阅读说明：本技术 一种维生素e琥珀酸酯的结晶纯化方法 (Crystallization and purification method of vitamin E succinate ) 是由 王彦飞 乔占博 许史杰 朱亮 杨立斌 赵晓昱 赵文立 韩梅 于 2020-06-05 设计创作，主要内容包括：本发明提供了一种维生素E琥珀酸酯的冷却结晶纯化方法,具体为：于冷却结晶器中先加入一定体积的饱和维生素E琥珀酸酯溶液,再加入一定量维生素E琥珀酸酯固体；恒温搅拌反应一段时间后以一定的降温速率进行降温结晶,结晶反应后静置一定时间；排出结晶器中产生的晶浆,晶浆经过滤、烘干处理后得到产品。本发明提供的维生素E琥珀酸酯的冷却结晶方法简单易行,收率高,纯化效果好,与传统纯化工艺相比,省去了原料试剂的生产以及反复洗涤除杂过程,缩短了工艺路线,降低了原料消耗和劳动强度,提高了维生素E琥珀酸酯与正己烷的回收率,使生产成本显著降低。(The invention provides a cooling crystallization purification method of vitamin E succinate, which comprises the following steps: firstly, adding a certain volume of saturated vitamin E succinate solution into a cooling crystallizer, and then adding a certain amount of vitamin E succinate solid; stirring at constant temperature for reaction for a period of time, cooling at a certain cooling rate for crystallization, and standing for a certain period of time after the crystallization reaction; discharging crystal slurry generated in the crystallizer, and filtering and drying the crystal slurry to obtain a product. Compared with the traditional purification process, the cooling crystallization method of the vitamin E succinate provided by the invention is simple and feasible, high in yield and good in purification effect, saves the production of raw material reagents and the repeated washing and impurity removal processes, shortens the process route, reduces the raw material consumption and labor intensity, improves the recovery rate of the vitamin E succinate and n-hexane, and obviously reduces the production cost.)

1. A crystallization and purification method of vitamin E succinate is characterized by comprising the following steps:

1) adding vitamin E succinate and n-hexane in a certain ratio into a cooling crystallizer to obtain a saturated vitamin E succinate solution;

2) adding a proper amount of vitamin E succinate solid into the saturated vitamin E succinate solution, and then starting stirring at the constant temperature of 30-45 ℃ for 1 h;

3) cooling and crystallizing at a cooling rate of 8-10 ℃/h, cooling to the final crystallization temperature, and standing at a constant temperature for a period of time;

4) and discharging the crystal slurry in the cooling crystallizer, and filtering and drying the discharged crystal slurry to obtain a product.

2. The process for the crystallization purification of vitamin E succinate according to claim 1, characterized in that: the saturated vitamin E succinate solution prepared in the step 1) is a saturated solution at the temperature of 30-45 ℃, wherein the vitamin E succinate accounts for 16.90% of the total mass of the solution; the addition amount of the vitamin E succinate solid in the step 2) is 0.1-10% of the total mass of the saturated vitamin E succinate solution.

3. The process for the crystallization purification of vitamin E succinate according to claim 1 or 2, characterized in that: the stirring speed in the constant-temperature stirring in the step 2) is 70-150 rpm; in the step 3), cooling crystallization is preferably carried out at a cooling rate of 10 ℃/h, and the final crystallization temperature of the cooling crystallization is 0 ℃; and the constant temperature standing time after the temperature is reduced to the final temperature of crystallization is 0.5 to 2 hours.

The technical field is as follows:

the invention relates to the field of purification and preparation of vitamin E succinate, and particularly relates to a cooling crystallization method of vitamin E succinate.

Background art:

vitamin E succinate is also known as tocopherol succinate, known by the english name: vitamin E succinate, its formula: c₃₃H₅₄O₅. The shape is usually white powder. Vitamin E succinate is poorly soluble in water and readily soluble in diethyl ether, acetone and n-hexane. The vitamin E succinate has no odor, no toxicity, no pungent smell, and good biocompatibility. Vitamin E is one of essential nutrients for human bodies, vitamin E succinate can be used for synthesizing medicaments, and vitamin E used in a large number of tablet and capsule nutritional supplements is vitamin E succinate, and the vitamin E succinate has a very obvious effect of inhibiting the growth of cultured tumor cells of human bodies. The vitamin E succinate can also be used in the field of food for preparing health products and the like.

Although the chemical synthesis route in the current domestic industrial production of vitamin E succinate is relatively mature, the problems of uneven product particle size distribution, low yield and the like still exist in the subsequent purification process. These problems restrict the production and use of vitamin E succinate, making it less desirable to meet market needs.

At present, vitamin E succinate is produced mainly by chemical synthesis, and in addition, by enzymatic synthesis. The main problems of chemical synthesis are high energy consumption and low yield. In contrast, enzymatic synthesis is environmentally friendly, green and pollution-free, but reaction cost cannot be controlled due to generally high market selling price of selected lipase, and synthesis time is not supported by clear data.

The invention content is as follows:

in view of the above problems, the present invention aims to provide a cooling crystallization method of vitamin E succinate, which can recycle the solvent, produce products with high purity and uniform average quality, and eliminate the batch-to-batch variation of product quality.

The technical scheme of the invention is as follows:

the cooling crystallization method of the vitamin E succinate comprises the following steps:

1) firstly, adding vitamin E succinate and n-hexane in a certain ratio into a cooling crystallizer to obtain a saturated vitamin E succinate solution;

2) adding a proper amount of vitamin E succinate solid into the saturated vitamin E succinate solution, and then starting stirring at the constant temperature of 30-45 ℃ for 1 h;

3) cooling and crystallizing at a cooling rate of 8-10 ℃/h, cooling to the final crystallization temperature, and standing at a constant temperature for a period of time;

4) and discharging the crystal mush in the cooling crystallizer, and filtering and drying the discharged crystal mush to obtain a vitamin E succinate crystal product.

Further, the saturated vitamin E succinate solution prepared in the step 1) is a saturated solution at the temperature of 30-45 ℃, wherein the vitamin E succinate accounts for 16.90% of the total mass of the solution; the addition amount of the vitamin E succinate solid in the step 2) is 0.1-10% of the total mass of the saturated vitamin E succinate solution.

Further, in the step 2), the stirring speed during constant-temperature stirring is 70-150 rpm.

Further, in the step 3), cooling crystallization is preferably carried out at a cooling rate of 10 ℃/h, and the crystallization final temperature of the cooling crystallization is 0 ℃; and the constant temperature standing time after the temperature is reduced to the final temperature of crystallization is 0.5 to 2 hours.

Compared with the traditional purification process, the cooling crystallization method of the vitamin E succinate provided by the invention has the advantages that the production of raw material reagents and repeated washing impurity removal processes are omitted, the process route is shortened, the raw material consumption and labor intensity are reduced, the recovery rate of the vitamin E succinate and n-hexane is improved, and the production cost is obviously reduced.

Description of the drawings:

FIG. 1 XRD spectra of vitamin E succinate crystal products obtained from example 1 and example 2 and of a standard substance (control).

FIG. 2 is a gas chromatogram of the vitamin E succinate crystal product obtained in example 2.

Fig. 3 polarization microscope characterization of the vitamin E succinate crystal product obtained in example 2.

Figure 4 DSC profile of vitamin E succinate crystal product obtained from example 2.

The specific implementation mode is as follows:

the technical solution of the present invention is further described in detail by examples below.