JPS6228939B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing sodium ferrous citrate. The ferrous sodium citrate molecule according to the present invention is composed of two citric acid groups, one ferrous atom, and four sodium atoms, as shown in the examples below, and the molecule is composed of two citric acid groups, one ferrous atom, and four sodium atoms. Taken together, it is estimated that it is a complex with an octahedral hexacoordination structure. In addition, the substance is well absorbed from the intestinal tract,
It is expected to be used for anemia treatment as a highly utilized iron agent. Now, as prior art related to the present invention, Japanese Patent Publication No. 48-46 discloses that 2 citric acid 1 ferrous atoms are composed of 2 citric acid groups, 1 ferrous atom, and 4 sodium atoms. A technique is disclosed in which a monoiron complex is obtained by the reaction of one molar equivalent of a water-soluble ferrous salt with three or more molar equivalents of trisodium citrate. That is, in the conventional technology, the amount of trisodium citrate required for producing the ferrous sodium citrate complex is 3 molar equivalents or more relative to the ferrous salt (the reaction system is alkaline).
It is a generally known fact that a large excess of trisodium citrate was usually added for the reaction. Therefore, in the prior art, unreacted trisodium citrate was wasted, which was uneconomical. In view of these circumstances, the present inventors investigated a method for efficiently producing a ferrous sodium citrate complex by simple and simple operations, and surprisingly found that water-soluble ferrous salt 1 The present invention was completed based on the knowledge that the desired object could be achieved by preparing 2.1 molar equivalents to less than 3 molar equivalents of trisodium citrate and reacting the two. That is, the present invention is a method for producing sodium ferrous citrate, which is characterized in that 1 molar equivalent of a water-soluble ferrous salt is reacted with 2.1 molar equivalents to less than 3 molar equivalents of trisodium citrate (the reaction agent is acidic). be. Next, the present invention will be explained in detail. As water-soluble ferrous salts, ferrous chloride and ferrous sulfate are mainly used, but FeSO ₄ · 7H ₂ O and FeSO ₄ · H ₂ O are usually used as stable raw materials that can be obtained.
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is used, with FeSO ₄ .7H ₂ O being particularly preferred. On the other hand, as trisodium citrate, a commonly available dihydrate may be used. The amount of trisodium citrate used is per mole equivalent of water-soluble ferrous salt.
2.1 molar equivalents to less than 3 molar equivalents are sufficient,
Within this range, there is no significant variation in the yield of the complex according to the present invention. For example, when the amount of trisodium citrate used was 2.1 molar equivalents and 2.5 molar equivalents, the yields were 81.0% and 87.9%, respectively. The reaction may normally be carried out in water, and specifically, heated aqueous solutions of both components may be prepared, mixed, and cooled. In order to facilitate crystal precipitation, each highly concentrated aqueous solution may be prepared by heating to, for example, 90°C or higher, mixed by stirring, and then cooled to, for example, 25°C. The reaction ends immediately after mixing, but stirring may be continued for 2 to 3 hours while heating. The precipitated crystals are almost insoluble in methanol, ethanol, acetone, ether, etc.
After collection, it is first washed with cold water and then with the above solvent to obtain green-white crystals. The complexes obtained by the method of the invention can be characterized by elemental analysis and IR spectra. The drawings are IR spectra obtained by the KBr disk method as shown in Examples below. The specific wave number is, for example, 1615 (s), 1592 (s), 1560 (s), 1485
(w), 1426 (m), 1412 (m), and 1395 (m). X-ray diffraction and effective magnetic moments can be shown as reference data, but they do not serve as limiting information for the present invention. By the way, measurement of the effective magnetic moment shows that it is 5.20BM. Next, the present invention will be explained in more detail with reference to Examples. Example 1 882 g (3.0 mol) of trisodium citrate 2H ₂ O and 792 ml of water were mixed and heated on a hot water bath (~94°C).
Heat to dissolve and place on a hot water bath while stirring (inner temperature 94℃ or higher). 333.6 g (1.2 mol) of FeSO ₄ 7H ₂ O and 334 ml of water
This was heated (approximately 60°C) to dissolve and suction filtered. The liquid is green. This liquid was added all at once into the flask containing the above trisodium citrate aqueous solution. The internal temperature was 94 degrees Celsius at one point.
The temperature drops to 80℃. The color is brown and transparent. The temperature reached 90°C 3 minutes after mixing, and crystals began to precipitate 4 minutes later. 90
The temperature was kept above ℃ and the reaction was stirred for 150 minutes. Cool (29℃), suction filter, water 300ml, 50%
Wash with 300 ml of methanol-denatured ethanol water and 300 ml of methanol-denatured ethanol. It was dried with warm air at 85°C for 24 hours. Green white. Yield 555g (87.9%). Elemental analysis of the obtained crystals revealed the following results. In addition, the molecules of the crystal are 2
It is composed of 1 citric acid group, 1 ferrous atom, and 4 sodium atoms, and has a molecular weight of 526. In addition, an IR spectrum (KBr disk method) was taken as shown in the drawing.

[Table] Example 2 Trisodium citrate. 292g of _2H2O (0.993
mol) was dissolved in 436 ml of water (corresponding to a saturated solution at 28°C). The pH of solution (A) is 8 (test paper). 110 g (0.396 mol) of FeSO ₄ .7H ₂ O was dissolved in water with slight heating (corresponding to a saturated solution at 28° C.).
The pH of solution (B) is 4 (test paper). Add the above solution (B) sequentially to solution (A) in one flask equipped with a stirring blade. The pH at the time of mixing (finished) is 5.5. Stir while keeping the temperature above 90℃ (internal temperature) on a hot water bath. Eventually (7 to 55 minutes) crystals begin to precipitate. After a certain period of time, cool (around 25°C), filter by suction, and wash sequentially with 100 ml of water, 100 ml of 50% methanol, 100 ml of methanol, and 100 ml of isopropyl ether. It was dried for 100 minutes under reduced pressure (20-30 mmHg) on a hot water bath. Green-white crystals were obtained. Example 3 Trisodium citrate/147 g (0.5 mol) of 2H ₂ O and 132 ml of water were dissolved with stirring while hot (94°C), and then
55.6 g (0.2 mol) of FeSO ₄ .7H ₂ O was dissolved in 56 ml of water by heating (around 60° C.), decanted, and added to the above solution. Stir and react for 150 minutes at an internal temperature of 90°C or higher, then cool (25
℃), then add 50 ml of water, 50% ethanol water 50 ml
ml, washed with 50 ml of ethanol, and placed on a hot water bath (90-95℃)
It was dried under reduced pressure (20-30 mmHg) for 1 hour. 〓〓〓〓〓
The yield is shown in the table below. In addition, in this example, trisodium citrate, 2H ₂ O147
The procedure was as described above, except that instead of using 132 ml of trisodium citrate, 2H ₂ O, and 110 ml of water, 123.5 g (0.42 mol) of trisodium citrate, 2H 2 O, and 110 ml of water were used. The yield for each is shown in the table below.

[Table] Example 4 50 kg (170.1 mol) of trisodium citrate/2H ₂ O and 80 kg of water were dissolved by heating (50 to 60°C). This was concentrated under reduced pressure. Concentrate to about 70%. Crystals precipitate during the process. There, it was heated and dissolved. _FeSO4・
20 kg (71.9 mol) of 7H ₂ O and 20 kg of water were added and dissolved by heating (70°C). The liquid was added to the sodium citrate solution all at once by suction. While I was putting it in, crystals started to precipitate. The molar ratio of FeSO ₄ .7H ₂ O:sodium citrate .2H ₂ O was 1:2.36. Stir and react at 90°C or higher for 2.5 hours (90-106°C (constant)). Cool with cold water and separate (centrifuge) when the internal temperature is 31℃. Wed 18,
Wash with 18% 50% methanol water and 18% methanol.
Dry at around 80℃ (75-82℃) using a box-type warm air dryer.
I went for 5 hours with the warm air. Yield 34.5Kg (90.3%). Example 5 According to Example 3, 2.7 molar equivalents of trisodium citrate/2H ₂ O were added to 1 molar equivalent of FeSO ₄ /7H ₂ O.
It was carried out using molar equivalents and a ratio of 2.9 molar equivalents. The results are shown below.

【table】 [Brief explanation of the drawing]

The drawing shows the IR spectrum of sodium ferrous citrate according to the invention. 〓〓〓〓〓

Claims (1)

[Scope of Claims] 1. A method for producing sodium ferrous citrate, which comprises reacting 1 molar equivalent of a water-soluble ferrous salt with 2.1 molar equivalents to less than 3 molar equivalents of trisodium citrate. 2. The method for producing sodium ferrous citrate according to claim 1, wherein the water-soluble ferrous salt is ferrous sulfate or ferrous chloride.