CN112156194A - Removing method177Method for endotoxin in Lu solution - Google Patents

Removing method177Method for endotoxin in Lu solution Download PDF

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Publication number
CN112156194A
CN112156194A CN202011047931.9A CN202011047931A CN112156194A CN 112156194 A CN112156194 A CN 112156194A CN 202011047931 A CN202011047931 A CN 202011047931A CN 112156194 A CN112156194 A CN 112156194A
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solution
endotoxin
resin
dga
nitric acid
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CN112156194B (en
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杨宇川
卓连刚
彭述明
钱达志
熊晓玲
岳海东
陈琪萍
王关全
党羽峰
魏洪源
涂俊
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Institute of Nuclear Physics and Chemistry China Academy of Engineering Physics
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Institute of Nuclear Physics and Chemistry China Academy of Engineering Physics
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Abstract

The invention provides a method for removing177A process for endotoxin in Lu solution comprising the steps of: (1) according to the initiation177Adding a nitric acid solution into the Lu solution according to the concentration and volume parameters of acid in the Lu solution to enable the concentration of the nitric acid in the solution to be more than 1M; (2) the flow rate of 0.1-2.0 BV/min is used to treat the mixture obtained in step (1)177Injecting the Lu solution into a resin column filled with DGA resin for leaching; the volume of DGA resin in the resin column is 0.2-2.0 cm3(ii) a (3) Injecting sterile water for injection into the resin column in the step (2) at the flow rate of 0.1-2.0 BV/min until the specified volume is reached; (4) and (4) injecting dilute hydrochloric acid into the resin column in the step (3) at the flow rate of 0.1-2.0 BV/min for elution, wherein the concentration of the dilute hydrochloric acid is 0.01-0.5M, filtering the effluent through a 0.02 mu M filter membrane, and collecting the filtrate, wherein the obtained filtrate is the endotoxin-removing filtrate177Lu solution. After treatment by the process of the invention177The Lu product has the advantages of high radiochemical purity, metal impurities and specific activity, and is in good accordance with medical use177Lu requirements.

Description

Removing method177Method for endotoxin in Lu solution
Technical Field
The invention belongs to the technical field of preparation of medicinal radioactive isotopes, and relates to a radioactive nuclide without endotoxin177Research on Lu, in particular to preparation177In-process removal of Lu177Method for endotoxin in Lu solution.
Background
177Lu radionuclides can be used for production177Lu labeled targeted drugs have achieved remarkable effects in the treatment of various tumors in recent years.177There are two main species of Lu nuclides: ' Carrier177Lu (direct production) "and" Carrier-free177Lu (indirect method of production) ". The clinical application mainly uses the carrier-free177Lu, in particular using monoclonal antibodies and polypeptides as carriers177Lu nuclide tumor treatment field. With a carrier177Lu is rarely used in clinic, but has a good prospect in bone metastasis tumor pain medicines.
177Lu nuclide is generally used for producing injection radiopharmaceuticals, and the endotoxin level needs to be controlled according to the general quality requirements of production raw materials of the injection radiopharmaceuticals. The control of the endotoxin level can be carried out during the production process,Endotoxin can also be removed by some endotoxin removal method after the end of production. Production of177The Lu process is complex, involves many processes (including target preparation, irradiation, target breaking, dissolution, purification, split charging, packaging, etc.), also involves a complex shielding and ventilation system for high radioactive operation, and needs to ensure that the whole production process is in a sterile environment. Namely, the current process flow is required to be ensured177The endotoxin level in Lu solution is not realistic from the economic cost and technical requirements, so that the endotoxin level in Lu solution is obtained177Effective removal of endotoxin from Lu solution is a more economical way.
Adsorption of endotoxin in solution with porous material has been a common method in the past, but because of the porous material177Lu nuclide belongs to high-valence metal positive ions and is easily adsorbed by a porous material, so that common activated carbon, molecular sieve, pottery clay, conventional chromatography and the like cannot be used, the requirement on an adsorbing material is extremely high, and a higher requirement is provided for an endotoxin removing method. The high temperature dry heat method may cause leakage of highly radioactive solvents causing environmental emissions and radiation safety problems. Chromatography uses an elution mobile phase with a complex composition and requires a series of process steps to remove impurities introduced by the mobile phase after removal of endotoxin. Ultrafiltration membranes require high-speed centrifuges, require special shielded fields for highly radioactive solution operations, and are prone to adsorbing large amounts of radioactive positive ions.177Lu ions are precipitated or formed into a colloid under an alkaline condition, so that an alkaline soaking method cannot be used. The only conventional way of removing endotoxin is by acid soaking, but the acid soaking method is generally used for the treatment of the surface of the container, and the applicant of the present patent found in the previous studies that: the acid soaking method can destroy a part of the raw material177Endotoxin in Lu solution, but even when it takes a long time (>10h) Can not be stably and reliably used for producing the injection sold on the market at present177Lu solution endotoxin requirement (20 EU/mL), and the additional acid still needs a series of subsequent process to remove. Therefore, the existing methods have obvious problems, and it is urgent to provide an unconventional and special purpose177A method for removing endotoxin in Lu solution, which aims to solve the problem in the prior art.
Disclosure of Invention
The present invention is to solve the above technical problems and to provide a method for removing177Method for endotoxin in Lu solution, so that177The endotoxin level of Lu solution meets the requirement of raw materials for producing injection, and has the advantages of simple and easy operation, controllable operation, easily obtained materials, small heat chamber occupation area, and treatment by the method177The technical indexes required in the Lu product including key indexes such as radiochemical purity, metal impurities, specific activity and the like can well accord with medical use177Lu requirements.
Specifically, the following are mentioned: the methods described herein are "carrier-free177Lu 'and' carriers177Lu "general endotoxin removal method, hereinafter unless specified otherwise, no distinction is made.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
removing method177A process for endotoxin in Lu solution, said process comprising the steps of:
(1) according to the initiation177Acid concentration and volume parameters in Lu solution, starting with177Adding a certain amount of nitric acid solution into the Lu solution to ensure that the concentration of nitric acid in the solution is more than 1M;
(2) the flow rate of 0.1-2.0 BV/min is used to treat the mixture obtained in step (1)177Injecting the Lu solution into a resin column filled with DGA resin for leaching; the volume of DGA resin in the resin column is 0.2-2.0 cm3Preferably 0.4 to 1.0cm3；
(3) Injecting sterile water for injection into the resin column in the step (2) at the flow rate of 0.1-2.0 BV/min until the specified volume is reached;
(4) injecting dilute hydrochloric acid into the resin column in the step (3) at the flow rate of 0.1-2.0 BV/min for elution, wherein the concentration of the dilute hydrochloric acid is 0.01-0.5M, preferably 0.04-0.05M, filtering the eluted effluent through a 0.02 mu M filter membrane, collecting filtrate until the specified volume is stopped, and obtaining the filtrate which is the' endotoxin-removing filtrate177Lu solution ".
The above-described process of the present invention employs the principle of using DGA resin pairs177Adsorption of Lu in high concentration nitric acid, complete washing and displacement of adsorbed small amount of nitric acid solvent by sterile water for injection and removal of endotoxin, followed by elution with dilute hydrochloric acid177Lu product. After being treated177Other required technical indexes in the Lu product, including radiochemical purity, metal impurities, specific activity and other key indexes, all meet medical requirements177Lu requirements. Although the prior DGA resins have been used for the study of some radionuclides, the method of the present invention has undergone a great deal of research and no report is made in the prior art on how to use DGA resins for the study of some radionuclides177When endotoxin in Lu is removed, the invention provides a good method for removing endotoxin by DGA resin177The method for removing endotoxin in Lu has remarkable effect, and other methods cannot effectively remove endotoxin in the process of searching by the inventor177Endotoxin in Lu.
Further, the initiation in step (1)177The acid in the Lu solution is hydrochloric acid or nitric acid, and the concentration and the volume of the acid are not limited. The concentration and volume of the acid described herein are not limited and refer to the starting177The acid concentration and volume in the Lu solution can be any parameters and can be treated according to the method of the invention; when starting177When the concentration of nitric acid in the Lu solution is more than 1M, the subsequent treatment steps are directly carried out without adding nitric acid solution.
Further, after adding a nitric acid solution in the step (1)177The concentration of the nitric acid solution in the Lu solution is 2-5M, and the nitric acid solution is added177The total volume of the Lu solution is not limited, and preferably 2-50 mL.
Further, the initiation in step (1)177Lu solution as carrier177Lu or without carrier177Lu, its total activity is unlimited; when starting177Lu solution as carrier177Lu, of which177Lu andnatthe total chemical content of Lu (stable Lu nuclide) is not higher than the limit sample loading amount of the resin column packing.
Further, the initiation in step (1)177Lu solution is produced under non-sterile conditions177Lu solution, the dilute hydrochloric acid in step (4) is subjected to aseptic processing.
Further, the DGA resin in step (2) may refer to a resin obtained by supporting a DGA-based organic compound on a base resin.
Further, the DGA-based organic compound includes TODGA or TEHDGA. Wherein TODGA is N, N, N ', N' -tetracotyldiglycolamide, and wherein TEHDGA is N, N, N ', N' -tetrackis-2-ethylhexyldiglycolamide.
Further, the base resin includes resin materials of different materials capable of supporting the DGA-based organic compound, including but not limited to silica gel materials, silica materials, acrylic polymers, or styrene polymers.
Preferably, the flow rates in the steps (2), (3) and (4) are all 0.3-1 BV/min.
Preferably, the designated volume of the sterile water for injection in step (3) is 3-15 BV, preferably 6-9 BV, and the injection volume of the dilute hydrochloric acid solution in step (4) is 2-15 BV, preferably 6-9 BV.
The invention has the following beneficial effects: the method of the invention provides a simple and easy removal177A method for endotoxin in Lu solution; after being treated by the method of the invention177Other required technical indexes in the Lu product, including radiochemical purity, metal impurities, specific activity and other key indexes, all meet medical requirements177Lu requirement and the whole process flow177The recovery rate of Lu is as high as 92-99%.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more clearly understood, the present invention is described in detail below with reference to the following embodiments, and it should be noted that the following embodiments are only for explaining and illustrating the present invention and are not intended to limit the present invention. The invention is not limited to the embodiments described above, but rather, may be modified within the scope of the invention.
Example 1
Initiation of177Lu solution: carrier-free process for production of non-sterile products177Lu solution, total activity 1.61Ci, volume 1.6mL, solvent 0.05 MHCl.
DGA resin column parameters: the resin column is made of quartz and is filled with commercial general-purpose DGA resin (manufactured by Triskem, with a composition of TODGA loaded with acrylic polymer) 0.4cm3Two ends of the filter are connected with a medical sterile PE peristaltic pump tube, and the outlet of the peristaltic pump tube is connected with a 0.02 mu m filter membrane. The solution is placed in a grade A clean shielding box and subjected to ultraviolet sterilization for 1h before the process flow is carried out, and is washed by 25mL of sterile water for injection in advance.
Step a: starting from above177Bottle of Lu solution was charged with 3.2mL of 3MHNO3And (4) uniformly mixing.
Step b: the above solution was injected into a DGA resin column at a flow rate of 0.4mL/min, and stopped after the injection was completed.
Step c: 3 mL of sterile water for injection was injected into the above resin column at a flow rate of 0.4 mL/min.
Step d: 0.05M hydrochloric acid solution was injected into the above resin column at a flow rate of 0.4mL/min, and the eluate was filtered through a 0.02 μ M filter, and 2mL of filtrate was collected in a 10mL vial.
Step e: adding a rubber plug and an aluminum cover, and pressing a cover. The activity tested was 1.57 Ci. (recovery rate was 97.5%).
177Lu ions are adsorbed by flow path materials such as pipelines, resin columns, filter membranes and the like in the production process, so that certain activity loss is caused in the production process (the recovery rate is generally 92-99% in actual production). The loss is the conventional loss in the column purification production process, and the use of the product per se is not influenced. The same applies below.
Tests show that the endotoxin in the product (about) is 3.8EU/mL, and meets the production requirement of injection (A)<20 EU/mL). The test results show that: the method of the invention can well remove the production under the non-aseptic condition177Endotoxin in Lu solution. In addition, in general, large amounts are easily caused for removing endotoxin177Lu loss, which is unacceptable, the process of the invention removes endotoxinsIn the process also well give consideration to177The recovery rate of Lu is as high as 97.5%.
Example 2
Initiation of177Lu solution: carrier-free process for production of non-sterile products177Lu solution, total activity 2.73Ci, volume about 45mL, solvent 3.5MHNO3。
DGA resin column parameters: the resin column is made of quartz, and is filled with commercially available branched DGA resin (TeHDGA supported by acrylic polymer, produced by Triskem Co., Ltd.) of 0.4cm3Two ends of the filter are connected with a medical sterile PE peristaltic pump tube, and the outlet of the peristaltic pump tube is connected with a 0.02 mu m filter membrane. The column was UV-sterilized in a class A clean shielded chamber for 1h prior to running the protocol, and previously rinsed with 25mL sterile water for injection, and equilibrated with 3.5M nitric acid (5 mL).
Step a: the above solution was injected into a DGA resin column at a flow rate of 0.4mL/min, and stopped after the injection was completed.
Step b: 3 mL of sterile water for injection was injected into the above resin column at a flow rate of 0.4 mL/min.
Step c: 0.05M hydrochloric acid solution was injected into the above resin column at a flow rate of 0.4mL/min, and the eluate was filtered through a 0.02 μ M filter, and 2.7mL of filtrate was collected in a 10mL vial.
Step e: adding a rubber plug and an aluminum cover, and pressing a cover. The activity tested was 2.71 Ci. (recovery rate 99.3%)
Through tests, the endotoxin in the product is (about) 1.1EU/mL, and meets the production requirement of injection (<20 EU/mL).
Example 3
Initiation of177Lu solution: carrier produced under non-aseptic conditions177Lu solution with a total activity of 2.18Ci (original target)176Lu (76.4% enriched target) 0.6mg, volume 1.5mL, solvent 1 MHCl.
DGA resin column parameters: the resin column is made of quartz, and is filled with DGA resin (self-made resin, and comprises acrylic polymer loaded TEHDGA)0.8cm3Two ends of the filter are connected with a medical sterile PE peristaltic pump tube, and the outlet of the peristaltic pump tube is connected with a 0.02 mu m filter membrane. The process flow is already subjected to A-level cleaningThe shielded chamber was UV-sterilized for 1h, and previously rinsed with 25mL sterile water for injection, and the resin column equilibrated with 2.0M nitric acid (5 mL).
Step a: starting from above177Bottle of Lu solution was charged with 3.0mL of 2MHNO3And (4) uniformly mixing.
Step b: the above solution was injected into a DGA resin column at a flow rate of 1.0mL/min, and was stopped after the injection was completed.
Step c: 5mL of sterile water for injection was injected into the above resin column at a flow rate of 0.5 mL/min.
Step d: 0.04M hydrochloric acid solution was injected into the above resin column at a flow rate of 0.5mL/min, and the eluate was filtered through a 0.02 μ M filter, and 4.8mL of filtrate was collected in a 10mL vial.
Step e: adding a rubber plug and an aluminum cover, and pressing a cover. The activity was tested at 2.09Ci (95.8% recovery).
Tests show that the endotoxin in the product is (about) 0.2EU/mL, which meets the production requirement of injection (less than or equal to 20 EU/mL).
It should be noted that in examples 1 to 3, the difference in endotoxin level in the product is not due to the instability of the method of the present invention, but due to two main reasons, firstly, the endotoxin level of each batch of raw material liquid is different because the raw material liquid is produced under non-aseptic conditions; secondly, the endotoxin level in the product treated by the method is far lower than the limit (less than or equal to 20EU/mL), and the radioactive endotoxin test is the test after dilution, so the quality test precision cannot be accurate at the lower endotoxin content. The same applies below.
Example 4
Initiation of177Lu solution: carrier-free process for production of non-sterile products177Lu solution, total activity 4.15Ci, volume about 40mL, solvent 3.2MHNO3In order to compare the endotoxin removing effect with that of the comparative example, 3 additional bacterial endotoxin working standards (80 EU/lot, produced by the Chinese food and drug testing institute) were added.
DGA resin column parameters: the resin column is made of quartz, and is filled with DGA resin (self-made resin, and comprises acrylic polymer loaded TEHDGA)0.6cm3At both endsConnecting with a medical sterile PE peristaltic pump tube, wherein the outlet of the peristaltic pump tube is connected with a 0.02 mu m filter membrane. The column was UV-sterilized in a class A clean shielded chamber for 1h prior to running the protocol, and previously rinsed with 25mL sterile water for injection, and equilibrated with 3.2M nitric acid (5 mL).
Step a: the above was initiated at a flow rate of 0.5mL/min177The Lu solution was injected into the DGA resin column and stopped after the injection was completed.
Step b: 5mL of sterile water for injection was injected into the above resin column at a flow rate of 0.6 mL/min.
Step c: 0.05M hydrochloric acid solution was injected into the above resin column at a flow rate of 0.5mL/min, and the eluate was filtered through a 0.02 μ M filter, and 4.0mL of filtrate was collected in a 10mL vial.
Step d: adding a rubber plug and an aluminum cover, and pressing a cover. The activity tested was 4.10 Ci. (recovery rate 98.8%)
The endotoxin in the product is tested. (about) 1.9EU/mL, meeting the production requirement of injection (<20 EU/mL).
Comparative example 1
Initiation of177Lu solution: carrier-free process for production of non-sterile products177Lu solution, total activity 1.35Ci, volume about 40mL, solvent 3.2MHNO3To compare the endotoxin removal effect of example 4, 3 additional working standards of bacterial endotoxin (80 EU/lot, produced by the Chinese food and drug testing institute) were added.
DGA resin column parameters: the resin column is made of quartz, and is filled with DGA resin (self-made resin, and comprises acrylic polymer loaded TEHDGA)0.6cm3The column was UV-sterilized in a class A clean shielded chamber for 1h prior to running the protocol, and previously rinsed with 25mL sterile water for injection, and equilibrated with 3.2M nitric acid (5 mL).
Step a: the above was initiated at a flow rate of 0.5mL/min177The Lu solution was injected into the DGA resin column and stopped after the injection was completed.
Step b: sterile water for injection (0.5 mL, which is insufficient in the amount of water for sterile injection and causes incomplete endotoxin washing) was injected into the above resin column at a flow rate of 0.5 mL/min.
Step c: 0.05M hydrochloric acid solution was injected into the above resin column at a flow rate of 0.5mL/min, and the eluate was filtered through a 0.02 μ M filter, and 3.8mL of filtrate was collected in a 10mL vial.
Step d: adding a rubber plug and an aluminum cover, and pressing a cover. The activity tested was 1.30 Ci. (recovery rate 96.3%)
The endotoxin in the product was tested to be 31EU/mL, which is higher than the requirement for injectable drug manufacture (. ltoreq.20 EU/mL), indicating that the conditions in this comparative example are not effective in removing endotoxin.
In this comparative example, the volume rinsed out of the sterile book for injection was mainly reduced (step b of this comparative example). The aseptic water for injection rinsing is used for removing endotoxin adsorbed and stained on a flow path (comprising a pipeline, a resin column and a filter membrane) in the loading process. This step reduces the amount of sterile water for injection, and thus endotoxin cannot be removed effectively.
Comparative example 2
Initiation of177Lu solution: carrier produced under non-aseptic conditions177Lu solution with a total activity of 1.55Ci (original target)176Lu (76.4% enriched target) 0.6mg), volume about 1.1 mL, solvent 0.05 MHCl.
DGA resin column parameters: the resin column is made of quartz, and is filled with DGA resin (self-made resin, and comprises acrylic polymer loaded TEHDGA)0.10cm3(reduce the amount of column packing, unable to effectively adsorb Lu), the column was placed in a class A clean shielded box and subjected to UV sterilization for 1h prior to the process flow, and previously rinsed with 25mL sterile water for injection, and the column was equilibrated with 1.2M nitric acid (5 mL).
Step a: starting from above177Bottle of Lu solution was charged with 3.0mL of 2MHNO3And (4) uniformly mixing.
Step b: the above was initiated at a flow rate of 0.5mL/min177The Lu solution was injected into the DGA resin column and stopped after the injection was completed.
Step c: 5mL of sterile water for injection was injected into the above resin column at a flow rate of 0.5 mL/min.
Step d: 0.05M hydrochloric acid solution was injected into the above resin column at a flow rate of 0.5mL/min, and the eluate was filtered through a 0.02 μ M filter, and 4.0mL of filtrate was collected in a 10mL vial.
Step e: adding a rubber plug and an aluminum cover, and pressing a cover. The activity was tested at 1.03Ci (66.5% recovery).
The endotoxin in the product is tested. (about) 1.9EU/mL, meeting the production requirement of injection (<20 EU/mL).
In this comparative example, the DGA resin column packing volume was mainly reduced. When the sample liquid is a carrier177Lu, because of its total chemical mass (0.6mg, inclusive)176Lu and177lu) is so high that it cannot effectively retain Lu element during loading. Although endotoxin in the product is satisfactory (the product can be used in the production of injection). However, the comparative method has an excessively low recovery rate and very high loss in production, which is unacceptable for production.

Claims (10)

1. Removing method177A process for endotoxin in Lu solution, which comprises the steps of:
(1) according to the initiation177Acid concentration and volume parameters in Lu solution, starting with177Adding a certain amount of nitric acid solution into the Lu solution to ensure that the concentration of nitric acid in the solution is more than 1M;
(2) the flow rate of 0.1-2.0 BV/min is used to treat the mixture obtained in step (1)177Injecting the Lu solution into a resin column filled with DGA resin for leaching; the volume of DGA resin in the resin column is 0.2-2.0 cm3Preferably 0.4 to 1.0cm3；
(3) Injecting sterile water for injection into the resin column in the step (2) at the flow rate of 0.1-2.0 BV/min until the specified volume is reached;
(4) injecting dilute hydrochloric acid into the resin column in the step (3) at the flow rate of 0.1-2.0 BV/min for elution, wherein the concentration of the dilute hydrochloric acid is 0.01-0.5M, preferably 0.04-0.05M, filtering the eluted effluent through a 0.02 mu M filter membrane, and collecting filtrate, wherein the obtained filtrate is the endotoxin-removing filtrate177Lu solution ".
2. Removal according to claim 1177Lu solution inA method for producing endotoxin, characterized in that the starting in the step (1)177The acid in the Lu solution is hydrochloric acid or nitric acid, and the concentration and the volume of the acid are not limited; when starting177When the concentration of nitric acid in the Lu solution is more than 1M, the nitric acid solution does not need to be added.
3. Removal according to claim 1177The method for endotoxin in Lu solution is characterized in that nitric acid solution is added in the step (1) and then177The concentration of the nitric acid solution in the Lu solution is 2-5M, and the nitric acid solution is added177The total volume of the Lu solution is not limited, and preferably 2-50 mL.
4. Removal according to claim 1177Process for the endotoxin of Lu solution, characterized in that the starting in step (1)177Lu solution as carrier177Lu or without carrier177Lu, its total activity is unlimited; when starting177Lu solution as carrier177Lu, of which177Lu andnatthe total chemical content of Lu is not higher than the limit sample loading of the resin column packing.
5. Removal according to claim 1177Process for the endotoxin of Lu solution, characterized in that the starting in step (1)177Lu solution is produced under non-sterile conditions177Lu solution, the dilute hydrochloric acid in step (4) is subjected to aseptic processing.
6. Removal according to claim 1177The method for endotoxin in Lu solution, wherein the DGA resin in the step (2) is a resin obtained by loading a DGA-based organic compound on a base resin.
7. Removal according to claim 6177A process for the endotoxin of Lu solution wherein said DGA-based organic compound comprises TODGA or TEHDGA.
8. According to the rightRemoval according to claim 6177The method for endotoxin in Lu solution is characterized in that the substrate resin is resin materials which are different in material and can load DGA organic compounds, and the resin materials comprise silica gel materials, silica materials, acrylic polymers or styrene polymers.
9. Removal according to claim 1177The method for removing endotoxin in the Lu solution is characterized in that the flow rates in the steps (2), (3) and (4) are all 0.3-1 BV/min.
10. Removal according to claim 1177The method for removing endotoxin in the Lu solution is characterized in that the specified volume of the sterile water for injection in the step (3) is 3-15 BV, preferably 6-9 BV; and (4) injecting the dilute hydrochloric acid solution into the container at a volume of 2-15 BV, preferably 6-9 BV.
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CN114836623A (en) * 2021-12-31 2022-08-02 中国工程物理研究院核物理与化学研究所 A kind of 160 Gd、 161 Tb、 161 Dy synchronous separation method
CN115240893A (en) * 2022-07-20 2022-10-25 中国核动力研究设计院 On-load body 177 Lu separation and purification method

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