Pharmaceutical composition for synergistic treatment of ovarian cancer

Abstract

This invention provides a pharmaceutical composition for the synergistic treatment of ovarian cancer, belonging to the field of biomedical technology. This invention provides a synergistic pharmaceutical composition comprising capivasertib and doxorubicin for the specific treatment of ovarian cancer. Compared with other similar drug combinations, the composition of this invention achieves a synergistic effect; furthermore, this composition did not exhibit synergistic killing activity in the tested control tumor cell lines, indicating that its synergistic effect is disease-selective. This invention provides a more effective pharmaceutical composition for the clinical treatment of ovarian cancer, with clear clinical application value and good commercial prospects.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and more particularly to a pharmacopoeia for the synergistic treatment of ovarian cancer. Background Technology

[0002] Ovarian cancer is one of the deadliest gynecological malignancies. Due to the lack of effective early screening methods, more than 70% of patients are already at stage III or IV in the FIGO staging system at the time of initial diagnosis, with the tumor having spread extensively in the abdominal cavity, severely impacting long-term survival. Although the concept of maintenance therapy has developed in recent years, the five-year survival rate for ovarian cancer remains stagnant at around 40%–50%.

[0003] Currently, cytoreductive surgery combined with platinum-based chemotherapy is the standard first-line treatment for ovarian cancer. However, tumor heterogeneity and the complex peritoneal microenvironment make it difficult for chemotherapy drugs to achieve effective concentrations in tumor tissue, and most patients eventually develop platinum resistance after multiple platinum-based chemotherapy regimens, leading to a sharp decline in the effectiveness of subsequent treatments. Furthermore, although polyadenylated ribose diphosphate polymerase (PARP) inhibitors can be used for maintenance therapy in patients with breast cancer susceptibility gene (BRCA) mutations, these drugs are only suitable for a limited population carrying specific gene mutations or with homologous recombination defects. For the majority of ovarian cancer patients who are platinum-resistant relapsed or have non-BRCA mutations, there is still a lack of effective treatment strategies that can significantly improve survival outcomes. Summary of the Invention

[0004] The purpose of this invention is to provide a pharmaceutical composition for the synergistic treatment of ovarian cancer, thereby solving the technical problem of the lack of synergistic pharmaceutical compositions that can effectively treat ovarian cancer in the prior art.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides the use of a pharmaceutical composition in the preparation of a medicament for the synergistic treatment of ovarian cancer, the pharmaceutical composition comprising capivasertib and doxorubicin.

[0006] Preferably, the concentration of capivasertib is 0.8 μM to 3.2 μM, and the concentration of doxorubicin is 100 nM to 400 nM.

[0007] Preferably, the concentration of capivasertib is 3.2 μM and the concentration of doxorubicin is 400 nM.

[0008] Preferably, the ovarian cancer cell line is selected from at least one of HO-8910PM and OVCAR-8.

[0009] Preferably, the capivasertib and / or doxorubicin are in the form of their pharmaceutically acceptable salts, hydrates, or solvates.

[0010] Preferably, the dosage form of the pharmaceutical composition is an injection or an oral preparation.

[0011] Preferably, the injection is a lyophilized powder injection or a liposome injection.

[0012] Preferably, the drug further comprises a pharmaceutically acceptable excipient selected from at least one of excipients, disintegrants, lubricants, and binders.

[0013] Preferably, when the drug is an injection, the content of doxorubicin is 10mg to 100mg per unit dose.

[0014] Preferably, when the drug is an oral preparation, the content of Capivasertib is 100mg to 400mg per unit dose.

[0015] The beneficial effects of this invention are: This invention provides a synergistic pharmaceutical composition comprising capivasertib and doxorubicin for the specific treatment of ovarian cancer. Compared with other similar drug combinations, the composition of this invention achieves a synergistic effect; furthermore, this composition did not exhibit synergistic killing activity in the tested control tumor cell lines, indicating that its synergistic effect is disease-selective. This invention provides a more effective pharmaceutical composition for the clinical treatment of ovarian cancer, with clear clinical application value and good commercial prospects. Attached Figure Description

[0016] Figure 1 The diagram shows the chessboard method and Chou-Talalay synergistic effect evaluation of the pharmaceutical composition of the present invention in HO-8910PM and OVCAR-8 cells. Figure 2 This is a statistical validation graph showing the multi-drug screening and synergistic effects of various compositions in ovarian cancer cell lines (HO-8910PM, OVCAR-8); Figure 3 This is a graph showing the efficacy evaluation and statistical analysis of the drug composition of the present invention in HCT116 colon cancer cells after combined drug administration. Figure 4 This is a graph showing the efficacy evaluation and statistical analysis of the drug composition of the present invention in glioblastoma U87MG cells after combined drug administration. Figure 5 This is a graph showing the efficacy evaluation and statistical analysis of the combined drug combination of the present invention in melanoma SK-SML-28 cells; Figure 6This is a graph showing the efficacy evaluation and statistical analysis of the drug composition of the present invention in combined use in Ishikawa and An3CA endometrial cancer cells. Detailed Implementation

[0017] This invention provides the use of a pharmaceutical composition in the preparation of a medicament for the synergistic treatment of ovarian cancer, the pharmaceutical composition comprising capivasertib and doxorubicin.

[0018] Ovarian cancer is one of the deadliest gynecological malignancies. Due to the lack of effective early screening methods, over 70% of patients are already at FIGO stage III or IV at initial diagnosis, with the tumor having spread extensively throughout the peritoneal cavity, severely impacting long-term survival. Although the concept of maintenance therapy has developed in recent years, the five-year survival rate for ovarian cancer remains stagnant at around 40%–50%. Currently, cytoreductive surgery combined with platinum-based chemotherapy is the standard first-line treatment for ovarian cancer. However, tumor heterogeneity and the complex peritoneal microenvironment make it difficult for chemotherapy drugs to achieve effective concentrations in tumor tissue, and most patients eventually develop platinum resistance after multiple platinum-based chemotherapy regimens, leading to a sharp decline in the effectiveness of subsequent treatments. Furthermore, although PARP inhibitors can be used for maintenance therapy in patients with BRCA gene mutations, these drugs are only suitable for a limited population carrying specific gene mutations or exhibiting homologous recombination defects. For the majority of ovarian cancer patients who are platinum-resistant relapsed or have non-BRCA mutations, there is still a lack of effective treatment strategies that can significantly improve survival outcomes.

[0019] Preferably, the concentration of capivasertib is 0.8 μM to 3.2 μM, and the concentration of doxorubicin is 100 nM to 400 nM.

[0020] In this invention, the concentration of capivasertib refers to the effective concentration of capivasertib in the pharmaceutical composition. The concentration range of 0.8 μM to 3.2 μM covers multiple effective concentration points where capivasertib exhibits synergistic activity in in vitro cell experiments. More preferably, the concentration of capivasertib can be 1.0 μM to 3.0 μM; more preferably, the concentration of capivasertib can be 2.0 μM to 3.2 μM. The concentration of doxorubicin refers to the effective concentration of doxorubicin in the pharmaceutical composition. The concentration range of 100 nM to 400 nM covers multiple effective concentration points where doxorubicin exhibits synergistic activity in in vitro cell experiments. More preferably, the concentration of doxorubicin can be 150 nM to 350 nM; more preferably, the concentration of doxorubicin can be 200 nM to 400 nM.

[0021] Preferably, the concentration of capivasertib is 3.2 μM and the concentration of doxorubicin is 400 nM.

[0022] In this invention, the concentration of capivasertib is further preferably 3.2 μM, and the concentration of doxorubicin is further preferably 400 nM. Under these preferred concentration conditions, the combination of capivasertib and doxorubicin can produce a more significant synergistic anticancer effect.

[0023] Preferably, the ovarian cancer cell line is selected from at least one of HO-8910PM and OVCAR-8.

[0024] In this invention, the ovarian cancer cell line is used as a cell model for in vitro validation of the antitumor activity of the pharmaceutical composition. The HO-8910PM cell line is a human ovarian cancer cell line with high metastatic potential. Its parental cell line, HO-8910, originated from a patient with serous cystadenocarcinoma of the ovary. After in vivo screening, the HO-8910PM subline exhibits stronger peritoneal implantation and distant metastasis capabilities, making it an ideal model for studying the invasion and metastasis mechanisms of ovarian cancer and screening anti-metastatic drugs. The OVCAR-8 cell line is one of the representative human ovarian cancer cell lines in the NCI-60 tumor cell line panel, derived from serous adenocarcinoma of the ovary, and is widely used for in vitro screening and mechanism studies of antitumor drugs. All of the above cell lines have good operability and experimental reproducibility, and can serve as effective validation models for the synergistic treatment of ovarian cancer with the pharmaceutical composition of this invention. The pharmaceutical composition of this invention has a synergistic inhibitory effect on at least one of the above cell lines.

[0025] Preferably, the capivasertib and / or doxorubicin are in the form of their pharmaceutically acceptable salts, hydrates, or solvates.

[0026] In this invention, "pharmaceutically acceptable salt" refers to the derivative form obtained by modifying the compound (Capivasertib or doxorubicin) by preparing its acid addition salt or base addition salt. Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues (such as amino groups), and alkali metal or organic salts of acidic residues (such as carboxylic acids). It is estimated that approximately 50% of marketed pharmaceutical products are administered in salt form. Salt formation can improve properties such as drug solubility, dissolution rate, bioavailability, or physicochemical stability. "Hydrate" refers to a solvate with water as the solvent, i.e., a complex formed by intermolecular interactions between compound molecules and water molecules. "Solvent" refers to a molecular complex formed by intermolecular interactions or complexation between a compound and one or more pharmaceutically acceptable solvent molecules. Pharmaceutically acceptable solvates include solvates with isotopically substituted solvents. From a scientific point of view, solvates and hydrates can be considered a subgroup of cocrystals, whose co-formation is either solvent or water. The capivasertib and / or doxorubicin described in this invention may be present and used in pharmaceutically acceptable salt, hydrate or solvate form, all of which are within the scope of protection of this invention.

[0027] Preferably, the dosage form of the pharmaceutical composition is an injection or an oral preparation.

[0028] In this invention, the pharmaceutical composition can be formulated into a suitable dosage form according to clinical needs and route of administration. Injectable and oral formulations are the two most common dosage forms in the field of pharmaceutical preparations. Injectables are characterized by rapid onset of action and high bioavailability, making them suitable for situations requiring rapid onset of action or where patients cannot take oral medication. Oral formulations offer advantages such as convenient administration and good patient compliance, making them suitable for chronic diseases or maintenance therapy scenarios requiring long-term administration. The pharmaceutical composition of this invention can be selected in either injectable or oral form according to actual treatment needs.

[0029] Preferably, the injection is a lyophilized powder injection or a liposome injection.

[0030] In this invention, the lyophilized powder injection refers to a sterile powder preparation obtained by freeze-drying a drug solution under sterile conditions, which is then reconstituted with an appropriate solvent before injection. The advantage of lyophilized powder injections is that they can improve the stability of drugs during storage and extend the shelf life of the preparation, especially suitable for drugs that are unstable to heat or moisture. The preparation of lyophilized powder injections usually involves the use of lyophilization protectants to protect the drug from denaturation or degradation during freezing and drying. Commonly used lyophilization protectants include, but are not limited to, mannitol, sucrose, trehalose, glucose, lactose, sorbitol, glycine, and polyethylene glycol. The preparation process of lyophilized powder injections typically includes steps such as formulation, sterile filtration, filling, freezing, primary drying (sublimation drying), secondary drying (desorption drying), stoppering, and capping. The liposome injection refers to an injectable dosage form in which the drug is encapsulated in liposomes (microvesicles composed of a phospholipid bilayer). The advantages of liposome injections lie in their ability to achieve targeted drug release, enhance passive or active drug accumulation in tumor tissues, and reduce drug exposure in normal tissues, thereby minimizing systemic toxicity. Furthermore, liposomes possess excellent biocompatibility and biodegradability, making them an ideal drug carrier. Liposome injection formulations typically include components such as active pharmaceutical ingredients, phospholipids, cholesterol, stabilizers, emulsifiers, lyophilization protectants, and pH adjusters.

[0031] Preferably, the drug further comprises a pharmaceutically acceptable excipient selected from at least one of excipients, disintegrants, lubricants, and binders.

[0032] In this invention, pharmaceutically acceptable excipients refer to materials added to pharmaceutical preparations, other than the active pharmaceutical ingredient, to meet purposes such as formulation shaping, stabilization, excipient formation, or improvement of user experience. Excipients, also known as diluents or fillers, are inert substances used in formulations to increase the volume or weight of the contents of tablets or capsules, enabling the formulation to achieve a suitable size and shape for ease of production and administration. Commonly used excipients include, but are not limited to: starch, pregelatinized starch, dextrin, sucrose, lactose, microcrystalline cellulose, mannitol, sorbitol, calcium hydrogen phosphate, calcium sulfate, and calcium carbonate. Excipients should have good flowability and compressibility and should not interact with the active pharmaceutical ingredient. Disintegrants are excipients that promote the rapid disintegration of tablets or capsules into fine particles in the gastrointestinal tract. Their function is to increase the contact area between the formulation and digestive juices, thereby promoting the dissolution and absorption of the active pharmaceutical ingredient. Commonly used disintegrants include, but are not limited to: sodium carboxymethyl starch, crospovidone, crospovidone carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, dry starch, and effervescent disintegrants (such as a combination of citric acid and sodium bicarbonate). The dosage and type of disintegrant need to be optimized according to the formulation composition and disintegration time requirements. Lubricants are excipients added during tableting or filling to reduce friction between particles and between particles and the mold wall. Their function is to improve material flowability, prevent sticking, smooth the tablet surface, and facilitate tablet ejection. Commonly used lubricants include, but are not limited to: magnesium stearate, stearic acid, sodium stearate fumarate, talc, micronized silica gel, polyethylene glycol, and sodium lauryl sulfate. The amount of lubricant used is usually small; excessive use may affect tablet hardness and disintegration performance. Binders are excipients added during wet granulation or direct tableting to increase the adhesion between material particles. Their function is to aggregate powdered materials into particles with a certain strength and hardness to ensure the mechanical strength of the formulation. Commonly used binders include, but are not limited to: hydroxypropyl methylcellulose, povidone (polyvinylpyrrolidone), sodium carboxymethyl cellulose, ethyl cellulose, methyl cellulose, starch paste, gelatin, sodium alginate, syrup, gum arabic, etc. The selection and dosage of binders must be determined based on the properties of the materials and the granulation process. Those skilled in the art can rationally select one or more of the above excipients according to specific dosage form requirements and formulation processes to achieve optimal formulation performance.

[0033] Preferably, when the drug is an injection, the content of doxorubicin is 10mg to 100mg per unit dose.

[0034] In this invention, when the pharmaceutical composition is prepared as an injection, the content of doxorubicin per unit dose is 10 mg to 100 mg. This content range covers the commonly used dosage range of doxorubicin in clinical injection administration and can be flexibly adjusted according to the patient's specific condition, weight, body surface area, and combination therapy regimen. For example, when doxorubicin is used as a monotherapy in clinical practice, the commonly used dose calculated based on body surface area is 60–75 mg / m² every three weeks; the commonly used dose calculated based on weight is 1.2–2.4 mg / kg every three weeks. The above-mentioned content range of 10 mg to 100 mg per unit dose can meet the clinical administration needs of patients with different weights and body surface areas. More preferably, the content of doxorubicin in the injection is 20 mg to 80 mg per unit dose; more preferably, the content of doxorubicin in the injection is 30 mg to 60 mg per unit dose. In addition, depending on the different injectable subtypes (such as conventional injections, liposome injections, or lyophilized powder injections), the unit dose of doxorubicin can be appropriately adjusted within the above range.

[0035] Preferably, when the drug is an oral preparation, the content of Capivasertib is 100mg to 400mg per unit dose.

[0036] In this invention, when the pharmaceutical composition is prepared as an oral formulation, the content of capivasertib per unit dose is 100 mg to 400 mg. Capivasertib, as an orally effective pan-AKT inhibitor, is typically administered orally in clinical practice. In clinical studies, the dosage range of capivasertib is relatively wide; for example, in some studies, the dosage of capivasertib has been explored and adjusted within the range of 80 mg to 800 mg. The content range of 100 mg to 400 mg per unit dose covers the effective dosage range for oral administration of capivasertib and can be individually adjusted according to the patient's specific condition, tolerability, and combination therapy regimen. More preferably, the content of capivasertib in the oral formulation is 150 mg to 350 mg per unit dose; more preferably, the content of capivasertib in the oral formulation is 200 mg to 300 mg per unit dose. The oral formulation can be made into various forms such as tablets, capsules, and granules. Each unit dose refers to the amount of capivasertib contained in each tablet, capsule, or unit package granule. Within the above content range, the dosage specifications can be further refined according to clinical needs, such as 100mg, 200mg, 400mg, etc., to facilitate flexible adjustment of clinical administration.

[0037] The technical solutions provided by the present invention will be 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.

[0038] Example 1 This embodiment provides a pharmaceutical composition that specifically kills ovarian cancer, comprising active ingredient A: Capivasertib (Capi) and active ingredient B: Doxorubicin (Dox).

[0039] The concentration of capivasertib was 0.8 μM, and the concentration of doxorubicin was 400 nM.

[0040] Example 2 This embodiment provides a pharmaceutical composition that specifically kills ovarian cancer, comprising active ingredient A: Capivasertib (Capi) and active ingredient B: Doxorubicin (Dox).

[0041] The concentration of capivasertib was 1.6 μM, and the concentration of doxorubicin was 400 nM.

[0042] Example 3 This embodiment provides a pharmaceutical composition that specifically kills ovarian cancer, comprising active ingredient A: Capivasertib (Capi) and active ingredient B: Doxorubicin (Dox).

[0043] The concentration of capivasertib was 2.4 μM, and the concentration of doxorubicin was 400 nM.

[0044] Example 4 This embodiment provides a pharmaceutical composition that specifically kills ovarian cancer, comprising active ingredient A: Capivasertib (Capi) and active ingredient B: Doxorubicin (Dox).

[0045] The concentration of capivasertib was 3.2 μM, and the concentration of doxorubicin was 400 nM.

[0046] Example 5 This embodiment verifies the in vitro efficacy and evaluates the synergistic specificity of the drug compositions described in Examples 1-4.

[0047] 1. Experimental Materials and Methods Cell lines: human ovarian cancer cell lines (HO-8910PM, OVCAR-8), and other tumor cell lines used for comparative specificity validation (glioblastoma U87MG, melanoma SK-SML-28, colon cancer HCT116, endometrial cancer Ishikawa and An3CA).

[0048] Drugs: Capivasertib (Capi, 3.2 μM), Doxorubicin (Dox, 400 nM), Cisplatin (Cis, 4 μM), 4-hydroperoxycyclophosphamide (4-HC, 2 μM).

[0049] Group setup: To comprehensively evaluate the effects of different single-drug and combination therapies, the experiment set up 8 treatment groups, namely: control group, capi monotherapy group, dox monotherapy group, cis monotherapy group, 4-HC monotherapy group, dox+capi combination group, cis+capi combination group, and 4-HC+capi combination group.

[0050] Processing and detection: Using the CCK-8 assay, cells were seeded at 5000-8000 cells / well in 96-well plates. After 24 hours of adhesion, the cells were treated with drugs for 48 hours. The absorbance was measured at 450 nm and the viability was calculated. The synergy index (CI) was assessed using the checkerboard assay and the Chou-Talalay algorithm.

[0051] 2. Summary of Core Data The original absorbance (OD value) data mentioned above are stored in the laboratory records. The cell viability percentage presented in this example is calculated by the formula [(OD value of experimental wells - OD value of blank wells) / (OD value of control wells - OD value of blank wells)] × 100%. The data in the table below are obtained by averaging the viability of multiple replicates in the same group. The statistical p-value is calculated by unpaired t-test.

[0052] As shown in Table 1 and as shown in the table below Figure 2 As shown, this experiment tested different single-drug and combination drug regimens in HO-8910PM and OVCAR-8 ovarian cancer cells. The results showed that among the experimental groups, the Dox+Capi combination group had the best proliferation inhibition effect, and the Dox+Capi combination group was significantly different from the Dox single-drug group (P values ​​were 0.007781 and 0.003329, respectively, both P<0.01) (n = 3).

[0053] Table 1: Comparison and significance analysis of cell viability (%) among different treatment groups Control 100±0 100±0 Capi monotherapy 95.34±3.37 97.31±2.1 Dox monotherapy 67.86±0.71 86.53±1.55 Cis monotherapy 73.78±1.56 92.74±0.7 4-HC monotherapy 97.57±0.8 103.35±4.5 Dox+Capi 58.07±3.35 83.39±4.21 Cis+Capi 67.84±0.24 91.14±1.32 4-HC+Capi 89.72±1.94 107.19±6.7 P-value (Dox vs Dox+Capi) P = 0.007781 P = 0.003329 Furthermore, such as Figure 1 As shown in Table 2, this experiment used a checkerboard method to combine different concentrations of Capi and Dox in HO-8910PM and OVCAR-8 cell lines, and calculated the combination index (CI) based on the Chou-Talalay method. As shown in Table 2, within the effective concentration range tested, the CI values ​​for each concentration combination were significantly less than 1, indicating a significant synergistic effect between the two drugs in ovarian cancer cells (Note: In the Chou-Talalay method, a combination index CI < 1 indicates a synergistic effect) (n = 3).

[0054] Table 2: Joint Index Analysis Using the Chessboard Method (Chou-Talalay Method) 0.8 400 70.22±8.57 74.75±3.53 CI < 1 (synergistic) 1.6 400 71.99±8.89 72.38±6.7 CI < 1 (synergistic) 2.4 400 69.93±5.78 75.63±14.58 CI < 1 (synergistic) 3.2 400 70.35±11.85 66.1±4.11 CI < 1 (synergistic) like Figure 3 , Figure 4 , Figure 5 and Figure 6 As shown in Table 3, to verify the tumor specificity of this drug composition, it was applied to four other solid tumor cell lines under the same treatment protocol. The statistical results show that in these control tumor cells, the cell survival rate of the Dox+Capi combination group was not statistically significantly different from that of the Dox monotherapy group (P > 0.05), demonstrating that this synergistic effect did not occur in colon cancer, glioblastoma, melanoma, and endometrial cancer (n = 3).

[0055] Table 3: Survival rate (%) and statistical analysis of other tumor cell lines specifically validated. cell lines HCT116 U87MG SK-SML-28 Ishikawa / An3CA Control 100±0 100±0 100±0 100±0 / 100±0 Capi monotherapy 78.79±2.81 87.02±4.89 94.34±1.37 53.01±3.45 / 94.46±0.9 Dox monotherapy 24.36±0.62 50.17±11.99 73.82±1.59 15.01±4.45 / 86.19±5.51 Dox+Capi 25.53±1.03 50.25±8.2 74±1.64 18.27±3.01 / 81.18±2.77 P-value (comparing the Dox group and the combined group) P = 0.165817 P = 0.993085 P = 0.901592 P = 0.352094 / 0.231812 3. Experimental Conclusions In summary, the above results indicate that the pharmaceutical composition Capivasertib and doxorubicin provided by this invention exhibit significant synergistic killing effects in ovarian cancer cells. Figure 1 , Figure 2 Furthermore, this synergistic effect is tumor-specific, and it has not produced a synergistic killing effect in colon cancer, glioblastoma, melanoma, and endometrial cancer. Figures 3 to 6 ).

[0056] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The use of a pharmaceutical composition in the preparation of a medicament for the synergistic treatment of ovarian cancer, characterized in that, The pharmaceutical composition comprises capivasertib and doxorubicin.

2. The application according to claim 1, characterized in that, The concentration of capivasertib is 0.8 μM to 3.2 μM, and the concentration of doxorubicin is 100 nM to 400 nM.

3. The application according to claim 2, characterized in that, The concentration of capivasertib was 3.2 μM, and the concentration of doxorubicin was 400 nM.

4. The application according to claim 1, characterized in that, The ovarian cancer cell line was selected from at least one of HO-8910PM and OVCAR-8.

5. The application according to claim 1, characterized in that, The capivasertib and / or doxorubicin are in their pharmaceutically acceptable salt, hydrate, or solvate forms.

6. The application according to claim 1, characterized in that, The dosage form of the pharmaceutical composition is an injection or an oral preparation.

7. The application according to claim 6, characterized in that, The injection is a lyophilized powder injection or a liposome injection.

8. The application according to claim 6, characterized in that, The drug also includes pharmaceutically acceptable excipients selected from at least one of excipients, disintegrants, lubricants, and binders.

9. The application according to claim 6, characterized in that, When the drug is an injectable preparation, the content of doxorubicin is 10mg to 100mg per unit dose.

10. The application according to claim 6, characterized in that, When the drug is an oral preparation, the content of Capivasertib is 100mg to 400mg per unit dose.

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