Application of mucuna sempervirens or extract in preparation of anti-cancer drugs

Abstract

The invention belongs to the technical field of medicines, discloses application of mucuna sempervirens or extracts in preparation of anti-cancer drugs, and provides the anti-tumor effect of the natural plant extracts of the mucuna sempervirens. In-vitro experiment results show that the ethanol extract of mucuna sempervirens can effectively inhibit the activity of liver cancer cells, colon cancer cells, melanoma cells and lung cancer cells, and IC50 is 49.5 [mu] g / mL, 51.4 [mu] g / mL, 103.4 [mu] g / mL and 221.7 [mu] g / mL in sequence. In-vivo experiment results show that the ethanol extract of mucuna sempervirens can significantly inhibit the size, volume and weight of transplanted tumors of mouse colon cancer, and has no obvious influence on each organ of a mouse. Compared with traditional drugs (such as paclitaxel), the pharmaceutical composition has lower toxic and side effects. Meanwhile, various anti-tumor effects can be achieved, the anti-cancer range is wide, the application dosage is low, and wide development prospects are achieved.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to the use of Mucuna sempervirens Hance or its extract in the preparation of anti-cancer drugs. Background Art

[0002] Mucuna sempervirens Hance (scientific name: Mucuna sempervirens Hemsl.) is an evergreen woody vine, belonging to the legume family, and has high ornamental and medicinal values. It is a large vine that can grow up to 25 meters long, and the diameter of the old stem exceeds 30 centimeters. The stem of Mucuna sempervirens Hance is brown or yellowish-brown, rough, the branches are slender, light green, smooth and hairless.

[0003] The vine stem of Mucuna sempervirens Hance is used as a medicinal material in traditional medicine. It is warm in nature and bitter in taste, and has the effects of promoting blood circulation and tonifying blood, dredging channels and activating collaterals. It can be used to treat arthralgia due to wind-dampness, numbness of limbs, blood deficiency, irregular menstruation and amenorrhea.

[0004] Yang Shenming et al. studied the microwave-assisted extraction process of total flavonoids from Mucuna sempervirens Hance flowers and their antioxidant properties, optimized the extraction process of total flavonoids from Mucuna sempervirens Hance flowers by microwave-assisted extraction, and determined the antioxidant properties of its total flavonoids. The test results showed that the total flavonoids from Mucuna sempervirens Hance flowers extracted by microwave-assisted extraction had strong antioxidant properties, had obvious scavenging effects on DPPH·, hydroxyl radicals and superoxide anion radicals, and there was a certain dose-effect relationship between its mass concentration and antioxidant activity. Wu Guiping et al. disclosed that Mucuna sempervirens Hance is warm in nature and bitter in taste, has the effects of promoting blood circulation and tonifying blood, dredging channels and activating collaterals, and can be used to treat rheumatic pain, numbness of limbs, irregular menstruation due to blood deficiency and amenorrhea.

[0005] At present, there is no relevant literature report on the use of Mucuna sempervirens Hance for anti-cancer. Summary of the Invention

[0006] The purpose of the first aspect of the present invention is to provide the application of Mucuna sempervirens Hance or its extract in the preparation of anti-tumor drugs.

[0007] In order to achieve the above purpose, the technical solution adopted by the present invention is:

[0008] The first aspect of the present invention provides the application of Mucuna sempervirens Hance or its extract in the preparation of anti-tumor drugs.

[0009] In some embodiments of the present invention, the extract is an ethanol extract of the vine stem of Mucuna sempervirens Hance.

[0010] In some embodiments of the present invention, the alcohol includes at least one of methanol, ethanol, and propanol; preferably ethanol.

[0011] In some embodiments of the present invention, the extraction method of the extract includes ultrasonic method, reflux method, decoction method, maceration method, percolation method, microwave extraction method or CO2 supercritical extraction method.

[0012] In some embodiments of the present invention, the extraction method of the extract includes the following steps: pulverize the vine stems of Mucuna sempervirens Hance and mix with an alcohol solution, and extract under boiling conditions.

[0013] In some embodiments of the present invention, the extraction time is 0.5 - 5 h.

[0014] In some embodiments of the present invention, the concentration of the alcohol solution is 60 v / v% - 95 v / v%.

[0015] In some embodiments of the present invention, the concentration of the alcohol solution is 75 v / v%.

[0016] In some embodiments of the present invention, the tumor includes at least one of colon cancer, lung cancer, melanoma and liver cancer.

[0017] In some embodiments of the present invention, the drug further includes a pharmaceutically acceptable excipient.

[0018] In some embodiments of the present invention, the pharmaceutically acceptable excipient includes at least one of solvent, propellant, solubilizer, cosolvent, emulsifier, colorant, binder, disintegrant, filler, lubricant, wetting agent, osmotic pressure regulator, stabilizer, glidant, flavoring agent, preservative, suspending agent, coating material, fragrance, antiadhesive, chelating agent, penetration enhancer, pH regulator, buffer, plasticizer, surfactant, foaming agent, defoaming agent, thickening agent, clathrate, humectant, absorbent, diluent, flocculant and deflocculant, filter aid, release retarder, carrier.

[0019] In some embodiments of the present invention, the drug further includes other active ingredients (drugs with anti-tumor effects) that are compatible with Mucuna sempervirens Hance or its extract and have a synergistic effect.

[0020] In some embodiments of the present invention, the dosage form of the drug includes capsule, tablet, pill, injection, tincture, suppository, powder, powder, granule, oral liquid preparation, freeze-dried preparation, dripping pill, sustained-release preparation, controlled-release tablet, suspension, aerosol, spray, extract, syrup or plaster.

[0021] The beneficial effects of the present invention are:

[0022] The present invention provides the effect of the plant extract from Mucuna sempervirens Hance of natural origin in anti-tumor. The in vitro experimental results show that the ethanol extract of Mucuna sempervirens Hance can effectively inhibit the activities of liver cancer cells, colon cancer cells, melanoma cells, lung cancer cells, etc., and the IC50 values are 49.5 μg / mL, 51.4 μg / mL, 103.4 μg / mL and 221.7 μg / mL respectively. The in vivo experimental results show that the ethanol extract of Mucuna sempervirens Hance can significantly inhibit the size, volume and weight of transplanted tumors of murine colon cancer, and has no obvious effect on the organs of mice. Compared with traditional drugs (such as paclitaxel), it has lower toxicity and side effects. At the same time, it can play a variety of anti-tumor roles, has a wide anti-cancer spectrum and a low application dose, and has broad development prospects. Description of the Drawings

[0023] Figure 1 It is the process flow chart of the extraction of Mucuna sempervirens Hance.

[0024] Figure 2 It is the HPLC chromatogram of the extract of Mucuna sempervirens Hance.

[0025] Figure 3 It is the determination result of the IC 50 value of MSE on normal human colon cells, and its IC 50 is 818.2 μg / mL.

[0026] Figure 4 It is the IC 50 value result of MSE on colon cancer HT-29 cells, and its IC 50 is 54.1 μg / mL.

[0027] Figure 5 It is the IC 50 value result of MSE on melanoma A375 cells, and its IC 50 is 103.4 μg / mL.

[0028] Figure 6 It is the IC 50 value result of MSE on lung cancer A549 cells, and its IC 50 is 221.7 μg / mL.

[0029] Figure 7 It is the IC 50 value result of MSE on liver cancer Hep3B cells, and its IC 50 is 49.5 μg / mL.

[0030] Figure 8 It is the process flow chart of the transplanted tumor experiment in mice.

[0031] Figure 9 It is the picture of the mouse tumor dissection and photographing.

[0032] Figure 10 It is the tumor growth curve of mice. In the figure, ** represents p < 0.01, and **** represents p < 0.001.

[0033] Figure 11 It is the statistical chart of the tumor weight of mice. In the figure, ** represents p < 0.01, and **** represents p < 0.001.

[0034] Figure 12 It is the statistical chart of the organ index of mice. In the figure, ** represents p < 0.01.

[0035] Figure 13 It is the trend chart of the body weight change of mice. In the figure, ** represents p < 0.01. Specific implementation mode

[0036] The content of the present invention will be further described in detail below through specific embodiments.

[0037] It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention.

[0038] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. For those not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0039] The features and performance of the present invention will be further described in detail below in combination with the embodiments.

[0040] Example 1 Extraction process of Mucuna sempervirens Hance

[0041] This example provides a preparation method for the freeze-dried powder of Mucuna sempervirens Hance extract (the flow chart is as Figure 1 shown), including the following steps:

[0042] The Mucuna sempervirens Hance medicinal materials (the dried vine stems of Mucuna sempervirens Hance) are cleaned, dried, and crushed into Mucuna sempervirens Hance powder, added to a round-bottom flask and placed in a heating stirrer. 10 times 75% ethanol is added to the round-bottom flask, and it is continuously boiled gently for 1.5 h. It is cooled to room temperature and the clear liquid is taken. The residue is extracted one more time. The two obtained extracts are placed in a rotary evaporator and concentrated under reduced pressure by distillation to an appropriate volume, and then transferred to a freeze dryer. After freeze-drying for several days, the freeze-dried powder of Mucuna sempervirens Hance extract (denoted as MSE) is obtained.

[0043] The components in the freeze-dried powder of the Mucuna sempervirens Hance extract were detected by HPLC. Among them, the chromatographic conditions of UPLC were as follows: the chromatographic column was ACQUITY UPLC HSS T3 column 1.8μm (2.1×100mm), acetonitrile was used as mobile phase A, and 0.1% phosphoric acid aqueous solution was used as mobile phase B for gradient elution. The gradient elution program was shown in Table 1; the flow rate was 3.0 mL / min; the detection wavelength was 254 nm; the column temperature was 35°C; and the injection volume was 5 μL.

[0044] Table 1 Gradient elution conditions

[0045] Time (min) A(％) B(％) 0 10 90 2 15 85 2.5 25 75 10 70 30 12 100 0 20 100 0

[0046] The detection results were as Figure 2 , and the detection results of the contents of three components, daidzein, formononetin, and 3,7-dihydroxyisoflavone, were shown in Table 2.

[0047] Table 2 Content table of daidzein, formononetin, and 3,7-dihydroxyisoflavone

[0048]

[0049] Example 2 Anticancer activity evaluation of the freeze-dried powder of the Mucuna sempervirens Hance extract

[0050] 1. Cell treatment

[0051] When the cells (colorectal cancer HT-29 cells, lung cancer A549 cells, melanoma A375 cells, liver cancer Hep3B cells, normal human colon cells) grew to 80%, the cells were digested, centrifuged and resuspended, and counted (take 50 μL, add 5 μL trypan blue and mix well; cell suspension: trypan blue = 10:1) (Note: if the counting result is N cells, then the concentration C0 of the resuspended cell solution is N×104×1.1 (dilution factor when adding trypan blue) cells / mL).

[0052] 2. Cell seeding

[0053] Colorectal cancer HT-29 cells, lung cancer A549 cells, melanoma A375 cells, and liver cancer Hep3B cells were seeded in 96-well plates, with a total of 4 plates; the above cells were all from the American ATCC cell bank;

[0054] (1) The number of seeded cells was 10,000 cells / well, and the volume of the cell solution was 100 μL / well;

[0055] (2) The freeze-dried powder of Mucuna sempervirens Hance extract (prepared in Example 1) was set at 7 concentrations (6.25, 12.5, 25, 50, 100, 200, 400 μg / mL) (corresponding crude drug amounts were 0.09, 0.17, 0.35, 0.7, 1.4, 2.9, 5.7 mg / mL) respectively. Each concentration had 3 replicate wells, and together with the control group with a concentration of 0, there were a total of 8 groups. A total of 8 groups × 3 wells required adding cells. The theoretically required volume of cell suspension was 8 × 3 × 100 μL = 2.4 mL, and 3 mL (V1) could be prepared for standby. Then the total number of cells required n = V1 × C1, that is, 3 mL × 1 × 10 5 cells / mL = 3 × 10 5 cells;

[0056] (3) Prepare the cell suspension with the cell suspension obtained in step (1): A total of 3 mL

[0057] V0 (cell suspension) × C0 = V1 × C1 (1);

[0058] V0 (cell suspension) = 3*105 / N * 104 * 1.1 (2);

[0059] The volume of the culture medium required to prepare the cell suspension: V = V1 - V0 = 10 - V0 (3);

[0060] (4) After mixing, use a multi-channel pipette to add cells to the 96-well plate, and the sample addition volume for each well is 100 μL;

[0061] (5) Observe whether the plating is uniform under the microscope and then place it in the incubator.

[0062] 3. Adding drugs to cells (16 h after plating)

[0063] (1) Prepare the drugs (taking the dosage for one cell line and three plates as an example)

[0064] ① Set 7 drug concentrations (6.25 μg / mL, 12.5 μg / mL, 25 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL, 400 μg / mL). Each concentration had 3 replicate wells, and the sample addition volume for each well was 100 μL. Theoretically, the volume of the Mucuna sempervirens Hance extract solution required for each concentration for each cell line was 0.3 mL, and 2.0 mL was prepared for standby.

[0065] Note: Since 100 μL of Mucuna sempervirens Hance extract solution and 100 μL of cell-containing culture medium are added to each well, the drug concentration will be diluted to 0.5 times the concentration of the added Mucuna sempervirens Hance extract solution, and it should be prepared at 2 times the concentration. That is, the concentrations of the 7 Mucuna sempervirens Hance extract solutions actually added should be 12.5 μg / mL, 25 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL, 400 μg / mL, and 800 μg / mL.

[0066] ②Dilution of Mucuna sempervirens Hance extract solutions with different concentrations (usage for one cell line, three plates)

[0067] To reduce errors, the gradient dilution method is adopted.

[0068] (2)Drug addition (take a photo before drug addition)

[0069] Add 100 μL of Mucuna sempervirens Hance extract solution with the corresponding concentration to the 96-well plate, and record the drug addition time (aspirate the old PBS in the top row and add an equal amount of drug-containing culture medium as the blank well to eliminate the influence of the drug color).

[0070] 4.CCK-8 assay

[0071] Aspirate the supernatant and replace it with 100 μL of fresh culture medium (to avoid the influence of the drug color on the measurement results; for cells with poor adhesion, do not aspirate with a pipette tip, and a syringe can be used). Add CCK8 in the dark, 10 μL per well.

[0072] The results are as Figures 3 to 7 shown. The IC 50 values of MSE for colon cancer HT-29 cells, lung cancer A549 cells, melanoma A375 cells, and liver cancer Hep3B cells are 51.4, 221.7, 103.4, and 49.5 μg / mL respectively, while the IC 50 value for normal colon cells is 818.2 μg / mL, which is about 16 times the IC 50 of colon cancer HT-29 cells. Therefore, it is suggested that MSE has high selectivity for cancer cells and low toxicity to normal cells.

[0073] Example 3 Evaluation of in vivo anti-cancer activity of freeze-dried powder of Mucuna sempervirens Hance extract

[0074] 1.Purchase and feeding of experimental animals

[0075] Fifteen male BALB / c nude mice, 4 - 5 weeks old, were purchased from Zhuhai Besttone Biotechnology Co., Ltd., with the use license number: SCXK(Yue)2020 - 0051. The nude mice were raised in an SPF-level environment and the experiment started after 3 days of adaptation.

[0076] 2.Construction of subcutaneous transplanted tumors in mice

[0077] (1) Cell culture and preparation

[0078] After digesting, centrifuging, and resuspending HT-29 cells in the logarithmic growth phase, cell counting was performed to calculate the number of culture flasks required. The cells were digested and centrifuged in batches and prepared into a cell concentration of 1.5×10 7 / mL. The cells were resuspended and centrifuged with pre-cooled PBS and repeated 3 times to completely remove residual serum. Discard the PBS, add matrigel dilution gel (matrigel:PBS = 1:1) to resuspend the cells, and pipette repeatedly to make the cells and matrigel gel evenly mixed. The cell suspension was aliquoted into 1.5 mL EP tubes (600 μL / tube) and inserted into an ice box for later use.

[0079] (2) Subcutaneous tumor inoculation

[0080] After entering the animal room, disinfect the operating table with 75% alcohol. Use an insulin syringe to aspirate 100 μL of cell suspension and inject it subcutaneously into the mouse. Select the injection site with rich blood vessels under the armpit. Wipe the injection site with an alcohol cotton ball, insert the needle forward, slowly inject, and slowly withdraw the needle after injection. An obvious bulge can be seen at the injection site.

[0081] (3) Experimental grouping and drug administration

[0082] When the tumor volume of the mice in the experiment reached 50 mm 3 , the successfully modeled mice were randomly divided into 5 groups (model group, low-dose MSE group, medium-dose MSE group, high-dose MSE group, and paclitaxel positive drug group) and drug administration was started. MSE was prepared in Example 1. The drug administration doses were as follows:

[0083] a. Model group: 0.9% normal saline / rat / day, administered by gavage;

[0084] b. Low-dose MSE group: 25 mg / kg / day, administered by gavage;

[0085] c. Medium-dose MSE group: 50 mg / kg / day, administered by gavage;

[0086] d. High-dose MSE group: 100 mg / kg / day, administered by gavage;

[0087] e. PTX positive drug group: 20 mg / kg / week, administered by intraperitoneal injection;

[0088] (4) Mouse sampling

[0089] a. Sampling time: When the tumor volume of any one mouse in the experiment reached 2000 mm 3 , the experiment was terminated and sampling was performed.

[0090] b. Tissue dissection

[0091] After the tumor tissue was dissected, the bloodstains were washed with PBS, and then placed on absorbent paper in sequence to dry the water, weighed and photographed. The tumor was cut into two parts. One part was transferred to an EP tube and stored in a -80 °C refrigerator for molecular biology experiments; the other part was fixed in 4% paraformaldehyde for subsequent immunohistochemical analysis. After the heart, liver, spleen, lung, and kidney tissues were taken out, they were weighed and fixed in 4% paraformaldehyde for subsequent pathological immunohistochemical analysis.

[0092] The experimental procedures were carried out strictly in accordance with the requirements of the animal house of the Zhuhai Institute for Advanced Study in Macau (Ethical Review Number: ZUMRI-ERAE-007-2024).

[0093] (5) Statistical analysis

[0094] The data were expressed as mean ± standard deviation (x±SD), and statistical graphs were drawn using GraphPad Prism 8.0. One-way ANOVA was performed using SPSS 20.0, and further analyzed by LSD or Tamhane's T2. A p value < 0.05 was considered to indicate a significant difference.

[0095] 3. Results of mouse transplanted tumor experiments

[0096] The experimental flow chart is as Figure 8 shown. This animal experiment lasted for 27 days. After 3 days of adaptive feeding of the mice, tumor implantation was started, and the tumor volume was measured daily. On the 5th day, it was found that the tumor volumes of the mice in each group exceeded 50 mm 3 , at which time, the treatment with Mucuna sempervirens Hance extract was immediately started, and the experiment was terminated on the 24th day after administration.

[0097] The photos of the dissected mouse tumors are as Figure 9 shown. From top to bottom are the model group (Model), low-dose group (MSE-L), medium-dose group (MSE-M), high-dose group (MSE-H), and paclitaxel group (PTX). It can be found that when the mice were given the freeze-dried powder of Mucuna sempervirens Hance extract at medium and high doses, the size of the transplanted tumors of mouse colon cancer could be significantly inhibited.

[0098] The growth curve of mouse tumors is as Figure 10 shown. On the 24th day after administration of the freeze-dried powder of Mucuna sempervirens Hance extract, the medium and high-dose groups of the freeze-dried powder of Mucuna sempervirens Hance extract could significantly reduce the tumor volume of mouse colon cancer.

[0099] The statistical graph of mouse tumor weight is as Figure 11 shown. The medium and high-dose groups of the freeze-dried powder of Mucuna sempervirens Hance extract could significantly reduce the weight of mouse colon cancer tumors.

[0100] The statistical chart of the organ indices of mice is as Figure 12 shown. There were no statistically significant differences in the organ indices of the heart, liver, spleen, lungs, and kidneys between the low-dose, medium-dose, and high-dose groups of the freeze-dried powder of Mucuna sempervirens Hance extract and the model group, indicating that while the freeze-dried powder of Mucuna sempervirens Hance extract could inhibit mouse colon cancer tumors, it had no obvious effect on each organ. On the contrary, the positive drug paclitaxel group caused an increase in the liver index, indicating that it caused hepatomegaly in mice.

[0101] The trend chart of the body weight change of mice is as Figure 13 shown. There were no statistically significant differences in the body weights of the mice in the freeze-dried powder of Mucuna sempervirens Hance extract treatment group and the model group during the entire administration and treatment period, indicating that the freeze-dried powder of Mucuna sempervirens Hance extract had no obvious effect on the normal growth of mice. On the contrary, the body weight of the positive drug paclitaxel group decreased significantly, indicating that it had a certain effect on the normal growth of mice.

[0102] The above experiments proved that the freeze-dried powder of Mucuna sempervirens Hance extract of the present invention could exert various anti-tumor effects.

[0103] At present, it has been reported in the prior art that daidzein has the effect of inhibiting the proliferation of liver cancer cells (Fu Yueya, Li Yinglu, Zhao Yao, et al. Daidzein inhibits the proliferation of liver cancer cells through macrophage migration inhibitory factor [J]. Journal of Zhejiang Chinese Medical University, 2023, 47(9): 976-985.), and formononetin has anti-tumor effects (Aliya, Sheik et al. “The potential role of formononetin in cancer treatment: An updated review.” Biomedicine & pharmacotherapy vol. 168 (2023): 115811. doi: 10.1016 / j.biopha.2023.115811). According to the literature reports, the effective administration concentration of daidzein is 50-150 μM, and the daidzein contained in the freeze-dried powder of Mucuna sempervirens Hance extract in the present invention at the effective anti-cancer concentration (49.5 μg / mL) is 0.17 μM; the literature reports that the effective administration concentration of formononetin is 10-300 μM, and the formononetin contained in the freeze-dried powder of Mucuna sempervirens Hance extract in the present invention at the effective anti-cancer concentration (49.5 μg / mL) is 0.15 μM; the literature reports (Hou Qian, Li Weiwei, Zhu Xiaoling, et al. Effects of estradiol and dihydroxyisoflavone on the cell cycle and proliferation activity of breast cancer MDA-MB-231 cells [J]. Science Technology and Engineering, 2006, (17): 2644-2646.) that the effective administration concentration of 3,7-dihydroxyisoflavone is 10-100 μM. The 3,7-dihydroxyisoflavone contained in the freeze-dried powder of Mucuna sempervirens Hance extract in the present invention at the effective anti-cancer concentration (49.5 μg / mL) is 0.31 μM. That is, the contents of daidzein, formononetin, and 3,7-dihydroxyisoflavone in the freeze-dried powder of Mucuna sempervirens Hance extract in the present invention are relatively low and cannot achieve the effective anti-cancer effect. Therefore, daidzein, formononetin, and 3,7-dihydroxyisoflavone in the freeze-dried powder of Mucuna sempervirens Hance extract in the present invention can be used as the index components of the extract, but not the main active components.

[0104] The embodiments of the present invention have been described in detail above in conjunction with the accompanying drawings. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those of ordinary skill in the art, various changes can be made without departing from the purpose of the present invention. In addition, without conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

Claims

1. Application of Gastrodia elata or its extract in the preparation of anti-tumor drugs.

2. The use according to claim 1, characterized in that: The extract is an alcohol extract of the stem of Glehnia littoralis.

3. The use according to claim 1, characterized in that: The tumor includes at least one of colon cancer, lung cancer, melanoma and liver cancer.

4. The use according to claim 2, characterized in that: The alcohol includes at least one of methanol, ethanol and propanol.

5. The use according to claim 3, characterized in that: The extraction method of the extract includes ultrasonic method, reflux method, decoction method, immersion method, percolation method, microwave extraction method or CO2 supercritical extraction method.

6. The use according to claim 2, characterized in that: The extraction method of the extract comprises the following steps: crushing the stems of Glehnia littoralis, mixing with an alcohol solution, and extracting under boiling conditions.

7. The use according to claim 6, characterized in that: The concentration of the alcohol solution is 60 v / v% to 95 v / v%.

8. The use according to any one of claims 1 to 7, characterized in that: The drug also includes pharmaceutically acceptable excipients.

9. The use according to claim 8, characterized in that: The pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrities, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, and carriers.

10. The use according to any one of claims 1 to 7, characterized in that: The dosage forms of the drug include capsules, tablets, pills, injections, tinctures, suppositories, powders, granules, oral liquid preparations, lyophilized preparations, drop pills, sustained-release preparations, controlled-release tablets, suspensions, aerosols, sprays, extracts, syrups or plasters.

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