WO2021230192A1 - Method for decomposing anti-cancer agent - Google Patents

Method for decomposing anti-cancer agent Download PDF

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Publication number
WO2021230192A1
WO2021230192A1 PCT/JP2021/017677 JP2021017677W WO2021230192A1 WO 2021230192 A1 WO2021230192 A1 WO 2021230192A1 JP 2021017677 W JP2021017677 W JP 2021017677W WO 2021230192 A1 WO2021230192 A1 WO 2021230192A1
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anticancer agent
ultraviolet
anticancer
decomposing
ultraviolet rays
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PCT/JP2021/017677
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French (fr)
Japanese (ja)
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敬祐 内藤
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ウシオ電機株式会社
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Priority to JP2022521899A priority Critical patent/JP7397416B2/en
Publication of WO2021230192A1 publication Critical patent/WO2021230192A1/en

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    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62D—CHEMICAL MEANS FOR EXTINGUISHING FIRES OR FOR COMBATING OR PROTECTING AGAINST HARMFUL CHEMICAL AGENTS; CHEMICAL MATERIALS FOR USE IN BREATHING APPARATUS
    • A62D3/00—Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances
    • A62D3/10—Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances by subjecting to electric or wave energy or particle or ionizing radiation
    • A62D3/17—Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances by subjecting to electric or wave energy or particle or ionizing radiation to electromagnetic radiation, e.g. emitted by a laser
    • A62D3/176—Ultraviolet radiations, i.e. radiation having a wavelength of about 3nm to 400nm

Definitions

  • the present invention relates to a method for decomposing an anticancer drug.
  • Non-Patent Document 1 a method of administering an anticancer drug is generally used.
  • therapies using such anticancer agents have come to be performed not only at the time of admission but also at the outpatient department.
  • a medical worker such as a doctor or a nurse may mix and prepare a drug in a ward or an outpatient treatment room to generate and use an anticancer drug after confirming the patient's condition.
  • Patent Document 1 proposes a method of decomposing an anticancer drug by allowing humidified air containing ozone to act.
  • Patent Document 2 proposes a method of decomposing an anticancer agent by spraying a photocatalytic aqueous composition containing titanium dioxide particles and a surfactant.
  • the photocatalytic aqueous composition is sprayed on the surface of the object to be treated, so that the particles of the photocatalyst and the surfactant remain on the surface of the object to be treated after the treatment.
  • the risk of If such a residue is left on the surface there is a concern about risks such as health damage due to inhalation of fine particles and overturning of the object to be treated due to lubricity.
  • the method for decomposing an anticancer agent according to the present invention is characterized by comprising a step (a) of irradiating the anticancer agent with ultraviolet rays exhibiting light output in a wavelength range of 200 nm or more and less than 300 nm.
  • the anticancer drug can be decomposed by ultraviolet rays showing light output in the wavelength range of 200 nm or more and less than 300 nm. Details will be described later in the section of embodiments for carrying out the invention.
  • the anticancer drug can be decomposed without using high concentration ozone. Further, since it is not necessary to spray the photocatalytic aqueous composition containing the titanium dioxide particles and the surfactant, no residue such as titanium dioxide particles remains on the surface of the object to be treated.
  • indicating an optical output may refer to a case where the optical intensity of 20% or more with respect to the optical intensity of the main peak wavelength is indicated on the spectrum.
  • the step (a) can be a step of irradiating the surface of the object to which the anticancer agent is attached with the ultraviolet rays.
  • Such objects include, for example, in the medical field, the pedestal of the safety cabinet where the anticancer drug is adjusted, the wall in the work space (work room), the floor in the room where the safety cabinet is installed, and the like. Walls, trays used during work, etc. are assumed. Moreover, it can be applied not only to medical sites but also to toilets, bathrooms, clothes and the like.
  • the excretion from the patient to whom the anticancer drug was administered may contain a part of the anticancer drug that was not consumed in the body. Therefore, for example, while a healthy person is performing cleaning work, the anticancer drug adhering to the toilet or the like is directly sucked, or is sucked through the adhering to the clothes or the like of the healthy person. Things can happen.
  • the anti-cancer drug can be decomposed by irradiating the place where the anti-cancer drug may be attached, such as a toilet or clothes, with the ultraviolet rays, so that the anti-cancer drug is healthy. Can reduce the risk of a person inhaling an anticancer drug.
  • the ultraviolet rays having a main peak wavelength of 200 nm or more and less than 300 nm may be irradiated.
  • the light source that emits such ultraviolet rays specifically, an excimer lamp, a low-pressure mercury lamp, an LED or the like containing KrCl, KrBr, XeI, XeBr or the like as a light emitting gas can be used.
  • the main peak wavelength of the ultraviolet rays is within the wavelength range of 200 nm or more and 230 nm or less. Even if the ultraviolet rays in this wavelength range are applied to the skin of the human body, they are absorbed by the stratum corneum of the skin and do not proceed to the inside (basal layer side). Since the stratum corneum contained in the stratum corneum is in a dead state as a cell, there is almost no risk that the DNA is destroyed by being absorbed by living cells such as the stratum spinosum, the stratum granulosum, and the dermis.
  • an excimer lamp in which a luminescent gas containing KrCl or KrBr is enclosed can be preferably adopted.
  • an excimer lamp in which a luminous gas containing KrCl is enclosed it is particularly preferable to use.
  • a solid-state light source such as an LED or LD may be used.
  • an aluminum gallium nitride (AlGaN) -based light-emitting element, an aluminum nitride (AlN) -based light-emitting element, and a magnesium oxide-zinc (MgZnO) -based light-emitting element are used as LEDs having a light emitting range with a wavelength of 190 nm or more and less than 240 nm. can do.
  • the light source may be combined with a wavelength conversion element.
  • a nonlinear optical crystal that doubles the frequency of light emitted from a gas laser or solid-state laser element and generates high-order high frequencies such as secondary high frequency (SHG) and tertiary high frequency (THG) is used as a wavelength conversion element. Therefore, ultraviolet light having a wavelength of 190 nm or more and less than 240 nm may be generated.
  • anticancer drug doxorubicin can be mentioned as an example.
  • Other anticancer agents include, for example, one or more belonging to the group consisting of methotrexate, cytarabine, vincristine, etoposide, mitomycin C, bendamustine, dacarbazine, docetaxel, and irinotecan.
  • the anticancer agent can be decomposed without using high concentration ozone, and no particulate residue is left after the treatment.
  • FIG. 6 is a drawing schematically showing a state in which the drawing of FIG. 1 is viewed from the direction of an operator. It is a top view which shows typically the structure of the excimer lamp as an example of a light source. 3 is a cross-sectional view taken along the line A1-A1 of FIG. It is a figure which shows the spectrum of the ultraviolet ray L1 emitted from the excimer lamp which contains KrCl in the luminescent gas. It is a figure which shows the absorption spectrum of doxorubicin hydrochloride. It is an HPLC chromatogram for an analytical sample not irradiated with ultraviolet rays.
  • 6 is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when mitomycin C is used as the anticancer agent. It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when cytarabine is used as an anticancer agent. It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when cytarabine is used as an anticancer agent. It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when bendamustine is used as an anticancer agent.
  • the method for decomposing an anticancer agent according to the present invention is characterized in that the anticancer agent is decomposed by irradiating the anticancer agent with a predetermined ultraviolet ray. Specifically, ultraviolet rays are applied to an object (object to be treated) to which an anticancer drug adheres to the surface.
  • FIG. 1 and 2 are drawings schematically showing one implementation state of the method for decomposing an anticancer agent according to the present invention.
  • FIG. 1 schematically illustrates a scene in which a worker 20 performs work such as drug preparation in the safety cabinet 1.
  • FIG. 2 corresponds to a schematic drawing when the safety cabinet 1 is viewed from the worker 20 side.
  • the worker 20 comes into direct contact with the anticancer drug or inhales atomized particles during the preparation work of the anticancer drug, there is a risk of skin inflammation and carcinogenesis. Further, the dispersion of the anticancer drug in the surroundings may pollute the environment and cause the same effect on humans other than the worker 20.
  • the safety cabinet 1 is installed on the indoor floor 2, and in the work room 4 (upper surface of the work table 3), the preparation of the drug for preparing the anticancer drug to be administered to the patient by the worker 20. Etc. are performed.
  • a HEPA (High Efficiency Particulate Air) filter 9 is installed in the safety cabinet 1 at a position above the workbench 3.
  • the atmosphere G1 in the safety cabinet 1 is exhausted after the fine particles of the drug contained in the atmosphere G1 and generated during the preparation work of the anticancer agent are adsorbed and removed by the HEPA filter 9.
  • a light source 10 is attached to the safety cabinet 1 of the present embodiment.
  • the light source 10 emits ultraviolet L1 indicating an optical output in a wavelength range of 200 nm or more and less than 300 nm.
  • 1 and 2 show an example in which the ultraviolet L1 from the light source 10 is irradiated toward the indoor floor 2 and the workbench 3.
  • the light source 10 is installed for the purpose of decomposing the anticancer agent adhering to the inside of the safety cabinet 1 or the surface of the indoor floor 2.
  • the light source 10 is composed of an excimer lamp that emits ultraviolet L1 as an example.
  • FIG. 3 is a plan view schematically showing the configuration of this excimer lamp, and
  • FIG. 4 is a sectional view taken along line A1-A1 of FIG.
  • the light source 10 has a light emitting tube 11 extending along the direction d1.
  • the arc tube 11 is made of a dielectric such as synthetic quartz glass and is a material that transmits ultraviolet L1.
  • the inside of the arc tube 11 is sealed, and the luminescent gas 12G that forms excimer molecules by electric discharge is sealed inside.
  • the light source 10 includes a pair of electrodes 13 (13a, 13b) formed on the tube wall of the arc tube 11.
  • the electrode 13a arranged on the side (+ d2 side) from which the ultraviolet L1 is taken out from the light source 10 has a mesh shape or a linear shape
  • the electrode 13b arranged on the opposite side has a film shape.
  • the electrode 13b is made of a metal material (for example, Al, Al alloy, etc.) that is reflective to the ultraviolet L1 or is attached to the tube wall of the arc tube 11 on the side where the electrode 13b is formed. It is preferable that a reflective film (not shown) is provided.
  • the reflective film Al, Al alloy, stainless steel, silica, silica alumina and the like can be used.
  • the light source 10 is installed near the wall surface of the safety cabinet 1, but for example, when it is installed near the center in the work room 4, both the + d2 direction and the ⁇ d2 direction from the light source 10 are installed. It is preferable that the ultraviolet L1 is taken out toward the direction.
  • the electrode 13b may also have a mesh shape or a linear shape like the electrode 13a.
  • the wavelength of ultraviolet L1 is set according to the type of luminescent gas 12G.
  • the luminescent gas 12G contains KrCl
  • ultraviolet L1 having a main peak wavelength in the vicinity of 222 nm is emitted from the light source 10 composed of an excimer lamp.
  • KrBr is contained in the luminescent gas 12G
  • ultraviolet L1 having a main peak wavelength in the vicinity of 207 nm is emitted from the light source 10.
  • the luminescent gas 12G contains XeI
  • ultraviolet L1 having a main peak wavelength of around 253 nm is emitted from the light source 10.
  • ultraviolet L1 having a main peak wavelength in the vicinity of 283 nm is emitted from the light source 10.
  • FIG. 5 is a drawing showing a spectrum of ultraviolet rays L1 emitted from a light source 10 composed of an excimer lamp containing KrCl in a light emitting gas 12G.
  • the light source 10 can also be configured by a low-pressure mercury lamp, an LED, or the like.
  • the main peak wavelength of the ultraviolet L1 is within the wavelength range of 200 nm or more and 230 nm or less. Even if the ultraviolet rays in this wavelength range are applied to the skin of the human body, they are absorbed by the stratum corneum of the skin and do not proceed to the inside (basal layer side). Therefore, the light source 10 can be turned on even when the worker 20 is working in the safety cabinet 1.
  • the light source 10 when the light source 10 exhibits light output in a wavelength range of 240 nm or more and less than 300 nm, such as a low-pressure mercury lamp, the worker 20 does not exist in the vicinity of the safety cabinet 1 in view of the influence on the human body of the worker 20. It is preferable to turn on the light source 10 only in the time zone.
  • the anticancer drug is applied to the wall surface of the safety cabinet 1, the upper surface of the work table 3, the upper surface of the indoor floor 2, and the like. Some of the agent may leak and adhere. Since the light source 10 is installed in the safety cabinet 1 of the present embodiment, the anticancer agent adhering to the wall surface or the like is decomposed by the irradiation of the ultraviolet L1 from the light source 10. Further, since the anticancer agent is decomposed simply by irradiating the light source 10 with ultraviolet L1, high-concentration ozone is introduced into the space or photocatalytic particles are formed on the surface of the object to be treated, as in the conventional method. No need to apply.
  • FIG. 6 is a drawing showing an absorption spectrum of doxorubicin, which is a kind of anticancer drug. Specifically, since it is used in the form of doxorubicin hydrochloride at the time of preparation, the absorption spectrum of doxorubicin hydrochloride is also shown in FIG.
  • doxorubicin hydrochloride exhibits a relatively high absorbance with respect to ultraviolet L1 in the wavelength range of 200 nm or more and 300 nm or less. It was verified that doxorubicin hydrochloride can be decomposed by irradiating such doxorubicin hydrochloride with ultraviolet L1 in the above wavelength band.
  • the test product Y1 was irradiated with ultraviolet rays L1 at an illuminance of 2 mW / cm 2 on the irradiation surface while changing the irradiation time.
  • the irradiated test product Y2 was placed in a tube, 2 mL of ultrapure water was added, the mixture was sealed, and the mixture was stirred. Then, centrifugation was performed and the supernatant was sampled to prepare a sample Z1 for analysis.
  • the light source for irradiating the ultraviolet L1 the KrCl excimer lamp (main peak wavelength 222 nm) and the low pressure mercury lamp (main peak wavelength 254 nm) described above with reference to FIGS. 3 to 5 were used. However, for low-pressure mercury lamps, a filter is provided to block sub-peaks (near 185 nm) that occur in wavelength ranges other than 254 nm.
  • FIG. 7A is an HPLC chromatogram for analytical sample Z0 prepared as Comparative Example 1.
  • FIGS. 7B to 7D are HPLC chromatograms for the analytical sample Z1 as an example obtained by irradiating the test product Y1 with ultraviolet L1 having a main peak wavelength of 222 nm. More specifically, FIG. 7B ⁇ -7D, respectively, HPLC chromatograms of the test substance 500 mJ / cm 2 exposure amount of ultraviolet L1 for Y1, 1000mJ / cm 2, 5000mJ / cm 2 analytical sample Z1 fabricated as Is.
  • FIG. 8A is a graph showing the relationship between the residual rate of doxorubicin calculated by the above method and the exposure amount of ultraviolet L1.
  • FIG. 8A shows data of both the case of being irradiated with the ultraviolet L1 having a main peak wavelength of 222 nm and the case of being irradiated with the ultraviolet L1 having a main peak wavelength of 254 nm.
  • the residual rate of doxorubicin decreases as the exposure amount increases with the ultraviolet L1 of any wavelength. That is, it is confirmed that doxorubicin is decomposed by irradiation with ultraviolet L1.
  • Doxorubicin hydrochloride is a substance represented by the following formula (1).
  • the binding energy of the CH bond is 408.9 kJ / mol, which is 293 nm in terms of wavelength. Therefore, when the ultraviolet L1 having a wavelength of less than 293 nm is incorporated into the CH bond, the CH bond is theoretically broken.
  • the binding energy of the CC bond is 353.2 kJ / mol, which is 339 nm in terms of wavelength.
  • doxorubicin hydrochloride exhibits a certain degree of absorbance with respect to ultraviolet L1 having a diameter of less than 300 nm.
  • the wavelength is in the range of 300 nm or more and 400 nm or less, the absorbance for doxorubicin hydrochloride is low. That is, when the doxorubicin hydrochloride is irradiated with ultraviolet L1 having a wavelength of less than 300 nm, a part of the ultraviolet L1 is absorbed by the doxorubicin hydrochloride, and as a result, a part of the chemical bond of the doxorubicin hydrochloride is broken.
  • doxorubicin is decomposed.
  • ultraviolet L1 having a wavelength of 300 nm or more and 400 nm or less is irradiated to doxorubicin, most of it is transmitted through doxorubicin, and sufficient light energy cannot be applied to doxorubicin. Conceivable.
  • the wavelength of the ultraviolet L1 is set to 200 nm or more and less than 300 nm.
  • FIG. 8B is a graph showing the results of verification using methotrexate instead of doxorubicin as a material for an anticancer drug in the same manner as described above, following FIG. 8A.
  • the residual rate of methotrexate decreases as the exposure amount increases in both the case of the ultraviolet L1 having the main peak wavelength of 222 nm and the ultraviolet ray having the main peak wavelength of 254 nm. That is, it is confirmed that methotrexate is decomposed by irradiation with ultraviolet L1.
  • Doxorubicin is an example of an anthracycline anticancer antibiotic
  • methotrexate is an example of a folic acid antagonist.
  • 9A-9E are drawings showing absorption spectra of methotrexate, cytarabine, vincristine (sulfate), etoposide, and mitomycin C, which are examples of anticancer agents other than doxorubicin. Since vincristine is used in the form of sulfate at the time of preparation, the absorption spectrum of vincristine sulfate is shown in FIG. 9C.
  • Cytarabine is an example of a pyrimidine antagonist.
  • Vincristine is an example of an anticancer drug of bin alkaloids.
  • Mitomycin C is an example of an anticancer agent of nitrogen mustards.
  • each of the anticancer agents shown in FIGS. 9A to 9E a certain degree of absorbance is confirmed for ultraviolet L1 in the range of 200 nm or more and less than 300 nm.
  • these anticancer agents also include a CC bond and a chemical bond of a C—H bond, as in the case of doxorubicin. Therefore, from the same viewpoint, methotrexate, cytarabine, vincristine sulfate, etoposide, and mitomycin C may also be exposed to ultraviolet L1 in the range of 200 nm or more and less than 300 nm to exhibit a decomposition effect. I understand.
  • Nitrogen mustards Bendamustine, Mitomycin C ⁇ Pyrimidin antagonist: Cytarabine ⁇ Anthracycline anticancer antibiotic: doxorubicin ⁇ Topoisomerase inhibitor: irinotecan, etoposide ⁇ Triazens: dacarbazine ⁇ Bin alkaloids: vincristine ⁇ Taxanes: docetaxel
  • Distilled water was mixed with each of the above-mentioned anticancer agents to be targeted in a predetermined container to purify the aqueous solution.
  • the absorption spectra of each aqueous solution before irradiation with ultraviolet rays were measured using an absorptiometer (NANODROP ONE manufactured by Thermo Fisher Science Co., Ltd.).
  • NANODROP ONE manufactured by Thermo Fisher Science Co., Ltd.
  • each aqueous solution was irradiated with ultraviolet L1 at an illuminance of 2 mW / cm 2 on the irradiation surface while changing the irradiation time, and the absorption spectrum after irradiation was measured by the same method as described above.
  • FIGS. 10A to 18B The absorption spectra of the aqueous solutions of the respective anticancer agents before and after the irradiation with the ultraviolet L1 are shown in FIGS. 10A to 18B. Each figure corresponds to:
  • FIG. 10A is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet L1 when mitomycin C is used as the anticancer agent.
  • FIG. 10B is an absorption spectrum of an aqueous solution of an anticancer agent after irradiating 5000 mJ of ultraviolet L1 emitted from a KrCl lamp when mitomycin C is used as the anticancer agent.
  • 11A, 12A, 13A, 14A, 15A, 16A, 17A, and 18A replace mitomycin C in FIG. 10A with cytarabine, bendamustine, doxorubicin, irinotecan, dacarbazine, etoposide, and vincristine, respectively.
  • 11B, 12B, 13B, 14B, 15B, 16B, 17B, and 18B replace mitomycin C in FIG. 10B with cytarabine, bendamustine, doxorubicin, irinotecan, dacarbazine, etoposide, and vincristine, respectively.
  • the shape of the absorption spectrum changes significantly before and after irradiation with the ultraviolet L1 regardless of which anticancer agent is used.
  • the substances constituting each of the verified anticancer agents show high absorbance in the wavelength range of the ultraviolet L1 emitted from the KrCl lamp before the irradiation with the ultraviolet L1. That is, when each of these anticancer agents is irradiated with ultraviolet L1 from the KrCl lamp, a part of the ultraviolet L1 is absorbed by the anticancer agent, and the chemical bond of the substance constituting the anticancer agent is obtained. It is suggested that a part of was cut off. That is, it can be seen that any of the above anticancer agents is decomposed by the ultraviolet L1 emitted from the KrCl lamp.
  • the residual rate of the substance constituting the anticancer agent can be calculated from the change in the shape of the absorption spectrum before and after the irradiation with the ultraviolet L1. More specifically, the residual rate of substances constituting the anticancer drug can be defined as follows. That is, the absorbance at the wavelength (peak wavelength ⁇ p ) indicating the peak value of the absorption spectrum of the anticancer agent before irradiation with ultraviolet L1 is defined as A 1, and the absorbance at the peak wavelength ⁇ p after irradiation with ultraviolet L1.
  • the residual ratio of the substances constituting the anticancer agent can be defined by the ratio A 2 / A 1 of the change in the absorbance of the peak wavelength ⁇ p before and after irradiation.
  • 19A to 19I are graphs showing the relationship between the residual rate of the substance constituting each anticancer agent and the exposure amount of ultraviolet L1 calculated by the above method.
  • 19A, 19B, 19C, 19D, 19E, 19F, 19G, 19H, and 19I are mitomycin C, cytarabine, bendamustine, doxorubicin, irinotecan, dacarbazine, etoposide, vincristine, and docetaxel, respectively. It is a graph which shows the relationship between the residual ratio and the exposure amount of ultraviolet L1.
  • FIGS. 19A to 19I when the KrCl excimer lamp (main peak wavelength 222 nm) is used and the low pressure mercury lamp (main peak wavelength 254 nm) is used as the light source for irradiating the ultraviolet L1 as in the verification 1. The result of is shown.
  • FIG. 19D a graph showing the relationship between the residual rate of doxorubicin obtained by the method of verification 1 and the exposure amount of ultraviolet L1 described above with reference to FIG. 8 is superimposed and shown. The result of this verification 1 is described as "HPLC" in FIG. 19D.
  • the tendency of the decomposition characteristics of doxorubicin obtained by the method of Verification 2 is consistent with the tendency of the decomposition characteristics of doxorubicin obtained by the method of Verification 1. That is, the result of the decomposition property obtained by the method of Verification 2 reflects the property of the anticancer drug.
  • the residual rate of each substance constituting the anticancer agent decreases as the exposure amount increases with the ultraviolet L1 having any wavelength of 222 nm and 254 nm. That is, it is confirmed that mitomycin C, cytarabine, bendamustine, irinotecan, dacarbazine, etoposide, vincristine, and docetaxel, which are anticancer agents other than doxorubicin, are also decomposed by irradiation with ultraviolet L1.
  • each of the above-mentioned anticancer agents did not show any change in the absorption spectrum simply by leaving them indoors. This suggests that the substances constituting the anticancer drug are not decomposed by irradiation with visible light.
  • the wall of the safety cabinet 1, the work table 3, and the indoor floor 2 have been described as the objects to be treated to be irradiated with the ultraviolet L1.
  • the method according to the present invention is not limited to the use for the safety cabinet 1 and its installation area.
  • the present invention includes the content of irradiating the surface (object surface) of an object to which an anticancer agent may be attached with ultraviolet L1 having a wavelength of 200 nm or more and less than 300 nm. It is not limited to the object.
  • the ultraviolet L1 preferably has a main peak wavelength of 200 nm or more and less than 300 nm, but the present invention is an ultraviolet L1 that exhibits a spectrum showing an optical output within a range of at least 200 nm or more and less than 300 nm. Can be used for. Such ultraviolet L1 is absorbed at a high rate with respect to anticancer agents such as doxorubicin, and can break a part of the chemical bond of the substance constituting the anticancer agent.
  • anticancer agents such as doxorubicin
  • the light source 2 may be fixedly attached to an object (safety cabinet 1 or the like) or a room (wall surface or ceiling surface) near the area where the object to be processed exists. Further, as another example, the light source 2 may have a portable structure.
  • the light source 2 By making the light source 2 portable, it is possible to irradiate the surface of the object to be treated with ultraviolet L1 at a short irradiation distance. That is, since the ultraviolet L1 can irradiate the object to be processed with high illuminance, the irradiation time required to achieve the same exposure amount can be shortened. However, in this case, in consideration of the influence of the exposure of the ultraviolet L1 to the human body of the worker carrying the light source 2, the light source 2 emits the ultraviolet L1 existing in the wavelength range of 200 nm or more and 230 nm or less as the main peak wavelength. Is preferable.
  • Safety cabinet 2 Indoor floor 3: Work table 4: Work room 9: HEPA filter 10: Light source 11: Emission tube 12G: Emission gas 13: Electrode 13a: Electrode 13b: Electrode 20: Worker G1: Atmosphere L1: Ultraviolet rays

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Abstract

Provided is a method for decomposing an anti-cancer agent which does not require the use of high-concentration ozone and which does not leave particulate residue after processing.　A method for decomposing an anti-cancer agent according to the present invention includes a step (a) for irradiating an anti-cancer agent with ultraviolet radiation that exhibits light output in a wavelength range of greater than or equal to 200 nm and less than 300 nm.

Description

抗がん剤の分解方法Decomposition method of anticancer drug
　本発明は、抗がん剤の分解方法に関する。 The present invention relates to a method for decomposing an anticancer drug.
　がんの治療方法の一つとして、抗がん剤を投与する方法が一般的に利用されている。近年、このような抗がん剤を用いた療法は、入院時のみならず、外来でも行われるようになってきている。例えば、医師や看護師等の医療従事者が、患者の容態を確認した上で、病棟や外来の処置室などで薬物を混合・調製して抗がん剤を生成し、使用する場合がある（非特許文献１、非特許文献２参照）。 As one of the cancer treatment methods, a method of administering an anticancer drug is generally used. In recent years, therapies using such anticancer agents have come to be performed not only at the time of admission but also at the outpatient department. For example, a medical worker such as a doctor or a nurse may mix and prepare a drug in a ward or an outpatient treatment room to generate and use an anticancer drug after confirming the patient's condition. (See Non-Patent Document 1 and Non-Patent Document 2).
　抗がん剤の多くは、細胞のＤＮＡに傷害を与えたり、細胞分裂を阻害することにより、がん細胞を死滅させる一方で、がん細胞だけでなく正常細胞にも影響を及ぼすことが知られている。具体的には、抗がん剤は通常、輸液に注入して使用されるが、その輸液の調製時、投与時、又は廃棄時において、医療従事者が抗がん剤を吸入したり、医療従事者の皮膚に付着したりする危険性が指摘されている（非特許文献１、非特許文献２参照）。 It is known that many anticancer drugs kill cancer cells by damaging the DNA of the cells or inhibiting cell division, while affecting not only cancer cells but also normal cells. Has been done. Specifically, an anticancer drug is usually used by injecting it into an infusion solution, but at the time of preparation, administration, or disposal of the infusion solution, a medical worker inhales the anticancer drug or performs medical treatment. It has been pointed out that there is a risk of adhesion to the skin of workers (see Non-Patent Document 1 and Non-Patent Document 2).
　上記課題への対策として、例えば特許文献１では、オゾンを含んだ加湿空気を作用させることで、抗がん剤を分解する方法が提案されている。また、別の方法として、例えば特許文献２では、二酸化チタン粒子及び界面活性剤を含有する光触媒水性組成物を噴霧することで、抗がん剤を分解する方法が提案されている。 As a countermeasure to the above problem, for example, Patent Document 1 proposes a method of decomposing an anticancer drug by allowing humidified air containing ozone to act. Further, as another method, for example, Patent Document 2 proposes a method of decomposing an anticancer agent by spraying a photocatalytic aqueous composition containing titanium dioxide particles and a surfactant.
国際公開第２０１４／２０８４２８号公報International Publication No. 2014/208428 特開２０１２－９１１１４号公報Japanese Unexamined Patent Publication No. 2012-91114
　しかし、特許文献１の方法を採用しようとすると、オゾンガス濃度（ｐｐｍ）と接触時間（分）との積で規定されるＣＴ値に鑑みた場合、極めて高濃度のオゾンを導入するか、又は、極めて長い時間にわたって処理対象物に対してオゾンを曝露しなければ、処理対象物に付着した抗がん剤を分解する効果が得られない可能性が高い。特に、前者の場合には、オゾンガスが他の空間に漏れ出すことで、人体に対して影響を及ぼす懸念も考えられる。 However, when the method of Patent Document 1 is to be adopted, an extremely high concentration of ozone is introduced or an extremely high concentration of ozone is introduced in view of the CT value defined by the product of the ozone gas concentration (ppm) and the contact time (minutes). Unless ozone is exposed to the object to be treated for an extremely long time, it is highly possible that the effect of decomposing the anticancer drug adhering to the object to be treated cannot be obtained. In particular, in the former case, there is a concern that ozone gas may leak to other spaces and affect the human body.
　また、特許文献２の方法を採用しようとすると、処理対象物の表面に対して光触媒水性組成物が噴霧されるため、処理後の処理対象物の表面に、光触媒の粒子や界面活性剤が残留するおそれがある。このような残留物が表面に残されると、微粒子吸入による健康被害や、潤滑性による処理対象物の転倒などのリスクが懸念される。 Further, when the method of Patent Document 2 is to be adopted, the photocatalytic aqueous composition is sprayed on the surface of the object to be treated, so that the particles of the photocatalyst and the surfactant remain on the surface of the object to be treated after the treatment. There is a risk of If such a residue is left on the surface, there is a concern about risks such as health damage due to inhalation of fine particles and overturning of the object to be treated due to lubricity.
　本発明は、上記の課題に鑑み、高濃度のオゾンを用いる必要がなく、また、処理後に粒子状の残留物を残すことのない、抗がん剤を分解する方法を提供することを目的とする。 In view of the above problems, it is an object of the present invention to provide a method for decomposing an anticancer agent, which does not require the use of high concentration ozone and does not leave particulate residue after treatment. do.
　本発明に係る抗がん剤の分解方法は、２００ｎｍ以上、３００ｎｍ未満の波長域に光出力を示す紫外線を抗がん剤に照射する工程（ａ）を含むことを特徴とする。 The method for decomposing an anticancer agent according to the present invention is characterized by comprising a step (a) of irradiating the anticancer agent with ultraviolet rays exhibiting light output in a wavelength range of 200 nm or more and less than 300 nm.
　本発明者の鋭意研究により、２００ｎｍ以上、３００ｎｍ未満の波長域に光出力を示す紫外線によって、抗がん剤を分解できることが確認された。詳細は、発明を実施するための形態の項で後述される。 Through the diligent research of the present inventor, it was confirmed that the anticancer drug can be decomposed by ultraviolet rays showing light output in the wavelength range of 200 nm or more and less than 300 nm. Details will be described later in the section of embodiments for carrying out the invention.
　かかる方法によれば、高濃度のオゾンを用いることなく、抗がん剤の分解が可能となる。また、二酸化チタン粒子及び界面活性剤を含有する光触媒水性組成物を噴霧する必要がないため、処理対象物の表面に、二酸化チタン粒子等の残留物が残ることもない。 According to this method, the anticancer drug can be decomposed without using high concentration ozone. Further, since it is not necessary to spray the photocatalytic aqueous composition containing the titanium dioxide particles and the surfactant, no residue such as titanium dioxide particles remains on the surface of the object to be treated.
　なお、本明細書において「光出力を示す」とは、スペクトル上において、主ピーク波長の光強度に対して、２０％以上の光強度を示す場合を指すものとして構わない。 Note that, in the present specification, "indicating an optical output" may refer to a case where the optical intensity of 20% or more with respect to the optical intensity of the main peak wavelength is indicated on the spectrum.
　より詳細には、前記工程（ａ）は、前記抗がん剤が付着した物体表面に対して前記紫外線を照射する工程とすることができる。 More specifically, the step (a) can be a step of irradiating the surface of the object to which the anticancer agent is attached with the ultraviolet rays.
　このような物体としては、例えば、医療現場であれば、抗がん剤の調整等が行われる安全キャビネットの台座や作業空間（作業室）内の壁、安全キャビネットが設置されている室内の床や壁、作業時に利用されるトレー等が想定される。また、医療現場に限られず、トイレ、浴室、被服等にも適用が可能である。 Such objects include, for example, in the medical field, the pedestal of the safety cabinet where the anticancer drug is adjusted, the wall in the work space (work room), the floor in the room where the safety cabinet is installed, and the like. Walls, trays used during work, etc. are assumed. Moreover, it can be applied not only to medical sites but also to toilets, bathrooms, clothes and the like.
　抗がん剤が投与された患者からの排泄物に、体内で消費されなかった抗がん剤の一部が含まれることがある。このため、例えば健常者が清掃作業などを行っている間に、トイレ等に付着していた抗がん剤を直接吸引したり、又は、前記健常者の被服等への付着を介して吸引する事態が生じる可能性がある。しかし、上記の方法によれば、トイレや被服等、抗がん剤が付着している可能性がある箇所に対して、前記紫外線を照射することで、抗がん剤を分解できるため、健常者が抗がん剤を吸引するリスクを低下できる。 The excretion from the patient to whom the anticancer drug was administered may contain a part of the anticancer drug that was not consumed in the body. Therefore, for example, while a healthy person is performing cleaning work, the anticancer drug adhering to the toilet or the like is directly sucked, or is sucked through the adhering to the clothes or the like of the healthy person. Things can happen. However, according to the above method, the anti-cancer drug can be decomposed by irradiating the place where the anti-cancer drug may be attached, such as a toilet or clothes, with the ultraviolet rays, so that the anti-cancer drug is healthy. Can reduce the risk of a person inhaling an anticancer drug.
　前記工程（ａ）は、主ピーク波長が２００ｎｍ以上、３００ｎｍ未満の前記紫外線を照射するものとしても構わない。このような紫外線を発する光源としては、具体的には、ＫｒＣｌ、ＫｒＢｒ、ＸｅＩ、ＸｅＢｒ等を発光ガスとして含むエキシマランプ、低圧水銀ランプ、ＬＥＤ等を利用できる。 In the step (a), the ultraviolet rays having a main peak wavelength of 200 nm or more and less than 300 nm may be irradiated. As the light source that emits such ultraviolet rays, specifically, an excimer lamp, a low-pressure mercury lamp, an LED or the like containing KrCl, KrBr, XeI, XeBr or the like as a light emitting gas can be used.
　特に、前記紫外線の主ピーク波長が、２００ｎｍ以上、２３０ｎｍ以下の波長範囲内であるのが好適である。この波長範囲内の紫外線は、仮に人体の皮膚に対して照射されても、皮膚の角質層で吸収され、それよりも内側（基底層側）には進行しない。角質層に含まれる角質細胞は細胞としては死んだ状態であるため、有棘層、顆粒層、真皮など、生きた細胞に吸収されてＤＮＡが破壊されるというリスクがほとんど存在しない。 In particular, it is preferable that the main peak wavelength of the ultraviolet rays is within the wavelength range of 200 nm or more and 230 nm or less. Even if the ultraviolet rays in this wavelength range are applied to the skin of the human body, they are absorbed by the stratum corneum of the skin and do not proceed to the inside (basal layer side). Since the stratum corneum contained in the stratum corneum is in a dead state as a cell, there is almost no risk that the DNA is destroyed by being absorbed by living cells such as the stratum spinosum, the stratum granulosum, and the dermis.
　つまり、上記波長範囲内の紫外線によって抗がん剤を分解することで、分解処理の実行中に、人間が近くに存在していた場合であっても、紫外線が曝露することによる人体への影響が抑制される。従って、紫外線の照射処理を、無人時に限定して行う必要がなく、より柔軟な分解処理が実現される。 In other words, by decomposing the anticancer drug with ultraviolet rays within the above wavelength range, even if a human is nearby during the decomposition process, the effect on the human body due to exposure to ultraviolet rays. Is suppressed. Therefore, it is not necessary to perform the ultraviolet irradiation treatment only when unattended, and a more flexible decomposition treatment is realized.
　このような主ピーク波長が、２００ｎｍ以上、２３０ｎｍ以下の紫外線を発する光源としては、例えば、ＫｒＣｌ又はＫｒＢｒを含む発光ガスが封入されたエキシマランプを好適に採用することができる。この中では、発光効率の観点からは、ＫｒＣｌを含む発光ガスが封入されたエキシマランプを採用するのが特に好ましい。 As a light source that emits ultraviolet rays having such a main peak wavelength of 200 nm or more and 230 nm or less, for example, an excimer lamp in which a luminescent gas containing KrCl or KrBr is enclosed can be preferably adopted. Among these, from the viewpoint of luminous efficiency, it is particularly preferable to use an excimer lamp in which a luminous gas containing KrCl is enclosed.
　また、前記光源として、ＬＥＤやＬＤ等の固体光源を用いても良い。例えば、波長が１９０ｎｍ以上２４０ｎｍ未満に発光域を有するＬＥＤとして、窒化アルミニウムガリウム（ＡｌＧａＮ）系の発光素子や、窒化アルミニウム（ＡｌＮ）系の発光素子、酸化マグネシウム亜鉛（ＭｇＺｎＯ）系の発光素子を採用することができる。さらに、光源に波長変換素子を組み合わせるものであってもよい。例えば、ガスレーザや固体レーザ素子から放射される光を周波数倍化させ、第二次高周波（ＳＨＧ）や第三次高周波（ＴＨＧ）等の高次高周波を発生させる非線形光学結晶を波長変換素子として用いることで、波長が１９０ｎｍ以上２４０ｎｍ未満の紫外光を生成しても良い。 Further, as the light source, a solid-state light source such as an LED or LD may be used. For example, an aluminum gallium nitride (AlGaN) -based light-emitting element, an aluminum nitride (AlN) -based light-emitting element, and a magnesium oxide-zinc (MgZnO) -based light-emitting element are used as LEDs having a light emitting range with a wavelength of 190 nm or more and less than 240 nm. can do. Further, the light source may be combined with a wavelength conversion element. For example, a nonlinear optical crystal that doubles the frequency of light emitted from a gas laser or solid-state laser element and generates high-order high frequencies such as secondary high frequency (SHG) and tertiary high frequency (THG) is used as a wavelength conversion element. Therefore, ultraviolet light having a wavelength of 190 nm or more and less than 240 nm may be generated.
　前記抗がん剤は、一例としてドキソルビシンを挙げることができる。その他の抗がん剤としては、例えば、メトトレキサート、シタラビン、ビンクリスチン、エトポシド、マイトマイシンＣ、ベンダムスチン、ダカルバジン、ドセタキセル、及びイリノテカンからなる群に属する一種以上が挙げられる。 As the anticancer drug, doxorubicin can be mentioned as an example. Other anticancer agents include, for example, one or more belonging to the group consisting of methotrexate, cytarabine, vincristine, etoposide, mitomycin C, bendamustine, dacarbazine, docetaxel, and irinotecan.
　本発明の方法によれば、高濃度のオゾンを用いることなく抗がん剤を分解することができ、処理後に粒子状の残留物を残すこともない。 According to the method of the present invention, the anticancer agent can be decomposed without using high concentration ozone, and no particulate residue is left after the treatment.
本発明の抗がん剤の分解方法の一実施形態を模式的に示す図面である。It is a figure which shows typically one Embodiment of the decomposition method of the anticancer agent of this invention. 図１の図面を作業者の方向から見た状態を模式的に示す図面である。6 is a drawing schematically showing a state in which the drawing of FIG. 1 is viewed from the direction of an operator. 光源の一例としてのエキシマランプの構成を模式的に示す平面図である。It is a top view which shows typically the structure of the excimer lamp as an example of a light source. 図３のＡ１－Ａ１線断面図である。3 is a cross-sectional view taken along the line A1-A1 of FIG. 発光ガスにＫｒＣｌが含まれるエキシマランプから出射される紫外線Ｌ１のスペクトルを示す図面である。It is a figure which shows the spectrum of the ultraviolet ray L1 emitted from the excimer lamp which contains KrCl in the luminescent gas. ドキソルビシン塩酸塩の吸収スペクトルを示す図面である。It is a figure which shows the absorption spectrum of doxorubicin hydrochloride. 紫外線が照射されていない分析用試料に対する、ＨＰＬＣクロマトグラムである。It is an HPLC chromatogram for an analytical sample not irradiated with ultraviolet rays. ５００ｍＪ／ｃｍ2の露光量で紫外線が照射された分析用試料に対する、ＨＰＬＣクロマトグラムである。It is an HPLC chromatogram for an analytical sample irradiated with ultraviolet rays at an exposure amount of 500 mJ / cm 2. １０００ｍＪ／ｃｍ2の露光量で紫外線が照射された分析用試料に対する、ＨＰＬＣクロマトグラムである。It is an HPLC chromatogram for an analytical sample irradiated with ultraviolet rays at an exposure amount of 1000 mJ / cm 2. ５０００ｍＪ／ｃｍ2の露光量で紫外線が照射された分析用試料に対する、ＨＰＬＣクロマトグラムである。It is an HPLC chromatogram for an analytical sample irradiated with ultraviolet rays at an exposure amount of 5000 mJ / cm 2. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、ドキソルビシン塩酸塩の残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of doxorubicin hydrochloride and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、メトトレキサートの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of methotrexate and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. メトトレキサートの吸収スペクトルを示す図面である。It is a figure which shows the absorption spectrum of methotrexate. シタラビンの吸収スペクトルを示す図面である。It is a figure which shows the absorption spectrum of cytarabine. ビンクリスチン硫酸塩の吸収スペクトルを示す図面である。It is a figure which shows the absorption spectrum of vincristine sulfate. エトポシドの吸収スペクトルを示す図面である。It is a figure which shows the absorption spectrum of etoposide. マイトマイシンＣの吸収スペクトルを示す図面である。It is a figure which shows the absorption spectrum of mitomycin C. 抗がん剤としてマイトマイシンＣを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。6 is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when mitomycin C is used as the anticancer agent. 抗がん剤としてマイトマイシンＣを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。6 is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when mitomycin C is used as the anticancer agent. 抗がん剤としてシタラビンを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when cytarabine is used as an anticancer agent. 抗がん剤としてシタラビンを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when cytarabine is used as an anticancer agent. 抗がん剤としてベンダムスチンを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when bendamustine is used as an anticancer agent. 抗がん剤としてベンダムスチンを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when bendamustine is used as an anticancer agent. 抗がん剤としてドキソルビシンを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when doxorubicin is used as an anticancer agent. 抗がん剤としてドキソルビシンを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when doxorubicin is used as an anticancer agent. 抗がん剤としてイリノテカンを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when irinotecan is used as an anticancer agent. 抗がん剤としてイリノテカンを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when irinotecan is used as an anticancer agent. 抗がん剤としてダカルバジンを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when dacarbazine is used as an anticancer agent. 抗がん剤としてダカルバジンを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when dacarbazine is used as an anticancer agent. 抗がん剤としてエトポシドを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when etoposide is used as an anticancer agent. 抗がん剤としてエトポシドを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when etoposide is used as an anticancer agent. 抗がん剤としてビンクリスチンを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when vincristine is used as an anticancer agent. 抗がん剤としてビンクリスチンを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when vincristine is used as an anticancer agent. 抗がん剤としてドセタキセルを用いた場合の、紫外線の照射前における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet rays when docetaxel is used as an anticancer agent. 抗がん剤としてドセタキセルを用いた場合の、紫外線の照射後における、抗がん剤の水溶液の吸収スペクトルである。It is an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with ultraviolet rays when docetaxel is used as an anticancer agent. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、マイトマイシンＣの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of mitomycin C and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、シタラビンの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual ratio of cytarabine and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、ベンダムスチンの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of bendamustine and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、ドキソルビシンの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of doxorubicin and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、イリノテカンの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of irinotecan and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、ダカルバジンの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual ratio of dacarbazine and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、エトポシドの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual ratio of etoposide and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、ビンクリスチンの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of vincristine and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively. ２２２ｎｍ及び２５４ｎｍの紫外線をそれぞれ照射したときの、ドセタキセルの残存率と露光量の関係を示すグラフである。It is a graph which shows the relationship between the residual rate of docetaxel and the exposure amount at the time of irradiation with ultraviolet rays of 222 nm and 254 nm, respectively.
　本発明に係る抗がん剤の分解方法は、抗がん剤に対して所定の紫外線を照射することで抗がん剤を分解することを特徴とするものである。具体的には、抗がん剤が表面に付着した物体（処理対象物）に対して紫外線が照射される。 The method for decomposing an anticancer agent according to the present invention is characterized in that the anticancer agent is decomposed by irradiating the anticancer agent with a predetermined ultraviolet ray. Specifically, ultraviolet rays are applied to an object (object to be treated) to which an anticancer drug adheres to the surface.
　以下では、この本発明に係る抗がん剤の分解方法の詳細につき、実施形態に則して説明される。ただし、本発明に係る抗がん剤の分解方法の利用態様は、以下の実施形態で説明される内容には限定されない。 Hereinafter, the details of the method for decomposing the anticancer agent according to the present invention will be described according to the embodiment. However, the usage mode of the method for decomposing the anticancer agent according to the present invention is not limited to the contents described in the following embodiments.
　図１及び図２は、本発明に係る抗がん剤の分解方法の一実施状態を模式的に示す図面である。図１では、安全キャビネット１内で作業員２０が薬剤調合等の作業を行う場面が模式的に図示されている。なお、図２は、作業員２０側から安全キャビネット１を見たときの模式的な図面に対応する。 1 and 2 are drawings schematically showing one implementation state of the method for decomposing an anticancer agent according to the present invention. FIG. 1 schematically illustrates a scene in which a worker 20 performs work such as drug preparation in the safety cabinet 1. Note that FIG. 2 corresponds to a schematic drawing when the safety cabinet 1 is viewed from the worker 20 side.
　抗がん剤の調製作業時に、作業員２０が抗がん剤に直接接触したり、霧状の粒子を吸入してしまうと、皮膚の炎症や発がんを生じるリスクがある。更に、抗がん剤が周囲に離散することにより、環境が汚染されて、作業員２０以外の人間に対して同様の影響を生じさせるおそれもある。 If the worker 20 comes into direct contact with the anticancer drug or inhales atomized particles during the preparation work of the anticancer drug, there is a risk of skin inflammation and carcinogenesis. Further, the dispersion of the anticancer drug in the surroundings may pollute the environment and cause the same effect on humans other than the worker 20.
　かかる観点から、作業員２０は、保護手袋、マスク、保護メガネといった保護具を装着した上で、安全キャビネット１の作業室４内で作業を行うことが推奨されている。安全キャビネット１は、室内床２の上に設置されており、作業室４内（作業台３の上面）において、作業員２０によって患者に投与するための抗がん剤を調製すべく薬剤の調合等の作業が行われる。安全キャビネット１には、作業台３よりも上方の位置にＨＥＰＡ（High Efficiency Particulate Air）フィルタ９が設置されている。安全キャビネット１内の雰囲気Ｇ１は、当該雰囲気Ｇ１に含まれる、抗がん剤の調製作業時に生じた薬剤の微粒子等がＨＥＰＡフィルタ９によって吸着除去された後、排気される。 From this point of view, it is recommended that the worker 20 wears protective equipment such as protective gloves, a mask, and protective goggles, and then works in the work room 4 of the safety cabinet 1. The safety cabinet 1 is installed on the indoor floor 2, and in the work room 4 (upper surface of the work table 3), the preparation of the drug for preparing the anticancer drug to be administered to the patient by the worker 20. Etc. are performed. A HEPA (High Efficiency Particulate Air) filter 9 is installed in the safety cabinet 1 at a position above the workbench 3. The atmosphere G1 in the safety cabinet 1 is exhausted after the fine particles of the drug contained in the atmosphere G1 and generated during the preparation work of the anticancer agent are adsorbed and removed by the HEPA filter 9.
　本実施形態の安全キャビネット１には、光源１０が取り付けられている。この光源１０は、２００ｎｍ以上、３００ｎｍ未満の波長域に光出力を示す紫外線Ｌ１を出射する。図１及び図２では、光源１０からの紫外線Ｌ１が、室内床２及び作業台３に向かって照射される例が図示されている。この光源１０は、後述するように、安全キャビネット１内や室内床２の面上に付着した抗がん剤を分解する目的で設置されている。 A light source 10 is attached to the safety cabinet 1 of the present embodiment. The light source 10 emits ultraviolet L1 indicating an optical output in a wavelength range of 200 nm or more and less than 300 nm. 1 and 2 show an example in which the ultraviolet L1 from the light source 10 is irradiated toward the indoor floor 2 and the workbench 3. As will be described later, the light source 10 is installed for the purpose of decomposing the anticancer agent adhering to the inside of the safety cabinet 1 or the surface of the indoor floor 2.
　光源１０は、一例として紫外線Ｌ１を発するエキシマランプで構成される。図３は、このエキシマランプの構成を模式的に示す平面図であり、図４は、図３のＡ１－Ａ１線断面図である。 The light source 10 is composed of an excimer lamp that emits ultraviolet L1 as an example. FIG. 3 is a plan view schematically showing the configuration of this excimer lamp, and FIG. 4 is a sectional view taken along line A1-A1 of FIG.
　光源１０は、方向ｄ１に沿って延伸する発光管１１を有する。発光管１１は、合成石英ガラスなどの誘電体からなり、紫外線Ｌ１を透過する材料である。発光管１１は内部が封止されており、内部には放電によってエキシマ分子を形成する発光ガス１２Ｇが封入されている。 The light source 10 has a light emitting tube 11 extending along the direction d1. The arc tube 11 is made of a dielectric such as synthetic quartz glass and is a material that transmits ultraviolet L1. The inside of the arc tube 11 is sealed, and the luminescent gas 12G that forms excimer molecules by electric discharge is sealed inside.
　光源１０は、発光管１１の管壁に形成された一対の電極１３（１３ａ，１３ｂ）を備える。図３及び図４の例では、光源１０から紫外線Ｌ１が取り出される側（＋ｄ２側）に配置された電極１３ａがメッシュ形状又は線形状を呈し、反対側に配置された電極１３ｂが膜形状を呈している。なお、この場合、電極１３ｂは、紫外線Ｌ１に対して反射性を示す金属材料（例えばＡｌ、Ａｌ合金等）で構成されるか、電極１３ｂが形成されている側における発光管１１の管壁に反射膜（不図示）が設けられるのが好ましい。この反射膜としては、Ａｌ、Ａｌ合金、ステンレス、シリカ、シリカアルミナなどを利用することができる。 The light source 10 includes a pair of electrodes 13 (13a, 13b) formed on the tube wall of the arc tube 11. In the examples of FIGS. 3 and 4, the electrode 13a arranged on the side (+ d2 side) from which the ultraviolet L1 is taken out from the light source 10 has a mesh shape or a linear shape, and the electrode 13b arranged on the opposite side has a film shape. ing. In this case, the electrode 13b is made of a metal material (for example, Al, Al alloy, etc.) that is reflective to the ultraviolet L1 or is attached to the tube wall of the arc tube 11 on the side where the electrode 13b is formed. It is preferable that a reflective film (not shown) is provided. As the reflective film, Al, Al alloy, stainless steel, silica, silica alumina and the like can be used.
　なお、図１では、光源１０が安全キャビネット１の壁面近傍に設置されているが、例えば、作業室４内の中央付近に設置される場合には、光源１０から＋ｄ２方向及び－ｄ２方向の双方に向かって紫外線Ｌ１が取り出されるのが好ましい。かかる場合には、電極１３ｂについても、電極１３ａと同様にメッシュ形状又は線形状を呈しているものとしてよい。 In FIG. 1, the light source 10 is installed near the wall surface of the safety cabinet 1, but for example, when it is installed near the center in the work room 4, both the + d2 direction and the −d2 direction from the light source 10 are installed. It is preferable that the ultraviolet L1 is taken out toward the direction. In such a case, the electrode 13b may also have a mesh shape or a linear shape like the electrode 13a.
　不図示の点灯電源から給電線を介して一対の電極１３（１３ａ，１３ｂ）間に、例えば５０ｋＨｚ～５ＭＨｚ程度の高周波の交流電圧が印加されると、発光ガス１２Ｇに対して、発光管１１を介して前記電圧が印加される。このとき、発光ガス１２Ｇが封入されている放電空間内で放電プラズマが生じ、発光ガス１２Ｇの原子が励起されてエキシマ状態となり、この原子が基底状態に移行する際にエキシマ発光を生じる。 When a high-frequency AC voltage of, for example, about 50 kHz to 5 MHz is applied between the pair of electrodes 13 (13a, 13b) from a lighting power source (not shown) via a feeder line, the arc tube 11 is attached to the light emitting gas 12G. The voltage is applied through. At this time, a discharge plasma is generated in the discharge space in which the light emitting gas 12G is enclosed, an atom of the light emitting gas 12G is excited to enter an excimer state, and when this atom shifts to the ground state, excimer light emission is generated.
　発光ガス１２Ｇの種類によって、紫外線Ｌ１の波長が設定される。例えば、発光ガス１２ＧにＫｒＣｌが含まれる場合には、エキシマランプで構成された光源１０からは主ピーク波長が２２２ｎｍ近傍の紫外線Ｌ１が出射される。発光ガス１２ＧにＫｒＢｒが含まれる場合には、光源１０から主たるピーク波長が２０７ｎｍ近傍の紫外線Ｌ１が出射される。発光ガス１２ＧにＸｅＩが含まれる場合には、光源１０から主たるピーク波長が２５３ｎｍ近傍の紫外線Ｌ１が出射される。発光ガス１２ＧにＸｅＢｒが含まれる場合には、光源１０から主たるピーク波長が２８３ｎｍ近傍の紫外線Ｌ１が出射される。 The wavelength of ultraviolet L1 is set according to the type of luminescent gas 12G. For example, when the luminescent gas 12G contains KrCl, ultraviolet L1 having a main peak wavelength in the vicinity of 222 nm is emitted from the light source 10 composed of an excimer lamp. When KrBr is contained in the luminescent gas 12G, ultraviolet L1 having a main peak wavelength in the vicinity of 207 nm is emitted from the light source 10. When the luminescent gas 12G contains XeI, ultraviolet L1 having a main peak wavelength of around 253 nm is emitted from the light source 10. When XeBr is contained in the luminescent gas 12G, ultraviolet L1 having a main peak wavelength in the vicinity of 283 nm is emitted from the light source 10.
　図５は、発光ガス１２ＧにＫｒＣｌが含まれるエキシマランプで構成された光源１０から出射される紫外線Ｌ１のスペクトルを示す図面である。 FIG. 5 is a drawing showing a spectrum of ultraviolet rays L1 emitted from a light source 10 composed of an excimer lamp containing KrCl in a light emitting gas 12G.
　なお、別の例として、光源１０は、低圧水銀ランプやＬＥＤ等で構成することもできる。 As another example, the light source 10 can also be configured by a low-pressure mercury lamp, an LED, or the like.
　特に、光源１０がＫｒＣｌ又はＫｒＢｒを発光ガス１２Ｇとして含むエキシマランプで構成される場合、紫外線Ｌ１の主ピーク波長が、２００ｎｍ以上、２３０ｎｍ以下の波長範囲内となる。この波長範囲内の紫外線は、仮に人体の皮膚に対して照射されても、皮膚の角質層で吸収され、それよりも内側（基底層側）には進行しない。よって、作業員２０が安全キャビネット１内で作業中であっても、光源１０を点灯できる。 In particular, when the light source 10 is composed of an excimer lamp containing KrCl or KrBr as a light emitting gas 12G, the main peak wavelength of the ultraviolet L1 is within the wavelength range of 200 nm or more and 230 nm or less. Even if the ultraviolet rays in this wavelength range are applied to the skin of the human body, they are absorbed by the stratum corneum of the skin and do not proceed to the inside (basal layer side). Therefore, the light source 10 can be turned on even when the worker 20 is working in the safety cabinet 1.
　一方、光源１０が低圧水銀ランプ等、２４０ｎｍ以上、３００ｎｍ未満の波長域に光出力を示す場合には、作業員２０の人体への影響に鑑み、作業員２０が安全キャビネット１の近傍に存在しない時間帯に限って、光源１０を点灯させるのが好ましい。 On the other hand, when the light source 10 exhibits light output in a wavelength range of 240 nm or more and less than 300 nm, such as a low-pressure mercury lamp, the worker 20 does not exist in the vicinity of the safety cabinet 1 in view of the influence on the human body of the worker 20. It is preferable to turn on the light source 10 only in the time zone.
　上述したように、作業員２０が作業室４内で抗がん剤の調製作業をすることで、安全キャビネット１の壁面や、作業台３の上面、室内床２の上面等に、抗がん剤の一部が漏れて付着する可能性がある。本実施形態の安全キャビネット１には、光源１０が設置されているため、光源１０からの紫外線Ｌ１が照射されることで、壁面等に付着した抗がん剤が分解される。また、単に光源１０から紫外線Ｌ１を照射することで抗がん剤が分解されるため、従来の方法のように、高濃度のオゾンを空間内に導入したり、処理対象物の表面に光触媒粒子を塗布する必要がない。 As described above, when the worker 20 prepares the anticancer drug in the work room 4, the anticancer drug is applied to the wall surface of the safety cabinet 1, the upper surface of the work table 3, the upper surface of the indoor floor 2, and the like. Some of the agent may leak and adhere. Since the light source 10 is installed in the safety cabinet 1 of the present embodiment, the anticancer agent adhering to the wall surface or the like is decomposed by the irradiation of the ultraviolet L1 from the light source 10. Further, since the anticancer agent is decomposed simply by irradiating the light source 10 with ultraviolet L1, high-concentration ozone is introduced into the space or photocatalytic particles are formed on the surface of the object to be treated, as in the conventional method. No need to apply.
　図６は、抗がん剤の一種であるドキソルビシンの吸収スペクトルを示す図面である。なお、具体的には、ドキソルビシン塩酸塩の形で調合時には利用されるため、図６においても、ドキソルビシン塩酸塩の吸収スペクトルが示されている。 FIG. 6 is a drawing showing an absorption spectrum of doxorubicin, which is a kind of anticancer drug. Specifically, since it is used in the form of doxorubicin hydrochloride at the time of preparation, the absorption spectrum of doxorubicin hydrochloride is also shown in FIG.
　図６に示すように、ドキソルビシン塩酸塩は、波長２００ｎｍ以上、３００ｎｍ以下の範囲内の紫外線Ｌ１に対して、比較的高い吸光度を示すことが確認される。このようなドキソルビシン塩酸塩に対して上記波長帯の紫外線Ｌ１を照射することで、ドキソルビシン塩酸塩が分解できることにつき、検証を行った。 As shown in FIG. 6, it is confirmed that doxorubicin hydrochloride exhibits a relatively high absorbance with respect to ultraviolet L1 in the wavelength range of 200 nm or more and 300 nm or less. It was verified that doxorubicin hydrochloride can be decomposed by irradiating such doxorubicin hydrochloride with ultraviolet L1 in the above wavelength band.
　［検証１］
　（手順）
　ドキソルビシン塩酸塩（富士フィルム和光純薬社製、０４０－２１５２１）に対して蒸留水を混合して、濃度２００μｇ／ｍＬのドキソルビシン水溶液Ｘ１を精製した。その後、２５ｍｍ×２０ｍｍ寸法のアルミホイル切片上に、ドキソルビシン水溶液を１００μＬ滴下し、乾燥させることで、試験物Ｙ１を作製した。 [Verification 1]
(procedure)
Distilled water was mixed with doxorubicin hydrochloride (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd., 040-21521) to purify the doxorubicin aqueous solution X1 having a concentration of 200 μg / mL. Then, 100 μL of an aqueous solution of doxorubicin was dropped onto an aluminum foil section having a size of 25 mm × 20 mm and dried to prepare a test product Y1.
　この試験物Ｙ１に対して、照射面における照度２ｍＷ／ｃｍ2で、照射時間を変化させながら紫外線Ｌ１を照射した。照射後の試験物Ｙ２をチューブに入れ、超純水２ｍＬを加えて密閉後、撹拌した。その後、遠心分離を行って上清をサンプリングし、分析用試料Ｚ１を作製した。なお、紫外線Ｌ１を照射する光源としては、図３～図５を参照して上述したＫｒＣｌエキシマランプ（主ピーク波長２２２ｎｍ）と、低圧水銀ランプ（主ピーク波長２５４ｎｍ）とが用いられた。ただし、低圧水銀ランプについては、２５４ｎｍ以外の波長域に生じる副ピーク（１８５ｎｍ近傍）については、遮断するためのフィルタが設けられた。 The test product Y1 was irradiated with ultraviolet rays L1 at an illuminance of 2 mW / cm 2 on the irradiation surface while changing the irradiation time. The irradiated test product Y2 was placed in a tube, 2 mL of ultrapure water was added, the mixture was sealed, and the mixture was stirred. Then, centrifugation was performed and the supernatant was sampled to prepare a sample Z1 for analysis. As the light source for irradiating the ultraviolet L1, the KrCl excimer lamp (main peak wavelength 222 nm) and the low pressure mercury lamp (main peak wavelength 254 nm) described above with reference to FIGS. 3 to 5 were used. However, for low-pressure mercury lamps, a filter is provided to block sub-peaks (near 185 nm) that occur in wavelength ranges other than 254 nm.
　それぞれの光源から紫外線Ｌ１が照射された各分析用試料Ｚ１に対して、高速液体クロマトグラフ（ＨＰＬＣ）装置を用いて分析を行った。なお、比較例として、試験物Ｙ１に対して、紫外線Ｌ１の照射を行わない点を除けば同様の方法で作製された分析用試料Ｚ０に対し、同様の分析を行った。 Analysis was performed on each analytical sample Z1 irradiated with ultraviolet L1 from each light source using a high performance liquid chromatograph (HPLC) device. As a comparative example, the same analysis was performed on the analysis sample Z0 prepared by the same method except that the test material Y1 was not irradiated with the ultraviolet L1.
　図７Ａは、比較例１として準備された分析用試料Ｚ０に対する、ＨＰＬＣクロマトグラムである。また、図７Ｂ～図７Ｄは、試験物Ｙ１に対して主ピーク波長２２２ｎｍの紫外線Ｌ１が照射されることで得られた、実施例としての分析用試料Ｚ１に対する、ＨＰＬＣクロマトグラムである。より詳細には、図７Ｂ～図７Ｄは、それぞれ、試験物Ｙ１に対する紫外線Ｌ１の露光量を５００ｍＪ／ｃｍ2、１０００ｍＪ／ｃｍ2、５０００ｍＪ／ｃｍ2として作製された分析用試料Ｚ１のＨＰＬＣクロマトグラムである。 FIG. 7A is an HPLC chromatogram for analytical sample Z0 prepared as Comparative Example 1. Further, FIGS. 7B to 7D are HPLC chromatograms for the analytical sample Z1 as an example obtained by irradiating the test product Y1 with ultraviolet L1 having a main peak wavelength of 222 nm. More specifically, FIG. 7B ~-7D, respectively, HPLC chromatograms of the test substance 500 mJ / cm 2 exposure amount of ultraviolet L1 for Y1, 1000mJ / cm 2, 5000mJ / cm 2 analytical sample Z1 fabricated as Is.
　図７Ａ～図７Ｄに示す各クロマトグラムでは、いずれも２つのピークが確認されている。これらのピーク値は、分析用試料（Ｚ０，Ｚ１）に含まれるドキソルビシンの量が多いほど、大きくなる。つまり、図７Ａに示す、紫外線Ｌ１が照射されていない比較例１における分析用試料Ｚ０のクロマトグラムにおいて、２つのピーク近傍の波形が表す領域の面積Ｓ０を基準とし、実施例の分析用試料Ｚ１の各クロマトグラムで得られた同領域の面積Ｓ１の基準値Ｓ０からの減少量（Ｓ０－Ｓ１）の、基準値Ｓ０に対する比率をもって、紫外線Ｌ１が照射された後のドキソルビシンの残存率とみなすことができる。 Two peaks have been confirmed in each of the chromatograms shown in FIGS. 7A to 7D. These peak values increase as the amount of doxorubicin contained in the analysis sample (Z0, Z1) increases. That is, in the chromatogram of the analytical sample Z0 in Comparative Example 1 not irradiated with the ultraviolet L1 shown in FIG. 7A, the analytical sample Z1 of the example is based on the area S0 of the region represented by the waveform near the two peaks. The ratio of the amount of decrease (S0-S1) from the reference value S0 of the area S1 of the same region obtained in each chromatogram to the reference value S0 is regarded as the residual rate of doxorubicin after irradiation with ultraviolet L1. Can be done.
　図８Ａは、上記の方法によって算定されたドキソルビシンの残存率と紫外線Ｌ１の露光量との関係を示すグラフである。図８Ａには、主ピーク波長２２２ｎｍの紫外線Ｌ１が照射された場合と、主ピーク波長２５４ｎｍの紫外線Ｌ１が照射された場合の双方のデータが示されている。 FIG. 8A is a graph showing the relationship between the residual rate of doxorubicin calculated by the above method and the exposure amount of ultraviolet L1. FIG. 8A shows data of both the case of being irradiated with the ultraviolet L1 having a main peak wavelength of 222 nm and the case of being irradiated with the ultraviolet L1 having a main peak wavelength of 254 nm.
　いずれの波長の紫外線Ｌ１によっても、露光量が増加するに従ってドキソルビシンの残存率も低下していることが分かる。つまり、紫外線Ｌ１の照射によって、ドキソルビシンが分解されることが確認される。 It can be seen that the residual rate of doxorubicin decreases as the exposure amount increases with the ultraviolet L1 of any wavelength. That is, it is confirmed that doxorubicin is decomposed by irradiation with ultraviolet L1.
　ドキソルビシン塩酸塩は、以下の（１）式で表される物質である。 Doxorubicin hydrochloride is a substance represented by the following formula (1).
Figure JPOXMLDOC01-appb-C000001
Figure JPOXMLDOC01-appb-C000001
　すなわち、ドキソルビシン塩酸塩には、Ｃ－Ｈ結合や、Ｃ－Ｃ結合、Ｃ＝Ｃ結合、Ｏ－Ｈ結合などの各分子結合が含まれる。例えば、Ｃ－Ｈ結合の結合エネルギーは４０８．９ｋＪ／ｍｏｌであり、波長に換算すると２９３ｎｍである。よって、波長２９３ｎｍ未満の紫外線Ｌ１がＣ－Ｈ結合に取り込まれると、理論的にＣ－Ｈ結合が切断されることとなる。 That is, doxorubicin hydrochloride includes each molecular bond such as C—H bond, CC bond, C = C bond, and OH bond. For example, the binding energy of the CH bond is 408.9 kJ / mol, which is 293 nm in terms of wavelength. Therefore, when the ultraviolet L1 having a wavelength of less than 293 nm is incorporated into the CH bond, the CH bond is theoretically broken.
　同様に、Ｃ－Ｃ結合の結合エネルギーは３５３．２ｋＪ／ｍｏｌであり、波長に換算すると３３９ｎｍである。 Similarly, the binding energy of the CC bond is 353.2 kJ / mol, which is 339 nm in terms of wavelength.
　ところで、図６によれば、３００ｎｍ未満の紫外線Ｌ１に対しては、ドキソルビシン塩酸塩はある程度の吸光度を示すことが分かる。一方、波長が３００ｎｍ以上、４００ｎｍ以下の範囲内では、ドキソルビシン塩酸塩に対する吸光度は低い。つまり、波長３００ｎｍ未満の紫外線Ｌ１がドキソルビシン塩酸塩に対して照射されると、ドキソルビシン塩酸塩に対して一部の紫外線Ｌ１が吸収される結果、ドキソルビシン塩酸塩の化学結合の一部が切断されることで、ドキソルビシンが分解されるものと考えられる。一方で、波長３００ｎｍ以上、４００ｎｍ以下の紫外線Ｌ１がドキソルビシンに対して照射された場合には、その大部分がドキソルビシンを透過してしまい、充分な光エネルギーをドキソルビシンに対して作用させることができないと考えられる。 By the way, according to FIG. 6, it can be seen that doxorubicin hydrochloride exhibits a certain degree of absorbance with respect to ultraviolet L1 having a diameter of less than 300 nm. On the other hand, when the wavelength is in the range of 300 nm or more and 400 nm or less, the absorbance for doxorubicin hydrochloride is low. That is, when the doxorubicin hydrochloride is irradiated with ultraviolet L1 having a wavelength of less than 300 nm, a part of the ultraviolet L1 is absorbed by the doxorubicin hydrochloride, and as a result, a part of the chemical bond of the doxorubicin hydrochloride is broken. Therefore, it is considered that doxorubicin is decomposed. On the other hand, when ultraviolet L1 having a wavelength of 300 nm or more and 400 nm or less is irradiated to doxorubicin, most of it is transmitted through doxorubicin, and sufficient light energy cannot be applied to doxorubicin. Conceivable.
　また、多くの結合を切断するには多くの露光量が必要になると考えられる。このことは、露光量の増加と共に、ドキソルビシンの残量率が低下する傾向を示す図８の結果にも現れている。 In addition, it is considered that a large amount of exposure is required to cut many bonds. This is also shown in the result of FIG. 8, which shows that the residual rate of doxorubicin tends to decrease as the exposure amount increases.
　一方で、紫外線Ｌ１の波長が２００ｎｍ未満である場合には、空気中の酸素によって吸収される量が増えてしまう。この結果、処理対象物である室内床２及び作業台３の表面に対して、充分な照度で紫外線Ｌ１を照射することができない。かかる観点から、紫外線Ｌ１の波長は、２００ｎｍ以上、３００ｎｍ未満に設定される。 On the other hand, when the wavelength of the ultraviolet L1 is less than 200 nm, the amount absorbed by oxygen in the air increases. As a result, the surfaces of the indoor floor 2 and the workbench 3 which are the objects to be treated cannot be irradiated with the ultraviolet L1 with sufficient illuminance. From this point of view, the wavelength of the ultraviolet L1 is set to 200 nm or more and less than 300 nm.
　図８Ｂは、抗がん剤の材料としてドキソルビシンに替えてメトトレキサートを用いて、、上記と同様の方法で検証を行った結果を、図８Ａにならって表示したグラフである。図８Ｂによれば、主ピーク波長２２２ｎｍの紫外線Ｌ１と、主ピーク波長２５４ｎｍの紫外線のいずれの場合においても、露光量が増加するに従ってメトトレキサートの残存率も低下していることが分かる。つまり、紫外線Ｌ１の照射によって、メトトレキサートが分解されることが確認される。なお、ドキソルビシンはアントラサイクリン系抗癌抗生物質の一例であり、メトトレキサートは葉酸拮抗薬の一例である。 FIG. 8B is a graph showing the results of verification using methotrexate instead of doxorubicin as a material for an anticancer drug in the same manner as described above, following FIG. 8A. According to FIG. 8B, it can be seen that the residual rate of methotrexate decreases as the exposure amount increases in both the case of the ultraviolet L1 having the main peak wavelength of 222 nm and the ultraviolet ray having the main peak wavelength of 254 nm. That is, it is confirmed that methotrexate is decomposed by irradiation with ultraviolet L1. Doxorubicin is an example of an anthracycline anticancer antibiotic, and methotrexate is an example of a folic acid antagonist.
　図９Ａ～図９Ｅは、ドキソルビシン以外の抗がん剤の一例である、メトトレキサート、シタラビン、ビンクリスチン（硫酸塩）、エトポシド、及びマイトマイシンＣの吸収スペクトルを示す図面である。ビンクリスチンは調合時には硫酸塩の形で利用されるため、図９Ｃではビンクリスチン硫酸塩の吸収スペクトルが示されている。 9A-9E are drawings showing absorption spectra of methotrexate, cytarabine, vincristine (sulfate), etoposide, and mitomycin C, which are examples of anticancer agents other than doxorubicin. Since vincristine is used in the form of sulfate at the time of preparation, the absorption spectrum of vincristine sulfate is shown in FIG. 9C.
　なお、シタラビンは、ピリミジン拮抗薬の一例である。ビンクリスチンは、ビンアルカロイド類の抗がん剤の一例である。マイトマイシンＣは、ナイトロジェンマスタード類の抗がん剤の一例である。 Cytarabine is an example of a pyrimidine antagonist. Vincristine is an example of an anticancer drug of bin alkaloids. Mitomycin C is an example of an anticancer agent of nitrogen mustards.
　これら図９Ａ～図９Ｅに示す各抗がん剤においても、２００ｎｍ以上、３００ｎｍ未満の範囲内の紫外線Ｌ１に対して、ある程度の吸光度が確認される。また、これらの抗がん剤についても、ドキソルビシンと同様に、Ｃ－Ｃ結合や、Ｃ－Ｈ結合の化学結合を含む。よって、同様の観点から、メトトレキサート、シタラビン、ビンクリスチン硫酸塩、エトポシド、及びマイトマイシンＣに対しても、２００ｎｍ以上、３００ｎｍ未満の範囲内の紫外線Ｌ１が照射されることで、分解作用が示されることが分かる。 Even in each of the anticancer agents shown in FIGS. 9A to 9E, a certain degree of absorbance is confirmed for ultraviolet L1 in the range of 200 nm or more and less than 300 nm. Further, these anticancer agents also include a CC bond and a chemical bond of a C—H bond, as in the case of doxorubicin. Therefore, from the same viewpoint, methotrexate, cytarabine, vincristine sulfate, etoposide, and mitomycin C may also be exposed to ultraviolet L1 in the range of 200 nm or more and less than 300 nm to exhibit a decomposition effect. I understand.
　［検証２］
　更に、複数種類の抗がん剤に対して、上記波長帯の紫外線Ｌ１を照射することで、分解できることにつき、別の方法で検証を行った。 [Verification 2]
Furthermore, it was verified by another method that a plurality of types of anticancer agents could be decomposed by irradiating them with ultraviolet L1 in the above wavelength band.
　（対象の抗がん剤）
　検証対象となる抗がん剤としては、以下の物質が採用された。
　・ナイトロジェンマスタード類：ベンダムスチン、マイトマイシンＣ
　・ピリミジン拮抗薬：シタラビン
　・アントラサイクリン系抗癌抗生物質：ドキソルビシン
　・トポイソメラーゼ阻害薬：イリノテカン、エトポシド
　・トリアゼン類：ダカルバジン
　・ビンアルカロイド類：ビンクリスチン
　・タキサン類：ドセタキセル (Target anti-cancer drug)
The following substances were adopted as the anticancer agents to be verified.
・ Nitrogen mustards: Bendamustine, Mitomycin C
・ Pyrimidin antagonist: Cytarabine ・ Anthracycline anticancer antibiotic: doxorubicin ・ Topoisomerase inhibitor: irinotecan, etoposide ・ Triazens: dacarbazine ・ Bin alkaloids: vincristine ・ Taxanes: docetaxel
　（手順）
　対象となる上記それぞれの抗がん剤に対して、所定の容器内で蒸留水を混合して水溶液を精製した。次に、それぞれの水溶液の、紫外線照射前における吸収スペクトルを吸光光度計（サーモフィッシャーサイエンス社製、NANODROP ONE）を用いて測定した。次に、それぞれの水溶液に対して照射面における照度２ｍＷ／ｃｍ2で、照射時間を変化させながら紫外線Ｌ１を照射し、照射後の吸収スペクトルを、上記と同様の方法で測定した。 (procedure)
Distilled water was mixed with each of the above-mentioned anticancer agents to be targeted in a predetermined container to purify the aqueous solution. Next, the absorption spectra of each aqueous solution before irradiation with ultraviolet rays were measured using an absorptiometer (NANODROP ONE manufactured by Thermo Fisher Science Co., Ltd.). Next, each aqueous solution was irradiated with ultraviolet L1 at an illuminance of 2 mW / cm 2 on the irradiation surface while changing the irradiation time, and the absorption spectrum after irradiation was measured by the same method as described above.
　それぞれの抗がん剤の水溶液に関する、紫外線Ｌ１の照射前、及び紫外線Ｌ１の照射後の吸収スペクトルを、図１０Ａ～図１８Ｂに示す。それぞれの図は、以下に対応する。 The absorption spectra of the aqueous solutions of the respective anticancer agents before and after the irradiation with the ultraviolet L1 are shown in FIGS. 10A to 18B. Each figure corresponds to:
　図１０Ａは、抗がん剤としてマイトマイシンＣを用いた場合の、紫外線Ｌ１の照射前における、抗がん剤の水溶液の吸収スペクトルである。図１０Ｂは、抗がん剤としてマイトマイシンＣを用いた場合の、ＫｒＣｌランプから出射された紫外線Ｌ１を５０００ｍＪ照射した後における、抗がん剤の水溶液の吸収スペクトルである。 FIG. 10A is an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet L1 when mitomycin C is used as the anticancer agent. FIG. 10B is an absorption spectrum of an aqueous solution of an anticancer agent after irradiating 5000 mJ of ultraviolet L1 emitted from a KrCl lamp when mitomycin C is used as the anticancer agent.
　図１１Ａ、図１２Ａ、図１３Ａ、図１４Ａ、図１５Ａ、図１６Ａ、図１７Ａ、及び図１８Ａは、図１０ＡにおけるマイトマイシンＣに替えて、それぞれ、シタラビン、ベンダムスチン、ドキソルビシン、イリノテカン、ダカルバジン、エトポシド、ビンクリスチン、及びドセタキセルを用いた場合の、紫外線Ｌ１の照射前における、抗がん剤の水溶液の吸収スペクトルである。 11A, 12A, 13A, 14A, 15A, 16A, 17A, and 18A replace mitomycin C in FIG. 10A with cytarabine, bendamustine, doxorubicin, irinotecan, dacarbazine, etoposide, and vincristine, respectively. , And an absorption spectrum of an aqueous solution of an anticancer agent before irradiation with ultraviolet L1 when docetaxel is used.
　図１１Ｂ、図１２Ｂ、図１３Ｂ、図１４Ｂ、図１５Ｂ、図１６Ｂ、図１７Ｂ、及び図１８Ｂは、図１０ＢにおけるマイトマイシンＣに替えて、それぞれ、シタラビン、ベンダムスチン、ドキソルビシン、イリノテカン、ダカルバジン、エトポシド、ビンクリスチン、及びドセタキセルを用いた場合の、ＫｒＣｌランプから出射された紫外線Ｌ１を５０００ｍＪ照射した後における、抗がん剤の水溶液の吸収スペクトルである。 11B, 12B, 13B, 14B, 15B, 16B, 17B, and 18B replace mitomycin C in FIG. 10B with cytarabine, bendamustine, doxorubicin, irinotecan, dacarbazine, etoposide, and vincristine, respectively. , And an absorption spectrum of an aqueous solution of an anticancer agent after irradiation with 5000 mJ of ultraviolet L1 emitted from a KrCl lamp when docetaxel is used.
　図１０Ａ～図１８Ｂの各図によれば、いずれの抗がん剤の場合であっても、紫外線Ｌ１の照射前後で吸収スペクトルの形状が大幅に変化していることが分かる。特に、検証を行った各抗がん剤を構成する物質は、紫外線Ｌ１の照射前において、ＫｒＣｌランプから出射される紫外線Ｌ１の波長域における高い吸光度を示している。つまり、これらの各抗がん剤に対してＫｒＣｌランプからの紫外線Ｌ１が照射されたことで、紫外線Ｌ１の一部が抗がん剤に吸収され、抗がん剤を構成する物質の化学結合の一部が切断されたことが示唆される。すなわち、上記いずれの抗がん剤についても、ＫｒＣｌランプから出射された紫外線Ｌ１によって分解されることが分かる。 According to each of FIGS. 10A to 18B, it can be seen that the shape of the absorption spectrum changes significantly before and after irradiation with the ultraviolet L1 regardless of which anticancer agent is used. In particular, the substances constituting each of the verified anticancer agents show high absorbance in the wavelength range of the ultraviolet L1 emitted from the KrCl lamp before the irradiation with the ultraviolet L1. That is, when each of these anticancer agents is irradiated with ultraviolet L1 from the KrCl lamp, a part of the ultraviolet L1 is absorbed by the anticancer agent, and the chemical bond of the substance constituting the anticancer agent is obtained. It is suggested that a part of was cut off. That is, it can be seen that any of the above anticancer agents is decomposed by the ultraviolet L1 emitted from the KrCl lamp.
　上記の観点から、紫外線Ｌ１の照射前後における吸収スペクトルの形状の変化をもって、抗がん剤を構成する物質の残存率を算定することができる。より詳細には、抗がん剤を構成する物質の残存率を以下のように規定することができる。すなわち、紫外線Ｌ１の照射前における、抗がん剤の吸収スペクトルのピーク値を示す波長（ピーク波長λp）での吸光度をＡ1とし、紫外線Ｌ１の照射後における前記ピーク波長λpでの吸光度をＡ2としたときに、照射前後におけるピーク波長λpの吸光度の変化の比率Ａ2／Ａ1によって、抗がん剤を構成する物質の残存率が規定できる。 From the above viewpoint, the residual rate of the substance constituting the anticancer agent can be calculated from the change in the shape of the absorption spectrum before and after the irradiation with the ultraviolet L1. More specifically, the residual rate of substances constituting the anticancer drug can be defined as follows. That is, the absorbance at the wavelength (peak wavelength λ p ) indicating the peak value of the absorption spectrum of the anticancer agent before irradiation with ultraviolet L1 is defined as A 1, and the absorbance at the peak wavelength λ p after irradiation with ultraviolet L1. When A 2 is set, the residual ratio of the substances constituting the anticancer agent can be defined by the ratio A 2 / A 1 of the change in the absorbance of the peak wavelength λ p before and after irradiation.
　図１９Ａ～図１９Ｉは、上記の方法で算定した、それぞれの抗がん剤を構成する物質の残存率と、紫外線Ｌ１の露光量との関係を示すグラフである。図１９Ａ、図１９Ｂ、図１９Ｃ、図１９Ｄ、図１９Ｅ、図１９Ｆ、図１９Ｇ、図１９Ｈ、及び図１９Ｉは、それぞれ、マイトマイシンＣ、シタラビン、ベンダムスチン、ドキソルビシン、イリノテカン、ダカルバジン、エトポシド、ビンクリスチン、及びドセタキセルの、残存率と紫外線Ｌ１の露光量との関係を示すグラフである。 19A to 19I are graphs showing the relationship between the residual rate of the substance constituting each anticancer agent and the exposure amount of ultraviolet L1 calculated by the above method. 19A, 19B, 19C, 19D, 19E, 19F, 19G, 19H, and 19I are mitomycin C, cytarabine, bendamustine, doxorubicin, irinotecan, dacarbazine, etoposide, vincristine, and docetaxel, respectively. It is a graph which shows the relationship between the residual ratio and the exposure amount of ultraviolet L1.
　なお、図１９Ａ～図１９Ｉでは、検証１と同様に、紫外線Ｌ１を照射する光源としてＫｒＣｌエキシマランプ（主ピーク波長２２２ｎｍ）を用いた場合と、低圧水銀ランプ（主ピーク波長２５４ｎｍ）を用いた場合の結果が示されている。 In FIGS. 19A to 19I, when the KrCl excimer lamp (main peak wavelength 222 nm) is used and the low pressure mercury lamp (main peak wavelength 254 nm) is used as the light source for irradiating the ultraviolet L1 as in the verification 1. The result of is shown.
　また、図１９Ｄでは、図８を参照して上述した、検証１の方法で得られたドキソルビシンの残存率と紫外線Ｌ１の露光量との関係を示すグラフが、重ね合わせられて図示されている。この検証１による結果は、図１９Ｄにおいて「ＨＰＬＣ」と表記されている。 Further, in FIG. 19D, a graph showing the relationship between the residual rate of doxorubicin obtained by the method of verification 1 and the exposure amount of ultraviolet L1 described above with reference to FIG. 8 is superimposed and shown. The result of this verification 1 is described as "HPLC" in FIG. 19D.
　図１９Ｄによれば、この検証２の方法で得られたドキソルビシンの分解特性の傾向が、検証１の方法で得られたドキソルビシンの分解特性の傾向と整合することが分かる。つまり、この検証２の方法で得られた分解特性の結果は、抗がん剤の特性が反映されたものである。 According to FIG. 19D, it can be seen that the tendency of the decomposition characteristics of doxorubicin obtained by the method of Verification 2 is consistent with the tendency of the decomposition characteristics of doxorubicin obtained by the method of Verification 1. That is, the result of the decomposition property obtained by the method of Verification 2 reflects the property of the anticancer drug.
　図１９Ａ～図１９Ｉによれば、２２２ｎｍ及び２５４ｎｍのいずれの波長の紫外線Ｌ１によっても、露光量が増加するに従って、抗がん剤を構成する各物質の残存率が低下していることが分かる。つまり、ドキソルビシン以外の抗がん剤である、マイトマイシンＣ、シタラビン、ベンダムスチン、イリノテカン、ダカルバジン、エトポシド、ビンクリスチン、及びドセタキセルについても、紫外線Ｌ１が照射されることで分解されることが確認される。 According to FIGS. 19A to 19I, it can be seen that the residual rate of each substance constituting the anticancer agent decreases as the exposure amount increases with the ultraviolet L1 having any wavelength of 222 nm and 254 nm. That is, it is confirmed that mitomycin C, cytarabine, bendamustine, irinotecan, dacarbazine, etoposide, vincristine, and docetaxel, which are anticancer agents other than doxorubicin, are also decomposed by irradiation with ultraviolet L1.
　なお、上述した各抗がん剤は、単に室内にそのまま放置しているだけでは、吸収スペクトルの変化は見られなかった。このことから、可視光の照射によっては、抗がん剤を構成する物質は分解されないことが示唆される。 In addition, each of the above-mentioned anticancer agents did not show any change in the absorption spectrum simply by leaving them indoors. This suggests that the substances constituting the anticancer drug are not decomposed by irradiation with visible light.
　［別実施形態］
　以下、別実施形態について説明する。 [Another Embodiment]
Hereinafter, another embodiment will be described.
　〈１〉上記実施形態では、紫外線Ｌ１が照射される処理対象物として、安全キャビネット１の壁、作業台３、及び室内床２を挙げて説明した。しかし、本発明に係る方法は、安全キャビネット１やその設置領域に対しての利用に限定されない。本発明は、抗がん剤が付着している可能性がある対象物の表面（物体表面）に対して、波長２００ｎｍ以上、３００ｎｍ未満の紫外線Ｌ１を照射する内容を包含するものであり、その対象物には限定されない。 <1> In the above embodiment, the wall of the safety cabinet 1, the work table 3, and the indoor floor 2 have been described as the objects to be treated to be irradiated with the ultraviolet L1. However, the method according to the present invention is not limited to the use for the safety cabinet 1 and its installation area. The present invention includes the content of irradiating the surface (object surface) of an object to which an anticancer agent may be attached with ultraviolet L1 having a wavelength of 200 nm or more and less than 300 nm. It is not limited to the object.
　〈２〉紫外線Ｌ１としては、主ピーク波長が２００ｎｍ以上、３００ｎｍ未満に含まれるのが好ましいが、少なくとも２００ｎｍ以上、３００ｎｍ未満の範囲内に光出力を示すスペクトルを示す紫外線Ｌ１であれば、本発明に用いることができる。このような紫外線Ｌ１であれば、ドキソルビシンを初めとする抗がん剤に対して高い割合で吸収され、抗がん剤を構成する物質の化学結合の一部を切断できる。 <2> The ultraviolet L1 preferably has a main peak wavelength of 200 nm or more and less than 300 nm, but the present invention is an ultraviolet L1 that exhibits a spectrum showing an optical output within a range of at least 200 nm or more and less than 300 nm. Can be used for. Such ultraviolet L1 is absorbed at a high rate with respect to anticancer agents such as doxorubicin, and can break a part of the chemical bond of the substance constituting the anticancer agent.
　〈３〉上記実施形態では、光源２が安全キャビネット１に設置されている場合について説明した。このように、光源２は、処理対象物が存在する領域近くの物体（安全キャビネット１等）や部屋（壁面や天井面）に固定的に取り付けられるものとしても構わない。また、別の例として、光源２は携帯可能な構造であっても構わない。 <3> In the above embodiment, the case where the light source 2 is installed in the safety cabinet 1 has been described. As described above, the light source 2 may be fixedly attached to an object (safety cabinet 1 or the like) or a room (wall surface or ceiling surface) near the area where the object to be processed exists. Further, as another example, the light source 2 may have a portable structure.
　光源２を携帯可能な構造とすることで、処理対象物の表面に対して短い照射距離で紫外線Ｌ１を照射することができる。つまり、処理対象物に対して高い照度で紫外線Ｌ１が照射できるため、同じ露光量を実現するために必要な照射時間を短くすることができる。ただし、この場合、光源２を携帯する作業員の人体に対する紫外線Ｌ１の被爆による影響を鑑みて、主ピーク波長が２００ｎｍ以上、２３０ｎｍ以下の波長範囲内に存在する紫外線Ｌ１を発する光源２であるのが好適である。 By making the light source 2 portable, it is possible to irradiate the surface of the object to be treated with ultraviolet L1 at a short irradiation distance. That is, since the ultraviolet L1 can irradiate the object to be processed with high illuminance, the irradiation time required to achieve the same exposure amount can be shortened. However, in this case, in consideration of the influence of the exposure of the ultraviolet L1 to the human body of the worker carrying the light source 2, the light source 2 emits the ultraviolet L1 existing in the wavelength range of 200 nm or more and 230 nm or less as the main peak wavelength. Is preferable.
１　　　：安全キャビネット
２　　　：室内床
３　　　：作業台
４　　　：作業室
９　　　：ＨＥＰＡフィルタ
１０　　：光源
１１　　：発光管
１２Ｇ　：発光ガス
１３　　：電極
１３ａ　：電極
１３ｂ　：電極
２０　　：作業員
Ｇ１　　：雰囲気
Ｌ１　　：紫外線 1: Safety cabinet 2: Indoor floor 3: Work table 4: Work room 9: HEPA filter 10: Light source 11: Emission tube 12G: Emission gas 13: Electrode 13a: Electrode 13b: Electrode 20: Worker G1: Atmosphere L1: Ultraviolet rays

Claims (7)

  1. 　２００ｎｍ以上、３００ｎｍ未満の波長域に光出力を示す紫外線を抗がん剤に照射する工程（ａ）を含むことを特徴とする、抗がん剤の分解方法。 A method for decomposing an anticancer agent, which comprises a step (a) of irradiating the anticancer agent with ultraviolet rays exhibiting light output in a wavelength range of 200 nm or more and less than 300 nm.
  2. 　前記工程（ａ）は、前記抗がん剤が付着した物体表面に対して前記紫外線を照射する工程であることを特徴とする、請求項１に記載の抗がん剤の分解方法。 The method for decomposing an anticancer agent according to claim 1, wherein the step (a) is a step of irradiating the surface of an object to which the anticancer agent is attached with the ultraviolet rays.
  3. 　前記工程（ａ）は、主ピーク波長が２００ｎｍ以上、３００ｎｍ未満の前記紫外線を照射することを特徴とする、請求項１又は２に記載の抗がん剤の分解方法。 The method for decomposing an anticancer agent according to claim 1 or 2, wherein the step (a) irradiates the ultraviolet rays having a main peak wavelength of 200 nm or more and less than 300 nm.
  4. 　前記工程（ａ）は、Ｋｒ及びＣｌを含む発光ガスが封入されたエキシマランプから前記紫外線を照射する工程であることを特徴とする、請求項３に記載の抗がん剤の分解方法。 The method for decomposing an anticancer agent according to claim 3, wherein the step (a) is a step of irradiating the ultraviolet rays from an excimer lamp filled with a luminescent gas containing Kr and Cl.
  5. 　前記抗がん剤が、アントラサイクリン系抗癌抗生物質、葉酸拮抗薬、ナイトロジェンマスタード類、ピリミジン拮抗薬、トポイソメラーゼ阻害薬、トリアゼン類、ビンアルカロイド類、及びタキサン類からなる群に属する１種以上であることを特徴とする、請求項１～４のいずれか１項に記載の抗がん剤の分解方法。 One or more of the anticancer agents belonging to the group consisting of anthracycline anticancer antibiotics, folic acid antagonists, nitrogen mustards, pyrimidine antagonists, topoisomerase inhibitors, triazens, bin alkaloids, and taxanes. The method for decomposing an anticancer agent according to any one of claims 1 to 4, wherein the method is characterized by the above.
  6. 　前記抗がん剤が、ドキソルビシンであることを特徴とする、請求項１～４のいずれか１項に記載の抗がん剤の分解方法。 The method for decomposing an anticancer agent according to any one of claims 1 to 4, wherein the anticancer agent is doxorubicin.
  7. 　前記抗がん剤が、メトトレキサート、シタラビン、ベンダムスチン、マイトマイシンＣ、シタラビン、イリノテカン、エトポシド、ダカルバジン、ビンクリスチン及びドセタキセルからなる群に属する１種以上であることを特徴とする、請求項１～４のいずれか１項に記載の抗がん剤の分解方法。 Any of claims 1 to 4, wherein the anticancer agent is at least one belonging to the group consisting of methotrexate, cytarabine, bendamustine, mitomycin C, cytarabine, irinotecan, etopocid, dacarbazine, vincristine and docetaxel. The method for decomposing an anticancer drug according to item 1.
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