Composition and application thereof in preparation of antitumor drugs

Abstract

The invention relates to the technical field of medicines, in particular to a composition and application thereof in preparation of antitumor drugs. The combination of the propofol and the chemotherapeutic drug provided by the invention can generate a more effective inhibition effect on tumors, and experiments prove that the combination of the two drugs can generate a remarkable synergistic effect. Especially, the combination of the two medicines has a good treatment effect on liver cancer, and the clinical problems that the liver cancer chemosensitivity is not high, and no clinically available chemosensitizer exists at present are solved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a composition and its application in preparing anti-tumor drugs. Background Art

[0002] In recent years, with the continuous deepening of medical research, significant progress has been made in the field of tumor treatment. The implementation of strategies such as targeted therapy, immunotherapy, and drug combination therapy has brought more hope of survival to patients. With the increase in the incidence of tumors worldwide, finding new treatments and drugs has become a hot topic in medical research.

[0003] Anti-tumor drugs are mainly divided into several categories, including chemical drugs, targeted drugs, and immunotherapy drugs. Each type of drug has its own characteristics in terms of mechanism of action, efficacy, and side effects. In addition, drug combination therapy has also become a common strategy in tumor treatment. Through a reasonable combination of drugs, multiple targets or signal transduction pathways of tumor cells can be intervened to achieve better therapeutic effects.

[0004] As a mature clinical anesthetic drug, propofol has been widely used in surgical procedures for liver cancer and other tumors, and is a drug that has been safely used in cancer patients. Propofol, also known as PROPOFOL, 2,6-diisopropylphenol, Profolf or Propofol, has the potential to both anti-cancer and chemotherapy sensitization. Considering that there is still a lack of clinically available chemotherapy sensitizers, the new drug development cycle is long, and the risk of clinical trial failure is high, if propofol is used as a chemotherapy sensitizer and combined with existing chemotherapy drugs, it is hoped that a better anti-liver cancer effect can be achieved. Summary of the invention

[0005] In view of this, the technical problem to be solved by the present invention is to provide a composition and its application in the preparation of anti-tumor drugs.

[0006] The composition provided by the present invention consists of propofol and a chemotherapeutic drug, wherein the chemotherapeutic drug is selected from at least one of epirubicin, platinum-based chemotherapeutic drugs or pentafluorouracil.

[0007] The platinum-based chemotherapy drugs include cisplatin and other platinum-based chemotherapy drugs; and their salts or derivatives of the same name. For example, cisplatin, carboplatin or oxaliplatin. The present invention has found that the combined use of propofol and chemotherapy drugs (epirubicin, cisplatin and 5-fluorouracil) has an inhibitory effect on liver cancer ( Figure 1 ), and proved that the combination of the two drugs can produce significant synergistic effects. In the present invention, the two drugs in the composition can be mixed or exist independently of each other, and the present invention does not limit this.

[0008] In the present invention, the mass ratio of propofol to the chemotherapy drug is 1:(0.0001-200), preferably, the mass ratio of propofol to the chemotherapy drug is 1:(0.0001-100). Preferably, the mass ratio of propofol to the chemotherapy drug is 1:(0.0001-100). For example, the mass ratio of propofol to the chemotherapy drug is 1:0.001, 1:0.002, 1:0.003, 1:0.004, 1:0.005, 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:1, 1:2, 1:3, 1:4, 1:5, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:20, 1:50 or 1:100.

[0009] In the embodiment of the present invention, epirubicin is used as an example to verify the effect of the combination of propofol and chemotherapeutic drugs. In some embodiments, the chemotherapeutic drug is epirubicin, and the mass ratio of propofol to epirubicin is 1:(0.0001-100). In a specific embodiment, the mass ratio of propofol to epirubicin is 1:0.005. Experiments show that the combination of propofol and epirubicin has a significant synergistic effect.

[0010] The present invention also provides use of the composition as described in any of the preceding items in the preparation of anti-tumor drugs.

[0011] In some embodiments, the tumor is liver cancer, gallbladder cancer, pancreatic cancer, small intestine tumor, colon cancer / colorectal cancer, esophageal cancer, gastric cancer, digestive system tumor, bladder cancer, blood system tumor, bone tumor, cartilage tumor, lung cancer, tracheal tumor, glottis cancer, brain cancer, central nervous system tumor, peripheral nervous system tumor, head and neck tumor, kidney cancer, laryngeal cancer, nasopharyngeal cancer, lung cancer, muscle tissue cancer, oral or nasal mucosal cancer, ovarian cancer, breast cancer, prostate cancer, cervical cancer, endometrial cancer, external genital tumor, urogenital tract tumor, adrenal tumor, skin cancer, spleen tumor, testicular cancer and / or thyroid cancer. In a specific embodiment, the tumor is liver cancer.

[0012] In some embodiments, the anti-tumor effect includes inhibiting tumor cell activity, promoting tumor cell apoptosis and / or reducing tumor volume.

[0013] In some specific embodiments, in the anti-tumor agent, the tumor cells are liver cancer cells, and more specifically, the liver cancer cells are MHCC97H and / or HepG2.

[0014] Furthermore, the present invention also provides an anti-tumor drug, which comprises the above-mentioned composition and a pharmaceutically acceptable excipient.

[0015] The pharmaceutically acceptable excipients include one or a mixture of two or more of flavoring agents, fillers, lubricants, preservatives, suspending agents, food coloring agents, diluents, emulsifiers, disintegrants or plasticizers.

[0016] The dosage form of the drug of the present invention is a dosage form for gastrointestinal administration and / or a dosage form for parenteral administration.

[0017] The dosage form for administration through the gastrointestinal tract is powder, tablet, granule, capsule, solution, emulsion or suspension.

[0018] The non-intestinal administration dosage form is an injection dosage form, a respiratory tract administration dosage form, a skin administration dosage form, a mucosal administration dosage form or a cavity administration dosage form.

[0019] The present invention does not limit the content of the composition in the medicine, nor does it limit the dosage of each administration. Preferably, the dosage is not less than the effective dose. In the medicine, the dosage of the composition is not less than the effective amount.

[0020] The drug of the present invention also includes other therapeutic agents with anti-tumor activity, and the therapeutic agent is selected from mitomycin, gemcitabine, capecitabine, irinotecan, oxaliplatin, cyclophosphamide, methotrexate, adriamycin, vincristine, sorafenib, sunitinib, bevacizumab, erlotinib, lenvatinib mesylate capsules, Mesylate), Regorafenib, Lenvima, Entecavir, Peginterferon Alfa-2a, Interferon, Lamivudine, Icariin, Huachansu Capsules, Kanglaite Injection, Cidan Capsules, Sodium Cantharidinate Vitamin B6 Injection, Jinlong Capsules, Biejia Jianwan, Huaier Granules, Elemene Injection, Kangai Injection, Aidi Injection, Ganfule Capsules, Brucea Oil Soft Capsules, Compound Cantharidae Capsules, Transfer Factor, Various Immune Checkpoint Drugs (PD-1 Antibody, PD-L1 Antibody, TIGIT Antibody, CTLA4 Antibody, etc.), Gamma Globulin Globulin); various Chinese herbal medicine combinations, including but not limited to Chaihu Shugan San plus or minus in Jingyue Complete Works, Gexia Zhuyu Tang plus or minus in Yilin Gaicuo, Xiaoyao San plus or minus in Taiping Huimin Heji Jufang, Yinchenhao Tang plus or minus Wuling San in Shanghan Lun, and Yiguanjian plus or minus in Liuzhou Medical Talks.

[0021] The present invention also provides an anti-tumor method, which comprises administering the above-mentioned drug or the above-mentioned composition.

[0022] In the anti-tumor method of the present invention, two or more active ingredients are administered simultaneously or successively, and the present invention does not limit this. The dosing interval of the pre- and post-administration is any time interval within 30 days, preferably any time interval within 3 days, preferably not longer than 24 hours, preferably not longer than 12 hours, preferably not longer than 6 hours, preferably not longer than 5 hours, more preferably not longer than 4 hours, even more preferably not longer than 3 hours, more preferably not longer than 2 hours and most preferably not longer than 1 hour and / or not longer than 6 hours, preferably not longer than 5 hours, more preferably not longer than 4 hours, even more preferably not longer than 3 hours, more preferably not longer than 2 hours and most preferably not longer than 1 hour after the administration of other therapeutic agents.

[0023] In the anti-tumor method described in the present invention, the administration method of the drug includes but is not limited to sublingual administration, oral administration, subcutaneous injection, intradermal injection, intramuscular injection, intravenous injection, intravenous drip, intraperitoneal administration, anal administration, airway administration, transdermal or other mucosal administration, etc.

[0024] In the anti-tumor method described in the present invention, the administration frequency of two or more drugs can be the same or different, and the present invention is not limited to this. For example, the administration frequency of two or more drugs in the drug is independently selected from 1 month / time, 15 days / time, 7 days / time, once every other day, 1 time / day, 2 times / day, 3 times / day or 4 times / day.

[0025] The present invention provides a combination of propofol and chemotherapy drugs that can produce a more effective inhibitory effect on tumors, and experiments have shown that the combination of the two drugs can produce a significant synergistic effect. In particular, the combination of the two drugs has a good therapeutic effect on liver cancer, solving the clinical problem that liver cancer has low chemotherapy sensitivity and there is currently no clinically available chemotherapy sensitizer. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram: Propofol combined with chemotherapy drugs (epirubicin, cisplatin and 5-Fu) for the treatment of liver cancer;

[0027] Figure 2-A Dose response matrix: combination synergy analysis of propofol and the chemotherapy drug epirubicin, propofol concentrations: 0μg / ml, 2.5μg / ml, 5μg / ml, 10μg / ml, 20μg / ml, 40μg / ml; epirubicin concentrations: 0μg / ml, 0.1μg / ml, 0.2μg / ml, 0.4μg / ml, 0.8μg / ml, 1.6μg / ml;

[0028] Figure 2-B .ZIP drug combination analysis model: The drug combination index of propofol / epirubicin in two liver cancer cell lines is MHCC97H (ZIP synergy score 9.258±2.66) and HepG2 (ZIP synergy score 14.131±2.93);

[0029] Figure 2-C.Bliss drug combination analysis model: propofol / epirubicin drug combination index is MHCC97H (Bliss synergy score 8.931±2.66) and HepG2 (Bliss synergy score14.062±2.93);

[0030] Figure 3 LOEWE combination index analysis for DrugComb propofol / epirubicin combination therapy: A., B., and C. are data for HepG2; D., E., and F. are data for MHCC97H;

[0031] The drug combination index of propofol / epirubicin in two liver cancer cell lines was MHCC97H (LOEWE score 8.37, 7.22, 5.72) and HepG2 (LOEWE score 11.42, 12.58, and 10.51);

[0032] Figure 4 HSA combination index analysis for DrugComb propofol / epirubicin combination therapy: A., B., and C. are data for HepG2; D., E., and F. are data for MHCC97H;

[0033] The drug combination index of propofol / epirubicin in two hepatoma cell lines was MHCC97H (HSA score 10.84, 9.75, and 7.02) and HepG2 (HSA score 16.41, 17.00, and 11.43);

[0034] Figure 5 The drug half-inhibitory concentration test verifies the combined effect of propofol / epirubicin:

[0035] A. The IC50 of MHCC97H were: epirubicin IC50 (0.7672 μg / ml, 0.5317 to 1.154 μg / ml), propofol + epirubicin IC50 (0.2387 μg / ml, 0.1852 to 0.3085 μg / ml);

[0036] B. The IC50 in HepG2 were: epirubicin IC50 (1.041 μg / ml, 0.9496-1.150 μg / ml), propofol + epirubicin IC50 (0.3967 μg / ml, 0.3562-0.4430 μg / ml);

[0037] Figure 6Flow cytometry was used to detect the effect of propofol + epirubicin combination on apoptosis of liver cancer cells: A. Flow cytometry was used to detect the effect of propofol + epirubicin combination on apoptosis of liver cancer cells (MHCC97H and HepG2); B. Further statistical analysis of the apoptotic cell results in Figure A; epirubicin (0.1μg / ml) or propofol + epirubicin combination (20μg / ml+0.1μg / ml), vehicle was the control group; T test, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; NS, not significance.

[0038] Figure 7 In vivo experiments were performed to verify that propofol enhances the inhibitory effect of the chemotherapy drug epirubicin on tumors: A. In the subcutaneous tumor models derived from MHCC97H and HepG21, four different treatments were given, including control / vehicle, propofol, epirubicin, and propofol+epirerubicin, and the volume and weight of the tumors were compared after removal; B. Statistical analysis of the volume (left figure) and weight (right figure) of MHCC97H tumors; C. Statistical analysis of the volume (left figure) and weight (right figure) of HepG2 tumors; Among them, propofol (20μg / ml), epirubicin (0.1μg / ml) or propofol+epirerubicin combination (20μg / ml+0.1μg / ml); One-way ANOVA, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; NS, not significance. DETAILED DESCRIPTION

[0039] The present invention provides a composition and its use in the preparation of an anti-tumor drug. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0040] Unless otherwise defined herein, scientific and technical terms related to the present invention shall have the meanings understood by those of ordinary skill in the art.

[0041] Furthermore, unless otherwise indicated herein, terms in the singular shall include pluralities and terms in the plural shall include the singular. More specifically, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless expressly indicated otherwise.

[0042] The terms "include", "comprising" and "having" are used interchangeably herein and are intended to indicate the inclusiveness of the solution, meaning that the solution may have other elements in addition to the listed elements. At the same time, it should be understood that the use of "include", "comprising" and "having" descriptions herein also provides a "consisting of..." solution.

[0043] The term "and / or" as used herein includes the meanings of "and", "or" and "all or any other combination of elements linked by the term". In this application, the term "and / or" describes the association relationship of associated objects, indicating that three relationships may exist. For example, A and / or B may represent: A exists alone, A and B exist at the same time, and B exists alone. A and B may be singular or plural.

[0044] In this application, "at least one" means one or more, "more than one" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items.

[0045] In this application, the numerical ranges and parameters involved have been presented in the specific embodiments as accurately as possible. However, any numerical value inherently inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise explicitly stated, it should be understood that all numerical ranges or specific data used in this disclosure may have certain reasonable deviations within a certain range, for example: within ±10%, ±5%, ±1% or ±0.5%.

[0046] In the embodiment of the present invention, propofol combined with epirubicin is used as an example to find that propofol combined with chemotherapy drugs can effectively inhibit liver cancer. In fact, propofol combined with various chemotherapy drugs can achieve the effect of treating liver cancer, not limited to propofol combined with epirubicin, propofol combined with cisplatin, propofol combined with 5-Fu and other combined medication schemes, and the medication method is not limited to simultaneous administration, asynchronous administration, sequential administration, administration of various mixtures, etc.

[0047] In the present application, the subject of the liver cancer inhibition is a human or a mammal, and the mammal includes bovines, equines, ovines, porcines, canines, felines, rodents, and primates.

[0048] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0049] Among them, propofol is also known as 2,6-diisopropylphenol, 2,6-diisopropylphenol, Propofol, Disoprofol, and Propofol; the English name is 2,6-DIISOPROPYLPHENOL, 2,6-BIS(1-METHYLETHYL)PHENOL, Diprivan10, Disoprofol, PD18215, Phenol,2,6-diisopropyl-, Phenol,2,6-bis(1-methylethyl)-, Phenol,2,6-diisopropyl-.

[0050] The epirubicin is also called epirubicin and its English name is Epidoxorubicin.

[0051] The cisplatin also includes other platinum-derived chemotherapy drugs; and their salts or derivatives with the same name.

[0052] The pentafluorouracil / 5-Fu is also called 5-fluorouridine nucleoside, and its English name is 5-Fluorouracil. The non-fluorouracil also includes its salts or derivatives with the same name.

[0053] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0054] Some cases are recorded in the embodiments of the present invention. The embodiments show some implementation methods of the present invention. However, this does not mean that the effects of the present invention can only be achieved in these cases. In fact, any concentration of each component between the two endpoint values ​​shown in the embodiments can achieve a good anti-tumor effect. In addition, many attempts have been made during the research and development process, such as using different chemotherapy drugs or propofol analogs, using different ratios, etc. to perform tumor cell inhibition experiments, but the effects of these attempts are not as good as those recorded in the embodiments, and will not be repeated here.

[0055] The present invention will be further described below in conjunction with embodiments:

[0056] Example

[0057] Taking propofol combined with epirubicin as an example, it is proved that propofol combined with chemotherapy drugs effectively inhibits liver cancer. In the preliminary experiment, a preliminary safety experiment (IC50) was carried out on the drug concentrations shown in the following examples, and the combined regimen for treating in vivo and in vitro liver cancer models was determined through combined drug experiments and IC50 concentration detection of liver cancer cells again. In the single combined regimen clearly used for treatment, the selected epirubicin drug combined drug concentration (0.1 μg / ml) was lower than its IC50 for liver cancer cells, and the selected propofol combined drug concentration (20 μg / ml) was the conventional safe in vivo drug concentration during anesthesia for clinical patients. In the scheme described in this case, the chemotherapy drug concentration (epirerubicin) was much lower than that recorded in existing literature (see J Nat Prod. 2016Sep 23;79(9):2397-402.doi:10.1021 / acs.jnatprod.6b00639.) has a median lethal concentration (epirubicin IC50, 0.273 μg / ml or 0.47 uM) for non-tumor HEK293T cells.

[0058] 1. Propofol and epirubicin were used to conduct a combined drug test on liver cancer cell lines (MHCC97H and HepG2). Each milliliter of culture system contained (propofol concentration: 0μg / ml, 2.5μg / ml, 5μg / ml, 10μg / ml, 20μg / ml, 40μg / ml; epirubicin concentration: 0μg / ml, 0.1μg / ml, 0.2μg / ml, 0.4μg / ml, 0.8μg / ml, 1.6μg / ml). We used two platforms to analyze the synergistic effect of drug combinations, namely DrugComb and Synergyfinder.

[0059] The baseline data of the dose matrix analysis showed that the combination of propofol and epirubicin had a significant inhibitory effect on liver cancer cell lines ( Figure 2-A ). Then, using the baseline data, four different drug synergy analyses were performed on DrugComb and Synergyfinder.

[0060] The ZIP synergy analysis performed on Synergyfinder showed that the combination of the two drugs was effective in MHCC97H (ZIP synergy score 9.258±2.66) and HepG2 (ZIP synergy score 14.131±2.93), and the scores were statistically significant ( Figure 2-B ).

[0061] Bliss synergy analysis was performed on Synergyfinder, showing that the synergy effects of MHCC97H (Bliss synergy score 8.931 ± 2.66) and HepG2 (Bliss synergy score 14.062 ± 2.93) were also significant, and the scores were statistically significant ( Figure 2-C ).

[0062] The LOEWE drug synergy analysis performed on DrugComb showed that the LOEWE scores of MHCC97H (LOEWE score 8.37, 7.22, 5.72) and HepG2 (LOEWE score 11.42, 12.58, and 10.51) were statistically significant ( Figure 3 ).

[0063] The HSA drug synergy analysis performed on DrugComb showed that the HSA scores of MHCC97H (HSA score 10.84, 9.75 and 7.02) and HepG2 (HSA score 16.41, 17.00 and 11.43) were statistically significant ( Figure 4 ).

[0064] Therefore, all synergistic analysis models support that the combination of propofol and epirubicin has a better therapeutic effect in the treatment of liver cancer. As shown in Figure 2, the drug combination index of propofol / epirubicin is ZIP drug combination analysis model: MHCC97H (ZIPsynergy score 9.258±2.66) and HepG2 (ZIP synergy score14.131±2.93); Bliss drug combination analysis model: MHCC97H (Bliss synergy score 8.931±2.66) and HepG2 (Bliss synergyscore 14.062±2.93); Figure 3 LOEWE drug combination analysis model: propofol / epirubicin drug combination index is: MHCC97H (LOEWE score 8.37, 7.22, 5.72) and HepG2 (LOEWE score 11.42, 12.58 and 10.51); Figure 4 HSA drug combination analysis model: propofol / epirubicin drug combination index is: MHCC97H (HSA score 10.84, 9.75 and 7.02) and HepG2 (HSA score 16.41, 17.00 and 11.43).

[0065] 2. The combined effect of the two drugs was further verified through the drug half-inhibitory concentration test (50% inhibitory concentration, IC50).

[0066] The results showed that propofol (20 μg / ml) could significantly reduce the IC50 of epirubicin in two liver cancer cells, that is, enhance the sensitivity of liver cancer cells to the chemotherapy drug epirubicin ( Figure 5 ). The IC50 values ​​in MHCC97H were: epirubicin IC50 (0.7672 μg / ml, 0.5317-1.154 μg / ml), epirubicin combined with propofol IC50 (0.2387 μg / ml, 0.1852 to 0.3085 μg / ml). The IC50 values ​​in HepG2 were: epirubicin IC50 (1.041 μg / ml, 0.9496-1.150 μg / ml), epirubicin combined with propofol IC50 (0.3967 μg / ml, 0.3562-0.4430 μg / ml).

[0067] And, if Figure 6 As shown in the figure, compared with the control group (vehicle) and single-agent epirubicin, the combination of propofol + epirubicin can significantly promote the apoptosis of liver cancer cells, further suggesting that propofol can improve the chemosensitivity of epirubicin to liver cancer cells. Among them, epirubicin (0.1μg / ml) or propofol + epirubicin combination (20μg / ml+0.1μg / ml).

[0068] 3. By constructing a nude mouse xenograft subcutaneous tumor model for in vivo animal experiments, the synergistic effect of propofol and epirubicin in vivo was further verified. The results showed that compared with the control group (vehicle), propofol (20μg / ml), epirubicin (0.1μg / ml) or propofol + epirubicin combined (20μg / ml + 0.1μg / ml) could inhibit the growth of tumors in nude mice, and the tumors were significantly reduced; compared with the chemotherapy drug alone (epirerubicin) group, the inhibitory effect of propofol + epirubicin combined on tumors was significantly enhanced, and the tumors were further reduced ( Figure 7 A). Statistical analysis after recording tumor volume and weight showed that compared with the control group and epirubicin alone, propofol + epirubicin combination therapy significantly reduced the volume and weight of MHCC97H-derived tumors ( Figure 7 Compared with the control group or epirubicin alone, the combination of propofol and epirubicin significantly reduced the volume and weight of HepG2-derived tumors ( Figure 7 In conclusion, propofol can significantly enhance the inhibitory effect of chemotherapy drugs (epibricin) on tumors.

[0069] The above are only preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A composition consisting of propofol and a chemotherapeutic drug, The chemotherapy drug is selected from at least one of epirubicin, cisplatin or pentafluorouracil.

2. The composition according to claim 1, It is characterized in that The mass ratio of the propofol to the chemotherapy drug is 1:(0.0001-200).

3. The composition according to claim 2, It is characterized in that The mass ratio of the propofol to the chemotherapy drug is 1:(0.0001-100).

4. The composition according to claim 1, It is characterized in that The chemotherapy drug is epirubicin, and the mass ratio of propofol to epirubicin is 1:0.

005.

5. Use of the composition according to any one of claims 1 to 4 in the preparation of anti-tumor drugs.

6. The use according to claim 4, It is characterized in that The tumor is liver cancer, gallbladder cancer, pancreatic cancer, small intestine tumor, large intestine cancer / colorectal cancer, esophageal cancer, gastric cancer, digestive system tumor, bladder cancer, blood system tumor, bone tumor, cartilage tumor, lung cancer, tracheal tumor, glottic cancer, brain cancer, central nervous system tumor, peripheral nervous system tumor, head and neck tumor, kidney cancer, laryngeal cancer, nasopharyngeal cancer, lung cancer, muscle tissue cancer, oral or nasal mucosal cancer, ovarian cancer, breast cancer, prostate cancer, cervical cancer, endometrial cancer, external genitalia tumor, urogenital tract tumor, adrenal tumor, skin cancer, spleen tumor, testicular cancer and / or thyroid cancer.

7. The use according to claim 4 or 5, It is characterized in that The anti-tumor effect includes inhibiting tumor cell activity, promoting tumor cell apoptosis and / or reducing tumor volume.

8. An anti-tumor drug comprising the composition according to any one of claims 1 to 4 and a pharmaceutically acceptable excipient.

9. The drug according to claim 8, It is characterized in that Other therapeutic agents with / potentially having anti-tumor activity are also included, and the therapeutic agents are selected from mitomycin, gemcitabine, capecitabine, irinotecan, oxaliplatin, cyclophosphamide, methotrexate, doxorubicin, vincristine, sorafenib, sunitinib, bevacizumab, erlotinib, lenvatinib mesylate capsules, regorafenib, lenvatinib, entecavir, extended polyethylene glycol, interferon, lamivudine, acoladine, Huachansu capsules, Kanglaite injection, Cidan capsules, sodium cantharidate vitamin B6 injection, Jinlong capsules, Biejiajian pills, Huaier granules, elemene injection, Kangai injection, Aidi injection, Ganfule capsules, Brucea javanica oil soft capsules, compound cantharidin capsules, transfer factors, immune checkpoint drugs, immunoglobulin G, Chaihu Shugan Powder, Gexia Zhuyu Decoction, Xiaoyao Powder, Yinchenhao Decoction combined with Wuling Powder or Yiguanjian.

10. The drug according to claim 8 or 9, It is characterized in that The dosage form is a dosage form for enteral administration and / or a dosage form for parenteral administration; The dosage form for administration via the gastrointestinal tract is powder, tablet, granule, capsule, solution, emulsion or suspension; The non-intestinal administration dosage form is an injection dosage form, a respiratory tract administration dosage form, a skin administration dosage form, a mucosal administration dosage form or a cavity administration dosage form.

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