A method for preparing a sucrose hydroxy ferric oxide complex

Abstract

The application provides a preparation method of a sucrose-hydroxyl iron oxide compound, relates to the field of compound preparation methods, and specifically comprises the following steps: (1) synthesis of hydroxyl iron oxide; (2) desalination; and (3) synthesis of the sucrose-hydroxyl iron oxide compound. In the process of removing the inorganic salt of the hydroxyl iron oxide in the preparation method of the sucrose-hydroxyl iron oxide compound, the hydroxyl iron oxide is first diluted with water and then filtered and desalted, so that the desalination efficiency is significantly improved, the overall production cycle is greatly shortened, the production efficiency is improved, and the production cost is saved.

Description

Technical Field

[0001] This invention relates to the field of compound preparation methods, and specifically to a method for preparing a sucrose hydroxyl iron oxide complex. Background Technology

[0002] Sucrose ferric hydroxide chewable tablets, as a novel iron-based non-calcium phosphate binder, offer a new treatment option for hyperphosphatemia. This drug has a unique complex structure composed of polynuclear iron hydroxide and carbohydrates (a mixture of polynuclear ferric hydroxide (III), sucrose, and starch), which effectively binds to phosphate in the serum, thereby lowering serum phosphorus levels. This mechanism helps prevent and treat complications of hyperphosphatemia, such as cardiovascular disease and bone disorders. Furthermore, sucrose ferric hydroxide contains approximately 20% iron, which may have a therapeutic effect on renal anemia.

[0003] The sucrose ferric hydroxide complex is prepared by complexing sucrose ferric hydroxide with sucrose, potato starch, and pregelatinized corn starch. The preparation method involves adding ferric chloride to a sodium carbonate solution and stirring the reaction. One major problem in all methods for preparing sucrose iron complexes is the removal of anions (e.g., chloride content) generated by the iron salts used (e.g., ferric chloride). This anion content is physiologically undesirable and affects the quality of the final product, sucrose ferric hydroxide. In known methods, this chloride content needs to be removed from the slurried ferric hydroxide suspension. However, experiments show that the synthesized ferric hydroxide suspension has extremely high viscosity, making the filtration of inorganic salts from the suspension very difficult and time-consuming. Therefore, optimizing the filtration process for inorganic salts in the ferric hydroxide solution is crucial for shortening the overall production cycle of the sucrose ferric hydroxide complex. Summary of the Invention

[0004] To address the technical problems of difficult removal of inorganic salts and long filtration cycles in the preparation process of sucrose ferric hydroxide complex in existing technologies, this invention provides a method for preparing sucrose ferric hydroxide complex, comprising the following steps:

[0005] (1) Synthesis of ferric hydroxide: Ferric chloride was added to sodium carbonate solution and stirred to react. A sample was taken to measure the pH and a suspension of ferric hydroxide was obtained.

[0006] (2) Desalting: Add purified water to the above iron hydroxy oxide suspension at a volume ratio of 1:1-8, stir and dilute, then filter to remove inorganic salts to obtain iron hydroxy oxide filter cake.

[0007] (3) Synthesis of sucrose ferric hydroxide complex: ferric hydroxide filter cake was mixed with water to form a suspension. Under continuous stirring, sucrose, potato starch and pregelatinized starch were added to it and the reaction was carried out under controlled temperature to obtain ferric hydroxide. A suspension composed of ferric hydroxide, sucrose and starch was obtained. The suspension was spray-dried to obtain sucrose ferric hydroxide complex.

[0008] In some specific embodiments, the specific operation in step (2) is as follows: after adding purified water to dilute the iron hydroxyl oxide suspension, filter to remove inorganic salts, obtain filter cake, and measure the conductivity of the filtrate;

[0009] If the conductivity of the filtrate meets the acceptable range, the desalination step is complete.

[0010] If the conductivity of the filtrate exceeds the acceptable range, add water to the filter cake for filtration, measure the conductivity of the filtrate, and repeat the filtration and purification operation until the conductivity of the filtrate meets the acceptable range. Then the desalination step is complete.

[0011] Preferably, the conductivity is within the acceptable range of less than 1 mS / cm. The inorganic salt content in the filtrate affects the conductivity value of the filtrate. This invention monitors the residual amount of inorganic salts in the ferric hydroxide filter cake by detecting the conductivity value in the filtrate. The monitoring method is convenient and easy to operate.

[0012] In some preferred embodiments, if the conductivity of the filtrate exceeds the acceptable range, water is added to the filter cake and stirred until evenly mixed, and filtration is continued to remove inorganic salts; specifically, water is added to the filter cake at a mass-to-volume ratio of 1:6-8.

[0013] In some preferred embodiments, the filtration is performed using a Buchner funnel.

[0014] In some specific embodiments, the pH in step (1) is between 6.8 and 8.

[0015] In some preferred embodiments, the addition of ferric chloride to the sodium carbonate solution and stirring reaction in step (1) specifically involves: controlling the temperature to be less than 20-35°C, and adding ferric chloride to the sodium carbonate solution and stirring reaction for 1-3 hours.

[0016] In some preferred embodiments, the temperature-controlled reaction in step (3) is specifically carried out at a temperature controlled at 35-50°C.

[0017] Compared with the prior art, the advantages of this invention are:

[0018] (1) In the preparation method of the sucrose ferric hydroxide complex of the present invention, in the process of removing inorganic salts of ferric hydroxide, the ferric hydroxide is first diluted with water and then filtered for desalination, which significantly improves the desalination efficiency. Furthermore, the ferric hydroxide suspension is filtered directly without dilution with water, saving more than half the time and greatly shortening the overall production cycle, thereby improving production efficiency and saving production costs.

[0019] (2) This invention utilizes the measurement of conductivity values ​​in the filtrate to monitor changes in the content of inorganic salts in the filtrate, thereby further determining the residual amount of inorganic salts in the iron hydroxide filter cake. The method for detecting the inorganic salt removal rate is simple and easy to operate. Detailed Implementation

[0020] The present invention will be further described below with reference to specific embodiments. These embodiments are provided to further understand the present invention and constitute a part of this application, but do not constitute an improper limitation of the present invention. The present invention is not limited to the following embodiments.

[0021] Example 1

[0022] (1) Synthesis of ferric hydroxide

[0023] Add purified water (19.76L) and Na2CO3 (5.88kg, 55.50mol) to a 100L reactor, stir to dissolve, and then add FeCl3·6H2O (5kg, 18.50mol) aqueous solution while stirring. Control the temperature to 20-35℃ and stir for 1 hour. Take a sample and measure the pH to 6.8-8 to obtain ferric hydroxide suspension.

[0024] (2) Desalination

[0025] Filter the ferric hydroxide suspension obtained in step (1) to obtain a filter cake. Remove the inorganic salts from the filter cake and measure the conductivity of the filtrate. If the conductivity is less than 1 mS / cm, proceed to the next reaction step. If the conductivity is greater than 1 mS / cm, add water to the filter cake and repeat the above filtration and desalination operation until the conductivity is less than 1 mS / cm, then proceed to the next step.

[0026] (3) Preparation of sucrose hydroxyl iron oxide complex

[0027] In a 50L reactor, 1L of purified water was added, and the filter cake obtained after desalination in step (2) was added with stirring. The mixture was stirred at room temperature for 0.5 hours, and then sucrose (1.33kg), potato starch (0.68kg), and pregelatinized starch (0.64kg) were added. After mixing, the mixture was heated to 35-50℃ and stirred for 1 hour. A suspension of ferric hydroxide, sucrose, and starch was obtained. The suspension was then spray-dried to obtain 3.3kg of brown powder, which is the target product, sucrose ferric hydroxide.

[0028] Example 2

[0029] Since the product obtained from step (1) is an iron hydroxide suspension, the solution has high viscosity, resulting in a long filtration cycle and increased production time. Furthermore, if the removal of inorganic salts from the iron hydroxide is not up to standard, it will affect the quality of the final product, sucrose iron hydroxide.

[0030] Implementation method 2.1

[0031] The synthesis of ferric hydroxyoxide was carried out using the preparation method of step (1) in Example 1.

[0032] After filtering the obtained ferric hydroxide suspension, a filter cake was obtained, and the conductivity of the filtrate was measured. 40L of purified water was added to a 100L reactor, and the filter cake was added at room temperature. The mixture was stirred for 0.5 hours and then filtered. The conductivity of the filtrate was measured. If the conductivity was less than 1 mS / cm, the desalination step was complete, and the next step could be performed. Otherwise, purified water was added to the filter cake at a mass-to-volume ratio of ferric chloride to the raw material (e.g., 6-8L of water for 1kg of ferric chloride as the starting material), and the mixture was stirred until homogeneous. Filtration and desalination were then performed, and the conductivity of the filtrate was measured. This filtration and desalination process was repeated until the conductivity of the filtrate met the requirements.

[0033] In this embodiment, all filtration operations were performed using a Buchner funnel. Table 1 below records the time taken for each filtration and desalination operation and the conductivity of the filtrate after desalination.

[0034] Table 1:

[0035] Serial Number Desalination operation Desalination time Filtrate conductivity (ms / cm) 1 Direct filtration desalination of ferric hydroxide suspension 7h 112.0 2 The first time, 8V of water was added to the filter cake for filtration and desalination. 6h 43.0 3 Add 8V of water to the filter cake for the second time for filtration and desalination. 4h 12.0 4 Add 8V water to the filter cake for the third time for filtration and desalination. 3h 4.0 5 Add 8V water to the filter cake for the fourth time for filtration and desalination. 3h 1.85 6 Add 8V water to the filter cake for the fifth time for filtration and desalination. 3h 0.72

[0036] 8V refers to the amount of water added to the filter cake according to the weight of the starting material ferric chloride, with a mass-to-volume ratio of ferric chloride to water of 1:8. For example, if 1 kg of ferric chloride is used for the synthesis reaction, then 8 L of water is added to the filter cake.

[0037] In this embodiment, it takes 26 hours to filter until there is no liquid in the filter cake and to desalinate until the conductivity is qualified.

[0038] Implementation Method 2.2

[0039] The synthesis of ferric hydroxyoxide was carried out using the preparation method of step (1) in Example 1.

[0040] After filtering the obtained ferric hydroxide suspension, a filter cake is obtained, and the conductivity of the filtrate is measured. 40L of purified water is added to a 100L reactor, and the filter cake is added at room temperature. The mixture is stirred for 0.5 hours and filtered until the suspension volume is half full. The conductivity of the filtrate is measured. If the conductivity is less than 1 mS / cm, the desalting step is complete, and the next step can be performed. If the conductivity is greater than 1 mS / cm, 4V of water is added to the filter cake, stirred, and filtered until the suspension volume is half full. Desalting is then performed, and the conductivity of the filtrate is measured until the conductivity meets the requirements.

[0041] In this embodiment, all filtration operations are performed using the Buchner funnel filtration method.

[0042] Table 2 below records the specific operations, time, and conductivity values ​​of the filtrate after desalination for each filtration and desalination operation in this embodiment.

[0043] Table 2:

[0044]

[0045] 8V refers to adding water to the filter cake according to the weight of the starting material ferric chloride, with a ferric chloride to water mass-to-volume ratio of 1:8. For example, if 1 kg of ferric chloride is used for the synthesis reaction, then 8 L of water is added to the filter cake. 4V refers to adding water to the remaining suspension according to the weight of the starting material ferric chloride, with a ferric chloride to water mass-to-volume ratio of 1:4. For example, if 1 kg of ferric chloride is used for the synthesis reaction, then 4 L of water is added to the remaining suspension.

[0046] In this embodiment, during filtration and desalination, when the suspension volume is reduced to half, 4V of water is added to continue filtration and desalination until the conductivity meets the requirements, which takes 30 hours. The conductivity of the filtrate is less than 1 mS / cm, which meets the requirements. However, after adding 8V of water to the qualified filter cake and stirring evenly, and repeating the filtration and desalination operation, the conductivity of the filtrate is measured to be greater than the qualified value of 1 mS / cm. This indicates that the desalination in this embodiment is uneven, and some inorganic salts in the filter cake were not removed.

[0047] Implementation method 2.3

[0048] The synthesis of ferric hydroxyoxide was carried out using the preparation method in step (1) of Example 1.

[0049] Add an appropriate amount of purified water to the prepared ferric hydroxide suspension, stir to dilute, and then filter to obtain a filter cake. Measure the conductivity of the filtrate. If the conductivity of the filtrate is less than 1 mS / cm, the desalination step is complete, and the next step can be performed. Otherwise, add purified water to the filter cake at a mass-to-volume ratio of 1:6-8 (add water to the filter cake according to the mass-to-volume ratio of the starting material ferric chloride to water), filter, and measure the conductivity of the filtrate. Repeat the filtration and desalination step until the conductivity of the filtrate is acceptable.

[0050] In this embodiment, all filtration operations were performed using a Buchner funnel. Table 3 below records the time taken for each filtration and desalination operation and the conductivity of the filtrate after desalination.

[0051] Table 3:

[0052]

[0053] 8V refers to the amount of water added to the filter cake according to the weight of the starting material ferric chloride, with a mass-to-volume ratio of ferric chloride to water of 1:8. For example, if 1 kg of ferric chloride is used for the synthesis reaction, then 8 L of water is added to the filter cake.

[0054] In this embodiment, the ferric hydroxide suspension is first diluted with water at a volume ratio of 1:1-8 before filtration and desalination. Each filtration is performed until there is no liquid in the filter cake, and the entire filtration and desalination process takes 14 hours to achieve the required conductivity.

[0055] In Implementation Method 2.2, when the suspension was filtered to half its volume, purified water was added to continue filtration. The filtration and desalination time was significantly longer than that in Implementation Methods 2.1 and 2.3. Furthermore, the filter cake obtained by the filtration and desalination method in Implementation Method 2.2 was not uniformly desalted, affecting the quality of the final product, sucrose ferric hydroxide complex.

[0056] Both Implementation Methods 2.1 and Implementation Methods 2.3 employ the Buchner funnel filtration method. The difference lies in that Implementation Method 2.3 dilutes ferric hydroxide with water before filtration and desalination, while Implementation Method 2.1 takes 26 hours to reach the required conductivity level, and Implementation Method 3 takes 14 hours to reach the required conductivity level. This significantly improves desalination efficiency, thereby shortening the overall production cycle and saving production costs.

Claims

1. A method for preparing a sucrose hydroxyl iron oxide complex, characterized in that, Includes the following steps: (1) Synthesis of ferric hydroxide: Ferric chloride was added to sodium carbonate solution and stirred to react. A sample was taken to measure the pH and a suspension of ferric hydroxide was obtained. (2) Desalting: Add purified water to the above iron hydroxy oxide solution at a volume ratio of 1:1-8, then filter to remove inorganic salts and obtain iron hydroxy oxide filter cake. (3) Synthesis of sucrose ferric hydroxide complex: ferric hydroxide filter cake was mixed with water until homogeneous. Sucrose, potato starch and pregelatinized starch were added to the mixture and the reaction was carried out under controlled temperature to obtain ferric hydroxide. A suspension of ferric hydroxide, sucrose and starch was obtained. The suspension was spray-dried to obtain sucrose ferric hydroxide complex.

2. The method for preparing the sucrose hydroxyl iron oxide complex according to claim 1, characterized in that, The specific operation in step (2) is as follows: after adding purified water to dilute the iron hydroxyl oxide suspension, filter to remove inorganic salts, obtain filter cake, and measure the conductivity of the filtrate. If the conductivity of the filtrate meets the acceptable range, the desalination step is complete. If the conductivity of the filtrate exceeds the acceptable range, add water to the filter cake for filtration, measure the conductivity of the filtrate, and repeat the filtration and purification operation until the conductivity of the filtrate meets the acceptable range. Then the desalination step is complete.

3. The method for preparing the sucrose hydroxyl iron oxide complex according to claim 2, characterized in that, The acceptable conductivity range is less than 1 mS / cm.

4. The method for preparing the sucrose hydroxyl iron oxide complex according to claim 2, characterized in that, The specific operation of adding water to the filter cake for filtration is to add water to the filter cake at a mass-to-volume ratio of 1:6-8.

5. The method for preparing the sucrose hydroxyl iron oxide complex according to claim 2, characterized in that, The filtration process employs a Buchner funnel for suction filtration.

6. The method for preparing the sucrose hydroxyl iron oxide complex according to claim 1, characterized in that, In step (1), the pH is between 6.8 and 8.

7. The method for preparing the sucrose hydroxyl iron oxide complex according to claim 1, characterized in that, In step (1), adding ferric chloride to the sodium carbonate solution and stirring the reaction specifically involves: controlling the temperature to 20-35℃, adding ferric chloride to the sodium carbonate solution and stirring the reaction for 1-3 hours.

8. The method for preparing the sucrose hydroxyl iron oxide complex according to claim 1, characterized in that, The temperature-controlled reaction in step (3) is specifically carried out at a temperature controlled at 35-50℃.

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