CN114728189A - Method for preventing exposure to anticancer agent - Google Patents

Method for preventing exposure to anticancer agent Download PDF

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CN114728189A
CN114728189A CN202080078466.7A CN202080078466A CN114728189A CN 114728189 A CN114728189 A CN 114728189A CN 202080078466 A CN202080078466 A CN 202080078466A CN 114728189 A CN114728189 A CN 114728189A
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hypochlorous acid
solution
anticancer agent
aqueous solution
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山下智荣子
中岛勇一
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Japan Advanced Corp
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    • AHUMAN NECESSITIES
    • A62LIFE-SAVING; FIRE-FIGHTING
    • A62DCHEMICAL MEANS FOR EXTINGUISHING FIRES OR FOR COMBATING OR PROTECTING AGAINST HARMFUL CHEMICAL AGENTS; CHEMICAL MATERIALS FOR USE IN BREATHING APPARATUS
    • A62D3/00Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances
    • A62D3/30Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances by reacting with chemical agents
    • A62D3/38Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances by reacting with chemical agents by oxidation; by combustion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L9/00Disinfection, sterilisation or deodorisation of air
    • A61L9/14Disinfection, sterilisation or deodorisation of air using sprayed or atomised substances including air-liquid contact processes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2209/00Aspects relating to disinfection, sterilisation or deodorisation of air
    • A61L2209/10Apparatus features
    • A61L2209/13Dispensing or storing means for active compounds
    • A61L2209/132Piezo or ultrasonic elements for dispensing

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Abstract

The present invention provides a method for preventing exposure of an anticancer agent by using a safe hypochlorous acid aqueous solution which does not affect the human body even when sprayed into a space. The present invention relates to a method for preventing exposure to an anticancer agent, and more particularly to a method for preventing exposure to an anticancer agent, which comprises detoxifying at least any one of cyclophosphamide, 6-mercaptopurine, cisplatin, bendamustine, gemcitabine, oxaliplatin, vincristine, Doxorubicin (Doxorubicin), fluorouracil, and paclitaxel.

Description

Method for preventing exposure to anticancer agent
Technical Field
The present invention relates to a method for preventing exposure to an anticancer agent, and more particularly to a method for preventing exposure to an anticancer agent, which comprises detoxifying at least any one of cyclophosphamide, 6-mercaptopurine, cisplatin, bendamustine, gemcitabine, oxaliplatin, vincristine, Doxorubicin (Doxorubicin), fluorouracil, and paclitaxel.
Background
Anticancer agents are agents that inhibit the proliferation of cancer cells and ultimately inhibit their proliferation and cause their death. The mechanism of action is that the infiltration into the target cancer cell causes inhibition of DNA replication or synthesis in the cell, inhibition of microtubule formation (inhibition of cell division), inhibition of intracellular metabolism, control of nutrient supply and blood flow, and the like. Therefore, although anticancer agents act on cancerous cells to cause cell death such as apoptosis, they are highly toxic to normal cells. Therefore, care should be taken in the treatment of the anticancer agent.
Various chemotherapies using anticancer agents have been used to treat various cancers. In the anticancer drug therapy, the dose of each anticancer drug to be used by a patient is determined by a doctor, and a pharmacist dispenses the anticancer drug into a drip container (infusion bag) or the like according to the prescription. When the operation of producing the anticancer agent is further observed in detail, droplets and aerosols of the anticancer agent scattered from injection needles, vials, drops and the like may adhere to the skin of pharmacists and the like, and there is a case of one exposure in which the droplets and aerosols are inhaled from respiratory organs. In addition, there is a secondary exposure to the skin of a pharmacist or the like via a medicine bag, a bottle, or the like which is in contact with the scattered droplets of the anticancer agent. In particular, the preparation of anticancer agents is carried out by specialised pharmacists. Therefore, the risk of occupational exposure to anticancer agents by medical staff such as pharmacists and nurses has been pointed out. In particular, there have been reports that medical staff themselves suffer from abortion, leukemia, bladder cancer, and the like due to long-term work. Therefore, medical staff are very important to take measures against exposure to anticancer agents.
Regarding this problem, in a guideline (non-patent document 1) prepared for measures against exposure in cancer drug therapy, it is strongly recommended to perform measures against exposure at the time of transportation and storage of a prepared drug solution and at the time of administration management. In the conventional preparation of anticancer agent, a waterproof apron, a double-layer glove and an activated carbon-containing mask are worn. The preparation of an anticancer agent is carried out in an environment where the scattering of the agent is reduced, such as a biosafety cabinet or a sealed preparation instrument, in which the aerosol generated during the preparation does not flow out to the outside.
In addition, various inventions have been proposed with respect to measures for dealing with exposure to anticancer agents.
The invention according to patent document 1 provides a sheet body that adsorbs urine containing an anticancer agent, and is effective for secondary exposure countermeasures in hospitals such as patients, medical staff, and hospital-related staff by adsorbing urine containing a highly toxic drug such as an anticancer agent and adsorbing a drug in urine.
The invention according to patent document 2 provides a bag body that can reduce the possibility of medical staff accidentally touching a liquid medicine when handling an infusion bag, and can safely and easily administer the medicine.
The invention according to patent document 3 provides a novel method for safely, inexpensively and simply performing a more effective measure for preventing or preventing leakage of dangerous medicines, which have adverse health effects if leaked, from medical administration instruments and medical administration instruments, and a measure for identifying a solution leakage site, a measure for preventing leakage, and a measure for preventing leakage, at a place where a plurality of medicines are administered in combination.
The invention according to patent document 4 provides an anticancer agent-adsorbing sheet that exhibits sufficient effects of adsorbing and holding a highly toxic drug such as an anticancer agent, and further improves the safety of medical staff in a medical environment.
The invention according to patent document 5 provides an infusion tube set and a method of using the same, which effectively reduce the risk of exposure to dangerous drugs such as anticancer agents.
However, the inventions of patent documents 1 to 5 limit the effect of reducing exposure to the prevention of leakage from the appliance, and in practice, environmental pollution is not completely prevented at all.
On page 66 of the above guideline, there is described "caution is given to minimize scattering to the surroundings at the time of excretion" for the treatment of excretion and body fluid of a patient 48 hours after administration of an anticancer agent. For example, if it is possible that both men and women use a western style toilet, men also urinate at the toilet bowl. Flushing is performed after closing the lid of the toilet. On page 68 of the manual, "washing the area where the anticancer agent is scattered with a washing agent (for cleaning)" and "rinsing with water" are repeated a plurality of times as a cleaning procedure when the anticancer agent is scattered. Or in the case of an agent for inactivating an anticancer agent, after wiping, it is impregnated in paper or cloth and wiped, and finally dried. ", sodium hypochlorite solution, sodium hydroxide, etc. are given as examples of the drug, and it was confirmed that 5.25% sodium hypochlorite is effective particularly for some anticancer agents.
Documents of the prior art
Patent document
Patent document 1, Japanese patent laid-open publication No. 2018-126316
Patent document 2 Japanese patent laid-open publication No. 2018-122023
Patent document 3 Japanese patent No. 6117973
Patent document 4 Japanese patent No. 6092445
Patent document 5 Japanese patent laid-open No. 2014-217555
Non-patent document
Non-patent document 1, Japan cancer Care society of general Community, Japan clinical Oncology of public welfare society, Japan clinical Oncology of general Community, and Japan clinical Oncology of general Community, collectively edit the 2015 annual edition of Joint guidelines for Exposure to countermeasures in cancer drug therapy, published by King-Yuan-publishing Co., Ltd., 10/15/2015, pp.66-68
Disclosure of Invention
Technical problems to be solved by the invention
However, in a toilet used by a patient who receives administration of an anticancer agent, it has been confirmed and proven that a trace amount of the anticancer agent contained in urine or excrement is scattered in a space or on the ground, and there is a concern that health may be impaired by indirectly sucking the anticancer agent by a healthy person.
Further, sodium hypochlorite, which is effective for neutralizing an anticancer agent as described above, is a so-called commercially available liquid chlorine bleaching agent, and contains an alkaline agent, and when it is mixed with an acidic detergent, chlorine gas is generated, so that it is dangerous, and "dangerous, do not mix" or the like is shown on a label. The alkaline agent is present in order to prevent decomposition of sodium hypochlorite in a container, but is strongly alkaline, and therefore, it is necessary to wear rubber gloves. Further, it has been pointed out that commercially available liquid chlorine bleaches are toxic due to volatilization and cannot be sprayed into a space. Therefore, in a medical site or a care site, particularly in a case where a trace amount of a drug contained in urine or excrement is apparently scattered in a space or a floor in a toilet used by a patient receiving administration of the drug, there is a concern that a healthy person indirectly takes in the drug and health is impaired.
In view of the above problems, the present invention provides a method for detoxifying an anticancer agent, particularly an alkylating agent, by using a safe aqueous hypochlorous acid solution which does not affect the human body even when sprayed into a space. That is, the present invention is for preventing exposure to an anticancer agent by spraying an aqueous hypochlorous acid solution developed by the applicant.
Means for solving the above technical problems
In order to achieve the above object, the present invention is a method for preventing exposure to an anticancer agent, characterized by comprising spraying a hypochlorous acid aqueous solution toward a subject to be treated or a space in which the subject to be treated is present, thereby detoxifying at least one of cyclophosphamide, 6-mercaptopurine, cisplatin, bendamustine, gemcitabine, oxaliplatin, vincristine, Doxorubicin (Doxorubicin), fluorouracil, and paclitaxel in the anticancer agent. The hypochlorous acid is sprayed by a sprayer which stores the hypochlorous acid aqueous solution and turns the hypochlorous acid aqueous solution into a gaseous or mist state. The spraying may be performed by an ultrasonic spraying device containing an aqueous hypochlorous acid solution. In addition, the pH of the hypochlorous acid aqueous solution is preferably 5.5 to 7.0.
Further, the present invention is characterized in that paclitaxel is detoxified by spraying a hypochlorous acid aqueous solution toward an object to be treated and leaving the solution for 24 hours.
Effects of the invention
According to the method for using an anticancer agent neutralizing agent of the present invention, exposure to an anticancer agent can be prevented safely and efficiently by spraying an aqueous hypochlorous acid solution.
Drawings
Fig. 1 is a diagram showing a state in which a hypochlorous acid aqueous solution is sprayed toward a toilet bowl.
Fig. 2 is a view showing a state in which a hypochlorous acid aqueous solution is sprayed toward a space in which an object to be treated is present.
Detailed Description
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In the drawings, the same components are denoted by the same reference numerals, and redundant description thereof will be omitted. Note that the drawings are exaggerated in some cases for the purpose of understanding the present invention and are not necessarily drawings that are finely illustrated. The technical scope of the present invention is not limited to the specific applications, shapes, sizes, and the like described in the following embodiments. Embodiments of the present invention will be described below with reference to the drawings.
The present inventors have invented a method and an apparatus for producing a slightly acidic hypochlorous acid aqueous solution, which can maintain a pH at a constant value in the range of 5.5 to 7.0 over a long period of time (japanese patent No. 6553955). For details, refer to this patent publication. It is understood that the present invention provides a method for using a neutralizing agent, which uses the hypochlorous acid aqueous solution produced by the above-described production method and sprays the hypochlorous acid aqueous solution into a space, thereby safely and efficiently preventing exposure to an anticancer agent.
[ example 1 ]
The present invention is a method for preventing exposure to an anticancer agent, characterized by detoxifying at least one of cyclophosphamide, 6-mercaptopurine, cisplatin, bendamustine, gemcitabine, oxaliplatin, vincristine, Doxorubicin (Doxorubicin), fluorouracil, and paclitaxel in the anticancer agent by spraying a hypochlorous acid aqueous solution toward a subject to be treated or a space in which the subject to be treated is present. The hypochlorous acid is sprayed by a sprayer which stores the hypochlorous acid aqueous solution and turns the hypochlorous acid aqueous solution into a gaseous or mist state. In addition, the pH of the hypochlorous acid aqueous solution is preferably 5.5 to 7.0.
The alkylating agent is any one of ifosfamide, cyclophosphamide, dacarbazine, temozolomide, nimustine, busulfan, procarbazine, melphalan and ramustine. Alkylating agents are representative agents of cytotoxic anticancer agents. The alkylating agent attaches an aggregate of atoms called alkyl groups to DNA of cancer cells, and binds two pieces of DNA twisted into a helix in an abnormal manner, thereby making it impossible to replicate DNA. When cancer cells continuously want to divide and proliferate in the state where an alkylating group is bonded, DNA is torn, and thus cancer cells die. Among them, cyclophosphamide (Androsan) is one of the most widely used anticancer agents, and can be used alone, in addition to being used as a central agent for CAV therapy for small-cell lung cancer, CHOP therapy for malignant lymphoma, and the like.
The method for producing a hypochlorous acid aqueous solution of the present invention comprises a) a step 1 of supplying raw water to a storage tank; b) a step 2 of supplying an acidic aqueous solution while stirring the raw water in the storage tank to generate a mixed aqueous solution of the raw water and the acidic aqueous solution; c) a 3 rd step of supplying sodium hypochlorite while stirring the aqueous solution mixture in the storage tank to generate a hypochlorous acid aqueous solution after the 2 nd step; d) and a 4 th step of repeating the supply of the acidic aqueous solution and the supply of the sodium hypochlorite in this order after the 3 rd step until the pH of the hypochlorous acid aqueous solution is stably maintained at a constant value within a range of 5.5 to 7.0 for 1 minute or more.
The pH of the hypochlorous acid aqueous solution produced in the above step is controlled to a constant value within a range of 5.5 to 7.0, preferably within a range of 6.0 to 7.0, and more preferably 7.0. That is, since the pH of the hypochlorous acid aqueous solution is approximately the same as the pH of human skin, the influence on the human body is extremely small, and it can be evaluated that the hypochlorous acid aqueous solution is excellent in safety.
Refer to fig. 1. Fig. 1 is a diagram showing a state in which a hypochlorous acid aqueous solution is sprayed toward a toilet bowl. As shown in fig. 1, a sprayer 10 stores a hypochlorous acid aqueous solution 1, and is used by spraying the solution toward a toilet bowl by operating a handle. The sprayer 10 may be a general commercially available sprayer. The hypochlorous acid aqueous solution 1 may be sprayed into a space where an object to be treated is present, or the hypochlorous acid aqueous solution 1 may be sprayed into a space after a non-treated object is treated.
[ example 2 ]
Example 2 will be described in detail. The present applicant has conducted an anticancer drug decomposition performance confirmation test on the hypochlorous acid aqueous solution according to the present application, and thus has described this.
The test was carried out by using SAYEYI pharmaceutical Co., Ltd. (Sandao No. 2 Dimo No. 5 Samo No.1, Osakafu, Ind.) as a test site from 25 to 27 days 9 months and 2019. The test method used LC/MS/MS.
First, for preparation of a test substance solution, a solution prepared by dissolving 5mL of physiological saline in 100mg of cyclophosphamide was used as a stock solution (20mL), 1mL of the stock solution was accurately weighed, and purified water was added thereto to prepare 20mL of the stock solution. Further, 5mL of this liquid was accurately weighed, and 50mL of purified water was added to prepare a test substance solution (100. mu.g/mL).
As the decomposition liquid A, a sample solution (decomposition liquid A) was prepared by adding 1mL of the above test substance solution to 9mL of the hypochlorous acid aqueous solution used in the present application and shaking and mixing the mixture. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times.
As the decomposition solution B, a solution obtained by adding 1mL of the test substance solution to 9mL of the solution diluted 10 times with strongly alkaline electrolytic water (P.W-No.135) and shaking and mixing the mixture was used as a sample solution (decomposition solution B). The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times. Further, it is assumed that a 10-fold diluted solution is used as strongly alkaline electrolyzed water (P.W-No.135) by ordinary cleaning.
Further, as a control solution, a solution obtained by adding 1mL of the test substance solution to 9mL of purified water and shaking and mixing the solution was used as a sample solution. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times.
Each of the decomposed solutions prepared by the above procedure was measured using LC/MS. Then, the decomposition liquids a and B were compared with the control solution to confirm the respective decomposition effects.
As a result of this confirmation test, as shown in table 1, the decomposition liquid B had an average decomposition rate of 4.0% with respect to cyclophosphamide, while the decomposition liquid a had an average decomposition rate of 99.5%.
Test investigation content anticancer drug decomposition Performance confirmation test
Test acceptance number JF19-G047
The test site is SAYEYI pharmaceutical Co Ltd (Osakafu ZUJIN, Sandao 2 Dimo No. 5 Samo No. 1)
Test day, 9 months and 25-27 days in 2019
Test method LC/MS
Sample cyclophosphamide (100 mg Daodasheng for injection)
Decomposition solution A aqueous solution of hypochlorous acid used in the present application
Decomposition liquid B is strong alkaline electrolyzed water (P.W-No.135)
[ TABLE 1 ]
Figure BDA0003638132960000071
The above results demonstrate that the hypochlorous acid aqueous solution used in example 1 decomposes cyclophosphamide at an average of 99% or more.
[ example 3 ]
Example 3 will be described in detail.
Refer to fig. 2. As shown in fig. 2, the ultrasonic spraying device 20 is provided on the floor surface of the space. The ultrasonic atomizing device contains the hypochlorous acid aqueous solution 1 in the tank, and causes the hypochlorous acid aqueous solution 1 to be in the form of a water mist and to be released into the space, thereby neutralizing a small amount of the anticancer agent remaining in the space. Further, the atomized water can be atomized into ultrafine particles having a particle size of about 4 to 5 μm by the force of ultrasonic waves, and can be sprayed softly and efficiently to the corners of the space. Further, since the hypochlorous acid aqueous solution 1 is produced from safe components, it does not affect health even when the sprayed mist is inhaled.
As a method of use, the hypochlorous acid aqueous solution 1 is continuously operated for about 10 to 20 minutes at the beginning to substantially spread over the space. When the hypochlorous acid aqueous solution 1 is distributed throughout the space, the effect of neutralizing the chemical agent is continued by additional spraying.
In example 3, the applicant of the present invention conducted a solution concentration measurement test in accordance with the spraying by the ultrasonic spraying apparatus 20 containing the hypochlorous acid aqueous solution 1, and thus described the test. The test was carried out by using SAYEYI pharmaceutical Co., Ltd. (Sandao No. 2 Dimo No. 5 No.1, Osakafu, Ind.) as a test site from 25 to 26 days in 9 months in 2019. The measurement value (ng/mL) and the detection amount (μ g) of cyclophosphamide as the target drug were confirmed by LC/MS/MS in the test method. After applying 100. mu.g of cyclophosphamide to 10 sampling pieces of 10 cm. times.10 cm, respectively, and completely drying the pieces, 20mL of the hypochlorous acid aqueous solution of the present application was accumulated, left for 1 minute, and the residue of cyclophosphamide on the pieces was measured by wiping the pieces sufficiently with 2 pieces of gauze.
As shown in Table 2, the limit of detection was 0.02/mL in all samples. In addition, the measured value is 1.20-15.7 ng/mL.
Content of Experimental investigation anticancer drug concentration measurement experiment
Test acceptance number: JF19-G019
The test site comprises: yan Ye Yi pharmaceutical Co., Ltd (Osakafu Zhanjin City Sandao No. 2 Dimo No. 5 Bi No. 1)
The test day is as follows: 19-26 days in 7 months in 2019
The test method comprises the following steps: LC/MS
The subject drug: cyclophosphamide is added in an amount of 100. mu.g
[ TABLE 2 ]
Sample numbering Detection limit Measured value
1 0.02 14.50
2 0.02 15.70
3 0.02 6.43
4 0.02 7.73
5 0.02 4.77
6 0.02 4.95
7 0.02 6.59
8 0.02 2.74
9 0.02 1.20
10 0.02 1.33
[ example 4 ]
Example 4 will be described in detail. The present applicant has conducted another test for confirming the decomposition performance of an anticancer agent on the hypochlorous acid aqueous solution according to the present application, and thus has described this.
The test was carried out using SAYEYI pharmaceutical Co., Ltd. (Sandao, Osakafu, Ind. No. 2, No. 5, No. 1) as a test site from 1 month to 9 months to 2 months and 12 days in 2020. The test method used LC/MS/MS.
First, for preparation of a test substance solution, a solution prepared by dissolving 5mL of physiological saline in 100mg of each of 6-mercaptopurine and cisplatin was used as a stock solution (20mL), 1mL of the stock solution was accurately weighed, and purified water was added thereto to prepare 20mL of the stock solution. Then, 5mL of this liquid was weighed accurately, and purified water was added thereto to prepare 50mL of the liquid accurately as a test substance solution (100. mu.g/mL).
As the decomposition liquid A, a sample solution (decomposition liquid A) was prepared by adding 1mL of the above test substance solution to 9mL of the hypochlorous acid aqueous solution used in the present application and shaking and mixing the mixture. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times.
As a control solution, a sample solution was prepared by adding 1mL of the test substance solution to 9mL of purified water and mixing the resulting solution with shaking. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times.
The decomposition liquid a and purified water prepared in the above manner were measured by LC/MC/MS, and the decomposition effect of each test substance was confirmed by comparing the decomposition liquid a with purified water as a control solution. Table 3 below shows the results of the test on 6-mercaptopurine and Table 4 below shows the results of the test on cisplatin.
As a result of this confirmation test, as shown in tables 3 and 4, the average decomposition rates of decomposition liquid A were 95% and 99.2% for 6-mercaptopurine and cisplatin, respectively.
Test investigation content anticancer drug decomposition Performance confirmation test
Test acceptance number JF19-M010, M012
Test site salt Yeyi pharmaceutical Co., Ltd (Osakafu Zujin City three island 2 Dimu No. 5 Fano. 1)
Test day, 1 month 9 days to 2 months 12 days in 2020
Test method LC/MS
6-mercaptopurine and cisplatin as samples
Decomposition solution A aqueous solution of hypochlorous acid used in the present application
[ TABLE 3 ]
Figure BDA0003638132960000091
[ TABLE 4 ]
Figure BDA0003638132960000092
The above results demonstrate that the hypochlorous acid aqueous solution used in example 1 is decomposed by 95% and 99.2% on average with respect to 6-mercaptopurine and cisplatin, respectively.
[ example 5 ]
Example 5 will be described in detail. The present applicant has conducted another test for confirming the decomposition performance of an anticancer agent on the hypochlorous acid aqueous solution according to the present application, and thus has described this test.
This test was carried out using SAYEYI pharmaceutical Co., Ltd. (Sandao, Osakafu, Ind. No. 2, No. 5, No. 1) as a test site from 8 months to 31 days to 10 months and 27 days in 2020. The test method used LC/MS/MS.
First, for the preparation of a test substance solution, a solution prepared by dissolving 5mL of physiological saline in 100mg of each of bendamustine, gemcitabine, oxaliplatin, vincristine, doxorubicin, and fluorouracil was used as a stock solution (20mL), and 1mL of the stock solution was accurately weighed and purified water was added to prepare 20mL of the stock solution. Further, 5mL of this liquid was accurately weighed, and 50mL of purified water was added to prepare a test substance solution (100. mu.g/mL).
As the decomposition liquid A, a sample solution (decomposition liquid A) was prepared by adding 1mL of the above test substance solution to 9mL of the hypochlorous acid aqueous solution used in the present application and shaking and mixing the mixture. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times.
As a control solution, a sample solution was prepared by adding 1mL of the test substance solution to 9mL of purified water and shaking and mixing the mixture. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times.
The decomposition liquid a and purified water prepared in the above manner were measured by LC/MC/MS, and the decomposition effect of each test substance was confirmed by comparing the decomposition liquid a with purified water as a control solution.
As a result of the confirmation test, the contents of bendamustine, gemcitabine and oxaliplatin are shown in table 5, the contents of vincristine, doxorubicin and fluorouracil are shown in table 6, and the average decomposition rates of decomposition liquid a were 100%, 99.5%, 99.8%, 100%, 99.9% and 100%, respectively.
Test investigation content anticancer drug decomposition Performance confirmation test
The test acceptance numbers are JF20-G003, H002, H003, K011, K012 and J008
The test site is SAYEYI pharmaceutical Co Ltd (Osakafu ZUJIN, Sandao 2 Dimo No. 5 Samo No. 1)
Test day, 8 month 27-8 month 31 in 2020 (bendamustine)
9-14 (gemcitabine) months in 2020
8-9-8-1 (oxaliplatin) in 2020
22-27 months (vincristine) 10-10 in 2020
23 days 10 to 27 days 10 in 2020 (Adriamycin)
9-28-10-5 months (fluorouracil) in 2020
Test method LC/MS
The sample comprises bendamustine, gemcitabine, oxaliplatin, vincristine, adriamycin and fluorouracil
Decomposition solution A aqueous solution of hypochlorous acid used in the present application
[ TABLE 5 ]
Figure BDA0003638132960000111
[ TABLE 6 ]
Figure BDA0003638132960000121
The above results demonstrate that the aqueous hypochlorous acid solution used in example 1 decomposes 100%, 99.5%, 99.8%, 100%, 99.9%, 100% with respect to bendamustine, gemcitabine, oxaliplatin, vincristine, doxorubicin, fluorouracil, respectively.
[ example 6 ]
Example 6 will be described in detail. The applicant of the present application has conducted a test for confirming the decomposition performance of an anticancer agent for paclitaxel on the hypochlorous acid aqueous solution of the present application, and thus, the present application will now describe this.
This test was carried out twice at 2 months and 12 days and 10 months and 2 to 13 days in 2020 using SAYEYI pharmaceutical Co., Ltd (SAKAIJIN, Osakafu, Sandao No. 2 Ding.5 No. 1) as a test site. The test method used LC/MS/MS.
First, for preparation of a test substance solution, a solution prepared by dissolving 5mL of physiological saline in 100mg of paclitaxel was used as a stock solution (20mL), 1mL of the stock solution was precisely weighed, and purified water was added to prepare 20mL of the stock solution. Further, 5mL of this liquid was accurately weighed, and 50mL of purified water was added to prepare a test substance solution (100. mu.g/mL).
As the decomposition liquid A, a sample solution (decomposition liquid A) was prepared by adding 1mL of the above test substance solution to 9mL of the hypochlorous acid aqueous solution used in the present application and shaking and mixing the mixture. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times. As a control solution, a sample solution was prepared by adding 1mL of the test substance solution to 9mL of purified water and shaking and mixing the mixture. The measurement was carried out immediately after the preparation of the solution, and this operation was repeated 3 times.
Each of the decomposed solutions prepared by the above procedure was measured using LC/MS. Then, the decomposition effect of the decomposition liquid a was confirmed by comparing the decomposition liquid a with the control solution. The results of the immediate measurement are shown in table 7 below, and the results of the test after 24 hours have elapsed are shown in table 8 below.
As a result of the confirmation test carried out on 12 days 2 months 2 in 2020, the average decomposition rate of decomposition liquid a was 1.3% for paclitaxel, as shown in table 6. That is, the decomposition effect of decomposition liquid A on paclitaxel was not confirmed.
However, in the test of day 2 to day 13 at 10 months 2 in 2020, the average decomposition rate of the decomposition liquid a was 99.1% as a result of measuring the amount of paclitaxel detected after 24 hours had elapsed after setting the concentration 10 times higher than that of the decomposition liquid a carried out at day 12 at 2 months 2 in 2020.
Test investigation content anticancer drug decomposition Performance confirmation test
Test acceptance number JF20-K004
The test site is SAYEYI pharmaceutical Co Ltd (Osakafu ZUJIN, Sandao 2 Dimo No. 5 Samo No. 1)
Test days including 12 days in month 2 and 2-13 days in month 10 in 2020
Test method LC/MS
Paclitaxel as the specimen
Decomposition liquid A aqueous solution of hypochlorous acid used in the present application
[ TABLE 7 ]
Figure BDA0003638132960000131
[ TABLE 8 ]
Figure BDA0003638132960000132
The above results demonstrate that although it is difficult for the aqueous hypochlorous acid solution used in example 6 to decompose paclitaxel immediately, if the concentration is increased and a certain time elapses, 99.1% of the decomposition occurs.
Although examples of the method of using the neutralizing agent for an anticancer agent according to the present invention have been described above, it should be understood that various modifications can be made without departing from the technical scope of the present invention.
Industrial applicability
According to the method for preventing exposure to an anticancer agent of the present invention, since exposure to an anticancer agent can be safely and efficiently prevented by spraying a hypochlorous acid aqueous solution, the method can be applied not only to the prevention of exposure to an anticancer agent in medical facilities such as hospitals but also to the prevention of exposure to an anticancer agent in a wide range of applications such as elderly facilities, living rooms and toilets of living homes, and animal hospitals.
Description of the reference numerals
1 aqueous hypochlorous acid solution
10 sprayer
20 ultrasonic sprayer.

Claims (6)

1. A method for preventing exposure of an anticancer agent, characterized by detoxifying at least one of cyclophosphamide, 6-mercaptopurine, cisplatin, bendamustine, gemcitabine, oxaliplatin, vincristine, doxorubicin, fluorouracil, and paclitaxel in the anticancer agent by spraying a hypochlorous acid aqueous solution onto a subject to be treated.
2. A method for preventing exposure of an anticancer agent, characterized by detoxifying at least one of cyclophosphamide, 6-mercaptopurine, cisplatin, bendamustine, gemcitabine, oxaliplatin, vincristine, doxorubicin, fluorouracil, and paclitaxel in the anticancer agent by spraying a hypochlorous acid aqueous solution into a space where a subject to be treated is present.
3. The method for preventing exposure to an anticancer agent according to claim 1 or 2, wherein the hypochlorous acid aqueous solution is sprayed by a nebulizer which receives the hypochlorous acid aqueous solution and turns the hypochlorous acid aqueous solution into a gaseous or atomized form.
4. The method for preventing exposure to an anticancer agent according to claim 2, wherein the spraying is performed by an ultrasonic spraying apparatus containing the hypochlorous acid aqueous solution.
5. The method for preventing exposure to an anticancer agent according to any one of claims 1 to 4, wherein the pH of the aqueous hypochlorous acid solution is 5.5 to 7.0.
6. A method for preventing exposure to an anticancer agent, characterized in that paclitaxel is detoxified by spraying an aqueous hypochlorous acid solution onto a subject to be treated and leaving the subject for 24 hours.
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