JP5613900B2 - Aqueous photocatalytic composition and anticancer agent decomposition method using the composition - Google Patents

Description

  The present invention relates to an aqueous photocatalyst composition and a method for decomposing an anticancer agent using the composition, and in particular, it contains titanium dioxide and is used by spraying onto an object to be decomposed. The present invention relates to a method for decomposing an anticancer agent attached to a medical safety cabinet using the composition and the composition.

  The exposure of anti-cancer drugs to medical workers who handle anti-cancer drugs such as pharmacists is a problem. Exposure to anticancer drugs has been reported to be associated with increased reproductive toxicity such as miscarriage and an increased risk of carcinogenesis due to the long-term exposure (SG Selevan, ML Lindbohm, RW Hornung, K. Hemminki, A study of occupational exposure to antineoplastic drugs and fetal loss in nurses, N. Engl. J. Med, 313, 1173-1178 (1985)).

  Regarding the handling of anticancer drugs, according to the “Guidelines for Aseptic Preparation of Injections and Anticancer Drugs” supervised by the Japan Hospital Pharmacists Association, perform in a 24-hour safety cabinet and regularly clean the safety cabinet. Etc. are recommended. As the cleaning method, the anticancer agent is deactivated with an alkali or the like and then wiped with alcohol, or regularly wiped with a 0.3 M sodium hydroxide solution, depending on the type of drug. It is recommended to use sodium chlorite water, 1% sodium thiosulfate water, etc. together.

  However, the use of these decomposition solutions is complicated in that they are used for each drug used, are irritating to the human body, and must be wiped off after use. In addition, some anticancer agents such as cyclophosphamide, which have been reported to be carcinogenic, are only 28.5% decomposed in a 0.3M aqueous sodium hydroxide solution recommended as a decomposition solution, and are not contained in the safety cabinet. It was reported that the removal rate of 70% was difficult even after three times of wiping (Chie Mochizuki, Sayo Fujikawa, Zhenmotojin, Hitoshi Yoshida, safety cabinet for anticancer drug preparation) Comparison of cleaning liquids for wiping, Journal of Japanese Hospital Pharmacists Association, 44, 601-604 (2008)).

  On the other hand, using photocatalytic activity of titanium dioxide, it has been proposed to decompose cyclophosphamide and 5-fluorouracil into harmless inorganic substances on a thin film of titanium dioxide coated on spiral borosilicate glass. (Non-Patent Document 1). Moreover, the aqueous composition containing the titanium dioxide sol utilized for the antimicrobial use etc. of a medical facility is also proposed (patent document 1).

JP 2009-84542 A

Environ. Sci. Technol., 25, 460-467, 1991

  When using the titanium dioxide photocatalyst, as shown in FIG. 2, the titanium dioxide is fixed on some base material, and an object to be decomposed (denoted by x in the figure) is present on the base material. It is normal to decompose in the state. Also in the said patent document 1, after apply | coating an aqueous composition to board | substrates, such as the wash | cleaned vinyl chloride board, with a brush, it is dried at normal temperature for two days, and is fixed to the film form (patent document 1, an Example). This is because the catalyst itself is not subject to change in the reaction, and therefore it is economically reasonable to use it by immobilizing it in order to utilize the catalytic activity repeatedly.

  However, safety cabinets already used and contaminated with anti-cancer drugs must be thoroughly cleaned and then fixed with titanium dioxide for safety reasons. Take it.

  Therefore, an object of the present invention is to provide a method capable of easily removing an anticancer agent even in a safety cabinet that is already used and contaminated with the anticancer agent.

That is, the present invention
0.1 to 1.0% by weight of photocatalytically active titanium dioxide particles, and 0.3 to 0.5% by weight of a surfactant,
An aqueous photocatalyst composition characterized by being used by spraying on an object to be decomposed,
It is.

  As shown in FIG. 1, in this invention, after spraying the said photocatalyst aqueous composition in a safety cabinet, it decomposes | disassembles by irradiating light. The point that the catalyst is present on the object to be decomposed and that the catalyst is temporarily applied without being fixed to the equipment are overturned. By applying a photocatalytic aqueous composition having a predetermined composition in the form of a mist to the stainless steel surface of the cabinet, it is possible to achieve a decomposition efficiency superior to that of using it in the form of a film. In addition, the cost disadvantage that the catalyst cannot be used repeatedly can be within the range of no problem since the aqueous photocatalyst composition does not contain a film-forming component such as a binder and does not require construction costs. If it is the photocatalyst aqueous composition of this invention, it can be easily used also with respect to the safety cabinet already contaminated with the anticancer agent.

It is a conceptual diagram which shows the usage method of the photocatalyst aqueous composition of this invention. It is a conceptual diagram which shows the usage method of the conventional titanium dioxide photocatalyst.

  First, after describing the aqueous photocatalyst composition of the present invention (hereinafter sometimes referred to as “photocatalyst composition”), a decomposition method using the composition will be described.

<Titanium dioxide>
In the photocatalytic composition of the present invention, titanium dioxide is not particularly limited as long as it has photocatalytic activity, and may be any of anatase type, brookite type, visible light reaction type photocatalytic titanium oxide, or a mixture thereof. May be. The brookite type is more preferable in view of high catalytic activity. Examples of such brookite type titanium dioxide include nano titania (registered trademark, manufactured by Showa Titanium Co., Ltd.).

  The particle size of the titanium dioxide measured by the dynamic light scattering method is preferably 5 nm to 150 nm, more preferably 10 nm to 100 nm.

  The content of titanium dioxide in the photocatalyst composition is 0.05 to 1% by weight, preferably 0.1 to 0.5% by weight, more preferably 0.1 to 0.3% by weight based on the total weight of the composition. % By weight. If the content is less than the lower limit value, a sufficient catalytic effect cannot be obtained. On the other hand, if the content exceeds the upper limit value, the dispersion stability of titanium dioxide in the composition tends to deteriorate.

<Surfactant>
As the surfactant, anionic, cationic, nonionic, and betaine surfactants can be used. Anionic surfactants include sulfonic acid surfactants such as alkylbenzene sulfonates, alkylnaphthalene sulfonates, alkyl sulfonates, α-olefin sulfonates; alkyl sulfates, polyoxyethylene alkyl ether sulfates , Sulfate surfactants such as polyoxyethylene alkyl phenyl ether sulfates, polyoxyethylene styrenated phenyl ether sulfates; carboxylic acid surfactants such as ether carboxylic acids; alkyl phosphates, polyoxyethylene alkyl ethers Examples thereof include phosphate ester-based surfactants such as phosphates.

  Examples of the cationic surfactant include primary to tertiary alkylamine salts; quaternary ammonium salts such as tetraalkylammonium salts and trialkylbenzylammonium salts; alkylpyridium salts and alkylimidazolium salts. it can.

  Nonionic surfactants include polyoxyalkylene surfactants such as polyoxyethylene alkyl ether and polyoxyethylene alkyl phenyl ether; polyhydric alcohol fatty acid partial ester, polyoxyethylene fatty acid ester, polyglycerin fatty acid ester, triethanol Examples include fatty acid esters such as amine fatty acid partial esters.

  Examples of the betaine surfactant include carboxybetaines such as N-trialkyl-N-carboxymethylammonium betaine and sulfobetaines such as N-trialkyl-N-sulfoalkylene ammonium betaine.

  Of these, preferably used are anionic surfactants, more preferably sulfonic acid surfactants such as alkylbenzene sulfonates, alkylnaphthalene sulfonates, alkyl sulfonates, and α-olefin sulfonates.

  The content of the surfactant in the photocatalyst composition is 0.1 to 3.0% by weight, preferably 0.3 to 0.5% by weight, based on the total weight of the composition. If the content is less than the lower limit, a sufficient wettability improving effect cannot be obtained, and even if the content exceeds the upper limit, the improvement of the wettability of titanium dioxide in proportion to the amount cannot be obtained.

<Water>
The water used in the photocatalyst composition may be any of distilled water, ion-exchanged water, purified water, ultrapure water, etc., as long as impurities such as sodium deactivating the catalytic activity of titanium dioxide are not contained. Preferably, purified water is used.

<Optional component>
In addition to the above components, the photocatalyst composition of the present invention can contain a binder, an organic solvent compatible with water, a viscosity modifier, and the like. Examples of the binder include an acrylic resin, for example, a copolymerized acrylic resin emulsion (solid content 50%, aqueous). By adding the binder, scattering of the titanium dioxide fine powder after spraying and drying can be suppressed, and safety and catalytic activity can be improved. The amount of the binder is 0.001 to 0.1% by weight, preferably 0.01 to 0.05% by weight, most preferably 0.02 to 0.03% by solid content, based on the total weight of the composition. % By weight.

  Examples of the organic solvent compatible with water include alcohols having 1 to 6 carbon atoms, that is, methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, t-butanol, pentanol and the like. And dihydric alcohols such as ethylene glycol. The content of the alcohol is 1 to 10% by weight, preferably 3 to 7% by weight, based on the total weight of the composition.

  Examples of the viscosity modifier include carboxymethyl cellulose, hydroxyethyl cellulose, polyacrylic acid soda, polyacrylamide, polyvinyl pyrrolidone, polyvinyl alcohol, xanthan gum and the like. Preferably, a polyacrylic acid-based viscosity modifier, for example, sodium polyacrylate is used, and sodium polyacrylate having a molecular weight of 3 million to 5 million is more preferable. The content of the viscosity modifier in the photocatalyst composition is such that the viscosity measured by the JIS-Z8803 viscosity measurement method of the photomedium composition is 2 to 5 mPa · s, preferably 3 to 4 mPa · s. is there. When an acrylic acid viscosity modifier is used, it is 0.1 to 1% by weight, preferably 0.4 to 0.8% by weight, based on the total weight of the composition.

  The photocatalyst composition of the present invention can be prepared by mixing the above-mentioned components and, if desired, optional components using a known stirring means such as a mixer.

  The method of using the photocatalyst composition thus obtained is as follows. First, the photocatalyst composition is stored in a spray container. The spray container may be of any type as long as the photocatalyst composition can be sprayed in a fine mist. For example, a pressurized hand spray, an electric spray, an air spray or the like can be used.

Next, the photocatalyst composition is uniformly sprayed on the inner wall of a medical safety cabinet that handles anticancer agents and the like. The spray amount is preferably adjusted as appropriate depending on the titanium dioxide concentration, decomposition target, etc., but if it is about 100 to 150 mL / m ² , the inner wall and work surface of the average safety cabinet will be uniformly wetted. It is possible. In general, although the cabinet is made of stainless steel, the droplets of the photocatalyst composition of the present invention can wet the stainless steel surface without being repelled, and do not fall as droplets.

  After spraying, it is naturally dried over 30 to 120 minutes. On the stainless steel surface after drying, titanium dioxide particles remain and the surface looks white. As long as the titanium dioxide particles are not rubbed forcibly, they do not flutter or peel off.

Next, the titanium dioxide is irradiated with light showing photocatalytic activity. As the irradiation light source, for example, a black light fluorescent lamp that emits ultraviolet rays of 315 to 380 nm can be used. The ultraviolet lamp mounted in the safety cabinet may be replaced with a black light fluorescent lamp. The irradiation time is preferably adjusted appropriately depending on the intensity of light and the degree of contamination of the cabinet, but when the irradiation intensity is about 0.2 mW / cm ² , the irradiation is good for about 10 to 15 hours. Results were obtained.

  In the present invention, the anticancer agent to be decomposed is not particularly limited, and any anticancer agent may be used as long as it can be decomposed by the oxidizing action of titanium dioxide. For example, 5-fluorouracil, methotrexate, cytarabine, gemcitabine, fludarabine, pemetrexed, nelarabine, eninotabine and other antimetabolites, cyclophosphamide, busulfan, dacarbazine, nimustine, ranimustine, ifosfamide, melphalan, actinomycin D, temozolomide, etc. Alkylating agents, platinum agents such as cisplatin, carboplatin, oxaliplatin, nedaplatin, topoisomerase inhibitors such as irinotecan, nogitecan, etoposide, microtubule polymerization inhibitors such as paclitaxel, docetaxel, vincristine, bunblastine, vindesine, vinorelbine, doxorubicin and the like Liposome preparation, aclarubicin, idarubicin, pirarubicin, daunomycin, epirubicin, mitoxant Examples include anticancer antibiotics such as Ron, amrubicin and gemtuzumab ozogamicin, antibody preparations, and other anticancer agents such as pentostatin, arsenic trioxide, bleomycin, mitomycin, cladribine and asparaginase.

  After light irradiation, it may be wiped off with alcohol or the like, or may be wiped and cleaned using sodium hydroxide or the like to ensure complete decomposition of the anticancer agent. As described at the beginning, in the case of cyclophosphamide, which is removed only about 70% even if the conventional wiping is performed three times, as shown in the following examples, spraying of the photocatalyst composition of the present invention alone is about Since it can be decomposed by about 60%, it can be decomposed by about 90% (88 = 60 + 40 × 0.7) when wiping is combined. Alternatively, the photocatalyst composition of the present invention may be sprayed after completion of daily work, light irradiation is performed in the night, and after several days, the wiping may be performed collectively.

  EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited to these.

  Brookite type titanium dioxide sol (Nano Titania, Showa Titanium Co., Ltd.) 3.0 w / v%, sulfonate type anionic surfactant (Nopco Wet, San Nopco Co., Ltd.) 0.5 w / v%, copolymer acrylic resin A composition having a photocatalytic titanium dioxide concentration of 0.1 w / v% by mixing an emulsion (PANTEX, solid content 50%, manufactured by Shinba Co., Ltd.) 0.05 w / v% and distilled water (residue). Was prepared.

  A composition having a photocatalyst concentration of 0.3 w / v% was prepared in the same manner as in Example 1 except that the photocatalytic titanium dioxide concentration was 0.3 w / v%.

<Comparative example>
For comparison, a nanotitania (trademark) sol manufactured by Showa Denko Co., Ltd., which was blended with a zirconia binder as an adhesive, was applied to a 10 cm × 10 cm stainless steel (SUS304) surface to a thickness of about 0.2 microns. Thereafter, it was baked and fixed at 120 ° C. to obtain a photocatalyst thin film.

[Evaluation of photocatalytic performance]
A stainless steel plate (SUS304; 10 cm × 10 cm) made of the same material as that used in the safety cabinet was placed on the work plane in the safety cabinet. Cyclophosphamide aqueous solution (endoxan 100 for injection (Shionogi Pharmaceutical Co., Ltd.) for injection) prepared with physiological saline was added dropwise to the stainless steel plate to give 1 mg and 4 mg as cyclophosphamide. In order to be repelled on the stainless steel surface without containing any agent, 100 μl or 2 μl of cyclophosphamide aqueous solution prepared to 10 and 20 mg / mL, respectively, was added dropwise using a pipette. After the solution was dried, the composition of Example 1 or 2 was sprayed at a volume of 150 mL / m ² from a location 20 cm away from the hand spray tip.

After the sprayed photocatalytic aqueous composition is dried, the UV light mounted inside the safety cabinet with a total width of 1.3 m is replaced with a black light (Toshiba FL20SBLB), and near ultraviolet light with a wavelength of 350 nm is placed on a test stainless steel plate placed on the work plane. Was irradiated at an intensity of about 0.2 mW / cm ² for 12 hours.

  After irradiation with near-ultraviolet light, wipe the drop spot from the test stainless steel plate using 10 mL distilled water and a cotton swab, extract with distilled water, filter the collected liquid with a 0.45 μm filter, and perform high-performance liquid chromatography (HPLC ) Used for analysis. The HPLC analysis conditions will be described later. In the control group, after the dripped cyclophosphamide aqueous solution was dried, the photocatalyst aqueous composition was recovered in the same manner without spraying.

  Similarly to the example, 1 mg of cyclophosphamide was dropped on the photocatalyst thin film prepared in the comparative example, and after irradiating near ultraviolet rays, the wipe was collected. In the control group, a cyclophosphamide aqueous solution was dropped onto a stainless steel plate not coated with a photocatalyst for coating, and after drying, collected in the same manner as the spray method.

  The above series of tests was performed at n = 2 or 3, and was performed at room temperature set to 20 ° C. to prevent vaporization of cyclophosphamide.

<Method of measuring cyclophosphamide>
Cyclophosphamide was quantified by HPLC. The measurement conditions are as follows. Water: acetonitrile = 75: 25 was flowed as a mobile phase to an analytical column (Kanto Chemical; RP-8, inner diameter 4.6 mm × length 250 mm, particle diameter 5 μm) maintained at 40 ° C. at a flow rate of 1.0 mL / min. . 20 μL of each sample was injected using an autosampler (n = 3) and detected at a wavelength of 195 nm. The limit of quantification was 0.3 μg / mL, and 300 μg / m ² when converted to the amount of wiping.

Using the HPLC quantitative results, the degradation rate was calculated from the amount of cyclophosphamide recovered in the test group relative to the control group. The results are shown in Table 1.

As shown in Table 1, with a 1 mg load of cyclophosphamide, the spray method of the present invention showed a higher decomposition rate than the thin film method of the comparative example. In the spray method, although the fluctuation of the numerical value considered to be due to the spraying condition was recognized, the tendency of the decomposition rate to improve as the amount of the catalyst increased or the amount of cyclophosphamide decreased was recognized. This time, due to the problem of the limit of quantification of measuring instruments, the loading amount of cyclophosphamide is reported as 0.1 to 6.6 ng / cm ² (J. Vandenbroucke, H. Robays, How to protect environment and employees against cytotoxic agents, the UZ Ghent experience, J. Oncol. Pharm. Pract, 6, 146-152 (2001)), but had to be 15,000-400,000 times higher. In the scattering state, it is considered that a higher decomposition rate than that shown in Table 1 can be achieved. Further, in this example, the stainless steel plate was disposed horizontally on the work plane in the safety cabinet, but there was no dripping even when the composition of the example was sprayed on a vertical wall.

  The photocatalytic aqueous composition of the present invention can be used by simply spraying it on a safety cabinet that is already contaminated with an anticancer agent, and is very useful for removing the anticancer agent.

Claims (6)

0.1-1.0 wt% photocatalytically active titanium dioxide particles, and 0.3-0.5 wt% surfactant,
The including, a photocatalyst aqueous composition for anti-cancer agents decompose and remove, the photocatalyst aqueous composition characterized in that it is used by spraying the medical safety cabinet interior and the work surface handling anticancer agents object.   The photocatalytic aqueous composition according to claim 1, wherein the titanium dioxide is brookite type.     The aqueous photocatalytic composition according to claim 1 or 2, wherein the surfactant is a sulfonic acid anionic surfactant.   The photocatalytic aqueous composition according to any one of claims 1 to 3, further comprising an aqueous acrylic resin emulsion in an amount of 0.001 to 0.1 wt% in terms of solid content. The spray for anticancer agent decomposition removal which consists of a container for spraying, and the photocatalyst aqueous composition of any one of Claims 1-4 accommodated in this container. Spraying the photocatalytic aqueous composition according to any one of claims 1 to 4 on the inner wall and the work surface of a medical safety cabinet;
A step of drying the sprayed aqueous photocatalyst composition, and a step of irradiating a medical safety cabinet inner wall and work surface with light of 315 to 380 nm for 10 to 15 hours,
A method for decomposing and removing an anticancer agent adhering to the inner wall and work surface of a medical safety cabinet.

Images