Preparation method of high-trans high-content canthaxanthin crystal

Abstract

The invention discloses a preparation method of a high-trans high-content canthaxanthin crystal, and belongs to the field of fine chemical engineering. The invention relates to a preparation method of a high-trans high-content canthaxanthin crystal. The preparation method comprises the following steps: adding crude canthaxanthin into an isomerization crystallization solvent A and an auxiliary agent B, and heating for isomerization; and cooling, crystallizing, centrifuging, and carrying out vacuum drying on a solid-phase material to obtain a canthaxanthin crystal. By combining isomerization and crystallization into one-step treatment, the total yield is higher, the raw materials are simple and easy to obtain, less three wastes are generated, and the method is environment-friendly.

Description

Technical Field

[0001] This invention belongs to the field of fine chemicals, specifically relating to a method for preparing high-trans-content flavin crystals. Background Technology

[0002] Canthaxanthin is an important carotenoid, mainly used as a feed additive and food coloring agent. As a feed additive, canthaxanthin can improve the color of poultry egg yolks and poultry meat. Canthaxanthin can also be used in food to color jams, candies, syrups, and sauces. The chemical structure of canthaxanthin is as follows:

[0003]

[0004] Currently, the main way to obtain canthaxanthin is through chemical synthesis, while microbial culture and fermentation have not yet achieved true industrial production due to technological limitations.

[0005] Current industrial production of canthaxanthin mainly involves the oxidation of β-carotene. Since β-carotene is a polyene with many active sites, it produces numerous oxidation byproducts and has many cis isomers. The cis isomers have low bioavailability and require isomerization to all-trans canthaxanthin. Industrial crude canthaxanthin contains 65-75% canthaxanthin, with a low trans content of only 50-60%, making it unsuitable for direct use. Traditional processes first isomerize the crude canthaxanthin in solvents such as water or acetone to achieve a trans / cis ratio of over 96%, followed by solid-liquid separation. The solid phase (crude canthaxanthin) is then crystallized using halogenated hydrocarbons or a mixture of halogenated hydrocarbons and alcohols to obtain canthaxanthin crystals with high trans content. This approach has a drawback: while water isomerization can achieve a high trans / cis ratio, the high isomerization temperature and the insolubility of canthaxanthin in water mean that water cannot provide adequate protection, resulting in significant losses. Subsequent crystallization using halogenated hydrocarbons or a mixture of halogenated hydrocarbons and alcohols further reduces the yield loss by over 20%. Using solvents like acetone, which can isomerize, provides protection during isomerization, but its impurity removal effect is limited. Crystallization still requires halogenated hydrocarbons or a mixture of halogenated hydrocarbons and alcohols, resulting in a yield loss of over 15%. Therefore, a method for preparing high-trans, high-content canthaxanthin crystals is proposed. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing high trans-content flavin crystals, which solves the problems in the prior art.

[0007] The objective of this invention can be achieved through the following technical solutions:

[0008] A method for preparing canthaxanthin crystals includes the following steps:

[0009] Crude canthaxanthin was added to isomerization crystallization solvent A and auxiliary agent B, and the mixture was heated for isomerization. Then the mixture was cooled for crystallization, centrifuged, and the solid phase was vacuum dried to obtain canthaxanthin crystals.

[0010] Furthermore, the heterogeneity temperature is 60–100°C.

[0011] Furthermore, the crystallization temperature is -10 to 20°C.

[0012] Furthermore, the crystallization temperature is 0–5°C.

[0013] Furthermore, the isomeric crystallization solvent A is one or more of the following: 3-pentanone, butanone, tetrahydrofuran, n-heptane, and dioxane.

[0014] Furthermore, the auxiliary agent B is one or both of DMSO or N-methylpyrrolidone.

[0015] Furthermore, the mass percentage of the auxiliary agent B in the isomeric crystallization solvent A is between 1% and 15%.

[0016] Furthermore, the mass ratio of the isomeric crystallization solvent A to the crude flavin is (2-10):1.

[0017] Furthermore, the mass percentage of the auxiliary agent B in the isomeric crystallization solvent A is 3% to 5%; the mass ratio of the isomeric crystallization solvent A to the crude flavin is (3 to 8): 1.

[0018] Furthermore, the effective content of canthaxanthin in the crude canthaxanthin is 65-75%, and the trans isomer accounts for 50-60% of the canthaxanthin.

[0019] The beneficial effects of this invention are:

[0020] This invention combines isomerization and crystallization into a single step by changing the isomer crystallization solvent A and adding auxiliary agent B to adjust the dielectric constant of the system. The resulting product meets quality standards. Due to the reduction in purification steps, the overall purification yield is also significantly improved. Solvent A and auxiliary agent B are readily available, solvent A is easier to recycle and reuse, gas phase loss is reduced, environmental pollution problems are significantly reduced, and the use of highly toxic halogenated hydrocarbons is avoided. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is the liquid phase spectrum of crude canthaxanthin;

[0023] Figure 2 This is the liquid phase spectrum of flavin crystals from Example 1. Detailed Implementation

[0024] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] A method for preparing high-trans-content flavin crystals includes the following steps:

[0026] Industrial crude canthaxanthin (effective content 65-75%; trans content 50-60%) was added to isomerization crystallization solvent A and auxiliary agent B, and the temperature was raised to start isomerization, which lasted for 5-8 hours. Then the temperature was lowered to crystallize, and the crystallization temperature was maintained for 2-3 hours before centrifugation. The solid phase material was then vacuum dried to obtain high trans content canthaxanthin crystals.

[0027] Wherein: the isomerization temperature is 60~100℃, preferably 80~90℃; the crystallization temperature is -10~20℃, preferably 0~5℃.

[0028] The isomeric crystallization solvent A is selected from one or more of 3-pentanone, butanone, tetrahydrofuran, n-heptane, and dioxane, with 3-pentanone being preferred.

[0029] Additive B is selected from one or both of DMSO or N-methylpyrrolidone, and their effects are comparable.

[0030] The mass percentage of additive B in the isomeric crystallization solvent A is 1% to 15%, preferably 3% to 5%.

[0031] The mass ratio of isomeric crystallization solvent A to crude canthaxanthin is (2-10):1, preferably (3-8):1.

[0032] The technical solution of the present invention will be described in detail below through the following embodiments; wherein, the method used to measure the sample content in the embodiments and comparative examples is as follows:

[0033] Liquid chromatography (LC) analysis conditions: Agilent LC was used, with reversed-phase chromatography for the detection of crude and purified samples. An ODS-C18-5μm column (4.6mm × 250mm) was used. The flow rate was 1 mL / min, the column temperature was 25℃, and the detection wavelength was 470 nm. Isocratic elution was performed for 20 min. The main peak with a retention time of 12-13 min was the target product. Purity was calculated using the area normalization method. The content of the sample was calculated using an external standard in the LC.

[0034] Example 1

[0035] 100 g of crude canthaxanthin (70% effective content; trans isomer 54.71%) was added to 600 g of 3-pentanone and 30 g of DMSO. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 95.32%, the all-trans isomer content in the obtained canthaxanthin crystals was 98.22%, and the external standard content of the canthaxanthin crystals was 99.36%.

[0036] The liquid phase spectrum of crude canthaxanthin is shown below. Figure 1 As shown in Table 1, peak 7 is the trans isomer, while peaks 6, 8, and 9 are the cis isomers.

[0037] Table 1. HPLC chromatogram of crude flavin

[0038] <Peak Table>

[0039] Detector A 470nm

[0040] Peak Retention time area high high% Area / Height area% 1 3.625 174016 9059 0.719 19.209 0.949 2 4.810 20381 1343 0.107 15.178 0.111 3 5.338 68214 7285 0.579 9.364 0.372 4 6.089 394228 31868 2.531 12.371 2.149 5 6.608 252529 15286 1.214 16.520 1.377 6 7.368 1335830 56552 4.491 23.621 7.283 7 8.467 10034923 809849 64.316 12.391 54.713 8 9.247 76078 7054 0.560 10.784 0.415 9 10.478 5950451 318915 25.327 18.658 32.443 10 11.453 6215 444 0.035 13.999 0.034 11 12.104 9162 485 0.039 18.872 0.050 12 13.178 10401 553 0.044 18.794 0.057 13 13.995 5392 303 0.024 17.768 0.029 14 15.023 3177 178 0.014 17.802 0.017 total 18340998 1259176 100.000 100.000

[0041] The liquid phase spectrum of the canthaxanthin crystals prepared in this embodiment is as follows: Figure 2 As shown in Table 2, peak 8 is the trans isomer, and peaks 7 and 9 are the cis isomers.

[0042] Table 2. HPLC chromatogram of flavin crystals

[0043] <Peak Table>

[0044] Detector A 470nm

[0045] Peak Retention time area high Separation Probability (USP) high% Area / Height area% 1 3.692 3714 418 -- 0.028 8.890 0.020 2 4.824 66343 5308 4.237 0.353 12.498 0.348 3 5.355 2413 405 2.053 0.027 5.951 0.013 4 5.642 376 61 1.630 0.004 6.219 0.002 5 6.106 32460 2898 2.062 0.193 11.199 0.170 6 6.734 19260 1748 2.197 0.116 11.018 0.101 7 7.660 22873 749 2.398 0.050 30.557 0.120 8 8.486 18706110 1481678 2.043 98.440 12.625 98.220 9 10.469 167028 10403 5.182 0.691 16.056 0.877 10 10.963 4932 454 1.342 0.030 10.871 0.026 11 11.445 8475 595 1.385 0.040 14.245 0.045 12 12.212 7891 250 1.173 0.017 31.537 0.041 13 13.833 3262 185 2.344 0.012 17.618 0.017 total 19045138 1505152 100.000 100.000

[0046] Comparing the data in Table 2 and Table 1, it can be seen that the trans isomer of canthaxanthin crystals increased from 54.71% to 98.22% under the combined action of solvent A and auxiliary agent B, fully meeting the purity standard of canthaxanthin crystals.

[0047] Example 2

[0048] 100 g of crude canthaxanthin (70% effective content; trans isomer 54.71%) was added to 600 g of butanone and 30 g of DMSO. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 89.69%, the all-trans isomer content in the obtained canthaxanthin crystals was 96.96%, and the external standard content of the canthaxanthin crystals was 99.43%.

[0049] Example 3

[0050] 100 g of crude canthaxanthin (70% effective content; trans isomer 54.71%) was added to 600 g of tetrahydrofuran and 30 g of DMSO. The mixture was heated to reflux (66 °C) for isomerization for 8 hours, then cooled to 5 °C for crystallization for 2 hours. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 80.5%, and the content of the all-trans isomer in the obtained canthaxanthin crystals was 96.73%, with an external standard content of 99.40%.

[0051] Example 4

[0052] 100 g of crude canthaxanthin (70% effective content; trans isomer 54.71%) was added to 600 g of n-heptane and 30 g of DMSO. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 85.3%, and the content of the all-trans isomer in the obtained canthaxanthin crystals was 93.6%, with an external standard content of 94.63%.

[0053] Example 5

[0054] 100 g of crude canthaxanthin (70% effective content; trans isomer 54.71%) was added to 1000 g of 3-pentanone, followed by 50 g of DMSO. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 85.3%, and the content of the all-trans isomer in the obtained canthaxanthin crystals was 98.2%, with an external standard content of 99.97%.

[0055] Example 6

[0056] 100 g of crude canthaxanthin (70% effective content; trans isomer 54.71%) was added to 600 g of 3-pentanone, followed by 30 g of N-methylpyrrolidone. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 95.1%, the all-trans isomer content in the obtained canthaxanthin crystals was 98.1%, and the external standard content of the canthaxanthin crystals was 99.95%.

[0057] Example 7

[0058] 100 g of crude canthaxanthin (70% effective content; trans-isomer content 54.71%) was added to 600 g of 3-pentanone and 18 g of DMSO. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 95.3%, the all-trans isomer content in the obtained canthaxanthin crystals was 97.2%, and the external standard content of the canthaxanthin crystals was 99.8%.

[0059] Example 8

[0060] 100 g of crude canthaxanthin (70% effective content; trans-isomer content 54.71%) was added to 600 g of 3-pentanone and 6 g of DMSO. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 95.8%, the all-trans isomer content in the obtained canthaxanthin crystals was 94.2%, and the external standard content of the canthaxanthin crystals was 98.9%.

[0061] Example 9

[0062] 100 g of crude canthaxanthin (70% effective content; trans-isomer content 54.71%) was added to 200 g of 3-pentanone and 30 g of DMSO. The mixture was heated to 85 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 93.3%, the all-trans isomer content in the obtained canthaxanthin crystals was 96.2%, and the external standard content of the canthaxanthin crystals was 99.7%.

[0063] Example 10

[0064] 100 g of crude canthaxanthin (70% effective content; trans-isomer content 54.71%) was added to 600 g of 3-pentanone and 30 g of DMSO. The mixture was heated to 60 °C for 8 hours for isomerization, then cooled to 5 °C for 2 hours for crystallization. After centrifugation, washing, and drying, canthaxanthin crystals were obtained. The isomerization crystallization yield was 82.3%, and the content of the all-trans isomer in the obtained canthaxanthin crystals was 92.2%, with an external standard content of 99.8%.

[0065] Comparative Example 1

[0066] 100 g of crude canthaxanthin (70% effective content; trans isomer 54.71%) was added to 600 g of water, heated to 100 °C and refluxed for 8 h, then cooled to 5 °C and centrifuged. The resulting solid was then added to 500 g of dichloromethane, heated to 40 °C and refluxed for 2 h, followed by the addition of 50 g of methanol. The mixture was stirred for 2 h, cooled to 5 °C and crystallized for 3 h. After centrifugation and drying, canthaxanthin crystals were obtained. The overall yield was 78.35%, the all-trans isomer content in the obtained canthaxanthin crystals was 98.97%, and the external standard content of the canthaxanthin crystals was 98.85%.

[0067] In summary, the experimental results show that, based on the results of Example 1 and Comparative Example 1, the isomer crystallization yield of the present invention is 16.97% higher than that of the traditional process. The all-trans isomer content and external standard content in the obtained canthaxanthin crystals are 98.22% and 99.36% respectively, which are not significantly different from those of the canthaxanthin crystals obtained by the traditional process, both being >96%.

[0068] 1) The trans proportion of canthaxanthin crystals prepared by the preferred reagents of the method disclosed in this invention is all >96%, the content of external standard is all >96%, and the isomer crystallization yield is high.

[0069] 2) Effectively shortens operation steps, reduces labor intensity, and improves the working environment for workers.

[0070] 3) The solvent is easier to recycle and reuse, and avoids the use of highly toxic halogenated hydrocarbons.

[0071] 4) After recovering the solvent from the crystallization mother liquor, the amount of residue in the reactor is much less than that in the traditional two-stage heterogeneous crystallization process, which significantly reduces environmental pollution problems.

[0072] In the description of this specification, references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0073] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the claimed invention.

Claims

1. A method for preparing canthaxanthin crystals, characterized in that, Includes the following steps: Crude canthaxanthin was added to isomerization crystallization solvent A and auxiliary agent B, and the mixture was heated for isomerization. Then the mixture was cooled for crystallization, centrifuged, and the solid phase was vacuum dried to obtain canthaxanthin crystals.

2. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The heterogeneity temperature is 60–100°C.

3. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The crystallization temperature is -10 to 20°C.

4. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The crystallization temperature is 0–5°C.

5. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The isomeric crystallization solvent A is one or more of the following: 3-pentanone, butanone, tetrahydrofuran, n-heptane, and dioxane.

6. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The auxiliary agent B is one or both of DMSO or N-methylpyrrolidone.

7. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The mass percentage of the auxiliary agent B in the isomeric crystallization solvent A is 1% to 15%.

8. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The mass ratio of the isomeric crystallization solvent A to the crude flavin is (2-10):

1.

9. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The mass percentage of the auxiliary agent B in the isomeric crystallization solvent A is 3% to 5%; the mass ratio of the isomeric crystallization solvent A to the crude flavin is (3 to 8):

1.

10. The method for preparing canthaxanthin crystals according to claim 1, characterized in that, The crude canthaxanthin contains 65-75% effective canthaxanthin, and the trans isomer accounts for 50-60% of the canthaxanthin.

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