Preparation method of calcium gluconate monohydrate

Abstract

The present invention discloses a preparation method of calcium gluconate monohydrate, which uses glucono-δ-lactone, calcium carbonate and water as starting materials, and obtains calcium gluconate monohydrate through hydrolysis, decolorization, crystallization and drying; wherein: the weight ratio of glucono-δ-lactone to calcium carbonate is 10:3 to 10:5; the hydrolysis reaction temperature is 95 to 105 °C, and the decolorization reaction temperature is 65 to 75 °C; the temperature for adding crystal seeds is 55 to 65 °C; the crystallization temperature is 5 to 15 °C, and the crystallization time is 5 to 10 h; the drying is fluidized bed drying, the time is 60 to 180 min, the inlet air temperature is 70 ± 10 °C, and the frequency of the induced draft fan is 40 ± 10 Hz. The method of the present invention can obtain a higher purity content of calcium gluconate monohydrate by appropriately increasing the temperature for adding crystal seeds; the method of the present invention can effectively improve the reaction yield by appropriately increasing the hydrolysis reaction temperature and simultaneously appropriately decreasing the decolorization reaction temperature.

Description

Technical Field

[0001] The invention belongs to the technical field of drug preparation, and particularly relates to a method for preparing calcium gluconate monohydrate. Background Art

[0002] Calcium gluconate is an organic calcium salt with the appearance of white crystals or granular powder. It is odorless, tasteless, does not lose water when dry, does not decompose, and is stable in the air. Its aqueous solution is neutral, easily soluble in water, and insoluble in other organic solvents such as ethanol and ether. Its main uses include buffers, chelating agents, curing agents, food additives, calcium fortifiers, and nutritional drugs.

[0003] Calcium gluconate exists as anhydrous calcium gluconate (CAS number is 299-28-5, molecular formula is C 12 H 22 CaO 14 , molecular weight 430.37) and calcium gluconate monohydrate (CAS number 18016-24-5, molecular formula C 12 H 22 CaO 14 ·H2O, molecular weight 448.39) of two crystal forms, of which calcium gluconate monohydrate has the largest market demand.

[0004] The main problem of the prior art is that the calcium gluconate monohydrate prepared by the prior method contains more anhydrous calcium gluconate, resulting in lower purity. Therefore, providing a calcium gluconate monohydrate with higher purity is a technical problem that needs to be solved urgently in the art.

[0005] According to the United States Pharmacopoeia, there are some differences in the infrared spectra of anhydrous calcium gluconate and monohydrate gluconic acid. The characteristic peak wave number of the former is mainly 766cm -1 (Medium), 865cm -1 (weak), 948cm -1 (Medium), 1007cm -1 (Medium), 1263-1250cm -1 (strong), 1329cm -1 (Medium), 1618cm -1 (strong); the latter’s characteristic peak wave number is mainly 878cm -1 (weak), 972cm -1 (weak), 1045cm -1 (Medium), 1236cm -1 (Medium), 1305cm -1 (Medium), 1595cm -1 (Strong), standard infrared spectrum of calcium gluconate monohydrate is shown in Figure 1 . Summary of the Invention

[0006] The object of the present invention is to solve the above problems and provide a method for preparing calcium gluconate monohydrate with relatively high purity.

[0007] The technical solution for achieving the object of the present invention is: a method for preparing calcium gluconate monohydrate, which uses glucono-δ-lactone, calcium carbonate and water as starting materials, and obtains calcium gluconate monohydrate through hydrolysis, decolorization, crystallization and drying.

[0008] In the crystallization step, the temperature for adding crystal seeds is 55 - 65°C.

[0009] In the prior art, the temperature for adding crystal seeds does not exceed 45°C. The applicant has found through a large number of experiments that appropriately increasing the temperature for adding crystal seeds can obtain calcium gluconate monohydrate with relatively high purity.

[0010] Furthermore, the hydrolysis reaction temperature is 95 - 105°C, and the decolorization reaction temperature is 65 - 75°C.

[0011] In the prior art, the hydrolysis reaction temperature is basically below 90°C (such as CN106565460A, CN109608328A, CN112552167A, CN113045409A, CN111875490A, etc.); the decolorization reaction temperature is mostly the same as the hydrolysis reaction temperature (such as CN106565460A, CN112552167A, CN113045409A, etc.), that is, there is no heating or cooling operation after the hydrolysis reaction.

[0012] The applicant has found through a large number of experiments that appropriately increasing the hydrolysis reaction temperature and simultaneously appropriately decreasing the decolorization reaction temperature can effectively improve the reaction yield.

[0013] The weight ratio of glucono-δ-lactone to calcium carbonate is 10:3 - 10:5.

[0014] The crystallization temperature is 5 - 15°C, and the crystallization time is 5 - 10 h.

[0015] The drying is fluidized bed drying, the time is 60 - 180 min, the inlet air temperature is 70 ± 10°C, and the frequency of the induced draft fan is 40 ± 10 Hz.

[0016] The positive effects of the present invention are:

[0017] (1) By appropriately increasing the temperature for adding crystal seeds in the method of the present invention, the content of calcium gluconate monohydrate with relatively high purity can be obtained.

[0018] (2) The method of the present invention can effectively improve the reaction yield by appropriately increasing the temperature of the hydrolysis reaction and appropriately reducing the temperature of the decolorization reaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is the standard infrared spectrum of calcium gluconate monohydrate.

[0020] Figure 2 This is the infrared spectrum of calcium gluconate monohydrate obtained in Example 1.

[0021] Figure 3 This is the infrared spectrum of calcium gluconate monohydrate obtained in Example 2.

[0022] Figure 4 The infrared spectrum of calcium gluconate monohydrate prepared in Comparative Example 1 is shown in FIG. DETAILED DESCRIPTION

[0023] (Example 1)

[0024] The preparation method of calcium gluconate monohydrate of the present embodiment comprises the following steps:

[0025] ①Hydrolysis.

[0026] 400 kg of purified water was added into the reactor, and 50 kg of glucono-δ-lactone and 15 kg of calcium carbonate were added into the reactor under stirring, and then the temperature was raised to 100±2° C. and the hydrolysis reaction was carried out at this temperature for 2 hours to obtain a calcium gluconate aqueous solution.

[0027] ②Decolorization.

[0028] After the reaction is completed, the reaction system obtained in step ① is cooled to 70±2°C, 1 kg of activated carbon is added, and the temperature is kept at this temperature for 30 minutes for decolorization reaction.

[0029] ③Crystallization.

[0030] The reaction system obtained in step ② was filtered while hot, and the filtrate was naturally cooled to 60±2°C, 2 kg of seed crystals were added, and then the temperature was lowered to 10±2°C, and stirred for crystallization for 8 hours.

[0031] ④ Drying.

[0032] The reaction system obtained in step ③ was filtered, and the filter cake was subjected to boiling drying for 70 minutes, wherein: the air inlet temperature of the dryer was 70°C, and the frequency of the induced draft fan was 40Hz. After the boiling drying was completed, the material was discharged and cooled to obtain 100kg of calcium gluconate monohydrate with a yield of 79.5%. The infrared spectrum is shown in FIG. Figure 2 .

[0033] Depend on Figure 2It can be seen that the infrared spectrum of calcium gluconate monohydrate obtained in this example is the same as that of Figure 1 which is very close, indicating that the calcium gluconate monohydrate obtained in this example has a high purity.

[0034] (Example 2)

[0035] This example is basically the same as Example 1, except that: in step ①, the hydrolysis reaction temperature is 85 ± 2 °C; in step ②, the decolorization reaction temperature is 85 ± 2 °C.

[0036] Finally, 85 kg of calcium gluconate monohydrate is obtained, and the yield is 67.5%. The infrared spectrum is shown in Figure 3 .

[0037] From Figure 3 it can be seen that the infrared spectrum of calcium gluconate monohydrate obtained in Example 2 is the same as that of Figure 1 which is also very close, indicating that the calcium gluconate monohydrate obtained in Example 2 also has a high purity, but the reaction yield is lower than that in Example 1.

[0038] (Comparative Example 1)

[0039] This comparative example is basically the same as Example 1, except that: in step ③, the filtrate to be cooled naturally to 40 ± 2 °C, and 2 kg of seed crystals are added.

[0040] Finally, 97 kg of calcium gluconate monohydrate is obtained, and the yield is 77.1%. The infrared spectrum is shown in Figure 4 .

[0041] From Figure 4 it can be seen that there are certain differences between the infrared spectrum of calcium gluconate monohydrate obtained in Comparative Example 1 and that of Figure 1 especially the characteristic peak wave number 948 cm of anhydrous calcium gluconate -1 , indicating that the calcium gluconate monohydrate obtained in Comparative Example 1 contains more anhydrous calcium gluconate and has a lower purity.

Claims

1. A preparation method of calcium gluconate monohydrate, which uses glucono-δ-lactone, calcium carbonate and water as starting materials, and obtains calcium gluconate monohydrate through hydrolysis, decolorization, crystallization and drying; characterized in that: In the crystallization step, the temperature for adding crystal seeds is 55 to 65 °C.

2. The preparation method of calcium gluconate monohydrate according to claim 1, characterized in that: The temperature of the hydrolysis reaction is 95 to 105 °C, and the temperature of the decolorization reaction is 65 to 75 °C.

3. The preparation method of calcium gluconate monohydrate according to claim 1 or 2, characterized in that: The weight ratio of glucono-δ-lactone to calcium carbonate is 10:3 to 10:

5.

4. The preparation method of calcium gluconate monohydrate according to claim 1 or 2, characterized in that: The temperature of the crystallization is 5 to 15 °C, and the crystallization time is 5 to 10 h.

5. The preparation method of calcium gluconate monohydrate according to claim 1 or 2, characterized in that: The drying is fluidized bed drying, the time is 60 to 180 min, the inlet air temperature is 70 ± 10 °C, and the frequency of the induced draft fan is 40 ± 10 Hz.

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