Solvent-free preparation method for α-tocopherol and betaine complex

Abstract

A solvent-free preparation method for an α-tocopherol and betaine complex, which method comprises mixing oily α-tocopherol with betaine which has been crushed to have a specific particle size range by means of high-speed dispersion, and then performing solidification under a heating condition to form the α-tocopherol and betaine complex. The α-tocopherol and betaine complex obtained by means of the method has a higher powder density. Compared with a traditional solvent crystallization method, the method has a high yield and a simple process, is green and environmentally friendly, and has a large cost advantage.

Description

A solvent-free preparation method for an α-tocopherol and betaine complex Technical Field

[0001] This invention relates to a solvent-free method for preparing an α-tocopherol and betaine complex. Background Technology

[0002] Vitamin E is an important fat-soluble vitamin with a wide range of physiological functions in animals and humans. As an effective antioxidant and immunomodulator, it plays a vital role in enhancing the immunity and antioxidant capacity of livestock and poultry, preventing infertility, improving livestock and poultry production performance, and improving meat quality. Therefore, it is widely used in food processing, animal feed, and human nutritional supplements.

[0003] CN110192655A discloses an α-tocopherol microsphere, which is a complex formed by α-tocopherol and betaine. The preparation method of this complex is a solution method, specifically, dissolving α-tocopherol and betaine in an organic solvent, and then cooling and crystallizing under stirring or vortexing to finally obtain spherical crystalline powder of the α-tocopherol and betaine complex. However, this preparation method still has problems such as low yield (yield less than 80%), use of environmentally unfriendly organic solvents, relatively complex process, and high cost. Summary of the Invention

[0004] The present invention aims to solve the process production problems of the above-mentioned α-tocopherol and betaine complex by providing a solvent-free preparation method. This method involves uniformly mixing α-tocopherol and betaine within a specific particle size range, and then curing them at a specific high temperature to form a complex. No solvent is required, and the resulting α-tocopherol and betaine complex has a higher yield and higher powder density.

[0005] This invention provides a solvent-free method for preparing an α-tocopherol and betaine complex, comprising the following steps:

[0006] S1: Crush betaine to a particle size of D50<40μm, D70<70μm;

[0007] S2: Mix the pulverized betaine from step S1 with oily α-tocopherol to form a viscous liquid; wherein the mass ratio of α-tocopherol to betaine is (60:40)-(90:10);

[0008] S3: Heat the homogeneous viscous liquid from step S2 to a temperature of 40-80℃ to solidify it and form a compound of α-tocopherol and betaine.

[0009] In some embodiments, the solvent-free preparation method of the α-tocopherol and betaine complex further includes:

[0010] S4: Crush the solidified material from step S3 to obtain a powder of the α-tocopherol and betaine complex.

[0011] In some embodiments, in step S1, the betaine is anhydrous or monohydrate; preferably, the betaine is anhydrous.

[0012] In step S1 of this invention, betaine is pulverized to a particle size of D50 < 40 μm and D70 < 70 μm. Specifically, in some embodiments, betaine is pulverized to a particle size of D50 < 30 μm, D70 < 60 μm, and D90 < 125 μm. Excessively large particle size of the pulverized betaine will result in poor curing and molding of the mixture after heating in step S3, leading to low hardness of the cured product, which is detrimental to the subsequent pulverization operation in step S4.

[0013] In some embodiments, in step S2, the α-tocopherol includes d-α-tocopherol or dl-α-tocopherol; the purity of the α-tocopherol is ≥95%, preferably ≥98%. Lower purity α-tocopherol results in poor curing and molding of the mixture after heating in step S3, and the hardness of the cured product is low, which is not conducive to the subsequent pulverization operation in step S4.

[0014] In step S2 of this invention, the mass ratio of α-tocopherol to betaine is (60:40)-(90:10). In particular, in some embodiments, the mass ratio of α-tocopherol to betaine is (70:30)-(85:15). Excessive α-tocopherol dosage results in poor curing and molding of the mixture after heating in step S3, with low hardness of the cured material, which is detrimental to the subsequent pulverization operation in step S4. Excessive betaine dosage results in a large amount of solids in step S2, making it difficult to mix the materials uniformly.

[0015] In some embodiments, in step S2, the mixing method is high-speed dispersion mixing, and the dispersion rate of the high-speed disperser is 500-2000 rpm, preferably 600-1500 rpm.

[0016] In some embodiments, during step S3, α-tocopherol and betaine interact through non-covalent bonds during heating, causing the viscous liquid to gradually solidify and take shape. The heating temperature is 40-80°C. Preferably, the temperature is 40-60°C. In some embodiments, the heating time in step S3 is 0.5-6 hours, preferably 1-3 hours, for example, 2 hours. The solidified product after heating forms crystals that cannot revert to a viscous liquid state after cooling.

[0017] In some embodiments, in step S4, the solidified material is pulverized to a particle size of less than 20 mesh. Beneficial effects:

[0018] Compared with solution methods, solid-phase methods have the following advantages:

[0019] (1) The yield is higher, reaching over 99%, no organic solvents are required, it is green and environmentally friendly, and the process is simple, with a great cost advantage;

[0020] (2) The composite powder prepared by solid-phase method has a higher density. Attached Figure Description

[0021] Figure 1 is a powder photograph of the dl-α-tocopherol-betaine complex obtained in Example 1;

[0022] Figure 2 is a powder photograph of the d-α-tocopherol-betaine complex obtained in Example 2;

[0023] Figure 3 is an X-ray powder diffraction pattern of the dl-α-tocopherol-betaine complex obtained in Example 1;

[0024] Figure 4 is the X-ray powder diffraction pattern of the d-α-tocopherol-betaine complex obtained in Example 2;

[0025] Figure 5 is a differential scanning calorimetry (DSC) curve of the dl-α-tocopherol-betaine complex obtained in Example 1;

[0026] Figure 6 is a differential scanning calorimetry (DSC) curve of the d-α-tocopherol-betaine complex obtained in Example 2;

[0027] Figure 7 is the infrared spectrum of the dl-α-tocopherol-betaine complex obtained in Example 1;

[0028] Figure 8 is the infrared spectrum of the d-α-tocopherol-betaine complex obtained in Example 2. Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0030] Unless otherwise specified, the raw materials, reagents, and methods used in the embodiments are all conventional raw materials, reagents, and methods in the art.

[0031] Anhydrous betaine: purchased from Jinan Asia Pharmaceutical Co., Ltd.;

[0032] dl-α-tocopherol oil: purchased from Zhejiang Xinhecheng Pharmaceutical Co., Ltd.;

[0033] d-α tocopherol oil: purchased from Shandong Shengdi Jiahe Biotechnology Co., Ltd.

[0034] Example 1 (Preparation of dl-α-tocopherol-betaine complex)

[0035] Step 1: Crush anhydrous betaine to a particle size of: D50 = 26 μm, D70 = 54 μm, D90 = 120 μm;

[0036] Step 2: Weigh 50.9 kg of dl-α tocopherol oil (purity 98%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 85:15), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0037] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 60℃ for 2 hours. The material will solidify and take shape after heating.

[0038] Step 4: Crush the solidified material from Step 3, pass it through a 100-mesh sieve, and collect the sieve-passing material to obtain a crystalline powder of the dl-α-tocopherol and betaine complex with a yield of 99%. The powder photograph is shown in Figure 1, and the corresponding XRPD, DSC, and infrared spectra are shown in Figures 3, 5, and 7, respectively.

[0039] Example 2 (Preparation of d-α-tocopherol-betaine complex)

[0040] Step 1: Crush anhydrous betaine to a particle size of: D50 = 22 μm, D70 = 45 μm, D90 = 110 μm;

[0041] Step 2: Weigh 51.4 kg of d-α-tocopherol oil (purity 97%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 85:15), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0042] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 60℃ for 2 hours. The material will solidify and take shape after heating.

[0043] Step 4: The solidified material from Step 3 is pulverized, passed through a 100-mesh sieve, and the sieve-passing material is collected to obtain a crystalline powder of the d-α-tocopherol and betaine complex, with a yield of 99%. A photograph of the powder is shown in Figure 2, and the corresponding XRPD, DSC, and infrared spectra are shown in Figures 4, 6, and 8, respectively. The crystal form is identical to that of the d-α-tocopherol and betaine complex in Example 1 disclosed in CN110192655A.

[0044] The product powder prepared according to the method of Example 1 of CN110192655A was passed through a 100-mesh sieve. The sieve-passing material was collected and its density was compared with that of the d-α-tocopherol-betaine complex powder prepared in this example. The results are shown in Table 1. The powder density test method was carried out according to the bulk density and tap density determination method in Part IV of the 2020 edition of the Pharmacopoeia.

[0045] Table 1

[0046] Example 3 (Preparation of d-α-tocopherol-betaine complex)

[0047] Step 1: Crush anhydrous betaine to a particle size of: D50 = 33 μm, D70 = 68 μm, D90 = 140 μm;

[0048] Step 2: Weigh 52.5 kg of d-α-tocopherol oil (purity 95%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 85:15), and stir and mix evenly using a high-speed disperser at a dispersion speed of 600 rpm. The mixed material is a viscous liquid.

[0049] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 60℃ for 2 hours. The material will solidify and take shape after heating.

[0050] Step 4: Crush the solidified material from Step 3, pass it through a 60-mesh sieve, and collect the sieve-passing material to obtain a crystalline powder of the d-α-tocopherol and betaine complex with a yield of 99%.

[0051] Example 4 (Preparation of d-α-tocopherol-betaine complex)

[0052] Step 1: Crush anhydrous betaine to a particle size of: D50 = 18 μm, D70 = 37 μm, D90 = 98 μm;

[0053] Step 2: Weigh 81.6 kg of d-α-tocopherol oil (purity 97%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 90:10), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1200 rpm. The mixed material is a viscous liquid.

[0054] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 60℃ for 2 hours. The material will solidify and take shape after heating.

[0055] Step 4: Crush the solidified material from Step 3, pass it through a 60-mesh sieve, and collect the sieve-passing material to obtain a crystalline powder of the d-α-tocopherol and betaine complex with a yield of 99%.

[0056] Example 5 (Preparation of d-α-tocopherol-betaine complex)

[0057] Step 1: Crush anhydrous betaine to a particle size of: D50 = 22 μm, D70 = 45 μm, D90 = 110 μm;

[0058] Step 2: Weigh 52.6 kg of d-α-tocopherol oil (purity 95%) into a reactor, and slowly add 21.4 kg of betaine (mass ratio of tocopherol to betaine is 70:30). Stir and mix the mixture evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0059] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 40°C for 2 hours. The material will solidify and take shape after heating.

[0060] Step 4: Crush the solidified material from Step 3, pass it through a 60-mesh sieve, and collect the sieve-passing material to obtain a crystalline powder of the d-α-tocopherol and betaine complex with a yield of 99%.

[0061] Comparative Example 1 (Preparation of d-α-tocopherol-betaine complex)

[0062] Step 1: Crush anhydrous betaine to a particle size of: D50 = 45 μm, D70 = 78 μm, D90 = 176 μm;

[0063] Step 2: Weigh 51.4 kg of d-α-tocopherol oil (purity 97%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 85:15), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0064] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 60℃ for 2 hours. After heating, the material solidifies and takes shape, but its hardness is low, making it difficult to perform subsequent pulverization operations.

[0065] Comparative Example 2 (Preparation of d-α-tocopherol-betaine complex)

[0066] Step 1: Crush anhydrous betaine to a particle size of: D50 = 30 μm, D70 = 68 μm, D90 = 116 μm;

[0067] Step 2: Weigh 53.6 kg of d-α-tocopherol oil (purity 93%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 85:15), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0068] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 60℃ for 2 hours. After heating, the material solidifies and takes shape, but its hardness is low, making it difficult to perform subsequent pulverization operations.

[0069] Comparative Example 3 (Preparation of d-α-tocopherol-betaine complex)

[0070] Step 1: Crush anhydrous betaine to a particle size of: D50 = 18 μm, D70 = 37 μm, D90 = 98 μm;

[0071] Step 2: Weigh 91.7 kg of d-α-tocopherol oil (purity 97%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 91:9), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0072] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 60℃ for 2 hours. After heating, the material solidifies and takes shape, but its hardness is low, making it difficult to perform subsequent pulverization operations.

[0073] Comparative Example 4 (Preparation of d-α-tocopherol-betaine complex)

[0074] Step 1: Crush anhydrous betaine to a particle size of: D50 = 18 μm, D70 = 37 μm, D90 = 98 μm;

[0075] Step 2: Weigh 11.1 kg of d-α tocopherol oil (purity 97%) into the reactor, and slowly add 8.8 kg of betaine (the mass ratio of tocopherol to betaine is 55:45). Stir the mixture at a dispersion speed of 1500 rpm using a high-speed disperser. However, due to the large amount of solids, it cannot be mixed evenly with the d-α tocopherol oil, so it is not suitable for large-scale production.

[0076] Comparative Example 5 (Preparation of d-α-tocopherol-betaine complex)

[0077] Step 1: Crush anhydrous betaine to a particle size of: D50 = 22 μm, D70 = 45 μm, D90 = 110 μm;

[0078] Step 2: Weigh 51.4 kg of d-α-tocopherol oil (purity 97%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 85:15), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0079] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 90℃ for 2 hours. After heating, the material solidifies and takes shape, but due to the excessively high temperature, close to the melting point of the composite, its hardness is poor, making it difficult to pulverize.

[0080] Comparative Example 6 (Preparation of d-α-tocopherol-betaine complex)

[0081] Step 1: Crush anhydrous betaine to a particle size of: D50 = 22 μm, D70 = 45 μm, D90 = 110 μm;

[0082] Step 2: Weigh 51.4 kg of d-α-tocopherol oil (purity 97%) into a reactor, slowly add 8.8 kg of betaine (mass ratio of tocopherol to betaine is 85:15), and stir and mix evenly using a high-speed disperser at a dispersion speed of 1500 rpm. The mixed material is a viscous liquid.

[0083] Step 3: Discharge the homogeneous viscous liquid from Step 2 and heat it in an oven at 30°C for 2 hours. After heating, the material solidifies and takes shape, but its hardness is poor, making it difficult to pulverize.

[0084] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A solvent-free method for preparing an α-tocopherol and betaine complex, comprising the following steps: S1: Crush betaine to a particle size of D50<40μm, D70<70μm; S2: Mix the pulverized betaine from step S1 with oily α-tocopherol to form a viscous liquid; wherein the mass ratio of α-tocopherol to betaine is (60:40)-(90:10); S3: Heat the homogeneous viscous liquid from step S2 to a temperature of 40-80℃ to solidify it and form a compound of α-tocopherol and betaine.

2. The preparation method according to claim 1, characterized in that, The solvent-free preparation method of the α-tocopherol and betaine complex further includes: S4: Crush the solidified material from step S3 to obtain a powder of the α-tocopherol and betaine complex.

3. The preparation method according to claim 1, characterized in that, In step S1, the betaine is anhydrous or monohydrate; preferably, the betaine is anhydrous.

4. The preparation method according to claim 1, characterized in that, In step S1, betaine is pulverized to a size of D50 < 30 μm, D70 < 60 μm, and D90 < 125 μm.

5. The preparation method according to claim 1, characterized in that, In step S2, the α-tocopherol includes d-α-tocopherol or dl-α-tocopherol.

6. The preparation method according to claim 1, characterized in that, In step S2, the purity of the α-tocopherol is ≥95%, preferably ≥98%.

7. The preparation method according to claim 1, characterized in that, In step S2, the mass ratio of α-tocopherol to betaine is (70:30)-(85:15).

8. The preparation method according to claim 1, characterized in that, In step S2, the mixing method is high-speed dispersion mixing, and the dispersion rate of the high-speed disperser is 500-2000 rpm, preferably 600-1500 rpm.

9. The preparation method according to claim 1, characterized in that, In step S3, the homogeneous viscous liquid from step S2 is heated to a temperature of 40-60°C; and / or The heating time is 0.5-6 hours, preferably 1-3 hours, for example 2 hours.

10. The preparation method according to claim 2, characterized in that, In step S4, the solidified material is pulverized to a particle size of less than 20 mesh.

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