Application of PLK1 inhibitor in preparation of medicine for treating ovarian hypercalcemia type small cell carcinoma

Abstract

The invention provides application of a PLK1 inhibitor in preparation of a medicine for treating ovarian hypercalcemia type small cell carcinoma. The medicine containing the PLK1 inhibitor can be used for effectively treating the ovarian hypercalcemia type small cell carcinoma and inhibiting the growth of the focus of the ovarian hypercalcemia type small cell carcinoma, takes effect quickly, and can generate an obvious treatment effect after being applied for 20 days.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and in particular relates to the use of a drug containing a PLK1 inhibitor in the preparation of a drug for treating ovarian hypercalcemia-type small cell carcinoma. Background Art

[0002] Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare gynecological tumor that originates from the ovary and is highly malignant and has a very poor prognosis. So far, no more than 500 cases have been reported worldwide. SCCOHT is common in young women (14 months to 58 years old, with a median age of 24 years). This tumor is prone to recurrence and has a poor prognosis. The one-year survival rate of patients is only 50%, and the five-year survival rate is less than 10%.

[0003] Due to the rarity of ovarian hypercalcemia type small cell carcinoma, clinical randomized controlled trials are difficult to conduct, and there is currently no standard treatment plan. In addition, ovarian hypercalcemia type small cell carcinoma is extremely malignant and has a very poor prognosis. The development of new therapeutic drugs has become an urgent problem to be solved in the clinical treatment of ovarian hypercalcemia type small cell carcinoma. Scientific research has found that the current potential therapeutic drugs for ovarian hypercalcemia type small cell carcinoma mainly include: ① epigenetic treatment, such as EZH2 inhibitors, histone deacetylase (HDAC) inhibitors, lysine-specific histone demethylase 1 (LSD1) inhibitors; ② kinase inhibitors, such as lipoprotein kinase (RTK) inhibitors, CDK4 / 6 inhibitors; ③ immunotherapy, PD-1 monoclonal antibody. However, not all patients respond to these drugs.

[0004] Although ovarian hypercalcemia-type small cell carcinoma is a rare ovarian malignancy, there are still many patients and families suffering from this disease in China, a country with a large population. Therefore, the invention of a new treatment method is of far-reaching significance for the treatment of patients with ovarian hypercalcemia-type small cell carcinoma, and may add hope to the treatment of this disease.

[0005] Therefore, there is an urgent need to provide a drug for the treatment of ovarian hypercalcemia-type small cell carcinoma that is universal, easy to use, and has good therapeutic effects. Summary of the invention

[0006] In view of the above-mentioned shortcomings of the prior art, the purpose of the present invention is to provide a drug containing a PLK1 inhibitor for use in preparing a drug for treating ovarian hypercalcemia type small cell carcinoma and a drug containing a PLK1 inhibitor for use in preparing a drug for inhibiting the growth of ovarian hypercalcemia type small cell carcinoma lesions, so as to solve the problems in the prior art.

[0007] To achieve the above-mentioned purpose and other related purposes, the present invention provides the use of a drug containing a PLK1 inhibitor in the preparation of a drug for treating ovarian hypercalcemia type small cell carcinoma and the use of a drug containing a PLK1 inhibitor in the preparation of a drug for inhibiting the growth of ovarian hypercalcemia type small cell carcinoma lesions. As a new therapeutic drug that may be effective for patients with ovarian hypercalcemia type small cell carcinoma, the life of patients with ovarian hypercalcemia type small cell carcinoma can be prolonged.

[0008] The first aspect of the present invention provides the use of a drug containing a PLK1 inhibitor in the preparation of a drug for treating ovarian hypercalcemia-type small cell carcinoma.

[0009] PLK1 inhibitors: PLK1 inhibitors are inhibitors of PLK1 protein. PLK1 is a serine / threonine protein kinase. PLK1 is highly expressed in many cancers and is necessary for the rapid proliferation of tumors. In some cancers, it is often associated with poor prognosis. It is inferred that PLK1, as an oncogene, accelerates the occurrence and development of tumors. PLK1 inhibitors can inhibit the function and activity of PLK1 protein.

[0010] Small cell carcinoma of the ovary (SCCOHT) is a rare and highly invasive ovarian malignancy that originates in the ovary. The genome of SCCOHT is diploid and is characterized by mutations in SMARCA4 and loss of expression of SMARCA2. The loss of expression of BRG1 and BRM proteins encoded by both in immunohistochemical staining has become an important means of distinguishing this tumor in pathological diagnosis. Because it is a rare ovarian cancer, most of the current studies are retrospective studies, and there are no randomized controlled studies. There is no internationally recognized optimal treatment plan.

[0011] As certain embodiments of the present invention, the PLK1 inhibitor in the drug containing a PLK1 inhibitor is selected from: BI 2536, CFI-400945, WAY-619275, TAK-960 dihydrochloride, Rigosertib (ON-01910), Onvansertib (PCM-075, NMS-1286937, NMS-P937), TC-S 7005, HMN-176, Mps1-IN-2, ON1231320, also known as GBO-006, SBE13 hydrochloride, HMN-214, TAK-960, Ro3280, MLN0905, GW843682X, Rigosertib (ON-01910) sodium, GSK461364, Volasertib (BI 6727), SBP-7455, BL-918, MRT68921 dihydrochloride, LYN-1604dihydrochloride, ULK-101, LYN-1604 2HCl.

[0012] As certain embodiments of the present invention, the medicine containing the PLK1 inhibitor further comprises a pharmaceutically acceptable carrier, excipient and / or stabilizer.

[0013] The carrier pharmaceutically acceptable carrier includes one or more components selected from the group consisting of a binder, a filler, a lubricant, a glidant, a disintegrant and a wetting agent.

[0014] The excipients include hydroxypropyl methylcellulose, microcrystalline cellulose, sodium starch glycolate, lactose and magnesium stearate.

[0015] The stabilizer includes adipic acid, DL-alanine, dl-camphor, D-sorbitol solution, d-borneol, D-sorbitol, D-mannitol, L-ascorbyl stearate, L-sodium ascorbate, L-aspartic acid, sodium L-aspartate, L-arginine, 1-menthol, β-cyclodextrin, ascorbic acid, aminoethanesulfonic acid, sodium alginate, propylene glycol alginate, albumin, sulfur, inositol, fennel powder, ethanol, calcium disodium edetate, sodium edetate, isoascorbic acid, sodium isoascorbate, cocoa butter, carboxyvinyl polymer, carboxymethylcellulose calcium, sodium carboxymethylcellulose, agar, xanthan gum, xylitol, citric acid, and calcium citric acid.

[0016] The binders include gum arabic, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, dextrates, dextrin, dextrose, ethyl cellulose, gelatin, liquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, magnesium aluminum silicate, maltodextrin, methyl cellulose, polymethacrylate, polyvinyl pyrrolidone, pregelatinized starch, sodium alginate, sorbitol, starch, and syrup.

[0017] The fillers include calcium carbonate, calcium phosphate, calcium sulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, concentrated sugar, confectionery sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, dibasic calcium phosphate, fructose, palmitostearin, glycerol, hydrogenated vegetable oil type-1, kaolin, lactose, corn starch, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polymethacrylate, potassium chloride, powdered cellulose, pregelatinized starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc, calcium phosphate and xylitol.

[0018] Examples of the lubricant include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, microcrystalline cellulose, sodium benzoate, sodium chloride, sodium lauryl sulfate, stearic acid, sodium stearyl fumarate, talc and zinc stearate.

[0019] The glidants include colloidal silicon dioxide, powdered cellulose, magnesium trisilicate, silicon dioxide and talc.

[0020] The disintegrants include alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, cross-linked carboxymethylcellulose sodium, polyvinylpolypyrrolidone, guar gum, magnesium aluminum silicate, microcrystalline cellulose, methylcellulose, polyvinylpyrrolidone, polacrilin potassium, pregelatinized starch, sodium alginate, sodium lauryl sulfate and sodium starch glycolate.

[0021] As certain embodiments of the present invention, the drug containing the PLK1 inhibitor is prepared as a solid, semisolid or liquid preparation for oral administration.

[0022] Preferably, the preparation of the drug containing the PLK1 inhibitor includes tablets, granules, microparticles, powders, capsules, soft capsules, pills, suspensions, emulsions, liquid preparations for oral administration, syrups or dry syrups; or before preparing the preparation, the drug containing the PLK1 inhibitor is first made into microparticles.

[0023] Preferably, the drug containing the PLK1 inhibitor is prepared into microcapsules, nanocapsules, microspheres or nanospheres.

[0024] As certain embodiments of the present invention, the drug containing the PLK1 inhibitor is administered orally, sublingually, by atomization, subcutaneously, intravenously, transdermally, or enterally.

[0025] As certain embodiments of the present invention, the dosage of the drug containing the PLK1 inhibitor for human body is 2-10 mg / kg based on the PLK1 inhibitor.

[0026] The dosage of the drug containing PLK1 inhibitor for human body is selected from 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, or 10.0 mg / kg.

[0027] The present invention also provides the use of a drug containing a PLK1 inhibitor in the preparation of a drug for inhibiting the growth of ovarian hypercalcemia-type small cell carcinoma lesions.

[0028] As certain embodiments of the present invention, the PLK1 inhibitor in the drug containing a PLK1 inhibitor is selected from: BI 2536, CFI-400945, WAY-619275, TAK-960 dihydrochloride, Rigosertib (ON-01910), Onvansertib (PCM-075, NMS-1286937, NMS-P937), TC-S 7005, HMN-176, Mps1-IN-2, ON1231320, also known as GBO-006, SBE13 hydrochloride, HMN-214, TAK-960, Ro3280, MLN0905, GW843682X, Rigosertib (ON-01910) sodium, GSK461364, Volasertib (BI 6727), SBP-7455, BL-918, MRT68921 dihydrochloride, LYN-1604dihydrochloride, ULK-101, LYN-1604 2HCl.

[0029] As certain embodiments of the present invention, the medicine containing the PLK1 inhibitor further comprises a pharmaceutically acceptable carrier, excipient and / or stabilizer.

[0030] The carrier pharmaceutically acceptable carrier includes one or more components selected from the group consisting of a binder, a filler, a lubricant, a glidant, a disintegrant and a wetting agent.

[0031] The excipients include hydroxypropyl methylcellulose, microcrystalline cellulose, sodium starch glycolate, lactose and magnesium stearate.

[0032] The stabilizer includes adipic acid, DL-alanine, dl-camphor, D-sorbitol solution, d-borneol, D-sorbitol, D-mannitol, L-ascorbyl stearate, L-sodium ascorbate, L-aspartic acid, sodium L-aspartate, L-arginine, 1-menthol, β-cyclodextrin, ascorbic acid, aminoethanesulfonic acid, sodium alginate, propylene glycol alginate, albumin, sulfur, inositol, fennel powder, ethanol, calcium disodium edetate, sodium edetate, isoascorbic acid, sodium isoascorbate, cocoa butter, carboxyvinyl polymer, carboxymethylcellulose calcium, sodium carboxymethylcellulose, agar, xanthan gum, xylitol, citric acid, and calcium citric acid.

[0033] The binders include gum arabic, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, dextrates, dextrin, dextrose, ethyl cellulose, gelatin, liquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, magnesium aluminum silicate, maltodextrin, methyl cellulose, polymethacrylate, polyvinyl pyrrolidone, pregelatinized starch, sodium alginate, sorbitol, starch, and syrup.

[0034] The fillers include calcium carbonate, calcium phosphate, calcium sulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, concentrated sugar, confectionery sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, dibasic calcium phosphate, fructose, palmitostearin, glycerol, hydrogenated vegetable oil type-1, kaolin, lactose, corn starch, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polymethacrylate, potassium chloride, powdered cellulose, pregelatinized starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc, calcium phosphate and xylitol.

[0035] Examples of the lubricant include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, microcrystalline cellulose, sodium benzoate, sodium chloride, sodium lauryl sulfate, stearic acid, sodium stearyl fumarate, talc and zinc stearate.

[0036] The glidants include colloidal silicon dioxide, powdered cellulose, magnesium trisilicate, silicon dioxide and talc.

[0037] The disintegrants include alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, cross-linked carboxymethylcellulose sodium, polyvinylpolypyrrolidone, guar gum, magnesium aluminum silicate, microcrystalline cellulose, methylcellulose, polyvinylpyrrolidone, polacrilin potassium, pregelatinized starch, sodium alginate, sodium lauryl sulfate and sodium starch glycolate.

[0038] As certain embodiments of the present invention, the drug containing the PLK1 inhibitor is prepared as a solid, semisolid or liquid preparation for oral administration.

[0039] Preferably, the preparation of the drug containing the PLK1 inhibitor includes tablets, granules, microparticles, powders, capsules, soft capsules, pills, suspensions, emulsions, liquid preparations for oral administration, syrups or dry syrups; or before preparing the preparation, the drug containing the PLK1 inhibitor is first made into microparticles.

[0040] Preferably, the drug containing the PLK1 inhibitor is prepared into microcapsules, nanocapsules, microspheres or nanospheres.

[0041] As certain embodiments of the present invention, the drug containing the PLK1 inhibitor is administered orally, sublingually, by atomization, subcutaneously, intravenously, transdermally, or enterally.

[0042] As certain embodiments of the present invention, the dosage of the drug containing the PLK1 inhibitor for human body is 2-10 mg / kg based on the PLK1 inhibitor.

[0043] The dosage of the drug containing PLK1 inhibitor for human body is selected from 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, or 10.0 mg / kg.

[0044] As described above, the use of the drug containing PLK1 inhibitor in the preparation of a drug for treating ovarian hypercalcemia type small cell carcinoma and the use of the drug containing PLK1 inhibitor in the preparation of a drug for inhibiting the growth of ovarian hypercalcemia type small cell carcinoma lesions of the present invention have the following beneficial effects:

[0045] It has a good effect on the treatment of ovarian hypercalcemia type small cell carcinoma, and can also effectively inhibit the growth of ovarian hypercalcemia type small cell carcinoma lesions. It works quickly and can produce obvious therapeutic effects 13 days after application. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 The CDX (cell derived xenograft) animal model of the present invention for patients with ovarian hypercalcemia type small cell carcinoma is injected with BI2536 and a control solvent twice a week, and the tumor size is compared after 30 days;

[0047] Figure 2 The CDX (cell derived xenograft) animal model of the present invention for patients with ovarian hypercalcemia type small cell carcinoma is shown, in which BI2536 and control solvent are injected twice a week, and the changes in tumor volume over time are shown. DETAILED DESCRIPTION

[0048] The present invention is further described below in conjunction with specific examples, and it should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of protection of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0049] It should be understood that the terms used in the examples of the present invention are intended to describe specific embodiments rather than to limit the scope of protection of the present invention; in the present specification and claims, unless otherwise expressly stated, the singular forms "a", "an" and "the" include plural forms. When the examples give numerical ranges, it should be understood that unless otherwise specified in the present invention, both endpoints of each numerical range and any value between the two endpoints can be selected.

[0050] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art. In addition to the specific methods, equipment, and materials used in the embodiments, any methods, equipment, and materials of the prior art that are similar or equivalent to the methods, equipment, and materials in the embodiments of the present invention may be used to implement the present invention, based on the prior art mastery of those skilled in the art and the description of the present invention.

[0051] Unless otherwise stated, the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt conventional techniques in the technical field and conventional techniques in related fields.

[0052] Materials and methods

[0053] 1. Experimental Materials and Methods

[0054] 1.1 Materials

[0055] The cell line transplant tumor model (cell derived xenograft, CDX) is to inoculate tumor cells cultured in vitro into immunodeficient mice, allowing tumors to form in nude mice.

[0056] Nude mouse tumor formation experiment is to inject tumor cells subcutaneously into nude mice to observe the formation and development of tumors and the effects of anti-tumor drugs.

[0057] 2. Experimental Methods

[0058] Eight 5-week-old nude mice were inoculated with 1×10 6SCCOHT-CH-1 (primary tumor cells of ovarian hypercalcemia type small cell carcinoma) were subcutaneously in nude mice. Five days after inoculation, when 8 nude mice had subcutaneous tumors and the average tumor volume reached 100mm 3 The mice were randomly divided into 2 groups, 4 mice in each group; the mice in the experimental group were intraperitoneally injected with 40 mg / kg of PLK1 drug BI2536 twice a week, and the mice in the control group were injected with control solvent without PLK1 twice a week.

[0059] Tumor size was measured twice a week and body weight was measured every day. The formula for calculating tumor size is: tumor volume = tumor long diameter × tumor short diameter 2 ×0.5

[0060] The PLK1 inhibitor and control reagent were administered for 30 days, and the size of subcutaneous tumors in the control and experimental groups was observed. The tumors in the control group mice reached 3000 mm 3 All mice were then killed, the tumors were removed, and the sizes of the tumors in the experimental and control groups were compared to determine the inhibitory effect of PLK1.

[0061] Tumor inhibition rate calculation formula:

[0062] Tumor inhibition rate (T / C) = (1-T / C) × 100, where T represents the average tumor size in the experimental group and C represents the average tumor size in the control group.

[0063] Example 1

[0064] After the experiment, the tumor sizes of the control group and the group given PLK1 inhibitor were measured and shown in Table 1:

[0065] Table 1

[0066] Group 1 2 3 4 Control group <![CDATA[3151mm 3 ]]> <![CDATA[2971mm 3 ]]> <![CDATA[2898mm 3 ]]> <![CDATA[3174mm 3 ]]> PLK1 inhibitor group <![CDATA[940mm 3 ]]> <![CDATA[2349mm 3 ]]> <![CDATA[303mm 3 ]]> <![CDATA[2157mm 3 ]]>

[0067] Comparison of tumor size between the two groups Figure 1 It can be seen that the injection of PLK1 inhibitor drug BI2536 can effectively reduce the size of tumors. According to the progress of the experiment, 13 days after the first injection of PLK1 inhibitor drugs, the size of tumors in the two groups changed significantly. After the 30th day of the experiment, the tumor volume of the group using PLK1 inhibitor drugs was significantly reduced.

[0068] Figure 2 The graph shows the changes in the average tumor size of the two groups over time. Based on the average tumor size of the two groups on the 30th day, the inhibitor efficiency of the PLK1 inhibitor drug on the tumor was calculated to be 53%, indicating that the PLK1 inhibitor drug can effectively inhibit tumor growth.

[0069] The above is only a preferred embodiment of the present invention, and is not any formal or substantial limitation of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the method of the present invention, and these improvements and supplements should also be regarded as the protection scope of the present invention. Any technician familiar with this profession, without departing from the spirit and scope of the present invention, can make some changes, modifications and evolutions of the technical content disclosed above, which are equivalent embodiments of the present invention; at the same time, any changes, modifications and evolutions of any equivalent changes made to the above embodiments based on the essential technology of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. Use of a drug containing a PLK1 inhibitor in the preparation of a drug for treating ovarian hypercalcemia-type small cell carcinoma.

2. The use according to claim 1, characterized in that: The PLK1 inhibitor in the drug containing the PLK1 inhibitor is selected from: BI 2536, CFI-400945, WAY-619275, TAK-960dihydrochloride, Rigosertib (ON-01910), Onvansertib (PCM-075, NMS-1286937, NMS-P937), TC-S 7005, HMN-176, Mps1-IN-2, ON1231320, also known as GBO-006, SBE13 hydrochloride, HMN-214, TAK-960, Ro3280, MLN0905, GW843682X, Rigosertib (ON-01910) sodium, GSK461364, Volasertib (BI 6727), SBP-7455, BL-918, MRT68921 dihydrochloride, LYN-1604dihydrochloride, ULK-101, LYN-16042HCl.

3. The use according to any one of claims 1 to 2, characterized in that: The drug containing the PLK1 inhibitor further comprises a pharmaceutically acceptable carrier, excipient and / or stabilizer; The carrier pharmaceutically acceptable carrier includes one or more components selected from the following: binders, fillers, lubricants, glidants, disintegrants and wetting agents; The excipients include hydroxypropyl methylcellulose, microcrystalline cellulose, starch glycolate, lactose and magnesium stearate; The stabilizer includes adipic acid, DL-alanine, dl-camphor, D-sorbitol solution, d-borneol, D-sorbitol, D-mannitol, L-ascorbyl stearate, L-sodium ascorbate, L-aspartic acid, sodium L-aspartate, L-arginine, 1-menthol, β-cyclodextrin, ascorbic acid, aminoethanesulfonic acid, sodium alginate, propylene glycol alginate, albumin, sulfur, inositol, fennel powder, ethanol, calcium disodium edetate, sodium edetate, isoascorbic acid, sodium isoascorbate, cocoa butter, carboxyvinyl polymer, carboxymethylcellulose calcium, sodium carboxymethylcellulose, agar, xanthan gum, xylitol, citric acid, and calcium citric acid.

4. The use according to any one of claims 1 to 3, characterized in that: The binder includes gum arabic, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, dextrates, dextrin, dextrose, ethyl cellulose, gelatin, liquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, magnesium aluminum silicate, maltodextrin, methyl cellulose, polymethacrylate, polyvinyl pyrrolidone, pregelatinized starch, sodium alginate, sorbitol, starch, syrup; The fillers include calcium carbonate, calcium phosphate, calcium sulfate, calcium carboxymethylcellulose, sodium carboxymethylcellulose, concentrated sugar, sugar paste, dextrates, dextrin, dextrose, calcium hydrogen phosphate dihydrate, calcium hydrogen phosphate, fructose, palm stearin, glycerol, hydrogenated vegetable oil type-1, kaolin, lactose, corn starch, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polymethacrylate, potassium chloride, powdered cellulose, pregelatinized starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc, calcium phosphate and xylitol; Examples of the lubricant include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, microcrystalline cellulose, sodium benzoate, sodium chloride, sodium lauryl sulfate, stearic acid, sodium stearyl fumarate, talc, and zinc stearate; The glidant includes colloidal silicon dioxide, powdered cellulose, magnesium trisilicate, silicon dioxide and talc; The disintegrants include alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, cross-linked carboxymethylcellulose sodium, polyvinylpolypyrrolidone, guar gum, magnesium aluminum silicate, microcrystalline cellulose, methylcellulose, polyvinylpyrrolidone, polacrilin potassium, pregelatinized starch, sodium alginate, sodium lauryl sulfate and sodium starch glycolate.

5. The use according to any one of claims 1 to 4, characterized in that: The drug containing the PLK1 inhibitor is prepared into a solid, semisolid or liquid preparation for oral administration; preferably, the preparation of the drug containing the PLK1 inhibitor includes tablets, granules, microgranules, powders, capsules, soft capsules, pills, suspensions, emulsions, liquid preparations for oral administration, syrups or dry syrups; or before preparing the preparation, the drug containing the PLK1 inhibitor is first prepared into microparticles; preferably, the drug containing the PLK1 inhibitor is prepared into microcapsules, nanocapsules, microspheres or nanospheres.

6. The use according to any one of claims 1 to 5, characterized in that: The drug containing the PLK1 inhibitor is administered orally, sublingually, by atomization, subcutaneously, intravenously, transdermally, or intestinally.

7. The use according to any one of claims 1 to 6, characterized in that: The dosage of the drug containing the PLK1 inhibitor for human body is 2-10 mg / kg based on the PLK1 inhibitor.

8. Use of a drug containing a PLK1 inhibitor in the preparation of a drug for inhibiting the growth of ovarian hypercalcemia-type small cell carcinoma lesions.

9. The use according to claim 8, characterized in that: The PLK1 inhibitor in the drug containing the PLK1 inhibitor is selected from: BI 2536, CFI-400945, WAY-619275, TAK-960dihydrochloride, Rigosertib (ON-01910), Onvansertib (PCM-075, NMS-1286937, NMS-P937), TC-S 7005, HMN-176, Mps1-IN-2, ON1231320, also known as GBO-006, SBE13 hydrochloride, HMN-214, TAK-960, Ro3280, MLN0905, GW843682X, Rigosertib (ON-01910) sodium, GSK461364, Volasertib (BI 6727), SBP-7455, BL-918, MRT68921 dihydrochloride, LYN-1604dihydrochloride, ULK-101, LYN-16042HCl; Or the drug containing the PLK1 inhibitor further comprises a pharmaceutically acceptable carrier, excipient and / or stabilizer; The carrier pharmaceutically acceptable carrier includes one or more components selected from the following: binders, fillers, lubricants, glidants, disintegrants and wetting agents; The excipients include hydroxypropyl methylcellulose, microcrystalline cellulose, starch glycolate, lactose and magnesium stearate; The stabilizer includes adipic acid, DL-alanine, dl-camphor, D-sorbitol solution, d-borneol, D-sorbitol, D-mannitol, L-ascorbyl stearate, L-sodium ascorbate, L-aspartic acid, sodium L-aspartate, L-arginine, 1-menthol, β-cyclodextrin, ascorbic acid, aminoethanesulfonic acid, sodium alginate, propylene glycol alginate, albumin, sulfur, inositol, fennel powder, ethanol, calcium disodium edetate, sodium edetate, isoascorbic acid, sodium isoascorbate, cocoa butter, carboxyvinyl polymer, carboxymethylcellulose calcium, sodium carboxymethylcellulose, agar, xanthan gum, xylitol, citric acid, calcium citric acid; Preferably, the binder comprises gum arabic, alginic acid, calcium carboxymethylcellulose, sodium carboxymethylcellulose, dextrates, dextrin, dextrose, ethyl cellulose, gelatin, liquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, magnesium aluminum silicate, maltodextrin, methyl cellulose, polymethacrylate, polyvinyl pyrrolidone, pregelatinized starch, sodium alginate, sorbitol, starch, syrup; The fillers include calcium carbonate, calcium phosphate, calcium sulfate, calcium carboxymethylcellulose, sodium carboxymethylcellulose, concentrated sugar, sugar paste, dextrates, dextrin, dextrose, calcium hydrogen phosphate dihydrate, calcium hydrogen phosphate, fructose, palm stearin, glycerol, hydrogenated vegetable oil type-1, kaolin, lactose, corn starch, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polymethacrylate, potassium chloride, powdered cellulose, pregelatinized starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc, calcium phosphate and xylitol; Examples of the lubricant include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, microcrystalline cellulose, sodium benzoate, sodium chloride, sodium lauryl sulfate, stearic acid, sodium stearyl fumarate, talc, and zinc stearate; The glidant includes colloidal silicon dioxide, powdered cellulose, magnesium trisilicate, silicon dioxide and talc; The disintegrants include alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, cross-linked carboxymethylcellulose sodium, polyvinylpolypyrrolidone, guar gum, magnesium aluminum silicate, microcrystalline cellulose, methylcellulose, polyvinylpyrrolidone, polacrilin potassium, pregelatinized starch, sodium alginate, sodium lauryl sulfate and sodium starch glycolate.

10. The use according to any one of claims 8 to 9, characterized in that: The drug containing the PLK1 inhibitor is prepared into a solid, semisolid or liquid preparation for oral administration; preferably, the preparation of the drug containing the PLK1 inhibitor includes tablets, granules, microgranules, powders, capsules, soft capsules, pills, suspensions, emulsions, liquid preparations for oral administration, syrups or dry syrups; or before preparing the preparation, the drug containing the PLK1 inhibitor is first prepared into microparticles; preferably, the drug containing the PLK1 inhibitor is prepared into microcapsules, nanocapsules, microspheres or nanospheres; Or, the drug containing the PLK1 inhibitor is administered orally, sublingually, by atomization, subcutaneously, intravenously, transdermally, or intestinally; The dosage of the drug containing the PLK1 inhibitor for human body is 2-10 mg / kg based on the PLK1 inhibitor.

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