阅读说明：本技术 葡萄糖酸钙的制备方法 (Preparation method of calcium gluconate ) 是由 马斌 尹文娟 吴燕枫 徐芳芳 于 2020-12-31 设计创作，主要内容包括：本发明公开了一种葡萄糖酸钙的制备方法,具有以下步骤：①由葡萄糖酸-δ-内酯与碳酸钙在80～90℃的温度下反应得到葡萄糖酸钙水溶液,然后加入药用活性炭,80～90℃下保温30min。②趁热过滤,滤液降温至30～40℃加入晶种,再降温至10～20℃,在该温度下以20±1Hz的频率搅拌结晶8h～12h。③离心过滤,滤饼经粉碎、干燥后得到葡萄糖酸钙成品。本发明经过大量实验发现,通过控制搅拌结晶的温度以及搅拌频率,能够保证结晶釜内温度均一稳定,从而解决了结晶结块、结晶包浆、以及过饱和度偏大等问题,显著提高了结晶效率,从而大大提高了反应收率。(The invention discloses a preparation method of calcium gluconate, which comprises the following steps: reacting gluconic acid-delta-lactone with calcium carbonate at the temperature of 80-90 ℃ to obtain a calcium gluconate aqueous solution, adding medicinal activated carbon, and preserving heat at the temperature of 80-90 ℃ for 30 min. ② filtering while hot, cooling the filtrate to 30-40 ℃, adding seed crystal, cooling to 10-20 ℃, stirring and crystallizing at the temperature with the frequency of 20 plus or minus 1Hz for 8-12 h. Thirdly, centrifugal filtration is carried out, and the finished product of the calcium gluconate is obtained after crushing and drying of a filter cake. According to the invention, a large number of experiments show that the temperature in the crystallization kettle can be ensured to be uniform and stable by controlling the temperature of stirring crystallization and the stirring frequency, so that the problems of crystallization agglomeration, crystallization slurry coating, large supersaturation degree and the like are solved, the crystallization efficiency is obviously improved, and the reaction yield is greatly improved.)

1. A preparation method of calcium gluconate comprises the following steps:

reacting gluconic acid-delta-lactone with calcium carbonate at the temperature of 80-90 ℃ to obtain a calcium gluconate aqueous solution, adding medicinal activated carbon, and preserving heat at the temperature of 80-90 ℃ for 30 min;

secondly, filtering while the solution is hot, cooling the filtrate to 30-40 ℃, adding seed crystals, cooling to 10-20 ℃, and stirring and crystallizing at the temperature for 8-12 hours at the frequency of 20 +/-1 Hz;

thirdly, centrifugal filtration is carried out, and the finished product of the calcium gluconate is obtained after crushing and drying of a filter cake.

2. The method for preparing calcium gluconate according to claim 1, wherein: in the third step, the molar ratio of the gluconic acid-delta-lactone to the calcium carbonate is 1: 0.4-1: 0.6.

3. The method for preparing calcium gluconate according to claim 2, wherein: in the step (c), the molar ratio of the gluconic acid-delta-lactone to the calcium carbonate is 1: 0.5.

4. The method of producing calcium gluconate according to any one of claims 1 to 3, wherein: and the drying in the third step is boiling drying, the temperature is 60-75 ℃, and the time is 1-3 h.

Technical Field

The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method of calcium gluconate.

Background

Calcium gluconate (also known as calcium gluconate monohydrate) is an organic calcium salt with chemical formula C₁₂H₂₄O₁₅Ca, white crystalline or granular powder, with melting point of 201 deg.C (decomposition), odorless, tasteless, and easily soluble in boiling water (20 g/100)mL) and is slightly soluble in cold water (3 g/100mL, 20 ℃) and insoluble in an organic solvent such as ethanol or diethyl ether. The aqueous solution was neutral (pH about 6-7). The calcium gluconate is mainly used as calcium enhancer, nutrient, buffering agent, solidifying agent and chelating agent of food.

At present, the method for preparing calcium gluconate mainly comprises the following two types:

(1) glucose oxidation method: that is, glucose and calcium carbonate are used as starting materials, and calcium gluconate is prepared by reaction in the presence of glucose oxidase and catalase [ see Chinese patent document CN106399404A, etc. ].

(2) Hydrolysis of gluconic acid-delta-lactone: namely, gluconic acid-delta-lactone is used as a starting material, is heated and dissolved to obtain gluconic acid, and then reacts with calcium carbonate to obtain calcium gluconate [ see Chinese patent document CN101434532A, etc. ].

At present, the biggest problems in the preparation of calcium gluconate are as follows: the yield is not high, and is usually only about 70%.

The main reasons for the low yield are as follows: the crystallization effect is not ideal, and the crystallization mother liquor contains a large amount of products.

Disclosure of Invention

The invention aims to solve the problems and provides a preparation method of calcium gluconate with higher product purity and higher reaction yield.

The technical scheme for realizing the purpose of the invention is as follows: a preparation method of calcium gluconate comprises the following steps:

reacting gluconic acid-delta-lactone with calcium carbonate at the temperature of 80-90 ℃ to obtain a calcium gluconate aqueous solution, adding medicinal activated carbon, and preserving heat at the temperature of 80-90 ℃ for 30 min.

② filtering while hot, cooling the filtrate to 30-40 ℃, adding seed crystal, cooling to 10-20 ℃, stirring and crystallizing at the temperature with the frequency of 20 plus or minus 1Hz for 8-12 h.

Thirdly, centrifugal filtration is carried out, and the finished product of the calcium gluconate is obtained after crushing and drying of a filter cake.

In the third step, the molar ratio of the gluconic acid-delta-lactone to the calcium carbonate is 1: 0.4-1: 0.6, and preferably 1: 0.5.

And the drying in the third step is boiling drying, the temperature is 60-75 ℃, and the time is 1-3 h.

The invention has the following positive effects: according to the invention, a large number of experiments show that the temperature in the crystallization kettle can be ensured to be uniform and stable by controlling the temperature of stirring crystallization and the stirring frequency, so that the problems of crystallization agglomeration, crystallization slurry coating, large supersaturation degree and the like are solved, the crystallization efficiency is obviously improved, and the reaction yield is greatly improved.

Detailed Description

(example 1)

The preparation method of calcium gluconate of the embodiment comprises the following steps:

adding 700L of purified water into a reaction kettle, starting stirring, adding 89kg (0.50 kmol) of gluconic acid-delta-lactone, adding 25kg (0.25 kmol) of calcium carbonate after complete stirring and dissolution, supplementing the purified water to reach the total volume of 850L, heating to 85 +/-1 ℃, and stirring for reaction for 1.5h to obtain a calcium gluconate aqueous solution. Then adding 1kg of 50-mesh medicinal activated carbon at one time under stirring, and keeping the temperature at 85 +/-1 ℃ for decoloring for 30 min.

② filtering while hot, cooling the filtrate to 35 plus or minus 1 ℃, adding 2kg of seed crystal, then cooling to 15 plus or minus 1 ℃, maintaining the temperature and stirring at the frequency of 20 plus or minus 1Hz for crystallization for 10 hours.

Thirdly, centrifugal filtration is carried out, and 106.6kg of calcium gluconate is obtained after filter cakes are crushed and boiled and dried for 2 hours at 70 ℃, the yield is 95.2 percent, and the purity (HPLC) is 98.9 percent.

(examples 2 to 3)

The preparation method of each example is substantially the same as that of example 1 except that see table 1.

(comparative examples 1 to 4)

The comparative examples were prepared in substantially the same manner as in example 1 except that the process is shown in Table 1.

TABLE 1

Crystallization temperature

Time of crystallization

Frequency of agitation

Weight (D)

Yield of

Purity of

Example 1

15±1℃

10h

20±1Hz

106.6kg

95.2%

99.5%

Example 2

12±1℃

12h

20±1Hz

104.9kg

93.7%

99.2%

Example 3

18±1℃

8h

20±1Hz

103.9kg

92.8%

99.0%

Comparative example 1

25±1℃

5h

20±1Hz

79.9kg

71.3%

98.2%

Comparative example 2

25±1℃

10h

20±1Hz

88.3kg

78.8%

98.8%

Comparative example 3

15±1℃

10h

30±1Hz

75.3kg

67.2%

96.5%

Comparative example 4

15±1℃

10h

10±1Hz

70.2kg

62.7%

95.7%