Use of phenyl-β-d-glucuronide in preparation of drug for induced exhalation detection of tumors

Abstract

A use of phenyl-β-D-glucuronide in preparation of a drug for induced exhalation detection of cancer. The phenyl-β-D-glucuronide is present in natural organisms, is verified to have no toxic or side effects by means of animal experiments, and is safe and reliable. In addition, by means of the in-vivo tumor part, the phenyl-β-D-glucuronide can be decomposed into phenol which is almost absent in vivo as a specific marker, so that the impact of individual factors on the detection accuracy in exhalation detection methods can be avoided.

Description

Application of phenyl-β-D-glucuronide in the preparation of drugs for inducible breath detection of tumors Technical Field

[0001] The present invention belongs to the technical field of cancer detection drugs, and particularly relates to the use of phenyl-β-D-glucuronide in the preparation of drugs for inducible breath detection of cancer. Background Art

[0002] Cancer is a serious threat faced by all mankind in the world and is an important cause of death. According to the World Health Organization, there were more than 19 million new cases of cancer and about 10 million cancer deaths in 2020, which placed a heavy physical and economic burden on patients. However, the early clinical symptoms of cancer are not obvious, and the disease deteriorates rapidly in the later stages. Therefore, early detection and early treatment of cancer are particularly important for improving cancer survival rates. The current methods used in clinical diagnosis of cancer mainly include computed tomography (CT), magnetic resonance imaging (MRI), ultrasound imaging, positron emission tomography (PET), endoscopy, and cell biological indicator examinations, etc., or a combination of one or more methods. However, these detection methods are expensive and have high equipment requirements. They cannot be promoted at the household level, which is not conducive to the timely detection of cancer.

[0003] Research has discovered the presence of cancer-related gaseous markers (volatile organic compounds) in human exhaled breath. By comparing the composition and levels of volatile organic compounds in breath samples from cancer patients and healthy controls, researchers have identified significant differences as exhaled breath markers for cancer screening. Breath analysis methods are gaining increasing attention due to their ease of sample collection, non-invasive nature, and low cost. However, this method of directly collecting the patient's exhaled breath for testing is a passive breath analysis, and its detection accuracy is greatly affected by individual differences. For example, dietary habits, metabolic levels, and regional differences will cause fluctuations in the components in the breath, resulting in low detection accuracy and unable to meet the requirements of practical applications; other studies have shown (Fabiola Djago, Justin Lange, Pauline Poinot, Induced Volatolomics of Pathologies, Nature Reviews, 5, 183-196 (2021)) that induced breath analysis technology analyzes specific enzymes and other substances present in the lesion site (tumor) and designs corresponding induction drugs. The drug specifically decomposes at the lesion site and produces specific volatile organic compound markers. The breath markers produced by drug induction do not exist in the original breath components or are extremely low in content, which can avoid the impact of individual differences on breath test results.

[0004] Therefore, it is necessary to develop an induction drug suitable for induction breath analysis technology.

[0005] Summary of the Invention

[0006] To address the above issues, the present invention discovered that phenyl-β-D-glucuronide can be decomposed by lesions in the body to produce phenol. The phenol content is different before and after breathing, and can be used as a marker for tumor detection; that is, phenyl-β-D-glucuronide can be used for inducible breath analysis technology to detect tumors.

[0007] In view of the above problems, the present invention can adopt the following technical solutions:

[0008] In one aspect, the present invention provides a use of phenyl-β-D-glucuronide in the preparation of a drug for inducible breath detection of tumors.

[0009] Another aspect of the present invention provides a drug for inducible breath detection of tumors, comprising an effective amount of phenyl-β-D-glucuronide and pharmaceutically acceptable excipients.

[0010] The beneficial effects of the present invention include at least: phenyl-β-D-glucuronide exists in natural plants (soybean metabolites, R. Gupta, CW Min, K. Kramer, GK Agrawal, R. Rakwal, KHPark, YMWang, I. Finkemeier, ST Kim, A Multi-Omics Analysis of Glycine max Leaves Reveals Alteration in Flavonoid and Isoflavonoid Metabolism Upon Ethylene and Abscisic Acid Treatment, Proteomics, 18, 1700366 (2018)), and has been verified by animal experiments to be non-toxic and side effects, safe and reliable; in addition, it can be decomposed into phenol, which is almost non-existent in the body, as a specific exhaled breath marker through the tumor portion in the body, which can avoid the influence of individual factors on the detection accuracy in the exhaled breath detection method. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 shows the UPLC-MS stability characterization of drug solutions; a is the freshly prepared drug, b is the drug solution after 2 weeks of storage in the refrigerator, c is the drug solution after 1 week of storage at room temperature, and d is the drug solution after heating in a 38.5°C water bath for 7 hours.

[0012] Figure 2 shows the stability profile of the drug solution. Figure a shows the newly prepared drug, b shows the drug solution after being stored in a refrigerator for 2 weeks, c shows the drug solution after being stored at room temperature for 1 week, and d shows the drug solution after being heated in a 38.5°C water bath for 7 hours.

[0013] Figure 3 shows the PDA peak comparison between the drug solution and the phenol standard after treatment under different conditions; among them, a is the phenol standard; b is the newly prepared drug, c is the drug solution after being stored in the refrigerator for 2 weeks, d is the drug solution after being stored at room temperature for 1 week, and e is the drug solution after being heated in a 38.5°C water bath for 7 hours.

[0014] FIG4 shows the production of phenol from phenyl-β-D-glucuronide under the action of β-glucuronidase;

[0015] Figure 5 shows the phenol production after phenyl-β-D-glucuronide drug was used in gastric cancer mouse model and healthy mice;

[0016] Figure 6 shows the changes in phenol content in exhaled air along with tumor volume after drug administration;

[0017] FIG7 is a graph showing the effect of different drug concentrations on cell viability as characterized by CCK-8. DETAILED DESCRIPTION

[0018] The examples are provided to better illustrate the present invention, but are not intended to limit the present invention to the examples. Therefore, non-essential improvements and adjustments to the embodiments made by those skilled in the art based on the above-mentioned invention still fall within the scope of protection of the present invention.

[0019] The terms used herein are only used to describe specific embodiments and are not intended to limit the present disclosure. Unless otherwise clearly defined in the context, expressions in the singular include expressions in the plural. As used herein, it should be understood that terms such as "include," "have," and "comprise" are intended to indicate the presence of features, numbers, operations, components, parts, elements, materials, or combinations. The terms of the present invention are disclosed in the specification and are not intended to exclude the possibility that one or more other features, numbers, operations, components, parts, elements, materials, or combinations thereof may exist or may be added. As used herein, " / " may be interpreted as "and" or "or," depending on the circumstances.

[0020] As used herein, the term "effective dose" refers to a dose of phenyl-β-D-glucuronide that is physiologically non-toxic but sufficient to achieve adequate production of inducible breath markers. The appropriate effective dose in any individual case can be determined by one of ordinary skill in the art using routine experimentation. The effective dose for a particular application will depend on the condition of the cancer or cancers being detected, the subject's condition, the route of administration, and other factors known to those skilled in the art. Determination of the effective dose of phenyl-β-D-glucuronide can be accomplished and optimized by one of ordinary skill in the art based on the protocols provided herein.

[0021] As used herein, the term "pharmaceutically acceptable" means that the agent used to dissolve the drug is biologically or otherwise acceptable, i.e., the substance can be administered to a subject without causing undesirable biological effects or interacting in a deleterious manner with any component of a composition containing the substance. As used herein, such agents are pharmaceutically acceptable agents known to those of ordinary skill in the art, including water, saline, PBS buffer, or glycerol.

[0022] One embodiment of the present invention provides a use of phenyl-β-D-glucuronide in the preparation of a drug for inducible breath detection of tumors.

[0023] It should be understood that phenyl-β-D-glucuronide is a naturally occurring component in soybeans, has a molecular formula of C12H14O7, a molecular weight of 270.23, and a CAS registration number of 17685-05-1.

[0024] It is important to note that β-glucuronidase selectively accumulates in the microenvironment of many solid tumors, whereas in healthy tissue, this enzyme is primarily found intracellularly. As a specific enzyme, it can be used in inducible breath detection for tumors. Phenyl-β-D-glucuronide is specifically broken down by β-glucuronidase to produce phenol. Since phenyl-β-D-glucuronide is highly hydrophilic, limiting its passive passage through cell membranes, this decomposition reaction primarily occurs within the tumor microenvironment. Furthermore, since phenol is virtually absent in human exhaled breath, this phenol marker, specifically induced at the tumor site, circulates through the bloodstream and reaches the lungs, where it is released into exhaled breath through alveolar gas exchange. Therefore, detecting the composition and content of phenol in exhaled breath can be used to determine the presence of tumors. This facilitates the early detection and treatment of cancer.

[0025] In some specific embodiments, the aforementioned tumors may include gastric cancer, colorectal cancer, liver cancer, intestinal cancer, ovarian cancer, glioma, kidney tumor, and lung tumor. It should be noted that the aforementioned tumors may be any tumor in the body, including benign or malignant tumors, such as the aforementioned gastric cancer, colorectal cancer, liver cancer, intestinal cancer, ovarian cancer, glioma, kidney tumor, or lung tumor.

[0026] In some specific embodiments, the drug for inducible breath detection of tumors may include an effective amount of phenyl-β-D-glucuronide and a pharmaceutically acceptable excipient. It should be noted that the effective amount of phenyl-β-D-glucuronide can be added to the pharmaceutically acceptable excipient to prepare different dosage forms for use, including solid, liquid, paste, or aerosol dosage forms.

[0027] In some specific embodiments, the pharmaceutically acceptable excipients may include one or more of PBS buffer or normal saline. It should be noted that an effective amount of phenyl-β-D-glucuronide can be added to PBS buffer or normal saline to prepare a liquid dosage form for inducible breath detection of tumors. Of course, PBS buffer or normal saline can be replaced with other alternative solutions known to those skilled in the art.

[0028] Another embodiment of the present invention provides a drug for inducible breath detection of tumors, comprising an effective amount of phenyl-β-D-glucuronide and a pharmaceutically acceptable excipient. It should be noted that, as described above, the effective amount of phenyl-β-D-glucuronide can be added to a pharmaceutically acceptable excipient to prepare different dosage forms for use, including solid, liquid, paste, or aerosol dosage forms. For example, an effective amount of phenyl-β-D-glucuronide can be added to a PBS buffer or saline solution to prepare a liquid dosage form.

[0029] It should also be noted that the method of using phenyl-β-D-glucuronide or the above-mentioned drug for inducible breath detection of tumors can be achieved using an active inhalation device known in the art.

[0030] In order to better understand the present invention, the content of the present invention is further explained below with reference to specific examples, but the content of the present invention is not limited to the following examples.

[0031] In the following examples, phenyl-β-D-glucuronide was purchased from Sigma-Aldrich, catalog number 78555, with a purity of ≥99.0% (HPLC); PBS was purchased from Gibco; β-glucuronidase was purchased from Sigma-Aldrich, catalog number 8162, with a quality level of 200; bovine serum albumin was purchased from ChromatoPur, catalog number 0218054950; DMEM culture medium, trypsin, and penicillin-streptomycin (double antibody) were purchased from Hyclone; fetal bovine serum was purchased from Gibco; MGC-803 cells were obtained from the cell bank of the Chinese Academy of Sciences; gastric mucosal epithelial cells were obtained from the cell bank of the Chinese Academy of Sciences; and other consumables and reagents used were conventionally used materials in the art.

[0032] 1. Stability Verification of Phenyl-β-D-Glucuronide Drug

[0033] Phenyl-β-D-glucuronide solution was prepared using PBS as the solvent at a concentration of 400ug / ml. 1ml was taken and added to 1.5ml injection vials and sealed. The four bottles of drug solutions were treated as follows: Bottle A contained the prepared drug and was immediately analyzed for composition using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS); Bottle B was placed in a 4°C refrigerator for 2 weeks and then analyzed for composition using UPLC-MS; Bottle C was placed at room temperature (25°C) for 1 week and then analyzed for composition using UPLC-MS; the prepared drug in Bottle D was heated in a 38.5°C water bath for 7h and then analyzed for composition using UPLC-MS and PDA detectors. In addition, a 20ppm phenol standard solution was prepared and analyzed by UPLC-MS and PDA.

[0034] The results are shown in Figures 1, 2 and 3. The HPLC-MS spectra and the spectral data of the PDA detector at 280 nm indicate that the peaks in the spectra are the active ingredients in the four bottles of solution, namely, the peak areas of phenyl-β-D-glucuronide are consistent (2143, 2142, 2144 and 2146, respectively), and no other new substance peaks are generated (see Figures 1 and 2); compared with the peak of the phenol standard, there is no phenol peak in the four bottles of solution (see Figure 3).

[0035] The above experimental results show that a PBS solution of phenyl-β-D-glucuronide can be stored at room temperature for at least one week and in a 4°C refrigerator for at least two weeks. These three temperatures are primarily intended to demonstrate that the drug can be stored for extended periods at 4°C or at room temperature without decomposition or deterioration. Peak area data indicate that the active ingredient, phenyl-β-D-glucuronide, remains essentially unchanged after two weeks in a 4°C refrigerator or one week at room temperature. Therefore, under suitable sealing conditions, the drug solution can be stored for extended periods, demonstrating potential for practical application. More importantly, within the normal human body temperature range (generally below 38.5°C) and without the action of enzymes, the drug does not decompose. This demonstrates the sufficient stability of a PBS solution of phenyl-β-D-glucuronide.

[0036] 2. In vitro enzymatic reaction of phenyl-β-D-glucuronide drugs

[0037] Sterile water was used to prepare a buffer solution containing 75 mM potassium phosphate (KH2PO4) and 1% bovine serum albumin (BSA). The pH was adjusted to 6.8 with 1 M potassium hydroxide (KOH). Deionized water was used to prepare a phenyl-β-D-glucuronide solution at a concentration of 0.75 g / L. The experiment was divided into a reaction group and a control group. 2.6 ml of deionized water, 2 ml of buffer solution, and 1 ml of phenyl-β-D-glucuronide solution were added to two 20 ml injection bottles, respectively. The mixture was shaken and then stabilized in a 37°C water bath for 10 min. 2 μl of glycerol solution of β-glucuronidase (enzyme content: 500 U) was added to the reagent bottle of the experimental group. 2 μl of glycerol was added to the control group; the lid was quickly tightened and the reaction was carried out in a 37°C water bath for 1 hour; after the reaction, headspace solid-phase microextraction was performed using an aged extraction core for 30 minutes; the gas composition was analyzed using a gas chromatography-mass spectrometer, and the extraction core was desorbed at the injection port at 260°C for 5 minutes; the chromatographic column was DB-WAX 30m×0.25μm×0.25mm, and the heating program was as follows: initial temperature 40°C, maintained for 5 minutes, and then heated to 250°C at a rate of 10°C / min and maintained for 5 minutes; the mass spectrometer scanned the full range of 29amu-400amu, and the carrier gas was high-purity helium at a flow rate of 1ml / min; the detected substances were analyzed using the NIST14 spectral library.

[0038] The results are shown in Figure 4. In the experimental group, phenyl-β-D-glucuronide produced phenol under the full action of β-glucuronidase, which volatilized into the headspace and was extracted. In the control group, no β-glucuronidase was added, the substrate phenyl-β-D-glucuronide did not decompose, and no phenol was produced. The in vitro enzymatic reaction experiment demonstrated the effectiveness of phenyl-β-D-glucuronide as an induction drug and that it could induce specific markers. At the same time, the phenol produced in the liquid phase reaction system could volatilize into the air at room temperature, indicating that the characteristic marker can conditionally enter the exhaled air through gas exchange in the alveoli.

[0039] 3. Establishment of tumor-bearing mouse model and construction of mouse exhaled breath extraction device

[0040] In the examples of the present invention, the mice used were 6-week-old female BALB / c-Nude nude mice, SPF grade, weighing 17±1.5 g at the time of purchase, and were purchased from Shanghai Jiesijie Experimental Animal Co., Ltd. The mice were housed in cages in a clean animal room. The cages were ventilated by a central control system and the room temperature was 25±2°C. The feed and water were autoclaved before use.

[0041] After one week of adaptive feeding, the nude mice weighed 20±2g. The growth and mental state of the mice were observed every day during the feeding period and then randomly divided into two groups: cancer group and healthy group. The cancer group used MGC-803 cells to construct a subcutaneous gastric cancer model. The complete culture medium for culturing MGC-803 included DMEM high-glucose medium, 10% fetal bovine serum and 1% double-antibody. MGC-803 cells were revived in 15ml of complete culture medium and placed in a 37℃ constant temperature incubator with 5% carbon dioxide. The culture medium was changed every 2 days. The adherent gastric cancer cells were digested with trypsin, centrifuged, collected, resuspended and counted at a rate of 1*10 6 The cells were dispersed in 15 ml of complete medium at a density of 10 cells / ml and passaged into cell culture flasks. The cells were cultured in a cell culture incubator at a constant temperature. After the cells adhered to the wall and grew confluently, they were digested with trypsin, centrifuged, washed twice with PBS to remove residual serum, and resuspended in PBS. The cell density was about 5*10 7 cells / ml, and the cell inoculation volume for each mouse is 100ul; the cell suspension used for inoculation should be inoculated within half an hour. During this period, the cells should be placed on ice to reduce the cell metabolic activity to maintain cell activity. The tumor is implanted in the blood-rich area in the middle and posterior part of the armpit. The tumor size is measured every week after the tumor is formed. Generally, the induced breath detection experiment can be started in the third week after the cell implantation.

[0042] The exhaled breath extraction device enriches volatile substances in the mouse's exhaled breath onto the extraction core of the headspace solid-phase microextraction (SPME) for analyzing the components and relative contents of the mouse's exhaled breath before and after administration. A large-mouthed glass container with a volume of approximately 400 mL is used. The bottle mouth is frosted and sealed with a sealing gasket, silicone plug, and fixing clamp to ensure sealing. The device is cleaned and dried before use. The mouse to be subjected to exhaled breath component extraction is placed in the glass container. The entire device is placed in a constant temperature environment at 25°C and sealed for 1 hour. Oxygen is supplemented every 15 minutes by injecting 10 mL of pure oxygen (99.9%) through the silicone plug with a glass syringe. After sealing for 1 hour, a 75 μmCar / PDMS extraction core is inserted into the glass container through the silicone plug, and the black extraction core is extended for headspace solid-phase microextraction. The extraction lasts for 30 minutes. The extraction process is carried out in a constant temperature environment at 25°C, and oxygen needs to be supplemented regularly according to the above process.

[0043] The cleanliness and sealing of the device were tested. The cleanliness test was carried out by introducing high-purity nitrogen into the device. After sealing for 1 hour, the gas in the device was adsorbed using an SPME extraction core, and the composition of the adsorbed substance was analyzed by gas chromatography-mass spectrometry. The results were compared with a blank extraction core to confirm that the device itself did not produce impurity gas. After the device was sealed, gas was injected into the device through the top silicone plug using a syringe, and leaks were checked with soapy water. No bubbles were generated in any part of the device, and the piston of the syringe returned to its original position after release, proving that the device had good sealing performance.

[0044] 4. Phenyl-β-D-glucuronide Drug Breath Detection in a Mouse Model of Gastric Cancer

[0045] Ten healthy mice and ten tumor-bearing mice were selected from the above-mentioned group. The day 0 of the experiment was when the mice were subcutaneously injected with MGC-803 cells. The mice were housed in cages in a clean-grade animal room. The cages were ventilated by a central control system. The room temperature was 25±2°C. Feed and water were autoclaved before use.

[0046] Ten tumor-bearing mice and ten healthy mice were injected with phenyl-β-D-glucuronide multiple times, with an injection interval of 4 days. A single dose of the drug (200 μg / kg) was injected intravenously based on the mouse body weight each time. The exhaled breath of the mice after administration was collected using the mouse exhaled breath extraction device constructed above. The exhaled breath components of the mice were collected using the above-mentioned mouse exhaled breath extraction device; the enriched gas components were separated and detected using a gas chromatography-mass spectrometer (GCMS): the extraction core was desorbed at the inlet at 260°C for 5 minutes; the chromatographic column was a DB-WAX 30m×0.25μm×0.25mm column, and the heating program was as follows: initial temperature 40°C, hold for 5 minutes, then increase to 250°C at a rate of 10°C / min, and hold for 5 minutes; the mass spectrometer scanned the full range of 29-400 amu, and the carrier gas was high-purity helium at a flow rate of 1 ml / min; the detected substances were analyzed using the NIST14 spectral library.

[0047] On Day 0, there were no solid tumors in the tumor-bearing mice because the tumor cells had just been injected subcutaneously. The independent sample Mann-Whitney U test was used to test the two groups of data (healthy mice and mice with solid tumors injected with 200ug / kg of drug). The results are shown in Figure 5. The results showed that the phenol content in the exhaled air of the tumor-bearing mice and the healthy mice was consistent, with no significant difference. From the tenth day onwards, solid tumors with a volume of approximately 100 (mm3) were formed in the tumor-bearing mice. In each subsequent induced breath test, the phenol content in the exhaled air of the tumor-bearing mice was significantly higher than that of the healthy group (p<0.01), indicating that the induced breath analysis technology developed in this project can better distinguish between gastric cancer and healthy mice.

[0048] At the same time, it can be seen from Figure 6 that the phenol content in the exhaled air of the tumor-bearing mice has the same trend as the tumor volume over time; as shown in the inset, it is the fitting curve of the phenol content in the exhaled air of the mice and the tumor volume, and the correlation coefficient R 2The fitted curve is 0.993, indicating that the phenol content in the induced breath has a good linear correlation with the tumor volume. This indicates that the induced breath diagnostic technology developed in this project can not only be used to screen for solid tumors in the body, but also to assist in determining the size of the tumor by detecting the phenol content in the exhaled breath. The fitting curve is: Tumor volume = A + B * phenol content in exhaled breath

[0049] Among them, A=2065116.64068±293370.09484, B=26167.51388±981.43159.

[0050] Therefore, by detecting the phenol content in the exhaled air, it is possible to determine whether the mouse contains a tumor and estimate the tumor volume, which is expected to achieve early screening of tumors and monitoring during treatment in clinical practice.

[0051] 5. Phenyl-β-D-glucuronide Cytotoxicity Experiment

[0052] The complete culture medium used to culture gastric mucosal epithelial cells includes DMEM high glucose medium, 10% fetal bovine serum and 1% double antibody. The gastric mucosal epithelial cells were revived in 15 ml of complete culture medium and placed in a 37°C constant temperature incubator containing 5% carbon dioxide. The culture medium was replaced every 1-2 minutes; 5*10 4 The cells were inoculated at a concentration of 100 μl cells / ml in a 96-well plate, with 100 μl inoculated in each well. Five replicates were set for each group of samples. After 30 h of cell culture, the culture medium was discarded and DMEM medium containing phenyl-β-D-glucuronide was added. The drug concentrations were set to 0 μg / ml, 0.1 μg / ml, 1 μg / ml, 10 μg / ml, 100 μg / ml and 500 μg / ml, as well as culture medium without inoculated cells. The culture medium in each well was 100 μl. After incubation for 40 h, the culture medium was discarded and 100 μl of DMEM medium containing 10% CCK-8 was added to each well. The cells were incubated in an incubator for 2 h, and the absorbance (OD) of each well at a wavelength of 450 nm was monitored by a microplate reader. The cell survival rate was calculated based on the absorbance value.

[0053] The results are shown in Figure 7. In the CCK-8 toxicity test on gastric mucosal epithelial cells, the cell survival rate was not significantly affected by the use of phenyl-β-D-glucuronide in the concentration range of 0-500 μg / mL. Specifically, even when the cell drug co-culture concentration was as high as 500 μg / mL, the cell survival rate was still greater than 90%. At a drug concentration of 10 μg / mL, the survival rate of gastric mucosal epithelial cells exceeded 99.3%. In the actual mouse induced breath test, the drug concentration was 200 μg / kg, and the dosage per mouse was approximately 4 μg, which was far lower than the safe concentration value in the CCK-8 test. This shows that within the concentration range used in the experiment, phenyl-β-D-glucuronide has no toxic effect on the cells.

[0054] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the purpose and scope of the technical solutions of the present invention, which should all be covered by the scope of the claims of the present invention.

Claims

1. Application of phenyl-β-D-glucuronide in the preparation of drugs for inducible breath detection of tumors.

2. The use according to claim 1, characterized in that: Tumors include gastric cancer, colon cancer, liver cancer, intestinal cancer, ovarian cancer, glioma, kidney tumor and lung tumor.

3. The use according to claim 1 or 2, characterized in that: The drug for inducible breath detection of tumors comprises an effective amount of phenyl-β-D-glucuronide and pharmaceutically acceptable excipients.

4. The use according to claim 3, characterized in that: Pharmaceutically acceptable excipients include one or more of PBS buffer or physiological saline.

5. The use according to claim 1 or 2, characterized in that: The dosage form of the drug used for inducible breath detection of tumors includes solid dosage form, liquid dosage form, paste dosage form or aerosol dosage form.

6. A drug for inducible breath detection of tumors, characterized in that: The invention comprises an effective amount of phenyl-β-D-glucuronide and pharmaceutically acceptable auxiliary materials.

7. The drug for inducible breath detection of tumors according to claim 6, characterized in that: Pharmaceutically acceptable excipients include one or more of PBS buffer or physiological saline.

8. The drug for inducible breath detection of tumors according to claim 6, characterized in that: The dosage forms of the drug include solid dosage forms, liquid dosage forms, paste dosage forms or spray dosage forms.

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