Application of flibaserin and derivative thereof in preparation of medicine for resisting prostate diseases

Abstract

According to the application of the flibaserin and the derivative thereof in preparing the medicine for resisting the prostate diseases, the flibaserin serves as a treatment medicine, proliferation of prostate cancer cells can be inhibited, growth of in-vivo tumors can be inhibited, on the premise of low toxic and side effects, the progress of castration-resistant prostate cancer can be relieved, and the prostate diseases can be prevented. Prostatic hyperplasia and prostatic hyperplasia are reduced; the method plays an important role in prolonging the lifetime of a patient and slowing down proliferation, migration and invasion of diseases.

Description

Technical Field

[0001] This invention relates to the application of flubancerine or its derivatives in the preparation of drugs for treating prostate diseases, and belongs to the field of biomedical technology. Background Technology

[0002] Prostate diseases include benign prostatic hyperplasia (BPH), enlarged prostate, and prostate cancer. Androgens play a very important role in all three types of prostate diseases.

[0003] For example, early-stage metastatic prostate cancer is primarily treated with endocrine therapy. Most prostate cancer patients who undergo androgen deprivation therapy (ADT) only experience an 18-24 month remission period and eventually develop castration-resistant prostate cancer (CRPC), with a five-year survival rate of only 30%. Diagnosis of CRPC requires meeting the following four criteria: 1. Serum testosterone levels reaching castration levels (<50 ng / dL or <1.7 nmol / L); 2. Three consecutive PSA elevations at one-week intervals, with an increase greater than 50% from the lowest value; 3. Failure of traditional anti-androgen withdrawal therapy; 4. Progression of bone or soft tissue metastases. Almost all patients with advanced prostate cancer who receive endocrine therapy will eventually progress to castration-resistant prostate cancer (CRPC).

[0004] In the castration-resistant prostate cancer (CRPC) stage, the median natural survival without effective treatment is 12-18 months. Disease progression accelerates, and the later effective treatment is initiated, the worse the outcome and prognosis. Current research, guidelines, and literature from both domestic and international sources indicate that in the castration-resistant stage, combined castration therapy can extend survival by using oral abiraterone, docetaxel chemotherapy, or enzalutamide. Summary of the Invention

[0005] The purpose of this invention is to provide the application of flubancerine or its derivatives in the preparation of drugs for treating prostate diseases (benign prostatic hyperplasia, benign prostatic hyperplasia, and prostate cancer, especially castration-resistant prostate cancer). Using flubancerine as a therapeutic agent can inhibit the proliferation of prostate cancer cells, suppress tumor growth in vivo, and, with low toxicity and side effects, alleviate the progression of castration-resistant prostate cancer, reduce benign prostatic hyperplasia and benign prostatic hyperplasia; it plays an important role in prolonging patient survival and slowing the proliferation, migration, and invasion of the disease.

[0006] To achieve this objective, the present invention provides the following technical solution: In a first aspect, the invention provides the use of fluorobanserine or a derivative thereof in the preparation of a medicament for treating prostate diseases.

[0007] In this invention, the chemical formula of fluorobanserine is as follows: .

[0008] Preferably, the prostate disease includes benign prostatic hyperplasia, prostatic hypertrophy, and prostate cancer; more preferably, the prostate cancer is castration-resistant prostate cancer.

[0009] Preferably, the concentration of flubancerin or its derivatives in the flubancerin is 1-2.3 mg / ml. More preferably, the concentration of flubancerin is 1.10 mg / ml, 1.11 mg / ml, 1.12 mg / ml, 1.13 mg / ml, 1.14 mg / ml, 1.15 mg / ml, 1.16 mg / ml, 1.17 mg / ml, 1.18 mg / ml, 1.19 mg / ml, 1.10 mg / ml, 1.21 mg / ml...2.20 mg / ml, 2.21 mg / ml, 2.22 mg / ml, 2.23 mg / ml, 2.24 mg / ml, 2.25 mg / ml, 2.26 mg / ml, 2.27 mg / ml, 2.28 mg / ml, 2.29 mg / ml, or 2.30 mg / ml.

[0010] Preferably, the flubancerine or its derivatives are in the form of tautomers, mesosomes, racemates, enantiomers, diastereomers, or mixtures thereof.

[0011] Preferably, the flubancerine or its derivatives include pharmaceutically acceptable salts, ethers, esters, prodrugs, metabolites, solvates, or crystals thereof. More preferably, the flubancerine or its derivatives include pharmaceutically acceptable salts, including but not limited to hydrochloride, sulfate, bromate, fumarate, acetate, or citrate.

[0012] Preferably, the drug includes, but is not limited to, tablets, capsules, oral solutions, pills, granules, powders, aerosols, patches, ointments, liniments, suppositories, and / or injections.

[0013] Preferably, the drug can inhibit the proliferation, migration, and growth of prostate cancer tumors, reduce the level of PSA in the body, and delay the progression of castration-resistant prostate cancer.

[0014] In a second aspect, the present invention provides a medicament for treating or preventing prostate diseases, the medicament comprising flubancerine or a derivative thereof, wherein the concentration of flubancerine in the flubancerine or the derivative thereof is 1-2.3 mg / ml.

[0015] Preferably, the prostate disease includes benign prostatic hyperplasia, prostatic hypertrophy, and prostate cancer; more preferably, the prostate cancer is castration-resistant prostate cancer.

[0016] Preferably, the flubancerine or its derivatives are in the form of tautomers, mesosomes, racemates, enantiomers, diastereomers, or mixtures thereof.

[0017] Preferably, the flubancerine or its derivatives include pharmaceutically acceptable salts, ethers, esters, prodrugs, metabolites, solvates, or crystals thereof. More preferably, the flubancerine or its derivatives include pharmaceutically acceptable salts, including but not limited to hydrochloride, sulfate, bromate, fumarate, acetate, or citrate.

[0018] Preferably, the drug includes, but is not limited to, tablets, capsules, oral solutions, pills, granules, powders, aerosols, patches, ointments, liniments, suppositories, and / or injections.

[0019] Preferably, the drug can inhibit the proliferation, migration, and growth of prostate cancer tumors, reduce the level of PSA in the body, and delay the progression of castration-resistant prostate cancer.

[0020] Compared with the prior art, the beneficial effects and significant progress of applying the technical solution of the present invention are as follows: 1. This invention verifies that flubanserine and its derivatives can be used as active ingredients in drugs for castration-resistant prostate cancer, opening up new applications for flubanserine and providing a new option for inhibiting castration-resistant prostate cancer. Specifically, flubanserine has an inhibitory effect on the proliferation of human prostate cancer cells; flubanserine can inhibit the growth of subcutaneous tumors of prostate cancer cells in nude mice. After gavage administration of 10 mg / kg to nude mice, the tumor weight decreased by 45% compared with the untreated group, and the expression levels of PSA and Ki67 in the tumor tissue were reduced. Therefore, flubanserine can slow the progression of castration-resistant prostate cancer.

[0021] 2. This invention verifies that flubanserine and its derivatives can be used as active ingredients in the treatment of benign prostatic hyperplasia (BPH) and prostatic hypertrophy, with a significant reduction in prostatic wet weight after 14 days of administration. Therefore, flubanserine has a therapeutic effect on BPH and prostatic hypertrophy.

[0022] 3. This invention verifies that low concentrations (1.17 mg / ml, 10 mg / kg) of flubancerline are more effective than high concentrations (2.3 mg / ml, 20 mg / kg). Furthermore, flubancerline causes virtually no damage to liver and kidney tissues. Therefore, flubancerline is safe at effective concentrations. Attached Figure Description

[0023] To more clearly illustrate the technical solution of the present invention, the accompanying drawings used in the embodiments of the present invention will be briefly described below.

[0024] Figure 1 This is a graph showing the weight measurement of nude mice during the drug administration process in Example 1; Figure 2 This is a graph showing the growth trend of fluorobanserine tumor volume in Example 1; Figure 3 This is a gross observation of the inhibition of tumor growth in nude mice by fluorobanserine in Example 1; Figure 4 These are comparative images of tumor removal from nude mice in Example 1; Figure 5 This is a comparison chart of tumor weight in nude mice in Example 1; Figure 6 This is a diagram showing the results of the CCK-8 assay in Example 2, which detected the inhibition of PC-3 cell line proliferation by fluorobanserine. Figure 7 HE staining of nude mouse tumor tissue from Example 3; Figure 8 HE staining of nude mouse liver and kidney tissue from Example 3; Figure 9 The tumor tissue in Example 3 was subjected to immunohistochemistry for Ki67, AR, and PSA. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the present invention is further described below in conjunction with specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and parts by weight. Unless otherwise specified, the experimental materials and reagents used in the following embodiments are commercially available.

[0026] Unless otherwise specified, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains. It should be noted that the terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the exemplary embodiments of this application.

[0027] To better understand this invention, the technical terms used in this invention will be explained below.

[0028] A tumor is a new growth formed by the proliferation of local tissue cells under the influence of various tumorigenic factors. Because these new growths often present as space-occupying, mass-like protrusions, they are also called neoplasms. Liver cancer and pancreatic cancer are both known as the "kings of cancers," being extremely malignant tumors. Research has found that tumor cells exhibit metabolic changes different from normal cells, and that tumor cells themselves can adapt to altered metabolic environments through switching between glycolysis and oxidative phosphorylation (OXPHOS).

[0029] Tautomers are functional group isomers that are produced by the rapid movement of an atom in two positions within a molecule. Tautomers are a special type of functional group isomer.

[0030] A meso compound is a molecule containing asymmetric atoms, but possessing symmetry factors that result in zero total optical rotation, i.e., no optical activity. It is usually denoted by meso or i.

[0031] A racemic mixture is an equimolar mixture of an optically active (see optical isomerism) chiral molecule and its enantiomer. Unlike a meso mixture, it is composed of equal amounts of molecules with opposite optical rotation directions and identical optical activity. Their optical activity cancels each other out due to intermolecular interactions, resulting in an optically inactive mixture. Furthermore, although enantiomers generally have the same physical properties, the physical properties of a racemic mixture, such as melting point and solubility, often differ from those of their corresponding enantiomers. Racemic mixtures are commonly labeled D or L-. The two molecules composing a racemic mixture have identical physical and chemical properties except for opposite optical rotation directions. A racemic mixture is the inevitable product of a molecule with a potential chiral center forming a chiral center.

[0032] Enantiomers are stereoisomers that are mirror images of each other but cannot be superimposed. Both enantiomers are optically active, one of which is left-handed and the other is right-handed. Therefore, enantiomers are also called optically active isomers.

[0033] Diastereoisomers are stereoisomers of molecules that have two or more chiral centers and are not mirror images of each other.

[0034] Example 1: Investigation of the in vivo activity of fluorobanserine in inhibiting castration-resistant prostate cancer. 1.1 Laboratory Animals The experimental animals were male BLAB / c nude mice, 5 weeks old, weighing 14-16g, purchased from Chengdu Enbocon Biotechnology Co., Ltd. The BLAB / c nude mice were tested in the barrier facility of the Animal Experiment Center of China Pharmaceutical University, at a temperature of 25±2℃ and humidity of 50%. The litter was kept at 70% light and dark, alternating between 12 hours of light and 12 hours of darkness. The animals were allowed free access to food and water, and the corn cob bedding was changed twice a week. The experiment began after the animals had adapted to the rearing environment for 7 days.

[0035] 1.2 Drug Preparation 1) Preparation of flubancerine gavage: Flubancerine hydrochloride was purchased from Yancheng Qiangzhong Chemical Co., Ltd., batch number: JZ20231022.

[0036] Preparation of low-dose flubancerine solution (10 mg / Kg): Dissolve 24.5 mg flubancerine powder in 210 μl of anhydrous ethanol, add 2 ml of PEG400 and 0.63 ml of Tween-80 to the solution, mix well, and then add physiological saline to make up to 21 ml.

[0037] Preparation of high-dose flubancerine solution (20 mg / Kg): Dissolve 48.3 mg flubancerine powder in 400 μl of anhydrous ethanol, add 3 ml of PEG400 and 0.83 ml of Tween-80 to the solution, mix well, add physiological saline to make up to 21 ml, dispense into containers and store at 4 degrees Celsius.

[0038] 2) Preparation of enzalutamide positive control drug via gavage: Enzalutamide powder was purchased from Shanghai Bid Pharmaceutical Technology Co., Ltd., product number 915087-33-1. Take 36.225mg of enzalutamide powder, add 100u LDMSO to dissolve it as the stock solution, add 1.5ml PEG400 and 0.7ml Tween-80, and make up to 21ml with physiological saline. Mix well to prepare the enzalutamide positive control drug via gavage. After dispensing, store at 4℃ for later use.

[0039] 3) Preparation of positive drug berberine for gavage: Take 36.225mg of berberine powder, add 100uLDMSO to dissolve and use as the stock solution. Slowly add 105mg of sodium carboxymethyl cellulose powder to 21ml of physiological saline. After swelling overnight, add it to the stock solution as a solvent and mix well to prepare the berberine for gavage. After dispensing, store at 4℃ for later use.

[0040] 4) 4% Chloral hydrate solution: Dissolve 2 g of chloral hydrate powder in 50 mL of physiological saline, filter through a 0.22 μm microporous membrane for sterilization, and store at 4℃ in the dark for later use. 1.3 Establishment of a nude mouse model of castration-resistant prostate cancer After digesting pc-3 cells in the logarithmic growth phase with 0.25% EDTA trypsin, the cells were counted and centrifuged. The cells were washed twice with PBS, and the cell density was adjusted to a concentration of 5 × 10⁻⁶ cells / mL. 7 Cell suspensions with a cell count / mL were prepared. Cell suspensions with a viability greater than 90% were used, as determined by trypan blue exclusion. 3 mL of pre-chilled PBS (4°C) and 3 mL of pre-chilled Matrigel gel (4°C) were added. 0.2 mL of the cell suspension was subcutaneously injected into the lateral side of the right leg of nude mice. The size and growth of the inoculated tumors and changes in body weight were observed daily. Tumor volume was calculated using the formula: Tumor volume = 0.5 × maximum diameter × minimum diameter². Approximately six days later, tumors appeared on the lateral side of the right leg of the nude mice. The tumor volume was measured to be 150 mm². 3 Nude mice were used for tumor suppression experiments. Based on tumor volume, the mice were divided into five groups for subsequent drug efficacy experiments.

[0041] 1.4 Evaluation of the therapeutic effect in nude mice with castration-resistant prostate cancer model Grouping: Model group, low-dose flubancerine group (10 mg / Kg), high-dose flubancerine group (20 mg / Kg), positive control drug enzalutamide group (15 mg / Kg), positive control drug berberine group (15 mg / Kg), six animals in each group.

[0042] Nude mice were administered the drug by gavage for 16 consecutive days, at a rate of 0.2 ml / day / mouse. The weight and tumor size of the mice were measured every two days. On day 17, tumor tissue, liver and kidney tissue were collected from the nude mice and fixed in 4% paraformaldehyde for subsequent HE staining and immunohistochemistry.

[0043] 1.5 Experimental Results Six days after the injection of prostate cancer cells, the average tumor volume in mice reached 146 mm. 3 This indicates successful tumorigenesis in nude mice. A 16-day course of oral administration was initiated, during which there was no significant difference in mouse body weight. Figure 1 This indicates that the drug had no significant effect on mouse body weight; the size of the mouse tumor was measured every other day, and a volume growth graph was obtained. Figure 2 As can be seen, the mouse tumors gradually increased in size over time. Compared with the model group, the tumor growth rate in the low-dose flubanoxetine group, berberine group, and enzalutamide group slowed down. Compared with the final average tumor volume of the model group, the low-dose flubanoxetine group decreased to 61.125%, the berberine group decreased to 67.5%, and the positive control drug enzalutamide group decreased to 62.2%. On day 17, after cervical dislocation and sacrifice of nude mice, gross observation images of the tumor sides of the nude mice were obtained. Figure 3 ), dissected the mouse to obtain tumors and liver and kidney tissues, and obtained tumor comparison images ( Figure 4By measuring tumor weight, we found that the average tumor weight in the low-dose flubanoxetine group was around 150 mg, while the average tumor weight in the model group was over 300 mg, a reduction of about 50%. This was not significantly different from the results of measurements with berberine and the positive control drug enzalutamide. Figure 5 ).

[0044] Example 2: Flubancerine inhibits the proliferation of prostate cancer cells. 2.1 Materials and Reagents Human prostate cancer PC-3 cells were cultured in F12-K medium; CCK8 assay reagent was used; fluorobenzamine was used. 2.2 Experimental Methods PC-3 cells were used at a rate of 1×10 5 Cells were cultured at a density of 0.5 g / well in 96-well plates using complete medium containing 10% FBS, and divided into solvent control and drug control groups. Flubanoxelin was added at concentration gradients of 0.2, 1, 5, 25, 50, and 100 μM; a solvent control group was also included. After 48 hours of drug treatment, PC-3 cell viability was measured using the CCK8 assay. Absorbance was read at 450 nm, and the proliferation inhibition rate was calculated using the following formula.

[0045] Cell viability = (Test sample A - Blank group A) / (Soluble group A - Blank group A) 2.3 Experimental Results The results are as follows Figure 6 As shown, flubancerin effectively inhibits the proliferation of PC-3 cells, and the inhibition rate is concentration-dependent. The inhibition rate is approximately 14% at a concentration of 0.2 μM, and reaches 80% when the concentration is increased to 50 μM. Furthermore, the inhibitory effect improves with increasing time; the inhibition rate gradually increases at the same drug concentration after 72 hours, 48 ​​hours, and 24 hours.

[0046] Example 3: Pathological detection of fluorobanserine inhibiting prostate cancer Experimental Groups: The model group (control group), low-dose flubancerine group, high-dose flubancerine group, berberine group, and enzalutamide positive control group were included.

[0047] Experimental steps: 3.1 Paraffin-embedded sections After collection, the tissues were washed three times with PBS buffer, and the tumor tissues, liver and kidney tissues were fixed in 4% paraformaldehyde solution at 25°C for 48 hours.

[0048] 1) Dehydration: Immerse the tissue in 75% ethanol, 85% ethanol, 95% ethanol I, 95% ethanol II, 100% ethanol I and 100% ethanol II for 10 min each.

[0049] 2) Transparency: The dehydrated tissues were immersed in 1 / 2 xylene II, xylene I, and xylene II for 10 minutes respectively.

[0050] 3) Paraffin embedding: Immerse the sample fully in liquid paraffin at 60-65℃ (2 hours × 2 times). Take care to control the temperature to prevent tissue protein loss. At this time, the sample can be embedded into a cube.

[0051] 4) Sectioning: Freeze the paraffin block at -20℃ for 30 min, use a microtome to cut the tissue in the paraffin block into 5μm thick sections, spread them in a 50℃ water bath, and retrieve the sections.

[0052] 5) Baking slices: Place the slices in a 60℃ oven for 4 hours, then remove and set aside.

[0053] 3.2 Pathological staining The sections were dewaxed (procedure as shown in Table 1). Then, the sections were stained with hematoxylin and eosin according to the manufacturer's instructions. After rinsing with PBS buffer for 5 min, the sections were sequentially dehydrated in 70% ethanol for 3 min, 90% ethanol for 5 min, and 100% ethanol for 8 min. After clearing, the sections were immersed in xylene for 3 min, mounted with neutral resin, scanned using a Hamamatsu slide scanner, and the images were processed using NDP view software.

[0054] Table 1. Dewaxing of mouse dorsal skin specimens. 3.3 Experimental Results The slice results are as follows Figure 7-8 As shown. Nude mice were dissected after drug administration, yielding tumor tissue, liver and kidney tissue. The tumor tissue was paraffin-embedded, sectioned, stained with hematoxylin and eosin (HE), and scanned to obtain HE-stained images. Because the model was created by subcutaneous injection of cancer cells, the tumor structures in each group of mice did not show large areas of necrosis; they generally appeared disordered, with small, uniform cells and foamy cytoplasm, consistent with the characteristics of subcutaneous colonomas. Figure 7 Liver and kidney sections from each group of nude mice, as shown in... Figure 8 As shown, the results indicated that the glomerular and tubular structures of the kidneys of mice in each group were clear and distinct, with no obvious brush border loss and no toxic lesions. No obvious cell vacuolation was observed in the liver, and HE staining results showed no drug toxicity in the mice. This indicates that flubancerine is safe and effective.

[0055] In addition, immunohistochemistry of Ki67, AR, and PSA in tumor tissue was performed in this embodiment. The results are as follows: Figure 9As shown, the model group exhibits greater Ki67 signal expression, larger area, and deeper color compared to the low-dose and high-dose flubancelin groups. This indicates that the untreated subcutaneous tumors showed a stronger proliferative effect. In contrast, the flubancelin-treated group, with relatively low Ki67 expression, did not show significant tumor cell proliferation or growth trends compared to the model group. This suggests that flubancelin can effectively inhibit the development of prostate tumors. The immunohistochemical results of the androgen receptor (AR) are as follows: Compared to the model group, the high-dose flubancelin group reduced androgen receptor expression in tumor tissue, even exceeding the inhibitory effect of the positive control drug enzalutamide. While the low-dose flubancelin group did not reduce androgen receptor expression, it reduced its nuclear translocation process. The immunohistochemical map shows that the low-dose group expressed more androgen receptors in the cytoplasm. Generally, androgen receptors play a crucial role in the development of prostate cancer. Decreased androgen receptor expression and slowed nuclear translocation are important for alleviating the disease process. Finally, we investigated the therapeutic effect of drugs on subcutaneous tumors in nude mice by detecting human prostate-specific antigen (PSA) in tumor tissue. Immunohistochemical staining revealed varying degrees of PSA expression in the tumor tissues of all groups of mice. Compared to the model group, the drug-treated groups all showed downregulated PSA expression. The berberine group and the enzalutamide positive control group showed the best PSA downregulation effect. Downregulation of PSA indicates decreased prostate cancer tumor activity and a reduced likelihood of tumor progression and metastasis. In conclusion, flubancerin at a dose of 10 mg / kg can slow the progression of prostate cancer in mice, providing a new therapeutic option for castration-resistant prostate cancer.

[0056] Example 4: Flubancerine inhibits benign prostatic hyperplasia and prostatic hypertrophy. This embodiment established a mouse model of benign prostatic hyperplasia (BPH) and benign prostatic hyperplasia (BPH). The effect of low-dose flubancelin (as in Example 1) on these conditions was determined. The results showed that the condition of the mice with BPH and BPH improved after 7 days of administration. After 14 days of administration, mice in the experimental group (low-dose flubancelin) and the control group (saline) were dissected. The wet weight of the prostate gland in the experimental group was significantly lower than that in the control group. Therefore, flubancelin has a therapeutic effect on BPH and BPH.

[0057] The applicant declares that, in the process of describing the above-mentioned specification: The terms "this embodiment," "an embodiment of the present invention," "as shown," "further," and "further improved technical solutions," etc., indicate that the specific features, structures, materials, or characteristics described in the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms are not necessarily directed at the same embodiment or example, and the specific features, structures, materials, or characteristics described can be combined or combined in any suitable manner in one or more embodiments or examples. Furthermore, without causing contradiction, those skilled in the art can combine or combine the different embodiments or examples described in this specification and the features of the different embodiments or examples.

[0058] Finally, it should be noted that: The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them; Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention. Non-essential improvements, adjustments or substitutions made by those skilled in the art based on the content of this specification are all within the scope of protection claimed by the present invention.

Claims

1. Use of flibanserin or its derivative in the preparation of a medicament for treating prostate diseases.

2. Use according to claim 1, characterized in that, The prostate diseases include benign prostatic hyperplasia, prostatic hypertrophy and prostate cancer.

3. Use according to claim 2, characterized in that, The prostate cancer is castration-resistant prostate cancer.

4. Use according to claim 1, characterized in that, The concentration of flibanserin in the flibanserin or its derivative is 1-2.3 mg / ml.

5. The use according to claim 1, characterized in that, The flibanserin or its derivative is in the form of tautomer, mesomer, racemate, enantiomer, diastereomer or mixture thereof.

6. Use according to claim 1 or 5, characterized in that, The flibanserin or its derivative includes pharmaceutically acceptable salts, ethers, esters, prodrugs, metabolites, solvates or crystals thereof.

7. Use according to claim 6, characterized in that, The flibanserin or its derivative includes pharmaceutically acceptable salts thereof, which include but are not limited to hydrochloride, sulfate, bromate, fumarate, acetate or citrate.

8. The use according to claim 1, characterized in that, The medicament includes but is not limited to tablet, capsule, oral solution, pill, granule, powder, aerosol, patch, ointment, paint, suppository and / or injection.

9. The use according to claim 1, characterized in that, The medicament can inhibit the proliferation, migration and growth of prostate cancer tumor, reduce the content of PSA in vivo and delay the progression of castration-resistant prostate cancer.

10. A medicament for treating or preventing a prostate disease, characterized by comprising the compound of claim 1. The medicament contains flibanserin or its derivative, and the concentration of flibanserin in the flibanserin or its derivative is 1-2.3 mg / ml.

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