Preparation method and application of tocopherol acetate with antioxidant and anti-inflammatory effects

Abstract

The present invention relates to a preparation method and application of tocopherol acetate with antioxidant and anti-inflammatory effects, the preparation method comprising: mixing D-α-tocopherol, ethyl acetate and a catalyst, reacting under vacuum and microwave action to obtain tocopherol acetate. The preparation method of tocopherol acetate provided by the present invention has simple process, safe operation and low production cost, and achieves the preparation of high-yield, high-purity tocopherol acetate, and the obtained tocopherol acetate has a small molecular weight, high stability and is easy to absorb, and can maximize its antioxidant, anti-inflammatory, moisturizing and other effects, and can be widely used in cosmetics.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a preparation method of tocopherol acetate with anti-oxidation and anti-inflammatory effects and application thereof. Background Art

[0002] Vitamin E is a fat-soluble vitamin and one of the most important antioxidants. It can promote gonadal development, so it is also called tocopherol. It was discovered by foreign scientists in 1922, named vitamin E in 1924, and successfully synthesized by Swiss chemists in 1938. Vitamin E mainly has the physiological functions of anti-aging and improving fertility. In recent years, it has been discovered that tocopherol acetate, a derivative of vitamin E, also has a certain effect on skin regulation. Tocopherol acetate, also known as vitamin E acetate, is a vitamin E derivative produced by the esterification of vitamin E and ethyl acetate. Tocopherol acetate is very popular in cosmetics and is usually used as an antioxidant with good antioxidant and anti-inflammatory effects.

[0003] At present, tocopherol acetate has certain applications in medicine, food and daily chemical industry. However, due to the uneven production technology, the difficulty and complexity of the technical innovation project itself, and the limited ability and strength of the innovator, the production cost is greatly increased, and the product efficacy is also affected to a certain extent. Through the innovation in the production of tocopherol acetate, its water solubility, absorbability and drug efficacy have been improved. In order to improve the chemical properties of tocopherol acetate, the extraction technology on the market is mainly chemical synthesis. For example, the acetic acid solution of 2,3,5-trimethylhydroquinone diester and isophytol are pumped into a microchannel reactor at the same time, and the modified resin is used as a catalyst for ester exchange reaction to obtain tocopherol acetate. Alternatively, tocopherol and acetic anhydride are subjected to esterification reaction in the presence of a solvent to obtain tocopherol acetate, etc.

[0004] The above-mentioned synthesis method has the disadvantages of high reaction cost and poor raw material stability. Therefore, it is necessary to provide a safe, efficient, low-cost preparation method of tocopherol acetate that can improve product yield, purity and efficacy. Summary of the invention

[0005] To solve the above technical problems, the present invention provides a method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects and its application. The method for preparing tocopherol acetate provided by the present invention has simple process, safe operation, low production cost, and realizes the preparation of tocopherol acetate with high yield and high purity, and the obtained tocopherol acetate has small molecular weight, high stability, and is easy to absorb, and can maximize its antioxidant, anti-inflammatory, moisturizing and other effects, and can be widely used in cosmetics.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a method for preparing tocopherol acetate having antioxidant and anti-inflammatory effects, the preparation method comprising:

[0008] D-α-tocopherol, ethyl acetate and a catalyst are mixed and reacted under vacuum and microwave to obtain tocopherol acetate.

[0009] In the present invention, D-α-tocopherol and ethyl acetate react under the action of a catalyst, vacuum and microwave to prepare tocopherol acetate. The vacuum is used to prevent oxidation during the reaction, and the microwave provides energy for the reaction, and the two cooperate to achieve the preparation of tocopherol acetate with high yield and high purity. At the same time, the preparation method provided by the present invention has simple process, safe operation, low production cost, and high practical application value.

[0010] The tocopherol acetate prepared by the preparation method provided by the present invention has a small molecular weight, high stability and is easy to absorb, which effectively solves the problems of poor transdermal absorption effect, poor solubility and poor stability of vitamin E itself, while also maximizing its antioxidant, anti-inflammatory, moisturizing and other effects, and can be widely used in cosmetics.

[0011] Preferably, the catalyst comprises any one of 4-dimethylaminopyridine, tin chloride or phosphorus pentoxide, or a combination of at least two thereof.

[0012] Preferably, the molar ratio of D-α-tocopherol, ethyl acetate and catalyst is 1:(1.75-2.25):(0.01-0.02).

[0013] The above numerical values ​​(1.75-2.25) may be, for example, 1.75, 1.8, 1.9, 2, 2.1, 2.2, 2.25, etc.; the numerical values ​​(0.01-0.02) may be, for example, 0.01, 0.012, 0.015, 0.018, 0.02, etc.

[0014] Preferably, the vacuum pressure is 0.95-1.05 kPa (for example, it can be 0.95 kPa, 0.98 kPa, 1 kPa, 1.02 kPa, 1.05 kPa, etc.), the temperature of the microwave is 110-120°C (for example, it can be 110°C, 112°C, 114°C, 116°C, 118°C, 120°C, etc.), the power of the microwave is 800-1000 W (for example, it can be 800 W, 850 W, 900 W, 950 W, 1000 W, etc.), and the reaction time is 10-20 h (for example, it can be 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, etc.).

[0015] In the present invention, vacuum prevents oxidation during the reaction, and microwaves provide energy for the reaction. When the reaction parameters are within the specified range of the present invention, the yield and purity of the obtained product are higher.

[0016] Preferably, the reaction further comprises a post-treatment step.

[0017] Preferably, the post-treatment includes fractionating and purifying the system after the reaction to obtain pure tocopherol acetate.

[0018] Preferably, the distillation pressure is 0.4-1.0 MPa (for example, it can be 0.4 MPa, 0.5 MPa, 0.6 MPa, 0.7 MPa, 0.8 MPa, 0.9 MPa, 1.0 MPa, etc.), and the heating temperature of the distillation is 100-120°C (for example, it can be 100°C, 105°C, 110°C, 115°C, 120°C, etc.).

[0019] Preferably, the preparation method of D-α-tocopherol comprises:

[0020] The tocopherol concentrate, methanol, an acid catalyst, a hydroxymethylation agent and Raney nickel are mixed and subjected to a high-pressure hydrogenation reaction to obtain D-α-tocopherol.

[0021] Preferably, the acid catalyst comprises any one of formic acid, p-toluenesulfonic acid or glacial acetic acid, or a combination of at least two thereof.

[0022] Preferably, the hydroxymethylation agent comprises any one of formaldehyde or paraformaldehyde or a combination of both.

[0023] Preferably, based on 100 parts by weight of the tocopherol concentrate, the amount of methanol is 200-400 parts (for example, 200 parts, 250 parts, 300 parts, 350 parts, 400 parts, etc.), the amount of the acid catalyst is 1.5-4 parts (for example, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, etc.), the amount of the hydroxymethylation agent is 10-25 parts (for example, 10 parts, 14 parts, 18 parts, 22 parts, 25 parts, etc.), and the amount of Raney nickel is 3-5 parts (for example, 3 parts, 3.4 parts, 3.8 parts, 4.2 parts, 4.6 parts, 5 parts, etc.).

[0024] Preferably, the pressure of the high-pressure hydrogenation reaction is 0.5-1.5 MPa (for example, it can be 0.5 MPa, 0.8 MPa, 1.0 MPa, 1.2 MPa, 1.5 MPa, etc.), the temperature is 80-120°C (for example, it can be 80°C, 90°C, 100°C, 110°C, 120°C, etc.), and the time is 2.5-3.5 h (for example, it can be 2.5 h, 2.8 h, 3 h, 3.2 h, 3.5 h, etc.).

[0025] In the present invention, D-α-tocopherol can be a commercially available product or can be prepared by the above preparation method.

[0026] Preferably, the method for preparing tocopherol acetate comprises:

[0027] D-α-tocopherol, ethyl acetate and a catalyst are mixed in a molar ratio of 1:(1.75-2.25):(0.01-0.02), and reacted for 10-20 hours at 0.95-1.05 kPa, 110-120° C. and 800-1000 W in vacuum and under microwave action to obtain tocopherol acetate.

[0028] In a second aspect, the present invention provides an application of the preparation method of tocopherol acetate with antioxidant and anti-inflammatory effects according to the first aspect in the preparation of cosmetics.

[0029] Compared with the prior art, the present invention has at least the following beneficial effects:

[0030] The preparation method of tocopherol acetate provided by the present invention has simple process, safe operation and low production cost, and realizes the preparation of tocopherol acetate with high yield and high purity. The obtained tocopherol acetate has small molecular weight, high stability and easy absorption, and effectively solves the problems of poor transdermal absorption effect, poor solubility and poor stability of vitamin E itself. At the same time, it also maximizes its antioxidant, anti-inflammatory, moisturizing and other effects, and can be widely used in cosmetics. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is the high performance liquid chromatogram in Example 1. DETAILED DESCRIPTION

[0032] The technical solution of the present invention is further described below in conjunction with the accompanying drawings and through specific implementation methods. However, the following examples are only simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0033] Example 1

[0034] This embodiment provides a method for preparing tocopherol acetate having antioxidant and anti-inflammatory effects, which specifically comprises:

[0035] D-α-tocopherol, ethyl acetate and a catalyst (4-dimethylaminopyridine) are mixed in a molar ratio of 1:2:0.015, and reacted for 20 hours under a vacuum of 1 kPa, 120°C and 1000 W and microwave action to obtain a crude tocopherol acetate; the crude tocopherol acetate is added to the upper part of a distillation tower through a feed part, the pressure of the distillation tower is controlled to be 0.8 MPa, and the bottom temperature of the tower is controlled to be 120°C, and the evaporated components are collected after condensation to obtain a pure tocopherol acetate.

[0036] The HPLC chromatogram of the obtained product is as follows: Figure 1 shown.

[0037] Example 2

[0038] This embodiment provides a method for preparing tocopherol acetate having antioxidant and anti-inflammatory effects, which specifically comprises:

[0039] D-α-tocopherol, ethyl acetate and a catalyst (tin chloride) are mixed in a molar ratio of 1:1.75:0.01, and reacted for 18 hours under a vacuum of 0.95 kPa, 110°C and 900 W and microwave action to obtain a crude tocopherol acetate; the crude tocopherol acetate is added to the upper part of a distillation tower through a feed part, the pressure of the distillation tower is controlled to be 0.4 MPa, and the bottom temperature of the tower is controlled to be 105°C, and the evaporated components are collected after condensation to obtain a pure tocopherol acetate.

[0040] Example 3

[0041] This embodiment provides a method for preparing tocopherol acetate having antioxidant and anti-inflammatory effects, which specifically comprises:

[0042] D-α-tocopherol, ethyl acetate and a catalyst (phosphorus pentoxide) are mixed in a molar ratio of 1:2.25:0.02, and reacted for 15 hours under a vacuum of 1.05 kPa, 105°C and 800 W and microwave action to obtain a crude tocopherol acetate; the crude tocopherol acetate is added to the upper part of a distillation tower through a feed part, the pressure of the distillation tower is controlled to be 1 MPa, and the bottom temperature of the tower is controlled to be 110°C, and the evaporated components are collected after condensation to obtain a pure tocopherol acetate.

[0043] Example 4

[0044] This embodiment provides a method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects. The only difference between this method and Example 1 is that the vacuum pressure is 1.2 kPa. The rest is reference to Example 1.

[0045] Example 5

[0046] This embodiment provides a method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects, which is different from Example 1 only in that the vacuum pressure is 0.7 kPa, and the rest is reference to Example 1.

[0047] Example 6

[0048] This embodiment provides a method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects. The only difference between this method and Example 1 is that the temperature of the microwave is 95° C., and the rest is reference to Example 1.

[0049] Example 7

[0050] This embodiment provides a method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects, which is different from Example 1 only in that the microwave temperature is 135° C., and the rest is reference to Example 1.

[0051] Example 8

[0052] This embodiment provides a method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects, which is different from Embodiment 1 only in that sodium chloride is used as a catalyst, and the rest is reference to Embodiment 1.

[0053] Comparative Example 1

[0054] This comparative example provides a method for preparing tocopherol acetate having antioxidant and anti-inflammatory effects, which is different from Example 1 only in that the reaction is carried out under normal pressure (101.325 kPa), and the rest is referred to Example 1.

[0055] Comparative Example 2

[0056] This comparative example provides a method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects, which is different from Example 1 only in that microwave treatment is not used, and the rest is reference to Example 1.

[0057] Test Example 1

[0058] Yield and purity

[0059] The yield and purity information of the above examples and comparative examples are summarized in Table 1.

[0060] Table 1

[0061] Grouping Yield (%) purity(%) Example 1 99.8％ 97.7％ Example 2 98.5％ 96.5％ Example 3 98.1％ 95.9％ Example 4 92.5％ 94.1％ Example 5 92.2％ 94.6％ Example 6 91.5％ 93.9％ Example 7 91.3％ 93.3％ Example 8 91.1％ 92.8％ Comparative Example 1 73.3％ 69.0％ Comparative Example 2 72.9％ 64.3％

[0062] The test results show that:

[0063] (1) It can be seen from Examples 1 to 8 that the reaction of D-α-tocopherol and ethyl acetate under the action of a catalyst, vacuum and microwave can achieve the preparation of tocopherol acetate with high yield and high purity.

[0064] (2) By comparing Example 1 with Examples 4 to 7, it can be seen that the yield and purity of the reaction can be further improved by further limiting the vacuum pressure and microwave temperature of the reaction;

[0065] By comparing Example 1 with Example 8, it can be seen that the present invention has higher catalytic efficiency and higher product yield and purity by adopting a specific catalyst system.

[0066] (3) By comparing Example 1 with Comparative Examples 1 to 2, it can be seen that vacuum conditions can prevent oxidation and microwave treatment provides energy for the reaction. When one of the conditions is missing, the yield and purity of the reaction decrease.

[0067] Test Example 2

[0068] Efficacy Test

[0069] Test method:

[0070] Prepare the sample into the test solution of the corresponding concentration, prepare the reaction system according to the instructions of the hydroxyl radical determination kit (Nanjing Jiancheng, A018-1-1), mix well, set up 3 replicates for each concentration, and use 0.3 mg / mL vitamin C as a positive control. Mix well, leave at room temperature for 20 minutes, take 200 μL from each tube and transfer to a 96-well plate, measure the absorbance value of each tube at a wavelength of 550 nm, and calculate the scavenging rate of the sample for hydroxyl free radicals according to the following formula:

[0071]

[0072] The efficacy test results of the tocopherol acetate prepared in Example 1 are shown in Table 2.

[0073] Table 2

[0074]

[0075]

[0076] Conclusion: The tocopherol acetate sample has excellent scavenging ability for hydroxyl free radicals when the concentration is 10-20%, and there is a statistical difference compared with the control group (p<0.01), indicating that the tocopherol acetate prepared by the specific preparation method of the present invention has excellent antioxidant capacity.

[0077] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing tocopherol acetate having antioxidant and anti-inflammatory effects, characterized in that: The preparation method comprises: D-α-tocopherol, ethyl acetate and a catalyst are mixed and reacted under vacuum and microwave to obtain tocopherol acetate.

2. The preparation method according to claim 1, characterized in that: The catalyst includes any one of 4-dimethylaminopyridine, tin chloride or phosphorus pentoxide, or a combination of at least two of them.

3. The preparation method according to claim 1 or 2, characterized in that: The molar ratio of the D-α-tocopherol, ethyl acetate and the catalyst is 1:(1.75-2.25):(0.01-0.02).

4. The preparation method according to any one of claims 1 to 3, characterized in that: The vacuum pressure is 0.95-1.05 kPa, the microwave temperature is 110-120° C., the microwave power is 800-1000 W, and the reaction time is 10-20 h.

5. The preparation method according to any one of claims 1 to 4, characterized in that: The reaction also includes a post-processing step; Preferably, the post-treatment includes fractionating and purifying the system after the reaction to obtain pure tocopherol acetate.

6. The preparation method according to claim 5, characterized in that: The pressure of the fractional distillation is 0.4-1.0 MPa, and the heating temperature of the fractional distillation is 100-120°C.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The preparation method of the D-α-tocopherol comprises: The tocopherol concentrate, methanol, an acid catalyst, a hydroxymethylation agent and Raney nickel are mixed and subjected to a high-pressure hydrogenation reaction to obtain D-α-tocopherol.

8. The preparation method according to claim 7, characterized in that: The acid catalyst includes any one of formic acid, p-toluenesulfonic acid or glacial acetic acid or a combination of at least two thereof; Preferably, the hydroxymethylation agent comprises any one of formaldehyde or paraformaldehyde or a combination of both; Preferably, based on 100 parts by weight of the tocopherol concentrate, the amount of methanol is 200 to 400 parts, the amount of the acid catalyst is 1.5 to 4 parts, the amount of the hydroxymethylation agent is 10 to 25 parts, and the amount of Raney nickel is 3 to 5 parts; Preferably, the pressure of the high-pressure hydrogenation reaction is 0.5-1.5 MPa, the temperature is 80-120° C., and the time is 2.5-3.5 h.

9. The preparation method according to any one of claims 1 to 8, characterized in that: The preparation method of tocopherol acetate comprises: D-α-tocopherol, ethyl acetate and a catalyst are mixed in a molar ratio of 1:(1.75-2.25):(0.01-0.02), and reacted for 10-20 hours at 0.95-1.05 kPa, 110-120° C. and 800-1000 W in vacuum and under microwave action to obtain tocopherol acetate.

10. Use of the method for preparing tocopherol acetate with antioxidant and anti-inflammatory effects according to any one of claims 1 to 9 in the preparation of cosmetics.

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