A method for preparing retinyl palmitate by oxidation of beta-carotene

Abstract

This invention discloses a method for preparing canthaxanthin by oxidizing β-carotene. Specifically, a method for preparing canthaxanthin is disclosed, comprising the following steps: oxidizing β-carotene in a solvent at a pH less than 7 in the presence of elemental iodine, alkali metal iodides, hydrogen peroxide, and alkali metal halide to obtain canthaxanthin; wherein the solvent is a mixture of a water-immiscible organic solvent and water. This preparation method has a high yield, which helps reduce production costs and is beneficial for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a method for preparing canthaxanthin by oxidizing β-carotene. Background Technology

[0002] Canthaxanthin, also known as canthaxanthin, is a carotenoid pigment. It is widely used in animal husbandry as a feed additive. Because canthaxanthin can make the meat and eggs of poultry more vibrant, it is generally used in poultry farming. In addition, canthaxanthin can also make the color of fish more vivid and pink, so it is also frequently used in aquaculture.

[0003] There are numerous methods for producing canthaxanthin, including bio-fermentation, chemical synthesis, and natural product extraction. Shandong Wanhua Chemical Group Co., Ltd. disclosed a chemical oxidation method for preparing canthaxanthin in 2022 (CN115073340A), and a photocatalytic oxidation method in February of the same year (CN111423349B). Zhejiang Pharmaceutical Co., Ltd. announced a hydrogen peroxide, sodium chlorate, and potassium iodide oxidation method for preparing canthaxanthin in 2010 (CN101633633A). Kuraray Co., Ltd. of Japan disclosed in 2000 a method for industrial-scale preparation of canthaxanthin by adding iodine halide or iodine to alkali metal chlorates or bromates (CN1277191A).

[0004] Each chemical synthesis method has its own advantages and disadvantages. Photocatalytic oxidation requires cerium dioxide, potassium iodide, and sulfuric acid, making it difficult to remove heavy metals completely. The oxidative coupling process for carotenoid aldehydes is lengthy, and improper control can lead to long-chain byproducts. In contrast, Kuraray's one-step oxidation method for β-carotene has the advantages of a short process route, easy oxidation operation, and the ability to be produced on an industrial scale. Wanhua Chemical Group has also improved its method and developed its own oxidant varieties. Summary of the Invention

[0005] The technical problem this invention aims to solve is to overcome the high cost of existing methods for preparing canthaxanthin, and to provide a method for preparing canthaxanthin by oxidizing β-carotene. This method involves the selective oxidation of β-carotene in the presence of elemental iodine, alkali metal iodides, and hydrogen peroxide, in conjunction with alkali metal halide salts. It achieves high yield, reduces production costs, is simple to operate, and can be implemented on a large scale. Furthermore, this method maximizes the rational utilization of the canthaxanthin mother liquor, making it suitable for industrial production.

[0006] This invention provides a method for preparing canthaxanthin, which includes the following steps: in a solvent, under pH less than 7 conditions, in the presence of elemental iodine, alkali metal iodides, hydrogen peroxide and alkali metal halide, β-carotene is oxidized to prepare canthaxanthin.

[0007] The solvent is a mixture of an organic solvent that is immiscible with water and water.

[0008] In one embodiment of the present invention, the water-immiscible organic solvent is a conventional organic solvent in the art for carrying out such oxidation reactions, preferably a halogenated hydrocarbon solvent, and more preferably one or more of dichloromethane, trichloromethane and carbon tetrachloride.

[0009] In one embodiment of the invention, the amounts of the water-immiscible organic solvent and the water are conventional amounts used in the art for this type of oxidation reaction. The preferred mass ratio of the water-immiscible organic solvent to the water is (2.5–7.5):1, for example, 5:1. The amount of water in the solvent does not include the amount of water used when the components are added in solution form.

[0010] In one embodiment of the present invention, the mass ratio of the water-immiscible organic solvent to the β-carotene is (2.5 to 7.5):1, for example, 5:1.

[0011] In one embodiment of the present invention, the purity of the β-carotene is 96-100%, preferably greater than 98%.

[0012] In one embodiment of the present invention, the β-carotene is preferably β-carotene crystals. The preparation method of the β-carotene crystals includes the following steps: mixing β-carotene and ethanol, heating (e.g., heating to reflux), and cooling to crystallize. The cooling temperature is preferably -20°C.

[0013] In one embodiment of the present invention, the pH is 4 to 5. The pH can be adjusted by adding an acid. The acid is an inorganic acid, preferably one or more of sulfuric acid, hydrochloric acid, and phosphoric acid, more preferably sulfuric acid. The acid is preferably added dropwise.

[0014] In one embodiment of the present invention, the molar ratio of the iodine to the β-carotene is preferably (0.005 to 0.015):1, for example, 0.01:1.

[0015] In one embodiment of the present invention, the alkali metal iodide is sodium iodide or potassium iodide. The molar ratio of the alkali metal iodide to the β-carotene is preferably (0.02-0.06):1, for example, 0.04:1.

[0016] In one embodiment of the present invention, the hydrogen peroxide has a mass fraction of 5-30%. The molar ratio of H2O2 to β-carotene in the hydrogen peroxide is preferably (0.01-0.03):1, for example, 0.02:1.

[0017] In one embodiment of the present invention, the molar ratio of the iodine to the hydrogen peroxide is preferably 1:(1 to 3), for example 1:2.

[0018] In one embodiment of the present invention, the alkali metal halide is sodium hypochlorite, sodium chlorate, or sodium perchlorate. The alkali metal halide is preferably added in the form of an aqueous solution; the mass ratio of the alkali metal halide to water is preferably (0.40–0.55):1, for example, 0.45:1; the molar ratio of the alkali metal halide to β-carotene is preferably (1.8–4.0):1, for example, 2.3:1.

[0019] In one embodiment of the present invention, when the alkali metal halide is sodium chlorate, the molar ratio of sodium chlorate to β-carotene is 2.3:1.

[0020] In one embodiment of the present invention, when the alkali metal halide is sodium hypochlorite, the molar ratio of sodium hypochlorite to β-carotene is 4.0:1.

[0021] In one embodiment of the present invention, when the alkali metal halide is sodium perchlorate, the molar ratio of sodium perchlorate to β-carotene is 1.8:1.

[0022] In one embodiment of the present invention, the reaction temperature of the oxidation reaction is the conventional temperature for carrying out such oxidation reactions in the art, preferably 10 to 80°C, more preferably 30 to 60°C, for example 45 to 50°C.

[0023] In one embodiment of the present invention, the reaction time of the oxidation reaction can be monitored by conventional means in the art (e.g., TLC, HPLC or LC-MS), preferably 2 to 6 hours, more preferably 4 hours.

[0024] In one embodiment of the present invention, the reaction reagents are the aforementioned water-immiscible organic solvent, water, β-carotene, acid, elemental iodine, alkali metal iodide, hydrogen peroxide, and alkali metal halide.

[0025] In one embodiment of the present invention, the method for preparing the canthaxanthin includes the following steps:

[0026] (1) Mixing solution A, water, the acid, iodine, alkali metal iodide and hydrogen peroxide to obtain solution B, wherein solution A is a mixed solution of β-carotene and the organic solvent that is immiscible with water;

[0027] (2) The mixture B is mixed with the aqueous solution of the alkali metal halide and then subjected to an oxidation reaction.

[0028] In one embodiment of the present invention, the method for preparing the canthaxanthin includes the following post-processing: after the reaction solution is separated into layers, the organic phase is washed with water and an aqueous solution of sodium thiosulfate, and then concentrated (preferably dried and then distilled to remove solvent) to obtain crude canthaxanthin. The volume ratio of the water to the aqueous solution of sodium thiosulfate is preferably 1:1. The volume ratio of the total volume of the water and the aqueous solution of sodium thiosulfate to the volume of the reaction solution is preferably 1:1.

[0029] In one embodiment of the present invention, the post-processing further includes the following steps: mixing the crude canthaxanthin with organic solvent A, heating to induce displacement, then adding organic solvent B for crystallization, and filtering to obtain pure canthaxanthin; wherein organic solvent A is an alkane solvent; and organic solvent B is one or more of alcohol solvents, ether solvents, aromatic solvents, and alkane solvents. Preferably, the filtrate obtained from filtration can be repeatedly subjected to displacement and crystallization until canthaxanthin can no longer precipitate.

[0030] The organic solvent A is preferably n-pentane, n-hexane, cyclohexane, or n-heptane, more preferably cyclohexane. The volume-to-mass ratio of the organic solvent A to the β-carotene is preferably 4–8 mL / g, for example, 6 mL / g.

[0031] The heating temperature is preferably 60-100℃, for example 80℃.

[0032] In the organic solvent B, the alcohol solvent is preferably methanol, ethanol, n-propanol, isopropanol, or n-butanol, for example, ethanol, isopropanol, or n-butanol. In the organic solvent B, the ether solvent is preferably tetrahydrofuran. In the organic solvent B, the aromatic solvent is preferably benzene. In the organic solvent B, the alkane solvent is preferably cyclohexane. The volume-to-mass ratio of the organic solvent B to the β-carotene is preferably 1–3 mL / g, for example, 2 mL / g.

[0033] The crystallization temperature is -50 to 0°C, preferably -30 to -5°C, and more preferably -25 to -15°C. The crystallization time is preferably 3 to 5 hours.

[0034] In one embodiment of the present invention, the volume ratio of the organic solvent A to the organic solvent B is preferably (2-4):1, for example 3:1.

[0035] In one embodiment of the present invention, the organic solvent A is cyclohexane, and the organic solvent B is ethanol, isopropanol, or n-butanol.

[0036] In one embodiment of the present invention, the number of times the translocation and crystallization are performed is preferably three.

[0037] In one embodiment of the present invention, the post-processing further includes the following steps: mixing the crude canthaxanthin with cyclohexane and heating at 80°C for displacement transformation, then adding organic solvent B for crystallization, and filtering to obtain pure canthaxanthin; wherein the organic solvent B is ethanol, isopropanol or n-butanol; the crystallization temperature is -25 to -15°C; the filtered filtrate can be repeatedly subjected to displacement transformation and crystallization, wherein the displacement transformation and crystallization are performed three times each.

[0038] In one embodiment of the present invention, in the oxidation reaction, the water-immiscible organic solvent is dichloromethane, trichloromethane, or carbon tetrachloride; the mass ratio of the water-immiscible organic solvent to water is 5:1; the mass ratio of the water-immiscible organic solvent to β-carotene is 5:1; the pH is 4-5; the molar ratio of elemental iodine to β-carotene is 0.01:1; the alkali metal iodide is sodium iodide; the molar ratio of the alkali metal iodide to β-carotene is 0.04:1; the mass fraction of hydrogen peroxide is 30%; the mass ratio of hydrogen peroxide to β-carotene is... The molar ratio of carotene is 0.02:1; the alkali metal halide is sodium hypochlorite, sodium chlorate, or sodium perchlorate; the molar ratio of the alkali metal halide to β-carotene is (1.8–4.0):1; the reaction temperature of the oxidation reaction is 30–50°C; the preparation method of the canthaxanthin includes the following steps: mixing mixture A, water, the acid, elemental iodine, alkali metal iodide, and hydrogen peroxide to obtain mixture B, wherein mixture A is a mixed solution of β-carotene and the organic solvent that is immiscible with water; mixing mixture B with an aqueous solution of the alkali metal halide and then carrying out the oxidation reaction.

[0039] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0040] The reagents and raw materials used in this invention are all commercially available.

[0041] The significant advantages of this invention are as follows: It utilizes elemental iodine, alkali metal iodides, hydrogen peroxide, and alkali metal halide salts to selectively oxidize β-carotene crystals, yielding canthaxanthin. This preparation method boasts high yield, reduces production costs, and is beneficial for industrial production. Detailed Implementation

[0042] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0043] Example 1:

[0044] (1) Dissolve 100g of β-carotene crystals (186.26mmol, purity greater than 98%) in dichloromethane (500g) and place it in a 1000mL three-necked flask.

[0045] The method for crystallizing β-carotene is as follows: Take 100g of commercially available β-carotene with a content of 95%, heat it in ethanol at 90℃ under reflux for 4 hours, cool it to -20℃ and stir to crystallize, filter and remove solvent to obtain β-carotene crystals (purity greater than 98%).

[0046] (2) Add 100g of water to the reaction flask from step (1), and add 30% dilute sulfuric acid dropwise to the reaction solution, controlling the pH of the reaction solution to 5 using a pH meter. Then add sodium iodide (1g, 6.67mmol, 0.04eq), elemental iodine (0.5g, 1.97mmol, 0.01eq), and 30% hydrogen peroxide (0.5g, 4.41mmol, 0.02eq); then add sodium chlorate aqueous solution (45g dissolved in 100g water, 422.77mmol, 2.3eq). Heat the reaction solution to 50℃ and react for 4 hours. The content of canthaxanthin external standard was determined by ultraviolet spectrophotometry, and the conversion rate was obtained by dividing it by the molar amount of carotene, which was 85.3%.

[0047] The detection method follows the People's Republic of China National Standard GB7300.902-2022. Transfer 5 mL of the test reaction solution to a 100 mL amber volumetric flask, dilute to the mark with cyclohexane, and mix well; this is the solution to be diluted. Accurately transfer 5 mL of the solution to a 50 mL amber volumetric flask, dilute to the mark with cyclohexane, and mix well; this is the test solution.

[0048] Using a 1 cm cuvette and cyclohexane as a blank reference, the maximum absorbance A1 of the test solution was measured at a wavelength of 468–472 nm.

[0049] Calculated according to the formula:

[0050] The content of canthaxanthin in the sample is expressed as a mass fraction w1. The value is expressed as a percentage (%).

[0051]

[0052] In the formula, A1 is the maximum absorbance value measured in the sample solution; 20000 is the dilution factor; m1 is the mass of the sample in grams (g); and 2200 is the standard percentage extinction value (1%, 1 cm) of canthaxanthin in the sample.

[0053] The measurement results are expressed as the arithmetic mean of parallel measurements, and are retained to two significant figures.

[0054] (3) Let the reaction solution stand to separate into layers. Wash the lower organic phase once with water and once with an aqueous solution of sodium thiosulfate, each time 250 mL.

[0055] (4) After separating the organic phase, distillation was performed to obtain crude canthaxanthin. 600 mL of cyclohexane was added to the crude canthaxanthin, and the mixture was heated and stirred at 80°C for 5 hours to induce displacement. The mixture was then cooled to room temperature, and 200 mL of ethanol was added. The mixture was first dissolved at room temperature, and then stirred and crystallized at -25°C for approximately 3 hours. The purified canthaxanthin was then obtained by filtration. The filtrate was recrystallized by desolventizing and heating with 600 mL of cyclohexane at 80°C with stirring. After three crystallization and displacement processes, a total of 83.2 g of canthaxanthin crystals was obtained, with a yield of 79.1%. The purity of the canthaxanthin was 98%, and the cis isomer content was less than 0.5%. The purity of the canthaxanthin was determined using the same method as above.

[0056] Melting point of canthaxanthin: 191.1~193.2℃; Infrared spectrum (KBr): 2919, 2858, 1652, 1580, 1556, 973, 959; 1 H NMR (400MHz, CDCl3): 6.70-6.64(m,4H), 6.47-6.23(m,10H), 2.52-2.49(t,J=6.4Hz,4H), 2.00-1.98(m,11H), 1.89-1.85(m,10H), 1.21(s,12H); 13 C NMR (100MHz, CDCl3): 199.2, 161.2, 141.3, 139.2, 136.6, 134.7, 134.4, 133.5, 129.7, 124.7, 124.1, 37.4, 35.7, 34.2, 27.6, 13.8, 12.8, 12.6.

[0057] Example 2

[0058] (1) Dissolve 100g of β-carotene crystals (same as in Example 1) in chloroform (500g) and place it in a 1000mL three-necked flask.

[0059] (2) Add 100g of water to the reaction flask from step (1) and adjust the pH to 4 with sulfuric acid. Then add sodium iodide (1g), elemental iodine (0.5g), and 30% hydrogen peroxide (0.5g, 4.41mmol, 0.02eq); then add sodium hypochlorite aqueous solution (55g dissolved in 100g water, 738.85mmol, 4eq). Heat the reaction solution to 45℃ and react for 4 hours. The content of canthaxanthin external standard was determined by ultraviolet spectrophotometry, and the conversion rate was 82.1% when divided by the molar amount of carotene.

[0060] (3) Let the reaction solution stand to separate into layers. Wash the lower organic phase once with water and once with an aqueous solution of sodium thiosulfate, each time 250 mL.

[0061] (4) After separating the organic phase, distillation was performed to obtain crude canthaxanthin. 600 mL of cyclohexane was added to the crude canthaxanthin, and the mixture was heated and stirred at 80°C for displacement. The mixture was then cooled to room temperature, and 200 mL of isopropanol was added. The mixture was first dissolved at room temperature, and then stirred and crystallized at -15°C for approximately 3 hours. The purified canthaxanthin was then obtained by filtration. The filtrate was recrystallized by desolventizing and heating with 600 mL of cyclohexane at 80°C for displacement. After three crystallization and displacement processes, a total of 78.6 g of canthaxanthin crystals was obtained, with a yield of 74.7%. The purity of canthaxanthin was 98%, and the cis isomer was less than 0.5%. The canthaxanthin structure confirmation data, conversion rate, and purity detection methods were the same as in Example 1.

[0062] Example 3

[0063] (1) Dissolve 100g of β-carotene crystals (same as in Example 1) in 500g of carbon tetrachloride and place them in a 1000mL three-necked flask.

[0064] (2) Add 100g of water to the reaction flask from step (1) and adjust the pH to 5 with sulfuric acid. Then add potassium iodide (1g), elemental iodine (0.5g), and 30% hydrogen peroxide (0.5g, 4.41mmol, 0.02eq); then add sodium perchlorate aqueous solution (40g dissolved in 100g water, 326.69mmol, 1.8eq). Heat the reaction solution to 30℃ and react for 4 hours. The content of canthaxanthin external standard was determined by ultraviolet spectrophotometry, and the conversion rate was obtained by dividing it by the molar amount of carotene, which was 90.7%.

[0065] (3) Let the reaction solution stand to separate into layers. Wash the lower organic phase once with water and once with an aqueous solution of sodium thiosulfate, each time 250 mL.

[0066] (4) After separating the organic phase, distillation was performed to obtain crude canthaxanthin. 600 mL of cyclohexane was added to the crude canthaxanthin, and the mixture was heated and stirred at 80°C for displacement. The mixture was then cooled to room temperature, and 200 mL of n-butanol was added. The mixture was first dissolved at room temperature, and then stirred and crystallized at -5°C for approximately 3 hours. The purified canthaxanthin was then obtained by filtration. The filtrate was recrystallized by desolventizing and heating with 600 mL of cyclohexane at 80°C for displacement. After three crystallization and displacement processes, a total of 88.4 g of canthaxanthin crystals was obtained, with a yield of 84.0%. The purity of canthaxanthin was 98%, and the cis isomer was less than 0.5%. The canthaxanthin structure confirmation data, canthaxanthin conversion rate, and purity detection methods were the same as in Example 1.

[0067] It should be stated that the above-described invention content and specific embodiments are intended to demonstrate the practical application of the technical solution provided by the present invention, and should not be construed as limiting the scope of protection of the present invention.

Claims

1. A method for preparing canthaxanthin, characterized in that, It includes the following steps: In a solvent, under pH less than 7 conditions, in the presence of elemental iodine, alkali metal iodides, hydrogen peroxide and alkali metal halide, β-carotene is oxidized to prepare canthaxanthin; The solvent is a mixture of an organic solvent that is immiscible with water and water; The molar ratio of the alkali metal halide to the β-carotene is (1.8 ~ 4.0): 1; The pH is 4-5; The molar ratio of iodine to β-carotene is (0.005~0.015):1; The molar ratio of the alkali metal iodide to the β-carotene is (0.02~0.06):1; The molar ratio of H2O2 in the hydrogen peroxide to β-carotene is (0.01~0.03):1; The oxidation reaction is carried out at a temperature of 10~80℃.

2. The method for preparing canthaxanthin according to claim 1, characterized in that, The method for preparing the canthaxanthin satisfies one or more of the following conditions: (1) The organic solvent that is immiscible with water is a halogenated hydrocarbon solvent; (2) The mass ratio of the water-immiscible organic solvent to the water is (2.5~7.5):1; (3) The mass ratio of the water-immiscible organic solvent to the β-carotene is (2.5~7.5):1; (4) The purity of the β-carotene is 96-100%; (5) The alkali metal iodide is sodium iodide or potassium iodide; (6) The mass fraction of the hydrogen peroxide is 5-30%; (7) The alkali metal halide is sodium hypochlorite, sodium chlorate or sodium perchlorate; (8) The alkali metal halide is added in the form of an aqueous solution.

3. The method for preparing canthaxanthin according to claim 2, characterized in that, The method for preparing the canthaxanthin satisfies one or more of the following conditions: (1) The organic solvent that is immiscible with water is one or more of dichloromethane, trichloromethane and carbon tetrachloride; (2) The mass ratio of the water-immiscible organic solvent to the water is 5:1; (3) The mass ratio of the water-immiscible organic solvent to the β-carotene is 5:1; (4) The pH is adjusted by adding acid; (5) The molar ratio of the iodine to the β-carotene is 0.01:1; (6) The molar ratio of the alkali metal iodide to the β-carotene is 0.04:1; (7) The molar ratio of hydrogen peroxide to β-carotene is 0.02:1; (8) When the alkali metal halide is added in the form of an aqueous solution, the mass ratio of the alkali metal halide to water is (0.40~0.55):1; (9) The molar ratio of the alkali metal halide to the β-carotene is 2.3:1; (10) The reaction temperature of the oxidation reaction is 30~60℃.

4. The method for preparing canthaxanthin according to claim 3, characterized in that, The method for preparing the canthaxanthin satisfies one or more of the following conditions: (1) The pH is adjusted by adding an acid; the acid is an inorganic acid; (2) When the alkali metal halide is added in the form of an aqueous solution, the mass ratio of the alkali metal halide to water is 0.45:1; (3) The reaction temperature of the oxidation reaction is 45~50℃.

5. The method for preparing canthaxanthin according to claim 4, characterized in that, The pH is adjusted by adding an acid; the acid is one or more of sulfuric acid, hydrochloric acid, and phosphoric acid.

6. The method for preparing canthaxanthin according to claim 5, characterized in that, The pH is adjusted by adding an acid, namely sulfuric acid.

7. The method for preparing canthaxanthin according to claim 6, characterized in that, The pH is adjusted by adding acid; the acid is added dropwise.

8. The method for preparing canthaxanthin according to claim 1, characterized in that, The method for preparing the canthaxanthin satisfies one or more of the following conditions: (1) The molar ratio of the iodine to the hydrogen peroxide is 1: (1~3); (2) When the alkali metal halide is sodium chlorate, the molar ratio of sodium chlorate to β-carotene is 2.3:1; (3) When the alkali metal halide is sodium hypochlorite, the molar ratio of sodium hypochlorite to β-carotene is 4.0:1; (4) When the alkali metal halide is sodium perchlorate, the molar ratio of sodium perchlorate to β-carotene is 1.8:1; (5) In the oxidation reaction, the reaction reagents are the organic solvents that are immiscible with water, water, β-carotene, acid, elemental iodine, alkali metal iodides, hydrogen peroxide and alkali metal halide.

9. The method for preparing canthaxanthin as described in claim 8, characterized in that, The molar ratio of the iodine to the hydrogen peroxide is 1:

2.

10. The method for preparing canthaxanthin according to claim 1, characterized in that, The preparation method of the canthaxanthin includes the following steps: (1) Mixing mixture A, water, acid, iodine, alkali metal iodide and hydrogen peroxide to obtain mixture B, wherein mixture A is a mixed solution of β-carotene and the organic solvent that is immiscible with water; (2) The mixture B is mixed with the aqueous solution of the alkali metal halide and then subjected to an oxidation reaction.

11. The method for preparing canthaxanthin according to claim 1, characterized in that, The preparation method of the canthaxanthin includes the following post-processing: after the reaction solution is separated into layers, the organic phase is washed with water and sodium thiosulfate aqueous solution and then concentrated to obtain crude canthaxanthin.

12. The method for preparing canthaxanthin according to claim 11, characterized in that, The post-processing further includes the following steps: mixing the crude canthaxanthin with organic solvent A, heating and repositioning, then adding organic solvent B for crystallization, and filtering to obtain pure canthaxanthin; wherein organic solvent A is an alkane solvent; and organic solvent B is one or more of alcohol solvents, ether solvents, aromatic solvents, and alkane solvents.

13. The method for preparing canthaxanthin according to claim 12, characterized in that, The method for preparing the canthaxanthin satisfies one or more of the following conditions: (1) The organic solvent A is n-pentane, n-hexane, cyclohexane or n-heptane; (2) The volume-to-mass ratio of the organic solvent A to the β-carotene is 4~8 mL / g; (3) The heating temperature is 60~100℃; (4) In the organic solvent B, the alcohol solvent is methanol, ethanol, n-propanol, isopropanol or n-butanol; (5) In the organic solvent B, the ether solvent is tetrahydrofuran; (6) In the organic solvent B, the aromatic solvent is benzene; (7) In the organic solvent B, the alkane solvent is cyclohexane; (8) The volume-to-mass ratio of the organic solvent B to the β-carotene is 1~3 mL / g; (9) The crystallization temperature is -50~0°C.

14. The method for preparing canthaxanthin according to claim 13, characterized in that, The method for preparing the canthaxanthin satisfies one or two of the following conditions: (1) The volume-to-mass ratio of the organic solvent A to the β-carotene is 6 mL / g; (2) The volume-to-mass ratio of the organic solvent B to the β-carotene is 2 mL / g.

15. The method for preparing canthaxanthin according to claim 12, characterized in that, The method for preparing the canthaxanthin satisfies one or more of the following conditions: (1) The heating temperature is 80℃; (2) The crystallization temperature is -30~-5°C; (3) The organic solvent A is cyclohexane, and the organic solvent B is ethanol, isopropanol or n-butanol; (4) The filtered liquid can be repeatedly translocated and crystallized.

16. The method for preparing canthaxanthin according to claim 15, characterized in that, The method for preparing the canthaxanthin satisfies one or two of the following conditions: (1) The crystallization temperature is -25~-15°C; (2) The filtered filtrate can be repeatedly translocated and crystallized; the translocation and crystallization are performed three times each.

17. The method for preparing canthaxanthin according to claim 1, characterized in that, In the oxidation reaction, the water-immiscible organic solvent is dichloromethane, trichloromethane, or carbon tetrachloride; the mass ratio of the water-immiscible organic solvent to water is 5:1; the mass ratio of the water-immiscible organic solvent to β-carotene is 5:1; the pH is 4-5; the molar ratio of elemental iodine to β-carotene is 0.01:1; the alkali metal iodide is sodium iodide; the molar ratio of the alkali metal iodide to β-carotene is 0.04:1; the mass fraction of hydrogen peroxide is 30%; the molar ratio of hydrogen peroxide to β-carotene is 0.02:1; the alkali metal halide is sodium hypochlorite, sodium chlorate, or sodium perchlorate; the molar ratio of the alkali metal halide to β-carotene is (1.8-4.0): 1; The reaction temperature of the oxidation reaction is 30~50℃; The preparation method of the canthaxanthin includes the following steps: mixing mixture A, water, the acid, iodine, alkali metal iodide and hydrogen peroxide to obtain mixture B, wherein mixture A is a mixed solution of β-carotene and the organic solvent that is immiscible with water; mixing mixture B with the aqueous solution of the alkali metal halide and then carrying out the oxidation reaction.

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