Pharmaceutical composition for treating or preventing ovarian cancer

Abstract

The invention discloses a pharmaceutical composition for treating or preventing ovarian cancer, the pharmaceutical composition comprises a PARP inhibitor, a VEGF inhibitor, an excipient, a disintegrating agent, a lubricant and a latent solvent, various raw materials are combined and mixed through a proper process to obtain the pharmaceutical composition for treating ovarian cancer, the PARP inhibitor and the VEGF inhibitor are matched for pharmaceutical production, the formula is novel, and the pharmaceutical composition is suitable for clinical application. The preparation method is simple, the process is ingenious, the growth of the ovarian tumor is synergistically inhibited through multiple mechanisms by utilizing the matched multi-target effect of various inhibitors, the treatment and inhibition effect on the ovarian tumor is improved, the selection and proportioning of auxiliary materials are adopted, the adverse reaction of the medicine is reduced, the workability of medicine granulation is improved, the production is convenient, and the quality of a finished product is ensured; meanwhile, by adopting an oral tablet mode, the traditional Chinese medicine composition has good oral property, the compliance of a patient is improved, and the traditional Chinese medicine composition has a good application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of ovarian cancer drug preparation, and in particular to a pharmaceutical composition for treating or preventing ovarian cancer. Background Art

[0002] Ovarian cancer is a type of malignant ovarian tumor, which refers to a malignant tumor that grows on the ovaries, of which 90% to 95% are primary ovarian cancers, and the other 5% to 10% are primary cancers in other parts of the body that have metastasized to the ovaries. Due to the lack of symptoms in the early stages of ovarian cancer, even if there are symptoms, they are not specific, and the role of screening is limited, early diagnosis is difficult. When seeking medical treatment, 60% to 70% of cases are already in the late stage, and the treatment effect of late-stage cases is poor. Therefore, although the incidence of ovarian cancer is lower than cervical cancer and endometrial cancer and ranks third among gynecological malignancies, its mortality rate exceeds the sum of cervical cancer and endometrial cancer, ranking first among gynecological cancers, and is the biggest disease that seriously threatens women's health.

[0003] The current treatment drugs for ovarian cancer have the following problems during the treatment process: Existing ovarian cancer treatment drugs mainly include chemotherapy drugs and targeted drugs. Chemotherapy drugs not only kill tumor cells, but also damage normal cells, leading to a series of side effects, such as nausea, vomiting, hair loss, bone marrow suppression, etc. Although targeted drugs have fewer side effects than chemotherapy drugs, some adverse reactions may still occur, such as drug-induced anemia, thrombocytopenia, neutropenia and other hematological toxicity, as well as hypertension, proteinuria and other side effects, which are problems that need to be solved at present. Summary of the invention

[0004] The purpose of the present invention is to provide a pharmaceutical composition for treating or preventing ovarian cancer, which has a synergistic effect through multiple mechanisms to improve the therapeutic effect and reduce side effects, has a novel formula, ingenious process, and has good application prospects.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] A pharmaceutical composition for treating or preventing ovarian cancer, comprising the following components and the weight proportions of each component are: PARP inhibitor: 50-80 parts;

[0007] VEGF inhibitor: 5-8 parts;

[0008] Excipient: 80-100 parts;

[0009] Disintegrant: 10-20 parts;

[0010] Lubricant: 5-8 parts;

[0011] Co-solvent: 10-15 parts.

[0012] Furthermore, the PARP inhibitors are olaparib and BSI-201, wherein the weight proportion of the olaparib component is 30-40 parts, and the weight proportion of the BSI-201 component is 20-40 parts.

[0013] Furthermore, the VEGF inhibitors are bevacizumab and axitinib, wherein the bevacizumab component is present in 2-4 parts by weight, and the axitinib component is present in 3-4 parts by weight.

[0014] Furthermore, the excipient is microcrystalline cellulose, the disintegrant is cross-linked polyvinylpyrrolidone, the lubricant is magnesium stearate, and the co-solvent is glycerol.

[0015] Furthermore, the method for preparing the pharmaceutical composition for treating or preventing ovarian cancer comprises the following steps:

[0016] Step A, 35 parts of olaparib material, 30 parts of BSI-201 material and 3 parts of bevacizumab material are put into a reactor for mixing for 20-30 minutes, then 3 parts of axitinib material and 6 parts of lubricant are added, and mixing is continued for 10-20 minutes;

[0017] Step B, after the mixing in step A is completed, add an appropriate amount of purified water, 13 parts of latent solvent material, and 6 parts of lubricant material into the mixture and continue mixing for 120-160 minutes;

[0018] Step C, adding 15 parts of disintegrant in the middle of mixing in step B;

[0019] Step D: After the mixing in step B is completed, 90 parts of excipients are added and the mixing process is continued for 160-180 minutes;

[0020] Step E, preparing granules by wet granulation of the mixed material in step D, during which a wetting agent is added to assist the formation of granules;

[0021] Step F, drying the particles obtained in step E to remove moisture or other volatile substances therein to ensure the stability of the particles;

[0022] Step G, tableting the material after the preliminary treatment in step F to prepare a solid preparation with stable morphology;

[0023] Furthermore, the wetting agent material used in step E is palmitic acid polysorbate.

[0024] The beneficial effects of the present invention are as follows: the pharmaceutical composition for treating or preventing ovarian cancer of the present invention adopts a PARP inhibitor and a VEGF inhibitor as main active ingredients, wherein the PARP inhibitors are olaparib and BSI-201, olaparib is an organic substance, acts on BRCA1 or BRCA2 mutations, blocks base excision repair, and is mainly targeted at cancer patients carrying BRCA1 or BRCA2 germline gene mutations, especially ovarian cancer patients whose tumor cells have specific DNA repair defects and are therefore particularly sensitive to olaparib, and olaparib binds to the catalytic site of PARP1 or PARP2, causing the PARP protein to be unable to fall off from the DNA damage site, Then, it causes double-strand breaks during DNA replication, activates the homologous recombination repair pathway, and ultimately leads to cell death. Olaparib has shown good efficacy in the treatment of ovarian cancer associated with BRCA gene mutations, and can prolong progression-free survival and improve survival rate. BSI-201, a compound, can non-selectively change specific components in tumor cells by binding to the first zinc finger structure of PARP1, covalently inhibiting the activity of PARP1. Instead of traditional intravenous treatment, it is mixed with Olaparib for granular pharmaceutical preparation to inhibit the DNA repair mechanism of cancer cells. VEGF inhibitors are bevacizumab and axitinib. Bevacizumab binds to free VEGF-A in the blood and inhibits VEGF-A It binds to VEGF receptor-2, thereby inhibiting tumor angiogenesis. Tumors need blood supply to obtain nutrients and oxygen, and bevacizumab can reduce the ability of tumor cells to induce new blood vessel formation, block tumor angiogenesis, and cause it to lack nutrient supply. It can significantly slow down the growth rate of tumors and reduce the ability of tumor cells to obtain nutrients and oxygen, thereby inhibiting tumor growth. At the same time, due to its anti-angiogenic effect, it can reduce the migration and spread of tumor cells and reduce the risk of distant metastasis of tumors in the body. Axitinib works by inhibiting tyrosine kinase receptors associated with pathological tumor angiogenesis. It can selectively inhibit VEGFR-1, VEGFR-2 and VEGFR-3. PARP receptors play a key role in the process of tumor angiogenesis. By inhibiting these receptors, axitinib can slow down the growth and spread of tumor cells. It is used in combination with bevacizumab as a VEGF inhibitor to prevent angiogenesis in ovarian tumors and reduce their nutrient supply. In the process of drug preparation, the added excipients are used to provide structural stability of the drug, and the disintegrants are used to ensure that the drug can quickly disintegrate in the intestine. Lubricants and wetting agents can improve the fluidity of the drug production process and accelerate the full mixing of the components. The mechanism by which latent solvents can improve the solubility of drugs changes the polarity of the mixed solvent and reduces the dielectric constant of the solvent, which is conducive to the dissolution of poorly soluble drugs. PARP inhibitors are used in combination with VEGF inhibitors for pharmaceutical production.The formula is novel and the process is ingenious. It utilizes the multi-target effects of various inhibitors to synergistically inhibit the growth of ovarian tumors through multiple mechanisms, thereby improving the treatment and inhibition of ovarian tumors. The selection and proportion of excipients reduce the adverse reactions of drugs, improve the ease of drug granulation, facilitate production, and ensure the quality of finished products. At the same time, it adopts the form of oral tablets, which has good accessibility, improves patient compliance, and has good application prospects. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit 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.

[0026] Embodiment 1

[0027] The pharmaceutical composition for treating or preventing ovarian cancer of the present invention comprises the following components and the weight proportions of each component are:

[0028] PARP inhibitors: 50 copies;

[0029] VEGF inhibitor: 5 parts;

[0030] Excipients: 80 parts;

[0031] Disintegrant: 10 parts;

[0032] Lubricant: 5 parts;

[0033] Co-solvent: 10 parts.

[0034] Wherein, the PARP inhibitors are olaparib and BSI-201, wherein the weight portion of the olaparib component is 30 parts, and the weight portion of the BSI-201 component is 20 parts.

[0035] Wherein, the VEGF inhibitors are bevacizumab and axitinib, wherein the bevacizumab component has 2 parts by weight, and the axitinib component has 3 parts by weight.

[0036] Wherein, the excipient is microcrystalline cellulose, the disintegrant is cross-linked polyvinylpyrrolidone, the lubricant is magnesium stearate, and the co-solvent is glycerol.

[0037] The method for preparing the pharmaceutical composition for treating or preventing ovarian cancer comprises the following steps:

[0038] Step A, 10 parts of olaparib material, 20 parts of BSI-201 material and 2 parts of bevacizumab material were put into a reactor for mixing for 20 minutes, and then 3 parts of axitinib material and 5 parts of lubricant were added, and mixing was continued for 10 minutes;

[0039] Step B, after the mixing in step A is completed, add an appropriate amount of pure water, 10 parts of latent solvent material, and 5 parts of lubricant material into the mixture and continue mixing for 120 minutes;

[0040] Step C, adding 11 parts of disintegrant in the middle of mixing in step B;

[0041] Step D: After the mixing in step B is completed, 80 parts of excipients are added and the mixing process is continued for 160 minutes;

[0042] Step E, preparing granules by wet granulation of the mixed material in step D, during which a wetting agent is added to assist the formation of granules;

[0043] Step F, drying the particles obtained in step E to remove moisture or other volatile substances therein to ensure the stability of the particles;

[0044] Step G, tableting the material after the preliminary treatment in step F to prepare a solid preparation with stable morphology;

[0045] Wherein, the wetting agent material used in step E is palmitic acid polysorbate.

[0046] The above-mentioned examples were used to prepare the drug and conduct animal experiments to verify the drug effect:

[0047] 1. Objective: To evaluate the antitumor efficacy and safety of the drug combination in a small number model of ovarian cancer.

[0048] 2. Establishment of animal model:

[0049] Species: Nude mice;

[0050] Quantity: 60;

[0051] Tumor Model: Transplanted human ovarian cancer cell line.

[0052] Human ovarian cancer cell lines were injected into mice to establish a tumor model. When the tumor volume reached a certain size, the mice were randomly divided into three groups.

[0053] 3. Grouping of nude mice:

[0054] Experimental group: 20 mice, transplanted with human ovarian cancer cell line and then regularly administered with the pharmaceutical composition prepared in this example;

[0055] Control group A: 20 mice, transplanted with human ovarian cancer cell lines and then given regular administration of existing commonly used drugs;

[0056] Control group B: 20 ​​mice, transplanted with human ovarian cancer cell line and fed regularly.

[0057] IV. Dosage regimen:

[0058] The experimental group: orally took the pharmaceutical composition prepared in this example every day, and the dosage was adjusted according to body weight;

[0059] Control group A: The patients were given existing standard drugs orally every day, and the dosage was the same as that of the experimental group.

[0060] Control group B: The mice were given normal feeding food every day.

[0061] 5. Observation Records:

[0062] The changes in tumor volume in mice were measured weekly, and the inhibition rate was calculated;

[0063] The survival time of mice in each group was recorded.

[0064] 6. Overall Assessment:

[0065] Observe and record the weight changes and behavioral status changes of mice;

[0066] Postmortem examination of mice was performed to evaluate the damage of major organs.

[0067] VII. Test results:

[0068] Comparing by tumor inhibition rate, the tumor inhibition rate of the experimental group was greater than that of the control group A, and the tumor inhibition rate of the control group A was greater than that of the control group B.

[0069] Comparing the survival periods, the survival period of the experimental group was longer than that of the control group A, and the survival period of the control group A was longer than that of the control group B.

[0070] According to the comparison of pathological conclusions after autopsy, the weight of mice in the experimental group was stable, and there was no obvious damage to the main organs; the weight of mice in the control group A changed greatly in the later period, and the damage to the main organs was obvious; the weight of mice in the control group B changed greatly, and the damage to the main organs was obvious.

[0071] 8. Test conclusion:

[0072] The pharmaceutical composition of this example showed good anti-tumor effect and low toxicity in an ovarian cancer mouse model, providing strong support for its clinical application.

[0073] Embodiment 2

[0074] The pharmaceutical composition for treating or preventing ovarian cancer of the present invention comprises the following components and the weight proportions of each component are:

[0075] PARP inhibitors: 65;

[0076] VEGF inhibitor: 6 parts;

[0077] Excipients: 90 parts;

[0078] Disintegrant: 15 parts;

[0079] Lubricant: 6 parts;

[0080] Co-solvent: 13 parts.

[0081] Wherein, the PARP inhibitors are olaparib and BSI-201, wherein the weight portion of the olaparib component is 35 parts, and the weight portion of the BSI-201 component is 30 parts.

[0082] Wherein, the VEGF inhibitors are bevacizumab and axitinib, wherein the bevacizumab component has 3 parts by weight, and the axitinib component has 3 parts by weight.

[0083] Wherein, the excipient is microcrystalline cellulose, the disintegrant is cross-linked polyvinylpyrrolidone, the lubricant is magnesium stearate, and the co-solvent is glycerol.

[0084] The method for preparing the pharmaceutical composition for treating or preventing ovarian cancer comprises the following steps:

[0085] Step A, 35 parts of olaparib material, 30 parts of BSI-201 material and 3 parts of bevacizumab material were put into a reactor for mixing for 25 minutes, and then 3 parts of axitinib material and 6 parts of lubricant were added, and mixing was continued for 15 minutes;

[0086] Step B, after the mixing in step A is completed, add an appropriate amount of pure water, 13 parts of latent solvent material, and 6 parts of lubricant material into the mixture and continue mixing for 140 minutes;

[0087] Step C, adding 15 parts of disintegrant in the middle of mixing in step B;

[0088] Step D: After the mixing in step B is completed, 90 parts of excipients are added and the mixing process is continued for 170 minutes;

[0089] Step E, preparing granules by wet granulation of the mixed material in step D, during which a wetting agent is added to assist the formation of granules;

[0090] Step F, drying the particles obtained in step E to remove moisture or other volatile substances therein to ensure the stability of the particles;

[0091] Step G, tableting the material after the preliminary treatment in step F to prepare a solid preparation with stable morphology;

[0092] Wherein, the wetting agent material used in step E is palmitic acid polysorbate.

[0093] The above-mentioned examples were used to prepare the drug and conduct animal experiments to verify the drug effect:

[0094] 1. Objective: To evaluate the antitumor efficacy and safety of the drug combination in a small number model of ovarian cancer.

[0095] 2. Establishment of animal model:

[0096] Species: Nude mice;

[0097] Quantity: 60;

[0098] Tumor Model: Transplanted human ovarian cancer cell line.

[0099] Human ovarian cancer cell lines were injected into mice to establish a tumor model. When the tumor volume reached a certain size, the mice were randomly divided into three groups.

[0100] 3. Grouping of nude mice:

[0101] Experimental group: 20 mice, transplanted with human ovarian cancer cell line and then regularly administered with the pharmaceutical composition prepared in this example;

[0102] Control group A: 20 mice, transplanted with human ovarian cancer cell lines and then given regular administration of existing commonly used drugs;

[0103] Control group B: 20 ​​mice, transplanted with human ovarian cancer cell line and fed regularly.

[0104] IV. Dosage regimen:

[0105] The experimental group: orally took the pharmaceutical composition prepared in this example every day, and the dosage was adjusted according to body weight;

[0106] Control group A: The patients were given existing standard drugs orally every day, and the dosage was the same as that of the experimental group.

[0107] Control group B: The mice were given normal feeding food every day.

[0108] 5. Observation Records:

[0109] The changes in tumor volume in mice were measured weekly, and the inhibition rate was calculated;

[0110] The survival time of mice in each group was recorded.

[0111] 6. Overall Assessment:

[0112] Observe and record the weight changes and behavioral status changes of mice;

[0113] Postmortem examination of mice was performed to evaluate the damage of major organs.

[0114] VII. Test results:

[0115] Comparing by tumor inhibition rate, the tumor inhibition rate of the experimental group was greater than that of the control group A, and the tumor inhibition rate of the control group A was greater than that of the control group B.

[0116] Comparing the survival periods, the survival period of the experimental group was longer than that of the control group A, and the survival period of the control group A was longer than that of the control group B.

[0117] According to the comparison of pathological conclusions after autopsy, the weight of mice in the experimental group was stable, and there was no obvious damage to the main organs; the weight of mice in the control group A changed greatly in the later period, and the damage to the main organs was obvious; the weight of mice in the control group B changed greatly, and the damage to the main organs was obvious.

[0118] 8. Test conclusion:

[0119] The pharmaceutical composition of this example showed good anti-tumor effect and low toxicity in an ovarian cancer mouse model, providing strong support for its clinical application.

[0120] Embodiment 3

[0121] The pharmaceutical composition for treating or preventing ovarian cancer of the present invention comprises the following components and the weight proportions of each component are:

[0122] PARP inhibitors: 80 parts;

[0123] VEGF inhibitor: 8 parts;

[0124] Excipient: 100 parts;

[0125] Disintegrant: 20 parts;

[0126] Lubricant: 8 parts;

[0127] Co-solvent: 15 parts.

[0128] Wherein, the PARP inhibitors are olaparib and BSI-201, wherein the weight portion of the olaparib component is 40 parts, and the weight portion of the BSI-201 component is 40 parts.

[0129] Wherein, the VEGF inhibitors are bevacizumab and axitinib, wherein the bevacizumab component has 4 parts by weight, and the axitinib component has 4 parts by weight.

[0130] Wherein, the excipient is microcrystalline cellulose, the disintegrant is cross-linked polyvinylpyrrolidone, the lubricant is magnesium stearate, and the co-solvent is glycerol.

[0131] The method for preparing the pharmaceutical composition for treating or preventing ovarian cancer comprises the following steps:

[0132] Step A, 40 parts of olaparib material, 40 parts of BSI-201 material and 4 parts of bevacizumab material were put into a reactor for mixing for 30 minutes, and then 4 parts of axitinib material and 8 parts of lubricant were added, and mixing was continued for 20 minutes;

[0133] Step B, after the mixing in step A is completed, add an appropriate amount of pure water, 15 parts of latent solvent material, and 8 parts of lubricant material into the mixture and continue mixing for 160 minutes;

[0134] Step C, adding 20 parts of disintegrant in the middle of mixing in step B;

[0135] Step D: After the mixing in step B is completed, 100 parts of excipient is added and the mixing process is continued for 180 minutes;

[0136] Step E, preparing granules by wet granulation of the mixed material in step D, during which a wetting agent is added to assist the formation of granules;

[0137] Step F, drying the particles obtained in step E to remove moisture or other volatile substances therein to ensure the stability of the particles;

[0138] Step G, tableting the material after the preliminary treatment in step F to prepare a solid preparation with stable morphology;

[0139] Wherein, the wetting agent material used in step E is palmitic acid polysorbate.

[0140] The above-mentioned examples were used to prepare the drug and conduct animal experiments to verify the drug effect:

[0141] 1. Objective: To evaluate the antitumor efficacy and safety of the drug combination in a small number model of ovarian cancer.

[0142] 2. Establishment of animal model:

[0143] Species: Nude mice;

[0144] Quantity: 60;

[0145] Tumor Model: Transplanted human ovarian cancer cell line.

[0146] Human ovarian cancer cell lines were injected into mice to establish a tumor model. When the tumor volume reached a certain size, the mice were randomly divided into three groups.

[0147] 3. Grouping of nude mice:

[0148] Experimental group: 20 mice, transplanted with human ovarian cancer cell line and then regularly administered with the pharmaceutical composition prepared in this example;

[0149] Control group A: 20 mice, transplanted with human ovarian cancer cell lines and then given regular administration of existing commonly used drugs;

[0150] Control group B: 20 ​​mice, transplanted with human ovarian cancer cell line and fed regularly.

[0151] IV. Dosage regimen:

[0152] The experimental group: orally took the pharmaceutical composition prepared in this example every day, and the dosage was adjusted according to body weight;

[0153] Control group A: The patients were given existing standard drugs orally every day, and the dosage was the same as that of the experimental group.

[0154] Control group B: The mice were given normal feeding food every day.

[0155] 5. Observation Records:

[0156] The changes in tumor volume in mice were measured weekly, and the inhibition rate was calculated;

[0157] The survival time of mice in each group was recorded.

[0158] 6. Overall Assessment:

[0159] Observe and record the weight changes and behavioral status changes of mice;

[0160] Postmortem examination of mice was performed to evaluate the damage of major organs.

[0161] VII. Test results:

[0162] Comparing by tumor inhibition rate, the tumor inhibition rate of the experimental group was greater than that of the control group A, and the tumor inhibition rate of the control group A was greater than that of the control group B.

[0163] Comparing the survival periods, the survival period of the experimental group was longer than that of the control group A, and the survival period of the control group A was longer than that of the control group B.

[0164] According to the comparison of pathological conclusions after autopsy, the weight of mice in the experimental group was stable, and there was no obvious damage to the main organs; the weight of mice in the control group A changed greatly in the later period, and the damage to the main organs was obvious; the weight of mice in the control group B changed greatly, and the damage to the main organs was obvious.

[0165] 8. Test conclusion:

[0166] The pharmaceutical composition of this example showed good anti-tumor effect and low toxicity in an ovarian cancer mouse model, providing strong support for its clinical application.

[0167] In summary, the pharmaceutical composition for treating or preventing ovarian cancer of the present invention uses a PARP inhibitor and a VEGF inhibitor as main active ingredients, wherein the PARP inhibitors are olaparib and BSI-201. Olaparib is an organic substance that acts on BRCA1 or BRCA2 mutations to block base excision repair. It is mainly targeted at cancer patients carrying BRCA1 or BRCA2 germline gene mutations, especially ovarian cancer patients whose tumor cells have specific DNA repair defects and are therefore particularly sensitive to Olaparib. Olaparib binds to the catalytic site of PARP1 or PARP2, resulting in the inability of PARP protein to fall off from the DNA damage site, thereby inhibiting the repair of DNA damage. A induces double-strand breaks during replication, activates the homologous recombination repair pathway, and ultimately leads to cell death. Olaparib has shown good efficacy in the treatment of ovarian cancer associated with BRCA gene mutations, and can prolong progression-free survival and improve survival rate. BSI-201, a compound, can non-selectively change specific components in tumor cells by binding to the first zinc finger structure of PARP1, covalently inhibiting the activity of PARP1. Instead of traditional intravenous treatment regimens, it is mixed with Olaparib for granular pharmaceutical preparation to inhibit the DNA repair mechanism of cancer cells. VEGF inhibitors are bevacizumab and axitinib. Bevacizumab binds to free VEGF-A in the blood and inhibits the reaction of VEGF-A with VEGF Bevacizumab can bind to the VEGF receptor-2, thereby inhibiting tumor angiogenesis. Tumors need blood supply to obtain nutrients and oxygen, and bevacizumab can reduce the ability of tumor cells to induce new blood vessel formation, block tumor angiogenesis, and make it lack of nutrient supply. It can significantly slow down the growth rate of tumors and reduce the ability of tumor cells to obtain nutrients and oxygen, thereby inhibiting tumor growth. At the same time, due to its anti-angiogenic effect, it can reduce the migration and spread of tumor cells and reduce the risk of distant metastasis of tumors in the body. Axitinib works by inhibiting tyrosine kinase receptors associated with pathological tumor angiogenesis. It can selectively inhibit VEGFR-1, VEGFR-2 and VEGFR-3, which are receptors in tumor blood. It plays a key role in the process of angiogenesis. By inhibiting these receptors, axitinib can slow down the growth and spread of tumor cells. It is used in combination with bevacizumab as a VEGF inhibitor to prevent angiogenesis in ovarian tumors and reduce their nutrient supply. In the process of drug preparation, the added excipients are used to provide structural stability of the drug, and the disintegrants are used to ensure that the drug can quickly disintegrate in the intestine. The lubricants and wetting agents can improve the fluidity of the drug production process and accelerate the full mixing of the components. The mechanism by which the latent solvent can improve the solubility of the drug changes the polarity of the mixed solvent and reduces the dielectric constant of the solvent, which is conducive to the dissolution of poorly soluble drugs. The PARP inhibitor and VEGF inhibitor are used in combination for pharmaceutical production, and the formula is novel.The process is ingenious, using the multi-target effects of various inhibitors to synergistically inhibit the growth of ovarian tumors through multiple mechanisms, thereby improving the treatment and inhibitory effects on ovarian tumors. The selection and proportion of excipients reduce the adverse reactions of drugs, improve the ease of drug granulation, facilitate production, and ensure the quality of finished products. At the same time, the oral tablet method has good accessibility, improves patient compliance, and has good application prospects.

[0168] The above shows and describes the basic principles, main features and advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention to be protected. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A pharmaceutical composition for treating or preventing ovarian cancer, characterized in that: The composition comprises the following components and the weight proportions of each component are: PARP inhibitors: 50-80 parts; VEGF inhibitor: 5-8 parts; Excipient: 80-100 parts; Disintegrant: 10-20 parts; Lubricant: 5-8 parts; Co-solvent: 10-15 parts.

2. The pharmaceutical composition for treating or preventing ovarian cancer according to claim 1, characterized in that: The PARP inhibitors are olaparib and BSI-201, wherein the weight portion of the olaparib component is 30-40 parts, and the weight portion of the BSI-201 component is 20-40 parts.

3. The pharmaceutical composition for treating or preventing ovarian cancer according to claim 2, characterized in that: The VEGF inhibitors are bevacizumab and axitinib, wherein the bevacizumab component accounts for 2-4 parts by weight, and the axitinib component accounts for 3-4 parts by weight.

4. The pharmaceutical composition for treating or preventing ovarian cancer according to claim 3, characterized in that: The excipient is microcrystalline cellulose, the disintegrant is cross-linked polyvinylpyrrolidone, the lubricant is magnesium stearate, and the co-solvent is glycerol.

5. The pharmaceutical composition for treating or preventing ovarian cancer according to claim 4, characterized in that: The method for preparing the pharmaceutical composition for treating or preventing ovarian cancer comprises the following steps: Step A, 35 parts of olaparib material, 30 parts of BSI-201 material and 3 parts of bevacizumab material are put into a reactor for mixing for 20-30 minutes, then 3 parts of axitinib material and 6 parts of lubricant are added, and mixing is continued for 10-20 minutes; Step B, after the mixing in step A is completed, add an appropriate amount of purified water, 13 parts of latent solvent material, and 6 parts of lubricant material into the mixture and continue mixing for 120-160 minutes; Step C, adding 15 parts of disintegrant in the middle of mixing in step B; Step D: After the mixing in step B is completed, 90 parts of excipients are added and the mixing process is continued for 160-180 minutes; Step E, preparing granules by wet granulation of the mixed material in step D, during which a wetting agent is added to assist the formation of granules; Step F, drying the particles obtained in step E to remove moisture or other volatile substances therein to ensure the stability of the particles; Step G, tableting the material after the preliminary treatment in step F to prepare a solid preparation with stable morphology.

6. The pharmaceutical composition for treating or preventing ovarian cancer according to claim 5, characterized in that: The wetting agent material used in step E is palmitic acid polysorbate.