Use of phenyl-β-D-glucuronide in the preparation of a drug for detecting tumors by induced breath testing

Abstract

This invention relates to the field of cancer detection drug technology, specifically to the use of phenyl-β-D-glucuronide in the manufacture of drugs for cancer detection by induced breath testing. Phenyl-β-D-glucuronide is naturally present in living organisms and has been verified in animal experiments to be safe and reliable with no toxic or side effects. Furthermore, it can be decomposed into phenol, which is virtually absent in the body as a specific marker for tumors, thereby avoiding the impact of personal factors on the detection accuracy of breath detection methods.

Description

[Technical Field]

[0001] The present invention is in the field of cancer detection drug technology, and specifically relates to the use of phenyl-β-D-glucuronide in the manufacture of drugs for detecting cancer in induced breath. [Background technology]

[0002] Cancer is a serious threat and a significant cause of death for people worldwide. According to the World Health Organization, there will be more than 19 million new cases of cancer and approximately 10 million cancer deaths in 2020, placing a significant physical and economic burden on patients. However, because cancer has unclear clinical symptoms in the early stages and rapidly progresses in the later stages, early detection and treatment are particularly important for improving cancer survival rates. Currently, clinical cancer diagnosis methods mainly include computed tomography (CT), magnetic resonance imaging (MRI), ultrasound imaging, positron emission tomography (PET), endoscopy, and cell biological indicator tests, either individually or in combination. However, these detection methods are expensive and require high equipment requirements, preventing their widespread use at the household level, which hinders timely cancer detection.

[0003] Research has revealed that human breath contains cancer-related gas markers (i.e., volatile organic compounds). Engineers compare the components and content of volatile organic compounds in breath samples from cancer patients and healthy controls to identify significantly different components as cancer breath markers for cancer screening. Breath analysis methods have attracted increasing attention due to their advantages of easy sample collection, non-invasiveness, and low cost. However, these methods, which directly collect and detect breath samples from patients, are passive breath analysis methods, and their detection accuracy is significantly affected by individual differences. For example, dietary habits, metabolic levels, and regional differences all lead to variations in breath components, resulting in low detection accuracy and failing to meet practical requirements. In addition, another study (Fabiola Djago, Justin Lange, Pauline Poinot, Induced Volatolomics of Pathologies, Nature Reviews, 5, 183-196 (2021)) revealed that induced breath analysis technology designs corresponding induced drugs by analyzing substances such as specific enzymes present in the lesion site (tumor), and the drugs are specifically decomposed at the lesion site to produce specific volatile organic markers.It was revealed that the breath markers produced by this drug induction method are not present in the original breath components or have extremely low concentrations, thereby avoiding the influence of individual differences on breath detection results.

[0004] Therefore, it is necessary to develop a derivatization drug suitable for the derivatization breath analysis technique. Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention addresses the above problem by demonstrating that phenyl-β-D-glucuronide can be decomposed to generate phenol through diseased areas in the body, and the phenol content differs before and after breathing, making it a useful marker for tumor detection. In other words, phenyl-β-D-glucuronide can be used to detect tumors using induced breath analysis technology. [Means for solving the problem]

[0006] The present invention can use the following technical solutions to the above problems.

[0007] In one aspect of the present invention there is provided the use of phenyl-β-D-glucuronide in the manufacture of a medicament for detecting tumours in induced breath.

[0008] In another aspect of the present invention, there is provided a medicament for detecting tumors in induced breath, comprising an effective amount of phenyl-β-D-glucuronide and a pharmaceutically acceptable adjuvant. [Effects of the Invention]

[0009] The beneficial effects of the present invention include at least the following: Phenyl-β-D-glucuronide is naturally present in plants (soybean metabolite, R. Gupta, CW Min, K. Kramer, GK Agrawal, R. Rakwal, KH Park, YM Wang, 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 animal experiments have demonstrated its safety and reliability with no toxicity or side effects. Furthermore, it can be broken down into phenol, which is virtually absent in the body, through tumor tissue in the body and can be used as a specific breath marker, thereby avoiding the impact of personal factors on the detection accuracy of breath detection methods. [Brief explanation of the drawings]

[0010] [Figure 1]UPLC-MS to characterize the stability of drug solutions, where a is freshly prepared drug, b is drug solution stored in a refrigerator for 2 weeks, c is drug solution stored at room temperature for 1 week, and d is drug solution heated in a water bath or kettle at 38.5 °C for 7 h. [Figure 2] PDA characterizing the stability of drug solutions, where a is freshly prepared drug, b is drug solution stored in a refrigerator for 2 weeks, c is drug solution stored at room temperature for 1 week, and d is drug solution heated in a water bath or kettle at 38.5°C for 7 h. [Figure 3] Comparison of PDA peaks between drug solutions treated under different conditions and a phenol standard, where a is the phenol standard, b is freshly prepared drug, c is drug solution stored in a refrigerator for 2 weeks, d is drug solution stored at room temperature for 1 week, and e is drug solution heated in a water bath or kettle at 38.5°C for 7 hours. [Figure 4] Phenyl-β-D-glucuronide produces phenol under the action of β-glucuronidase. [Figure 5] Phenol production after administration of phenyl-β-D-glucuronide drugs in a gastric cancer mouse model and healthy mice. [Figure 6] Changes in phenol content in exhaled air depending on tumor volume after administration. [Figure 7] Figure 1 shows the effect of different drug concentrations characterized by CCK-8 on cell viability. DETAILED DESCRIPTION OF THE INVENTION

[0011] The examples given are for the purpose of better illustrating the present invention, and the content of the present invention is not limited to the examples given. Any non-essential improvements or adjustments made to the implementation plans by those skilled in the art according to the above content of the invention still fall within the scope of protection of the present invention.

[0012] The terms used herein are merely for the purpose of describing particular embodiments and are not intended to limit the present disclosure. Singular expressions include plural expressions unless the context clearly dictates otherwise. As used herein, terms such as "comprises," "has," and "includes" are intended to indicate the presence of features, numbers, operations, components, parts, elements, materials, or combinations. Although the terms "invention" are disclosed herein, they are not intended to exclude the possibility that one or more other features, numbers, operations, components, parts, elements, materials, or combinations thereof may be present or added. As used herein, " / " may be interpreted as "and" or "or," as the case may be.

[0013] The term "effective dose" as used herein refers to a dose of phenyl-β-D-glucuronide sufficient to achieve sufficient production of an induced breath marker without physiological toxicity. The appropriate effective dose in any individual case can be determined by one skilled in the art using routine experimentation. The effective dose for a particular application depends on the type or types of cancer to be detected, the condition of the subject, the route of administration, and other factors known to those skilled in the art. The determination of the effective dose of phenyl-β-D-glucuronide can be achieved and optimized by those skilled in the art according to the solutions provided in the present invention.

[0014] The term "pharmaceutically acceptable" as used herein means that the agent used to dissolve the drug is biologically or otherwise acceptable, i.e., the substance can be administered to an individual without causing undesirable biological effects or interacting in a harmful way with any of the components in the composition containing the substance. As used herein, such agents refer to pharmaceutically acceptable agents, including water, saline, PBS buffer, glycerin, etc., which are well known to those skilled in the art.

[0015] One embodiment of the present invention provides the use of phenyl-β-D-glucuronide in the manufacture of a medicament for detecting tumors in induced breath.

[0016] It will be appreciated that phenyl-β-D-glucuronide is a naturally occurring component of soybeans with the molecular formula C12H14O7, a molecular weight of 270.23, and a CAS Registry Number of 17685-05-1.

[0017] Although β-glucuronidase selectively accumulates in the microenvironment of many solid tumors, in healthy tissues, this enzyme is essentially present only intracellularly and can be used as a specific enzyme for induced exhaled breath detection of tumors. Phenyl-β-D-glucuronide is specifically degraded by β-glucuronidase to produce phenol, and because phenyl-β-D-glucuronide is highly hydrophilic and its passive passage through cell membranes is limited, this degradation reaction occurs primarily in the tumor microenvironment. Furthermore, since phenol is rarely present in human exhaled breath, this phenol marker, which is specifically induced and produced at tumor sites, reaches the lungs via the bloodstream and then enters exhaled breath after gas exchange within the alveoli. Therefore, detecting the phenol components and their content in exhaled breath can be used to determine the presence or absence of tumors in the body. This is advantageous for early cancer detection and timely treatment.

[0018] In some specific embodiments, the tumor may include gastric cancer, nodular liver cancer, intestinal cancer, ovarian cancer, glioma, kidney tumor, and lung tumor, and the tumor may be any tumor in the body, including benign or malignant tumors, such as gastric cancer, nodular liver cancer, intestinal cancer, ovarian cancer, glioma, kidney tumor, or lung tumor.

[0019] In some specific embodiments, the drug for detecting tumors by induced exhalation may comprise an effective amount of phenyl-β-D-glucuronide and a pharmaceutically acceptable adjuvant. The effective amount of phenyl-β-D-glucuronide may be prepared in various dosage forms, including solid, liquid, cream, and mist dosage forms, by adding a pharmaceutically acceptable adjuvant.

[0020] In some specific examples, the pharmaceutically acceptable adjuvant may include one or more of PBS buffer or saline. An effective amount of phenyl-β-D-glucuronide can be prepared into a liquid formulation by adding PBS buffer or saline, which can then be used to detect tumors by induced exhalation. Of course, PBS buffer or saline may be replaced with other alternative solutions known to those skilled in the art.

[0021] Another embodiment of the present invention provides a drug for detecting tumors by induced exhalation, comprising an effective amount of phenyl-β-D-glucuronide and a pharmaceutically acceptable adjuvant. As described above, the effective amount of phenyl-β-D-glucuronide can be prepared into various dosage forms, including solid, liquid, cream, and mist, by adding a pharmaceutically acceptable adjuvant. For example, the effective amount of phenyl-β-D-glucuronide can be prepared into a liquid form by adding PBS buffer or saline.

[0022] Furthermore, the method of using phenyl-β-D-glucuronide or any of the drugs for detecting tumors in induced breath described above can be carried out using active inhalation devices known to those skilled in the art.

[0023] Hereinafter, in order to facilitate a better understanding of the present invention, the present invention will be further described with reference to specific examples, but the present invention is not limited to the following examples.

[0024] In the following examples, phenyl-β-D-glucuronide was purchased from Sigma-Aldrich, product number 78555, with a purity of ≥99.0% (HPLC); PBS was purchased from Gibco; β-glucuronidase was purchased from Sigma-Aldrich, product number 8162, with a quality level of 200; bovine serum albumin was purchased from ChromatoPur, product number 0218054950; DMEM medium, pancreatin, and penicillin-streptomycin (double antibody) were purchased from Hyclone Corporation; fetal bovine serum was purchased from Gibco; MGC-803 cells were obtained from the Cell Bank of the Chinese Academy of Sciences; and gastric mucosal epithelial cells were obtained from the Cell Bank of the Chinese Academy of Sciences. Other consumables and reagents used are materials conventionally used in the art.

[0025] 1. Verification of the stability of phenyl-β-D-glucuronide drugs A 400 μg / ml phenyl-β-D-glucuronide solution was prepared using PBS as the solvent, and 1 ml of each solution was added to 1.5 ml sample bottles and sealed. Four bottles of drug solution were processed as follows: Bottle A was immediately analyzed for its freshly prepared components using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS); Bottle B was stored in a 4°C refrigerator for two weeks and then analyzed for its components using UPLC-MS; Bottle C was stored at room temperature (25°C) for one week and then analyzed for its components using UPLC-MS; and Bottle D was heated in a 38.5°C water bath or kettle for 7 hours and then analyzed for its components using UPLC-MS and a PDA detector. A 20 ppm phenol standard solution was also prepared and analyzed for UPLC-MS and a PDA detector.

[0026] The results are shown in Figures 1, 2, and 3. The HPLC-MS spectra and the spectral data at 280 nm from the PDA detector showed that the peak areas of the peaks in the spectra were consistent with those of the active ingredient, i.e., phenyl-β-D-glucuronide, in the solutions from the four bottles (2143, 2142, 2144, and 2146, respectively), and no new peaks were generated (see Figures 1 and 2). Compared with the peak of the phenol standard, none of the solutions from the four bottles had a phenol peak (see Figure 3).

[0027] The above experimental results indicate that the PBS solution of phenyl-β-D-glucuronide can be stored for at least one week at room temperature and for at least two weeks in a 4°C refrigerator. These three temperature settings are primarily intended to characterize the drug's ability to withstand prolonged storage in a 4°C refrigerator or at room temperature without decomposition or degradation. Peak area data indicates 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, as long as the storage conditions are met, the drug solution can be stored for longer, making it suitable for practical application. More importantly, within the normal human body temperature range (generally below 38.5°C), the drug will not decompose without enzyme activity. These results demonstrate that the PBS solution of phenyl-β-D-glucuronide has sufficient stability.

[0028] II. In vitro enzyme reactions of phenyl-β-D-glucuronide drugs A buffer solution containing 75 mM potassium phosphate (KH2PO4) and 1% bovine serum albumin (BSA) was prepared with sterile water. The pH was adjusted to 6.8 with 1 M potassium hydroxide (KOH). A 0.75 g / L phenyl-β-D-glucuronide solution was prepared with deionized water. The experiment was divided into two groups: a reaction group and a control group. 2.6 ml of deionized water, 2 ml of buffer, and 1 ml of phenyl-β-D-glucuronide solution were added sequentially to two 20 ml sample bottles. After shaking, the mixture was stabilized in a 37°C water bath for 10 minutes. The experimental vials were filled with 2 μL of β-glucuronidase glycerol solution (500 U enzyme content), and the control vials were filled with 2 μL of glycerol. The vials were quickly capped and incubated in a 37°C water bath for 1 hour. After the reaction was complete, headspace solid-phase microextraction was performed for 30 minutes using an aged extraction wick. The gas components were analyzed using a gas chromatography-mass spectrometer. The extraction wick was used to desorb the sample at 260°C for 5 minutes. The chromatography column was a 30 m x 0.25 μm x 0.25 mm DB-WAX column. The heating procedure was as follows: the initial temperature was maintained at 40°C for 5 minutes, then the temperature was increased to 250°C at a rate of 10°C / min and maintained for 5 minutes. The mass spectrometer scanned the entire range of the carrier gas (29 amu to 400 amu) using high-purity helium at a flow rate of 1 mL / min. The detected substances were analyzed using the NIST14 spectral library.

[0029] The results are shown in Figure 4. In the experimental group, phenyl-β-D-glucuronide produced phenol under the sufficient action of β-glucuronidase, which then volatilized and was extracted into the headspace. In the control group, β-glucuronidase was not added, so the substrate phenyl-β-D-glucuronide was not decomposed and no phenol was produced. In vitro enzyme reaction experiments demonstrated the effectiveness of phenyl-β-D-glucuronide as an induction drug and its ability to induce specific markers. Furthermore, the phenol produced in the liquid-phase reaction system can volatilize into the air at room temperature, which also indicates that characteristic markers can be conditionally exhaled through gas exchange in the alveoli.

[0030] 3. Establishment of tumor-bearing mouse model and construction of mouse breath sampling device In the examples of the present invention, the mice used were 6-week-old female BALB / c-Nude nude mice, SPF grade, weighing 17±1.5g at the time of purchase. They were purchased from Shanghai Jieshijie Laboratory Animal Co., Ltd. The mice were kept in cages in a clean-level animal room, the ventilation status of the cages was maintained by a central control system, and the room temperature was set at 25±2°C. The feed and water were both autoclaved before use.

[0031] After one week of adaptive breeding, the nude mice weighed 20±2g. During the breeding period, the mice were observed daily for growth and mental status. They were randomly divided into two groups: a cancer group and a healthy group. In the cancer group, MGC-803 cells were used to establish a subcutaneous gastric cancer model. Specifically, a complete medium for culturing MGC-803 cells containing DMEM high-sugar medium, 10% fetal bovine serum, and 1% double antibody was used. MGC-803 cells were resuscitated in 15ml of complete medium and placed in a 37°C incubator containing 5% carbon dioxide. The culture medium was changed every two days. Gastric cancer cells adhering to and growing on the wall were digested using pancreatin, centrifuged, collected, resuspended, and counted. 1*10 6 The cells were dispersed in 15 ml of complete medium at a density of 10 cells / ml, subcultured in a cell culture flask, and incubated in a cell incubator. After the cells adhered to the wall and grew to their full size, they were digested with pancreatin, centrifuged, washed twice with PBS to remove the remaining serum, and resuspended in PBS. The cell density was 5 × 10 7 The cell density is 100 cells / ml, and the cell inoculation volume per mouse is 100 μl. The cell suspension for inoculation should be completed within 30 minutes, during which time the cells are placed on ice to reduce metabolic activity and maintain cell activity. The tumor is implanted in a site with a rich blood supply at the back of the axilla. After tumor formation, the size of the tumor mass is measured weekly. Generally, induced breath detection experiments can be started from the third week after cell implantation.

[0032] A breath sampling device was used to collect volatile compounds in mouse breath onto a headspace solid-phase microextraction (SPME) extraction wick for analysis of the breath components and relative content of mice before and after administration. A large-mouth glass container with a volume of approximately 400 mL was used, with a polished bottle neck and a sealing gasket, silica gel stopper, and clamp to ensure a tight seal. The device was washed and dried before use. The mouse to be sampled was placed in the glass container, and the entire device was sealed at 25°C for 1 hour. Oxygen was replenished every 15 minutes. 10 mL of pure oxygen (99.9%) was injected through the silica gel stopper with a glass syringe. After sealing for 1 hour, a 75 μm Car / PDMS extraction wick was inserted into the glass container through the silica gel stopper, with the black extraction wick protruding. Headspace solid-phase microextraction was performed for 30 minutes. The extraction process was carried out at 25°C in a constant temperature environment, with oxygen periodically replenished according to the above procedure.

[0033] The cleanliness and sealing of the device were tested. For the cleanliness test, high-purity nitrogen gas was poured into the device and sealed for 1 hour. Then, an SPME extraction wick was used to adsorb the gas in the device. The components of the adsorbed material were analyzed using a gas chromatography mass spectrometer. Compared with a blank extraction wick, it was confirmed that no impure gas was generated by the device itself. After the device was sealed, a needle was used to inject gas into the device through the silica gel plug on the top. Leaks were detected with soapy water. No bubbles were generated in any part of the device. The needle piston could return to its original position after being released, demonstrating the device's good sealing properties.

[0034] IV. Use of phenyl-β-D-glucuronide drugs in the breath detection of gastric cancer in mouse models Ten healthy mice and ten tumor-bearing mice were selected and subcutaneously injected with MGC-803 cells on Day 0 of the experiment. The mice were housed in cages in a clean animal room, with the ventilation status of the cages maintained by a central control system and the room temperature at 25±2°C. Feed and water were autoclaved before use.

[0035] Ten tumor-bearing mice and ten healthy mice were given multiple, consecutive injections of phenyl-β-D-glucuronide drugs every four days. A single dose (200 μg / kg) of the drug was intravenously administered according to the mouse's weight. The breath samples were collected after administration using the constructed mouse breath sampling device. The components of the breath samples were then separated and detected using a gas chromatograph mass spectrometer (GCMS). The extraction wick was desorbed at a 260°C sample inlet for 5 minutes. The chromatography column was DB-WAX 30 m × 0.25 μm × 0.25 mm, and the heating schedule was as follows: The initial temperature was maintained at 40°C for 5 min, then increased to 250°C at a rate of 10°C / min and maintained for 5 min. The mass spectrometer was scanned over the entire range using high-purity helium, 29-400 amu carrier gas, at a flow rate of 1 ml / min. The detected substances were analyzed using the NIST14 spectral library.

[0036] On day 0, tumor cells had just been subcutaneously injected, so there were no solid tumors in the tumor-bearing mice. An independent sample Mann-Whitney U test was performed on the data from both groups (healthy mice and mice injected with solid tumors at 200 μg / kg of drug). The results are shown in Figure 5. The results show that the phenol content in the breath of tumor-bearing mice was consistent and not significantly different from that of healthy mice. From day 10, solid tumors with a volume of 100 mm3 were formed in the tumor-bearing mice. In every subsequent induced breath test, the phenol content in the breath of the tumor-bearing mice was significantly higher than that of the healthy group (p<0.01). This indicates that the induced breath analysis technology developed in this project can effectively distinguish between gastric cancer mice and healthy mice.

[0037] Furthermore, as can be seen from Figure 6, the phenol content in the breath of mice in the tumor-bearing group and the tumor volume showed the same change trend over time. As shown in the inset, the fitting curve of the phenol content in the breath of mice that changed according to the tumor volume was obtained, and the correlation coefficient R 2is 0.993, that is, the content of phenol in the induced breath has a good linear correlation with tumor volume. This means that the induced breath diagnostic technology developed in this project can not only be used to screen for the presence of solid tumors in the body, but also to determine the size of tumors in the body by detecting the content of phenol in the breath. The fitting curve is as follows: Tumor volume = A + B * phenol content in exhaled breath Here, A = 2065116.64068 ± 293370.09484 and B = 26167.51388 ± 981.43159.

[0038] Therefore, by detecting the amount of phenol in exhaled breath, it is possible to determine whether a tumor is present in a mouse's body and estimate the tumor volume, which is expected to enable early screening of tumors and monitoring during treatment in clinical settings.

[0039] V. Cell toxicity test of phenyl-β-D-glucuronide The complete medium for culturing gastric mucosal epithelial cells contains DMEM high-sugar medium, 10% fetal bovine serum, and 1% double antibody. Gastric mucosal epithelial cells were resuscitated in 15 ml of complete medium and placed in a 37°C incubator containing 5% carbon dioxide. The culture medium was changed every 1-2 days. 5*10 4 The cells were seeded into a 96-well plate at a concentration of 10 cells / ml, with 100 μl of each well, and five replicate wells were used for each sample group. After culturing the cells for 30 hours, the culture medium was discarded, and DMEM medium containing phenyl-β-D-glucuronide was added at drug concentrations of 0 μg / ml, 0.1 μg / ml, 1 μg / ml, 10 μg / ml, 100 μg / ml, and 500 μg / ml. 100 μl of the uninoculated culture medium was added to each well. These were then incubated for 40 hours, after which the culture medium was discarded, and 100 μl of DMEM medium containing 10% CCK-8 was added to each well. The wells were then placed in an incubator and incubated for 2 hours. The optical density (OD) of each well at 450 nm was monitored using a microplate reader, and the cell viability was calculated based on the absorbance value.

[0040] As shown in Figure 7, in the CCK-8 toxicity experiment conducted on gastric mucosal epithelial cells, the use of phenyl-β-D-glucuronide in the concentration range of 0-500 μg / mL did not significantly affect cell viability. Here, even when the drug co-incubation concentration of cells reached 500 μg / mL, the cell viability was still above 90%. At an administration concentration of 10 μg / mL, the gastric mucosal epithelial cell viability exceeded 99.3%. However, when the mouse-induced exhalation experiment was actually conducted, the administration concentration was 200 μg / kg, and the dose per mouse was approximately 4 μg, which is far lower than the safe concentration value in the CCK-8 experiment. This indicates that the drug phenyl-β-D-glucuronide has no toxic effect on cells within the concentration range used in the experiment.

[0041] Finally, the above embodiments are intended to explain the technical solutions of the present invention, not to limit the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art will understand that any modifications or equivalent substitutions made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention will fall within the scope of the claims of the present invention.

Claims

1. Use of phenyl-β-D-glucuronide in the manufacture of a medicament for detecting tumors in induced breath.

2. The use according to claim 1, characterized in that the tumors include gastric cancer, nodular 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 detecting tumors by induced exhalation comprises an effective amount of phenyl-β-D-glucuronide and a pharmaceutically acceptable adjuvant.

4. 4. The use according to claim 3, wherein the pharmaceutically acceptable adjuvant comprises one or more of PBS buffer or saline.

5. The use according to claim 1 or 2, characterized in that the dosage form of the drug for detecting tumors by induced exhalation includes a solid dosage form, a liquid dosage form, a cream dosage form or a mist dosage form.

6. A drug for detecting tumors by induced exhalation, comprising an effective amount of phenyl-β-D-glucuronide and a pharmaceutically acceptable adjuvant.

7. The drug for detecting tumors by induced exhalation according to claim 6, characterized in that the pharmaceutically acceptable adjuvant comprises one or more of PBS buffer or saline.

8. The drug for detecting tumors by induced exhalation according to claim 6, characterized in that the drug dosage form includes a solid dosage form, a liquid dosage form, a cream dosage form or a mist dosage form.

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