JP2020174900A - Medicine and method for decomposing anticancer agent - Google Patents

Abstract

To provide a method and a decomposer which can quickly and simply decompose and remove anticancer agent residual in a medical site in order to prevent health damage by anticancer agent exposure to a medical worker and patient's family.SOLUTION: There is provided a decomposer for decomposing anticancer agent containing hypochlorous acid. Further, there is provided a method for decomposing anticancer agent residual in an object or an objective space including a process of spraying solution containing hypochlorous acid on the object or into the objective space.SELECTED DRAWING: None

Description

The present invention relates to a method and a decomposing agent for decomposing and removing a residual anticancer agent in a medical field.

In recent years, many kinds of anticancer agents have been used for the treatment of cancer. Although anti-cancer drugs are very useful for cancer treatment, it has been pointed out that they may cause health hazards to the medical staff and the families of patients who handle them.

Drugs that may cause health problems to people, such as anticancer drugs, are also called hazard drugs (HD). HD is described by the National Institute for Occupational Safety and Health (NIOSH) as 1) carcinogenic, 2) teratogenic, 3) reproductive toxicity, 4) organ damage, 5) genetic toxicity, and 6 ) It is defined as a drug that meets one or more of the six items that are similar in structure or toxicity to a dangerous drug.

Globally, exposure of anti-cancer drugs to medical workers such as nurses who handle anti-cancer drugs has become a problem. Exposure to antineoplastic agents can cause health hazards such as carcinogenicity, teratogenicity, organ damage and acute symptoms. Acute symptoms include hypersensitivity reactions, immune reactions, digestive symptoms, cardiovascular symptoms and neurological symptoms.

Exposure to anti-cancer drugs can occur, for example, in the preparation of anti-cancer drugs, preparation for administration, transportation, storage, administration (intravenous drip, injection and oral administration), treatment of spilled drugs, handling and disposal of deposits, and handling of patient excrement. In recent years, exposure to family members and caregivers by administration of anticancer drugs at home has also become a problem. It is generally said that the drug remains in the patient's body fluid for 48 hours after treatment with the anticancer drug, and there is a risk of exposure to the anticancer drug due to the patient's urine, stool and vomitus. There is also a risk of exposure to anticancer drugs when handling clothing, sheets, etc. to which the patient's body fluids are attached. Furthermore, the anticancer drug may remain on the surface and space of the floor and walls of the hospital room.

As a method of decomposing such an anticancer agent, a method of using a plurality of decomposition solutions, a method of using ozone water, and the like are known. However, all of these methods are complicated, and there is a demand for a means for quickly and easily decomposing an anticancer drug in the medical field. In addition, a means for wiping off the anticancer agent with sodium hypochlorite, which is a bleaching agent, is used, but sodium hypochlorite does not have a high anticancer agent decomposing effect and cannot effectively remove the anticancer agent.

Further, Patent Document 1 discloses an anticancer agent decomposition method using a photocatalytic aqueous composition. This photocatalytic aqueous composition contains photocatalytic titanium dioxide particles and a surfactant, and is used by spraying on an anticancer agent which is a decomposition target. However, even with this method, it is difficult to completely remove the anticancer drug.

Japanese Unexamined Patent Publication No. 2012-91114

An object of the present invention is to provide a method and a decomposing agent capable of quickly and easily decomposing and removing an anticancer agent remaining in a medical field in order to prevent health damage due to exposure of the antineoplastic agent to medical staff and a patient's family. ..

The present inventors have found that when an aqueous solution containing hypochlorous acid is sprayed on an object to which the anticancer agent adheres, the anticancer agent is almost decomposed in a short time, and the present invention has been completed.

The present invention provides a decomposing agent for decomposing an anticancer agent, including hypochlorous acid.

The present invention also provides the above-mentioned decomposing agent having hypochlorous acid of 10 ppm or more.

The present invention also provides the above-mentioned decomposing agent contained in a spray container.

Further, the present invention is a method for decomposing an anticancer agent remaining in an object or a target space, which comprises a step of spraying a solution containing hypochlorous acid onto the object or the target space to bring it into contact with the anticancer agent. provide.

The present invention also provides the above method, further comprising a step of spraying and contacting, followed by a step of allowing to stand for 1 minute or more.

The present invention also provides the above method, further comprising the step of wiping off the sprayed solution after the step of spraying and contacting.

The present invention also provides the above method in which the amount of hypochlorous acid contained in the solution is 10 ppm or more.

According to the present invention, the anticancer agent remaining in the medical field can be quickly and easily decomposed and removed. Therefore, the decomposing agent and the decomposing method of the present invention can prevent health hazards due to exposure of anticancer agents to medical staff and patient families.

The present invention provides a decomposing agent for decomposing an anticancer agent, including hypochlorous acid.

An anticancer agent refers to a chemotherapeutic agent aimed at suppressing the growth of a malignant tumor (cancer). The type of anticancer agent that can be decomposed by the present invention is not particularly limited. The degrading agent of the present invention is not particularly limited, and is, for example, an alkylating agent such as cyclophosphamide, iphosphamide, merphalan, busulfan, thiotepa, nimustin, lanimustin, dacarbazine, procarbacin, temozolomide, carmustin, streptozotocin and bendamstin, cisplatin, Platinum preparations such as carboplatin, oxaliplatin and nedaplatin, fluorouracil (5-FU), frucitocin, methotrexate, trimetprim, pyrimetamin, citarabin, gemcitabine, fludarabin phosphate, cladribine, pemetrexed, neralabine, enocitabine, 6-mercaptopurine, Metabolic antagonists such as statins, topoisomerase inhibitors such as irinotecan, nogitecane and etopocid, microtubule inhibitors such as paclitaxel, docetaxel, vincristin, vinblastin, bindesin and binorerbin, and acralubicin, idalubicin, pirarubicin, daunomycin, epirubicin, It can be used in anti-cancer agents such as antibiotics such as amrubicin and gemtuzumab ozogamicin.

Exposure to anti-cancer drugs includes, for example, skin absorption, inhalation and ingestion of anti-cancer drugs, contact with environmental surfaces and substances contaminated with anti-cancer drugs, needle stick accidents with needles used to collect from vials when using anti-cancer drugs, outside of vials of anti-cancer drugs. Contact with anti-cancer drugs adhering to the drug, excrement of patients who received anti-cancer drugs, bedding and leaked anti-cancer drugs, ingestion of food contaminated by eating and drinking in areas where anti-cancer drugs are handled, and inhalation of vaporized or aerosolized anti-cancer drugs. Inhalation exposure caused by Therefore, the decomposing agent of the present invention can quickly and easily decompose the anticancer agent of the object or the target space that is expected to be exposed to the anticancer agent as described above. For example, the decomposing agent of the present invention includes a disease, a treatment room, a nurse's workbench, a drip, a disposal box, gloves, a patient's excrement bag, a hospital room curtain, an excrement waste box, and a urinal lid. Rapid anti-cancer agents in objects or spaces such as urine cups, gowns, safety cabinet interiors and outlets, near PCs, Western-style toilet seats, men's urinals, floors, walls, shelves, doorknobs, beds, and patient linen sets. And it can be easily disassembled.

Hypochlorous acid is one of the oxo acids of chlorine and is represented by the composition formula of HClO. The decomposing agent of the present invention may be in the form of any solution such as an aqueous solution of hypochlorous acid.

The concentration of hypochlorous acid in the decomposing agent of the present invention is not particularly limited, but may be preferably 10 ppm or more, more preferably 20 ppm or more, for example, 50 ppm and 100 ppm or more. The upper limit of the concentration of hypochlorous acid in the decomposing agent of the present invention is not particularly limited, but may be preferably 10000 ppm or less, more preferably 1000 ppm or less, still more preferably 500 ppm or less and 200 ppm or less. For example, the decomposing agent of the present invention can be a 20-100 ppm hypochlorous acid aqueous solution.

The pH of the decomposing agent of the present invention is not particularly limited, but may be weakly acidic. The decomposing agent of the present invention can increase the proportion of hypochlorous acid present in the molecular form at pH 3.5 to 7.5, particularly 4.0 to 7.0. In general, it is known that the concentration of hypochlorous acid in an aqueous solution generalizes according to its pH. It is considered that the hypochlorous acid aqueous solution does not substantially generate chlorine gas at pH 4.0 and does not generate chlorine gas up to about pH 3.5. Therefore, the pH of the decomposing agent of the present invention includes a pH range of such pH or higher. It is also known that the concentration of hypochlorous acid in the solution reaches its maximum around pH 6.5. Therefore, it is considered that the pH of the decomposing agent of the present invention has the highest activity when it is around 6.5. In addition, if the pH of the solution is high, the decomposing agent is not easy to use because it has an alkaline property. Therefore, the pH of the decomposing agent of the present invention is preferably 4.0 to 7.0, for example.

Hypochlorous acid can be produced by any conventionally known method. For example, by lowering the pH of an aqueous solution of hypochlorite such as sodium hypochlorite, an aqueous solution having a high content of hypochlorous acid can be produced. Specifically, for example, an aqueous hypochlorous acid solution can be obtained by mixing an aqueous solution of sodium hypochlorite and hydrochloric acid. It is also possible to produce an aqueous solution having a high hypochlorous acid content of pH 3.5 to 7.5 by an electrolytic method or ion exchange conventionally known as a method for producing hypochlorous acid.

In addition, as a method for safely producing hypochlorous acid, a method of treating a hypochlorite solution with a weakly acidic ion exchanger having a buffering action at a pH higher than the pH at which chlorine gas is generated, for example, pH 3.5 to 7.5. Can be used. For example, an aqueous hypochlorous acid solution can be produced by passing a hypochlorite solution through a column packed with a weakly acidic ion exchanger. As the hypochlorite solution, solutions such as sodium hypochlorite, potassium hypochlorite and calcium hypochlorite can be used. As the weakly acidic ion exchanger, for example, an ion exchanger having a carboxylic acid group (-COOH) as an exchange group can be used, for example, a methacrylic acid-based weakly acidic cation exchange resin and an acrylic acid-based weakly acidic cation exchange. A weakly acidic ion exchange resin such as a resin can be used. For example, Amberlite IRC-76 (Organo Corporation) can be used as the weakly acidic ion exchanger.

If hypochlorous acid is produced by the method of treating with the weakly acidic ion exchanger described above, the pH of the solution after being treated with the weakly acidic ion exchanger is in the range of pH 3.5 to 7.5, and chlorine gas is generated. There is no risk and it can be manufactured safely.

The decomposing agent of the present invention may be sprayed or applied to the object in order to decompose the anticancer agent adhering to the object. Further, a cloth, a non-woven fabric, absorbent cotton or the like impregnated with the decomposing agent of the present invention may be brought into contact with the object. The decomposing agent of the present invention may be sprayed into the target space in order to decompose the anticancer agent staying in the target space.

The decomposing agent of the present invention may be contained in a spray container. The spray container is not particularly limited as long as it has a function of spraying the contents into the target object or the target space in the form of mist. The spray container can be, for example, a conventionally known spray container, an aerosol container, an ultrasonic sprayer, a vaporization sprayer, or the like.

The decomposing agent of the present invention may further contain components other than hypochlorous acid. For example, the decomposing agent of the present invention may further contain other decomposing agents and the like.

The present invention also provides a method for decomposing an anticancer agent remaining in an object or a target space, which comprises a step of spraying a solution containing hypochlorous acid onto the object or the target space to bring it into contact with the anticancer agent. To do.

The object is prepared from anything that the anticancer drug can adhere to and remain on the object, such as floors, walls, shelves, beds, and other surfaces of patients to whom the anticancer drug is administered, such as hospital rooms and treatment rooms, and anticancer drugs. Includes the surface of the workbench, etc. The target space includes any place where the anticancer drug can stay in the space, such as a hospital room, a treatment room, and a space in a dispensing room.

The above-mentioned decomposing agent of the present invention can be used for the solution containing hypochlorous acid.

In the spraying step in the method of the present invention, conventionally known spraying means can be used. For example, spraying means such as spray type, aerosol type, ultrasonic type and vaporization type can be used. In addition, in the method of the present invention, the solution may be sprayed on a cloth, a non-woven fabric or cotton wool placed on the object.

The method of the present invention may include a step of allowing to stand for 1 minute or more, for example, 1 to 5 minutes after the step of spraying. By allowing the solution to stand for several minutes after being sprayed, the anticancer drug can be more reliably decomposed.

The method of the present invention may further include the step of wiping the sprayed solution after the step of spraying or after the step of spraying and the step of standing. By spraying the solution and then wiping it off, the anticancer drug can be more reliably removed from the object. In order to wipe off the solution, a material such as cloth, non-woven fabric and absorbent cotton, which can wipe off the liquid, can be used without particular limitation.

(Example 1 Effect on anti-cancer agent by mixing with hypochlorous acid aqueous solution)
As a decomposing agent, a 200 ppm hypochlorous acid aqueous solution (Eva water 200 ppm: Heartful Kyushu Co., Ltd.) was used. Purified water (ultrapure water) was used as a control.

Cyclophosphamide and fluorouracil were used as test substances. The cyclophosphamide stock solution (20 mg / mL) was prepared by adding 5 ml of physiological saline to 100 mg of endoxan for injection and dissolving it in a solution. 5 mL of this stock solution was accurately weighed, and purified water was added to make exactly 200 ml of a diluted solution (500 μg / mL). 5 mL of this diluted solution was accurately weighed, and purified water was added to make exactly 25 ml to prepare a cyclophosphamide test substance solution (100 μg / mL). In addition, 250 mg of 5-FU injection was used as the undiluted solution of fluorouracil (50 mg / mL). 5 mL of this stock solution was accurately weighed, and purified water was added to make exactly 50 ml of the diluted solution (5 mg / mL). 5 mL of this diluted solution was accurately weighed, and purified water was added to make exactly 250 mL to prepare a fluorouracil test substance solution (100 μg / mL).

A sample solution was prepared by adding 1 ml of each test substance solution (100 μg / mL) to 9 ml of a decomposition agent (EVA water 200 ppm) and shaking. After standing for 10 minutes, the measurement was carried out immediately using LC / UV. The measurement was performed 3 times. In addition, as a control, purified water to which each test substance solution was added was measured in the same manner.

The results for cyclophosphamide are shown in Table 1, and the results for fluorouracil are shown in Table 2. As shown in Tables 1 and 2, the degrading agent had a decomposition rate of 100% for cyclophosphamide and fluorouracil all three times.

(Example 2 Effect on anti-cancer agent by mixing with hypochlorous acid aqueous solution)
As a decomposing agent, a 200 ppm hypochlorous acid aqueous solution (Eva water 200 ppm: Heartful Kyushu Co., Ltd.) was used. Purified water (ultrapure water) was used as a control.

Cyclophosphamide and fluorouracil were used as test substances. Cyclophosphamide stock solution (20 mg / mL) was prepared by adding 5 ml of physiological saline to 100 mg of endoxan for injection and dissolving it. 2.5 mL of this stock solution was accurately weighed, and purified water was added to make exactly 100 ml of the diluted solution (500 μg / mL). 10 mL of this diluted solution was accurately weighed, and purified water was added to make exactly 50 ml to prepare a cyclophosphamide test substance solution (100 μg / mL). In addition, 250 mg of 5-FU injection was used as the undiluted solution of fluorouracil (50 mg / mL). 2 mL of this stock solution was accurately weighed, and purified water was added to make a diluted solution of exactly 20 ml (5 mg / mL). 5 mL of this diluted solution was accurately weighed, and purified water was added to make exactly 250 mL to prepare a fluorouracil test substance solution (100 μg / mL).

First, a SUS304 plate (10 cm x 10 cm) was set in a plastic container. Then, 1 ml of each of the test substance solutions was uniformly added dropwise in a circle 6 cm from the center. After confirming that the dropped solution was dry, spray the decomposing agent on the center, left and right of the SUS304 plate a total of 3 times, and immediately after spraying, after leaving for 1 minute, after leaving for 3 minutes and after leaving for 5 minutes, on each SUS304 plate. The remaining test substance was extracted in a plastic container to prepare a sample solution. These operations were repeated 3 times to obtain 3 types of sample solutions. In addition, as a control, purified water was used instead of the decomposing agent, and the same operation was performed.

The resulting sample solution was measured using LC / UV. Based on the control results, the amount of decomposition by the decomposing agent (μg) and the decomposition rate (%) were calculated. The results for cyclophosphamide are shown in Table 3, and the results for fluorouracil are shown in Table 4. As shown in Tables 3 and 4, the decomposition effect on the test substance was observed immediately after spraying the decomposition agent. Further decomposition effect was observed after 1 minute and 3 minutes, and most of the test substances were decomposed after leaving for 5 minutes. It was shown that the decomposing agent of the present invention can rapidly decompose an anticancer agent in a short time.

(Example 3)
As a decomposing agent, a 200 ppm hypochlorous acid aqueous solution (Eva water 200 ppm: Heartful Kyushu Co., Ltd.) was used. It was used.

Cyclophosphamide and fluorouracil were used as test substances. A solution prepared by adding 5 ml of physiological saline to 100 mg of endoxan for injection was used as a cyclophosphamide stock solution (20 mg / mL). Weigh accurately 2.5 mL of this stock solution and add purified water to make exactly 100 ml of diluted solution (500 μg / mL). Weigh accurately 10 mL of this solution and add purified water to make exactly 50 ml. Cyclophosphamide test substance It was prepared as a solution (100 μg / mL). In addition, 250 mg of 5-FU injection was used as the undiluted solution of fluorouracil (50 mg / mL). 2 mL of this stock solution was accurately weighed, and purified water was added to make exactly 20 ml of the diluted solution (5 mg / mL). 5 mL of this diluted solution was accurately weighed, and purified water was added to make exactly 250 mL to prepare a fluorouracil test substance solution (100 μg / mL).

First, a SUS304 plate (10 cm x 10 cm) was set in a plastic container. Then, 1 ml of each of the test substance solutions was uniformly added dropwise in a circle 6 cm from the center. After confirming that the dropped solution had dried, cotton soaked with a decomposing agent (ClariS3) was placed without a gap on the solution-spraying site. Immediately after placing the cotton, leaving it for 1 minute, leaving it for 3 minutes, and leaving it for 5 minutes, each SUS304 plate was wiped off with the placed cotton, and the remaining test substance was extracted in a plastic container to prepare a sample solution. These operations were repeated 3 times to obtain 3 types of sample solutions.

The obtained sample solution was measured using the LC / UV method, and the removal rate (%) of the anticancer agent by the decomposing agent was calculated. The results for cyclophosphamide are shown in Table 5, and the results for fluorouracil are shown in Table 6. As shown in Tables 5 and 6, a high removal effect was observed immediately after the cotton soaked with the decomposing agent was placed. It has been shown that the decomposing agent of the present invention can remove the anticancer agent more easily and reliably by immersing it in cotton and wiping it off.

INDUSTRIAL APPLICABILITY The present invention can be suitably used for chemicals and devices for preventing residual antineoplastic agents in the medical field.

Claims (7)

A decomposing agent for decomposing antineoplastic agents, including hypochlorous acid. The decomposing agent according to claim 1, wherein the hypochlorous acid is 10 ppm or more. The decomposing agent according to claim 1 or 2, contained in a spray container. A method of decomposing an anticancer drug remaining in an object or an object space.
A method comprising the step of spraying a solution containing hypochlorous acid onto the object or target space to bring it into contact with an anticancer agent. The method according to claim 4, further comprising a step of allowing to stand for 1 minute or more after the step of contacting. The method of claim 4, further comprising a step of wiping the sprayed solution after the contacting step. The method according to any one of claims 4 to 6, wherein the amount of hypochlorous acid contained in the solution is 10 ppm or more.