Method for preparing clinical medicinal grade iodine 131 by separating medical radioactive wastes

Abstract

The invention discloses a method for preparing clinical medicinal grade iodine 131 by separating medical radioactive waste, and relates to the technical field of pharmaceutical engineering, the clinical medicinal grade iodine 131 is prepared by pre-treating the used molybdenum-technetium generator medical radioactive waste liquid through selective precipitation, microorganism-electrochemical catalytic reduction, oxidative distillation, chromatographic refining and degerming filtration blending. The method has the advantages that the purity and the yield of the iodine 131 separated from the medical waste liquid are remarkably improved by establishing a set of multi-stage synergistic purification process comprising pretreatment, selective precipitation, microorganism-electrochemical catalytic reduction, oxidative distillation and chromatographic refining; wherein filtration acidification and carrier addition in the pretreatment stage effectively guarantee the stability of an initial material, and subsequent precipitation and reduction operations deeply remove isotope impurities such as technetium and molybdenum and radioactive interference nuclides, so that the problems of low product purity and high impurity residue caused by single purification step in the traditional process are thoroughly solved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical engineering technology, specifically to a method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste. Background Technology

[0002] Iodine-131, as an important medical radionuclide, is widely used in the diagnosis and treatment of diseases such as hyperthyroidism and thyroid cancer. Currently, medical iodine-131 is mainly produced by nuclear reactor irradiation, but its raw material supply is limited and the cost is high. The waste liquid from the molybdenum-technetium generator contains a certain amount of iodine-131. If clinical pharmaceutical grade iodine-131 can be efficiently and safely recovered and purified from this type of medical radioactive waste, it will not only realize the resource utilization of radioactive waste, but also alleviate the supply pressure of medical iodine-131.

[0003] Existing methods for separating and purifying iodine-131 from medical radioactive waste still have the following problems: First, traditional processes often employ single or simple purification steps, making it difficult to effectively remove isotopic impurities such as technetium and molybdenum, as well as interference from other radionuclides. This results in low purity and high impurity residues in the final product, failing to meet pharmaceutical standards. Second, the recovery rate of iodine in conventional extraction processes is generally low, and radioactive loss is easily caused during operation due to volatilization and adsorption. Furthermore, there are safety hazards such as high operational environmental risks and serious cross-contamination. In addition, existing methods are weak in subsequent formulation preparation and quality control, lacking systematic aseptic processing, formulation stability control, and comprehensive quality analysis strategies. This makes it difficult to ensure that the final product meets the stringent requirements of the Pharmacopoeia of the People's Republic of China in terms of radionuclear purity, radiochemical purity, sterility, pyrogen-free environment, and chemical impurity limits. Therefore, we propose a method for separating and preparing clinical pharmaceutical-grade iodine-131 from medical radioactive waste. Summary of the Invention

[0004] The purpose of this invention is to provide a method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste, comprising a separation and preparation method, wherein the separation and preparation method includes the following steps:

[0006] The medical radioactive waste liquid obtained after the use of the molybdenum-technetium generator is pretreated, including filtration and acidification. Then, the pretreated solution is subjected to selective precipitation reaction to achieve preliminary decontamination. The pre-purified iodine-containing solution is subjected to microbial-electrochemical catalytic reduction treatment to deeply remove radioactive nuclide impurities. Iodine-131 is then separated and enriched through oxidation and distillation. The enriched product is then purified by chromatography. The purified solution is then sterilized by filtration and formulation preparation. The obtained formulation is subjected to comprehensive quality analysis. After passing the quality test, it is packaged to obtain clinical pharmaceutical grade iodine-131 finished product.

[0007] As a further aspect of the present invention: in the pretreatment step, the raw material liquid is filtered with a microporous membrane to remove insoluble particulate matter, then dilute nitric acid is added to adjust the pH value of the system to 1-3, and potassium iodide with a concentration range of 0.1g / L-1.0g / L is added as a carrier and mixed evenly.

[0008] As a further aspect of the present invention: In the selective precipitation reaction step, barium nitrate with a concentration of 0.05 mol / L to 0.2 mol / L is added to the pretreatment solution as a soluble barium salt and disodium hydrogen phosphate with a concentration of 0.02 mol / L to 0.1 mol / L as a phosphate. The pH is adjusted to 7.5 to 9.0 using a sodium hydroxide solution with a concentration of 0.1 mol / L to 0.5 mol / L. At the same time, ethylenediaminetetraacetic acid with a concentration of 0.01 mol / L to 0.05 mol / L is added as a complexing agent. After standing for 1 to 2 hours, the precipitate is removed by centrifugation to obtain a preliminarily purified iodine-containing supernatant.

[0009] As a further aspect of the present invention: the microbial-electrochemical catalytic reduction treatment is carried out in a bioelectrochemical reactor. The treatment includes: inoculating the iodine-containing supernatant with genetically engineered Shewanella bacteria that have specific reduction capabilities for pertechnetate and iodooxy anions, while controlling the working electrode of the reaction system to be a cathode, maintaining the potential at -0.4V to -0.6V, utilizing the synergistic effect of extracellular electron transfer of microorganisms and electrochemical cathode reduction, reducing interfering radioactive nuclide impurities in the solution from their high-valence, easily soluble anionic form to low-valence, insoluble precipitates or immobilizing them on the surface of the bacteria, the treatment time is 6h-24h, and after treatment, the bacteria and immobilized impurities are separated and removed using a microporous filter membrane.

[0010] As a further aspect of the present invention: In the oxidation and distillation steps, after the microbial-electrochemical catalytic reduction process is completed, a 5%-10% hydrogen peroxide solution is added to the reaction solution as an oxidant, and nitric acid is added to maintain the acidity of the system at 1 mol / L-3 mol / L, oxidizing iodide ions to elemental iodine. Subsequently, the solution is heated to 80℃-100℃ and distilled with nitrogen gas at a flow rate of 0.5L / min-1.5L / min. The generated iodine vapor is guided to a receiving bottle containing a 0.5%-2% sodium bisulfite absorbent solution and is absorbed and reduced.

[0011] As a further aspect of the present invention: in the terminal purification step, the absorbed and reduced solution is passed through a chromatographic column packed with a strong basic anion exchange resin, and a phosphate buffer solution with a pH value adjusted to 8-10 is used as the mobile phase for elution at a flow rate of 1 mL / min-3 mL / min, and the main elution peak fraction containing iodine 131 is collected.

[0012] As a further aspect of the present invention: in the sterilization filtration and preparation steps, the collected iodine-containing fraction is sterilely filtered through a 0.22μm-0.45μm polyethersulfone microporous membrane, and water for injection is added to the filtrate to adjust the radioactivity concentration to 740MBq / mL-3700MBq / mL. The pH value is then adjusted to 7.0-8.5 using a sterile 0.1mol / L-1.0mol / L sodium hydroxide solution to obtain iodine […]. 131 [Initial product of sodium chloride solution]

[0013] As a further aspect of the present invention: in the quality analysis and dispensing steps, the iodine […] 131 The initial sodium chloride solution underwent quality testing, including testing for the use of high-purity germanium. Its radionuclear purity was determined by energy dispersive spectroscopy, and its radiochemical purity was determined by high performance liquid chromatography-radioactive detector. Aseptic testing was performed by membrane filtration, bacterial endotoxin testing by gel electrophoresis, pH measurement, and chemical impurity content testing by atomic absorption spectrometry. After all indicators met the requirements of the Pharmacopoeia of the People's Republic of China, it was dispensed into sterile, pyrogen-free glass bottles and sealed in a GMP-compliant Class A clean environment.

[0014] Compared with the prior art, the beneficial effects of the present invention by adopting the above technical solution are as follows:

[0015] 1. This invention significantly improves the purity and yield of iodine-131 separation from medical waste by establishing a multi-stage synergistic purification process that includes pretreatment, selective precipitation, microbial-electrochemical catalytic reduction, oxidative distillation, and chromatographic purification. The filtration acidification and carrier addition in the pretreatment stage effectively ensure the stability of the initial materials, while the subsequent precipitation and catalytic reduction operations deeply remove isotopic impurities such as technetium and molybdenum, as well as radioactive interfering nuclides. This completely solves the problem of low product purity and high impurity residue caused by the single purification step in traditional processes, laying a high-purity raw material foundation for subsequent pharmaceutical preparation.

[0016] 2. This invention introduces microbial-electrochemical catalytic reduction technology into the deep removal process of radiopharmaceutical impurities. Through the synergy of genetically engineered bacteria and electrochemical systems, it achieves highly selective and efficient targeted removal of radionuclides such as technetium and molybdenum. This method completely abandons the traditional passive approach that relies on time decay or physical purging, and transforms into an active, controllable, and efficient bioelectrochemical precision purification. This is not only a paradigm shift in technology, but also significantly shortens the processing time and greatly improves the recovery rate and radionuclides purity of the target product iodine-131. It solves the industry problem that traditional processes cannot achieve both high purity and high recovery rate.

[0017] 3. This invention ensures the final iodine content by integrating sterilization filtration, formulation preparation, and a comprehensive quality analysis system at the refining stage. 131 The sodium chloride solution fully complies with the requirements of the Chinese Pharmacopoeia in terms of radionuclear purity, radiochemical purity, sterility, pyrogen-free status, and limits on chemical impurities. This comprehensive quality control strategy effectively solves the clinical medication safety risks caused by the lack or inadequacy of quality control links in previous radiopharmaceutical preparations, and ensures the batch consistency and clinical applicability of the final product. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the separation and preparation method of the present invention. Detailed Implementation

[0019] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings. It should be noted that the description of these embodiments is for the purpose of helping to understand the present invention, but does not constitute a limitation of the present invention.

[0020] Furthermore, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0021] Please see the appendix Figure 1 This invention discloses a method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste, comprising the following steps:

[0022] The medical radioactive waste liquid obtained after the use of the molybdenum-technetium generator is pretreated, including filtration and acidification. Then, the pretreated solution is subjected to selective precipitation reaction to achieve preliminary decontamination. The pre-purified iodine-containing solution is subjected to microbial-electrochemical catalytic reduction treatment to deeply remove radioactive nuclide impurities. Iodine-131 is then separated and enriched through oxidation and distillation. The enriched product is then purified by chromatography. The purified solution is then sterilized by filtration and formulation preparation. The obtained formulation is subjected to comprehensive quality analysis. After passing the quality test, it is packaged to obtain clinical pharmaceutical grade iodine-131 finished product.

[0023] In one embodiment of the present invention: In the pretreatment step, the raw material solution is filtered using a microporous membrane made of polyethersulfone or mixed cellulose ester with a diameter of 0.22μm-0.45μm to efficiently remove insoluble particulate matter. After filtration, 1mol / L-3mol / L dilute nitric acid is added to adjust the pH of the system to 1-3. At the same time, potassium iodide with a concentration range of 0.1g / L-1.0g / L is added as a carrier. Potassium iodide can maintain the stability of iodine in the solution and prevent premature precipitation of iodide ions. The mixture is stirred at room temperature of 25℃-30℃ for 10min-15min until the potassium iodide is completely dissolved to ensure uniform mixing.

[0024] In one embodiment of the present invention: in the selective precipitation reaction step, a barium nitrate solution with a concentration of 0.05 mol / L to 0.2 mol / L is slowly added dropwise to the pretreatment solution. After stirring for 30 min, a disodium hydrogen phosphate solution with a concentration of 0.02 mol / L to 0.1 mol / L is added. Subsequently, the pH is adjusted to 7.5 to 9.0 using a sodium hydroxide solution with a concentration of 0.1 mol / L to 0.5 mol / L. At the same time, ethylenediaminetetraacetic acid with a concentration of 0.01 mol / L to 0.05 mol / L is added. The complexing agent can complex the residual calcium, magnesium and other metal ions in the solution to prevent them from forming impurities with phosphate and affecting the iodine recovery rate. After standing for 1 h to 2 h, the solution is centrifuged at 3000 rpm to 5000 rpm for 15 min to 20 min. The supernatant is transferred using a sterile pipette to obtain a pre-purified iodine-containing supernatant.

[0025] The core mechanism of the selective precipitation step is that the soluble barium salt added to the solution reacts with the phosphate to form a fine barium phosphate precipitate. During the formation of this precipitate, it can effectively encapsulate and carry away radioactive nuclide impurities in the waste liquid in the form of molybdate, pertechnetate, etc., through adsorption and co-precipitation. At the same time, the added complexing agent ethylenediaminetetraacetic acid can preferentially complex the calcium, magnesium and other macro-metal ions in the solution to prevent them from forming competitive phosphate precipitates, thereby ensuring the selective removal effect of barium phosphate on the target radioactive impurities and achieving the preliminary purification of the iodine-containing supernatant.

[0026] In one embodiment of the present invention: the microbial-electrochemical catalytic reduction treatment is carried out in a bioelectrochemical reactor. The treatment includes: inoculating the iodine-containing supernatant with genetically engineered Shewanella bacteria that have specific reduction capabilities for pertechnetate and iodoxy anions, while controlling the working electrode of the reaction system to be a cathode, maintaining the potential at -0.4V to -0.6V, utilizing the synergistic effect of extracellular electron transfer of microorganisms and electrochemical cathode reduction, interfering radioactive nuclide impurities (such as pertechnetate, molybdate, and iodoxy anions) in the solution are reduced from their high-valence, easily soluble anionic form to low-valence, insoluble precipitates or fixed on the surface of the bacterial cells. The treatment time is 6h-24h. After treatment, the bacterial cells and immobilized impurities are separated and removed using a microporous filter membrane.

[0027] The microbial-electrochemical catalytic reduction process was carried out in a two-chamber bioelectrochemical reactor with a three-electrode system. The preliminarily purified iodine-containing supernatant was transferred to the cathode chamber and inoculated with a suspension of genetically engineered Shewanella bacteria with an OD600 value of 0.5-1.0. This strain was modified to highly express cytochrome c and specific reductase, and has enhanced affinity and reducing ability for impurity anions such as pertechnetate and iodate. The anode and cathode chambers were separated by a proton exchange membrane. The anolyte was 50 mmol / L phosphate buffer. The cathode potential was kept constant at -0.5 V and the temperature was maintained at 30℃-35℃ using an electrochemical workstation, with slow stirring at 50-100 rpm for 12-18 h. After treatment, the solution was cross-flow filtered using a 0.22 μm polyethersulfone microporous membrane to retain and remove the bacterial cells loaded with reduction products, obtaining a deeply purified iodine-containing 131 solution.

[0028] The core mechanism of the microbial-electrochemical catalytic reduction process lies in the fact that genetically engineered Shewanella bacteria, acting as a biocatalyst, utilize the cytochrome c protein network on their cell membrane as a "bionanowire" to effectively capture electrons from the cathode. These electrons are then used by reductases specifically expressed by the bacteria to target and reduce competitive radioactive nuclide impurities in the solution. This process creates a localized, highly reducing microenvironment, enabling precise targeting of specific impurities under mild conditions while avoiding the loss of the target product iodine-131. This provides extremely high-purity raw materials for subsequent processes, effectively preventing the loss of iodine-131.

[0029] In one embodiment of the present invention: in the oxidation and distillation step, after the microbial-electrochemical catalytic reduction process is completed, a 5%-10% hydrogen peroxide solution is slowly added dropwise to the reaction solution at 5%-8% of the solution volume, with the dropwise addition rate controlled at 1mL / min-2mL / min. Meanwhile, 6mol / L concentrated nitric acid is added to maintain the acidity of the system at 1mol / L-3mol / L, so as to fully oxidize iodide ions to elemental iodine. Subsequently, an oil bath is used for heating at a rate of 5℃ / min-10℃ / min to avoid local overheating and loss of iodine volatilization. The solution temperature is raised to 80℃-100℃, and distillation is carried out using high-purity nitrogen gas at a flow rate of 0.5L / min-1.5L / min. The generated iodine vapor is guided to a receiving bottle containing a 0.5%-2% sodium bisulfite absorbent solution, where it is absorbed and reduced to iodide ions.

[0030] Controlling the rate of hydrogen peroxide addition is crucial. Hydrogen peroxide decomposes rapidly under heating and acidic conditions. If added quickly in one go, it may cause local overheating of the solution, generating a large number of bubbles, leading to premature volatilization and loss of iodine, and posing operational safety hazards. Therefore, a slow dropwise addition under mild heating conditions can ensure that the oxidation reaction proceeds smoothly and fully, quantitatively converting iodide ions into elemental iodine, thus creating favorable conditions for subsequent efficient distillation and enrichment.

[0031] In one embodiment of the present invention: in the end-of-pipe purification step, the chromatographic column used is packed with D201 type macroporous strong basic anion exchange resin. The column specifications are 20cm-30cm in length and 1cm-1.5cm in inner diameter. The absorbed and reduced solution is first pretreated by passing it through a 0.22μm filter membrane and then pumped into the chromatographic column. The mobile phase is a phosphate buffer solution prepared by sodium dihydrogen phosphate and disodium hydrogen phosphate in a mass ratio of 1:3-1:5. Before elution, the column needs to be equilibrated with this buffer solution at the same flow rate for 30min-60min until the column efficiency is stable. The elution flow rate is controlled at 1mL / min-3mL / min. The radioactivity intensity of the eluent is monitored online using a radioactivity meter. The fraction with a radioactivity intensity of 80% or more of the peak value is collected. After elution, the column is washed with 2mol / L sodium chloride solution for 30min and then equilibrated with phosphate buffer solution for later use, thereby realizing resin regeneration.

[0032] In one embodiment of the present invention: in the sterilization filtration and preparation steps, the collected iodine-containing fraction is sterilely filtered through a 0.22μm-0.45μm polyethersulfone microporous membrane, and the radioactivity concentration is measured three times in parallel at 20℃-25℃ using a well-type ionization chamber dosimeter to adjust the concentration to 740MBq / mL-3700MBq / mL. Then, a 0.1mol / L-1.0mol / L sodium hydroxide solution, sterile filtered through a 0.22μm membrane, is used to adjust the pH of the solution to 7.0-8.5, yielding iodine […]. 131 The initial sodium chloride solution should be temporarily stored in a sterile container protected from light at 4℃-8℃ for no more than 24 hours.

[0033] Example 1, please refer to the appendix. Figure 1 Pretreatment: Take 500 mL of medical radioactive waste liquid generated by the molybdenum-technetium generator after use, filter it with a 0.45 μm microporous membrane to remove insoluble particulate matter, add dilute nitric acid to the filtrate to adjust the pH to 2.0, add potassium iodide carrier at a concentration of 0.5 g / L, and mix well.

[0034] Selective precipitation: 0.1 mol / L barium nitrate and 0.05 mol / L disodium hydrogen phosphate were added to the pretreatment solution. The pH was adjusted to 8.5 using sodium hydroxide solution. At the same time, 0.03 mol / L ethylenediaminetetraacetic acid was added as a complexing agent. After standing for 1.5 h, the solution was centrifuged at 4000 rpm to obtain a preliminarily purified iodine-containing supernatant.

[0035] Microbial-electrochemical catalytic reduction treatment: The above iodine-containing supernatant was transferred to the cathode chamber of the bioelectrochemical reactor, and a genetically engineered Shewanella suspension with an OD600 value of 0.8 was inoculated. The cathode potential was controlled to be constant at -0.5V, and the temperature was maintained at 32℃ for 16h. After treatment, cross-flow filtration was performed using a 0.22μm polyethersulfone microporous membrane to retain and remove the bacterial cells loaded with reduction products, obtaining a deeply purified iodine-containing 131 solution.

[0036] Oxidation and distillation: 8% hydrogen peroxide solution was added as an oxidant to the deeply purified iodine-containing 131 solution, and nitric acid was added to maintain the acidity at 2 mol / L. The solution was heated to 90°C, and nitrogen gas was passed through at a flow rate of 1.0 L / min for distillation. The iodine vapor was guided to a receiving bottle containing sodium bisulfite absorbent for absorption and reduction.

[0037] End-point purification: The absorbent was passed through a chromatographic column packed with a strong basic anion exchange resin, and eluted with phosphate buffer solution as the mobile phase at a flow rate of 2 mL / min. The main elution peak containing iodine-131 was collected.

[0038] Sterilization filtration and preparation: The fraction was aseptically filtered through a 0.22 μm polyethersulfone membrane. Water for injection was added to the filtrate to adjust the radioactivity concentration to 1850 MBq / mL, and the pH was adjusted to 8.0 using sterile sodium hydroxide solution to obtain iodine. 131 [Initial product of sodium chloride solution]

[0039] Quality Analysis and Packaging: The initial product undergoes quality testing, including radionuclear purity, radiochemical purity, sterility testing, bacterial endotoxin testing, pH value, and chemical impurity content. Once all indicators meet the requirements, it is packaged into sterile glass bottles in a GMPA-level clean environment.

[0040] Performance test results:

[0041] Radioactive purity: Iodine-131 content ≥99.8%, other radionuclides not detected;

[0042] Radiochemical purity: ≥99.2%;

[0043] Iodine-131 recovery rate: ≥90%;

[0044] Chemical impurities: The residual amounts of barium, phosphate, etc., are all below the pharmacopoeia limits;

[0045] Sterility and endotoxins: Meets pharmacopoeia standards.

[0046] Stability: After being placed at 25℃ for 30 days, no significant changes were observed in any of the indicators.

[0047] Example 2, please refer to the appendix. Figure 1 Pretreatment: Take 500 mL of medical radioactive waste liquid, filter it, adjust the pH to 1.5, and add potassium iodide carrier with a concentration of 0.8 g / L.

[0048] Selective precipitation: Add 0.15 mol / L barium nitrate and 0.08 mol / L disodium hydrogen phosphate, adjust the pH to 7.5, add 0.04 mol / L ethylenediaminetetraacetic acid, let stand for 2 hours, and then centrifuge.

[0049] Microbial-electrochemical catalytic reduction treatment: The preliminarily purified iodine-containing supernatant was transferred to the cathode chamber of the bioelectrochemical reactor and inoculated with a genetically engineered Shewanella suspension with an OD600 value of 1.0. The cathode potential was controlled to be constant at -0.45V and the temperature was maintained at 35℃ for 12 hours. After treatment, the bacterial cells and immobilized impurities were separated and removed through a 0.22μm microporous membrane system to obtain a deeply purified iodine-containing 131 solution.

[0050] Oxidation and distillation: 10% hydrogen peroxide solution was added to the deeply purified iodine-131-containing solution, and nitric acid was added to maintain the acidity of the system at 1.5 mol / L. The solution was heated to 85°C and distilled with nitrogen gas at a flow rate of 0.8 L / min. The iodine vapor was absorbed and reduced by 1.5% sodium bisulfite absorbent.

[0051] End-stage purification: chromatographic elution flow rate 1.5 mL / min, buffer pH 8.5.

[0052] Sterilization filtration and preparation: Adjust the radioactivity concentration to 3000 MBq / mL and the pH to 7.5.

[0053] Quality Analysis and Packaging: The initial product undergoes quality testing, including radionuclear purity, radiochemical purity, sterility testing, bacterial endotoxin testing, pH value, and chemical impurity content. Once all indicators meet the requirements, it is packaged into sterile glass bottles in a GMPA-level clean environment.

[0054] Performance test results:

[0055] Radioactive purity: ≥99.95%;

[0056] Radiochemical purity: ≥99.2%;

[0057] Iodine-131 recovery rate: ≥90%;

[0058] Chemical impurities: Meets pharmacopoeia requirements;

[0059] Sterility and endotoxins: Pass;

[0060] Stability: No change within 30 days.

[0061] Comparison ratio, ingredients and steps:

[0062] Traditional simple distillation method is used, eliminating the need for multi-stage purification:

[0063] Pretreatment: Take 500 mL of medical radioactive waste liquid directly, filter it, and adjust the pH to 2.0 without adding any carrier.

[0064] Simple distillation: Add 5% hydrogen peroxide and nitric acid with an acidity of 1 mol / L to the waste liquid, heat to 80°C, and directly distill by passing nitrogen gas at a flow rate of 1.0 L / min. Iodine vapor is absorbed by sodium hydroxide solution.

[0065] Rough purification: After simple filtration, the radioactivity concentration of the absorption solution was adjusted to 2000 MBq / mL and the pH to 8.0.

[0066] Quality analysis: Only basic radioactivity testing was performed; no comprehensive quality control was conducted.

[0067] Performance test results:

[0068] Radioactive purity: Iodine-131 accounted for only 95.2%, and impurities such as technetium-99m (2.1%) and molybdenum-99 (1.5%) were detected;

[0069] Radiochemical purity: ≤90.3%;

[0070] Iodine-131 recovery rate: ≤60%;

[0071] Chemical impurities: Barium, phosphate, and other residues exceeded the standard;

[0072] Sterility and Endotoxins: The bacterial endotoxin test was unsatisfactory.

[0073] Stability: After being placed at 25°C for 7 days, precipitation and radioactive decay occurred.

[0074] Examples 1 and 2, through a multi-stage synergistic purification process including pretreatment, selective precipitation, microbial-electrochemical catalytic reduction, oxidative distillation, and chromatographic purification, achieved high radionuclear purity, high radiochemical purity, and high recovery rate. Furthermore, comprehensive quality control ensured that the product met pharmacopoeia standards. In contrast, the comparative example used a traditional simple distillation method, which involved a single purification step, resulting in low purity, high impurities, poor recovery rate, and failure to meet sterility and endotoxin standards. This fully demonstrates the significant progress of this invention in improving product purity, yield, safety, and batch consistency.

[0075] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make possible changes and modifications without departing from the spirit and scope of the present invention. Therefore, any modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention shall fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste, comprising a separation and preparation method, characterized in that, The separation and preparation method includes the following steps: The medical radioactive waste liquid obtained after the use of the molybdenum-technetium generator is pretreated, including filtration and acidification. Then, the pretreated solution is subjected to selective precipitation reaction to achieve preliminary decontamination. The pre-purified iodine-containing solution is subjected to microbial-electrochemical catalytic reduction treatment to deeply remove radioactive nuclide impurities. Iodine-131 is then separated and enriched through oxidation and distillation. The enriched product is then purified by chromatography. The purified solution is then sterilized by filtration and formulation preparation. The obtained formulation is subjected to comprehensive quality analysis. After passing the quality test, it is packaged to obtain clinical pharmaceutical grade iodine-131 finished product.

2. The method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste according to claim 1, characterized in that: In the pretreatment step, the raw material liquid is filtered with a microporous membrane to remove insoluble particulate matter. Then, dilute nitric acid is added to adjust the pH of the system to 1-3, and potassium iodide with a concentration range of 0.1g / L-1.0g / L is added as a carrier and mixed evenly.

3. The method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste according to claim 2, characterized in that: In the selective precipitation reaction step, barium nitrate at a concentration of 0.05 mol / L to 0.2 mol / L is added to the pretreatment solution as a soluble barium salt and disodium hydrogen phosphate at a concentration of 0.02 mol / L to 0.1 mol / L as a phosphate. The pH is adjusted to 7.5 to 9.0 using sodium hydroxide solution at a concentration of 0.1 mol / L to 0.5 mol / L. At the same time, ethylenediaminetetraacetic acid at a concentration of 0.01 mol / L to 0.05 mol / L is added as a complexing agent. After standing for 1 to 2 hours, the precipitate is removed by centrifugation to obtain a pre-purified iodine-containing supernatant.

4. The method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste according to claim 3, characterized in that: The microbial-electrochemical catalytic reduction treatment is carried out in a bioelectrochemical reactor. The treatment includes: inoculating the iodine-containing supernatant with genetically engineered Shewanella bacteria that have specific reduction capabilities for pertechnetate and iodooxy anions, while controlling the working electrode of the reaction system to be a cathode, maintaining the potential at -0.4V to -0.6V, utilizing the synergistic effect of extracellular electron transfer of microorganisms and electrochemical cathode reduction, the interfering radioactive nuclide impurities in the solution are reduced from their high-valence, easily soluble anionic form to low-valence, insoluble precipitates. The treatment time is 6h-24h. After treatment, the bacterial cells and immobilized impurities are separated and removed using a microporous filter membrane.

5. The method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste according to claim 4, characterized in that: In the oxidation and distillation steps, after the microbial-electrochemical catalytic reduction process is completed, a 5%-10% hydrogen peroxide solution is added to the reaction solution as an oxidant, and nitric acid is added to maintain the acidity of the system at 1 mol / L-3 mol / L to oxidize iodide ions to elemental iodine. Subsequently, the solution is heated to 80℃-100℃ and distilled with nitrogen gas at a flow rate of 0.5L / min-1.5L / min. The generated iodine vapor is guided to a receiving bottle containing a 0.5%-2% sodium bisulfite absorbent solution and is absorbed and reduced.

6. The method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste according to claim 5, characterized in that: In the final purification step, the absorbed and reduced solution is passed through a chromatographic column packed with a strong basic anion exchange resin, and eluted using a phosphate buffer solution with a pH adjusted to 8-10 as the mobile phase at a flow rate of 1 mL / min-3 mL / min. The main elution peak fraction containing iodine-131 is collected.

7. The method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste according to claim 6, characterized in that: In the sterilization filtration and preparation steps, the collected iodine-containing fraction is sterilely filtered through a 0.22μm-0.45μm polyethersulfone microporous membrane. Water for injection is added to the filtrate to adjust the radioactivity concentration to 740MBq / mL-3700MBq / mL, and the pH is adjusted to 7.0-8.5 using a sterile 0.1mol / L-1.0mol / L sodium hydroxide solution to obtain iodine […]. 131 [Initial product of sodium chloride solution] 8. The method for separating and preparing clinical pharmaceutical grade iodine-131 from medical radioactive waste according to claim 7, characterized in that: In the aforementioned quality analysis and dispensing steps, iodine [ 131 The initial sodium chloride solution underwent quality testing, including testing for the use of high-purity germanium. Its radionuclear purity was determined by energy dispersive spectroscopy, and its radiochemical purity was determined by high performance liquid chromatography-radioactive detector coupled with a radioactive detector. It was also subjected to sterility testing by membrane filtration, bacterial endotoxin testing by gel electrophoresis, pH measurement, and chemical impurity content testing by atomic absorption spectrometry. After all indicators met the requirements, it was dispensed into sterile and pyrogen-free glass bottles and sealed in a GMP-compliant Class A clean environment.

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