Combined medication composition of platinum chemotherapeutic drugs

Abstract

The invention provides a drug combination composition for tumor chemotherapy. The drug combination composition comprises a safe and effective dose of a platinum chemotherapeutic drug and a safe and effective dose of an NAMPT inhibitor. Compared with a single platinum chemotherapeutic drug, the combined drug composition provided by the invention has higher sensitivity to cancers such as liver cancer, gastric cancer, colorectal cancer, lung cancer, cervical cancer, kidney cancer, pancreatic cancer, breast cancer and the like, the effective rate is remarkably improved, and the toxic and side effects are remarkably reduced, so that the combined drug composition has a wide application prospect.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a combined drug composition of platinum-based chemotherapy drugs. Background Art

[0002] Tumor refers to a new organism formed by the proliferation of local tissue cells under the action of various tumorigenic factors. It is divided into benign tumors and malignant tumors. Cancer refers to all malignant tumors. It is a disease caused by abnormal cell proliferation and can occur in any part of the body. It has unlimited proliferation and metastasis capabilities. Cancer has become a global public health issue. It is one of the main causes of death in countries around the world today and the second killer of humans after cardiovascular disease. In recent years, cancer has become younger, and the incidence and mortality rates have increased year by year, becoming a major malignant disease threatening human life and health.

[0003] Conventional treatments for tumors include surgery, chemotherapy, and radiotherapy. Surgery is generally only suitable for benign tumors and early malignant tumors that have not metastasized. Comprehensive treatment plans are often used for mid- and late-stage malignant tumors. Now biological therapy (mainly targeted therapy and immune enhancement, such as immune checkpoint inhibitors) is gradually emerging. Targeted therapy is a hot area in current tumor treatment, and new immunotherapy technologies targeting immune checkpoints represented by PD-1 / PD-L1 have shown encouraging therapeutic effects. However, since many patients lack tumor targets, the application scope of targeted drugs is still limited. Therefore, chemotherapy still plays a major role in tumor treatment, and cancer treatment drugs are still mainly chemotherapy drugs.

[0004] Platinum drugs are non-specific drugs for the cell cycle. They mainly form Pt-DNA adducts with DNA after entering tumor cells, thereby mediating tumor cell necrosis or apoptosis, thereby producing anticancer effects. Since the discovery of cisplatin's anticancer activity in 1967, the application and research of platinum metal anticancer drugs have developed rapidly. In clinical practice, almost all chemotherapy regimens for tumors are monotherapy or combination therapy based on platinum chemotherapy. Platinum anticancer drugs have become the cornerstone of chemotherapy. Platinum drugs such as oxaliplatin, cisplatin, and carboplatin are first-line chemotherapy drugs for a variety of solid tumors such as liver cancer, colorectal cancer, and cervical cancer. Although platinum chemotherapy drugs are the most widely used broad-spectrum anticancer drugs in clinical practice and have good efficacy on a variety of cancers, platinum has large toxic side effects, especially strong hepatotoxicity and renal toxicity, which greatly limits its clinical application; and platinum has the disadvantages of poor pharmacokinetics and congenital or acquired drug resistance. In particular, drug resistance inhibits the efficacy of platinum chemotherapy drugs, resulting in a continuous decrease in their anti-tumor sensitivity. According to statistics, the median survival time of patients with advanced cancer who receive chemotherapy is only 8 to 10 months, and resistance to platinum-based chemotherapy drugs is one of the important reasons for the patients' shorter survival time.

[0005] How to minimize the drug resistance of platinum chemotherapy drugs, improve the sensitivity and efficacy of platinum drugs, enhance their anti-cancer effects, and reduce their toxic side effects has always been a clinical issue of great concern. There is no ideal solution in the existing technology. Summary of the invention

[0006] In order to effectively solve the above problems, the present invention provides a combination drug composition of platinum-based chemotherapy drugs, wherein the combination drug composition comprises a therapeutically safe and effective amount of a platinum-based chemotherapy drug and a therapeutically safe and effective amount of a NAMPT inhibitor.

[0007] In some embodiments, the platinum chemotherapy drug is selected from any one or more of cisplatin, carboplatin, cyclothiaplatin, nedaplatin, oxaliplatin or lobaplatin.

[0008] In some embodiments, the platinum is oxaliplatin.

[0009] In some embodiments, the NAMPT inhibitor is selected from any one or more of FK866, CHS828, CB30865, and IS001;

[0010] In some embodiments, the NAMPT inhibitor is FK866.

[0011] In some embodiments, the therapeutically safe and effective amount of the platinum chemotherapy drug is administered in a dosage of 3 to 10 mg / kg / week; the therapeutically safe and effective amount of the NAMPT inhibitor is administered in a dosage of 2 to 20 mg / kg / day.

[0012] In some embodiments, the administration of the pharmaceutical composition includes any one or more of gastrointestinal administration, peritumoral subcutaneous administration, and intratumoral injection.

[0013] In some embodiments, the pharmaceutical composition is administered by intraperitoneal injection.

[0014] Application of a NAMPT inhibitor in the preparation of an anti-tumor synergistic and toxicity-reducing agent for platinum-based chemotherapy drugs.

[0015] In some embodiments, the tumor includes one or more of liver cancer, gastric cancer, colorectal cancer, lung cancer, cervical cancer, kidney cancer, pancreatic cancer, and breast cancer.

[0016] The beneficial effects of the present invention are:

[0017] The combined drug composition provided by the present invention comprises a platinum chemotherapy drug and a NAMPT inhibitor, which exert a synergistic effect, reduce the drug resistance of the platinum chemotherapy drug, improve the sensitivity and efficacy of the platinum chemotherapy drug, and significantly reduce the toxic and side effects of the platinum drugs. Compared with a single platinum chemotherapy drug, the combined drug composition has higher sensitivity to liver cancer, gastric cancer, colorectal cancer, lung cancer, cervical cancer, kidney cancer, pancreatic cancer, breast cancer and other cancers, significantly improves the effective rate, and significantly reduces the toxic and side effects, thereby having broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0019] Figure 1 This is a statistical chart of the tumor weights of mice with liver cancer after group treatment in Example 1 of the present invention.

[0020] Figure 2 This is a statistical chart of the tumor volume of liver cancer mice after group treatment in Example 1 of the present invention.

[0021] Figure 3 This is a statistical chart of tumor weights in mice with colorectal cancer after group treatment in Example 2 of the present invention.

[0022] Figure 4 This is a statistical graph of the tumor volume of colorectal cancer mice after group treatment in Example 2 of the present invention.

[0023] Figure 5 This is a statistical chart of tumor weights of cervical cancer mice after group treatment in Example 3 of the present invention.

[0024] Figure 6 This is a statistical chart of the tumor volume of cervical cancer mice after group treatment in Example 3 of the present invention.

[0025] Figure 7 This is a statistical chart of the serum ALP and UREA levels of liver cancer mice after group treatment in Example 4 of the present invention. DETAILED DESCRIPTION

[0026] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. Therefore, the following detailed description of the embodiments of the present invention provided in the drawings is not intended to limit the scope of the invention claimed for protection, but merely represents the selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0027] An embodiment of the present invention provides a combination drug composition of a platinum-based chemotherapeutic drug, wherein the combination drug composition comprises a therapeutically safe and effective amount of the platinum-based chemotherapeutic drug and a therapeutically safe and effective amount of a NAMPT inhibitor.

[0028] The anti-tumor efficacy of NAMPT inhibitors is described as follows:

[0029] Nicotinamide phosphoribosyltransferase (NAMPT) is a gene-encoded protein molecule distributed in the cytoplasm, nucleus and mitochondria. It is the rate-limiting enzyme in the salvage synthesis pathway of nicotinamide adenine dinucleotide (NAD) in mammals and is involved in the cell's material energy metabolism, DNA repair and protein synthesis. Unlike normal cells, tumor cells mainly rely on the glycolysis pathway to quickly obtain adenosine triphosphate (ATP) to provide energy for their rapid proliferation and survival. Therefore, tumor cells have a high demand for nicotinamide adenine dinucleotide (NAD), an important coenzyme in the glycolysis pathway. + ) is significantly higher than that of normal cells. Studies have shown that tumor cells mainly obtain NAD through the main salvage synthesis pathway, and nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme of this pathway. NAMPT can control NAD + The synthesis of NAD directly regulates cell metabolism; it can also + Relying on the activity of enzymes, it upregulates the level of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and indirectly regulates cell metabolism to improve cell survival. Currently, NAMPT is considered an important target for tumor treatment, and many studies have confirmed that NAMPT inhibitors have significant anti-tumor effects.

[0030] In the embodiments of the present invention, the NAMPT inhibitor and the platinum-based chemotherapy drugs cooperate with each other, and the two exert a synergistic effect, thereby reducing the drug resistance of the platinum-based chemotherapy drugs, improving the sensitivity and efficacy of the platinum-based chemotherapy drugs, and significantly reducing the toxic side effects of the platinum-based drugs.

[0031] In certain embodiments, the platinum chemotherapeutic drug is selected from any one or more of cisplatin, carboplatin, cyclothioplatin, nedaplatin, oxaliplatin or lobaplatin. For example, cisplatin can be used alone, or carboplatin can be used in combination with cyclothioplatin to achieve better therapeutic effect. In addition, nedaplatin or oxaliplatin can also be selected, or lobaplatin can be used in combination with other platinum drugs to achieve a wider range of treatment and higher efficacy.

[0032] In certain specific embodiments, the platinum drug selected is oxaliplatin. Oxaliplatin is a chemotherapy drug widely used in cancer treatment, especially in the treatment of colorectal cancer. It binds to the DNA of cancer cells to prevent their replication and proliferation, thereby achieving the purpose of inhibiting tumor growth. In clinical applications, oxaliplatin is usually used in combination with other chemotherapy drugs or targeted drugs to improve the therapeutic effect and reduce the occurrence of drug resistance.

[0033] In some embodiments, the NAMPT inhibitor is selected from any one or more of FK866 (also known as Daporinad), CHS828, CB30865, and IS001; these compounds have been studied and developed for inhibiting the activity of the NAMPT enzyme, thereby playing a role in treating certain diseases.

[0034] In some embodiments, the NAMPT inhibitor is FK866. FK866 is a drug that has been extensively studied and has shown significant efficacy in inhibiting the NAMPT enzyme, and is therefore preferred in certain treatment regimens.

[0035] In some embodiments, the dosage of the platinum chemotherapy drug with a safe and effective amount of treatment is 3 to 10 mg / kg / week; the dosage of the NAMPT inhibitor with a safe and effective amount of treatment is 2 to 20 mg / kg / day. Such a dosage range is intended to ensure that the drug exerts its anti-cancer effect while minimizing possible toxic side effects.

[0036] In some embodiments, the pharmaceutical composition can be administered through a variety of different routes of administration to ensure that the drug can effectively reach the target site and exert its expected therapeutic effect. These administration methods include, but are not limited to, gastrointestinal administration, peritumoral subcutaneous administration, and intratumoral injection. In some cases, these administration methods can be used alone or in combination as needed to achieve the best therapeutic effect.

[0037] In some embodiments, the pharmaceutical composition is administered by intraperitoneal injection. Intraperitoneal injection refers to injecting the drug directly into the abdominal cavity, so that the drug can directly enter the blood circulation in the abdominal cavity and be quickly distributed to various parts of the body. Intraperitoneal injection is particularly suitable for treatment situations that require a higher drug concentration in the abdominal cavity, such as certain intraperitoneal tumors or inflammatory diseases. Through intraperitoneal injection, the drug can directly act on the lesion site in the abdominal cavity, improve the treatment effect, and reduce the potential side effects of the drug on other tissues and organs.

[0038] A NAMPT inhibitor is used to prepare a synergistic and toxic-reducing agent that can enhance the anti-tumor effect of platinum chemotherapy drugs and reduce their toxic side effects. This synergistic and toxic-reducing agent significantly improves the efficacy of platinum drugs through synergistic effects, thereby showing more significant anti-tumor activity in the treatment of various cancers and significantly reducing the toxic side effects of platinum chemotherapy drugs.

[0039] In some specific embodiments, the tumor types include a variety of common malignant tumors, including but not limited to liver cancer, gastric cancer, colorectal cancer, lung cancer, cervical cancer, kidney cancer, pancreatic cancer and breast cancer. These cancer types have high morbidity and mortality rates clinically, so it is of great clinical significance to develop a synergistic and toxic-reducing agent that can effectively enhance the effect of existing chemotherapeutic drugs. This synergistic and toxic-reducing agent can play a significant synergistic role in the treatment of different types of tumors, thereby providing cancer patients with more effective treatment options.

[0040] Example 1: NAMPT inhibitor FK866 enhances the inhibitory effect of oxaliplatin on liver cancer growth.

[0041] Animal model construction: 2-4 week old Balb / c male nude mice were taken and fed adaptively for 2 weeks at 25±1℃ with a 12-hour light-dark cycle in an isolation barrier environment without specific pathogens. Animal husbandry and operation were strictly carried out in accordance with the ethical standards and operation guidelines for experimental animals. After 2 weeks, human liver cancer cells HuH-7 (purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences) were inoculated subcutaneously in the forelimbs of Balb / c male nude mice, and the tumors were allowed to grow freely for 2 weeks. The liver cancer animal model was completed.

[0042] Group intervention experiment: After 2 weeks, the model mice were randomly divided into 4 groups: ① control group, ② oxaliplatin group, ③ FK866 group, and ④ FK866 + oxaliplatin group. FK866: intraperitoneal injection once a day (10 mg / kg mouse body weight); oxaliplatin: intraperitoneal injection once a week (5 mg / kg mouse body weight); control group: intraperitoneal injection of an equal volume of saline once a day. Treatment continued for 2 weeks.

[0043] Experimental results measurement: After the start of group treatment, the tumor volume was measured with a vernier caliper every 3 days. The tumor volume calculation formula is: tumor volume = 0.5 × long diameter × short diameter 2 (mm 3 After 2 weeks of group treatment, the mice were killed by cervical dislocation, the tumor tissues were removed, and the tumor weight was measured using an analytical balance. The measurement results are shown in Table 1 and Figure 1 , Figure 2 shown.

[0044] Table 1 Effect of the combined drug of the present invention on tumor weight and volume in mice with liver cancer

[0045]

[0046] The analysis showed that two weeks after group treatment, the tumor weight and volume of the FK866+oxaliplatin group were significantly smaller than those of the other single-use groups. At the same time, compared with the control group, the sum of the reductions in tumor weight and volume in the FK866 group and the oxaliplatin group was still smaller than that in the FK866+oxaliplatin group. This suggests that FK866 and oxaliplatin cooperate with each other, play a synergistic role, and jointly improve the inhibitory effect on liver cancer growth.

[0047] Example 2: NAMPT inhibitor FK866 enhances the effect of oxaliplatin in inhibiting the growth of colorectal cancer.

[0048] Animal model construction: 2-4 week old Balb / c male mice were taken and fed adaptively for 2 weeks at 25±1℃ with a 12-hour light-dark cycle in an isolation barrier environment without specific pathogens. Animal husbandry and operation were strictly carried out in accordance with the ethical standards and operation guidelines for experimental animals. After 2 weeks, human colorectal cancer cells CT26 (purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences) were inoculated subcutaneously in the forelimbs of Balb / c male mice, and the tumors were allowed to grow freely for 2 weeks. The colorectal cancer animal model was completed.

[0049] Group intervention experiment: After 2 weeks, the model mice were randomly divided into 4 groups: ① control group, ② oxaliplatin group, ③ FK866 group, and ④ FK866 + oxaliplatin group. FK866: intraperitoneal injection once a day (10 mg / kg mouse body weight); oxaliplatin: intraperitoneal injection once a week (5 mg / kg mouse body weight); control group: intraperitoneal injection of an equal volume of saline once a day. Treatment continued for 2 weeks.

[0050] Experimental results measurement: After the start of group treatment, the tumor volume was measured with a vernier caliper every 3 days. The tumor volume calculation formula is: tumor volume = 0.5 × long diameter × short diameter 2 (mm 3After 2 weeks of treatment, the mice were killed by cervical dislocation, and the tumor tissues were removed and weighed using an analytical balance. The measurement results are shown in Table 2 and Figure 3 , Figure 4 shown.

[0051] Table 2 Effect of the combined drug of the present invention on tumor weight and volume in mice with colorectal cancer

[0052]

[0053] The analysis showed that two weeks after group treatment, the tumor weight and volume of the FK866+oxaliplatin group were significantly smaller than those of the other single-drug groups. At the same time, compared with the control group, the sum of the reductions in tumor weight and volume in the FK866 group and the oxaliplatin group was still smaller than that in the FK866+oxaliplatin group. This suggests that FK866 and oxaliplatin cooperate with each other, play a synergistic role, and jointly improve the inhibitory effect on the growth of colorectal cancer.

[0054] Example 3: NAMPT inhibitor FK866 enhances the effect of oxaliplatin in inhibiting the growth of cervical cancer.

[0055] Animal model construction: 2-4 week old Balb / c female nude mice were taken and fed adaptively for 2 weeks at 25±1℃ with a 12-hour light-dark cycle in an isolation barrier environment without specific pathogens. Animal husbandry and operation were strictly carried out in accordance with the ethical standards and operation guidelines for experimental animals. After 2 weeks, human cervical cancer cells Hela (purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences) were inoculated subcutaneously in the forelimbs of Balb / c female nude mice, and the tumors were allowed to grow freely for 2 weeks. The cervical cancer animal model was completed.

[0056] Group intervention experiment: After 2 weeks, the model mice were randomly divided into 4 groups: ① control group, ② oxaliplatin group, ③ FK866 group, and ④ FK866 + oxaliplatin group. FK866: intraperitoneal injection once a day (10 mg / kg mouse body weight); oxaliplatin: intraperitoneal injection once a week (5 mg / kg mouse body weight); control group: intraperitoneal injection of an equal volume of saline once a day. Treatment continued for 2 weeks.

[0057] Experimental results measurement: After the start of group treatment, the tumor volume was measured with a vernier caliper every 3 days. The tumor volume calculation formula is: tumor volume = 0.5 × long diameter × short diameter 2 (mm 3 After 2 weeks of group treatment, the mice were killed by cervical dislocation, the tumor tissues were removed, and the tumor weight was measured using an analytical balance. The measurement results are shown in Table 3 and Figure 5 , Figure 6 shown.

[0058] Table 3 Effect of the combined drug of the present invention on tumor weight and volume of cervical cancer mice

[0059]

[0060] The analysis showed that two weeks after group treatment, the tumor weight and volume of the FK866+oxaliplatin group were significantly smaller than those of the other single-use groups. At the same time, compared with the control group, the sum of the reductions in tumor weight and volume in the FK866 group and the oxaliplatin group was still smaller than that in the FK866+oxaliplatin group. This suggests that the FK866 group and oxaliplatin cooperated with each other, exerted a synergistic effect, and jointly improved the inhibitory effect on the growth of cervical cancer.

[0061] Example 4: NAMPT inhibitor FK866 reduces the toxic side effects of oxaliplatin in the treatment of liver cancer.

[0062] Animal model construction: 2-4 week old Balb / c male nude mice were taken and fed adaptively for 2 weeks at 25±1℃ with a 12-hour light-dark cycle in an isolation barrier environment without specific pathogens. Animal husbandry and operation were strictly carried out in accordance with the ethical standards and operation guidelines for experimental animals. After 2 weeks, human liver cancer cells HuH-7 (purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences) were inoculated subcutaneously in the forelimbs of Balb / c male nude mice, and the tumors were allowed to grow freely for 2 weeks. The liver cancer animal model was completed.

[0063] Group intervention experiment: After 2 weeks, the model mice were randomly divided into 4 groups: ① control group, ② oxaliplatin group, ③ FK866 group, and ④ FK866 + oxaliplatin group. FK866: intraperitoneal injection once a day (10 mg / kg mouse body weight); oxaliplatin: intraperitoneal injection once a week (5 mg / kg mouse body weight); control group: intraperitoneal injection of an equal volume of saline once a day. Treatment continued for 2 weeks.

[0064] Experimental results: After 2 weeks of group treatment, the serum of mice was collected for blood biochemical analysis, mainly to measure the levels of alkaline phosphatase (ALP), a marker of liver damage, and urea (UREA), a marker of kidney damage. The measurement results are shown in Table 4 and Figure 7 shown.

[0065] Table 4 Effect of the combined use of the present invention on the levels of serum ALP and UREA in mice with liver cancer

[0066]

[0067] The analysis showed that after two weeks of group treatment, oxaliplatin alone treatment significantly increased the levels of ALP and UREA in the serum of mice, indicating that oxaliplatin alone treatment caused liver and kidney damage in mice; FK866 alone treatment also significantly increased the levels of ALP and UREA in the serum of mice, indicating that FK866 alone treatment also caused liver and kidney damage in mice; while the FK866 + oxaliplatin combination treatment group significantly reduced the levels of ALP and UREA in the serum of mice, indicating that the NAMPT inhibitor FK866 can significantly reduce the toxic side effects of oxaliplatin in the treatment of liver cancer.

[0068] In summary, compared with a single platinum chemotherapy drug, the combination drug composition provided by the present invention has a synergistic effect between the two drugs, reduces the drug resistance of platinum chemotherapy drugs, improves the sensitivity and efficacy of platinum drugs, and significantly reduces the toxic and side effects of platinum drugs. Compared with a single platinum chemotherapy drug, it has higher sensitivity to liver cancer, gastric cancer, colorectal cancer, lung cancer, cervical cancer, kidney cancer, pancreatic cancer, breast cancer and other cancers, significantly improves the effective rate, and significantly reduces the toxic and side effects, thereby having broad application prospects.

[0069] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A combination drug composition of a platinum-based chemotherapy drug, characterized in that: The combined drug composition comprises a therapeutically safe and effective amount of a platinum-based chemotherapy drug and a therapeutically safe and effective amount of a NAMPT inhibitor.

2. The combined pharmaceutical composition according to claim 1, characterized in that: The platinum chemotherapy drug is selected from any one or more of cisplatin, carboplatin, cyclothioplatin, nedaplatin, oxaliplatin or lobaplatin.

3. The combined pharmaceutical composition according to claim 1, characterized in that: The platinum compound is oxaliplatin.

4. The combined pharmaceutical composition according to claim 1, characterized in that: The NAMPT inhibitor is selected from any one or more of FK866, CHS828, CB30865, and IS001.

5. The combined pharmaceutical composition according to claim 1, characterized in that: The NAMPT inhibitor is FK866.

6. The pharmaceutical composition according to claims 1 to 5, characterized in that The dosage of the platinum chemotherapy drug with a safe and effective therapeutic amount is 3 to 10 mg / kg / week; the dosage of the NAMPT inhibitor with a safe and effective therapeutic amount is 2 to 20 mg / kg / day.

7. The pharmaceutical composition according to claims 1 to 5, characterized in that The administration method of the pharmaceutical composition includes any one or more of gastrointestinal administration, peritumoral subcutaneous administration, and intratumoral injection.

8. The pharmaceutical composition according to claims 1 to 5, characterized in that The pharmaceutical composition is administered by intraperitoneal injection.

9. Application of a NAMPT inhibitor in the preparation of an anti-tumor synergistic and toxicity-reducing agent for platinum-based chemotherapy drugs.

10. The use according to claim 8, characterized in that The tumor includes one or more of liver cancer, gastric cancer, colorectal cancer, lung cancer, cervical cancer, kidney cancer, pancreatic cancer, and breast cancer.

Images