Pharmaceutical composition for treating tumors and application
Through the combination of bevirvir and PD-1 monoclonal antibody, the problems of poor selectivity of existing anti-tumor drugs and poor immunotherapy effects were solved, and the synergistic inhibitory effect on breast cancer and esophageal cancer was achieved, and a new strategy for tumor treatment was provided.
Patent Information
- Application Number
- CN202510787396.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-12
- Publication Date
- 2025-08-15
AI Technical Summary
Existing anti-tumor drugs have defects such as poor selectivity, large toxic side effects and drug resistance. Tumor immunotherapy used alone is not effective and it is difficult to effectively cure tumors.
The combination of bevirvir and PD-1 monoclonal antibody is used, with a mass ratio of 200: (540-660). It is used to prepare a drug composition for treating tumors. It is administered by injection or oral administration to significantly inhibit tumor cell growth.
It significantly inhibits the growth of breast cancer and esophageal cancer, and the combination of drugs shows synergistic effects in tumor treatment, which is better than the single use of PD-1 monoclonal antibody or beviril.
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Figure CN120478619A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to a pharmaceutical composition for treating tumors and its application. Background Art
[0002] Malignant tumors are currently a major cause of death and a serious threat to human life. Comprehensive tumor treatment primarily involves surgery, radiotherapy, and chemotherapy. However, these methods currently have limitations and are difficult to completely cure.
[0003] Drugs play a vital role in chemotherapy for malignant tumors. In recent years, research and development of anti-tumor drugs has led to significant progress in cancer chemotherapy. The application of drugs such as carboplatin and paclitaxel in the last century has resulted in high cure rates for certain specific tumors. However, due to limitations of anti-tumor drugs, such as poor selectivity, significant toxic side effects, and drug resistance, more than half of cancer patients currently do not respond to treatment or develop drug resistance, ultimately leading to treatment failure.
[0004] Bevirimat is a maturation inhibitor targeting HIV-1 viral particles. It mainly inhibits the final rate-limiting step in Gag processing, preventing the release of mature capsid protein from its precursor, thereby producing immature non-infectious viral particles, thereby achieving the purpose of inhibiting HIV infection. PD-1 (programmed death receptor 1), also known as CD279 (cluster of differentiation 279), is an important immunosuppressive molecule. It regulates the immune system and promotes self-tolerance by downregulating the immune system's response to human cells and by inhibiting T cell inflammatory activity. Although immunotherapy has made good progress in clinical research, due to the heterogeneity of tumor cells and the complexity of the tumor microenvironment, tumor immunotherapy still faces many important obstacles, and its effect when used alone is not satisfactory. Therefore, it is necessary to find combination drugs with synergistic effects to further improve the treatment effect of cancer. Summary of the Invention
[0005] In view of this, the object of the present invention is to provide a pharmaceutical composition and application for treating tumors.
[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:
[0007] The present invention provides a pharmaceutical composition for treating tumors, which comprises bevirimab and PD-1 monoclonal antibody.
[0008] Preferably, the mass ratio of the PD-1 monoclonal antibody to bevirimab is 200:(540-660).
[0009] Preferably, the pharmaceutical composition comprises pharmaceutically acceptable excipients.
[0010] Preferably, the pharmaceutical composition is a single compound preparation or a combination of separate single preparations.
[0011] Preferably, the preparation is in any pharmaceutically acceptable dosage form.
[0012] The present invention provides an application of the above-mentioned pharmaceutical composition in preparing drugs for treating tumors.
[0013] Preferably, the tumor includes one or both of breast cancer and esophageal cancer.
[0014] Preferably, the pharmaceutical composition significantly inhibits the growth of tumor cells.
[0015] Preferably, the pharmaceutical composition has a synergistic effect in inhibiting the growth of tumor cells.
[0016] Preferably, the mass ratio of the pharmaceutical composition to the tumor drug is 50% to 90%.
[0017] Compared with the prior art, the present invention has the following beneficial effects:
[0018] The present invention provides a pharmaceutical composition and application for treating tumors. This invention, for the first time, discovers that the combined administration of a PD-1 monoclonal antibody and bevirimab exerts a synergistic inhibitory effect on tumor growth. Specifically, the pharmaceutical composition exhibits a synergistic, synergistic effect in treating tumors, significantly outperforming either PD-1 monoclonal antibody or bevirimab alone in its tumor cell inhibitory effect. This invention provides an effective drug combination strategy for tumor treatment and holds great promise for the selection of therapeutic agents for tumor treatment. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Figure 1 To detect the expression results of p63, SOX2, Ki67 and KRAS markers of primary esophageal cancer cells in MCS cells;
[0020] Figure 2 The results of the tumorigenicity test of MCS cells are shown in Figure A. From left to right, they are the tumor growth curve of Balb / c-nu mice, the body weight curve of Balb / c-nu mice, and the metastasis of MCS cells to the liver surface of Balb / c-nu mice. From left to right, they are the tumor growth curve of C57BL / 6 mice, the body weight curve of C57BL / 6 mice, and the metastasis of MCS cells to the lung surface of C57BL / 6 mice.
[0021] Figure 3The results of different groups on the inhibition of breast cancer cell growth in mice are compared. * indicates that compared with the control group, ***P<0.001; ※ indicates that compared with the PD-1 group, ※※※P<0.001; ns indicates no statistical difference.
[0022] Figure 4 Comparison of the growth curves of primary esophageal cancer cells in mice at different times in different groups, * indicates that compared with the control group, *P<0.05; # indicates that compared with the bevirima group, #P<0.05;
[0023] Figure 5 The following are the comparison results of the growth of primary esophageal cancer cells in mice among different groups after the experiment. * indicates that compared with the control group, *P<0.05, **P<0.01; ※ indicates that compared with the PD-1 group, ※※※P<0.001; # indicates that compared with the bevirima group, #P<0.05. DETAILED DESCRIPTION
[0024] The present invention provides a pharmaceutical composition for treating tumors, which comprises bevirimab and PD-1 monoclonal antibody.
[0025] In the present invention, as a preferred embodiment, the ingredients of the pharmaceutical composition are composed of bevirimab and PD-1 monoclonal antibody. The mass ratio of the PD-1 monoclonal antibody to bevirimab is preferably 200:(540-660), more preferably 200:540, 200:570, 200:630, 200:600 or 200:660. The present invention does not specifically limit the sources of the PD-1 monoclonal antibody and bevirimab, and they can be prepared using commercially available products or known preparation methods in the art. The pharmaceutical composition includes pharmaceutically acceptable excipients, which are selected from one or more of diluents, binders, surfactants, lubricants, solubilizers, buffers, fillers and disintegrants. As an embodiment, the pharmaceutical composition of the present invention can also be used in combination with other compounds that can be used to treat tumors, or the pharmaceutical composition of the present invention can be used as the sole active ingredient to treat tumors. The pharmaceutical composition is a single compound preparation or a combination of separate single preparations. The compound preparation refers to a preparation made with two or more active ingredients, and the single compound preparation refers to a compound preparation containing bevirimab and PD-1 monoclonal antibody. The single preparation refers to a preparation made with a single active ingredient. When the pharmaceutical composition of the present invention is a separate single preparation combination, the separate single preparation combination comprises a combination of bevirimab single preparation and a single preparation containing PD-1 monoclonal antibody. The administration mode of the separate single preparation combination is simultaneous administration or sequential administration. When the separate single preparation combination is administered sequentially, the single preparation containing bevirimab can be administered first, and then the single preparation containing PD-1 monoclonal antibody can be administered; or the single preparation containing PD-1 monoclonal antibody can be administered first, and then the single preparation containing bevirimab can be administered. The preparation is any dosage form acceptable in pharmaceutical science. The dosage form includes one or two of injection, pills, granules, capsules, tablets and aerosols.
[0026] The present invention provides an application of the above-mentioned pharmaceutical composition in preparing drugs for treating tumors.
[0027] In a specific embodiment of the present invention, the present invention has experimentally discovered for the first time that the combined use of PD-1 monoclonal antibody and bevirimab can produce a synergistic effect in the treatment of tumors, significantly inhibiting the growth of tumor cells, wherein the tumors include one or both of breast cancer and esophageal cancer. The breast cancer is constructed from murine breast cancer cells 4T1; the construction method is to inject murine breast cancer cells 4T1 subcutaneously into female Balb / c mice once, with an injection density of 1×10 7The esophageal cancer model was constructed by subcutaneously injecting mouse-derived esophageal cancer primary cells (MCS) into male C57BL / 6 mice at a density of 2×10 7 The injection volume was 100 μL per mouse, and the esophageal cancer model mice were obtained after 7 days of inoculation.
[0028] In a specific embodiment of the present invention, the present invention uses the Jin Zhengyun q value method to calculate the interaction of the drug composition, and further verifies the synergistic effect of the combined use of PD-1 monoclonal antibody and bevirimab. The study found that the combined use of PD-1 monoclonal antibody and bevirimab has a synergistic effect on the treatment of esophageal cancer.
[0029] In the present invention, the mass ratio of the pharmaceutical composition to the tumor drug is preferably 50% to 90%. In some embodiments, the drug can be administered by injection and / or oral administration. The injection can be subcutaneous injection, intramuscular injection, intravenous injection or intraperitoneal injection.
[0030] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.
[0031] In the following examples, data analysis was performed using SPSS 21.0 and Graphpad Prism 6. The data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison between groups. P < 0.05 was considered to be statistically significant.
[0032] Example 1
[0033] A pharmaceutical composition for treating tumors, comprising PD-1 monoclonal antibody and bevirimab.
[0034] Example 2
[0035] A pharmaceutical composition for treating tumors, comprising PD-1 monoclonal antibody and bevirimab, wherein the mass ratio of the PD-1 monoclonal antibody to bevirimab is 1:3.
[0036] Example 3
[0037] A pharmaceutical composition for treating tumors, comprising PD-1 monoclonal antibody and bevirimab, wherein the mass ratio of the PD-1 monoclonal antibody to bevirimab is 200:540.
[0038] Example 4
[0039] A pharmaceutical composition for treating tumors, comprising PD-1 monoclonal antibody and bevirimab, wherein the mass ratio of the PD-1 monoclonal antibody to bevirimab is 200:660.
[0040] Example 5
[0041] Application of the pharmaceutical composition of Example 1 in the preparation of drugs for treating tumors
[0042] 1. Experimental Materials
[0043] Murine breast cancer cells 4T1 were purchased from ATCC, stored in liquid nitrogen, and revived and passaged before use.
[0044] Murine esophageal cancer primary cells (MCS) were isolated from the cancerous tissue of a 4-NQO-induced C57BL / 6 mouse esophageal cancer model. They were stored in liquid nitrogen and revived and passaged before use.
[0045] RPMI1640 (ATCC modified) medium, DMEM / F12, and FBS were purchased from GIBCO, USA.
[0046] Mouse esophageal epithelial cell complete culture medium was purchased from Wuhan Punosai Life Science Technology Co., Ltd. with the catalog number CM-M027.
[0047] PD-1 monoclonal antibody and IgG isotype control were purchased from BioXcell, USA, with catalog numbers BE0146 and BE0089, respectively.
[0048] Bevelima comes from Wuhan Qiongge Biotechnology Co., Ltd., with the product number CYK-Z1790.
[0049] SBE-β-CD was purchased from Shanghai Yuanye Biotechnology Co., Ltd.
[0050] C57BL / 6 and Balb / c mice were purchased from Sibeifu (Beijing) Biotechnology Co., Ltd.
[0051] The preparation method of mouse esophageal cancer primary cells MCS was based on the literature (Tuxiong Huang, Jiao Yang, Beilei Liu, Li Fu. A new mouse esophageal cancer cell line (mEC25)-derived pre-clinical syngeneic tumor model for immunotherapy. Cancer Commun (Lond). 2020 Jul; 40(7): 316-320.), and the steps are as follows:
[0052] C57BL / 6 male mice were housed in an SPF animal room. A primary mouse esophageal cancer model was established by inducing the chemical carcinogen 4-nitroquinoline-N-oxide (4-NQO) in drinking water. 4-Nitroquinoline-1-oxide was prepared into a 5 mg / mL stock solution using 1,2-propylene glycol as a solvent, and then a 100 μg / mL 4-NQO aqueous solution was prepared using sterile water. The mice were fed with the 100 μg / mL 4-NQO aqueous solution for 16 weeks and then fed with normal water. Mice were cultured for 12 weeks to obtain mouse esophageal cancer orthotopic tumor tissue; the obtained orthotopic esophageal cancer tumor tissue was transplanted subcutaneously into Balb / c-nu mice and cultured in vivo to obtain transplanted tumor tissue; the obtained transplanted tumor tissue was partially removed of fibrocytes by a rapid attachment method and cultured in mouse esophageal epithelial cell complete culture medium for 5 generations to remove the fibrocytes, and then cultured in DMEM / F2 culture medium containing 10% by volume of FBS (fetal bovine serum) for a further 50 generations to obtain the mouse esophageal cancer primary cell line MCS.
[0053] Since normal cells no longer grow after about 20 to 30 passages, it can be considered that MCS cells that can be continuously passaged for 50 generations are mouse esophageal cancer tumor cells.
[0054] Identification of primary mouse esophageal cancer cells:
[0055] The marker expression and tumorigenic ability of esophageal cancer primary cells were verified according to the reference (Tuxiong Huang, Jiao Yang, Beilei Liu, Li Fu. A new mouse esophageal cancer cell line (mEC25)-derived pre-clinical syngeneic tumor model for immunotherapy. Cancer Commun (Lond). 2020 Jul; 40(7): 316-320.).
[0056] Cell immunofluorescence staining: The MCS cells prepared above were seeded into a culture dish with a pre-treated coverslip. When the cells were close to growing into a monolayer, the coverslip was removed and washed twice with PBS. Then, neutral formaldehyde fixative was added to fix the cells. The fixed cells were permeabilized with TritonX-100 and then incubated overnight with p63, SOX2, Ki67 and KRAS protein antibodies. Then, fluorescent secondary antibodies with Cy3 were added and the cell nuclei were stained with DAPI. The staining of the corresponding proteins was observed under a fluorescence microscope and photographed. The results are shown in Figure 1 .
[0057] Figure 1The results showed that MCS cells expressed p63, SOX2, Ki67 and KRAS proteins, confirming that the cells were primary mouse esophageal cancer cell lines.
[0058] MCS cell tumorigenicity assay: Male 4- to 6-week-old Balb / c-nu (top) and C57BL / 6 (bottom) mice were subcutaneously inoculated with 1×10 MCS cells. 6 The inoculation volume was 100 μL. The body weight of mice and the long and short diameters of subcutaneous tumors were measured twice a week. The tumor growth curve (left) and body weight curve (middle) of tumor-bearing mice were drawn. Balb / c-nu mice were killed 25 days after inoculation, and C57BL / 6 mice were killed 28 days after inoculation to observe the organ metastasis of cells in vivo.
[0059] Figure 2 Results showed that after inoculation with the primary mouse esophageal cancer cell line MCS, tumor size increased over time, demonstrating its tumorigenicity. Multiple gray-white metastatic nodules (arrows) were observed on the surface of the livers of Balb / c-nu mice and the lungs of C57BL / 6 mice, indicating that the esophageal cancer formed using the primary mouse esophageal cancer cell line MCS was metastatic.
[0060] 2. Experimental Methods
[0061] 1. Cell culture
[0062] Murine breast cancer cells 4T1 were cultured in RPMI1640 (ATCC modified) medium containing 10% FBS, and murine esophageal cancer primary cells MCS were cultured in DMEM / F12 medium containing 10% FBS. Both cells were cultured in a 5% CO2, 37°C incubator and passaged every 2 to 3 days. After the cells grew to the required number, they were used in subsequent animal experiments.
[0063] 2. Animal model construction, drug grouping, and drug administration
[0064] (1) Effect of the drug combination on breast cancer inhibition
[0065] Mouse breast cancer cells 4T1 in the logarithmic growth phase were digested under sterile conditions, centrifuged at 800 rpm for 5 min at room temperature, and the cell pellet was collected. The pellet was resuspended in 15 mL of DPBS and centrifuged at 800 rpm for 5 min at room temperature. The cell pellet was collected and resuspended in DPBS again and the cells were counted. Then, the cells were prepared into 1×10 7Cell suspensions with a concentration of 100 μL / mL were inoculated subcutaneously into female Balb / c mice using a 1 mL sterile syringe at a volume of 100 μL / mouse. Seven days after inoculation, the inoculated mice (breast cancer model mice) were randomly divided into groups and then given corresponding drug treatments. The specific grouping and dosing are as follows:
[0066] The breast cancer model mice were divided into 4 groups, namely control group, PD-1 group, bevirima group and combination group, with 5 mice in each group. Among them, the control group was given 0.2 mL of SBE-β-CD solution per oral administration to each breast cancer model mouse once a day, and 200 μg of IgG isotype control was injected intraperitoneally twice a week for a total of 3 weeks; the PD-1 group was given 0.2 mL of SBE-β-CD solution per oral administration to each breast cancer model mouse once a day, and 200 μg of PD-1 monoclonal antibody was injected intraperitoneally twice a week for a total of 3 weeks; the bevirimab group was given 30 mg / kg of bevirimab solution (the solvent of bevirimab solution is SBE-β-CD solution) per oral administration to each breast cancer model mouse once a day, and 200 μg of IgG isotype control was injected intraperitoneally twice a week for a total of 3 weeks; the combination group was given 30 mg / kg of bevirimab solution (the solvent of bevirimab solution is SBE-β-CD solution) per oral administration to each breast cancer model mouse once a day, and 200 μg of PD-1 monoclonal antibody was administered once, twice a week, for a total of 3 weeks.
[0067] After the administration, the maximum length and maximum transverse diameter of the subcutaneous tumor of the mice were measured with a vernier caliper to calculate the volume of the tumor in each group and weigh the tumor at the same time. 3 ) = long diameter (mm) × short diameter (mm) 2 / 2.
[0068] Figure 3 The results showed that compared with the control group, the PD-1 group, Bevirima group and the combination group significantly reduced the growth of breast cancer cells in mice; and compared with the PD-1 group, the combination group significantly reduced the growth of breast cancer cells in mice.
[0069] (2) Effect of the drug combination on the inhibition of esophageal cancer
[0070] The primary mouse esophageal cancer cells (MCS) in the logarithmic growth phase were digested under sterile conditions, centrifuged at 800 rpm for 5 min at room temperature, and the cell pellet was collected. The pellet was resuspended in 15 mL of DPBS and centrifuged at 800 rpm for 5 min at room temperature. The cell pellet was collected and resuspended in DPBS again and the cells were counted. The cells were then prepared into 2 × 10 7Cell suspensions with a concentration of 100 μL / mL were inoculated subcutaneously into male C57BL / 6 mice using a 1 mL sterile syringe at a volume of 100 μL / mouse. Seven days after inoculation, the inoculated mice (esophageal cancer model mice) were randomly divided into groups and then given corresponding drug treatments. The specific grouping and dosing are as follows:
[0071] The esophageal cancer model mice were divided into a control group, a PD-1 group, a bevirimab group and a combination group, with a total of 4 groups and 6 mice in each group. Among them, the control group was given 0.2 mL of SBE-β-CD solution to each esophageal cancer model mouse by gavage once a day, and 200 μg of IgG isotype control was injected intraperitoneally twice a week for a total of 9 times for 31 days; the PD-1 group was given 0.2 mL of SBE-β-CD solution to each esophageal cancer model mouse by gavage once a day, and 200 μg of PD-1 monoclonal antibody was injected intraperitoneally twice a week for a total of 9 times for 31 days; the bevirimab group was given 30 mg / kg of bevirimab solution (the solvent of bevirimab solution is SBE-β-CD solution) to each esophageal cancer model mouse by gavage once a day, and 200 μg was injected intraperitoneally each time. IgG isotype control, injected twice a week, a total of 9 injections, for 31 days; combination group, each esophageal cancer model mouse was given 30 mg / kg of bevirimab solution (the solvent of bevirimab solution is SBE-β-CD solution) by gavage once a day, and 200 μg of PD-1 monoclonal antibody was given by intraperitoneal injection each time, twice a week, a total of 9 injections, for 31 days.
[0072] The maximum length and maximum transverse diameter of the subcutaneous tumor of the mouse were measured twice a week with a vernier caliper, the tumor volume was calculated, and the tumor growth curve was drawn. After the administration, the mouse was killed, the subcutaneous tumor was removed, and the maximum length and transverse diameter of the tumor were measured with a vernier caliper to calculate the tumor volume. The tumor weight was also weighed. Tumor volume calculation formula: Volume (mm 3 ) = long diameter (mm) × short diameter (mm) 2 / 2.
[0073] Figures 4 and 5 The results showed that compared with the control group, the PD-1 group, the bevirima group and the combination group significantly reduced the growth of esophageal cancer cells in mice; and compared with the PD-1 group or the bevirima group, the combination group significantly reduced the growth of esophageal cancer cells in mice.
[0074] In the breast cancer model and esophageal cancer model experiments, the tumor weights of different groups after treatment are shown in Table 1.
[0075] Table 1 Tumor weight (mg) in different groups
[0076] Tumor model name control group PD-1 group Bevelima Group Combination group Breast cancer model 1151.46±344.39 766.61±149.74 527.02±237.20 333.89±141.44 Esophageal cancer model 3197.36±1634.22 1329.19±519.45 1474.63±898.66 118.56±118.84
[0077] The results in Table 1 show that compared with the PD-1 group and the Bevirima group, the combination group reduced the weight of breast cancer and esophageal cancer tumors.
[0078] The inhibition rate of tumor growth in each group was calculated based on the tumor volume after treatment. Tumor growth inhibition rate = (1-tumor volume of the treatment group ÷ tumor volume of the control group) × 100%.
[0079] Table 2 Inhibition rate of tumor growth in different groups
[0080] Tumor model name PD-1 group Bevelima Group Combination group Breast cancer model 37.68±2.53 36.25±3.19 61.13±2.35 Esophageal cancer model 58.43±16.25 53.88±28.11 96.39±3.72
[0081] The results in Table 2 show that compared with the PD-1 group and the bevirimab group, the combination group inhibited the growth of breast cancer and esophageal cancer.
[0082] Kim Jong-kyun's q value is a calculation value used to evaluate whether there is a synergistic inhibitory effect between two different drugs. The calculation formula is: q = E a+b / (E a +E b -E a ×E b ); where E a 、E b is the inhibition rate of the two inhibitors acting alone, E a+b is the inhibition rate of the combined action of the two inhibitors (i.e., the combined drug inhibition rate). The numerator in the calculation formula represents the "measured combined effect" and the denominator represents the "expected combined effect." Different numerical ranges of Kim Jung-kyun's q value represent three results: q < 0.85: the inhibition of the two drugs has an antagonistic effect; 0.85 ≤ q < 1.15: the inhibition of the two drugs is a simple additive effect; q ≥ 1.15: the inhibition of the two drugs has a synergistic effect.
[0083] According to the results in Table 2, the calculated gold average q value for the combination of bevirimab and PD-1 monoclonal antibody in the breast cancer model was 1.014, and the gold average q value for the combination of bevirimab and PD-1 monoclonal antibody in the esophageal cancer model was 1.191. This indicates that the combination of bevirimab and PD-1 monoclonal antibody has an additive effect on the inhibition of breast cancer, while the combination of bevirimab and PD-1 monoclonal antibody has a synergistic effect on the inhibition of esophageal cancer.
[0084] The above is only a preferred embodiment 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 within the scope of protection of the present invention.
Claims
1. A pharmaceutical composition for treating tumors, characterized in that: The pharmaceutical composition includes bevirimab and PD-1 monoclonal antibody.
2. The pharmaceutical composition according to claim 1, characterized in that The mass ratio of the PD-1 monoclonal antibody to Bevirimab is 200:(540-660).
3. The pharmaceutical composition according to claim 1 or 2, characterized in that The pharmaceutical composition includes pharmaceutically acceptable excipients.
4. The pharmaceutical composition according to claim 1 or 2, characterized in that The pharmaceutical composition is a single compound preparation or a combination of separate single preparations.
5. The pharmaceutical composition according to claim 4, characterized in that The preparation is in any pharmaceutically acceptable dosage form.
6. Use of the pharmaceutical composition according to any one of claims 1 to 5 in the preparation of drugs for treating tumors.
7. The use according to claim 6, characterized in that The tumor includes one or both of breast cancer and esophageal cancer.
8. The use according to claim 6, characterized in that The pharmaceutical composition significantly inhibits the growth of tumor cells.
9. The use according to claim 8, characterized in that The pharmaceutical composition has a synergistic effect in inhibiting the growth of tumor cells.
10. The use according to claim 6, characterized in that The mass ratio of the pharmaceutical composition to the tumor drug is 50% to 90%.