Device and method for preparing pure chlorine dioxide liquid and method for storing pure chlorine dioxide liquid

Abstract

The invention provides a preparation device and method of pure chlorine dioxide liquid and a storage method, and relates to the field of chemical pharmacy preparation, in particular to a chlorine dioxide injection precursor. The device comprises a reaction chamber and a freezing chamber communicated with the reaction chamber, and chlorine dioxide gas generated in the reaction chamber is conveyed into the freezing chamber to be directly liquefied, so that high-purity chlorine dioxide liquid is obtained. The invention solves the problems of inaccurate concentration control, insufficient stability, difficulty in meeting medicine quality management specifications and the like in the production process of the pure chlorine dioxide liquid in the prior art, and provides the stable and controllable preparation device and method of the pure chlorine dioxide liquid meeting the medicine quality requirements. The preparation method is particularly suitable for preparing and storing precursor liquid of the chlorine dioxide injection, and meets the medicine quality management standard.

Description

Technical Field

[0001] The present invention relates to the field of chemical pharmaceutical preparation, and in particular to a precursor of chlorine dioxide injection, and specifically to the production, preparation and storage of chlorine dioxide liquid. Background Art

[0002] Chlorine dioxide (ClO2) is a strong oxidant and is widely used in industrial fields such as drinking water treatment, food processing, pulp bleaching and air disinfection. In these traditional applications, ClO2 is usually used in the form of an aqueous solution. The preparation process aims at high efficiency output, mainly focuses on the sterilization and disinfection effect, and has relatively low requirements for concentration fluctuation, gas escape and impurity control.

[0003] For the production of chlorine dioxide liquid, chlorine dioxide (ClO2) is usually generated in a gaseous form, and then it can be mixed with water through an absorption system (such as a water injector and an absorption device) to form a liquid chlorine dioxide solution.

[0004] Water injector absorption method. A negative pressure is generated through a water injector (Venturi tube), and gaseous ClO2 is inhaled and mixed with water to form a solution. The operation is simple and the conversion efficiency is high.

[0005] Countercurrent absorption tower method. Gaseous ClO2 enters from the bottom of the tower and contacts and dissolves countercurrently with the absorption liquid (stabilizer containing sodium carbonate and sodium borate) sprayed from the top of the tower.

[0006] In a typical preparation process of chlorine dioxide liquid, sodium chlorate solution, methanol and sulfuric acid react chemically under certain conditions to generate chlorine dioxide and sodium sulfate. The generated chlorine dioxide gas is cooled and absorbed to obtain an aqueous solution of chlorine dioxide. As Figure 1 shown, the production device includes a chlorine dioxide reactor, a chlorine dioxide absorption tower, a reactor reboiler and an intercooler. The sodium chlorate solution, concentrated sulfuric acid and methanol are added to the reactor in a certain proportion, and continuous reaction is carried out under high negative pressure conditions. The generated chlorine dioxide gas is diluted by the evaporated water vapor and enters the intercooler from the top of the reactor for cooling. The cooled mixed gas enters the absorption tower from the bottom and is absorbed by chilled water to form an 8-10 g / L chlorine dioxide solution, which is sent to the chlorine dioxide solution storage tank.

[0007] With the development of medical technology, due to its broad-spectrum antibacterial activity and selective oxidation ability, ClO2 has begun to be explored for use in pharmaceutical preparations, especially in the fields of local treatment, wound care and anti-tumor injections. However, converting industrial-grade chlorine dioxide aqueous solution into an injectable preparation meeting pharmaceutical quality standards still faces multiple technical challenges, including:

[0008] High volatility and easy decomposition, resulting in unstable concentration during the preparation process;

[0009] The preparation system is vulnerable to interference from external air, moisture, and temperature fluctuations;

[0010] By-products or impurities may be mixed in the solution obtained by the conventional process, making it difficult to meet the requirements of pharmaceutical purity;

[0011] Lacking a stable, safe, and controllable production and storage system, it is difficult to meet the requirements of the pharmaceutical-grade continuous process;

[0012] The concentration consistency of the solution between different batches is poor, making it difficult to ensure the standardization and repeatability of the final product.

[0013] Up to now, there is no public literature providing a preparation and storage system for pure chlorine dioxide liquid that can meet the requirements of pharmaceutical purity, long-term stability, and concentration consistency control. Therefore, the present invention proposes a breakthrough new solution. Summary of the Invention

[0014] Regarding the conversion of industrial-grade aqueous chlorine dioxide solution into an injectable preparation meeting the pharmaceutical quality standards, Patent Application CN201610126960.1A proposed to upgrade the traditional industrial-grade ClO2 preparation process for pharmaceutical use. This patent application proposed a method for preparing and collecting high-purity aqueous ClO2 solution under low-temperature conditions, including:

[0015] Generating ClO2 gas in a reaction vessel;

[0016] Introducing the gas into a cooling water phase for absorption through a cold trap;

[0017] Utilizing low temperature to inhibit the decomposition of ClO2 and improve the stability of the solution;

[0018] Generating an aqueous ClO2 solution with controllable concentration and certain storage capacity, aiming to meet the preliminary requirements of medical applications.

[0019] However, the inventors found that this solution still has obvious deficiencies in several key aspects. For example:

[0020] It fails to effectively prevent the escape of ClO2;

[0021] The entire reaction and absorption process is based on laboratory-level operations and lacks the ability of industrial continuous production;

[0022] The storage system is not specifically designed for pharmaceutical-grade usage scenarios;

[0023] Lacking systematic control over long-term cold-chain storage and batch quality consistency;

[0024] In particular, the product concentration fluctuates, making it difficult to ensure the concentration consistency between multiple batches and not meeting the quality control requirements of injectable drugs.

[0025] Therefore, there is an urgent need to develop an integrated system for the preparation and storage of high-concentration and high-purity chlorine dioxide liquid applicable to the pharmaceutical scenario, to ensure that the product meets the strict standards of injection dosage forms in terms of purity, concentration, stability, safety, and batch consistency, and to lay a formulation foundation for the application of chlorine dioxide in clinical injection uses.

[0026] The present invention provides a device and method for preparing pure chlorine dioxide liquid, and the obtained pure chlorine dioxide liquid can be used as a chlorine dioxide injection or its precursor liquid.

[0027] The present invention provides a device for preparing pure chlorine dioxide liquid, including (i) a reaction chamber: for accommodating a mixed solution and providing a place for generating chlorine dioxide. The mixed solution can generate chlorine dioxide gas through the reaction of sodium chlorite and an acid solution, or by electrolyzing sodium chlorite or sodium chloride solution. (ii) A freezing chamber: unidirectionally fluid-connected to the reaction chamber, for liquefying the chlorine dioxide gas generated in the reaction chamber into pure chlorine dioxide liquid. This device can achieve full-process control such as airtight reaction, low-temperature absorption, pressure and humidity control, automatic transfer, and cold-chain storage. Through the trinity architecture of airtight reaction - low-temperature liquefaction - environmental joint control, the device has upgraded the preparation of chlorine dioxide from the traditional gas-liquid mixing process to a pure liquid direct generation system, greatly increasing the chlorine dioxide concentration, reducing the batch concentration fluctuation, and extending the storage stability to more than 6 months, providing a reliable solution for high-end applications such as pharmaceutical preparations and precision disinfection.

[0028] On the one hand, the present invention provides a device for preparing pure chlorine dioxide liquid, and the device is hermetically set, including:

[0029] (i) A reaction chamber, for a mixed solution capable of generating chlorine dioxide gas to generate chlorine dioxide gas through its own reaction or by applying external electricity, and not generating or generating substantially no chlorine gas; the temperature in the reaction chamber is set to 30°C - 90°C;

[0030] (ii) A freezing chamber, connected after the reaction chamber through a connecting pipeline, for transporting the chlorine dioxide gas generated in the reaction chamber to the freezing chamber and liquefying it, and the temperature in the freezing chamber is set to -21°C to -59°C, further set to -30°C to -58°C, and still further set to -40°C to -55°C.

[0031] The gaseous chlorine dioxide from the reaction chamber is liquefied in the freezing chamber to generate the pure chlorine dioxide liquid;

[0032] The pure chlorine dioxide liquid refers to that the content of chlorine dioxide in the chlorine dioxide liquid is not less than 95%.

[0033] In the present invention, the freezer is a sealed gas-phase liquefaction structure, and no water phase is introduced during the liquefaction process of chlorine dioxide gas in the reaction chamber, thereby obtaining a stable, undiluted high-purity chlorine dioxide liquid with a purity of not less than 95%.

[0034] The device is a preparation system with airtightness constructed by a reaction chamber, a freezer, and connecting pipelines. The entire device / system (reaction chamber, freezer, connecting pipelines, etc.) is set to be airtight through flanges, threaded interfaces, seals, etc., to ensure the airtightness of the entire system and enable the preparation process to be carried out in an airtight environment.

[0035] On the other hand, the present invention provides a method for preparing pure chlorine dioxide liquid. Using any of the above devices, it includes the following steps:

[0036] Load a mixed solution capable of generating chlorine dioxide gas into the reaction chamber. The mixed solution can generate chlorine dioxide gas through its own reaction or by applying external electricity, and does not generate or basically does not generate chlorine gas.

[0037] Set the entire device including the reaction chamber and the freezer to be airtight.

[0038] Heat the temperature in the reaction chamber to 30°C - 90°C to ensure that the mixed solution capable of generating chlorine dioxide gas generates chlorine dioxide gas.

[0039] Cool the temperature in the freezer to -21°C to -59°C, further cool it to -30°C to -58°C, and further cool it to -40°C to -55°C to transfer the chlorine dioxide gas generated in the reaction chamber to the freezer for liquefaction.

[0040] On the other hand, the present invention provides a storage method for pure chlorine dioxide liquid. The pure chlorine dioxide liquid prepared by any of the above methods is encapsulated in a storage container, stored in the dark, and the storage temperature is controlled at -21°C to -59°C, or at a temperature that can ensure that the retention rate of chlorine dioxide is not less than 95% for 6 months. The storage container is configured to have low gas permeability, resistance to low temperature, and resistance to oxidation corrosion.

[0041] Compared with the prior art, the present invention has the following beneficial effects:

[0042] 1. Chlorine dioxide has the characteristics of volatility, instability, and easy decomposition. Existing methods are difficult to precisely control the concentration of chlorine dioxide aqueous solution. The process of introducing chlorine dioxide gas into water involves multiple variables that are difficult to control and monitor. Therefore, the concentration of each batch of chlorine dioxide aqueous solution cannot be determined without precise measurement. This makes it difficult to effectively control the quality differences between batches, especially the fluctuations in concentration. The preparation device of the present invention realizes the upgrade of chlorine dioxide preparation from the traditional gas-liquid mixing process to a pure liquid direct generation system through a three-in-one architecture of closed reaction - low-temperature liquefaction - environmental joint control, significantly improving the chlorine dioxide concentration and reducing the batch concentration fluctuation, providing a reliable solution for high-end applications such as pharmaceutical preparations and precision disinfection.

[0043] 2. The present invention produces chlorine dioxide liquid as the precursor of chlorine dioxide injection. Through appropriate storage methods, the stability of the injection precursor is ensured, and precise control of the concentration and dosage of chlorine dioxide injection during use is achieved, ensuring the consistency and reproducibility from preparation to use, and meeting the strict requirements of pharmaceutical preparations for the accuracy of concentration and dosage.

[0044] 3. The present invention significantly extends the storage life of pure chlorine dioxide liquid through optimized storage conditions (low temperature, light protection, dryness, small-dose packaging, appropriate container materials), effectively preventing its volatilization, decomposition, and quality change, and ensuring the stability for long-term use. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0046] Figure 1 Shows the preparation process of chlorine dioxide liquid in the prior art.

[0047] Figure 2 Shows the preparation device of pure chlorine dioxide liquid according to an embodiment of the present invention.

[0048] Figure 3 Shows the preparation device of pure chlorine dioxide liquid according to another embodiment of the present invention, showing the freezing room temperature control device.

[0049] Figure 4 Shows the preparation device of pure chlorine dioxide liquid according to another embodiment of the present invention, showing the vacuum pumping unit;

[0050] Figure 5Shows the preparation device of pure chlorine dioxide liquid shown in another embodiment of the present invention, and shows the condensation and dehumidification unit;

[0051] Figure 6 Shows the preparation device of pure chlorine dioxide liquid shown in another embodiment of the present invention; shows the inlet pipe of the reaction chamber;

[0052] Figure 7 Shows the preparation device of pure chlorine dioxide liquid shown in another embodiment of the present invention, and shows the flowmeter and valve;

[0053] Figure 8 Shows the preparation device of pure chlorine dioxide liquid shown in another embodiment of the present invention, and shows the temperature adjustment unit.

[0054] Illustration: 1. Reaction chamber; 11. Feeding port; 12. Gas outlet; 13. Reaction chamber heating equipment; 14. Stop valve; 151. Pressure relief valve; 152. Barometer; 16. Inlet pipe; 17. Inlet valve; 2. Freezing chamber; 21. Inlet port; 22. Freezing chamber temperature control equipment; 23. Vacuum pumping unit; 231. Vacuum pump; 232. Vacuum pump valve; 24. Liquid outlet; 3. Connecting pipeline; 31. Solenoid valve; 32. Flowmeter; 33. Regulating valve; 4. Condensation and dehumidification unit; 41. Water outlet; 42. Constant temperature water tank; 43. Titanium metal tube condenser; 5. Temperature adjustment unit. Detailed implementation manners

[0055] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0056] As Figure 2 shown, the present invention provides a device (system) for preparing pure chlorine dioxide liquid, including a reaction chamber 1, which is used for a mixed solution capable of generating chlorine dioxide gas to generate chlorine dioxide gas through its own reaction or applying external electric power, and does not generate or basically does not generate chlorine gas; the temperature in the reaction chamber is set to 30°C - 90°C;

[0057] A freezing chamber 2, which is connected after the reaction chamber 1 through a connecting pipeline 3, is used for transporting the chlorine dioxide gas generated in the reaction chamber 1 to the freezing chamber 2 and liquefying it. The temperature in the freezing chamber is set to -21°C to -59°C, and the inlet port of the freezing chamber is located at the upper part of the freezing chamber;

[0058] The gaseous chlorine dioxide from the reaction chamber 1 is liquefied in the freezing chamber 2 to generate pure chlorine dioxide liquid;

[0059] The so-called pure chlorine dioxide liquid means that the content of chlorine dioxide in the chlorine dioxide liquid is more than 95%.

[0060] The present invention is particularly suitable for the preparation and storage of the precursor liquid of chlorine dioxide injection, meeting the drug quality management standards. The pure chlorine dioxide liquid prepared by the device of the present invention can be used as the chlorine dioxide injection or its precursor liquid.

[0061] The statement in this specification that "the purity of chlorine dioxide liquid is more than 95%" refers to the estimated value of the weight percentage of chlorine dioxide in all dissolved substances in the liquid.

[0062] Under the existing analysis means, the ClO2 content can be preliminarily estimated by gas-phase collection or ultraviolet spectrophotometry, but due to the large differences in the operating environment, there is currently no unified international determination standard.

[0063] The concentration standard described in the present invention is used to characterize the system stability and process efficiency, and is not used as a clinical concentration standard.

[0064] The mixed solution capable of generating chlorine dioxide gas can be, for example, a mixed solution of sodium chlorite and an acid solution.

[0065] As Figure 2 shown, the mixed solution capable of generating chlorine dioxide gas is loaded into the reaction chamber through the feeding port 11. The mixed solution generates chlorine dioxide gas through its own reaction or by applying external electricity, and does not generate chlorine gas; the generated chlorine dioxide gas is transported to the freezing chamber 2 through the air outlet 12 via the connecting pipeline 3 through the air inlet 21 and is directly liquefied in the freezing chamber.

[0066] The device can adopt the method of separately feeding materials on-site and directly introduce the mixed solution capable of generating chlorine dioxide gas into the reaction chamber 1. The mixed solution can generate chlorine dioxide gas by reacting sodium chlorite with an acid (such as sulfuric acid, hydrochloric acid or other strong or weak acids), or by electrolyzing sodium chlorite or sodium chloride solution.

[0067] In one embodiment, the structure of the reaction chamber 1 is configured as a cylindrical container. The mixed raw materials are mixed before the mixed solution is put into the reaction chamber 1. The pre-prepared sodium chlorite solution (usually with a concentration greater than 5%) and the acid solution (the acid needs to be in excess and with a moderate concentration) are respectively prepared and separately put into the reaction chamber on-site, so that they quickly mix and react to generate chlorine dioxide gas in a closed state.

[0068] In another embodiment, the structure of the reaction chamber 1 is configured as a cylindrical container. Each raw material of the mixed solution is separately put into the reaction chamber 1. Sodium chlorite and the acid solution are directly poured into the reaction chamber respectively. The separate feeding of the raw materials can enable the reaction to proceed simultaneously on-site, avoiding the out-of-control reaction speed caused by pre-mixing.

[0069] In another embodiment, the structure of the reaction chamber 1 is configured as a two-chamber electrolytic cell. The anode gas outlet is communicated with the freezer through a connecting pipeline. A mixed solution generates chlorine dioxide gas by applying external power. Electrolysis is directly carried out in the reaction chamber, and chlorine dioxide gas is generated by electrolyzing sodium chlorite or sodium chloride solution. During the reaction process, a sufficient amount of sodium chlorite is fed at one time, or solid sodium chlorite or liquid raw materials can be continuously fed to ensure continuous gas generation.

[0070] The reaction chamber is a closed container, which can be made of high borosilicate glass, PTFE, titanium alloy or Hastelloy, and has sufficient corrosion resistance and temperature resistance. The container is provided with a feeding port, an air inlet and an air outlet to ensure rapid sealing after separate feeding on site. The reaction chamber is equipped with a heating device and a temperature control system.

[0071] It should be noted that the entire device / system (including the reaction chamber 1, the freezer 2, the connecting pipeline 3, etc.) is set to be airtight through flanges, threaded interfaces and seals, etc., to ensure the airtightness of the entire system, so that the preparation process is carried out in an airtight environment to ensure safety. After feeding, the feeding port is immediately closed to ensure that the reaction system operates under closed conditions, so that the reaction only generates the target product - chlorine dioxide gas, while suppressing side reactions such as chlorine generation.

[0072] As Figure 2 shown, a heating device 13 is arranged below the reaction chamber 1, which can be, for example, a water bath heater 13, an oil bath heater, an electric heater, etc., for heating the reaction chamber 1 and maintaining the temperature inside the reaction chamber 1.

[0073] The temperature inside the reaction chamber can be set to 30°C - 90°C, preferably 40°C - 80°C, 50°C - 70°C, etc. The temperature control of the mixed solution inside the reaction chamber is the key to ensuring the generation and escape efficiency of chlorine dioxide. Appropriate temperature helps chlorine dioxide escape from the liquid phase and escape from the reaction chamber 1 to enter the freezer 2, while increasing the reaction rate, enabling the raw materials to be quickly converted into chlorine dioxide gas. And too high temperature may trigger violent reactions or side reactions, resulting in chlorine generation and explosion risks; too low temperature will reduce the reaction rate and liquefaction efficiency.

[0074] During the operation of the device, the temperature of the reaction chamber can be dynamically adjusted. When the temperature is higher than the set range, the cooling device can be started to keep the temperature within the target range; on the contrary, when the temperature is lower than the set range, the heating device is started to supplement heat.

[0075] The reaction chamber 1 can also be configured with a temperature sensor, a pressure sensor and a pressure relief valve to realize real-time monitoring of the reaction process.

[0076] The chlorine dioxide gas generated in the reaction chamber 1 is transmitted to the freezing chamber 2 via the connecting pipe 3. The connecting pipe 3 can be made of corrosion-resistant material, such as Hastelloy or stainless steel lined with PTFE.

[0077] In order to ensure that the chlorine dioxide gas enters the freezing chamber in a predetermined direction and flow rate, a valve is provided on the connecting pipe 3 near the freezing chamber 2 end.

[0078] like Figure 4 As shown, a valve 31 is provided on the connecting pipe 3 and between the reaction chamber 1 and the freezing chamber 2. The valve can be configured as a solenoid valve 31. The valve 31 can be designed in a one-way manner and can be controlled manually, electromagnetically or pneumatically. The following functions can be achieved through the valve: 1) Regulate the gas flow rate, accurately control the speed at which the gas enters the freezing chamber according to the pressure in the reaction chamber and the liquefaction requirements of the freezing chamber, ensure the pressure in the system is stable, and the gas is evenly distributed. 2) Prevent gas reflux, the valve ensures that chlorine dioxide gas can only flow from the reaction chamber to the freezing chamber in one direction, and avoids the liquefied gas from flowing back to the reaction chamber due to pressure reaction after liquefaction. 3) Assist in the construction of a closed system, the entire production system (including the reaction chamber, connecting pipes and freezing chamber) adopts strict sealing measures, such as flange connections, threaded interfaces and corrosion-resistant sealing gaskets, to ensure that there is no gas leakage in the entire system during the production process, and the appropriate internal pressure is conducive to the liquefaction process. The closed system can significantly increase the liquefaction rate of chlorine dioxide at a lower temperature through pressure assistance, effectively reducing resource waste and environmental risks.

[0079] like Figure 7 As shown, a flow control unit, such as a flow meter 32, can also be provided on the connecting pipeline 3. The flow meter 32 can be equipped with a regulating valve 33. The flow meter can be set as a Coriolis mass flow meter, a thermal mass flow meter or a corrosion-resistant differential pressure type, a vortex flow meter. The chlorine dioxide gas flow can be monitored in real time by the flow meter 32, and both precise regulation and dynamic regulation are provided. According to the flow meter data, the regulating valve (electric or pneumatic valve) is controlled by a PID controller to match the gas flow with the reaction chamber pressure, the freezing chamber temperature and the liquefaction rate to achieve precise regulation. The gas flow is dynamically adjusted according to real-time data, such as appropriately increasing the flow when the reaction chamber pressure is high, or reducing the flow when the freezing chamber liquefaction rate decreases, so as to achieve the best liquefaction efficiency and product purity, and realize dynamic regulation.

[0080] like Figure 8 As shown, a temperature regulating unit 5 is provided between the reaction chamber 1 and the freezing chamber 2 to achieve a smooth transition of the gas temperature. Since the temperature of the reaction chamber is significantly higher than that of the freezing chamber, directly sending the high-temperature gas into the freezing chamber will not only affect the liquefaction effect, but may also cause the freezing chamber to be overloaded or liquefy in advance.

[0081] In one embodiment, the temperature regulation unit 5 is set as a heat exchanger. A pipeline with good heat exchange effect with the ambient air is adopted, and its temperature can be naturally stabilized near the room temperature, so that the gas temperature is reduced to a range suitable for liquefaction.

[0082] In another embodiment, as Figure 8 shown, the temperature regulation unit 5 is set as a jacketed pipeline 5. By using a jacketed pipeline with a constant temperature medium (such as water or oil), the gas is gradually cooled to about 11°C - 20°C during the passing process, and part of the water vapor is condensed and removed at this stage. This gradually transitional temperature control not only helps to improve the liquefaction rate of chlorine dioxide, but also makes the gas flow more evenly, reduces the unstable factors caused by local temperature differences, and at the same time avoids the problem of gas condensation before liquefaction caused by a sudden drop in the internal temperature of the freezer.

[0083] During the liquefaction process of chlorine dioxide, water vapor has a significant impact on the liquefaction rate and product purity. In the device of the present invention, a condensation and dehumidification unit 4 is provided between the freezer 1 and the reaction chamber 2 to condense the water vapor entrained when the chlorine dioxide gas escapes from the reaction chamber 1 and discharge it after the production ends.

[0084] The condensation and dehumidification unit 4 can be adjacent to the temperature regulation unit 5 or parallel to the temperature regulation unit 5. The condensation and dehumidification unit 4 can be configured as a condensation and dehumidifier, and the water vapor during the liquefaction process of chlorine dioxide is removed by the following methods:

[0085] 1) Low-temperature condensation and dehumidification

[0086] The gas temperature is reduced below the dew point by using a low-temperature circulating medium or refrigerant, so as to promote the condensation of water vapor into liquid water and discharge it. This method has a simple structure and stable operation, but is limited by the lowest temperature.

[0087] 2) Adsorption dehumidification

[0088] High-efficiency adsorption materials such as molecular sieves, activated alumina or silica gel are selected to deeply adsorb the residual water vapor. This method is suitable for occasions with extremely high requirements for dryness.

[0089] 3) Membrane separation

[0090] A special permeable polymer membrane is used to separate water vapor, with relatively low energy consumption, but the equipment cost is relatively high, and gas pretreatment is required.

[0091] 4) Composite dehumidification

[0092] The above methods 1) - 3) are combined and used. First, most of the water vapor is removed by condensation and dehumidification, and then adsorption or membrane separation is used to further reduce the dew point to achieve a more thorough dehumidification effect.

[0093] As Figure 5As shown, the condensation dehumidification unit 4 and the temperature regulation unit 5 are arranged in parallel. The temperature regulation unit 5 is a constant temperature water tank 42 (with the temperature set at 11°C to 20°C), and the condensation dehumidification unit 4 is configured as a titanium metal tube condenser 43. The titanium metal tube condenser 43 is immersed in the constant temperature water of the constant temperature water tank 42. Through efficient dehumidification, the system can significantly improve the liquefaction rate and product purity of chlorine dioxide, while reducing the unstable factors caused by moisture in the liquid product.

[0094] As Figure 7 shown, a condensation dehumidifier 4 is provided between the freezer 2 and the reaction chamber 1 to condense the water vapor entrained when chlorine dioxide gas escapes from the reaction chamber 1 and discharge it from the water outlet 41 (after the production ends).

[0095] As Figure 3 shown, a solenoid valve 31 is provided between the condensation dehumidification unit 4 and the air inlet 21 of the freezer 2 to ensure that the chlorine dioxide gas enters the freezer in a predetermined direction and flow rate.

[0096] In the preparation device of the present invention, the interior of the freezer 2 adopts a double-layer structure. The outer layer has vacuum insulation or is filled with heat-insulating materials, and a coil is provided inside for the circulation of low-temperature refrigerant to ensure that the temperature is accurately controlled between -21°C and -59°C.

[0097] As Figure 3 shown, a freezing unit 22 can also be connected after the freezer 2 to lower the temperature inside the freezer and control it between -21°C and -59°C.

[0098] Precisely controlling the temperature of the freezer and the pressure inside the system is very important for the liquefaction of chlorine dioxide. The temperature of the cooling chamber can be controlled between -21°C and -59°C. Preferably, it can be between -30°C and -58°C, and more preferably, it can be controlled between -40°C and -55°C under better conditions. This low-temperature range not only enables the chlorine dioxide gas to quickly condense into a liquid, but also effectively reduces its volatility through low temperature, ensuring that the liquefaction rate is much higher than that of an open system (the temperature of the open system is generally set below -20°C, and the liquefaction rate is usually lower than 5%).

[0099] A liquid level sensor and a temperature control device can be installed inside the freezer to provide real-time feedback on the liquefaction situation and ensure that the chlorine dioxide gas is quickly condensed into a liquid and then introduced into the collection container.

[0100] The freezer 2 is equipped with a vacuum pumping unit 23 to evacuate the freezer before the generation of chlorine dioxide starts. By evacuating the freezer to create a negative pressure, an obvious pressure gradient is formed between the reaction chamber and the freezer, which can improve the transmission efficiency of chlorine dioxide gas during the reaction process and reduce the interference of moisture and oxygen in the air.

[0101] As Figure 4As shown, the vacuum pumping unit 23 can be a vacuum pump 231. Before starting the generation of chlorine dioxide, first close the valve between the reaction chamber and the freezer, and use the vacuum pump to evacuate the freezer, usually reducing its pressure to -0.01 MPa to -0.05 MPa. A significant pressure gradient is formed between the reaction chamber and the freezer, prompting the generated chlorine dioxide gas to flow directionally into the freezer, shortening its residence time in the reaction chamber. In addition, if there is a slight leak in the system, due to the internal negative pressure, external air will leak inwards, reducing the risk of chlorine dioxide leakage and helping to reduce the entry of water vapor into the system.

[0102] As Figure 5 shown, a vacuum pump valve 232 is also provided between the vacuum pump 231 and the freezer 2. This negative pressure start-up technology for vacuum pumping ensures that at the initial stage of chlorine dioxide generation, the gas is quickly introduced into the freezer for liquefaction, thereby improving the overall liquefaction rate and reaction efficiency.

[0103] As Figure 7 shown, a liquid outlet 24 is arranged below the freezer 2, which is used to discharge the pure chlorine dioxide gas obtained in the freezer 2 and collect and store it in a storage container.

[0104] When the reaction is approaching the end, there may be residual chlorine dioxide gas in the device. Air, inert gas, or nitrogen can be introduced into the device from the reaction chamber.

[0105] As Figure 7 shown, an inlet pipe 16 is provided above the reaction chamber 12. The inlet pipe 16 passes through the feeding port 11 from top to bottom and enters the bottom of the reaction chamber 1. When the reaction is approaching the end, close the original feeding path, and slowly introduce external gas (such as air, inert gas, or nitrogen) from the inlet pipe 16. The external gas passes through the mixed solution and forms a pressure pushing effect in the reaction chamber, quickly introducing the chlorine dioxide gas remaining in the reaction chamber, the temperature regulation area, and the pipeline into the freezer. By monitoring the color of the mixed solution, the pressure change, and the feedback of the gas flow detector, it is judged whether the chlorine dioxide gas in the system has been fully discharged.

[0106] The pure chlorine dioxide liquid prepared in the freezer 2 can be exported and stored in a storage container.

[0107] During the process of encapsulating pure chlorine dioxide liquid in a storage container, it is carried out in an environment with low temperature, dryness and relative humidity below 10%. During the liquid preparation and encapsulation process, the environmental temperature and humidity must be strictly controlled. Throughout the encapsulation process, the environmental temperature should be kept consistent with the freezer temperature to avoid the evaporation of chlorine dioxide liquid caused by environmental temperature fluctuations. The encapsulation operation should be carried out in a drying oven, glove box or other humidity control equipment to ensure that the indoor relative humidity is below 5% - 10%. During this process, the operator needs to wear clean work clothes and gloves that have been dried to prevent the introduction of water vapor. In addition, desiccants (such as silica gel or phosphorus pentoxide) or dehumidifiers are used to assist in maintaining environmental dryness to ensure that the liquid chlorine dioxide has an extremely low water content before encapsulation.

[0108] It should be noted that the entire device (reaction chamber, pipeline, freezer) is assembled using flanges, threaded connections and high-efficiency seals to ensure the airtightness of the entire system. The device can also be equipped with an automatic pressure relief valve, on-line temperature and pressure monitoring equipment and a PLC control system. When the system is abnormal (such as excessive temperature, pressure or gas concentration), it can automatically initiate interlocking measures and alarm. Valves (including flow regulating valves, feed valves and tail gas treatment valves) can also be provided in the reaction chamber, freezer and connecting pipelines to be automatically controlled in an electric or pneumatic manner, realizing full-automatic production and monitoring, and improving operation safety and production efficiency.

[0109] As Figure 7 shown, the device of the present invention can be configured with an intake valve 17, a stop valve 14, a regulating valve 33, a solenoid valve 31, a vacuum pump valve 232 and a flow meter 32. Therefore, the device can be automatically controlled in an electric or pneumatic manner, realizing full-automatic production and monitoring, and improving operation safety and production efficiency.

[0110] The present invention provides a method for preparing pure chlorine dioxide liquid by using the above preparation device, which solves the problems existing in the production and storage of pure chlorine dioxide liquid in the prior art, such as inaccurate concentration / dosage control, low production efficiency, poor safety, insufficient stability and difficulty in meeting the pharmaceutical quality management specifications.

[0111] The reaction chamber is directly connected to the freezer through a well-sealed connecting pipeline, enabling the chlorine dioxide gas generated by the reaction to smoothly enter the freezer for liquefaction without additional gas transfer steps.

[0112] The entire production system remains completely sealed during the production process, effectively preventing the leakage of chlorine dioxide gas, significantly improving the safety of the production process, and ensuring that the chlorine dioxide gas is liquefied in a strictly controlled environment to avoid the introduction of impurities.

[0113] The method includes the following steps:

[0114] Fill a reaction chamber with a mixed solution capable of generating chlorine dioxide gas. The mixed solution can generate chlorine dioxide gas through its own reaction or by applying external electricity, and does not generate or basically does not generate chlorine gas;

[0115] Set the entire device including the reaction chamber and the freezer to be airtight;

[0116] Heat the temperature in the reaction chamber to 30°C - 90°C to ensure that the mixed solution capable of generating chlorine dioxide gas generates chlorine dioxide gas;

[0117] Cool the temperature in the freezer to -21°C to -59°C to transfer the chlorine dioxide gas generated in the reaction chamber to the freezer for liquefaction.

[0118] Specifically, the method includes the following operations:

[0119] (i) Fill a reaction chamber with a mixed solution capable of generating chlorine dioxide gas. The mixed solution can generate chlorine dioxide gas through its own reaction (e.g., mixing sodium chlorite and an acid) or by applying external electricity (e.g., electrolyzing sodium chlorite or sodium chloride solution). The key is that the selected mixed solution should be able to efficiently generate chlorine dioxide and basically not generate impurities such as chlorine gas to ensure the purity of the final product.

[0120] (ii) Control the temperature of the mixed solution in the reaction chamber within the range of 30°C - 90°C. This can be achieved by the following means: using a constant temperature water bath with a heating function, an electric heating film, or a heating plate equipped with a temperature control system and other devices to control the temperature of the reaction chamber. Specifically, a heating unit can be set on the outer wall of the reaction chamber, and combined with a temperature sensor and a feedback control system to achieve dynamic monitoring and precise adjustment of the solution temperature. When necessary, the target temperature can also be stably maintained by circulating and heating a liquid (such as heat transfer oil or water) through a jacket to improve the generation efficiency of chlorine dioxide gas and inhibit the generation of by-products.

[0121] (iii) Control the temperature of the freezer within a range higher than the melting point of chlorine dioxide but lower than -21°C to liquefy the chlorine dioxide gas and form pure chlorine dioxide liquid. The temperature of the freezer is controlled within a range higher than the melting point of chlorine dioxide but lower than -21°C. The melting point of chlorine dioxide is about -59°C. Therefore, keep the temperature of the freezer above -59°C (e.g., -58°C, -57°C). Avoid using a temperature lower than -59°C because this will cause chlorine dioxide to solidify into a solid, increasing the difficulty of collection and treatment, and may require additional steps (e.g., heating) to convert it into a liquid state.

[0122] Another aspect of the present invention provides a method for storing pure chlorine dioxide liquid. The pure chlorine dioxide liquid is encapsulated in a storage container and stored away from light. The storage temperature is controlled between -21°C and -59°C, or at a temperature that can ensure the retention rate of chlorine dioxide is not less than 95% for 6 months. The storage container is configured to have low gas permeability, resistance to low temperature, and resistance to oxidation corrosion.

[0123] Chlorine dioxide liquid has strong volatility, is prone to decomposition, and is extremely sensitive to moisture at room temperature. In traditional technologies, it is mostly stored at 0°C to -20°C, but there are still obvious volatilization problems with chlorine dioxide at this temperature. Through a large number of experiments, it is found that when the storage temperature is controlled within the range of -21°C to -59°C, the volatilization of chlorine dioxide can be effectively inhibited, while maintaining its high purity and quality. The preferred storage temperature is -30°C to -55°C, and the specific temperature is selected according to the product use and storage period.

[0124] The storage container of the present invention is configured to have low gas permeability, resistance to low temperature, and resistance to oxidation corrosion, and preferably materials such as high borosilicate glass, polytetrafluoroethylene (PTFE), PFA, or titanium metal are used to ensure that the container will not undergo penetration, chemical reactions, or material aging under low temperature and strong oxidation conditions of chlorine dioxide.

[0125] In the storage container of the present invention, the pure chlorine dioxide liquid encapsulated in each storage container does not exceed 10 grams, and the capacity of a single storage container does not exceed 100 times the volume of the pure chlorine dioxide liquid filled. By limiting the encapsulation, the risks of explosion and leakage caused by container breakage or temperature fluctuations can be reduced, and at the same time, the gasification of part of the liquid can be prevented.

[0126] The encapsulation operation uses a container that has been pre-dried and strictly cleaned, and the transfer and encapsulation of chlorine dioxide liquid are carried out in a low-temperature and dry environment. After encapsulation, the container should be placed in a low-temperature constant temperature box (the temperature is set between -21°C and -55°C) and stored away from light. Subsequently, the liquid content and purity in the storage container are regularly detected, and a precision balance is used to monitor the change in the total weight of the container to calculate the retention rate of the active ingredient. Experimental data shows that when using high-specification containers at -55°C and -21°C, the liquid retention rates can reach 99% and 95% respectively after 6 months, while ordinary glass bottles (at -20°C) only maintain about 30%.

[0127] The preparation device, method, and storage method of the pure chlorine dioxide liquid described in the present invention are further elaborated in detail below in combination with specific embodiments.

[0128] Example 1:

[0129] 1. Set up the device: Adopt as Figure 2The device shown constructs a completely sealed chlorine dioxide liquid production system, including a reaction chamber (500 ml, made of borosilicate glass and tetrafluoroethylene materials), a connecting pipeline (made of tetrafluoroethylene materials), and a freezer (1000 ml, made of borosilicate glass and tetrafluoroethylene). All joints are sealed with seals with good airtightness.

[0130] The reaction chamber, connecting pipeline, and freezer are equipped with temperature sensors and pressure sensors; the connecting pipeline is equipped with a flowmeter. All joints are sealed with seals with good airtightness, which are not shown in the figure.

[0131] 2. Preparation of reactants: Solutions prepared by dissolving 40 grams of sodium chlorite in 70 mL of water at 90 degrees and 60 grams of citric acid in 60 mL of water at 90 degrees are used as reactants and are respectively filled into the reaction chamber, and the feeding port is immediately closed.

[0132] 3. Heating the mixed solution: The temperature of the reaction chamber (i.e., the temperature of the mixed solution) is controlled at 60 °C by water bath heating.

[0133] 4. Liquefaction in the freezer: The temperature of the freezer is controlled at -45 °C. Chlorine dioxide gas enters the freezer for liquefaction.

[0134] Result: The preparation time is 1 hour, 2.7 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution, the total amount of chlorine dioxide produced is estimated to be 3.7 grams (including water vapor), and the liquefaction rate of chlorine dioxide can be calculated to be 73%.

[0135] Example 2:

[0136] 1. Setup of the device: The same as in Example 1.

[0137] 2. Preparation of reactants: 130 mL of 30% (w / v) sodium chlorite solution and an appropriate amount of 15% (w / v) hydrochloric acid solution (adjusting the pH to 2.5) are respectively filled into the reaction chamber and mixed, and the feeding port is immediately closed.

[0138] 3. Heating the mixed solution: The temperature of the reaction chamber is controlled at 90 °C.

[0139] 4. Liquefaction in the freezer: The temperature of the freezer is controlled at -55 °C.

[0140] 5. Result: The preparation time is 1 hour, 10.4 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution, the total amount of chlorine dioxide produced is estimated to be 12.5 grams (including water vapor), and the liquefaction rate of chlorine dioxide can be calculated to be 83%.

[0141] Example 3:

[0142] 1. Setup of the device: The same as in Example 1.

[0143] 2. Preparation of reactants: The same as in Example 1

[0144] 3. Heating the mixed solution: Control the temperature of the reaction chamber at 30°C.

[0145] 4. Liquefaction in the freezer: Control the temperature of the freezer at -40°C.

[0146] 5. Results: The preparation time is 1 hour, 1.5 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution, the total amount of chlorine dioxide generated is estimated to be 2.5 grams (including water vapor), and the liquefaction rate of chlorine dioxide can be calculated as 60%.

[0147] Example 4:

[0148] 1. Set up the device: The same as in Example 1.

[0149] 2. Preparation of reactants: The same as in Example 2.

[0150] 3. Heating the mixed solution: Control the temperature of the reaction chamber at 65°C.

[0151] 4. Liquefaction in the freezer: Control the temperature of the freezer at -25°C.

[0152] 5. Results: The preparation time is 1 hour, 4.1 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution, the total amount of chlorine dioxide generated is estimated to be 10.9 grams (including water vapor), and the liquefaction rate of chlorine dioxide can be calculated as 38%.

[0153] Example 5:

[0154] 1. Set up the device: The same as in Example 1.

[0155] 2. Preparation of reactants: The same as in Example 1.

[0156] 3. Heating the mixed solution: Control the temperature of the reaction chamber at 55°C.

[0157] 4. Liquefaction in the freezer: Control the temperature of the freezer at -59°C.

[0158] 5. Results: The preparation time is 1 hour, 3.6 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution, the total amount of chlorine dioxide generated is estimated to be 3.9 grams (including water vapor), and the liquefaction rate of chlorine dioxide can be calculated as 93%.

[0159] Example 6: Condensation and dehumidification

[0160] 1. Set up the device: Use Figure 5The device shown builds a completely sealed chlorine dioxide liquid production system, including a reaction chamber (500 ml, made of high borosilicate glass and tetrafluoroethylene material), connecting pipelines (made of tetrafluoroethylene material), and a freezer (1000 ml, made of high borosilicate glass and tetrafluoroethylene). All joints use seals with good airtightness. A condenser tube made of titanium metal is installed between the reaction chamber and the freezer, and the condenser tube is immersed in constant temperature water at 12 °C, and the whole system is sealed.

[0161] 2. Preparation of reactants: The same as in Example 1.

[0162] 3. Heating the mixed solution: Control the temperature of the reaction chamber at 62 °C.

[0163] 4. Liquefaction in the freezer: Control the temperature of the freezer at -47 °C.

[0164] 5. Results: The preparation time is 1 hour, 9.1 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution and subtracting the liquid collected in the condenser tube, the total amount of chlorine dioxide produced is estimated to be 9.6 grams, and the liquefaction rate of chlorine dioxide can be calculated as 94%.

[0165] Example 7: Vacuum pumping

[0166] 1. Setup of the device: Use Figure 4 the device shown to build a completely sealed chlorine dioxide liquid production system, the same as in Example 1, except that the freezer is equipped with a vacuum pumping device.

[0167] 2. Preparation of reactants: The same as in Example 1.

[0168] 3. Heating the mixed solution: Control the temperature of the reaction chamber at 58 °C.

[0169] 4. Liquefaction in the freezer: Control the temperature of the freezer at -30 °C. A valve is installed between the freezer and the reaction chamber. Before the chlorine dioxide gas is generated, close the valve and evacuate the freezer to a negative pressure (-0.05 MPa); when the chlorine dioxide gas is generated, open the valve to allow the chlorine dioxide gas to flow into the freezer for liquefaction.

[0170] 5. Results: The preparation time is 1 hour, 10.1 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution, the total amount of chlorine dioxide produced is estimated to be 13.6 grams, and the liquefaction rate of chlorine dioxide can be calculated as 74%.

[0171] Example 8: Vacuum pumping + inert gas purging

[0172] 1. Setup of the device: Use Figure 6The device shown constructs a completely sealed chlorine dioxide liquid production system, which is the same as Example 7, except that a vacuum pumping device is connected to the freezer. The reaction chamber has a feeding port and an air inlet pipe for loading the reaction solution and introducing external gas, and the feeding port and the air inlet pipe are closed when chlorine dioxide is generated; the production system composed of the reaction chamber and the freezer has overall tightness to prevent the leakage of chlorine dioxide gas.

[0173] 2. Preparation of reactants: The same as Example 2.

[0174] 3. Heating the mixed solution: Control the temperature of the reaction chamber at 72 °C.

[0175] 4. Liquefaction in the freezer: Control the temperature of the freezer at -52 °C.

[0176] 5. Tail gas treatment: A valve is installed between the freezer and the reaction chamber. Before the generation of chlorine dioxide gas, the valve is closed and the freezer is evacuated to a negative pressure; when chlorine dioxide gas is generated, the valve is opened to allow the chlorine dioxide gas to flow into the freezer for liquefaction. When the reaction is approaching the end, dry nitrogen is slowly introduced through the air inlet pipe of the reaction chamber to push the residual chlorine dioxide gas in the system into the freezer.

[0177] 6. Results: The preparation time is 1 hour, 16.9 grams of pure chlorine dioxide liquid is collected. By weighing the weight change of the mixed solution, the total amount of chlorine dioxide generated is estimated to be 18.6 grams, and the liquefaction rate of chlorine dioxide can be calculated as 91%.

[0178] Note: The production rate of chlorine dioxide is the weight of chlorine dioxide gas generated / the weight of chlorine dioxide that can be generated by the complete reaction of 100% of sodium chlorite (23 grams).

[0179] Table 1 Statistical data of preparation results

[0180]

[0181]

[0182] Example 9: Preparation of chlorine dioxide liquid by electrolyzing sodium chlorite solution

[0183] In this example, chlorine dioxide liquid is collected by electrolyzing sodium chlorite solution under a closed system and negative pressure conditions.

[0184] Constructing the device

[0185] The reaction chamber is configured as a two-chamber electrolytic cell: a DuPont Nafion 324 cation exchange membrane is used to separate the cathode chamber and the anode chamber.

[0186] Anode: A titanium sheet (60 mm × 40 mm) with a RuO2-IrO2 / Ti catalytic layer on the surface.

[0187] Cathode: A titanium sheet (60 mm × 40 mm) treated by pickling (10% hydrochloric acid, 30 minutes).

[0188] Closed system: The anode gas outlet is connected to a borosilicate glass freezer through a tetrafluoroethylene pipeline and a tetrafluoroethylene valve. The entire system (including the electrolytic cell, pipeline, and freezer) has passed the airtightness test to ensure no leakage.

[0189] Heating equipment: A constant temperature water bath used to control the temperature of the electrolytic cell.

[0190] Freezing equipment: A low-temperature circulating bath used to control the temperature of the freezer.

[0191] Vacuum pump: A rotary vane vacuum pump used to evacuate the freezer.

[0192] Power supply: An adjustable DC regulated power supply that provides the direct current required for electrolysis.

[0193] Thermometer: Used to measure the temperature of the electrolyte and the freezer.

[0194] Pressure gauge / sensor: Used to monitor the pressure in the anode chamber and the freezer.

[0195] Experimental procedure:

[0196] 1. Preparation of electrolyte:

[0197] Anode chamber: Fill it with 200 mL of 30% (w / v) NaClO2 solution.

[0198] Cathode chamber: Fill it with 200 mL of 30% (w / v) NaCl solution.

[0199] 2. System sealing and evacuation:

[0200] Carefully check and ensure the airtightness of the entire system (electrolytic cell, connecting pipeline, freezer).

[0201] Close the valve connecting the anode gas outlet and the freezer.

[0202] Use the vacuum pump to evacuate the freezer to a negative pressure of -0.08 MPa.

[0203] 3. Electrolysis and heating:

[0204] Turn on the power supply and set the current density to 50 mA / cm 2 , and perform constant current electrolysis.

[0205] Use the constant temperature water bath to control the temperature of the electrolytic cell at 60 °C, and use a thermometer to monitor the temperature of the electrolyte.

[0206] 4. Condensation collection:

[0207] After the electrolysis starts, chlorine dioxide gas is generated at the anode.

[0208] When the pressure in the anode chamber rises, open the valve connecting the anode gas outlet and the freezer.

[0209] Control the temperature of the freezer at -42 °C. Under negative pressure and low temperature conditions, chlorine dioxide gas condenses into a liquid in the freezer.

[0210] 5. Result measurement:

[0211] After electrolysis for 1 hour, turn off the power supply and the valve.

[0212] Collect the pure chlorine dioxide liquid in the freezer and weigh it, which is 15.7.

[0213] In this example, chlorine dioxide is prepared by electrolysis. 60 grams of sodium chlorite is electrolyzed for 1 hour. Theoretically, if sodium chlorite reacts 100% and is completely converted into chlorine dioxide gas, 44.72 grams of chlorine dioxide can be produced. Actually, 15.7 grams of liquefied chlorine dioxide is collected, indicating that the liquefaction rate of the whole process from sodium chlorite raw material to the final liquid chlorine dioxide product is 35.11% (the liquefaction rate of the whole process is different from that in Table 1). This efficiency is acceptable in the field of pharmaceutical preparations.

[0214] Example 10: Open system control (open system + nitrogen)

[0215] 1. Reactant preparation:

[0216] Sodium chlorite solution: Weigh sodium chlorite solid and dissolve it in distilled water to prepare a 300 mL 35% (w / v) sodium chlorite solution.

[0217] Sulfuric acid solution: Measure concentrated sulfuric acid and slowly add it to water to prepare 200 mL of 40% (w / v) sulfuric acid.

[0218] 2. Reaction and condensation:

[0219] Reaction vessel: Use a reaction kettle which has an air inlet, an air outlet and a feeding port. Condensation vessel: Use a glass container as the condensation vessel. The upper part of this container has an air inlet and an air outlet. Place it in a low-temperature refrigerator and connect the air outlet to a gas duct leading to the outside.

[0220] Connection: Connect the air outlet of the reaction kettle to the air inlet of the condensation vessel through a gas duct. The gas duct extends into the condensation vessel. Ensure that the duct is inserted into the bottom of the condensation vessel from top to bottom.

[0221] Nitrogen introduction: Connect the air inlet of the reaction kettle to a nitrogen cylinder and insert the inlet pipe below the liquid level.

[0222] Operation:

[0223] Add the prepared 300 mL of 35% sodium chlorite solution to the reaction kettle.

[0224] Pre-cool the condensation container to -10 °C and maintain the temperature.

[0225] Add 200 mL of 40% sulfuric acid solution to the sodium chlorite solution in the reaction kettle and close the feeding port.

[0226] Immediately start blowing nitrogen into the reaction kettle.

[0227] Adjust the nitrogen.

[0228] 3. Results and analysis:

[0229] After reacting for 1 hour, the weight is 0.2 g of pure chlorine dioxide liquid. By weighing the weight change of the mixed solution before and after the reaction, the total amount of chlorine dioxide produced is estimated to be 23 g. Calculate the liquefaction rate of chlorine dioxide to be 0.87%.

[0230] Since nitrogen is blown in, the only possibility is that the condensation container is of an open design, and in this case, only a very small amount of chlorine dioxide liquid is produced.

[0231] Example 11: Study on the influence of different reaction conditions and system types on the production of chlorine dioxide liquid

[0232] In this example, through three comparative experiments, the effects of reaction temperature, freezer temperature, and system type (open / closed) on the production efficiency of chlorine dioxide liquid were studied. The main inspection indexes were the liquefaction rate and estimated yield of chlorine dioxide.

[0233] Reactants:

[0234] Sodium chlorite solution: 40 g of sodium chlorite is dissolved in 70 mL of water (pre-heated according to the needs of different experimental groups)

[0235] Citric acid solution: 60 g of citric acid is dissolved in 60 mL of water (pre-heated according to the needs of different experimental groups)

[0236] Experimental grouping and steps:

[0237] Experimental group 1 (open system, high-temperature reaction, low-temperature freezing):

[0238] Reactant preparation: Dissolve 40 g of sodium chlorite in 70 mL of water at 90 °C, and dissolve 60 g of citric acid in 60 mL of water at 90 °C.

[0239] Reaction and Condensation: The reaction chamber is a high-borosilicate glass container with a feeding port and a single outlet. Pour the two solutions into the container and mix them, then immediately close the feeding port. The reaction chamber is connected to the freezer by a gas pipe. After mixing, the generated gas is introduced into the freezer through the gas pipe, and the gas pipe is inserted from top to bottom close to the bottom of the freezer container. There is an outlet above the freezer container to balance the air pressure, but it is not completely sealed.

[0240] Temperature Control: The reaction temperature is maintained at about 60 °C (open system, the temperature will fluctuate, record the actual temperature). The temperature of the freezer is controlled at -20 °C.

[0241] Results: After reacting for 1 hour, the weight of the pure chlorine dioxide liquid is 0.2 g. By weighing the weight change of the mixed solution before and after the reaction, the total amount of chlorine dioxide generated is estimated to be 5.7 g. Calculate the liquefaction rate of chlorine dioxide to be 3.5% (0.2 g / 5.7 g * 100%).

[0242] Experimental Group 2 (Closed System, Room Temperature Reaction, Low Temperature Freezing):

[0243] System Setup: Set up a completely closed chlorine dioxide liquid production system, including a reaction chamber (500 mL, made of high-borosilicate glass and polytetrafluoroethylene), connecting pipes (polytetrafluoroethylene material), and a freezer (1000 mL, made of high-borosilicate glass and polytetrafluoroethylene). All connections use seals with good airtightness.

[0244] Reactant Preparation: Dissolve 40 g of sodium chlorite in 70 mL of water, and dissolve 60 g of citric acid in 60 mL of water. Pour the two solutions into the reaction chamber respectively and immediately close the feeding port.

[0245] Temperature Control: The temperature of the reaction chamber (i.e., the temperature of the mixed solution) is controlled at 20 °C (room temperature). The temperature of the freezer is controlled at -20 °C.

[0246] Results: After reacting for 1 hour, collect the product in the freezer and weigh it to be 0.15 g of pure chlorine dioxide liquid. By weighing the weight change of the mixed solution before and after the reaction, the total amount of chlorine dioxide generated is estimated to be 1.3 g. Calculate the liquefaction rate of chlorine dioxide to be 11.5% (0.15 g / 1.3 g * 100%).

[0247] Experimental Group 3 (Closed System, High Temperature Reaction, Low Temperature Freezing):

[0248] System Setup: Same as Experimental Group 2.

[0249] Reactant Preparation: Dissolve 40 g of sodium chlorite in 70 mL of water at 50 °C, and dissolve 60 g of citric acid in 60 mL of water at 50 °C. Pour the two solutions into the reaction chamber respectively and immediately close the feeding port.

[0250] Temperature control: The temperature of the reaction chamber is 30 degrees Celsius, and the liquefaction in the freezer: The temperature of the freezer is controlled at -21°C.

[0251] Results: After reacting for 1 hour, the product in the freezer was collected and weighed as 0.7 g of pure chlorine dioxide liquid. By weighing the change in the weight of the mixed solution before and after the reaction, the total amount of chlorine dioxide produced was estimated to be 2.3 g. The liquefaction rate of chlorine dioxide was calculated to be 30% (0.7 g / 2.3 g * 100%).

[0252] Table 2

[0253]

[0254]

[0255] Conclusion:

[0256] The comparative experiment shows that the preparation of chlorine dioxide in a closed system can significantly improve the liquefaction rate of chlorine dioxide compared to an open system.

[0257] The combination of the closed system, reaction at a specific temperature, and low-temperature freezing adopted in the embodiment of the present invention (experimental group 3) obtained the highest yield of liquid chlorine dioxide compared to the prior art (experimental groups 1 and 2).

[0258] Example 12: Storage stability test of pure chlorine dioxide liquid

[0259] The experimental materials include: pure chlorine dioxide liquid prepared in Example 1 of the present invention; storage container A (high-borosilicate glass bottle, equipped with a tetrafluoroethylene stopper and a low-temperature-resistant fluororubber sealing ring) and storage container B (ordinary glass bottle, equipped with a polypropylene (PP) lid and a silica gel pad, as a control); constant-temperature equipment (low-temperature constant-temperature boxes capable of providing -21°C and -55°C, and a -20°C constant-temperature box); humidity control equipment (drying oven, desiccator, etc.); analytical instrument (precision balance with an accuracy of at least 0.01 g).

[0260] The experimental steps are as follows: First, prepare pure chlorine dioxide liquid according to Example 1 of the present invention; then, perform encapsulation operation in a drying oven, controlling the relative humidity to be lower than 10%; divide the chlorine dioxide liquid into three groups: Group A1, weigh about 5 grams of chlorine dioxide liquid into container A using a precision balance, record the total weight (W2), and place it in a -55°C constant temperature oven; Group A2, weigh about 5 grams of chlorine dioxide liquid into container A, record the total weight (W2), and place it in a -21°C constant temperature oven; Group B1 (control group), weigh about 5 grams of chlorine dioxide liquid into container B, record the total weight (W2), and place it in a -20°C constant temperature oven; use a pipette or dropper to transfer the chlorine dioxide liquid to a storage container and seal it immediately; place the encapsulated samples in the corresponding constant temperature equipment and store them in the dark; after 6 months of storage, take out the samples from each group and weigh the total weight of the samples and the containers (W3) using a precision balance; calculate the initial weight of chlorine dioxide: Winitial = W2 - W1 (W1 is the pre-weighed weight of the container), calculate the weight of chlorine dioxide after storage: Wafter storage = W3 - W1, and calculate the retention rate of chlorine dioxide: Retention rate (%) = (Wafter storage / Winitial) × 100%.

[0261] Table 3 Storage Test Results

[0262] Group Container Storage Temperature Storage Time Retention Rate (%) A1 Borosilicate + Teflon + Fluororubber -55℃ 6 months 99 A2 Borosilicate + Teflon + Fluororubber -21℃ 6 months 95 B1 Ordinary Glass + PP + Silicone -20℃ 6 months 30

[0263] Experimental conclusion: Under low temperature conditions (-55°C and -21°C), when using a high borosilicate glass bottle with a tetrafluoroethylene stopper (low temperature resistant fluororubber sealing ring) to store pure chlorine dioxide liquid, a relatively high retention rate can still be maintained after 6 months (99% and 95% respectively), which is significantly better than the storage effect of using an ordinary glass bottle and a PP lid at -20°C (the retention rate is only 30%). The experimental results verify the effectiveness of the storage method of the present invention, that is, low temperature and the selection of a storage container with low gas permeability, low temperature resistance, and oxidation corrosion resistance are crucial for the long-term storage of pure chlorine dioxide liquid.

[0264] It should be noted that chlorine dioxide has strong oxidizing and corrosive properties. When operating, protective glasses, gloves and other protective equipment should be worn; the encapsulation operation should be carried out in a fume hood; avoid violent vibration or impact on the storage container; regularly check the tightness of the storage container; when weighing, avoid weight changes caused by other factors, such as wiping the container, sample contamination, container wear, etc. It is recommended to use the same balance for each weighing.

[0265] The present invention achieves the following beneficial effects:

[0266] 1. Precise control of concentration / dosage: The present invention produces chlorine dioxide liquid as the precursor of chlorine dioxide injection. Through appropriate storage methods, the stability of the injection precursor is ensured, enabling precise control of the concentration and dosage of chlorine dioxide injection during use, ensuring the consistency and reproducibility from preparation to use, and meeting the strict requirements of pharmaceutical preparations for the accuracy of concentration and dosage.

[0267] 2. High production efficiency: The present invention adopts technical means such as a fully enclosed system design, optimized reaction and freezing conditions, dehumidification measures, flow control, and tail gas treatment, significantly improving the generation rate, conversion rate, and liquefaction efficiency of chlorine dioxide gas, thereby enhancing the overall production efficiency of pure chlorine dioxide liquid.

[0268] 3. High safety: The fully enclosed system design effectively prevents the leakage of chlorine dioxide gas; the reaction chamber is equipped with a pressure monitoring and pressure relief device; the production process is strictly controlled within the safe parameter range, fundamentally eliminating potential safety hazards during the production process.

[0269] 4. Good storage stability: Through optimized storage conditions (low temperature, light protection, dryness, small-dose packaging, suitable container materials), the storage life of pure chlorine dioxide liquid is significantly extended, effectively preventing its volatilization, decomposition, and quality change, ensuring stability for long-term use.

[0270] 5. Compliance with pharmaceutical quality management specifications: The present invention has established a perfect quality control system, strictly monitoring all key parameters during the production and storage processes to ensure the stability and reliability of product quality, fully meeting pharmaceutical quality standards.

[0271] 6. Simple operation and wide applicability: The method and equipment provided by the present invention are easy to operate and control, enabling automated production, and are applicable to the production of pure chlorine dioxide liquid of different scales, which can be flexibly adjusted and optimized according to actual needs.

[0272] 7. The fully automated equipment and safety interlock system adopted by the present invention ensure the efficient, stable, and reliable operation of the entire production process, providing a strong guarantee for large-scale industrial production and the preparation of pharmaceutical-grade products. The data of each embodiment show that under different process conditions, the present invention can achieve ideal liquefaction rates and output rates, fully demonstrating its superiority and practicality.

[0273] The above is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims

1. An apparatus for preparing pure chlorine dioxide liquid, characterized in that The device is set to be airtight and includes: (i) A reaction chamber for generating chlorine dioxide gas from a mixed solution capable of producing chlorine dioxide gas through its own reaction or by applying external power, and producing no or substantially no chlorine gas; the temperature inside the reaction chamber is set to 30°C - 90°C; (ii) A freezer connected after the reaction chamber through a connecting pipeline for transporting the chlorine dioxide gas generated in the reaction chamber to the freezer and liquefying it, and the temperature inside the freezer is set to -21°C to -59°C; The gaseous chlorine dioxide from the reaction chamber is liquefied in the freezer to form the pure chlorine dioxide liquid; The pure chlorine dioxide liquid refers to a chlorine dioxide liquid with a chlorine dioxide content of not less than 95%.

2. The device according to claim 1, wherein The device is used for preparing chlorine dioxide injection or its precursor liquid.

3. The device according to claim 1, characterized in that A reaction chamber heating device is provided below the reaction chamber for heating the reaction chamber and controlling the temperature; the reaction chamber heating device is a water bath heater.

4. The device according to claim 1, characterized in that, A feeding port is provided above the reaction chamber for feeding a mixed solution capable of producing chlorine dioxide gas into the reaction chamber, and closing the feeding port after the feeding is completed.

5. The device according to claim 1, characterized in that An air outlet is provided above the reaction chamber, and the reaction chamber is communicated with the freezer through a connecting pipeline.

6. The device according to claim 5, characterized in that The connecting pipeline is provided with a valve, and the reaction chamber is fluidly connected to the freezer via the valve through the pipeline.

7. The device according to claim 1, characterized in that, A freezer temperature control device is provided on the side of the freezer for cooling the freezer and controlling the temperature.

8. The device according to claim 1, characterized in that, A vacuum pumping device is connected after the freezer, and this vacuum pumping device is used to evacuate the freezer to a negative pressure before the generation of chlorine dioxide gas to promote the preferential flow of the chlorine dioxide gas generated in the reaction chamber into the freezer.

9. The device according to claim 8, characterized in that, A control valve is provided on the connecting pipeline between the reaction chamber and the freezer, and the device is set to: evacuate the freezer to a negative pressure before the generation of chlorine dioxide gas; after the generation of chlorine dioxide gas, open the control valve to allow the gas to flow into the freezer and complete liquefaction.

10. The device according to claim 1, characterized in that, A condensation and dehumidification unit or a temperature adjustment unit is provided between the reaction chamber and the freezer, The condensation and dehumidification unit or the temperature adjustment unit is used to condense the water vapor from the reaction chamber into liquid water through condensation and discharge it from the device through a drain port; The condensation and dehumidification unit can be a condenser, or the temperature adjustment unit is a cooling pipeline structure provided with a constant temperature water tank, and the temperature of the constant temperature water tank is set to 11 - 20°C.

11. The device according to claim 1, wherein A flow control unit is provided on the connecting pipeline between the reaction chamber and the freezer for controlling the fluid flow rate transferred from the reaction chamber to the freezer.

12. The device according to claim 1, characterized in that, The reaction chamber is equipped with a barometer and a pressure relief valve for monitoring and adjusting the air pressure inside the reaction chamber.

13. The device according to claim 1, characterized in that, The temperature of the freezer is set to -30°C to -58°C, preferably -40°C to -55°C, to improve the liquefaction efficiency and stability.

14. A method for preparing pure chlorine dioxide liquid, characterized in that, The method uses the device according to claim 1 and includes the following steps: Loading a mixed solution capable of producing chlorine dioxide gas into the reaction chamber, and the mixed solution can generate chlorine dioxide gas through its own reaction or by applying external power, and produces no or substantially no chlorine gas; Setting the entire device including the reaction chamber and the freezer to be airtight; Heat the temperature in the reaction chamber to 30°C - 90°C to ensure that a mixed solution capable of generating chlorine dioxide gas generates chlorine dioxide gas; Cool the temperature in the freezer to -21°C to -59°C to transfer the chlorine dioxide gas generated in the reaction chamber to the freezer for liquefaction.

15. The method according to claim 14, wherein A condensation and dehumidification area is provided between the reaction chamber and the freezer to remove the water vapor from the reaction chamber through condensation via the condensation and dehumidification area.

16. The method according to claim 14, wherein Before the chlorine dioxide gas is generated, evacuate the freezer to a negative pressure.

17. The method according to claim 14, wherein When the generation rate of the chlorine dioxide gas slows down, introduce air or an inert gas into the reaction chamber to push the chlorine dioxide gas in the reaction chamber and the temperature regulation area into the freezer through the mixed solution.

18. The method according to claim 14, wherein Encapsulate pure chlorine dioxide liquid in a storage container under an environment of low temperature, dryness and relative humidity below 10%.

19. A storage method for pure chlorine dioxide liquid, characterized in that, Encapsulate the pure chlorine dioxide liquid prepared by the method described in claim 14 in a storage container, store it in the dark, control the storage temperature at -21°C to -59°C, or at a temperature that can ensure the retention rate of chlorine dioxide is not less than 95% for 6 months. The storage container is configured to have low gas permeability, resistance to low temperature, and resistance to oxidation corrosion.

20. The storage method according to claim 19, wherein, The pure chlorine dioxide liquid encapsulated in each storage container does not exceed 10 grams, and the capacity of a single storage container does not exceed 100 times the volume of the pure chlorine dioxide liquid filled.

Images