阅读说明：本技术 一种高收率制备高稳定性角黄素的方法 (Method for preparing high-stability canthaxanthin in high yield ) 是由 宋军伟 李剑鹏 张弈宇 张旭 沈宏强 于 2021-08-25 设计创作，主要内容包括：本发明公开了一种高收率制备高稳定性角黄素的方法,包括如下步骤：(1)β-胡萝卜素在催化剂和氧化剂的作用下发生氧化反应；(2)反应结束后,淬灭、水洗、脱溶剂,得到角黄素粗品；(3)角黄素粗品在异构溶剂的作用下,发生异构反应；(4)经离心、洗涤、干燥操作,得到角黄素晶体；其中,所述步骤(1)β-胡萝卜素中TPPO的含量≤1000ppm。本发明的方法制备的角黄素收率高且存储稳定性良好,能满足下游的应用需求。(The invention discloses a method for preparing high-stability canthaxanthin with high yield, which comprises the following steps: (1) the beta-carotene is subjected to oxidation reaction under the action of a catalyst and an oxidant; (2) after the reaction is finished, quenching, washing and desolventizing to obtain a canthaxanthin crude product; (3) carrying out isomerization reaction on the canthaxanthin crude product under the action of an isomerization solvent; (4) centrifuging, washing and drying to obtain canthaxanthin crystals; wherein the content of TPPO in the beta-carotene in the step (1) is less than or equal to 1000 ppm. The canthaxanthin prepared by the method has high yield and good storage stability, and can meet the downstream application requirements.)

1. A method for preparing high-stability canthaxanthin with high yield comprises the following steps:

(1) carrying out an oxidation reaction on beta-carotene under the action of a catalyst and an oxidant, wherein the content of TPPO in the beta-carotene is controlled to be less than or equal to 1000 ppm;

(2) after the reaction is finished, quenching, washing and desolventizing to obtain a canthaxanthin crude product;

(3) carrying out isomerization reaction on the canthaxanthin crude product under the action of an isomerization solvent;

(4) the canthaxanthin crystal is obtained by centrifugation, washing and drying.

2. The method according to claim 1, wherein the content of TPPO in the beta-carotene is controlled to be 10-500ppm in the step (1); preferably, the content of TPPO in the beta-carotene is controlled to be 10-200 ppm.

3. The method according to claim 1, wherein the oxidant in step (1) is at least one selected from the group consisting of potassium chlorate, sodium chlorate, hydrogen peroxide, sodium chlorite and sodium hypochlorite.

4. The method according to any one of claims 1 to 3, wherein the catalyst in the step (1) is at least any one selected from sodium iodide and potassium iodide.

5. The method according to any one of claims 1 to 4, wherein in the step (1), the catalyst and the oxidant are dissolved in water, a mixed solution of beta-carotene and an organic solvent is added, and the beta-carotene is subjected to an oxidation reaction under the action of the catalyst and the oxidant; preferably, the organic solvent is selected from at least any one of chloroform, dichloromethane, dichloroethane, ethyl acetate and acetone.

6. The method according to claim 5, wherein the mass ratio of the beta-carotene to the catalyst to the oxidant to the water to the organic solvent is 1:0.01-0.1:0.2-2:5-40:10-80, preferably 1:0.02-0.08:0.5-1:10-20: 20-60.

7. The method according to any one of claims 1 to 6, wherein the oxidation reaction in step (1) is carried out at a reaction temperature of-10 to 30 ℃, preferably 0 to 20 ℃; the reaction pressure is 0.1MPaA to 0.5MPaA, preferably 0.1MPaA to 0.3 MPaA; the reaction time is 8-24h, preferably 10-15 h.

8. The method according to any one of claims 1 to 7, wherein the isomerization solvent in the step (3) is at least any one selected from ethanol, acetone, ethyl acetate, n-hexane, toluene and methanol.

9. The process according to any one of claims 1 to 8, wherein the mass ratio of the crude canthaxanthin and the isomeric solvent in the step (3) is 1:5 to 50, preferably 1:10 to 25.

10. The process according to any one of claims 1 to 9, wherein the reaction temperature of the isomerization reaction in step (3) is 50 to 150 ℃, preferably 70 to 100 ℃; the reaction pressure is 0.1MPaA-1MPaA, preferably 0.1MPaA-0.5 MPaA; the reaction time is 4-24h, preferably 8-12 h.

Technical Field

The invention belongs to the field of nutritional chemicals, and particularly relates to a method for preparing high-stability canthaxanthin in high yield.

Background

Canthaxanthin (also known as canthaxanthin) is a carotenoid found in certain mushrooms, crustaceans, fish, algae, eggs, blood and liver. In 1984, the FDA/WHO approved cantharis yellow to be included in food additives and set quality standards. Canthaxanthin can be used as food additive for beverage, ice cream, waffle without adjuvant, flavoring paste, tomato processed product, meat processed product, etc. Cantharis yellow is added into the feed of poultry such as chicken and duck, and the yellow yolk is a yellow orange color which is popular with consumers.

US4212827A discloses a process for the preparation of canthaxanthin by oxidation of beta-carotene with chlorate or bromate in the presence of a catalyst, which has the disadvantages of long reaction time, difficult initiation, unstable process and low yield.

CN1417207A discloses that hypobromous acid generated by sulfurous acid, bisulfite or combination of bisulfite and bromate is used as oxidant, so that canthaxanthin can be obtained with good yield, and the reaction time is obviously shortened. The method has the disadvantage that the generated hypobromous acid is unstable and is difficult to apply to industrialization.

The above method for preparing canthaxanthin using beta-carotene as a raw material has a low overall reaction yield, and the obtained canthaxanthin crystals have poor storage stability.

Therefore, how to increase the yield of the oxidation reaction and improve the storage stability of canthaxanthin are important.

Disclosure of Invention

The present inventors have found that triphenylphosphine oxide (TPPO), a key impurity in β -carotene, is derived from the β -carotene production process, and inevitably enters β -carotene crystals, but the progress of the oxidation reaction and the storage stability of canthaxanthin crystals are affected by controlling the content of TPPO in β -carotene, thereby completing the present invention. The invention aims to provide a method for preparing high-stability canthaxanthin with high hand rate, which achieves the aim of preparing the high-stability canthaxanthin with high yield by controlling the content of TPPO in beta-carotene.

In order to achieve the above purpose, the technical scheme of the invention is as follows:

a method for preparing high-stability canthaxanthin with high yield comprises the following steps:

(1) carrying out an oxidation reaction on beta-carotene under the action of a catalyst and an oxidant, wherein the content of TPPO in the beta-carotene is controlled to be less than or equal to 1000 ppm;

(2) after the reaction is finished, quenching, washing and desolventizing to obtain a canthaxanthin crude product;

(3) carrying out isomerization reaction on the canthaxanthin crude product under the action of an isomerization solvent;

(4) the canthaxanthin crystal is obtained by centrifugation, washing and drying.

In a preferred embodiment, the content of TPPO in the beta-carotene is controlled to be 10-500ppm in the step (1); preferably, the content of TPPO in the beta-carotene is controlled to be 10-200 ppm.

In a specific embodiment, the oxidant in step (1) is at least one selected from the group consisting of potassium chlorate, sodium chlorate, hydrogen peroxide, sodium chlorite and sodium hypochlorite.

In a specific embodiment, it is characterized in that the catalyst in the step (1) is selected from at least any one of sodium iodide and potassium iodide.

In a specific embodiment, in the step (1), the catalyst and the oxidant are dissolved in water, and a mixed solution of beta-carotene and an organic solvent is added, so that the beta-carotene is subjected to an oxidation reaction under the action of the catalyst and the oxidant; preferably, the organic solvent is selected from at least any one of chloroform, dichloromethane, dichloroethane, ethyl acetate and acetone.

In a specific embodiment, the mass ratio of the beta-carotene to the catalyst to the oxidant to the water to the organic solvent is 1:0.01-0.1:0.2-2:5-40:10-80, preferably 1:0.02-0.08:0.5-1:10-20: 20-60.

In a specific embodiment, the reaction temperature of the oxidation reaction in the step (1) is-10 to 30 ℃, and preferably 0 to 20 ℃; the reaction pressure is 0.1MPaA to 0.5MPaA, preferably 0.1MPaA to 0.3 MPaA; the reaction time is 8-24h, preferably 10-15 h.

In a specific embodiment, the isomerization solvent in the step (3) is at least one selected from ethanol, acetone, ethyl acetate, n-hexane, toluene and methanol.

In a specific embodiment, the mass ratio of the canthaxanthin crude product to the isomeric solvent in the step (3) is 1:5 to 50, preferably 1:10 to 25.

In a specific embodiment, the reaction temperature of the isomerization reaction in the step (3) is 50 to 150 ℃, preferably 70 to 100 ℃; the reaction pressure is 0.1MPaA-1MPaA, preferably 0.1MPaA-0.5 MPaA; the reaction time is 4-24h, preferably 8-12 h.

Compared with the prior art, the invention adopts the technical scheme, and has the following beneficial effects:

(1) according to the method disclosed by the invention, the yield of the oxidation reaction can be effectively improved by strictly controlling the content of TPPO in the beta-carotene, the yield of the canthaxanthin crystal is obviously improved finally, and the storage stability of the canthaxanthin crystal prepared by the method disclosed by the invention is unexpectedly found to be obviously improved.

(2) The method can achieve corresponding technical effects only by controlling the content of TPPO in the raw material beta-carotene, has strong compatibility with the prior art, and is suitable for industrial production.

Detailed Description

The following examples will further illustrate the method provided by the present invention in order to better understand the technical solution of the present invention, but the present invention is not limited to the listed examples, and also includes any other known modifications within the scope of the claims of the present invention.

A method for preparing high-stability canthaxanthin with high yield comprises the following steps:

(1) the beta-carotene is subjected to oxidation reaction under the action of a catalyst and an oxidant;

(2) after the reaction is finished, quenching, washing and desolventizing to obtain a canthaxanthin crude product;

(3) carrying out isomerization reaction on the canthaxanthin crude product under the action of an isomerization solvent;

(4) the canthaxanthin crystal is obtained after the operations of centrifugation, washing and drying.

Wherein the content of TPPO in the beta-carotene in the step (1) is controlled to be less than or equal to 1000ppm, preferably not more than 1000ppm and not less than 10ppm, such as but not limited to controlling the content of TPPO to be not more than 1000ppm, 900ppm, 800ppm, 700ppm, 600ppm, 500ppm, 400ppm, 300ppm, 200ppm, 100ppm, 50ppm and 10 ppm; preferably, the content of TPPO is controlled to be 10-500 ppm; more preferably, the content of TPPO is controlled to be 10 to 200 ppm. Among them, as can be understood by those skilled in the art, controlling the content of TPPO in β -carotene to be less than 10ppm is also suitable for the present invention, but since the smaller the content of TPPO is, the more complicated the post-treatment process is, the more the post-treatment cost is undoubtedly increased; it is critical that after TPPO is controlled at a level of less than 10ppm, further reduction of TPPO has little effect on the yield of the oxidation reaction and the storage stability of canthaxanthin crystals. Therefore, the invention preferably controls the TPPO content in the beta-carotene to be 10-1000ppm, but the condition of less than 10ppm also falls into the protection scope of the invention.

The process for the preparation of beta-carotene can be referred to patent CN110452147A, in which process TPPO inevitably enters into beta-carotene crystals, thereby affecting the subsequent oxidation reaction and finally entering into canthaxanthin. The TPPO content in the beta-carotene prepared by the method is generally as high as 5000-10000 ppm.

In the invention, the TPPO content in the beta-carotene can be effectively controlled by washing with dichloromethane and ethanol mixed solvent with different dosage and proportion. In the mixed solvent, the mass ratio of the dichloromethane to the ethanol is 1:0.5-2, and the washing time is 3-6 h.

Specifically, when the dosage of the mixed solvent is 10-20 times of that of the beta-carotene, the TPPO content can be reduced to below 1000 ppm; when the dosage of the mixed solvent is 20-50 times of that of the beta-carotene, the content of TPPO can be reduced to be below 500 ppm; when the dosage of the mixed solvent is 50-100 times of that of the beta-carotene, the TPPO content can be reduced to 10-200 ppm.

The method of the invention is based on the existing canthaxanthin preparation method, and only needs to control the TPPO content in the beta-carotene to be in a specified range, and other preparation processes can refer to the prior art. For example, the oxidizing agent used in the oxidation reaction of β -carotene is at least one selected from the group consisting of potassium chlorate, sodium chlorate, hydrogen peroxide, sodium chlorite, and sodium hypochlorite, and preferably sodium chlorate and hydrogen peroxide. The catalyst for the oxidation reaction is, for example, at least any one selected from sodium iodide and potassium iodide.

In a specific embodiment, for example, a catalyst and an oxidizing agent are dissolved in water, β -carotene is mixed with an organic solvent to form a raw material solution, and an aqueous solution in which the catalyst and the oxidizing agent are dissolved is added to the raw material solution containing β -carotene, whereby β -carotene is oxidized by the catalyst and the oxidizing agent. The organic solvent used in the raw material liquid is at least one selected from chloroform, dichloromethane, dichloroethane, ethyl acetate and acetone, and dichloromethane and chloroform are preferred. Specifically, the mass ratio of the beta-carotene to the catalyst to the oxidant to the water to the organic solvent is 1:0.01-0.1:0.2-2:5-40:10-80, preferably 1:0.02-0.08:0.5-1:10-20: 20-60.

The reaction temperature of the oxidation reaction is-10 to 30 ℃, for example, but not limited to-10 ℃, 5 ℃, 0 ℃, 5 ℃, 10 ℃, 15 ℃, 20 ℃, 25 ℃ and 30 ℃, preferably 0 to 20 ℃; the reaction pressure is from 0.1MPaA to 0.5MPaA, including for example but not limited to 0.1MPaA, 0.15MPaA, 0.2MPaA, 0.25MPaA, 0.3MPaA, 0.35MPaA, 0.4MPaA, 0.45MPaA, 0.5MPaA, preferably 0.1MPaA to 0.3 MPaA; the reaction time is 8-24h, for example, but not limited to, 8h, 10h, 12h, 14h, 16h, 18h, 20h, 22h, 24h, preferably 10-15 h.

In the present invention, the quenching, water washing and solvent removing processes in the step (2) may adopt a scheme known in the industry, and are not particularly limited. For example, after the reaction solution in the step (1) is quenched by sodium thiosulfate 3 times the mass of the catalyst, phase separation is carried out; separating the obtained organic phase, washing by using 1 time of the mass of the reaction water, and carrying out phase splitting; and (4) carrying out vacuum distillation on the separated organic phase to remove the solvent, thus obtaining the canthaxanthin crude product.

In the present invention, the isomerization reaction of step (3) can also be referred to the prior art, for example, the document "improvement of process for synthesizing canthaxanthin by one-step oxidation" 2013,42(02) in Shandong chemical industry. Specifically, the isomerization solvent is at least one selected from ethanol, acetone, ethyl acetate, n-hexane, toluene, and methanol, and preferably ethanol, ethyl acetate, and n-hexane. In the present invention, the mass ratio of the canthaxanthin crude product to the isomeric solvent is 1:5-50, for example, including but not limited to 1: 5. 1: 10. 1: 15. 1: 20. 1: 25. 1: 30. 1: 35. 1: 40. 1: 45. 1:50, preferably 1: 10-25. In addition, the isomerization reaction temperature is 50-150 deg.C, including but not limited to 50 deg.C, 60 deg.C, 70 deg.C, 0 deg.C, 100 deg.C, 110 deg.C, 120 deg.C, 130 deg.C, 140 deg.C, 150 deg.C, preferably 70-100 deg.C; pressures of 0.1MPaA to 1MPaA, including for example but not limited to 0.1MPaA, 0.15MPaA, 0.2MPaA, 0.25MPaA, 0.3MPaA, 0.35MPaA, 0.4MPaA, 0.45MPaA, 0.5MPaA, 0.55MPaA, 0.6MPaA, 0.65MPaA, 0.7MPaA, 0.75MPaA, 0.8MPaA, 0.85MPaA, 0.9MPaA, 0.95MPaA, 1.0MPaA, preferably 0.1MPaA to 0.5 MPaA; the reaction time is 4 to 24 hours, for example, but not limited to, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 24 hours, preferably 8 to 12 hours.

In the invention, the centrifugation, washing and drying processes in the step (4) are all conventional operations in the field, and reference can be made to the prior art. For example, after the isomerization reaction suspension is cooled to room temperature, the operation of centrifugation is carried out; washing with 1 time of the mass of the isomerization reaction solvent, and drying in vacuum under reduced pressure to obtain canthaxanthin crystals.

The production process of the present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the following examples.

The following examples and comparative examples use the following information on the main raw materials:

beta-carotene containing different TPPO contents is prepared by self;

chloroform, dichloromethane, dichloroethane, ethyl acetate, acetone, ethanol, n-hexane, toluene, methanol, analytically pure, welength technologies ltd;

potassium chlorate, sodium chlorate, hydrogen peroxide, sodium chlorite, sodium hypochlorite, sodium iodide, potassium iodide, analytically pure, alatin.

The reaction yield test, the canthaxanthin purity test and the TPPO content test are all carried out by using liquid chromatography.

The canthaxanthin purity test conditions of the invention are as follows: the chromatographic type is as follows: agilent 1260; a chromatographic column: a C30 column; mobile phase: a: acetonitrile, B: isopropyl alcohol; column temperature: 40 ℃; flow rate: 1.0 mL/min; sample introduction amount: 5 mu L of the solution; detection wavelength: 474 nm.

TPPO test conditions: the chromatographic type is as follows: agilent 1260; a chromatographic column: a C18 column; mobile phase: a: methanol, B: 0.1% phosphoric acid in water; column temperature: 40 ℃; flow rate: 1.0 mL/min; sample introduction amount: 10 mu L of the solution; detection wavelength: 225 nm.

Preparation example

Beta-carotene with high content of TPPO was prepared by the method of patent CN110452147A example 2, and the TPPO content of the obtained beta-carotene was about 6000 ppm. Washing the beta-carotene by using a mixed solvent of dichloromethane and ethanol, wherein the mass ratio of the dichloromethane to the ethanol in the mixed solvent is 1:1, controlling the dosage of the mixed solvent to be 10-100 times of the dosage of the beta-carotene, and controlling the washing time to be 3-6h to obtain the beta-carotene with different TPPO contents.

When the dosage of the mixed solvent is 28 times and the washing time is 4 hours, the TPPO content is reduced to 450 ppm;

when the dosage of the mixed solvent is 55 times and the washing time is 6 hours, the TPPO content is reduced to 180 ppm;

when the dosage of the mixed solvent is 18 times and the washing time is 3 hours, the TPPO content is reduced to 980 ppm;

when the dosage of the mixed solvent is 95 times and the washing time is 6 hours, the TPPO content is reduced to 18 ppm;

when the dosage of the mixed solvent is 48 times and the washing time is 4 hours, the TPPO content is reduced to 210 ppm;

when the using amount of the mixed solvent is 500 times and the washing time is 6 hours, the TPPO content is reduced to 8 ppm;

when the amount of the mixed solvent is 10 times and the washing time is 2 hours, the TPPO content is reduced to 1050 ppm.

Example 1

Mixing beta-carotene (TPPO content is 450ppm), sodium hypochlorite, sodium iodide, water and dichloroethane according to the mass ratio of 1:0.08:1:20:60, reacting for 10 hours at 20 ℃ and 0.3MPaA, quenching with sodium thiosulfate, washing and desolventizing, mixing the obtained canthaxanthin crude product with ethyl acetate according to the mass ratio of 1:10, reacting for 8 hours at 100 ℃ and 0.5MPaA, centrifuging, washing and drying to obtain the canthaxanthin crystal. The yield of the oxidation reaction was 83%, and the yield of the isomerization reaction was 95%. The obtained crystal is stored in a nitrogen atmosphere for 30 days, and the purity of the crystal is reduced from 99.5 percent to 99.2 percent.

Example 2

Mixing beta-carotene (TPPO content of 180ppm), sodium chlorate, potassium iodide, water and dichloromethane according to a mass ratio of 1:0.02:0.5:10:20, reacting for 15 hours at 0 ℃ and 0.1MPaA, quenching with sodium thiosulfate, washing, and removing a solvent, mixing the obtained canthaxanthin crude product with acetone according to a mass ratio of 1:25, reacting for 12 hours at 70 ℃ and 0.3MPaA, centrifuging, washing, and drying to obtain the canthaxanthin crystal. The yield of the oxidation reaction was 84% and the yield of the isomerization reaction was 96%. The obtained crystal is stored in a nitrogen atmosphere for 30 days, and the purity of the crystal is reduced from 99.6 percent to 99.3 percent.

Example 3

Mixing beta-carotene (the content of TPPO is 980ppm), hydrogen peroxide, sodium iodide, water and ethyl acetate according to the mass ratio of 1:0.1:0.2:40:80, reacting for 8 hours at 30 ℃ and 0.2MPaA, quenching with sodium thiosulfate, washing, and removing solvent, mixing the obtained canthaxanthin crude product with n-hexane according to the mass ratio of 1:50, reacting for 4 hours at 150 ℃ and 1MPaA, centrifuging, washing, and drying to obtain the canthaxanthin crystal. The yield of the oxidation reaction was 81%, and the yield of the isomerization reaction was 95%. The obtained crystal is stored in a nitrogen atmosphere for 30 days, and the purity of the crystal is reduced from 99.6 percent to 99.1 percent.

Example 4

Mixing beta-carotene (TPPO content is 18ppm), sodium chlorite, potassium iodide, water and chloroform according to the mass ratio of 1:0.01:0.2:5:10, reacting for 24 hours at-10 ℃ and 0.5MPaA, quenching with sodium thiosulfate, washing, and removing solvent, mixing the canthaxanthin crude product with toluene according to the mass ratio of 1:5, reacting for 24 hours at 50 ℃ and 0.1MPaA, centrifuging, washing, and drying to obtain the canthaxanthin crystal. The yield of the oxidation reaction was 82%, and the yield of the isomerization reaction was 97%. The obtained crystal is stored in a nitrogen atmosphere for 30 days, and the purity of the crystal is reduced from 99.4 percent to 99.0 percent.

Example 5

Mixing beta-carotene (TPPO content is 210ppm), potassium chlorate, sodium iodide, water and acetone according to the mass ratio of 1:0.06:0.8:15:40, reacting for 13 hours at 10 ℃ and 0.2MPaA, quenching with sodium thiosulfate, washing, and removing solvent, mixing the obtained canthaxanthin crude product with methanol according to the mass ratio of 1:15, reacting for 10 hours at 80 ℃ and 0.4MPaA, centrifuging, washing, and drying to obtain the canthaxanthin crystal. The yield of the oxidation reaction was 85% and the yield of the isomerization reaction was 96%. The obtained crystal is stored in a nitrogen atmosphere for 30 days, and the purity of the crystal is reduced from 99.7 percent to 99.4 percent.

Comparative example 1

The beta-carotene in example 1 was replaced with beta-carotene having a TPPO content of 1050ppm, and the other reaction parameters were exactly the same as in example 1, to finally obtain canthaxanthin crystals. The yield of the oxidation reaction was 75%, and the yield of the isomerization reaction was 94%. The obtained crystal was stored in a nitrogen atmosphere for 30 days, and the purity of the crystal was reduced from 98.9% to 95.3%.

Comparative example 2

No organic solvent was added in the oxidation reaction, and the other reaction parameters were the same as in example 1. The yield of the oxidation reaction was 25% and the yield of the isomerization reaction was 56%. The canthaxanthin crystal purity is only 85%.

Comparative example 3

No oxidizing agent was added in the oxidation reaction, and other reaction parameters were the same as in example 1. The yield of the oxidation reaction was 0%.

Comparative example 4

No catalyst was added in the oxidation reaction, and the other reaction parameters were the same as in example 1. The yield of the oxidation reaction was 0%.

Comparative example 5

The isomerization reaction was carried out without adding an isomerization solvent, and the other reaction parameters were the same as in example 1. The yield of the oxidation reaction is unchanged, and the yield of the isomerization reaction is only 71 percent. The purity of the obtained crystal is only 91%.

Comparative example 6

Beta-carotene in example 1 was replaced with beta-carotene having a TPPO content of 8ppm, and the other reaction conditions were the same as in example 1. The yield of the oxidation reaction was 83%, and the yield of the isomerization reaction was 96%. The obtained crystal is stored in a nitrogen atmosphere for 30 days, and the purity of the crystal is reduced from 99.6 percent to 99.3 percent.

The amount of a dichloromethane and ethanol mixed solvent used for obtaining the beta-carotene with the TPPO content of 8ppm is 500 times of the mass of the beta-carotene, the consumed solvent amount is too large, and the reaction yield and the product stability are not obviously improved.

As is clear from comparison of example 1 with comparative example 1, when the TPPO content is higher, the oxidation reaction yield is significantly reduced, the isomerization reaction yield is substantially unchanged, and the stability of the obtained crystal is deteriorated. This is because the presence of oxygen in TPPO increases the degree of progress of the oxidation reaction and increases the amount of over-oxidized impurities, thereby reducing the yield of the oxidation reaction; in addition, the TPPO enters into the crystals of canthaxanthin, thereby causing deterioration in the storage stability of canthaxanthin. Therefore, the TPPO content in the raw material beta-carotene needs to be strictly controlled, and the reaction yield and the storage stability of canthaxanthin are improved fundamentally.

While the present invention has been described in detail with reference to the preferred embodiments, it should be understood that the above description should not be taken as limiting the invention. It will be appreciated by those skilled in the art that modifications or adaptations to the invention may be made in light of the teachings of the present specification. Such modifications or adaptations are intended to be within the scope of the present invention as defined in the claims.