Same as Example 1, except that after saponification, 3.2 kg of water was added and stirred to prepare a mixture. The extract was collected and evaporated to dryness to obtain 1083 g of crude cholesterol.

[0095] Crude cholesterol was recrystallized by adding 5090g of a formic acid solution with a mass content of 20% methanol to obtain 773g of cholesterol (cholesterol mass content 90.6%).

[0096] Example 9

[0097] Same as Example 1, except that the inlet flow rate at inlet #2 was reduced to 3L / hour. The extract was collected and evaporated to dryness to obtain 1112g of crude cholesterol.

[0098] 5230g of formic acid solution with a mass content of 20% methanol was added to the crude cholesterol and recrystallized to obtain 775g of cholesterol (cholesterol mass content ≥97%).

[0099] Example 10

[0100] Same as Example 1, except that the inlet flow rate at inlet #2 was increased to 12 L / hour. The extract was collected and evaporated to dryness to obtain 1196 g of crude cholesterol.

[0101] Crude cholesterol was recrystallized by adding 4250g of a formic acid solution with a mass content of 20% methanol to obtain 824g of cholesterol (cholesterol mass content 95.3%).

[0102] Comparative Example 3

[0103] Same as Example 1, except that no phase transfer catalyst was added during the saponification reaction. The extract was collected and evaporated to dryness to obtain 1053g of crude cholesterol.

[0104] Crude cholesterol was recrystallized by adding 4900g of a formic acid solution with a methanol content of 20% by mass to obtain 736g of cholesterol (cholesterol content of 81%).

[0105] Example 11

[0106] Same as Example 1, except that the extraction temperature in the continuous extraction column was reduced to 20°C. The extract was collected and evaporated to dryness to obtain 1004g of crude cholesterol.

[0107] Crude cholesterol was recrystallized by adding 4700g of a formic acid solution with a mass content of 20% methanol to obtain 701g of cholesterol (cholesterol mass content ≥97%).

[0108] Example 12

[0109] Same as Example 1, except that the amount of alkali added was changed, the pH value was 10 after the saponification reaction was completed, and the extract was collected and evaporated to dryness to obtain 1081g of crude cholesterol.

[0110] 5080g of formic acid solution with a methanol content of 20% by mass was added to the crude cholesterol and recrystallized to obtain 771g of cholesterol (cholesterol content of 85%).

[0111] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for extracting cholesterol, characterized by, The method comprises the following steps: a. First mixing of cholesterin-containing raw material, alkali source, catalyst and solvent, and then second mixing of the obtained reaction solution with salt to obtain a mixed solution; b. Continuous extraction of the mixed solution with an extractant to obtain an extract solution; c. Concentration of the extract solution to obtain cholesterin crude product, and recrystallization to obtain cholesterin; The continuous extraction is carried out in a continuous extraction column, and at least two half partitions are arranged along the cavity axis in the cavity of the continuous extraction column in a staggered manner, each of the half partitions at both ends forms two static zones with the inner wall of the extraction column, and the half partitions at both ends form an extraction zone with the inner wall of the extraction column; the continuous extraction column is provided with a mixing device, a temperature control device arranged on the outer wall of the extraction column, and at least one mixed solution inlet, at least one extractant inlet, at least one extract solution outlet and at least one raffinate outlet; The conditions of the first mixing include: pH≮11; temperature 30-100℃; The extractant is a mixed system of polar and non-polar, the content of polar solvent in the extractant is 5-45% by weight, the non-polar solvent is selected from at least one of toluene, xylene, petroleum ether and C6-C8 alkane, and the polar solvent is selected from at least one of C1-C8 monohydric alcohol; The catalyst is selected from at least one of tetrabutylammonium chloride, tetrabutylammonium bromide, dodecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, benzyltriethylammonium bromide and benzyltriethylammonium chloride; The salt is selected from at least one of potassium acetate, sodium acetate, sodium sulfate, sodium chloride, potassium chloride, calcium chloride and lithium chloride; The cholesterin-containing raw material is selected from fish oil residue or fish oil; The saponification value of the cholesterin-containing raw material is 80-180 mgKOH / g; The mass percentage of cholesterin in the cholesterin-containing raw material is 8-12%.

2. The extraction method of claim 1, wherein, The cholesterin-containing raw material is fish oil residue.

3. The extraction method according to claim 1, wherein, The solvent is selected from at least one of water, methanol and ethanol; and / or The alkali source is selected from at least one of potassium hydroxide, sodium hydroxide and lithium hydroxide.

4. The extraction method according to claim 1, wherein, The weight ratio of the cholesterin-containing raw material, solvent and catalyst is 1:(0.5-5):(0.01-0.15); and / or The weight ratio of the reaction solution and salt is 1:(0.05-0.5).

5. The extraction method according to claim 4, wherein, The weight ratio of the cholesterin-containing raw material, solvent and catalyst is 1:(0.5-1):(0.01-0.12); and / or The weight ratio of the reaction solution and salt is 1:(0.05-0.25).

6. The extraction method according to claim 1, wherein, The conditions of the first mixing include: time 1-12h; And / or The conditions of the second mixing include: temperature 20-90℃; And / or The conditions of the extraction include: extraction temperature 20-90℃.

7. The extraction method according to claim 6, wherein, The conditions of the first mixing include: temperature is 35-75℃; and / or time is 2-5h; and / or the second mixing conditions include: temperature is 30-75℃; and / or the extraction conditions include: extraction temperature is 30-50℃.

8. The extraction method of claim 1, wherein, the polar solvent content in the extractant is 15-35wt%.

9. The extraction method of claim 1, wherein, the ratio of mixed solution feed volume flow rate to extractant feed volume flow rate is 1:(3-12).

10. The extraction method of claim 9, wherein, the ratio of mixed solution feed volume flow rate to extractant feed volume flow rate is 1:(4-8).

11. The extraction method according to claim 1, wherein, the concentration method is evaporation concentration; and / or the recrystallization is carried out in a mixed solution of C1-C4 alcohol and C1-C3 organic acid.

12. The extraction method according to claim 11, wherein, the C1-C4 alcohol content in the mixed solution is 20-40wt%; and / or the C1-C3 organic acid is formic acid and / or acetic acid; and / or the recrystallization conditions include: the weight ratio of mixed solution to crude cholesterols is (4-12):

1.

13. The extraction method according to any one of claims 1 to 12, wherein, The method includes the following steps: a. First mixing cholesterols-containing raw material, alkali source, catalyst and solvent to obtain a reaction solution, and then second mixing the reaction solution with salt to obtain a mixed solution; b. In a continuous extraction column, the mixed solution is countercurrently contacted with polar and non-polar mixed organic solvent to carry out continuous extraction, and then separated to obtain an extraction solution; c. After the extraction solution is concentrated to obtain crude cholesterols, the crude cholesterols are mixed with a mixed solvent of C1-C3 organic acid and C1-C4 alcohol to carry out recrystallization and obtain cholesterols.

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