Carotenoid preparations, preparation methods, and applications thereof

Abstract

The present disclosure provides a carotenoid formulation, its preparation method and application, which includes the steps of: mixing carotenoid with an ethanol aqueous solution, stirring, dispersing by high-speed shear, adding an antioxidant, and removing the solvent until the ethanol solution residue is less than 10 ppm to obtain a pre-treated carotenoid, the moisture content of the pre-treated carotenoid being within the range of 10%-30%, mixing, stirring, and dispersing a wall material and a carbohydrate to prepare an aqueous solution having a first solid content to obtain a pre-treated gelled wall material, and mixing, emulsifying, and granulating the pre-treated carotenoid and the pre-treated gelled wall material to obtain a carotenoid formulation.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to Chinese Patent Application No. 202111633948.7 filed on December 28, 2021, Chinese Patent Application No. 202111682238.3 filed on December 28, 2021, and Chinese Patent Application No. 202210083689.3 filed on January 23, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to the technical field of microparticulate formulations, and in particular to carotenoid formulations, preparation methods, and applications thereof. [Background technology]

[0003] As the main source of vitamin A in the human body, carotenoids possess immunomodulatory, antioxidant, anticancer, and anti-aging functions, which can have beneficial effects on human health. However, carotenoids are insoluble in water, have low solubility in oil, and are unstable in light, oxygen, and heat environments, limiting the application of carotenoid-related formulations. Furthermore, carotenoids such as lutein can be prepared by saponification, which requires a large amount of alkali and takes a long time, resulting in alkaline wastewater and is not environmentally friendly.

[0004] Therefore, there is a need to provide carotenoid preparations, preparation methods and applications to optimize the preparation process of carotenoids and improve the stability and application of carotenoid preparations. Summary of the Invention

[0005] One or more embodiments of the present disclosure provide a carotenoid preparation. The carotenoid preparation is obtained by mixing, emulsifying, and granulating a pre-processed carotenoid and a pre-processed gelling wall material. The amount of the pre-processed gelling wall material is 40% to 80% by weight of the carotenoid preparation. The raw materials for the pre-processed gelling wall material include a wall material and a carbohydrate. The wall material includes a modified starch or a mixture of starch and a cellulose derivative. The carbohydrate includes at least one of sucrose, glucose, glucose syrup, xylose, malto-oligosaccharides, fructooligosaccharides, and corn syrup solids.

[0006] One or more embodiments of the present disclosure provide a method for preparing a carotenoid formulation, the method including the steps of: mixing a carotenoid with an aqueous ethanol solution, stirring, and dispersing by high-speed shear; adding an antioxidant; and removing the solvent until the ethanol solution residue is less than 10 ppm to obtain a pre-processed carotenoid, wherein the moisture content of the pre-processed carotenoid is within the range of 10% to 30%; mixing, stirring, and dispersing a wall material and a carbohydrate to prepare an aqueous solution having a first solid content to obtain a pre-processed gelled wall material; and mixing, emulsifying, and granulating the pre-processed carotenoid and the pre-processed gelled wall material to obtain a carotenoid formulation.

[0007] One or more embodiments of the present disclosure provide applications for carotenoid formulations, including applications in the fields of food, beverages, healthcare products, and pharmaceuticals. [Brief explanation of the drawings]

[0008] The present disclosure will be further described with reference to exemplary embodiments, which will be described in detail with reference to the drawings, in which like numerals represent like structures. [Figure 1] 1 is an exemplary flow chart illustrating a process for a method for preparing a carotenoid formulation according to some embodiments of the present disclosure. [Figure 2A] FIG. 1 is an exemplary view of a soft candy of lutein product A according to some embodiments of the present disclosure. [Figure 2B] FIG. 1 is an exemplary appearance diagram of a soft candy of Zeaxanthin Product B according to some embodiments of the present disclosure. [Figure 3] 1 is an exemplary flow chart illustrating a process for a method for preparing a carotenoid formulation according to some embodiments of the present disclosure. [Figure 4A] FIG. 1 is an exemplary view of a soft candy of lutein product A according to some embodiments of the present disclosure. [Figure 4B] FIG. 1 is an exemplary external view of β-carotene product B according to some embodiments of the present disclosure. [Figure 5] 1 is an exemplary curve showing the absorbance of lutein standard solutions of different concentrations, according to some embodiments of the present disclosure. [Figure 6] 1 is an exemplary bar graph of cellular uptake rates of lutein crystals and lutein product A, according to some embodiments of the present disclosure. [Figure 7] 1 is an exemplary curve showing the absorbance of zeaxanth standard solutions of different concentrations, according to some embodiments of the present disclosure. [Figure 8] 1 is an exemplary bar graph of cellular uptake rates of zeaxanthin crystals and zeaxanthin product A, according to some embodiments of the present disclosure. [Figure 9] FIG. 1 is an exemplary diagram of the detection results of the chiral structure of zeaxanthin according to some embodiments of the present disclosure. [Figure 10] 1 is an exemplary flow chart illustrating a process for a method for preparing lutein according to some embodiments of the present disclosure. [Figure 11] 1 is an exemplary schematic diagram of a "Y" type connection valve connecting pipelines, according to some embodiments of the present disclosure. FIG. DETAILED DESCRIPTION OF THE INVENTION

[0009] In order to more clearly explain the technical scheme of the embodiments of the present specification, a brief description of the accompanying drawings necessary for describing the embodiments is provided below. Obviously, the following accompanying drawings are merely some examples or embodiments of the present specification, and those skilled in the art can apply the present specification to other similar scenarios according to these accompanying drawings without creative efforts. Unless clearly derived from the context or unless the context explains otherwise, the same symbols in the drawings refer to the same structures or operations.

[0010] It should be understood that the terms "system," "device," "unit," and / or "module" used in this disclosure are ways used to distinguish between different components, elements, parts, portions, or assemblies at different levels, although other terms may be substituted if they achieve a similar purpose.

[0011] As used in this specification and claims, the words "one," "a," "a kind," and / or "the" are not specifically singular but may include plural forms unless the context clearly suggests otherwise. Generally speaking, the terms "comprising" and "including" only mean the inclusion of explicitly identified steps and elements, and do not constitute an exclusive list, and the method or apparatus may include other steps or elements.

[0012] Carotenoids are physiological antioxidants that can prevent lipid peroxidation and have beneficial effects on health. However, carotenoids are insoluble in water and have very low solubility in fats and oils. At the same time, carotenoids are unstable to light, oxygen, and heat. Conventional methods involve microencapsulation of carotenoids, which can improve their bioavailability and simultaneously improve their coloring properties. As a result, carotenoid products tend to stain clothing and hands, affecting aesthetics and creating an unpleasant consumer experience.

[0013] Carotenoids include lutein, which has antioxidant properties and may protect eyesight and delay early arteriosclerosis. Currently, traditional processes generally involve the saponification of lutein esters to prepare lutein, but this process requires a large amount of alkali, which generates alkaline wastewater, and a large amount of organic solvents, making it unfriendly to the environment. The saponification time is relatively long, and the purity of the lutein in the prepared product is low.

[0014] Some embodiments of the present disclosure provide carotenoid preparations, preparation methods, and applications. In some embodiments, carotenoids may be pretreated, and pretreated gelling wall materials may be prepared using different materials and carbohydrate wall materials in different weight ratios. Carotenoid preparations may be prepared using the pretreated carotenoids and the pretreated gelling wall materials. This not only reduces the release rate of carotenoids in hydrochloric acid solution, avoids destruction by gastric acid, and maintains the biological activity of carotenoids, but also effectively reduces the pigment dissolution rate and prevents staining of clothes, tongues, hands, etc. during use of carotenoid products. In some embodiments, when preparing lutein crystals, lutein is prepared by a tube reaction combined with alcoholysis, and the lutein is purified using a complexing agent. This shortens production time, reduces the amount of alkali, is environmentally friendly, and improves the production efficiency of lutein crystals.

[0015] In some embodiments, the carotenoid formulations may be applied in various fields, such as food, beverages, health products, pharmaceuticals, or other fields. In some embodiments, the carotenoid formulations may also be applied in the preparation of products requiring nutrient visualization, soft candy, solid drinks, liquid drinks, tablets, solid dosage forms, eye gels, or eye drops.

[0016] Carotenoids are physiological antioxidants that can prevent lipid peroxidation and provide beneficial health effects. However, carotenoids are insoluble in water and have very low solubility in fats and oils. At the same time, carotenoids are unstable, being vulnerable to light, oxygen, and heat. Conventional methods involve microencapsulating carotenoids, which can improve bioavailability and simultaneously improve dyeability, resulting in increased staining of clothing, hands, and other surfaces during use of carotenoid products. In some embodiments of the present disclosure, carotenoid formulations are obtained by pretreating carotenoids, adding antioxidants, and encapsulating the pretreated carotenoids using a gelling wall material. This not only maintains the biological activity of the carotenoids, but also effectively reduces the pigment dissolution rate.

[0017] In some embodiments, the carotenoid formulation can be obtained by mixing, emulsifying, and granulating the pre-processed carotenoid and the pre-processed gelling wall material. For details on the preparation of the carotenoid formulation, see Figure 1 and the associated description, which will not be repeated here.

[0018] In some embodiments, the amount of pre-treated gelling wall material may be in the range of 40% to 80% by weight of the carotenoid formulation. In some embodiments, the amount of pre-treated gelling wall material may be in the range of 60% to 80% by weight of the carotenoid formulation. In some embodiments, the amount of pre-treated gelling wall material may be in the range of 65% to 70% by weight of the carotenoid formulation.

[0019] In some embodiments, the raw materials for the pretreated gelling wall material may include a wall material and a carbohydrate. In some embodiments, the weight ratio of the wall material to the carbohydrate may be in the range of 1:(1-5). In some embodiments, the weight ratio of the wall material to the carbohydrate may be in the range of 1:(2-4). In some embodiments, the weight ratio of the wall material to the carbohydrate may be in the range of 1:(3-4). In some embodiments, the wall material may include a mixture of starch and a cellulose derivative. Starch is a type of natural macromolecular compound of polysaccharide substances polymerized from glucose molecules. For example, starch may include, but is not limited to, corn starch, tapioca starch, potato starch, etc. In some embodiments, the wall material may also include gum arabic. In some embodiments, the carbohydrate may include at least one of sucrose, glucose, glucose syrup, xylose, malto-oligosaccharides, fructooligosaccharides, and corn syrup solids.

[0020] In some embodiments, the carotenoid may include at least one of lutein, lutein fatty acid esters, zeaxanthin, lycopene, alpha-carotene, beta-carotene, canthaxanthin, and astaxanthin.

[0021] In some embodiments, the total pigment content of the pre-processed carotenoids may be greater than 70%. In some embodiments, the total pigment content of the pre-processed carotenoids may be greater than 80%. In some instances, the total pigment content of the pre-processed carotenoids may be greater than 90%.

[0022] In some embodiments, the preprocessed carotenoid source can be obtained by mixing lutein or lutein fatty acid esters, zeaxanthin, and β-carotene in a weight ratio of (1-3):(1-3):(1-3). In some embodiments, the preprocessed carotenoid source can be obtained by mixing lutein or lutein fatty acid esters, zeaxanthin, and β-carotene in a weight ratio of (2-3):(1-2):(1-2). In some embodiments, the preprocessed carotenoid source can be obtained by mixing lutein or lutein fatty acid esters, zeaxanthin, and β-carotene in a weight ratio of (1-2):(1-2):(1-2).

[0023] In some embodiments, the pretreated zeaxanthin crystals may contain two isomers, (3R,3'R)-zeaxanthin and (3R,3'S)-zeaxanthin, and the two isomers may account for more than 80% of the weight of the zeaxanthin crystals. In some embodiments, the weight ratio of the two isomers, (3R,3'R)-zeaxanthin to (3R,3'S)-zeaxanthin, may be in the range of (5-15%):(95-85%).

[0024] In some embodiments, the wall material may be a mixture of starch and a cellulose derivative in a weight ratio of 1:(1-2). In some embodiments, the wall material may be a mixture of starch and a cellulose derivative in a weight ratio of 1:(1-1.8). In some embodiments, the wall material may be a mixture of starch and a cellulose derivative in a weight ratio of 1:(1.2-1.5).

[0025] In some embodiments, the carotenoid formulation may have a pigment solubility in water of less than 1%. In some embodiments, the carotenoid formulation may have a pigment solubility in water of less than 0.5%. In some embodiments, the carotenoid formulation may have a pigment solubility in water of less than 0.3%.

[0026] 1 is an exemplary flow chart illustrating a process for a method for preparing a carotenoid formulation according to some embodiments of the present disclosure. Process 100 may include the following steps:

[0027] Step S110: Carotenoid and ethanol aqueous solution are mixed, stirred, dispersed by high speed shear, antioxidant is added, and solvent is removed until the ethanol solution residue is less than 10 ppm, thereby obtaining pre-treated carotenoid.

[0028] In some embodiments, the moisture content of the pre-processed carotenoid may be in the range of 10% to 30%. In some embodiments, the moisture content of the pre-processed carotenoid may be in the range of 10% to 25%. In some embodiments, the moisture content of the pre-processed carotenoid may be in the range of 20% to 30%.

[0029] In some embodiments, the carotenoid source can be obtained by mixing lutein or lutein fatty acid esters, zeaxanthin, and β-carotene in a weight ratio of (1-3):(1-3):(1-3). For details about the carotenoid source, please refer to the above description and will not be repeated here.

[0030] In some embodiments, the carotenoid may be mixed with a 3-5x aqueous solution of ethanol, in some embodiments, a 3-3.8x aqueous solution of ethanol, in some embodiments, a 4-5x aqueous solution of ethanol.

[0031] In some embodiments, the mass fraction of the aqueous ethanol solution may be in the range of 50% to 70%. In some embodiments, the mass fraction of the aqueous ethanol solution may be in the range of 50% to 60%. In some embodiments, the mass fraction of the aqueous ethanol solution may be in the range of 55% to 70%.

[0032] In some embodiments, the mixed solution may be dispersed by high-speed shearing while being stirred for at least 20 minutes at a temperature of 40° C. to 50° C. In some embodiments, the mixed solution may be dispersed by high-speed shearing while being stirred for at least 20 minutes at a temperature of 40° C. to 45° C.

[0033] In some embodiments, the pretreated carotenoid can be obtained by adding an antioxidant to the mixed solution and removing the solvent at a temperature of 70°C to 80°C until the ethanol solution residue is less than 10 ppm.

[0034] In some embodiments, the amount of antioxidant added may be in the range of 5% to 30% of the weight of the carotenoid. In some embodiments, the amount of antioxidant added may be in the range of 5% to 20% of the weight of the carotenoid. In some embodiments, the amount of antioxidant added may be in the range of 15% to 30% of the weight of the carotenoid.

[0035] In some embodiments, the antioxidant may comprise at least one of ascorbic acid, ascorbyl palmitate, sucrose fatty acid esters, tocopherol, fatty acid ascorbates, butylated hydroxytoluene, butylated hydroxyanisole, propyl gallate, and tert-butylhydroxyquinone. In some embodiments, the antioxidant may be a mixture of ascorbic acid, ascorbyl palmitate, and sucrose fatty acid esters.

[0036] In some embodiments, the weight ratio of ascorbic acid, ascorbyl palmitate, and sucrose fatty acid ester may be within the range of (2-5):(0.1-3):(0.1-3). In some embodiments, the weight ratio of ascorbic acid, ascorbyl palmitate, and sucrose fatty acid ester may be within the range of (2-4):(0.1-2):(0.1-2). In some embodiments, the weight ratio of ascorbic acid, ascorbyl palmitate, and sucrose fatty acid ester may be within the range of (2-4):(2-3):(2-3).

[0037] Step S120: Mix the wall material and the carbohydrate in a weight ratio of 1:(1-5) to prepare an aqueous solution having a first solid content, and then stir and disperse the aqueous solution to obtain a pretreated gelled wall material.

[0038] In some embodiments, the wall material and carbohydrate may also be mixed in a weight ratio of 1:(1-4). In some embodiments, the wall material and carbohydrate may be mixed in a weight ratio of 1:(3-5).

[0039] In some embodiments, the aqueous solution having a first solid content may be an aqueous solution having a solid content of 50% to 70%. In some embodiments, the aqueous solution having a first solid content may be an aqueous solution having a solid content of 50% to 60%. In some embodiments, the aqueous solution having a first solid content may be an aqueous solution having a solid content of 55% to 70%.

[0040] In some embodiments, the aqueous solution may be stirred to disperse at 50°C to 70°C, and stirred at 80°C to 90°C for 15 to 45 minutes.

[0041] In some embodiments, the wall material may be a mixture of starch and a cellulose derivative. In some embodiments, the starch and the cellulose derivative may be mixed in a weight ratio of 1:(1 to 2). In some embodiments, the starch and the cellulose derivative may be mixed in a weight ratio of 1:(1.2 to 1.5).

[0042] In some embodiments, the cellulose derivative may include at least one of hypromellose, methylcellulose, ethylcellulose, and sodium carboxymethylcellulose. In some embodiments, the viscosity of the cellulose derivative may be in the range of 2 cP to 15 cP. In some embodiments, the viscosity of the cellulose derivative may be in the range of 5 cP to 12 cP. In some embodiments, the viscosity of the cellulose derivative may be in the range of 7 cP to 10 cP.

[0043] Step S130: The pre-processed carotenoid and the pre-processed gelling wall material are mixed, emulsified and granulated to obtain a carotenoid preparation.

[0044] According to the above process, the carotenoid preparation is prepared by pretreating carotenoids, adding antioxidants, and then encapsulating the pretreated carotenoids in a gelling wall material. This effectively reduces the pigment dissolution rate of the product, improves the stability of the carotenoids, and maintains their biological activity. Furthermore, since no organic solvents are used in the preparation process, the entire preparation process is more environmentally friendly.

[0045] The method for preparing a carotenoid preparation is described in detail in the following embodiments A1 to A4, comparative embodiments A5 to A7, and effect embodiments A8 to A9. It should be noted that the reaction conditions, reaction materials, and amounts of reaction materials in embodiments A1 to A4 are only intended to illustrate the method for preparing a carotenoid preparation and do not limit the scope of protection of the present disclosure. Each of embodiments A1 to A4 uses different reaction conditions and material weight ratios. Comparative embodiments A5 to A7 are controls for embodiments A2 to A4. Effect embodiments A8 to A9 compare the actual effects of a product prepared according to embodiment A2 with those prepared according to the prior art.

[0046] In this disclosure, percentages and contents are calculated by mass unless otherwise specified. Unless otherwise noted, the experimental methods used are conventional methods, and the materials and reagents used can be purchased from commercial sources.

[0047] In the preparation process of the carotenoid formulation in the present disclosure, one or more of the following ingredients may be optionally added according to conventional dosages in this field:

[0048] (1) Water-soluble components: The water-soluble components include, but are not limited to, one or more of glucose, lactose, malto-oligosaccharides, polyethylene glycol, sodium carboxymethylcellulose, and solid glucose syrup.

[0049] (2) Surfactants. Surfactants can be used to solve the problem that products made of water-insoluble fats or waxy substances usually float on the water surface and to improve the water dispersibility of the product. The surfactants may include, but are not limited to, one or more of Tween 60, Tween 80, or sucrose fatty acid esters.

[0050] (3) Binders: The binders may include, but are not limited to, one or more of povidone, glycerin, propylene glycol, polyglycerol fatty acid esters, soluble soy polysaccharides, and sodium carboxymethylcellulose.

[0051] (4) Suspending agents may include, but are not limited to, one or more of guar gum, xanthan gum, sodium alginate, hydroxypropyl methylcellulose, methylcellulose, gellan gum, and carrageenan.

[0052] (5) Diluents: Diluents may include, but are not limited to, one or more of starch, maltodextrin, and calcium hydrogen phosphate.

[0053] (6) Stabilizers: The stabilizers may include, but are not limited to, one or more of sodium lactate, sodium citrate, magnesium carbonate, sodium bicarbonate, and microcrystalline cellulose.

[0054] (7) Lubricants: Lubricants may include, but are not limited to, one or more of silicon dioxide, corn starch, and calcium silicate.

[0055] (8) Antioxidants: Antioxidants may include, but are not limited to, one or more of vitamin E, vitamin C, vitamin E derivatives, and vitamin C derivatives.

[0056] (9) pH Adjusting Agents: The pH adjusting agent may include, but is not limited to, one or more of citric acid, lactic acid, and malic acid.

[0057] In this disclosure, the following methods are used to measure and evaluate products.

[0058] The method for measuring the dye dissolution rate described in this disclosure is to take 1g of the product, add 50mL of water, dissolve under 90℃ temperature and 100rpm rotation speed for 30 minutes, then filter, transfer the filtrate into a measuring flask, wash the filtrate once with 30mL of water, combine the filtrates, and measure the optical density (OD) at the maximum absorption wavelength after a constant volume. The dye dissolution rate is (OD / mass of product) x 100%.

[0059] The accelerated stability evaluation method for the product in this disclosure is the following method provided by the Chinese Pharmacopoeia: Stability is determined by measuring the pigment content at different times under conditions of 40°C temperature and 75% relative humidity, and the pigment retention rate is used to indicate the stability of the product. The pigment retention rate is the ratio of the product content at different times to the initial content, and can be expressed as a percentage.

[0060] Embodiment A1: Effect of crystal processing method on crystal stability

[0061] (1) Zeaxanthin crystal A can be obtained by mixing 160 g of zeaxanthin crystals with four volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 28 g of ascorbic acid, 10 g of ascorbyl palmitate, and 10 g of sucrose fatty acid ester, and removing the solvent at 75°C. The ethanol-soluble residue in zeaxanthin crystal A is 8 ppm, and the moisture content of the zeaxanthin crystals is 12.3%.

[0062] (2) Zeaxanthin crystal B can be obtained by mixing 160 g of zeaxanthin crystals with four times the volume of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 28 g of ascorbic acid and 10 g of ascorbyl palmitate, and removing the solvent at 75°C. The ethanol-soluble residue in zeaxanthin crystal B is 55 ppm, and the moisture content of the zeaxanthin crystals is 25%.

[0063] (3) Zeaxanthin crystal C can be obtained by mixing 160 g of zeaxanthin crystals with 8 volumes of 80% ethanol aqueous solution, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 28 g of ascorbic acid, 10 g of ascorbyl palmitate, and 10 g of sucrose fatty acid ester, and removing the solvent at 75°C. The ethanol-soluble residue in zeaxanthin crystal C is 155 ppm, and the moisture content of the zeaxanthin crystals is 32%.

[0064] (4) Zeaxanthin crystal D can be obtained by mixing 160 g of zeaxanthin crystal, 28 g of ascorbic acid, 10 g of ascorbyl palmitate, and 10 g of sucrose fatty acid ester.

[0065] (5) The pigment retention rate at different times can be measured by heating the above zeaxanthin crystals A to D at 60° C. The measurement results are shown in Table 1. Table 1. Dye retention rate at different times JPEG0007734198000001.jpg55170

[0066] Comparing the pigment retention rates of zeaxanthin crystals A to D, zeaxanthin crystal B, which has an ethanol-soluble residue of over 10 ppm after solvent removal, zeaxanthin crystal C, obtained by mixing carotenoids with more than five times the volume of aqueous ethanol, and zeaxanthin crystal D, obtained without pretreatment, reveals that the pigment retention rate of zeaxanthin crystal A is significantly greater. Zeaxanthin crystal A, with a water content of 12.3% (within the range of 10% to 30%), is obtained by mixing carotenoids with four times the volume (within the range of 3 to 5 times the volume of aqueous ethanol), stirring, high-speed shear dispersion, adding antioxidants, and removing the solvent until the ethanol-soluble residue is 8 ppm (less than 10 ppm).

[0067] In some embodiments, zeaxanthin crystals containing different isomer ratios are also selected for comparative experiments according to embodiment A1. That is, the zeaxanthin crystals contain two isomers of zeaxanthin, (3R, 3'R)-zeaxanthin and (3R, 3'S)-zeaxanthin, and the two isomers account for more than 80% of the weight of the zeaxanthin crystals. In some embodiments, the weight ratio between the two isomers (3R, 3'R)-zeaxanthin and (3R, 3'S)-zeaxanthin can be within the range of (5% to 15%):(95% to 85%), which does not affect the pigment retention results of the zeaxanthin crystals A prepared according to step (1) of embodiment A1.

[0068] Embodiment A2

[0069] Processed lutein crystals can be obtained by mixing 178 g of lutein crystals with three volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester, and removing the solvent at 75°C. The processed lutein crystals are frozen at -20°C for standby storage. The ethanol-soluble residue of the processed lutein crystals is 7 ppm, and the moisture content of the lutein crystals is 10%. An aqueous solution with 50% solids is obtained by mixing 160 g of corn starch, 480 g of sucrose, and 160 g of hydroxypropyl methylcellulose (viscosity of 15 cP). After stirring and dispersing at 60°C, the aqueous solution is heated to 90°C, stirred at a constant speed for 45 minutes, and then left at room temperature. The gelling wall material and the treated lutein crystals are mixed, stirred, emulsified, and spray-dried to obtain Lutein Product A, whose pigment solubility is 0.2%.

[0070] Embodiment A3

[0071] Treated β-carotene crystals were obtained by mixing 212 g of β-carotene crystals with 5 volumes of 50% aqueous ethanol, stirring at 40°C for 40 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 17 g of ascorbic acid, 25.5 g of ascorbyl palmitate, and 25.5 g of sucrose fatty acid esters, and removing the solvent at 70°C. The treated β-carotene crystals were frozen at -20°C for standby storage. The ethanol-soluble residue of the treated β-carotene crystals was 5 ppm, and the moisture content of the β-carotene crystals was 15%. An aqueous solution with 50% solids was obtained by mixing 160 g of tapioca starch, 480 g of sucrose, and 160 g of hydroxypropyl methylcellulose (viscosity of 2.5 cP). After stirring and dispersing at 50°C, the aqueous solution is heated to 80°C, stirred at a constant speed for 15 minutes, and then left at room temperature. The gelled wall material and the treated β-carotene crystals are mixed, stirred, emulsified, and spray-dried. β-carotene crystal product A is obtained, with a pigment dissolution rate of 0.4%.

[0072] Embodiment A4

[0073] The processed composite crystals were obtained by mixing 81 g of β-carotene crystals, 162 g of lutein ester crystals, 81 g of zeaxanthin crystals, and 4 volumes of 70% aqueous ethanol, stirring at 50°C for 55 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 73 g of ascorbic acid, 1.5 g of ascorbyl palmitate, and 1.5 g of sucrose fatty acid ester, and removing the solvent at 80°C. The processed composite crystals were frozen at -20°C for standby storage. The ethanol-soluble residue in the processed composite crystals was 3 ppm, and the moisture content of the composite crystals was 30%. An aqueous solution with 50% solids was prepared using 100 g of potato starch, 300 g of sucrose, and 200 g of hydroxypropyl methylcellulose (viscosity of 5 cP). After stirring and dispersing at 70°C, the solution is heated to 82°C, stirred at a constant speed for 30 minutes, and then left at room temperature. The gelling wall material and the treated composite crystals are mixed, stirred, emulsified, and spray-dried. Product A is obtained, which has a 2:1:1 ratio of lutein esters, zeaxanthin, and β-carotene, and its pigment solubility is 0.26%.

[0074] From embodiments A2 to A4, carotenoid crystals with an ethanol-soluble residue of less than 10 ppm and a moisture content of 10% to 30% can be obtained by mixing carotenoid with 3 to 5 times the volume of a 50% to 70% ethanol aqueous solution, stirring, high-speed shear dispersion, adding an antioxidant, and removing the solvent. At least starch and cellulose derivatives are used as wall materials, and the wall material and carbohydrate are mixed in a weight ratio of 1:(1 to 5) to obtain an aqueous solution with a solid content of 50 to 70%. The pretreated gelled wall material is obtained by stirring and dispersing the aqueous solution. A carotenoid preparation is prepared by mixing the treated carotenoid crystals with the gelled wall material. The pigment solubility of the carotenoid preparation is less than 1%, which makes it less likely to stain clothes, tongue, etc. during use.

[0075] Comparative embodiment A5

[0076] Treated zeaxanthin crystals were obtained by mixing 178 g of zeaxanthin crystals with three volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing at 10,000 rpm, adding 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester, and removing the solvent at 75°C. The treated zeaxanthin crystals were frozen at -20°C for storage. The ethanol-soluble residue in the treated zeaxanthin crystals was 7 ppm, and the moisture content of the treated zeaxanthin crystals was 12.8%. An aqueous solution with 50% solids was prepared using 160 g of tapioca starch, 480 g of sucrose, and 160 g of hydroxypropyl methylcellulose (viscosity of 10 cP). The treated zeaxanthin crystals were then added to the aqueous solution. Zeaxanthin Product B is obtained after stirring, emulsifying, and spray drying. The pigment dissolution rate of Zeaxanthin Product B is 67.7%.

[0077] Compared with embodiments A2 to A4, the wall material of comparative embodiment A5 is not subjected to a gelling treatment (heating, stirring, and static treatment to gel the wall material are not performed), and therefore the pigment dissolution rate of the prepared product increases, and the effect of use decreases.

[0078] Comparative embodiment A6

[0079] 200g of lutein crystals, 20g of ascorbic acid, 1g of ascorbyl palmitate, and 1g of sucrose fatty acid esters were mixed. An aqueous solution with a 50% solids content was prepared using 160g of tapioca starch, 480g of sucrose, and 160g of hydroxypropyl methylcellulose (viscosity of 10cP). After stirring and dispersing at 50°C, the aqueous solution was heated to 80°C, stirred at a constant speed for 15 minutes, and then allowed to stand at room temperature. Lutein Product B was obtained by mixing, stirring, emulsifying, and spray-drying the gelling wall material and lutein crystals, and its pigment solubility was 30.2%.

[0080] Compared with embodiments A2 to A4, the lutein crystals in comparative embodiment A6 are not pre-treated (the lutein crystals are not mixed and stirred with an ethanol solution, and are not pre-treated by high-speed shear dispersion and solvent removal), which increases the pigment dissolution rate of the prepared product and reduces the use effect.

[0081] Comparative embodiment A7

[0082] The processed lutein ester crystals were obtained by mixing 200 g of lutein ester crystals with three volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester, and removing the solvent at 75°C. The processed lutein ester crystals were frozen at -20°C for standby storage. The ethanol-soluble residue in the processed lutein ester crystals was 7 ppm, and the moisture content of the processed lutein ester crystals was 10%. The processed lutein ester crystals were added to the gelling wall material compositions shown in Table 2 and processed according to the gelling method of embodiment A2. The product effects are shown in Table 2 below. Table 2 Comparison of dissolution effects when using different gelling wall materials JPEG0007734198000002.jpg109170

[0083] Compared with Embodiments A2 to A4, lutein ester product A and lutein ester product B in Comparative Embodiment A7 combine only one wall material (corn starch or hydroxypropyl methylcellulose) with a carbohydrate (sucrose), resulting in increased pigment dissolution rates and reduced efficacy. Lutein ester product C in Comparative Embodiment A7 is formulated without a carbohydrate, resulting in increased pigment dissolution rates and reduced efficacy. Lutein ester product D in Comparative Embodiment A7 uses corn starch and gum arabic as wall materials and gelatinizes with sucrose, but the weight ratio of wall material to carbohydrate is not within the range of 1:(1 to 5), resulting in increased pigment dissolution rates and reduced efficacy. Lutein ester product E in Comparative Embodiment A7 uses highly viscous hydroxypropyl methylcellulose as a wall material, resulting in increased pigment dissolution rates and reduced efficacy. The products of embodiments A2 to A4 are prepared by the preparation method of the present disclosure, and the pigment dissolution rate of the products is lower than that of each product of comparative embodiment A7, and the use effect is better.

[0084] Effect embodiment A8

[0085] Combined Product 1 is obtained by using lutein, zeaxanthin, and beta-carotene prepared according to the method of Patent CN108185424B (Patent Application No. CN201711456450.1) in a weight ratio of 1:1:1. Combined Product 2 is obtained by using lutein, zeaxanthin, and beta-carotene prepared according to the method of Embodiment A2 in a weight ratio of 1:1:1. The comparative parameters of the two products are shown in Table 3 below. Table 3 Comparison parameters of the two products JPEG0007734198000003.jpg34170

[0086] Comparing composite product 1 and composite product 2, it can be seen that the pigment dissolution rate of composite product 2 prepared by the preparation process of the present disclosure (embodiment A2) is lower than that of composite product 1 prepared according to the preparation method of patent CN108185424B. This indicates that compared with composite product 1, composite product 2 is less likely to cause staining on hands, tongues, and other parts, and has better application value, and therefore the effect of composite product 2 prepared using embodiment A2 is better.

[0087] Effect embodiment A9: Application evaluation of soft candy

[0088] Solution I is obtained by weighing 8 g of gelatin, 44 g of white sugar, and 55 g of glucose syrup, adding water at 20% solid content, stirring to dissolve, boiling the sugar at 120 °C until the solid content is about 85%, and adjusting the pH to 3-4.

[0089] 20 g of lutein Product A prepared according to the method of Embodiment A2 or 20 g of zeaxanthin Product B prepared according to the method of Comparative Embodiment A5 was added to Solution I, and the solution was stirred uniformly and maintained at 90°C for 40 minutes. After injection molding and drying, soft candies containing lutein Product A and zeaxanthin Product B were obtained, the appearances of which are shown in Figures 2A and 2B, respectively. It can be seen that lutein Product A did not stain the soft candies and was completely preserved within the soft candies, achieving a nutritional visualization effect. However, zeaxanthin Product B stained the soft candies red, reducing their transparency.

[0090] The above is merely a preferred embodiment of the present invention, and the protection scope of the present invention is not limited thereto. Any modifications or replacements that can be easily thought up by those skilled in the art within the scope of the present disclosure shall be included within the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be determined by the protection scope of the claims.

[0091] In some embodiments, a carotenoid formulation may be prepared by mixing a pretreated carotenoid with a pretreated gelling wall material having a different composition or different composition ratio. For details on the preparation method of the carotenoid formulation, see Figure 3 and the related description, which will not be repeated here. In some embodiments of the present disclosure, a carotenoid is pretreated, starch is used as the wall material raw material, a pretreated gelling wall material is prepared using a wall material and a carbohydrate in a weight ratio of (1-5:1), and a carotenoid formulation is prepared using the pretreated carotenoid and the gelling wall material. This not only reduces the release rate of the carotenoid in hydrochloric acid solution, preventing its destruction by gastric acid, but also maintains the biological activity of the carotenoid, while also achieving a relatively high release rate in phosphate buffer, thereby facilitating intestinal absorption. The carotenoid formulation also effectively reduces the pigment dissolution rate, preventing staining of clothes, tongues, hands, etc. during use of the carotenoid product.

[0092] In some embodiments, the preprocessed carotenoid source can be obtained by mixing lutein or lutein fatty acid esters, zeaxanthin, and β-carotene in a weight ratio of (1-3):(1-3):(1-3). In some embodiments, the preprocessed carotenoid source can be obtained by mixing lutein or lutein fatty acid esters, zeaxanthin, and β-carotene in a weight ratio of (2-3):(1-2):(1-2). In some embodiments, the preprocessed carotenoid source can be obtained by mixing lutein or lutein fatty acid esters, zeaxanthin, and β-carotene in a weight ratio of (1-2):(1-2):(1-2).

[0093] In some embodiments, the pretreated zeaxanthin crystals comprise two isomers, (3R,3'R)-zeaxanthin and (3R,3'S)-zeaxanthin, with the two isomers comprising greater than 80% by weight of the zeaxanthin crystals. In some embodiments, the weight ratio of the two isomers, (3R,3'R)-zeaxanthin to (3R,3'S)-zeaxanthin, may be within the range of (5-15%):(95-85%).

[0094] In some embodiments, the amount of pre-treated gelling wall material may be in the range of 40% to 70% by weight of the carotenoid formulation. In some embodiments, the amount of pre-treated gelling wall material may be in the range of 45% to 60% by weight of the carotenoid formulation. In some embodiments, the amount of pre-treated gelling wall material may be in the range of 50% to 70% by weight of the carotenoid formulation.

[0095] In some embodiments, the raw materials for the pretreated gelling wall material may include a wall material and a carbohydrate. In some embodiments, the weight ratio of the wall material to the carbohydrate may be within a range of (1-5):1. In some embodiments, the weight ratio of the wall material to the carbohydrate may be within a range of (2-4):1. In some embodiments, the weight ratio of the wall material to the carbohydrate may be within a range of (3-3.5):1. In some embodiments, the wall material may include a modified starch. Modified starch refers to a polymeric compound obtained by introducing new functional groups into starch molecules or by changing the size of the starch molecules or the properties of the starch granules using physical, chemical, or enzymatic methods. In some embodiments, the modified starch may include, but is not limited to, starch sodium octenyl succinate. In some embodiments, the wall material may also include gum arabic. In some embodiments, the wall material may also include a cellulose derivative.

[0096] For details regarding the potential carbohydrate components, the potential carotenoid components, and the total pigment content in the pre-processed carotenoids, please see the relevant descriptions above.

[0097] In some embodiments, the carotenoid formulation may have a pigment solubility in water of less than 5%. In some embodiments, the carotenoid formulation may have a pigment solubility in water of less than 4%. In some embodiments, the carotenoid formulation may have a pigment solubility in water of less than 3%.

[0098] In some embodiments, the carotenoid formulation is released into gastrointestinal fluid at a rate of less than 35% in 0.5 hours. In some embodiments, the carotenoid formulation is released into gastrointestinal fluid at a rate of less than 30% in 0.5 hours. In some embodiments, the carotenoid formulation is released into gastrointestinal fluid at a rate of less than 25% in 0.5 hours.

[0099] In some embodiments, the 4-hour release rate of the carotenoid formulation into gastrointestinal fluid is greater than 90%. In some embodiments, the 4-hour release rate of the carotenoid formulation into gastrointestinal fluid is greater than 95%. In some embodiments, the 4-hour release rate of the carotenoid formulation into gastrointestinal fluid is greater than 98%.

[0100] 3 is an exemplary flow chart illustrating a process for a method for preparing a carotenoid formulation according to some other embodiments of the present disclosure. Process 300 may include the following steps:

[0101] Step S310: Pre-treated carotenoid is obtained by mixing carotenoid with an aqueous ethanol solution, stirring, dispersing by high-speed shear, adding antioxidant, and removing the solvent until the ethanol solution residue is less than 10 ppm.

[0102] For more details of step S310, please refer to the related description of step S110 above.

[0103] In step S320, the wall material and the carbohydrate are mixed in a weight ratio of (1-5):1 to prepare an aqueous solution having a first solid content, and the aqueous solution is stirred and dispersed to obtain a pretreated gelled wall material.

[0104] In some embodiments, the wall material and carbohydrate may also be mixed in a weight ratio of (1-3): 1. In some embodiments, the wall material and carbohydrate may also be mixed in a weight ratio of (4-5): 1.

[0105] For more details about the aqueous solution having the first solid content, please refer to the associated description of FIG. 1, which will not be repeated here.

[0106] In some embodiments, the aqueous solution may be stirred and dispersed at 50°C to 70°C, stirred at 80°C to 90°C for 15 to 45 minutes, and cooled to 60°C to 65°C for 100 to 150 minutes.

[0107] In some embodiments, the wall material may comprise starch sodium octenyl succinate. In some embodiments, the carbohydrate may comprise glucose or glucose syrup and combinations thereof.

[0108] In step S330, the pre-processed carotenoid and the pre-processed gelling wall material are mixed, emulsified, and granulated to obtain a carotenoid preparation.

[0109] The preparation method of the carotenoid preparation may be described in detail below through embodiments B1 to B4, comparative embodiments B5 to B8, and effect embodiments B9 to B13. It should be noted that the reaction conditions, reaction materials, and amounts of reaction materials in embodiments B1 to B4 are only for illustrating the preparation method of the carotenoid preparation and do not limit the scope of protection of this description. Embodiments B1 to B4 are embodiments using different reaction conditions and weight ratios of materials, respectively. Comparative embodiments B5 to B8 are the control group for embodiments B2 to B4. Effect embodiments B9 to B13 are comparisons of the actual effects of the product prepared according to embodiment B2 with other products.

[0110] In this disclosure, percentages and contents are calculated by mass unless otherwise specified. Unless otherwise noted, the experimental methods used are conventional methods, and the materials and reagents used can be purchased from commercial sources.

[0111] In the preparation process of the carotenoid formulation of the present disclosure, one or more of several components can be selectively added according to the dosages conventional in this field. For more details on the selective addition of one or more of several components, please refer to the description, and the details will not be repeated here.

[0112] In this disclosure, the following methods are used to measure and evaluate products.

[0113] For more details of the method for measuring the dye dissolution rate in the present disclosure, please refer to the above description, which will not be repeated here.

[0114] For more details on how to evaluate the accelerated stability of the products of the present disclosure, please refer to the above description, which will not be repeated here.

[0115] For the determination of release rates in this disclosure, see USP <711> Referring to DISSOLUTIO, Apparatus 2 is used, the rotation speed is 50 rpm, and the release rate experiment is carried out according to DELAYED-RELEASE DOSAGEFORMS Method B. 0.1N hydrochloric acid solution is selected as the release medium within 2 hours, and pH=6.8 phosphate buffer solution is selected as the release medium within 2 hours to 8 hours.

[0116] The method for evaluating the intracellular absorption and utilization of the products disclosed herein is as follows. Caco2 cell lines are used in this study. Cells in logarithmic growth phase are uniformly seeded on 100 mm cell culture dishes for subsequent cellular uptake experiments. All experiments are performed using 20th generation Caco2 cells. The test sample is dissolved in sterile dimethyl sulfoxide (DMSO), vortex-mixed, and diluted to 20 μM using cell culture medium. Drugs are then added and the cells are cultured. For the blank control group, cells are cultured in regular cell culture medium. After drug treatment, the cells are cultured for 24 hours in a CO2 incubator. The cells are harvested and lysed using 3 mL of lysate. The dye is extracted with 3 mL of tetrahydrofuran and 3 mL of absolute ethanol. The absorbance is detected using an ultraviolet spectrophotometer at wavelengths of 446 nm (lutein), 453 nm (zeaxanthin), and 455 nm (β-carotene), and the intracellular carotenoid content is calculated by substituting the absorbance into a standard curve.

[0117] Determination of chiral isomerism of zeaxanthin in the present disclosure: Detect meso-zeaxanthin stereoisomeric composition according to USP43.

[0118] Embodiment B1: Effect of Crystal Processing Method on Crystal Stability

[0119] The specific content of embodiment B1 is the same as that of embodiment A1, so please refer to the above description for details.

[0120] Embodiment B2

[0121] The processed lutein crystals were obtained by mixing 200 g of lutein crystals with three volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester, and removing the solvent at 75°C. The processed lutein crystals were frozen at -20°C for standby storage. The ethanol-soluble residue of the processed lutein crystals was 7 ppm, and the moisture content of the processed lutein crystals was 10%. An aqueous solution with 50% solids was prepared using 583 g of sodium starch octenyl succinate and 195 g of glucose. After stirring and dispersing at 60°C, the aqueous solution was heated to 90°C and stirred at a constant speed for 35 minutes. The aqueous solution was then cooled to 60°C and stirred for 100 minutes. Lutein Product A was obtained by mixing, stirring, emulsifying, and spray-drying the gelling wall material and the processed lutein crystals, and its pigment dissolution rate was 3.1%, the 30-minute release rate was 30.5%, and the 4-hour release rate was 103.3%. The release rates of Lutein Product A at different times are shown in Table 4 below. Table 4. Release rate at different times JPEG0007734198000004.jpg64170

[0122] Embodiment B3

[0123] Treated β-carotene crystals were obtained by mixing 233 g of β-carotene crystals with 5 volumes of 50% aqueous ethanol, stirring at 40°C for 40 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 17 g of ascorbic acid, 25.5 g of ascorbyl palmitate, and 25.5 g of sucrose fatty acid ester, and removing the solvent at 70°C. The treated β-carotene crystals were frozen at -20°C for standby storage. The ethanol-soluble residue of the β-carotene crystals was 5 ppm, and the moisture content of the β-carotene crystals was 15%. An aqueous solution with 70% solids was prepared using 560 g of sodium starch octenyl succinate and 140 g of glucose. After stirring and dispersing at 50°C, the aqueous solution was heated to 80°C, stirred at a constant speed for 50 minutes, cooled to 65°C, and stirred for 120 minutes. β-carotene Product A was obtained by mixing, stirring, emulsifying, and spray-drying the gelling wall material and the treated β-carotene crystals, and its pigment dissolution rate was 2.3%, the release rate in 30 minutes was 28.3%, and the release rate in 4 hours was 100.2%. The release rates of β-carotene Product A at different times are shown in Table 5 below. Table 5. Release rate at different times JPEG0007734198000005.jpg65170

[0124] Embodiment B4

[0125] The processed composite crystals were obtained by mixing 106 g of β-carotene crystals, 212 g of lutein ester crystals, 106 g of zeaxanthin crystals, and 4 volumes of 70% aqueous ethanol, stirring at 50°C for 55 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 73 g of ascorbic acid, 1.5 g of ascorbyl palmitate, and 1.5 g of sucrose fatty acid ester, and removing the solvent at 80°C. The processed composite crystals were frozen at -20°C for standby storage. The ethanol-soluble residue in the processed composite crystals was 3 ppm, and the moisture content of the processed composite crystals was 30%. An aqueous solution with 60% solids was prepared using 416.7 g of starch sodium octenyl succinate and 83.3 g of glucose syrup. After stirring and dispersing at 70°C, the aqueous solution was heated to 85°C, stirred at a constant speed for 45 minutes, cooled to 63°C, and stirred for 130 minutes. Product A, which had a 2:1:1 ratio of lutein esters, zeaxanthin, and β-carotene, was obtained by mixing, stirring, emulsifying, and spray-drying the gelling wall material and the processed composite crystals. Its pigment dissolution rate was 3.5%, the 30-minute release rate was 22.4%, and the 4-hour release rate was 99.7%. The release rates of Product A, which had a 2:1:1 ratio of lutein esters, zeaxanthin, and β-carotene, at different times are shown in Table 6 below. Table 6. Release rate at different times JPEG0007734198000006.jpg65170

[0126] In embodiments B2 to B4, carotenoid crystals are obtained by mixing carotenoids with 3 to 5 times the volume of a 50% to 70% aqueous ethanol solution, stirring, high-speed shear dispersion, adding an antioxidant, and removing the solvent. The ethanol-soluble residue of the carotenoid crystals is less than 10 ppm, and the moisture content of the carotenoid crystals is within the range of 10% to 30%. An aqueous solution with a 50 to 70% solids content is prepared by mixing at least starch as the wall material with a carbohydrate in a weight ratio of (1 to 5:1), and a pre-treated gelled wall material is obtained by stirring and dispersion. A carotenoid preparation is prepared by mixing the treated carotenoid crystals with the gelled wall material. The pigment solubility of the carotenoid preparation is less than 5%, making it less likely to stain clothes, tongue, etc. during use. Furthermore, the release rate of the carotenoid formulation in hydrochloric acid solution after 0.5 hours was less than 35%, which may effectively protect the carotenoids from being destroyed in the stomach. The release rate of the carotenoid in phosphate buffer solution after 4 hours was more than 90%, which facilitates subsequent intestinal absorption.

[0127] Comparative embodiment B5

[0128] Treated β-carotene crystals were obtained by mixing 200 g of β-carotene crystals with three volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, and dispersing by high-speed shearing at 10,000 rpm. Then, 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester were added, and the solvent was removed at 75°C. The treated β-carotene crystals were frozen at -20°C for standby storage. The ethanol-soluble residue in the treated β-carotene crystals was 7 ppm, and the moisture content of the treated β-carotene crystals was 12.8%. β-Carotene Product B was obtained by using 583 g of sodium starch octenyl succinate and 195 g of glucose, stirring and dissolving them at 60°C to prepare an aqueous solution with 50% solids, adding β-carotene crystals, stirring, emulsifying, and spray-drying. Its dye dissolution rate is 65.8%, 30-minute release rate is 99.1%, and 4-hour release rate is 98.9%.

[0129] Compared with embodiments B2 to B4, the wall material of comparative embodiment B5 is not subjected to gelation treatment (heating, stirring, and cooling treatments for gelation of the wall material are not performed), which increases the pigment dissolution rate of the product prepared by comparative embodiment B5 and increases the release rate of the product in the hydrochloric acid solution, which may destroy the carotenoids in the gastric juice and prevent them from being properly absorbed in the intestinal tract, resulting in a worsening effect.

[0130] Comparative embodiment B6

[0131] The processed lutein ester crystals were obtained by mixing 200 g of lutein ester crystals with three volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester, and removing the solvent at 75°C. The processed lutein ester crystals were frozen at -20°C for standby storage. The ethanol-soluble residue in the processed lutein ester crystals was 5.3 ppm, and the moisture content of the processed lutein ester crystals was 25%. An aqueous solution with 50% solids was prepared using 583 g of starch sodium octenyl succinate and 195 g of glucose. After stirring and dispersing at 60°C, the aqueous solution was heated to 100°C and stirred at a constant speed for 60 minutes. Lutein ester product A is obtained by mixing, stirring, emulsifying, and spray-drying the gelling wall material and the treated lutein ester crystals, and has a pigment dissolution rate of 85.2%, a 30-minute release rate of 97.7%, and a 4.5-hour release rate of 102.3%.

[0132] Compared with embodiments B2 to B4, in comparative embodiment B6, the wall material is processed under conditions other than the gelation method described in the present disclosure (stirring and dispersing at 60°C, heating to 100°C, and uniformly stirring for 60 minutes), which increases the pigment dissolution rate of the product prepared by comparative embodiment B6 and increases the product's release rate into the hydrochloric acid solution, potentially destroying the carotenoids in the solution and preventing them from being properly absorbed by the intestinal tract, resulting in poor efficacy.

[0133] Comparative embodiment B7

[0134] Mixed lutein crystals were obtained by mixing 200 g of lutein crystals, 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester. An aqueous solution with a 50% solids content was prepared using 583 g of starch sodium octenyl succinate and 195 g of glucose syrup. After stirring and dispersing at 60°C, the aqueous solution was heated to 90°C, stirred at a constant speed for 35 minutes, cooled to 60°C, and stirred for 100 minutes. Lutein Product B was obtained by mixing the mixed lutein crystals with a gelling wall material, stirring, emulsifying, and spray-drying. Its pigment dissolution rate was 33.2%, its 30-minute release rate was 90.1%, and its 4-hour release rate was 95.5%. Compared with Embodiments B2 to B4, the lutein crystals of Comparative Embodiment B7 are not pre-treated (the lutein crystals are not mixed and stirred with an ethanol solution, and are not pre-treated by high-speed shear dispersion and solvent removal), which increases the pigment dissolution rate of the product prepared according to Comparative Embodiment B7 and increases the release rate of the product into the hydrochloric acid solution, which may destroy carotenoids in gastric juice and prevent them from being properly absorbed in the intestinal tract, thereby worsening their effectiveness.

[0135] Comparative embodiment B8

[0136] The processed lutein crystals were obtained by mixing 200 g of lutein crystals with three volumes of 60% aqueous ethanol, stirring at 45°C for 30 minutes, dispersing by high-speed shearing at 10,000 rpm, adding 20 g of ascorbic acid, 1 g of ascorbyl palmitate, and 1 g of sucrose fatty acid ester, and removing the solvent at 75°C. The processed lutein crystals were frozen at -20°C for standby storage. The ethanol-soluble residue of the processed lutein crystals was 7 ppm, and the moisture content of the processed lutein crystals was 10%. An aqueous solution with 50% solids was prepared using 583 g of corn starch and 195 g of glucose. After stirring and dispersing at 60°C, the aqueous solution was heated to 90°C, stirred at a constant speed for 35 minutes, cooled to 60°C, and stirred for 100 minutes. Lutein Product C is obtained by mixing, stirring, emulsifying, and spray-drying the gelling wall material and the processed lutein crystals, and has a pigment dissolution rate of 73.5%, a 30-minute release rate of 99.5%, and a 4-hour release rate of 101.3%.

[0137] Compared with embodiments B2 to B4, in comparative embodiment B8, starch sodium octenyl succinate is replaced with corn starch, and the pigment dissolution rate of the product prepared according to comparative embodiment B8 increases, and the release rate of the product in hydrochloric acid solution increases, which may cause the carotenoids in gastric juice to be destroyed and not be properly absorbed in the intestinal tract, resulting in a poor effect of the product. It has been shown that the effects of the products prepared according to embodiments B2 to B4, which use starch sodium octenyl succinate as a wall material, are better.

[0138] Effect embodiment B9

[0139] Complex product 3 is obtained by mixing lutein, zeaxanthin, and beta-carotene in a weight ratio of 1:1:1. Lutein is prepared using the method of patent CN108185424B (patent application number CN201711456450.1). Complex product 4 is obtained by mixing lutein, zeaxanthin, and beta-carotene in a weight ratio of 1:1:1. Lutein is prepared using the method of embodiment B2. The comparative parameters of the two products are shown in Table 7 below. Table 7 Comparison parameters of the two products JPEG0007734198000007.jpg44170

[0140] Comparing Composite Product 3 and Composite Product 4, the pigment dissolution rate of Composite Product 4 prepared by the disclosed preparation process (Embodiment B2) was lower than that of Composite Product 3 prepared according to the preparation method of Patent CN108185424B, and the release rate of Composite Product 4 prepared by the disclosed preparation process (Embodiment B2) was lower than that of Composite Product 3 prepared according to the preparation method of Patent CN108185424B. The release rate of Composite Product 4 in hydrochloric acid solution (within 30 minutes) was significantly lower than that of Composite Product 3, indicating that Composite Product 4 can effectively protect carotenoids from destruction by gastric juice in the stomach. However, the release rate of Composite Product 4 in phosphate buffer solution (within 4 hours) was 98.2%, indicating that Composite Product 4 is well absorbed after entering the intestinal tract and has better application effects.

[0141] Effect embodiment B10: Application evaluation of soft candy

[0142] Solution II is obtained by weighing 8 g of gelatin, 44 g of white sugar, and 55 g of glucose syrup, adding water at 20% solid content, stirring to dissolve, boiling the sugar at 120 °C until the solid content is about 85%, and adjusting the pH to 3-4.

[0143] 20 g of lutein Product A prepared according to the method of Embodiment B2 or 20 g of β-carotene Product B prepared according to the method of Comparative Embodiment B5 was added to Solution II, and the resulting solution was stirred uniformly and maintained at 90°C for 40 minutes. Soft candies containing lutein Product A and β-carotene Product B were obtained by injection molding and drying, and their appearances are shown in Figures 4A and 4B, respectively. It can be seen that lutein Product A did not stain the soft candy and was completely preserved within the soft candy, achieving a nutrition visualization effect. However, β-carotene Product B stained the soft candy red, reducing its transparency.

[0144] Effect embodiment B11: Application evaluation of solid beverages

[0145] Lutein Product A prepared by the method of embodiment B2 and beta-carotene Product B prepared by the method of comparative embodiment B5 were mixed with appropriate amounts of 0.03% citric acid, 20% maltodextrin, 0.6% xanthan gum, etc. to prepare solid beverages, which were then brewed and evaluated. The evaluation results for the two products are shown in Table 8. Table 8 Comparison parameters of the two products JPEG0007734198000008.jpg43170

[0146] Comparing the solid beverages made with lutein product A (prepared by the method of embodiment B2) and beta-carotene product B (prepared by the method of comparative embodiment B5), the solid beverage made with lutein product A does not stain the tongue and has better application effects.

[0147] Effect embodiment B12: Comparison of lutein bioavailability

[0148] Lutein standard solutions of 0.5, 1, 2, 4, 6, 8, and 10 μM were prepared, and the absorbance of the lutein standard solutions was measured at a wavelength of 446 nm using an ultraviolet spectrophotometer. As shown in Figure 5, a standard curve was plotted using concentration (μM) as the abscissa and absorbance as the ordinate. Lutein product A (XanGuard® Lutein Microparticles 10% GF) prepared by the method of embodiment B2 and lutein crystals were used to prepare 20 μM solutions, and Caco2 cells were treated for 24 hours. The cellular uptake rates were compared as shown in Figure 6 (n=3, *p<0.05, **p<0.01, ***p<0.001). The results showed that lutein product group A significantly increased the cellular uptake rate compared to the lutein crystal group, with the cellular uptake rate being 2.1 times that of the lutein crystal group. This demonstrates that the products prepared according to the present disclosure improve the bioavailability of lutein.

[0149] Effect embodiment B13: Comparison of zeaxanthin bioavailability

[0150] Zeaxanthin was used to prepare standard solutions of 0.2, 0.5, 1, 2, 5, 8, and 10 μM, and the absorbance of the standard solutions was measured using a UV spectrophotometer at a wavelength of 453 nm. A standard curve was plotted using the concentration (μM) as the abscissa and the absorbance as the ordinate, as shown in Figure 7. Zeaxanthin product A (XanGuard® Zeaxanthin Microparticles 5% GF) prepared by the method of embodiment B2 and zeaxanthin crystals were used to prepare 20 μM solutions, and Caco2 cells were treated with the solutions for 24 hours. The cellular uptake rates were compared as shown in Figure 8 (n=3, *p<0.05, **p<0.01, ***p<0.001). The results showed that zeaxanthin product A significantly increased the cellular uptake rate compared with the zeaxanthin crystal group, with the cellular uptake rate being 2.2 times that of the zeaxanthin crystal group. Products prepared according to the present disclosure are demonstrated to improve the bioavailability of zeaxanthin.

[0151] The zeaxanthin used in this embodiment includes two isomers, (3R,3'R)-zeaxanthin and (3R,3'S)-zeaxanthin, with the two isomers accounting for more than 80% of the zeaxanthin's weight. When the weight ratio between the two isomers, (3R,3'R)-zeaxanthin and (3R,3'S)-zeaxanthin, is within the range of (5-15%):(95-85%), zeaxanthin does not affect the cellular absorption of zeaxanthin. The results of detecting the chiral structure of zeaxanthin in the sample absorbed into the cells are shown in Figure 9. The results indicate that zeaxanthin remains in the mesosomal form within the cells after absorption by Caco2 cells and is not converted to other forms. This indicates that there is no specific preference for (3R,3'R)-zeaxanthin or (3R,3'S)-zeaxanthin for cellular absorption.

[0152] The above is merely a preferred embodiment of the present invention, and the protection scope of the present invention is not limited thereto. Any modifications or replacements that can be easily thought up by those skilled in the art within the technical scope disclosed in this disclosure shall be included in the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be determined by the protection scope of the claims.

[0153] In some embodiments, the carotenoid may include lutein. Currently, traditional processes generally employ saponification to prepare lutein, but the preparation process uses a large amount of alkali, resulting in the generation of alkaline wastewater that is not environmentally friendly and the prepared product has low purity of lutein.

[0154] In some embodiments of the present disclosure, a marigold extract solution is obtained by mixing marigold extract with a lower alcohol. The marigold extract solution and the mixed alcohol solution are then introduced into a preheated pipeline, with the reaction flow rate ratio controlled. The saponification reaction is carried out at a constant temperature and pressure. An acid is added to the saponified reaction solution for neutralization, and a complexing agent is added to the saponified reaction solution for lutein extraction. Crystallized lutein is obtained after subsequent processing. This process uses a tubular reactor to preheat the reactants and the mixed reactants. This allows for continuous reactions in lutein preparation, significantly shortening the reaction time. At the same time, the alcoholysis method is used to convert lutein esters to lutein with only a small amount of alkali. Furthermore, the complexation method is used to directly isolate lutein. The isolated lutein has a high content and yield, and the reaction time is short.

[0155] 10 is a flow chart illustrating a process for preparing lutein according to some embodiments of the present disclosure. Process 1000 may include the following steps:

[0156] Step S1010: Connect the first pipeline, the second pipeline, and the third pipeline to the "Y" type connecting valve respectively.

[0157] In some embodiments, the first pipeline and the second pipeline may be preheated pipelines for transporting reaction raw materials. As shown in FIG. 11, the first pipeline may be used to transport a marigold extract solution, and the second pipeline may be used to transport an alcohol mixture solution. In some embodiments, the third pipeline is used to mix the reaction raw materials and perform the saponification reaction. In some embodiments, the first pipeline and the second pipeline may be straight or coiled pipes. In some embodiments, the diameters of the first pipeline and the second pipeline may be within a range of 0.2 cm to 2 cm. In some embodiments, the diameters of the first pipeline and the second pipeline may be within a range of 0.5 cm to 1.6 cm. In some embodiments, the diameters of the first pipeline and the second pipeline may be within a range of 1.0 cm to 1.5 cm. In some embodiments, the length of the first pipeline and the second pipeline may be within a range of 0.5 m to 3 m. In some embodiments, the length of the first pipeline and the second pipeline may be within a range of 1.5 m to 2.5 m. In some embodiments, the length of the first pipeline and the length of the second pipeline may be in the range of 2 m to 2.5 m. In some embodiments, the third pipeline may be a straight pipe or a coiled pipe. In some embodiments, the diameter of the third pipeline may be in the range of 1.2 cm to 1.6 cm. In some embodiments, the diameter of the third pipeline may be in the range of 1.0 cm to 1.5 cm. In some embodiments, the diameter of the third pipeline may be in the range of 0.7 cm to 0.9 cm. In some embodiments, the length of the third pipeline may be in the range of 30 m to 100 m. In some embodiments, the length of the third pipeline may be in the range of 3 m to 60 m. In some embodiments, the length of the third pipeline may be in the range of 9 m to 20 m.

[0158] Step S1020: Mix marigold extract and lower alcohol, and feed the mixture of marigold extract and lower alcohol into a first pipeline at a first flow rate and preheat it to obtain a marigold extract solution.

[0159] In some embodiments, the lower alcohol may be a C1-C4 lower alcohol. In some embodiments, the lower alcohol may be at least one of anhydrous methanol, ethanol, isopropanol, and n-butanol. In some embodiments, the weight ratio of the marigold extract to the lower alcohol is within the range of 1:(2-10). In some embodiments, the weight ratio of the marigold extract to the lower alcohol is within the range of 1:(3-8). In some embodiments, the weight ratio of the marigold extract to the lower alcohol is within the range of 1:(5-7).

[0160] The first flow rate is the flow rate of the mixed solution of marigold extract and lower alcohol (i.e., marigold extract solution). In some embodiments, the first flow rate may be in the range of 2 mL / min to 800 mL / min. In some embodiments, the first flow rate may be in the range of 50 mL / min to 600 mL / min. In some embodiments, the first flow rate may be in the range of 100 mL / min to 500 mL / min. In some embodiments, the first flow rate may be in the range of 200 mL / min to 400 mL / min. In some embodiments, the first flow rate may be in the range of 250 mL / min to 300 mL / min.

[0161] The preheat temperature may refer to the temperature to which the reactants in the preheat pipelines (i.e., the first pipeline and the second pipeline) are heated. In some embodiments, the preheat temperature may be in the range of 60°C to 100°C. In some embodiments, the preheat temperature may be in the range of 70°C to 90°C. In some embodiments, the preheat temperature may be in the range of 80°C to 85°C.

[0162] Step S1030: Add the marigold extract solution to the alcohol mixed solution, and the ratio of the flow rate of the marigold extract solution to the flow rate of the alcohol mixed solution is a first flow rate ratio.

[0163] The second flow rate is the flow rate of the alcohol mixed solution entering the second pipeline. In some embodiments, the second flow rate may be in a range of 2 mL / min to 1200 mL / min. In some embodiments, the second flow rate may be in a range of 50 mL / min to 1000 mL / min. In some embodiments, the second flow rate may be in a range of 100 mL / min to 800 mL / min. In some embodiments, the second flow rate may be in a range of 300 mL / min to 600 mL / min. In some embodiments, the second flow rate may be in a range of 400 mL / min to 500 mL / min.

[0164] In some embodiments, the mass concentration of the alcohol mixture solution may be in the range of 0.01% to 8%. In some embodiments, the mass concentration of the alcohol mixture solution may be in the range of 0.1% to 0.7%. In some embodiments, the mass concentration of the alcohol mixture solution may be in the range of 0.3% to 0.5%. In some embodiments, the alcohol mixture solution may include at least one of a sodium ethoxide ethanol solution, a sodium methoxide methanol solution, a potassium methoxide methanol solution, a potassium ethoxide ethanol solution, a sodium hydroxide alcohol solution, and a potassium hydroxide alcohol solution.

[0165] The first flow ratio refers to the ratio of the flow rate of the marigold extract solution to the flow rate of the alcohol mixed solution when the reaction raw materials enter the third pipeline. In some embodiments, the first flow rate ratio may be within a range of 1:(1-5). In some embodiments, the first flow rate ratio may be within a range of 1:(2-4). In some embodiments, the first flow rate ratio may be within a range of 1:(3-4). For example, if the flow rate of the marigold extract solution is 150 mL / min, the flow rate of the alcohol mixed solution is 250 mL / min.

[0166] Step S1040: The marigold extract solution and the alcohol mixed solution are mixed in the third pipeline, and the third pipeline is maintained at a first temperature and a first pressure to carry out a saponification reaction, thereby obtaining a saponified reaction solution.

[0167] 11 is a schematic diagram of a "Y" type connecting valve connecting pipelines in some embodiments of the present disclosure. In some embodiments, as shown in FIG. 11, the marigold extract solution in the first pipeline and the alcohol mixed solution in the second pipeline are mixed in the third pipeline after passing through the "Y" type connecting valve. The mixed marigold extract solution and alcohol mixed solution are saponified in the third pipeline at a first temperature and a first pressure to obtain a reaction solution.

[0168] In some embodiments, the first temperature may be in the range of 60°C to 120°C. In some embodiments, the first temperature may be in the range of 80°C to 110°C. In some embodiments, the first temperature may be in the range of 90°C to 100°C. In some embodiments, the first pressure may be in the range of 0 to 5 MPa. In some embodiments, the first pressure may be in the range of 0.5 MPa to 4 MPa. In some embodiments, the first pressure may be in the range of 1 MPa to 3 MPa.

[0169] The marigold extract solution and alcohol mixed solution are preheated through the first and second pipelines, respectively, before entering the third pipeline for the saponification reaction. The marigold extract solution and alcohol mixed solution are rapidly saponified at high temperatures to obtain lutein, achieving a continuous reaction process for the preparation of lutein. Furthermore, a "Y"-type connecting valve is used to connect the three pipelines for the mixing reaction. This effectively shortens the saponification time, reduces manual labor, and lowers labor costs.

[0170] Step S1050: Add an acid to the saponified reaction solution to neutralize it to a first pH, add a complexing agent, and stir at room temperature to precipitate lutein crystals, followed by filtering to obtain a first filter cake.

[0171] In some embodiments, the acid used for neutralization may include at least one of glacial acetic acid, sulfuric acid, phosphoric acid, citric acid, hydrochloric acid, sodium dihydrogen phosphate, and potassium dihydrogen phosphate. In some embodiments, the weight ratio of acid to marigold extract is within the range of (5-10):1. In some embodiments, the weight ratio of acid to marigold extract is within the range of (6-9):1. In some embodiments, the weight ratio of acid to marigold extract is within the range of (7-8):1. In some embodiments, the first pH may be within the range of 4-8. In some embodiments, the first pH may be within the range of 6-8. In some embodiments, the first pH may be within the range of 5-7.

[0172] In some embodiments, the complexing agent may be tributyl phosphate or trioctylamine. In some embodiments, the weight ratio of complexing agent to marigold extract may be in the range of (0.0005-0.01):1. In some embodiments, the weight ratio of complexing agent to marigold extract may be in the range of (0.0005-0.005):1. In some embodiments, the weight ratio of complexing agent to marigold extract may be in the range of (0.001-0.0025):1.

[0173] High-purity lutein crystals can be obtained by purifying the lutein crystals with a complexing agent after the saponification reaction, which improves the yield of lutein crystals and allows for the preparation of high-purity lutein crystals in an environmentally friendly manner, since no other organic solvents are used for purification.

[0174] Step S1060: Add the alkali-alcohol solution to the first filter cake, stir at room temperature, and filter to obtain a second filter cake, and add water to the second filter cake, stir, filter, and dry to obtain lutein crystals.

[0175] In some embodiments, the alkali in the alkaline alcohol solution may include at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate. In some embodiments, the alcohol in the alkaline alcohol solution may include at least one of methanol or ethanol. In some embodiments, the mass concentration of the alkaline alcohol solution may be in the range of 0.1% to 2.0%. In some embodiments, the mass concentration of the alkaline alcohol solution may be in the range of 0.1% to 1.0%. In some embodiments, the mass of the alkaline alcohol solution is 0.5 to 5 times the mass of the marigold extract. In some embodiments, the mass of the alkaline alcohol solution is 1 to 4 times the mass of the marigold extract. In some embodiments, the amount of the alkaline alcohol solution is 2 to 3 times the mass of the marigold extract. In some embodiments, the mass of water added to the second filter cake may be 0.5 to 5 times the mass of the marigold extract. In some embodiments, the mass of water added to the second filter cake may be 1 to 4 times the mass of the marigold extract. In some embodiments, the mass of water added to the second filter cake may be two to three times the mass of the marigold extract. In some embodiments, the stirring time may be in the range of 20 minutes to 60 minutes. In some embodiments, the stirring time may be in the range of 30 minutes to 50 minutes. In some embodiments, the stirring time may be in the range of 40 minutes to 45 minutes. In some embodiments, the drying temperature may be in the range of 30°C to 60°C. In some embodiments, the drying temperature may be in the range of 40°C to 50°C. In some embodiments, the drying temperature may be in the range of 40°C to 45°C.

[0176] The method for preparing lutein will be described in detail below through Embodiments C1 to C8 and Comparative Embodiments C1 to C5. It should be noted that the reaction conditions, reaction materials, and amounts of reaction materials in Embodiments C1 to C8 are only for illustrating the lutein preparation method and do not limit the scope of protection of this description. Embodiments C1 to C8 are embodiments using different reaction conditions and material weight ratios. Comparative Embodiment C1 is an embodiment that does not use a tubular reaction (three pipelines connected by a "Y"-type connecting valve), and Comparative Embodiment C2 is an embodiment that performs a tubular reaction without using an alcoholysis method or a complexing agent and without using three pipelines connected by a "Y"-type connecting valve. Comparative Embodiments C3 to C5 are embodiments for preparing lutein using methods in other patent applications. Comparative Embodiments C1 to C5 are controls for Embodiments C1 to C8.

[0177] Embodiment C1

[0178] (1) Two pipelines, each 2 m long and 0.8 cm in diameter, are used as the first and second pipelines. The first and second pipelines are connected to both ends of a "Y" connector (also called a "Y" connection valve), and the other end of the "Y" connector is connected to the third pipeline, which is a 9 m long pipeline with a diameter of 0.8 cm.

[0179] (2) Take 200 kg of marigold extract and add 800 kg of absolute ethanol. Pump the marigold extract and absolute ethanol into the first pipeline at a flow rate of 150 mL / min while stirring. Take 0.375 kg of sodium ethylate and dissolve it in 800 kg of absolute ethanol. Pump the resulting solution into the second pipeline at a flow rate of 250 mL / min.

[0180] (3) The reaction temperature in the third pipeline is set to 85°C, the pressure in the third pipeline is set to 0.2 MPa, the saponification reaction is carried out, and the reaction solution is received at the end of the third pipeline.

[0181] Experimental results: The liquid phase composition of the reaction solution was measured, and the transesterification rate of lutein ester in the reactant marigold extract reached 99.4%, the residual rate of lutein ester was 0.6%, and the saponification time was 13 minutes.

[0182] Embodiment C2

[0183] (1) Two pipelines, each 2 m long and 0.8 cm in diameter, are selected as the first and second pipelines. The first and second pipelines are connected to both ends of a "Y" connector (also called a "Y" connection valve), and the other end of the "Y" connector is connected to the third pipeline, which is 54 m long and 1.4 cm in diameter.

[0184] (2) Take 20 kg of marigold extract and add 60 kg of absolute ethanol. Pump the resulting solution into the first pipeline at a flow rate of 200 mL / min while stirring. Take 0.75 kg of potassium ethylate and dissolve it in 80 kg of absolute ethanol, and pump the solution into the second pipeline at a flow rate of 300 mL / min.

[0185] (3) The reaction temperature in the third pipeline is set to 85°C, the pressure in the third pipeline is set to 0.2 MPa, the saponification reaction is carried out, and the reaction solution is received at the end of the third pipeline.

[0186] Experimental results: The liquid phase composition of the reaction solution was measured, and the transesterification rate of lutein ester in the reactant marigold extract reached 99.73%, the residual rate of lutein ester was 0.3%, and the saponification time was 8 minutes.

[0187] Embodiment C3

[0188] (1) Two pipelines, each 3 m long and 0.6 cm in diameter, are selected as the first and second pipelines. The first and second pipelines are connected to both ends of a "Y" connector (also called a "Y" connection valve), and the other end of the "Y" connector is connected to the third pipeline, which is 48 m long and 1.6 cm in diameter.

[0189] (2) Take 20,000 kg of marigold extract and add 80,000 kg of anhydrous methanol. Pump the resulting solution into the first pipeline at a flow rate of 300 mL / min while stirring. Take 50 kg of sodium methoxide and dissolve it in 80,000 kg of anhydrous methanol, and pump the solution into the second pipeline at a flow rate of 500 mL / min.

[0190] (3) The reaction temperature of the third pipeline is set to 110°C, the pressure in the third pipeline is set to 1 MPa, the saponification reaction is carried out, and the reaction solution is received at the end of the third pipeline.

[0191] Experimental results: The liquid phase composition of the reaction solution was measured, and the transesterification rate of lutein ester in the reactant marigold extract reached 98.15%, the residual rate of lutein ester was 0.2%, and the saponification time was 7 minutes.

[0192] Embodiment C4

[0193] (1) Two pipelines, each 3 m long and 0.8 cm in diameter, are selected as the first and second pipelines. The first and second pipelines are connected to both ends of a "Y" connector (also called a "Y" connection valve), and the other end of the "Y" connector is connected to the third pipeline, which is a 96 m long pipeline with a diameter of 1.6 cm.

[0194] (2) Take 200 kg of marigold extract and add 800 kg of absolute ethanol. Pump the resulting solution into the first pipeline at a flow rate of 600 mL / min while stirring. Take 0.2 kg of sodium hydroxide and dissolve it in 800 kg of absolute ethanol, and pump the solution into the second pipeline at a flow rate of 1000 mL / min.

[0195] (3) The reaction temperature of the third pipeline is set to 90°C, the pressure in the third pipeline is set to 2 MPa, the saponification reaction is carried out, and the reaction solution is received at the end of the third pipeline.

[0196] Experimental results: The liquid phase composition of the reaction solution was measured, and the transesterification rate of lutein ester in the reactant marigold extract reached 99.73%, the residual rate of lutein ester was 0.2%, and the saponification time was 7 minutes.

[0197] Comparing embodiments C1 to C4, the transesterification rate of the lutein esters obtained by the tubular reactor for the saponification reaction exceeded 98%, and the saponification time was less than 13 minutes. This indicates that when the tubular reactor is used, the preheating pipeline (i.e., the first and second pipelines) has a certain length (e.g., 2 m) and is maintained at a preheating temperature (e.g., 85°C), allowing the reaction materials to be preheated before passing through the preheating pipeline. This facilitates rapid saponification of the subsequent lutein esters under high-temperature conditions to obtain lutein. The alcoholysis method also allows lutein esters to be converted to lutein using only a small amount of alkali. In the alcoholysis method, lutein esters are decomposed with alcohol to obtain lutein. In this process, an anhydrous short-chain alcohol is used as the main reactant for decomposing the lutein esters, and alkali is used as a catalyst. This process requires only a small amount of alkali, thereby shortening the saponification time and reducing labor and raw material costs.

[0198] Embodiment C5

[0199] (1) Recover the reaction solution of embodiment C1, add glacial acetic acid dropwise to the reaction solution, adjust the pH of the reaction solution to 8, add 0.1 kg of tributyl phosphate to the reaction solution, and stir the reaction solution at room temperature to precipitate the lutein crystal complex.

[0200] (2) Prepare a 0.5% sodium hydroxide solution. Add the 0.5% sodium hydroxide solution to the lutein complex and stir at room temperature for 30 minutes. After filtering, wash the lutein crystals with purified water and dry the filter cake at 40°C. The lutein content in the resulting product is 97.3%, and the lutein crystal yield is 94%.

[0201] Embodiment C6

[0202] (1) The reaction solution of embodiment C2 is recovered, glacial acetic acid is added dropwise to the reaction solution, the pH of the reaction solution is adjusted to 8, 0.1 kg of tributyl phosphate is added to the reaction solution, and the reaction solution is stirred at room temperature to precipitate the lutein crystal complex.

[0203] (2) Prepare a 1% sodium hydroxide solution. Add the 1% sodium hydroxide solution to the lutein complex. Stir the solution at room temperature for 30 minutes, then filter. Wash the lutein crystals with purified water and dry the filter cake at 40°C. The lutein content in the resulting product is 92.3%, and the lutein crystal yield is 88%.

[0204] Embodiment C7

[0205] (1) The reaction solution of embodiment C3 is recovered, hydrochloric acid is added dropwise to the reaction solution to adjust the pH of the reaction solution to 7, 10 kg of tributyl phosphate is added, and the reaction solution is stirred at room temperature to precipitate the lutein crystal complex.

[0206] (2) Prepare a 1.3% potassium hydroxide solution. Add the 1.3% potassium hydroxide solution to the lutein complex. Stir the solution at room temperature for 30 minutes, then filter. Wash the lutein crystals with purified water and dry the filter cake at 40°C. The lutein content in the resulting product is 94.67%, and the lutein crystal yield is 92%.

[0207] Embodiment C8

[0208] (1) Recover the reaction solution of embodiment C4, add concentrated sulfuric acid dropwise to the reaction solution, adjust the pH of the reaction solution to 6, add 0.5 kg of trioctylamine to the reaction solution, and stir the reaction at room temperature to precipitate the lutein crystal complex.

[0209] (2) Prepare a 1.8% sodium hydroxide solution. Add the 1.8% sodium hydroxide solution to the lutein complex and stir at room temperature for 30 minutes. After filtering, the lutein crystals are washed with purified water and the filter cake is dried at 40°C. The lutein content in the resulting product is 95.57%, and the lutein crystal yield is 90%.

[0210] Comparing embodiments C5 to C8, it can be seen that lutein crystals can be directly isolated using a complexing agent, with the content of the isolated lutein crystals exceeding 92% and the yield of the isolated lutein crystals exceeding 88%. The method of extracting lutein by complexation does not require the use of organic solvents for extraction, making it environmentally friendly, effectively reducing post-treatment processes, shortening production time, and improving lutein crystal production efficiency.

[0211] Comparative embodiment C1

[0212] (1) 200 kg of marigold extract was placed in a reactor, and 4 kg of sodium hydroxide and 1,200 kg of absolute ethanol were added to the reactor. The solution in the reactor was stirred and reacted at 60°C for 3 hours. After the reaction, the reaction solution was obtained and its liquid phase composition was measured. The transesterification rate of lutein ester in the marigold extract, the reactant, reached 99.73%, and the residual rate of lutein ester was 0.27%.

[0213] (2) Glacial acetic acid is added dropwise to the resulting reaction solution to adjust the pH of the reaction solution to 8, 0.1 kg of tributyl phosphate is added to the reaction solution, the reaction solution is stirred at room temperature, and filtered to obtain the precipitated lutein crystal complex.

[0214] (3) Prepare a 1.3% potassium hydroxide solution. Add the 1.3% potassium hydroxide solution to the lutein complex and stir at room temperature for 30 minutes. Then filter the mixture. Wash the lutein crystals with purified water and dry the filter cake at 40°C. The lutein content in the resulting product is 93.11%, and the lutein crystal yield is 88.02%. Table 9. Transesterification rate of lutein esters and residual rate of lutein esters after different reaction times JPEG0007734198000009.jpg40170

[0215] In comparative example C1, marigold extract was added to a reaction vessel and reacted as shown in Table 9. After 1 hour of reaction, the transesterification rate of lutein esters was 84.72%, and the residual rate of lutein esters was 15.28%. After 2 hours of reaction, the transesterification rate of lutein esters was 90.94%, and the residual rate of lutein esters was 9.06%. When the saponification time was up to 3 hours, the transesterification rate of lutein esters reached 99.73%, and the residual rate of lutein esters was 0.27%. Compared with embodiment C4, in comparative embodiment C1, the transesterification rate of lutein ester reaches 99.73% after 3 hours of reaction, while in embodiment C4, when a tubular reaction is used for the reaction, the transesterification rate of lutein ester reaches 99.73% when the saponification time is only 7 minutes, indicating that the tubular reaction using a pipeline connected by a "Y" type connecting valve can rapidly react at high temperature to obtain lutein, realizing a continuous reaction for preparing lutein and significantly reducing the reaction time. At the same time, the tubular reaction reduces manual labor and reduces labor costs.

[0216] Comparative embodiment C2

[0217] (1) 200 kg of marigold extract was placed in a reactor, and 50 kg of sodium hydroxide and 1,200 kg of 95% ethanol were added to the reactor. The solution in the reactor was stirred and reacted at 60°C for 3 hours. After the reaction, the reaction solution was obtained and its liquid phase composition was measured. The transesterification rate of lutein esters reached 99.61%, and the residual rate of lutein esters was 0.39%.

[0218] (2) Add glacial acetic acid dropwise to the resulting reaction solution to adjust the pH to 6-7, add 1000 kg of water, stir the reaction solution for 30 minutes, and filter to obtain crude lutein crystals. Add 800 kg of 95% ethanol to the crude lutein crystals, maintain the temperature of the reactor between 45°C and 50°C, stir the reaction solution for 30 minutes, and filter to obtain a filter cake. The filter cake is dried at 40°C. The resulting lutein crystal content is 88.52%, and the yield of the resulting lutein crystals is 83.74%. Table 10. Transesterification rate of lutein esters and residual rate of lutein esters at different reaction times JPEG0007734198000010.jpg39170

[0219] In Comparative Example C2, marigold extract was added to a reaction vessel and reacted, as shown in Table 10. After 1 hour of reaction, the transesterification rate of lutein esters was 77.22%, and the residual rate of lutein esters was 22.78%. After 2 hours of reaction, the transesterification rate of lutein esters was 94.27%, and the residual rate of lutein esters was 5.73%. When the saponification time was up to 3 hours, the transesterification rate of lutein esters reached 99.61%, and the residual rate of lutein esters was 0.39%. Compared to Comparative Example C1, Comparative Example C2 used 50 kg of sodium hydroxide, but the transesterification rate of lutein esters was lower than that of Comparative Example C1, which used only 4 kg of sodium hydroxide. This indicates that the preparation of lutein crystals by alcoholysis (decomposition of lutein esters with ethanol) in Comparative Example C1 can reduce the amount of alkali and more completely prepare lutein crystals by alcoholysis, thereby improving the utilization rate of lutein esters.

[0220] Comparing embodiment C4 with comparative embodiment C2, embodiment C4 uses less alkali (for the same reaction of 200 kg of marigold extract, embodiment C4 uses 1.2 kg of sodium hydroxide, while comparative embodiment C2 uses 50 kg of sodium hydroxide), the saponification time is shorter (the saponification time for embodiment C4 is 7 minutes, while the saponification time for comparative embodiment C2 is 3 hours), and the transesterification rate of lutein esters is higher (the transesterification rate of lutein esters for embodiment C4 is 99.73%, while the transesterification rate of lutein esters for comparative embodiment C2 is 99.61%), which indicates that embodiment C4 uses a tubular reaction combined with an alcoholysis method to reduce alkali usage, is environmentally friendly, saves costs, and significantly shortens the reaction time, thus improving economic benefits.

[0221] Compared with embodiments C5 to C8, in comparative embodiment C2, lutein is extracted using 95% ethanol without using a complexing agent, and the lutein crystal content in the product is 88.52%, with a lutein crystal yield of 83.74%, both of which are lower than the lutein crystal content and lutein crystal yield of lutein extracted with a complexing agent in embodiments C5 to C8. This indicates that the complexing method can better separate lutein, thereby increasing the lutein crystal content and yield, avoiding the use of large amounts of organic solution for extraction, and further reducing the need for solvent washing or crystallization in later stages, as well as other operations to improve lutein purity.

[0222] Comparing Comparative Embodiments C1 and C2 with Embodiments C1 to C4, the saponification time in Comparative Embodiments C1 and C2 is long at 3 hours, indicating that the preparation of lutein using the tubular reaction in Embodiments C1 to C4 can shorten the reaction time for preparing lutein from lutein esters.

[0223] Comparing Comparative Example C2 with Examples C1 to C4, in Comparative Example C2, 200 kg of marigold extract was reacted using 50 kg of sodium hydroxide, and the transesterification rate of lutein esters was only 77.22% after 1 hour of reaction. In Example C1, 200 kg of marigold extract was reacted using only 0.375 kg of sodium methylate, and the transesterification rate of lutein esters was as high as 99.4% after 13 minutes of reaction. In Example C2, 20 kg of marigold extract was reacted using only 0.75 kg of potassium methylate, and the transesterification rate of lutein esters was as high as 99.73% after 8 minutes of reaction. In Example C3, 20,000 kg of marigold extract was reacted using only 50 kg of sodium methylate, and the transesterification rate of lutein esters was as high as 98.15% after 7 minutes of reaction. In embodiment C4, 200 kg of marigold extract requires only 1.2 kg of sodium hydroxide for reaction, and the transesterification rate of lutein esters is as high as 99.73% after 7 minutes of reaction. This indicates that, compared to comparative embodiment C2, which uses a large amount of sodium hydroxide for reaction, and embodiments C1 to C4, which use the alcoholysis method to prepare lutein crystals, the amount of alkali can be reduced when preparing the same mass of lutein crystals, and at the same time, a higher transesterification rate of lutein esters can be achieved within a shorter reaction time, making the reaction more complete and improving the utilization rate of lutein esters.

[0224] Comparing comparative embodiment C2 with embodiments C5 to C8, comparative embodiment C2 does not use a complexing agent to extract lutein, and the lutein content and lutein yield are smaller, while embodiments C1 to C4 use a complexing method to extract lutein, thereby increasing the lutein crystal content and lutein crystal yield, avoiding the use of large amounts of organic solution for extraction, and further reducing the need for solvent washing or crystallization in later stages, thereby improving the lutein purity.

[0225] Comparative embodiment C3

[0226] Lutein is prepared according to the method described in patent application CN106316909A.

[0227] (1) Prepare 68.62 kg of lutein extract with a lutein content of 16.023% and store at 40°C. Prepare 37.28 kg of 35.0% potassium hydroxide solution by mass concentration and mix it with 82.02 L of 95% ethanol solution to form an alcohol-alkali solution. First, add 30.0 kg of the alcohol-alkali solution and 20.0 kg of the lutein extract to a saponifier, heat the saponifier to 60°C, and maintain for 1.5 hours to pre-saponify the mixture to obtain a saponified lutein extract mixture.

[0228] (2) The saponification equipment has an effective saponification capacity of 20 kg. Lutein extract and alcohol-alkali solution are added to the saponified lutein extract mixture at rates of 16.27 kg and 24.41 kg per hour, respectively, for 3 hours. Rapid continuous saponification takes 29.5 minutes to obtain a saponified lutein solution.

[0229] (3) The lutein saponification solution was diluted with heated water, filtered, and the filter cake was vacuum dried to a weight of 11.01 kg. The total carotenoid content was 87.32%, and the carotenoid yield by UV detection was 87.19%.

[0230] Comparing Comparative Example C3 with Examples C1 to C8, Comparative Example C3 does not use a tubular reaction or a complexing agent. The preparation process in Comparative Example C3 involves a pre-saponification process before starting the continuous saponification. The pre-saponification takes 1.5 hours, while the continuous saponification takes nearly 30 minutes, for a total of 2 hours, which is too long. The pre-saponification process is achieved using a forced mixing device, which is complex and cumbersome to operate.

[0231] Comparative embodiment C4

[0232] Lutein is prepared according to the method described in patent application CN101260071A.

[0233] Weigh out 60 g of lutein extract, 120 mL of isopropanol, and 60 mL of methanol, and add the weighed materials to the saponification apparatus. Weigh out 14 g of potassium hydroxide and 6 g of vitamin C, and add the weighed materials to the mixing system. Stir thoroughly and mix the materials, then saponify at 70°C for 6 hours. Nitrogen is introduced into the saponification system, and the material is distilled under reduced pressure. Add 250 mL of water to the resulting concentrate, stir at room temperature for 40 minutes, transfer to a separatory funnel, and add 280 mL of dichloromethane to extract the lutein, forming a dichloromethane layer and an aqueous layer. Wash the aqueous phase until it becomes colorless and neutral, obtaining a dichloromethane layer and an aqueous phase free of water-soluble impurities. Calcium chloride was added to the resulting aqueous phase each time to separate the fatty acid soaps. The separated fatty acid calcium soaps were then combined and filtered. The filter cake was washed with dichloromethane, and the filtrate was combined with the dichloromethane layer, free of water-soluble impurities, and then the solvent was recovered by vacuum distillation to obtain crude lutein. 14 g of calcium chloride was added. 24 mL of a mixed solvent consisting of ethyl acetate and petroleum ether was added to the crude lutein, and the solution was stirred at room temperature for 30 minutes. The solution was then filtered under reduced pressure. The filter cake was washed with anhydrous methanol until the filtrate was colorless, yielding lutein crystals. The lutein crystals were dried under vacuum at 50°C for 72 hours to yield 4.0131 g of lutein crystals. High-performance liquid chromatography (HPLC) revealed a total translutein content of 92.71%.

[0234] Comparing Comparative Example C4 with Examples C1 to C8, Comparative Example C4 does not use a tubular reaction system or a complexing agent, and the saponification time in the preparation process is as long as 6 hours, resulting in low production capacity. Furthermore, the use of large amounts of potassium hydroxide and dichloromethane as an extraction solvent is not environmentally friendly, and the recovery and disposal of the solvent is complicated.

[0235] Comparative embodiment C5

[0236] Lutein is prepared according to the method described in patent application CN106748947A.

[0237] (1) 100 g of lutein extract (the content of lutein ester is 32%) is dissolved in 250 mL of dichloromethane solution at 33°C, the solution is stirred and refluxed for 0.5 hours, and centrifuged to remove insoluble matter to obtain a centrifuged solution.

[0238] (2) 250 mL of methanol is added to the obtained centrifuged solution, and the obtained solution is stirred and refluxed at 33°C for 0.5 hours to form a homogeneous solution, and then left to stand at 10°C for 10 hours to crystallize, and filtered to obtain filter cake I (crude lutein esters), and the filtrate is collected.

[0239] (3) The obtained filtrate is transferred to a reaction vessel, and the low-boiling solvent dichloromethane is recovered at 40°C. 350 mL of n-hexane and 13 g of solid sodium hydroxide are added to the remaining solution, and the vessel is filled with nitrogen for protection. The vessel is then saponified at 50°C for 2.5 hours to obtain a saponified solution.

[0240] (4) Add 600 mL of deionized water to the obtained saponified solution, stir and heat the obtained solution at 45°C for 0.5 hours, adjust the pH of the obtained solution to 7.4 with acetic acid, and filter to obtain filter cake II (crude lutein).

[0241] (5) Filter cake I (crude lutein esters) and filter cake II (crude lutein) were washed with an aqueous ethanol solution (isopropanol:water ratio = 1:1), and the washed filter cakes I and II were vacuum-dried at 25°C and -0.095 MPa for 10 hours to obtain 24.93 g of lutein esters and 2.71 g of lutein. UV-visible spectrophotometric detection revealed that the purity of lutein esters was 86.68% and that of lutein was 89.01%. HPLC detection revealed that the purity of total trans-lutein esters was 91.38% and that of total trans-lutein was 92.16%. The total utilization rate of the raw materials was calculated to reach 93.51%.

[0242] Comparing Comparative Embodiment C5 with Embodiments C1 to C8, the preparation process in Comparative Embodiment C5 uses environmentally unfriendly dichloromethane as the extraction solvent, and the saponification time is long at 2.5 hours. In addition, the preparation process in Comparative Embodiment C5 requires purification of the lutein esters in the marigold extract before saponification, which makes the process complicated.

[0243] Potential beneficial effects of some embodiments of the present disclosure include, but are not limited to, the following: (1) Carotenoids are pretreated, a mixture of starch and cellulose derivatives is used as the wall material, and a weight ratio of wall material to carbohydrate of 1:(1-5) is used to prepare the pretreated gelling wall material. A carotenoid formulation is prepared based on the pretreated carotenoid and the pretreated gelling wall material, which not only reduces the release rate of carotenoids in hydrochloric acid solution but also prevents destruction by gastric acid. The carotenoid formulation maintains the biological activity of carotenoids and effectively reduces the pigment dissolution rate, preventing staining of clothes, tongues, hands, etc. during the use of carotenoid products. (2) Carotenoids are pretreated, and starch is used as the wall material. A weight ratio of wall material to carbohydrate of (1-5):1 is used to prepare the pretreated gelling wall material. A carotenoid formulation is prepared using the pretreated carotenoid and gelling wall material. This reduces the carotenoid release rate in hydrochloric acid solution, avoiding its destruction by gastric acid and maintaining its biological activity. It also increases the release rate in phosphate buffer, promoting intestinal absorption. The carotenoid formulation effectively reduces the pigment dissolution rate, preventing staining of clothing, tongue, hands, etc. during use. (3) Lutein is prepared by a tubular reaction combined with alcoholysis, which not only shortens the saponification time but also converts lutein esters to lutein with only a small amount of alkali, thereby reducing the environmental impact and labor and raw material costs. (4) Lutein is purified using a complexing agent without the need for organic solvents for extraction, which is environmentally friendly and effectively reduces post-treatment processes, shortens production time, and improves the production efficiency of lutein crystals. It should be noted that different embodiments may produce different beneficial effects. In different embodiments, the beneficial effects that may be produced may be any one or combination of the above, or any other beneficial effects that may be obtained.

[0244] It should be noted that the above embodiments are only used to explain the technical solutions of the present disclosure, and are not intended to limit the technical solutions. Those skilled in the art should understand that, without departing from the purpose and scope of the technical solutions, any modifications or equivalent replacements of the technical solutions of the present disclosure should be included in the claims of the present disclosure.

[0245] However, the present invention uses specific terms to describe embodiments of the present invention. With respect to embodiments, "one embodiment," "one embodiment," and / or "some embodiments" refers to particular features, structures, or characteristics associated with at least two embodiments of the present disclosure. Therefore, it is emphasized and should be understood that two or more references to "one embodiment" or "one embodiment" or "alternative embodiments" in various parts of the present disclosure do not necessarily all refer to the same embodiment. Furthermore, particular features, structures, or characteristics of one or more embodiments of the present disclosure may be combined as appropriate.

Claims

1. A carotenoid preparation, the carotenoid preparation being obtained by mixing, emulsifying, and granulating a pre-processed carotenoid and a pre-processed gelling wall material, wherein the amount of the pre-processed gelling wall material is 40% to 80% by weight of the carotenoid preparation; the pre-treated gelling wall material raw material comprises a wall material and a carbohydrate; the wall material comprises a modified starch or a mixture of starch and a cellulose derivative; the carbohydrates include at least one of sucrose, glucose, glucose syrup, xylose, malto-oligosaccharides, fructooligosaccharides, and corn syrup solids; The pre-treated carotenoid is obtained by mixing the carotenoid with an ethanol solution, stirring, and pre-treating the carotenoid by high-speed shear dispersion and solvent removal; A carotenoid preparation, characterized in that the pre-treated gelling wall material is obtained by mixing the wall material with a carbohydrate, heating, stirring, and allowing to stand.

2. 2. The carotenoid preparation according to claim 1, wherein the carotenoid comprises at least one of lutein, lutein fatty acid ester, zeaxanthin, lycopene, α-carotene, β-carotene, canthaxanthin, and astaxanthin.

3. 2. The carotenoid preparation according to claim 1, wherein the raw material of the pretreated carotenoid is obtained by mixing lutein or lutein fatty acid ester, zeaxanthin, and β-carotene in a weight ratio of (1-3):(1-3):(1-3).

4. 2. The carotenoid preparation of claim 1, wherein the pigment content of the pretreated carotenoid is greater than 70%.

5. 2. The carotenoid preparation according to claim 1, wherein the starch and the cellulose derivative are mixed in a weight ratio of 1:(1 to 2).

6. 2. The carotenoid formulation of claim 1, wherein the modified starch comprises starch sodium octenyl succinate.

7. 2. The carotenoid preparation according to claim 1, wherein the wall material and the carbohydrate are mixed in a weight ratio of 1:(1-5) or (1-5):

1.

8. 2. The carotenoid preparation according to claim 1, wherein the pigment solubility in water of the carotenoid preparation is less than 1%.

9. 2. The carotenoid formulation of claim 1, wherein the carotenoid formulation has a pigment solubility in water of less than 5%, a release rate of the carotenoid formulation into gastrointestinal fluid of less than 35% in 0.5 hours, and a release rate of the carotenoid formulation into gastrointestinal fluid of more than 90% in 4 hours.

10. 1. A method for preparing a carotenoid formulation, comprising: obtaining a pre-processed carotenoid by mixing carotenoid with an aqueous ethanol solution, stirring, dispersing by high speed shear, adding an antioxidant, and removing the solvent until the ethanol solution residue is less than 10 ppm, wherein the moisture content of the pre-processed carotenoid is in the range of 10% to 30%; preparing an aqueous solution having a first solid content by mixing, heating, stirring, dispersing, and statically treating a wall material and a carbohydrate to obtain a pretreated gelled wall material; and mixing, emulsifying, and granulating the pre-processed carotenoid and the pre-processed gelling wall material to obtain a carotenoid formulation.

11. 11. The method of claim 10, wherein the antioxidant comprises at least one of ascorbic acid, ascorbyl palmitate, sucrose fatty acid esters, tocopherol, fatty acid ascorbates, butylhydroxytoluene, butylhydroxyanisole, propyl gallate, and tert-butylhydroxyquinoline.

12. 11. The method of claim 10, wherein the wall material and the carbohydrate are mixed in a weight ratio of 1:(1-5) or (1-5):

1.

13. The carotenoid comprises lutein crystals, and the lutein crystals are connecting the first pipeline, the second pipeline, and the third pipeline to a "Y" type connecting valve, respectively; Mixing marigold extract and lower alcohol, and then introducing the mixture of marigold extract and lower alcohol into the first pipeline at a first flow rate and preheating it to obtain a marigold extract solution; introducing an alcohol mixture solution into the second pipeline at a second flow rate, wherein the ratio of the flow rates of the marigold extract solution and the alcohol mixture solution is a first flow rate ratio; mixing the marigold extract solution and the alcohol mixed solution in the third pipeline, and maintaining the third pipeline at a first temperature and a first pressure to carry out a saponification reaction, thereby obtaining a saponified reaction solution; adding an acid to the saponified reaction solution to neutralize it to a first pH, adding a complexing agent, stirring at room temperature to precipitate lutein crystals, and filtering to obtain a first filter cake; 11. The method of claim 10, wherein the lutein crystals are prepared by the steps of: adding an alkali-alcohol solution to a first filter cake, stirring at room temperature, and filtering to obtain a second filter cake; and adding water to the second filter cake, stirring, filtering, and drying to obtain the lutein crystals.

14. 14. The method of claim 13, wherein the lower alcohol comprises a C1-C4 lower alcohol, the mixed alcohol solution comprises at least one of sodium ethoxide ethanol solution, sodium methoxide methanol solution, potassium methoxide methanol solution, potassium ethoxide ethanol solution, sodium hydroxide alcohol solution, and potassium hydroxide alcohol solution, the first flow ratio is in the range of 1:(1-5), and the mass ratio of the complexing agent to the marigold extract is in the range of (0.0005-0.01):

1.

15. 10. Use of the carotenoid formulation according to any one of claims 1 to 9, including use for producing products in the fields of food, beverages, healthcare products and pharmaceuticals.

Images