Process for the preparation of sodium polystyrene sulfonate for the treatment of hyperkalemia

Abstract

The application discloses a preparation method of sodium polystyrene sulfonate for treating hyperkalemia, and comprises the following steps: after raw material pretreatment, sodium polystyrene sulfonate resin is sequentially subjected to ion exchange transformation in an ion exchange column, including once passing alkali, once water washing, once passing acid, twice passing acid, thrice passing acid, twice water washing, twice passing alkali and thrice water washing; then the transformed resin is dehydrated, and is sequentially subjected to soaking treatment by using recovered ethanol and fresh ethanol, and is subjected to water washing; finally, centrifugal dehydration, crushing, drying, secondary crushing, sieving and packaging are carried out to obtain a finished product. Through the optimized multi-step acid-base transformation process and the specific solvent treatment process, the transformation efficiency and the purity of the resin are significantly improved, the residual solvent and heavy metal content are effectively controlled, and the particle size uniformity of the final product is improved. The method is stable and controllable, the obtained sodium polystyrene sulfonate product is high in purity and good in quality consistency, and is suitable for large-scale production.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and more specifically to a method for preparing sodium polystyrene sulfonate for the treatment of hyperkalemia. Background Technology

[0002] Hyperkalemia is a common and serious complication in patients with acute and chronic renal failure, mainly caused by decreased renal potassium excretion, metabolic acidosis, and increased tissue catabolism, leading to elevated serum potassium levels. When serum potassium levels exceed 5.5 mmol / L, it can cause myocardial depression, arrhythmias, and even cardiac arrest, seriously threatening the patient's life. Currently, the main treatments for hyperkalemia include dialysis and drug therapy. While dialysis is effective, it requires specialized equipment, is complex to perform, and is expensive, making it particularly inaccessible to patients in rural and remote areas.

[0003] Sodium polystyrene sulfonate is an oral cation exchange resin widely used clinically to treat hyperkalemia. Its mechanism of action is as follows: after oral administration, in the acidic environment of the stomach, sodium ions on the resin are replaced by hydrogen ions to form a hydrogen-form resin. This hydrogen-form resin then enters the intestines and exchanges with potassium ions, causing excess potassium ions to be excreted in the feces, thereby effectively reducing serum potassium levels. This drug is convenient to use, has high patient compliance, and is particularly suitable for controlling hyperkalemia in patients in the early stages and maintenance phase of renal insufficiency. It can significantly delay or reduce the need for dialysis treatment, thus reducing the medical burden.

[0004] In addition to its potassium-lowering effect, recent clinical studies have shown that sodium polystyrene sulfonate also has the additional effect of reducing blood urea nitrogen (BUN). Clinical observations of multiple patients with chronic renal failure showed that BUN levels decreased significantly after taking sodium polystyrene sulfonate, and serum creatinine levels also decreased in some patients. Research suggests that this drug, in addition to exchanging potassium ions in the intestine, can also bind with ammonium ions, reducing urea synthesis and absorption, thereby improving azotemia. This discovery further expands the clinical value of sodium polystyrene sulfonate in the treatment of chronic kidney disease.

[0005] Currently, the preparation methods for sodium polystyrene sulfonate still have room for optimization in terms of resin purification, conversion efficiency, residual solvent control, and product particle size uniformity. In existing processes, incomplete ion exchange conversion may lead to insufficient product purity, heavy metal residues may affect drug safety, and improper solvent treatment may introduce organic solvent residues, affecting product quality stability. Therefore, providing a stable process for preparing sodium polystyrene sulfonate with high product purity suitable for large-scale production has significant industrial and clinical value. Summary of the Invention

[0006] Therefore, the present invention provides a method for preparing sodium polystyrene sulfonate for the treatment of hyperkalemia, in order to solve the problems in the prior art.

[0007] To achieve the above objectives, the present invention provides the following technical solution: A method for preparing sodium polystyrene sulfonate for the treatment of hyperkalemia includes the following steps: Step (1) Raw material pretreatment: After rinsing the sodium polystyrene sulfonate resin, it is packed into the ion exchange column and backflushed. Step (2) Ion exchange transformation: The sodium polystyrene sulfonate resin in the ion exchange column after backflushing is subjected to one alkali purging, one water washing, one acid purging, two acid purgings, three acid purgings, two water washings, two alkali purgings and three water washings in sequence to obtain the transformed sodium polystyrene sulfonate resin. Step (3), solvent treatment and purification: the transformed sodium polystyrene sulfonate resin is dehydrated, and then soaked in recycled ethanol and fresh ethanol in sequence, and washed with water after soaking. Step (4), solid-liquid separation and drying: the washed sodium polystyrene sulfonate resin is centrifuged to dehydrate and pulverize, and then dried to a moisture content of ≤5%. The dried material is pulverized again and sieved to obtain sodium polystyrene sulfonate powder. Step (5), Packaging: The sodium polystyrene sulfonate powder is packaged.

[0008] Furthermore, the specific details of the ion exchange transformation in step (2) are as follows: 1) First alkali flushing: Pass a 1.5-2.5 mol / L NaOH solution into the ion exchange column; 2) First wash: Wash with purified water until the pH of the effluent is 8-9; 3) First acid flush: Pass in 1.5-2.5 mol / L HCl solution; 4) Secondary acid flushing: Pass in 3.5-4.5 mol / L HCl solution, then soak for more than 8 hours; 5) Three acid flushing: Continue to flush with 3.5-4.5 mol / L HCl solution until the effluent is colorless and the iron ion concentration is <30 ppm; 6) Secondary washing: Wash with purified water until the pH of the effluent is 5-6; 7) Secondary alkali flushing: Pass in 1.5-2.5 mol / L NaOH solution; 8) Three washes: Wash with purified water until the pH of the effluent is 8-9.

[0009] Furthermore: the flow rate of the solution for the first alkali inlet, the first acid inlet, and the second alkali inlet is 75-80 L / h; the flow rate of the solution for the second acid inlet and the third acid inlet is 45-50 L / h.

[0010] Further: The ethanol soaking treatment in step (3) is specifically as follows: first soak in recycled ethanol at 50-60℃ for 2 hours, then drain, and then soak in fresh ethanol with a concentration of 95% at 50-60℃ for 2 hours. The solvent is drained after each soaking. The recycled ethanol comes from the second ethanol soaking solution in the previous batch of production.

[0011] Furthermore: the water washing in step (3) includes two purified water washes, after which the water is drained and after the second wash, the water layer is retained.

[0012] Further: the drying temperature in step (4) is 90±5℃; after pulverizing again, it needs to be passed through a 100-mesh sieve.

[0013] Further: The backflushing process in step (1) is as follows: drinking water is introduced into the ion exchange column filled with resin for backflushing, so that the resin floats in the water for 3-5 minutes and then settles, so that the resin layer is uniform and dense, and finally the liquid level is controlled to be maintained 5-15 cm above the resin layer.

[0014] Furthermore, the sodium polystyrene sulfonate resin is of pharmaceutical grade.

[0015] This invention offers the following advantages: Through an optimized multi-step gradient ion exchange transformation process, including acid-base treatment at specific concentrations and flow rates, and deep purification with high-concentration hydrochloric acid, the resin transformation is ensured to be thorough and heavy metal impurities are effectively removed, significantly improving product purity and ion exchange efficiency. The process parameters are clearly defined and controllable, resulting in good production reproducibility and suitability for large-scale manufacturing. The solvent treatment employs a "recovery-fresh ethanol" secondary soaking and recycling model, achieving cost reduction and emission reduction while ensuring effective impurity removal and residue control.

[0016] Other features and advantages of the present invention will be set forth in the following description. Detailed Implementation

[0017] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. It should be understood that these embodiments are merely for further explanation of the present invention and should not be construed as limiting the scope of protection of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above-described content.

[0018] A method for preparing sodium polystyrene sulfonate for the treatment of hyperkalemia includes the following steps: Raw material pretreatment: Take pharmaceutical-grade sodium polystyrene sulfonate resin, rinse it with drinking water until clean, and evenly distribute it into at least two ion exchange columns. Perform backflushing and degassing treatment to make the resin layer uniform and dense, and maintain the liquid level 5-15cm above the resin layer.

[0019] (2) Ion exchange conversion is carried out in the following order: 1) Pass alkali once, pass 1.5-2.5 mol / L NaOH solution into the exchange column at a flow rate of 75-80 L / h and a dosage of 150-160 L / column, so that the resin is converted to sodium form; 2) Wash once with purified water until the pH of the effluent is 8-9; 3) Pass acid once, using 1.5-2.5 mol / L HCl solution at a flow rate of 75-80 L / h, with a volume of 225-240 L / column; 4) Secondary acid flushing: Pass in 3.5-4.5 mol / L HCl solution at a flow rate of 45-50 L / h, using 160-175 L / column, followed by soaking for more than 8 hours; 5) Pass acid through three times, and continue to pass 4.5 mol / L HCl solution at a flow rate of 45-50 L / h until the effluent is colorless and the iron ion concentration is <30 ppm; 6) Second wash with purified water until the pH of the effluent is pH 5-6; 7) Secondary alkali flushing: introduce 2.2 mol / L NaOH solution at a flow rate of 75-80 L / h and a dosage of 300-320 L / column to convert the resin back to the sodium form. 8) Wash three times with purified water until the pH of the effluent is 8-9 to obtain the transformed resin.

[0020] (3) Solvent treatment and purification: The transformed resin is transferred into a mixing tank and the water is removed; then it is soaked in ethanol and washed with water. The specific process of ethanol soaking is as follows: first, recycled ethanol is used, followed by fresh 95% ethanol, and each soaking is carried out at 50-60℃ for 2 hours. After each soaking, the ethanol is drained. The recycled ethanol comes from the second ethanol soaking solution in the previous batch of production. Washing: Wash twice with purified water. After the first wash, dry the container and after the second wash, retain the water layer.

[0021] (4) Solid-liquid separation and drying: The resin is centrifuged to remove water; the wet resin is initially pulverized and then dried at 90±5℃ until the moisture content is ≤5%; the dried material is pulverized again and then passed through a 100-mesh sieve to obtain sodium polystyrene sulfonate raw material powder.

[0022] (5) Packaging: The powder is packaged in 35 kg / barrels, lined with low-density polyethylene bags, sealed tightly, labeled and put into storage. Example

[0023] S1. First, prepare the required acid and base solutions, including a 2.2 mol / L NaOH solution, a 2.2 mol / L HCl solution, and a 4.5 mol / L HCl solution; a. Specifically, the preparation process of 2.2 mol / L NaOH solution is as follows: According to the production order, 85.3 kg of sodium hydroxide was collected, with a preparation volume of approximately 950 L, excluding any remaining portion in the mixing tank. The sodium hydroxide was divided into two portions, placed in a mixing container, and then an appropriate amount of purified water was added. The mixture was stirred and dissolved, and set aside. In the NaOH solution mixing tank, approximately 500 L of purified water was added. Simultaneously, the valve leading to the high-level tank was closed, the circulation valve was opened, and the transfer pump was started. The dissolved NaOH concentrate was then pumped into the NaOH solution mixing tank using a diaphragm pump. Purified water was added again to bring the solution level to the required volume. The solution was refluxed for 2 hours. After reflux, a sample was taken for testing. Workshop personnel determined the solution concentration and filled out the operation record. The required concentration was 1.9-2.5 mol / L. If the solution concentration exceeds the specified range, the workshop process engineer shall recalculate the amount of sodium hydroxide and purified water, and replenish (or add) the corresponding amount of sodium hydroxide (or purified water) until the specified concentration is reached.

[0024] b. The preparation process of 2.2 mol / L HCl solution is as follows: According to the production order, 223 kg of concentrated hydrochloric acid was collected, with a preparation volume of approximately 1000 L, for two batches, excluding any remaining portion in the mixing tank. Approximately 500 L of purified water was added to the 2.2 mol / L HCl solution mixing tank. Simultaneously, the valve leading to the high-level tank was closed, the circulation valve was opened, and the transfer pump was started. The collected concentrated hydrochloric acid was then pumped into the 2.2 mol / L HCl solution mixing tank using a diaphragm pump. Purified water was then added to bring the solution level to the required volume. The solution was refluxed for 2 hours. After reflux, a sample was taken for testing. Workshop personnel determined the solution concentration and filled out the operation record. The required concentration was 1.9-2.5 mol / L. If the solution concentration exceeded the specified range, the workshop process engineer recalculated the hydrochloric acid and purified water quantities, and replenished (or added) the corresponding amount of hydrochloric acid (or purified water) until the specified concentration was reached.

[0025] The preparation process of c.4.5mol / L HCl solution is as follows: According to the production order, 228.1 kg of concentrated hydrochloric acid was collected, with a preparation volume of approximately 500 L, excluding any remaining portion in the mixing tank. In the 4.5 mol / L HCl solution mixing tank, approximately 200 L of purified water was added. Simultaneously, the valve leading to the high-level tank was closed, the circulation valve was opened, and the transfer pump was started. The collected concentrated hydrochloric acid was then pumped into the mixing tank using a diaphragm pump, and purified water was added again to reach the required solution volume. After reflux for 2 hours, a sample was taken for testing. Workshop personnel determined the solution concentration and filled out the operation record. The required concentration was 4.2-4.8 mol / L. If the solution concentration exceeds the specified range, the workshop process engineer shall recalculate the amount of hydrochloric acid and purified water, and replenish (or add) the corresponding amount of hydrochloric acid (or purified water) until the specified concentration is reached.

[0026] S2. Rinse and pack sodium polystyrene sulfonate (pharmaceutical resin) into the column and backflushing; Take an appropriate amount of sodium polystyrene sulfonate (pharmaceutical resin), pour it into a basin and rinse it repeatedly with drinking water, then pour it into a transfer bucket; divide the batch of sodium polystyrene sulfonate (pharmaceutical resin) into two equal portions, and use a diaphragm pump to load them into the No. 1 and No. 2 exchange columns respectively. When packing the column, be careful not to leave any air bubbles or gaps inside the column, otherwise it will cause a short circuit and incomplete ion exchange: open the bottom valve, adjust the switch to slowly drain the water until the liquid level is 5-15cm above the sodium polystyrene sulfonate layer, then close the bottom valve. Backflushing: Open the bottom valve of the ion exchange column and introduce drinking water. Backflushing will cause the sodium polystyrene sulfonate to float in the water. Backflushing for 3-5 minutes, then close the inlet valve. After the sodium polystyrene sulfonate has settled evenly and there are no gaps, open the bottom valve and adjust the switch to slowly drain the water until the liquid level is 5-15cm above the sodium polystyrene sulfonate layer. Then close the bottom valve. When backflushing the No. 2 ion exchange column, the bottom valve of the No. 1 ion exchange column must be closed.

[0027] S3. Perform acid-base treatment on the pre-treated sodium polystyrene sulfonate (pharmaceutical resin); details are as follows: 1) One-time alkali flushing; Open the valve on the ion exchange column that connects to the high-level tank of 2.2 mol / L NaOH solution, adjust the flow rate to 75-80 L / h, and then adjust the flow rate of the bottom valve to control the liquid level to 10-15 cm above the sodium polystyrene sulfonate layer. Pour the 2.2 mol / L NaOH solution through the tank for approximately 2 hours, recording the flow rate every hour. The volume used per ion exchange column is 150-160 L. When the liquid level in the high-level tank drops, open the high-level tank valve and transfer pump to send an appropriate amount of solution from the mixing tank to the high-level tank, then close the transfer pump. The alkali solution flows through the bottom valve to the neutralization tank for centralized treatment.

[0028] 2) One wash; Close the valve connecting the exchange column to the high-level tank of 2.2 mol / L NaOH solution. When the liquid level drops to about 5 cm, open the purified water inlet valve and adjust the flow rate to 75-85 L / h. Record the flow rate value every hour. Adjust the bottom valve to control the liquid level to 10-15 cm above the sodium polystyrene sulfonate layer. Test the pH value with pH test paper at the outlet until the pH value of the effluent is 8-9. Then close the purified water inlet valve. The washing liquid flows through the bottom valve to the neutralization tank for centralized treatment.

[0029] 3) One-time acid flushing Open the valve connecting the high-level tank of 2.2 mol / L HCl solution, adjust the flow rate to 75-80 L / h, and then adjust the bottom valve to control the liquid level 10-15 cm above the sodium polystyrene sulfonate layer. Pour the 2.2 mol / L HCl solution through the tank for approximately 3 hours, recording the flow rate every hour. The volume used for each ion exchange column is 225-240 L. When the liquid level in the high-level tank drops, open the valve of the mixing tank and the transfer pump to transfer an appropriate amount of solution from the mixing tank to the high-level tank, then close the transfer pump. The acid solution flows through the bottom valve to the neutralization tank for centralized treatment.

[0030] 4) Secondary acid infusion Close the valve connecting the ion exchange column to the high-level tank of 2.2 mol / L HCl solution, and open the valve connecting the high-level tank of 4.5 mol / L HCl solution. Adjust the flow rate to 45-50 L / h, and adjust the bottom valve opening to keep the liquid level 10-15 cm above the sodium polystyrene sulfonate layer. Pour 4.5 mol / L HCl solution over the column for approximately 3.5 hours, recording the flow rate every hour. The volume of solution used per ion exchange column is 160-175 L. When the liquid level in the high-level tank drops, the valve of the high-level tank of the mixing tank and the transfer pump can be opened to send an appropriate amount of solution from the mixing tank to the high-level tank, and then the transfer pump can be turned off. The acid solution flows to the neutralization tank for centralized treatment through the bottom valve. After the acid flow time or amount is reached, the bottom valve and the valve connecting to the high-level tank of 4.5 mol / L HCl solution are closed, and the sodium polystyrene sulfonate is soaked for more than 8 hours.

[0031] 5) Three-stage acid infusion Open the valve connecting the high-level tank of 4.5 mol / L HCl solution, adjust the flow rate to 45-50 L / h, then open the bottom valve and adjust the flow rate to keep the liquid level 5-15 cm above the sodium polystyrene sulfonate layer; observe the color of the effluent, and when it becomes colorless, take a sample from the outlet to test the iron ion concentration in the effluent; the amount of 4.5 mol / L HCl used per ion exchange column is approximately 70-80 L; When the liquid level in the high-level tank drops, the valve of the high-level tank of the mixing tank and the transfer pump can be opened to send an appropriate amount of solution from the mixing tank to the high-level tank, and then the transfer pump can be turned off; the acid solution flows through the bottom valve to the neutralization tank for centralized treatment.

[0032] 6) Secondary water washing After three acid flushing cycles, iron ions are measured. When the iron ion concentration is less than 30 ppm, the valve connecting the high-level tank of 4.5 mol / L HCl solution is closed, the purified water inlet valve is opened, the flow rate is adjusted, and the flow rate is controlled at 75-85 L / h. The flow rate value is recorded once per hour. The bottom valve is adjusted to control the liquid level at 5-15 cm above the sodium polystyrene sulfonate layer. Test the pH value with pH test paper at the outlet until the pH value of the outflow is 5-6; when the liquid level in the tank drops, open the purified water valve to add an appropriate amount of purified water and then close the valve; the washing liquid flows through the bottom valve to the neutralization tank for centralized treatment.

[0033] 7) Secondary alkali supply First, open the valve connecting the high-level tank of 2.2 mol / L NaOH solution and adjust the flow rate to 75-80 L / h. Then, adjust the bottom valve to control the liquid level 10-15 cm above the sodium polystyrene sulfonate layer. Pour NaOH solution through the tank for approximately 4 hours, recording the flow rate every hour. The amount of solution used per ion exchange column is 300-320 L. When the liquid level in the high-level tank drops, open the valve of the mixing tank and the transfer pump to transfer an appropriate amount of solution from the mixing tank to the high-level tank. Then, turn off the transfer pump. The alkali solution flows through the bottom valve to the neutralization tank for centralized treatment.

[0034] 8) Three washes Close the valve connecting the ion exchange column to the high-level tank of 2.2 mol / L NaOH solution, open the purified water inlet valve, adjust the flow rate to control the flow rate at 75-85 L / h, adjust the bottom valve to control the liquid level at 10-15 cm above the sodium polystyrene sulfonate layer; record the flow rate value every hour, test the pH value at the outlet with pH test paper until the pH value of the effluent is 8-9; the washing solution flows through the bottom valve to the neutralization tank for centralized treatment; use vacuum to pump the material in the ion exchange column into the preparation tank (Y-13) in the clean area purification room.

[0035] S4. Sodium polystyrene sulfonate that has been treated with acid and alkali is soaked in ethanol and then thoroughly washed. (1) The ethanol soaking process is as follows: 1) Initial ethanol soaking; (a) Turn on the vacuum pump, open the feed valve and vacuum valve on the mixing tank, close other valves, and pump the acid-alkali treated sodium polystyrene sulfonate into the 500L mixing tank. Then close the vacuum valve and feed valve, open the mixing tank lid, open the vacuum valve on the storage tank and the valve connected to the mixing tank, and insert the pumping pipe into the mixing tank to pump out the water (about 0.5-1 hour). Close the vacuum valve and the valve connected to the mixing tank, remove the pumping pipe, open the drain valve of the storage tank, and drain the water from the storage tank.

[0036] (b) Tighten the lid of the mixing tank, open the vacuum valve, draw the required amount of ethanol into the mixing tank, close the vacuum, open the reflux pipe valve and cooling water valve, and start stirring; open the steam outlet valve of the mixing tank, and then slowly open the steam inlet valve to heat the mixing tank. When the temperature rises to 50°C, start timing, control the material temperature at 50-60°C, and keep it warm for 2 hours.

[0037] (c) After the heat preservation is completed, first close the steam inlet valve of the batching tank, then close the steam outlet valve, and then open the cooling water inlet and outlet valves of the batching jacket tank in turn to cool down the batching tank. When the temperature drops to ≤40℃, close the cooling water inlet and outlet valves in turn.

[0038] (d) Turn on the vacuum pump, open the lid of the mixing tank, open the vacuum valve on the storage tank and connect the valve on the mixing tank, insert the pumping pipe into the mixing tank to pump out the ethanol (about 0.5-1 hour); close the vacuum valve and connect the valve on the mixing tank, take out the pumping pipe, open the discharge valve of the storage tank, and recover the ethanol in the storage tank.

[0039] 2) Second ethanol soak; the procedure is the same as the previous step "Initial ethanol soak". The ethanol used for the first soaking of each batch is the recovered ethanol from the second soaking of the previous batch. After soaking, the recovered ethanol is discarded. For the second soaking, fresh 95% ethanol is used. After soaking, the recovered ethanol is used for the first soaking of the next batch.

[0040] (2) The process for fine washing (water washing) is as follows: (a) Cover the mixing tank and open the purified water valve to add purified water to a depth of 10-15cm above the material surface, approximately 100kg; (b) Start stirring. After 1 hour, turn off stirring, turn on vacuum pump, open the lid of mixing tank, open the vacuum valve on the storage tank and the valve on the mixing tank, insert the suction pipe into the mixing tank to drain the purified water (about 0.5-1 hour); close the vacuum valve and the valve on the mixing tank, take out the suction pipe, open the discharge valve of the storage tank, and drain the purified water in the storage tank. (c) Repeat steps (a) and (b) once more. This time, the purified water in the washing tank does not need to be vacuumed out.

[0041] S5. After soaking and fine washing, sodium polystyrene sulfonate is centrifuged to dry; the specific steps are as follows: (a) Place the clean centrifugal filter bag into the SS450 centrifuge, rotate the centrifuge to make the centrifugal filter bag fit the drum, open the discharge valve of the mixing tank, put sodium polystyrene sulfonate into the centrifuge to make up 1 / 3 of its volume, and close the discharge valve. (b) Start the centrifuge and begin centrifugation. Once no liquid flows out, turn off the centrifuge. When the centrifuge stops rotating, transfer the sodium polystyrene sulfonate from the filter bag into a clean transfer container.

[0042] (c) Repeat the operation until the sodium polystyrene sulfonate in the mixing tank is completely centrifuged.

[0043] S6. The sodium polystyrene sulfonate, after centrifugation, is then pulverized and dried; the specific steps are as follows: (a) Clean the grinder with 75% ethanol, install a 100-mesh sieve, turn on the grinder, and grind the centrifuged sodium polystyrene sulfonate twice; after grinding, clean the grinder. (b) Spread an appropriate amount of pulverized sodium polystyrene sulfonate on a drying tray lined with drying cloth, place it on a drying cart and push it into a hot air circulating oven for drying. Turn on the oven, set the temperature to 90°C, control the temperature at 90±5°C, and dry until the moisture content is below 5%, then pulverize it again. (c) Start the crusher and slowly add the dried sodium polystyrene sulfonate for crushing. Do not add the material too quickly. After crushing, pass it through a 100-mesh sieve into a barrel lined with two layers of low-density polyethylene bags. Tie the bag opening tightly, weigh it, and proceed to the inner packaging process.

[0044] S7 packages the pulverized sodium polystyrene sulfonate; details are as follows: a. Inner packaging: Fill out the inspection request form, request inspection, and notify QA (Quality Department) to take samples; after each barrel is sampled, repackage according to the 35kg specification of each barrel, with the remainder being odd weight. After repackaging, tie the bag tightly, affix the label card, weigh it, and transfer it to the outer packaging; b. Outer Packaging: Inform the production scheduler of the gross weight and net weight of each barrel, and prepare barrel labels. After verification, affix the barrel labels to the outer packaging, fill out the warehousing slip, and enter the raw materials warehouse.

[0045] The method of this invention adopts a two-stage soaking process of "first recovering ethanol, then using fresh ethanol", and uses the second ethanol soaking solution of the previous batch as the first ethanol for the current batch. While ensuring the thorough removal of water-soluble and fat-soluble impurities and effectively reducing ethanol residue, it realizes the recycling of solvent, significantly reduces production costs, and reduces the discharge of organic solvent waste liquid, which is in line with the concept of green production. By employing a multi-step, gradient ion exchange transformation process of "alkali-acid-high-concentration acid-alkali", especially including the steps of soaking and washing with high-concentration hydrochloric acid to a specific iron ion concentration, the resin is fully and thoroughly transformed from other ionic forms (such as calcium form, magnesium form, etc.) to sodium form, and the heavy metal impurities (such as iron ions) entrained in the resin are effectively removed, thereby significantly improving the chemical purity and ion exchange efficiency of the final pharmaceutical raw material. In addition, key process parameters (such as the concentration, flow rate, dosage, soaking time, and pH value at the washing endpoint of each step of the acid and alkali solution) have been clearly defined and optimized, which makes the entire production process highly standardized, highly controllable, and ensures stable product quality and good reproducibility between different production batches, making it particularly suitable for large-scale industrial production.

[0046] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing sodium polystyrene sulfonate for treating hyperkalemia, characterized in that, Includes the following steps: Step (1) Raw material pretreatment: After rinsing the sodium polystyrene sulfonate resin, it is packed into the ion exchange column and backflushed. Step (2) Ion exchange transformation: The sodium polystyrene sulfonate resin in the ion exchange column after backflushing is subjected to one alkali purging, one water washing, one acid purging, two acid purgings, three acid purgings, two water washings, two alkali purgings and three water washings in sequence to obtain the transformed sodium polystyrene sulfonate resin. Step (3), solvent treatment and purification: the transformed sodium polystyrene sulfonate resin is dehydrated and then soaked in fresh ethanol in sequence, and then washed with water. Step (4), solid-liquid separation and drying: the washed sodium polystyrene sulfonate resin is centrifuged to dehydrate and pulverize, and then dried to a moisture content of ≤5%. The dried material is pulverized again and sieved to obtain sodium polystyrene sulfonate powder. Step (5), Packaging: The sodium polystyrene sulfonate powder is packaged.

2. The method for preparing sodium polystyrene sulfonate for treating hyperkalemia according to claim 1, characterized in that, The specific details of the ion exchange transformation in step (2) are as follows: 1) First alkali flushing: Pass a 1.5-2.5 mol / L NaOH solution into the ion exchange column; 2) First wash: Wash with purified water until the pH of the effluent is 8-9; 3) First acid flush: Pass in 1.5-2.5 mol / L HCl solution; 4) Secondary acid flushing: Pass in 3.5-4.5 mol / L HCl solution, then soak for more than 8 hours; 5) Three acid flushing: Continue to flush with 3.5-4.5 mol / L HCl solution until the effluent is colorless and the iron ion concentration is <30 ppm; 6) Secondary washing: Wash with purified water until the pH of the effluent is 5-6; 7) Secondary alkali flushing: Pass in 1.5-2.5 mol / L NaOH solution; 8) Three washes: Wash with purified water until the pH of the effluent is 8-9.

3. The method for preparing sodium polystyrene sulfonate for treating hyperkalemia according to claim 2, characterized in that, The flow rate of the solution for the first alkali inlet, the first acid inlet, and the second alkali inlet is 75-80 L / h; the flow rate of the solution for the second acid inlet and the third acid inlet is 45-50 L / h.

4. The method for preparing sodium polystyrene sulfonate for treating hyperkalemia according to claim 1, characterized in that, The ethanol soaking process in step (3) is as follows: first, soak in recycled ethanol at 50-60℃ for 1-4 hours, then drain, and then soak in fresh ethanol with a concentration of 95% at 50-60℃ for 1-4 hours. The solvent is drained after each soaking. The recycled ethanol comes from the second ethanol soaking solution in the previous batch of production.

5. The method for preparing sodium polystyrene sulfonate for treating hyperkalemia according to claim 1, characterized in that, The water washing in step (3) includes two purified water washes. After the first wash, the water is drained, and after the second wash, the water layer is retained.

6. The method for preparing sodium polystyrene sulfonate for treating hyperkalemia according to claim 1, characterized in that, The drying temperature in step (4) is 90±5℃; after pulverizing again, it needs to be passed through a 100-mesh sieve.

7. The method for preparing sodium polystyrene sulfonate for treating hyperkalemia according to claim 1, characterized in that, The backflushing process in step (1) specifically involves: introducing drinking water into the ion exchange column filled with resin for backflushing, allowing the resin to float in the water for 3-5 minutes and then settle, making the resin layer uniform and dense, and finally controlling the liquid level to be maintained 5-15 cm above the resin layer.

8. The method for preparing sodium polystyrene sulfonate for treating hyperkalemia according to any one of claims 1-7, characterized in that, The sodium polystyrene sulfonate resin is of pharmaceutical grade.