Preparation process for producing water for injection based on hollow fiber deoxidation membrane

Abstract

The invention relates to a preparation process for producing water for injection based on a hollow fiber deoxidation membrane, and belongs to the technical field of preparation of water for injection medicines. According to the preparation process of the water for injection, dissolved oxygen in a water body can be stably removed, reproduction of microorganisms, bacteria and the like in the water can be effectively restrained by strictly controlling the content of oxygen and carbon dioxide in the water, meanwhile, due to removal of carbon dioxide in the water body, the conductivity of the water body is further reduced, the pH value of the finished water is stabilized to be 6.5-7.5, and the water quality is improved. The related industrial standards of the water for injection are met, and the content of microorganisms and endotoxin meets the strict requirements of the 2025 edition pharmacopoeia. Compared with a traditional distillation method, the membrane method integration process does not need to consume a large amount of industrial steam, energy consumption can be remarkably reduced, and the operation cost is reduced; by optimizing the position of the hollow fiber deoxidation membrane device, the water quality and the storage stability of the water for injection can be improved, and the production cost and the maintenance cost can be reduced.

Description

A preparation process for producing water for injection based on hollow fiber deoxygenation membrane Technical Field

[0001] This invention relates to a preparation process for producing water for injection based on hollow fiber deoxygenation membrane, belonging to the technical field of preparing injectable pharmaceutical water. Background Technology

[0002] In pharmaceutical production, the quality of water for injection is crucial, as its purity and stability directly affect the safety and efficacy of drugs. This is especially true in high-end injectables and biopharmaceuticals, where extremely stringent requirements are placed on water quality indicators such as gas content, pH, and microbial control. With the official implementation of the 2025 edition of the Chinese Pharmacopoeia, the standards for water for injection have fully aligned with and improved upon the international mainstream pharmacopoeias (USP / EP). Key indicators such as conductivity (≤1.3µS / cm at 25℃), total organic carbon (TOC≤500ppb, listed as a mandatory release test for the first time), bacterial endotoxins (≤0.25 EU / mL), and microbial limits (≤10 CFU / 100 mL) have been clarified. At the same time, restrictions on preparation processes have been relaxed, allowing the use of purification processes "proven equivalent to distillation" (such as RO+EDI). However, new requirements have been added regarding elemental impurity risk assessment and storage conditions, further strengthening the control over water quality stability and safety.

[0003] For a long time, the preparation of water for injection in my country has mainly relied on distillation. Although this method can meet basic water quality standards, it has significant drawbacks: on the one hand, it has extremely high energy consumption and high equipment investment and operating costs, which is not in line with the green and low-carbon development trend of the pharmaceutical industry; on the other hand, the distillation method has limited ability to remove dissolved oxygen from water, making it difficult to reduce the dissolved oxygen content to extremely low levels. As a result, when the prepared water for injection is used to dissolve easily oxidized biological drugs, the excessive oxygen content can cause oxidation reactions, leading to drug deterioration and endangering patients' lives. At the same time, it cannot effectively control the residual carbon dioxide, which in turn leads to a low pH value in the water, affecting the stability of the drugs and making it difficult to meet the new requirements of the 2025 edition of the Pharmacopoeia for shelf life verification and strict microbial control.

[0004] With scientific advancements, membrane-based preparation technologies are gradually becoming a potential alternative to distillation. Existing technologies include water-for-injection preparation systems that use ultrafiltration devices to replace traditional distillation machines. For example, Chinese patent document CN 212451018U (application number 202020273693.2) provides a water-for-injection preparation device that uses an ultrafiltration device instead of the original distillation machine, effectively reducing energy consumption and enabling real-time monitoring of the effluent quality from the ultrafiltration unit. However, it is difficult to meet the stringent requirements of the 2025 edition of the Pharmacopoeia for the stability of release indicators and storage validation, limiting its application in high-end pharmaceutical fields.

[0005] It is important to clarify that while the 2025 edition of the Chinese Pharmacopoeia and mainstream international pharmacopoeias do not list oxygen content as a direct detection indicator, the inventors discovered through experiments that residual dissolved oxygen and carbon dioxide in water are key implicit factors affecting the compliance rate and stability of core pharmacopoeia indicators: oxygen accelerates the oxidation of trace organic matter in water, leading to increased TOC; dissolved carbon dioxide forms carbonic acid, increasing water conductivity and disrupting pH stability; and the presence of an oxygen-rich environment promotes the proliferation of aerobic microorganisms, increasing the risk of endotoxin exceeding limits. As a finished product, water for injection contains a relatively high amount of oxygen. When dissolving easily oxidized biological drugs, excessive oxygen content can trigger oxidation reactions, causing drug deterioration and endangering patients' lives. Therefore, removing oxygen and carbon dioxide from water is crucial for ensuring that the water quality of water for injection fully meets the requirements of the 2025 edition of the Pharmacopoeia and improving storage stability. This understanding provides a new approach to addressing existing technological challenges.

[0006] In summary, existing technologies for preparing water for injection suffer from high energy consumption and incomplete deoxygenation, and fail to recognize the implicit impact of oxygen content on core pharmacopoeia indicators. Therefore, developing a highly efficient and energy-saving technology for preparing water for injection that achieves deep deoxygenation and decarbonization, stable water quality, and strong adaptability has become a key issue that urgently needs to be addressed in this field. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides a preparation process for producing water for injection based on hollow fiber deoxygenation membranes.

[0008] The technical solution of the present invention is as follows: A preparation process for producing water for injection based on hollow fiber deoxygenation membrane includes the following steps: (1) the raw water first enters the pretreatment stage for pretreatment to obtain softened water; (2) the softened water is purified through the reverse osmosis stage to obtain permeate water; (3) the permeate water is passed through the deoxygenation stage for treatment to obtain low dissolved oxygen water; (4) the low dissolved oxygen water enters the deep desalination and depyrogenation stage for purification to obtain pre-pure water; (5) the pre-pure water is treated through the disinfection stage to obtain water for injection, which is stored in a storage tank.

[0009] According to a preferred embodiment of the present invention, the deoxygenation stage includes a hollow fiber deoxygenation membrane device for removing oxygen and carbon dioxide from the permeate water.

[0010] More preferably, the operating parameters of the hollow fiber deoxygenation membrane device are: inlet water pressure 0.05-0.18MPa, inlet water flow rate 1000-1500 L / h, and inlet water temperature 20-30℃.

[0011] More preferably, the hollow fiber deoxidizing membrane device is equipped with a backwashing system, and the backwashing frequency is 30-60 seconds of online backwashing every 8-12 hours.

[0012] More preferably, the hollow fiber deoxygenation membrane device is sterilized periodically using pasteurization, with a sterilization frequency of once every 7-14 days.

[0013] According to a preferred embodiment of the present invention, the device for the pretreatment stage includes a multi-media filter, an activated carbon filter, and a softener. The raw water first passes through the multi-media filter to initially remove suspended solids and particulate impurities from the water. Next, it enters the activated carbon filter to adsorb organic pollutants and residual chlorine from the water. Then, it passes through the softener to replace calcium and magnesium ions in the water with sodium ions, thereby reducing the hardness of the water and obtaining softened water.

[0014] More preferably, the multi-media filter and activated carbon filter are equipped with an automatic backwashing system that can periodically start the backwashing procedure.

[0015] More preferably, the operating parameters of the multi-media filter are: filtration speed of 6-12 m / h and backwashing frequency of once every 24-48 hours.

[0016] More preferably, the operating parameters of the activated carbon filter are: adsorption time 20-50 min and backwashing cycle 72-144 h.

[0017] More preferably, the softener is equipped with an automatic regeneration system. When the exchange capacity of the ion exchange resin decreases, the regeneration program is started to restore its exchange capacity. The regeneration cycle of the ion exchange resin is 1-2 times per week.

[0018] According to a preferred embodiment of the present invention, the reverse osmosis stage includes a primary reverse osmosis device and a secondary reverse osmosis device. Softened water enters the primary reverse osmosis device and the secondary reverse osmosis device in sequence to remove most of the salt, microorganisms, bacterial endotoxins and other small molecule impurities from the water, thereby obtaining permeated water.

[0019] More preferably, the operating parameters of the first-stage reverse osmosis unit are: inlet water pressure 1.5-2.5 MPa and recovery rate 75%-85%.

[0020] More preferably, the operating parameters of the secondary reverse osmosis unit are: inlet water pressure 1.5-2.5 MPa and recovery rate 75%-85%.

[0021] More preferably, the primary reverse osmosis unit is arranged in a primary-two-stage configuration.

[0022] More preferably, the secondary reverse osmosis device is arranged in a one-stage, two-section configuration.

[0023] According to a preferred embodiment of the present invention, the deep desalination and pyrogen removal stage includes an electro-deionization device and an ultrafiltration device. After the permeate water is deoxygenated to obtain low dissolved oxygen water, it enters the electro-deionization device and the ultrafiltration device in sequence. The electro-deionization device is used to further remove residual ions in the water, and the ultrafiltration device is used to remove bacteria, endotoxins and other microorganisms that may be present in the water for a second time. After treatment, pre-pure water is obtained.

[0024] More preferably, the operating parameters of the electro-deionization device are: conductivity 0.05-0.2 μS / cm, flow rate 1-5 m³ / min. 3 / h, current density 0.5 - 1.5A / dm 2 The pH value of the influent is 6.5-7.5.

[0025] More preferably, the ultrafiltration device uses an ultrafiltration membrane with a molecular weight cutoff of 1000-5000 Daltons.

[0026] More preferably, the operating parameters of the ultrafiltration device are: filtration speed 1-3 m / h.

[0027] More preferably, the ultrafiltration device is equipped with a backwashing system with a backwashing cycle of 24-72 hours.

[0028] According to a preferred embodiment of the present invention, the disinfection stage includes an ultraviolet disinfection device, in which the pre-purified water is disinfected by ultraviolet light to kill residual microorganisms, thereby obtaining water for injection, which is then stored in a storage tank.

[0029] More preferably, the operating parameters of the ultraviolet disinfection device are: ultraviolet intensity 30-70 μW / cm². 2 Disinfection time: 20-30 minutes.

[0030] More preferably, the storage tank is equipped with a node-type ozone disinfection device.

[0031] More preferably, the operating parameters of the node-type ozone disinfection device are: ozone concentration 20-50 ppb, contact time ≥6h.

[0032] Beneficial effects: The injection water preparation process provided by this invention can stably remove dissolved oxygen from water. By strictly controlling the oxygen and carbon dioxide content in the water, the reproduction of microorganisms and bacteria in the water can be effectively inhibited. At the same time, due to the removal of carbon dioxide, the conductivity of the water is further reduced, and the pH of the finished water is stable at 6.5-7.5, which meets the relevant industry standards for injection water. The content of microorganisms and endotoxins meets the stringent requirements of the 2025 edition of the Pharmacopoeia.

[0033] Compared to traditional distillation methods, the membrane integration process of this invention does not require the consumption of large amounts of industrial steam, which can significantly save energy and reduce operating costs. By optimizing the position of the "hollow fiber deoxygenation membrane device", not only can the water quality and storage stability of water for injection be improved, but also production and maintenance costs can be reduced. Attached Figure Description

[0034] Figure 1 is a schematic diagram of the preparation process of water for injection provided in Example 1. Detailed Implementation

[0035] The preparation process of water for injection according to the present invention will be described below with reference to the schematic diagram, which shows the preferred embodiments of the present invention. It should be understood that those skilled in the art can modify the present invention described herein while still achieving the advantageous effects of the present invention.

[0036] Example 1 This example provides a process for preparing water for injection, as shown in Figure 1. The process includes a pretreatment stage, a reverse osmosis stage, a deoxygenation stage, a deep desalination and pyrogen removal stage, a disinfection stage, and a storage stage connected in series. After the raw water is drawn from the raw water unit, it flows through a multi-media filter, an activated carbon filter, and a softener (pretreatment stage) in sequence according to the process order; then it enters a first-stage reverse osmosis device and a second-stage reverse osmosis device (reverse osmosis stage); subsequently, it undergoes deoxygenation treatment through a hollow fiber deoxygenation membrane device; after being treated by the above units, it passes through an electro-deionization device and an ultrafiltration device (deep desalination and pyrogen removal stage) in sequence; finally, it undergoes a disinfection stage to obtain water for injection, which is stored in a storage tank. The specific device parameters are selected as follows: (1) Raw water unit: The raw water unit is equipped with a raw water tank and a raw water pump. The raw water tank is used to store the raw water, and the raw water pump is responsible for transporting the raw water to the subsequent treatment units. The raw water can come from the municipal water supply system or surface water or groundwater that has undergone preliminary treatment. In this example, municipal water supply is used. The raw water unit is also equipped with water quality monitoring equipment to monitor key water quality parameters such as turbidity, residual chlorine, and hardness of the raw water in real time, ensuring the stability of the water quality entering the subsequent treatment units. The water quality parameters of the municipal water supply used in this embodiment are as follows: ① Microbiological indicators: Total coliforms: not detected; thermotolerant coliforms: not detected; Escherichia coli: not detected; total colony count: 5 CFU / mL; Cryptosporidium: not detected; Giardia lamblia: not detected.

[0037] ②Toxicological indicators: Arsenic: 0.005 mg / L; Cadmium: 0.0001 mg / L; Chromium (hexavalent): 0.005 mg / L; Lead: 0.005 mg / L; Mercury: 0.0001 mg / L; Selenium: 0.001 mg / L; Cyanide: 0.005 mg / L; Fluoride: 0.12 mg / L; Nitrate (as nitrogen): ≤2 mg / L; Chloroform: 0.006 mg / L; Carbon tetrachloride: 0.0005 mg / L; Benzo[a]pyrene: 0.001 μg / L; DDT: 0.0001 mg / L; HCH: 0.0003 mg / L.

[0038] ③ Sensory properties and general chemical indicators: Color: 0.5 degrees, no other abnormal colors; Turbidity: <1 degree; Odor and taste: no abnormal odor or taste; Visible matter: none; pH value: 6.6-8.2; Total hardness (calculated as calcium carbonate): 150 mg / L; Iron: 0.1 mg / L; Manganese: 0.01 mg / L; Copper: 0.1 mg / L; Zinc: 0.2 mg / L; Volatile phenols (calculated as phenol): 0.0002 mg / L; Anionic synthetic detergents: 0.03 mg / L; Sulfate: 140 mg / L; Chloride: 207 mg / L; Total dissolved solids: 409 mg / L; Oxygen consumption (COD) Mn ): 0.9 mg / L.

[0039] ④ Radioactivity indicators: Total alpha radioactivity: 0.01 Bq / L; Total beta radioactivity: 0.3 Bq / L.

[0040] (2) Multi-media filter: The multi-media filter is filled with two layers of filter media, specifically anthracite (particle size 0.8-2.0 mm) and quartz sand (particle size 0.5-1.2 mm). Through physical interception and adsorption, it effectively removes suspended solids and particulate impurities from the water. The filter is equipped with an automatic backwashing system, which is activated periodically to restore the filter's filtration performance. The operating parameters of the multi-media filter include filtration speed and backwashing frequency. In this embodiment, the filtration speed is 8 m / h and the backwashing frequency is once every 36 hours. In actual applications, the specific parameters can be optimized according to the raw water quality and treatment requirements.

[0041] (3) Activated carbon filter: The activated carbon filter is filled with activated carbon. Through the adsorption of activated carbon, organic pollutants and residual chlorine in the water are removed, thereby protecting the subsequent membrane modules from damage by oxidants. The activated carbon filter is also equipped with an automatic backwashing system to clean the activated carbon filter media regularly and ensure its adsorption performance. The operating parameters of the activated carbon filter include adsorption time and backwashing cycle. In this embodiment, the adsorption time is 30 minutes and the backwashing cycle is 120 hours. In actual applications, the specific parameters can be adjusted according to the raw water quality and treatment requirements.

[0042] (4) Softener: The softener is filled with ion exchange resin. Through ion exchange reaction, calcium and magnesium ions in the water are replaced with sodium ions, thereby reducing the water hardness and obtaining softened water. The softener is equipped with an automatic regeneration system. When the exchange capacity of the ion exchange resin decreases, the regeneration program is started to restore its exchange capacity. In this embodiment, the ion exchange resin is regenerated twice a week, on Wednesday and Sunday evenings, without affecting normal water use during the day. In actual applications, specific parameters can be optimized according to the hardness of the raw water and the treatment requirements.

[0043] (5) First-stage reverse osmosis unit: The first-stage reverse osmosis unit is one of the core devices in the deep treatment stage. Its main function is to remove most of the salt, microorganisms, bacterial endotoxins and other small molecule impurities from the softened water through the action of a semi-permeable membrane. The first-stage reverse osmosis unit uses anti-fouling reverse osmosis membrane modules. In this embodiment, the membrane modules are arranged in a two-stage configuration. The inlet water pressure is maintained at 1.5-2.5 MPa, and the recovery rate is 75%-85%. In actual applications, the specific parameters can be adjusted according to the raw water quality and treatment requirements.

[0044] (6) Secondary reverse osmosis unit: The permeate from the primary reverse osmosis unit is further purified to reduce residual trace impurities and obtain permeate water. The secondary reverse osmosis unit also uses anti-fouling reverse osmosis membrane modules, arranged in a two-stage configuration. The inlet pressure is maintained at 1.5-2.5 MPa, and the recovery rate is 75%-85%. In actual applications, the specific parameters can be optimized according to the quality of the primary reverse osmosis permeate and the treatment requirements.

[0045] (7) Hollow fiber deoxygenation membrane device: Through the selective deoxygenation membrane, the oxygen content in the permeate water can be reduced to below 5 ppb, while removing carbon dioxide from the water, further reducing the conductivity of the water, and obtaining low dissolved oxygen water. The deoxygenation device is equipped with a backwashing system, which regularly uses pasteurization. Before starting the entire equipment, hot water above 80℃ is flushed into the membrane device for disinfection and cleaning to eliminate potential microorganisms attached to the membrane device. At the same time, real-time monitoring equipment is installed. The data collected by the sensor during the deoxygenation process can be uploaded to the client through the module to display the dissolved oxygen concentration and conductivity of the water in real time, ensuring that the deoxygenation effect is stable and meets the standards. The operating parameters of the deoxygenation device are: inlet water pressure 0.05-0.18 MPa, inlet water flow rate 1000-1500 L / h, inlet water temperature 20-30℃, backwashing frequency of the deoxygenation membrane 60s for every 10 hours online, and sterilization cycle once a week. In actual application, the specific parameters can be optimized according to the water quality and treatment requirements of the ultrafiltration permeate. The changes in water quality before and after deoxygenation in this embodiment are as follows: oxygen content decreased from 11 ppb to 2 ppb, carbon dioxide content decreased from 4 mg / L to 0.3 mg / L, and conductivity decreased from 6 μS / cm to 0.05 μS / cm.

[0046] (8) Electrodeionization (EDI) device: The EDI device further removes residual ions in the aforementioned low dissolved oxygen water through the synergistic effect of ion exchange resin and ion-selective permeable membrane. This invention employs titanium-based electrodes and ion exchange membranes to improve ion exchange efficiency and current utilization, while reducing energy consumption. Simultaneously, the operating parameters of the EDI device are optimized, controlling the conductivity to 0.05-0.2 μS / cm and maintaining a flow rate of 1-5 m³ / cm. 3 / h, ensuring stable operation of the EDI system. The operating parameters of the EDI device are: current density 0.5-1.5A / dm³. 2 The pH of the influent is 6.5-7.5. (In an EDI system, the use of a deoxygenation membrane and its location significantly affect the pH and conductivity of the influent. Using a deoxygenation membrane effectively reduces dissolved CO2 and H2CO3 formation in the water, thus preventing a significant drop in pH. If there is no deoxygenation membrane in the system, or if the membrane is improperly positioned, the pH of the influent to the EDI system may drop to around 5.0 or even lower, which will affect the desalination efficiency and effluent quality stability. Therefore, in this embodiment, a deoxygenation membrane is installed before the EDI unit to ensure that the influent pH is maintained within the range of 6.5-7.5, thereby improving the overall performance of the system.) In practical applications, specific parameters can be adjusted according to the quality of the secondary reverse osmosis permeate and treatment requirements.

[0047] (9) Ultrafiltration unit: The ultrafiltration unit uses an ultrafiltration membrane with a molecular weight cutoff of 3000 Daltons, which can effectively remove bacteria, endotoxins and other microorganisms that may be present in the water to obtain pre-purified water. The operating parameters of the ultrafiltration unit are: filtration rate 1-3 m / h, equipped with a backwashing system, and a backwashing cycle of 24-72 hours. In actual application, the specific parameters can be optimized according to the EDI product water quality and treatment requirements.

[0048] (10) Ultraviolet disinfection device: The ultraviolet disinfection device is used to perform preliminary disinfection on the pre-purified water obtained in the above steps to kill any microorganisms that may remain in the water. The operating parameters of the ultraviolet disinfection device are: ultraviolet intensity 50 μW / cm². 2 The disinfection time is 30 minutes. In actual application, the specific parameters can be adjusted according to the water quality and treatment requirements of the water for injection.

[0049] (11) Storage device: The storage device is made of 316L stainless steel with electropolished inner walls to reduce biofilm adhesion. The storage tank and distribution network system have good sealing properties to prevent contact with outside air, bacteria, etc. During storage and distribution, node-type ozone disinfection technology is used to release ozone at pipe branches, valve interfaces, and other areas prone to microbial growth to ensure that bacteria and microorganisms do not grow in the pipeline network. The ozone concentration is 20-50 ppb, and the contact time is ≥6h. At the same time, the water for injection is circulated in the pipeline network by a circulating pump to ensure the uniformity and stability of water quality. The storage tank used in this embodiment has a capacity of 10m³. 3 The flow rate of the circulating pump is 3m³ / h. 3 / h, in practical applications, the specific parameters can be optimized according to the production scale and processing requirements.

[0050] Before filling, the water for injection in the storage tank must undergo a final ultrafiltration step, and finally the water for injection in the storage tank is filled into the final container for drug production.

[0051] Water for injection was prepared using the above system and parameters. The water quality indicators and testing methods for water for injection were performed according to the 2025 edition of the Pharmacopoeia of the People's Republic of China. The test results are shown in Table 1. After 7 days of storage, the water quality stabilized, and all indicators met the requirements of the 2025 edition of the Pharmacopoeia. Furthermore, because the hollow fiber deoxygenation membrane device is located before the EDI device, the pH value of the influent is within the neutral range, which avoids membrane corrosion and significantly reduces subsequent maintenance costs.

[0052] Table 1. Test results of water for injection

[0053] Comparative Example 1 provides a process for preparing water for injection. The apparatus and operating parameters of this comparative example are the same as those in Example 1, except that the entire process does not include a deoxygenation stage. The test results are shown in Table 2. The water quality is slightly acidic, and the conductivity, bacterial endotoxins, and total organic carbon content all exceed the limits set in the 2025 edition of the Pharmacopoeia. The water quality further deteriorated after 7 days of storage.

[0054] Table 2. Test results of water for injection

[0055] Comparative Example 2: To further verify the importance of the deoxygenation stage in the preparation of water for injection in this invention, this comparative example provides a water for injection preparation apparatus in which the position of the "hollow fiber deoxygenation membrane device" was swapped with that of other devices to observe its impact on the final water quality. The apparatus and operating parameters in this comparative example are consistent with those in Example 1, except that the "hollow fiber deoxygenation membrane device" is moved after the electrodeionization (EDI) device. The results are shown in Table 3. The obtained water for injection is slightly acidic. Furthermore, the change in the device's position also affected the deoxygenation effect of the deoxygenation stage to some extent, resulting in a slight increase in dissolved oxygen content compared to Example 1. After 7 days of storage, the conductivity, bacterial endotoxins, and total organic carbon content increased significantly, exceeding the limits set in the 2025 edition of the Pharmacopoeia. Overall, the water quality was inferior to the water for injection prepared in Example 1.

[0056] Table 3. Test results of water for injection

[0057] The experimental results of the examples and Comparative Example 1 show that if the deoxygenation stage is removed from the entire process, not only will the dissolved oxygen content and conductivity be uncontrollable, but the bacterial endotoxin content of the final water for injection will also increase. The reason for this is that the entire water production cycle is relatively long, about 4 hours. If there is too much oxygen before disinfection, microorganisms will multiply rapidly within 4 hours and produce a large amount of bacterial endotoxins. Even after the final disinfection process, not all of them can be removed, and a large amount of residue remains.

[0058] The experimental results of Comparative Example 2 show that placing the hollow fiber deoxygenation membrane device before the EDI device cannot effectively control residual carbon dioxide. If carbon dioxide in the reverse osmosis permeate is not removed before EDI, it will dissolve to form H2CO3, causing the pH value of the EDI feed water to deviate from the optimal operating range, thereby reducing the desalination efficiency of EDI and resulting in higher conductivity of the permeate. It will also affect the deoxygenation effect of the subsequent deoxygenation stage to some extent. At the same time, the trace carbon dioxide remaining in the water after EDI treatment will continue to affect pH stability. After 7 days of storage, the pH value drops to 5.8. If deoxygenation is not performed in the early stage, the presence of an oxygen environment will lead to the accumulation of microorganisms, resulting in a significant increase in bacterial endotoxins, total organic carbon, and microbial content, ultimately failing to meet the requirements of the 2025 edition of the Pharmacopoeia. Therefore, after optimizing the position of the hollow fiber deoxygenation membrane device and placing it before the EDI device, it can ensure that the prepared water for injection meets the strict requirements of the 2025 edition of the Pharmacopoeia, while reducing production and maintenance costs.

Claims

1. A preparation process for producing water for injection based on hollow fiber deoxygenation membrane, characterized in that, The process includes the following steps: (1) The raw water first enters the pretreatment stage for pretreatment to obtain softened water; (2) The softened water is purified through the reverse osmosis stage to obtain permeate water; (3) The permeate water is passed through the deoxygenation stage for treatment to obtain low dissolved oxygen water; (4) The low dissolved oxygen water enters the deep desalination and pyrogen removal stage for purification to obtain pre-pure water; (5) The pre-pure water is treated through the disinfection stage to obtain water for injection, which is stored in a storage tank.

2. The preparation process according to claim 1, characterized in that, The deoxygenation stage includes a hollow fiber deoxygenation membrane device for removing oxygen and carbon dioxide from the permeate water.

3. The preparation process according to claim 2, characterized in that, The operating parameters of the hollow fiber deoxygenation membrane device are: inlet water pressure 0.05-0.18 MPa, inlet water flow rate 1000-1500 L / h, and inlet water temperature 20-30℃.

4. The preparation process according to claim 2, characterized in that, The hollow fiber deoxygenation membrane device is equipped with a backwashing system, and the backwashing frequency is 30-60 seconds of online backwashing every 8-12 hours; more preferably, the hollow fiber deoxygenation membrane device is periodically sterilized by pasteurization, and the sterilization frequency is once every 7-14 days.

5. The preparation process according to claim 1, characterized in that, The pretreatment stage device includes a multi-media filter, an activated carbon filter, and a softener. The raw water first passes through the multi-media filter to remove suspended solids and particulate impurities. Next, it enters the activated carbon filter to adsorb organic pollutants and residual chlorine in the water. Then, it passes through the softener to replace calcium and magnesium ions in the water with sodium ions, thereby reducing the hardness of the water and obtaining softened water.

6. The preparation process according to claim 5, characterized in that, The multi-media filter and activated carbon filter are equipped with an automatic backwashing system, which can periodically initiate the backwashing program. More preferably, the operating parameters of the multi-media filter are: filtration speed 6-12 m / h, backwashing frequency once every 24-48 hours; more preferably, the operating parameters of the activated carbon filter are: adsorption time 20-50 min, backwashing cycle 72-144 h; more preferably, the softener is equipped with an automatic regeneration system, which initiates a regeneration program to restore the exchange capacity of the ion exchange resin when the exchange capacity decreases, and the regeneration cycle of the ion exchange resin is 1-2 times per week.

7. The preparation process according to claim 1, characterized in that, The reverse osmosis stage includes a primary reverse osmosis unit and a secondary reverse osmosis unit. Softened water enters the primary and secondary reverse osmosis units sequentially to remove most of the salt, microorganisms, bacterial endotoxins and other small molecule impurities from the water, resulting in permeated water.

8. The preparation process according to claim 7, characterized in that, The operating parameters of the first-stage reverse osmosis unit are: inlet water pressure 1.5-2.5 MPa and recovery rate 75%-85%; more preferably, the operating parameters of the second-stage reverse osmosis unit are: inlet water pressure 1.5-2.5 MPa and recovery rate 75%-85%; more preferably, the arrangement of the first-stage reverse osmosis unit is one stage and two sections; more preferably, the arrangement of the second-stage reverse osmosis unit is one stage and two sections.

9. The preparation process according to claim 1, characterized in that, The deep desalination and pyrogen removal stage includes an electro-deionization device and an ultrafiltration device. After the permeate water undergoes a deoxygenation stage to obtain low dissolved oxygen water, it sequentially enters the electro-deionization device and the ultrafiltration device. The electro-deionization device is used to further remove residual ions in the water, and the ultrafiltration device is used to remove bacteria, endotoxins, and other microorganisms that may be present in the water. After treatment, pre-purified water is obtained. More preferably, the operating parameters of the electro-deionization device are: conductivity 0.05-0.2 μs / cm, flow rate 1-5 m³ / min. 3 / h, current density 0.5 - 1.5A / dm 2 The pH value of the influent is 6.5-7.5; more preferably, the ultrafiltration device uses an ultrafiltration membrane with a molecular weight cutoff of 1000-5000 Daltons; more preferably, the operating parameters of the ultrafiltration device are: filtration speed 1-3 m / h; more preferably, the ultrafiltration device is equipped with a backwashing system with a backwashing cycle of 24-72 h.

10. The preparation process according to claim 1, characterized in that, The disinfection stage includes an ultraviolet (UV) disinfection device. The pre-purified water is passed through the UV disinfection device to kill residual microorganisms, yielding water for injection, which is then stored in a storage tank. More preferably, the operating parameters of the UV disinfection device are: UV intensity 30-70 μW / cm². 2 The disinfection time is 20-30 minutes; more preferably, the storage tank is equipped with a node-type ozone disinfection device; more preferably, the operating parameters of the node-type ozone disinfection device are: ozone concentration 20-50 ppb, contact time ≥6h.

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