Broad-spectrum combined medicine for treating liver cancer as well as preparation method and application of broad-spectrum combined medicine

Abstract

The invention discloses a broad-spectrum combined medicine for treating liver cancer, which comprises purified water, tripterygium wilfordii alkaloid, tripterygium hypoglaucum alkaloid, chamaejasmine, gelsmium elegans alkaloid, xanthoxylin and various B medicines, and further comprises folic acid, vitamins, copper sulfate, zinc sulfate, manganese sulfate, yeast and penicillin sodium. Through the multi-component, multi-target and multi-path design, the medicine disclosed by the invention shows a potential effect of inhibiting the progress of liver cancer and good safety in cell experiments, animal models and human individual case observation. Cellular immunity and humoral immunity can be enhanced, the treatment cost is lower than that of a traditional treatment scheme, and no pain is caused during treatment.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine, in particular to a broad-spectrum combined medicine for treating liver cancer and its preparation method and application. BACKGROUND

[0002] Liver cancer, especially hepatocellular carcinoma, is one of the common malignant tumors worldwide. It has high incidence and strong concealment, and most patients are in the middle and advanced stages when diagnosed, missing the best surgical opportunity. At present, the treatment methods for liver cancer mainly include surgical resection, hepatic arterial chemoembolization, radiofrequency ablation, targeted drug therapy and immunotherapy, etc. However, these treatment methods generally have the problems of large side effects, easy drug resistance, high cost and limited efficacy for advanced patients.

[0003] Traditional Chinese medicine has accumulated rich experience in the adjuvant therapy of tumors, and some traditional Chinese medicine compounds and active ingredients have been confirmed to have the effects of regulating immunity, inhibiting tumor cell proliferation and inducing apoptosis, etc. For example, tanshinone, curcumin and other ingredients have shown certain anti-liver cancer activity in research. However, the existing traditional Chinese medicine anti-liver cancer preparations are mostly single component, or only focus on one direction of strengthening the body resistance or eliminating evil, which is difficult to cope with the complex pathogenesis of liver cancer, and lack of a broad-spectrum combined medicine which can have multi-target, multi-link synergistic effect and has the effect of attacking and tonifying. SUMMARY

[0004] In view of the above technical deficiencies, the purpose of the present application is to provide a broad-spectrum combined medicine for treating liver cancer and its preparation method and application, so as to solve the problems mentioned in the background art.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: The present invention provides a broad-spectrum combination drug for treating liver cancer, comprising the following components in parts by weight: 100 parts purified water, 38-90 parts Tripterygium wilfordii alkaloids, 38-90 parts Kunming Mountain crabapple alkaloids, 28-85 parts Euphorbia fischeriana toxicum, 28-85 parts Gelsemium elegans alkaloids, 28-85 parts Zanthoxylum bungeanum alkaloids, 16-80 parts Osthol, 16-80 parts Sophora flavescens alkaloids, 16-80 parts Lonicera japonica chlorogenic acid, 16-80 parts Tanshinone, 16-80 parts Curcumin, 16-80 parts Paeoniflorin, and Zanthoxylum bungeanum alkaloids. 16-80 parts of Rehmannia glutinosa extract, 16-80 parts of Artemisia capillaris flavonoids, 16-80 parts of rose volatile oil, 16-80 parts of milk thistle organic acids, 16-80 parts of Cyperus rotundus volatile oil, 16-80 parts of Prunella vulgaris alkaloids, 16-80 parts of Scutellaria barbata alkaloids, 16-80 parts of Selaginella tamariscina alkaloids, 16-80 parts of rhein, 16-80 parts of Ganoderma lucidum polysaccharides, 16-80 parts of Spatholobus suberectus alkaloids, 16-80 parts of Angelica sinensis volatile oil, 16-80 parts of Psoralea corylifolia volatile oil, 16-80 parts of Astragalus membranaceus saponins, 16-80 parts of Aucklandia lappa volatile oil, and 16-80 parts of Magnolia officinalis alkaloids. 0 parts, Areca peel alkaloids 16-80 parts, Sturgeon sterol 16-80 parts, Atractylodes macrocephala volatile oil 16-80 parts, Ophiopogon japonicus glucose 16-80 parts, Dioscorea opposita germanium 16-80 parts, Cassia seed extract 16-80 parts, Citrus reticulata flavonoids 16-80 parts, Lycium barbarum betaine 16-80 parts, Lygodium japonicum chlorogenic acid 16-80 parts, Panax notoginseng saponins 16-80 parts, Costus root lactone 16-80 parts, Amomum villosum volatile oil 16-80 parts, Cistanche deserticola minerals 16-80 parts, Azadirachtin 16-80 parts, Pharbitis nil alkaloids 16-80 parts, Safflower glycoside 16-80 parts, Cynanchum paniculatum phenylacetone 16 -80 parts, Pinellia ternata sitosterol 16-80 parts, Piper longum volatile oil 16-80 parts, Menthol 16-80 parts, Leonurus japonicus trace elements 16-80 parts, Gentiana macrophylla alkaloids 16-80 parts, Taraxacum mongolicum sterol 16-80 parts, Crataegus pinnatifida flavonoids 16-80 parts, Bergamot alcohol 16-80 parts, Phytolacca saponins 16-80 parts, Lycopodium clavatum 16-80 parts; also includes folic acid 0.4-0.8 parts, vitamin 0.05-0.08 parts, copper sulfate 2-10 parts, zinc sulfate 10-16 parts, manganese sulfate 5-10 parts, strychnine 2-8 parts, and sodium penicillin 0.01-0.08 parts.

[0006] Preferably, the vitamins include vitamin B1, vitamin B2, vitamin B6, and vitamin B12.

[0007] Preferably, the dispersion and homogenization process in step c is performed using a high-speed shear emulsifier with a rotation speed of 8000-12000 rpm and a time of 3-10 minutes; the sterilization process in step e is performed by filtration sterilization.

[0008] The broad-spectrum combined medicine for treating liver cancer provided by the present application is applied to oral administration, and is taken half an hour before meals every day, with a total treatment course of 3-8 months.

[0009] The broad-spectrum combined medicine for treating liver cancer provided by the present application is applied to the preparation of medicines for treating liver cancer.

[0010] A preparation method of a broad-spectrum combined medicine for treating liver cancer comprises the following steps: a. providing the ingredients in the weight parts as described in claim 1; b. dissolving the folate, vitamins, copper sulfate, zinc sulfate, manganese sulfate, mother's milk and penicillin sodium in part of the purified water to obtain solution A; c. mixing all other ingredients except those used in step b with the remaining purified water, and performing dispersion homogenization treatment to obtain suspension B; d. mixing solution A and suspension B, stirring uniformly, adjusting pH, and constant volume; e. sterilizing the liquid medicine obtained in step d, and dispensing into unit dosage forms.

[0011] Preferably, the dispersion homogenization treatment in step c adopts a high-speed shearing emulsifier, with a rotation speed of 8000-12000 rpm and a time of 3-10 minutes; and the sterilization treatment in step e is filter sterilization.

[0012] The present application has the following beneficial effects: Multi-target synergistic anti-liver cancer: the present application combines powerful components such as tripterygium alkaloids and kunming mountain tetrodotoxin alkaloids to attack and detoxify and resolve blood stasis, components such as ganoderma lucidum polysaccharide and astragalus saponin to support the body and regulate immunity, and components such as danshensu and curcumin to promote blood circulation and induce apoptosis, forming a synergistic treatment system of “eliminating evil- supporting the body-regulating”, which may inhibit liver cancer progression from multiple pathological links.

[0013] Liver protection and choleretic effect and toxicity reduction and efficacy enhancement: components such as capillaris flavone and silymarin organic acid in the formula have a clear liver protection and choleretic effect, may antagonize the liver toxicity of toxic components such as tripterygium and gelsemium, and optimize drug metabolism by promoting bile excretion, thereby playing a potential role in toxicity reduction and efficacy enhancement.

[0014] Nutritional support and overall regulation: the added folate, B vitamins, trace elements (copper, zinc, manganese) and mother's milk, etc. can provide necessary nutritional support for the body, improve the cachexia state caused by tumors, and enhance patient tolerance and overall function.

[0015] In vitro and in vivo experiments support this finding: In vitro MTT assays showed that the composition significantly inhibited the proliferation of human hepatocellular carcinoma HepG2 cells. More importantly, in the H22 tumor-bearing mouse model, the drug of this invention significantly inhibited tumor growth, improved liver function indicators (such as reducing serum ALT and AST levels), and prolonged the survival of the model animals. Furthermore, no significant systemic toxicity was observed at the experimental dose, preliminarily demonstrating a balance between efficacy and safety.

[0016] In summary, the drug of this invention, through its multi-component, multi-target, and multi-pathway design, has demonstrated potential efficacy and good safety in inhibiting liver cancer progression in cell experiments, animal models, and human case observations. It can enhance cellular and humoral immunity, is less expensive than traditional treatment options, is virtually painless, and its flexible formulation allows for personalized clinical application. Detailed Implementation

[0017] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0018] Example 1: Drug preparation Take 100 parts purified water, 38 parts Tripterygium wilfordii alkaloids, 38 parts Malus kunmingensis alkaloids, 28 parts Euphorbia fischeriana toxicum, 28 parts Gelsemium elegans alkaloids, 28 parts Zanthoxylum bungeanum alkaloids, and various B drugs: Osthol, Sophora flavescens alkaloids, Lonicera japonica chlorogenic acid, Tanshinone, Curcumin, Paeoniflorin, Zanthoxylum bungeanum toxin, Rehmannia glutinosa flavonoids, Artemisia capillaris flavonoids, Rosa rugosa volatile oil, Silybum marianum organic acids, Cyperus rotundus volatile oil, Prunella vulgaris alkaloids, Scutellaria barbata alkaloids, Selaginella tamariscina alkaloids, Emodin, Ganoderma lucidum polysaccharides, Spatholobus suberectus volatile oil, Angelica sinensis volatile oil, Psoralea corylifolia volatile oil, Astragalus membranaceus saponins, Aucklandia lappa volatile oil, Magnolia officinalis alkaloids, Areca catechu alkaloids, Bovine Sixteen parts each of the following ingredients were prepared: styracil, Atractylodes macrocephala volatile oil, Ophiopogon japonicus glucose, Dioscorea opposita germanium, Cassia tora flavonoids, Citrus reticulata flavonoids, Lycium barbarum betaine, Lygodium japonicum chlorogenic acid, Panax notoginseng saponins, Costus root lactone, Amomum villosum volatile oil, Cistanche deserticola minerals, Melia toosendan, Pharbitis nil alkaloids, Safflower glycoside, Cynanchum paniculatum phenylacetone, Pinellia ternata sitosterol, Piper longum volatile oil, Menthol, Leonurus japonicus trace elements, Gentiana macrophylla alkaloids, Taraxacum mongolicum sterol, Crataegus pinnatifida flavonoids, Bergamotol, Phytolacca acinosa saponins, and Lycopodium clavatum. And take folic acid 0.4 parts, vitamin B1 0.01 parts, vitamin B2 0.008 parts, vitamin B6 0.005 parts, vitamin B12 0.002 parts, copper sulfate 2 parts, zinc sulfate 10 parts, manganese sulfate 5 parts, food mother 2 parts, penicillin sodium 0.01 parts.

[0019] Preparation method: Solution A preparation: take about 30 parts of purified water, under stirring, add folic acid, vitamin B group, copper sulfate, zinc sulfate, manganese sulfate, food mother, penicillin sodium in turn, stirring until completely dissolved, ready for use.

[0020] Suspension B preparation: mix all herbal extract powders with the remaining purified water, and process through a high-speed shear emulsifier (8000 rpm, 5 minutes) to form a uniform suspension.

[0021] Total volume and constant volume: slowly add solution A to suspension B under continuous stirring, stir evenly, and add purified water to the total volume of 100 parts.

[0022] Sterilization and sub-packaging: filter the liquid medicine through a 0.22 μm microporous filter to remove bacteria, and sub-packaging in oral liquid bottles under sterile conditions.

[0023] Example 2: Preparation of drugs Take 100 parts of purified water, tripterygium alkaloids 90 parts, Kunming mountain tangerine alkaloids 90 parts, wolf poison 85 parts, hook Hu Man Feng alkaloids 85 parts, and pepper 85 parts, and various B drugs: Osthole, sophora alkaloids, honeysuckle chlorogenic acid, tanshinone, curcumin, paeonol, south saikong pepper toxin, radix rehmanniae glabra, scutellaria flavone, rose volatile oil, silymarin organic acid, volatile oil, summer grass alkaloids, half branch of the plant alkaloids, stone cypress alkaloids, rhein, ganoderma lucidum polysaccharide, radix mori, volatile oil of angelica sinensis, volatile oil of psoralea corylifolia, radix astragali saponins, volatile oil of inula helenium, lycopene, radix stephaniae dielsiana, sterol, volatile oil of atractylodes, radix ophiopogonis glucose, georgia, cassia seed, citrus peel flavone, sea cucumber chlorogenic acid, radix notoginseng saponins, costunolide, volatile oil of piper nigrum, cistanche mineral, xiangxuezi alkaloids, gossypium herb alkaloids, safflower glycosides, xuchangqing phenyl ketone, pinellia ternata sterol, volatile oil of piper longum, menthol, motherwort trace elements, gentian alkaloids, taraxasterol, hawthorn flavone, bergamot alcohol, pokeweed saponins, thunderball 80 parts; And take folic acid 0.8 parts, vitamin B1 0.03 parts, vitamin B2 0.02 parts, vitamin B6 0.015 parts, vitamin B12 0.008 parts, copper sulfate 10 parts, zinc sulfate 16 parts, manganese sulfate 10 parts, food mother 8 parts, penicillin sodium 0.08 parts.

[0024] Preparation method: same as example 1. The formulation has a higher dose and stronger effect, and is suitable for patients with good constitution and severe conditions. Close observation should be made during use.

[0025] Example 3 Preparation of the medicine Take 100 parts of purified water, 65 parts of tripterygium alkaloids, 65 parts of radix kuimingshanhuateng alkaloids, 55 parts of wolf poison, 55 parts of hook Huamengteng alkaloids, 55 parts of zanthoxylum, and various types of B medicine: Osthole, matrine, honeysuckle chlorogenic acid, tanshinone, curcumin, paeonol, nanshanxianhuangteng zanthoxylum toxin, radix rehmanniae glabrae, scutellaria baicalensis georgi, rose volatile oil, silymarin, volatile oil of cyperus rotundus, prunella vulgaris alkaloids, radix isatidis alkaloids, rhein, ganoderma lucidum polysaccharide, radix salviae miltiorrhizae volatile oil, volatile oil of psoralea corylifolia, radix stephaniae dielsiana, lupeol, radix astragali saponins, radix ligustici wallichii volatile oil, radix ophiopogonis glucose, radix polygonati germanium, cassia senna, sea cucumber chlorogenic acid, radix notoginseng saponins, costunol, volatile oil of piper methysticum, clematis acontium alkaloids, cucurbitacins, safflower glycosides, radix stephaniae tetrandrae benzaldehyde, radix pinelliae sterols, menthol, motherwort trace elements, gentiana macrophylla alkaloids, taraxacum sterols, fructus mume volatile oil, bergamot alcohol, phytolaccaceae saponins, and 48 parts of radix mori; Take 0.6 parts of folic acid, 0.02 parts of vitamin B1, 0.015 parts of vitamin B2, 0.01 parts of vitamin B6, 0.005 parts of vitamin B12, 5 parts of copper sulfate, 13 parts of zinc sulfate, 7 parts of manganese sulfate, 5 parts of food mother, 0.05 parts of penicillin sodium.

[0026] Preparation method: same as example 1. The formulation is a balanced formulation, taking into account potential efficacy and safety, and is suitable for most patients.

[0027] Test example 1: evaluation of in vitro anti-liver cancer activity (MTT method) Purpose of the experiment: Quantitative evaluation of the inhibitory effect of the drug on the proliferation of human liver cancer cell line HepG2, and calculation of the half inhibitory concentration (IC50), to provide direct evidence for the in vitro anti-tumor activity of the drug.

[0028] Experimental materials: Cell line: human liver cancer cell HepG2, purchased from American Type Culture Collection (ATCC).

[0029] Test drug: The drug of the present application, prepared according to Example 3 (medium dose formulation). Before use, prepare a stock solution of 100 mg / mL with sterile dimethyl sulfoxide (DMSO) and store at -20°C. Before use, dilute with DMEM medium containing 10% fetal bovine serum to the required working concentration (final DMSO concentration <0.1%, non-toxic to cells).

[0030] Main reagents: DMEM high-glucose medium, fetal bovine serum (FBS), 0.25% trypsin-EDTA digestion solution, penicillin-streptomycin double-antibiotic solution, phosphate buffer (PBS, pH 7.4), MTT reagent (thiazolyl blue, 5 mg / mL, dissolved in PBS).

[0031] Main instruments: CO2 thermostat cell incubator, super-clean workbench, inverted phase-contrast microscope, enzyme marker, centrifuge, hemocytometer.

[0032] Experimental method: Cell culture: HepG2 cells were routinely cultured in a cell incubator at 37°C, 5% CO2 and saturated humidity, using DMEM medium containing 10% FBS and 1% double-antibiotic. Cells in the logarithmic growth phase were used for experiments.

[0033] Cell inoculation: Cells were digested with 0.25% trypsin and the digestion was terminated with serum-containing medium, then blown into a single-cell suspension. The cell density was adjusted to 5x10^4 cells / mL using a hemocytometer. 100 μL (i.e. 5000 cells / well) was inoculated into each well of a 96-well cell culture plate. The culture plate was placed in the incubator for 24 hours of pre-culture to allow the cells to adhere completely.

[0034] Drug treatment: After the cells adhered, the original culture medium was removed. The experimental setup was as follows:

[0035] Blank control group: containing only medium, no cells.

[0036] Negative control group: containing cells and medium, adding an equal volume of 0.1% DMSO solution.

[0037] Experimental group: containing cells, adding medium containing different final concentrations (25, 50, 100, 200 μg / mL) of the drug of the present application, respectively.

[0038] Positive control group: containing cells, adding medium containing 5-fluorouracil (5-FU, final concentration 20 μg / mL).

[0039] Six replicate wells were set for each concentration. 100 μL of the corresponding drug solution was added to each well. The culture plate was returned to the incubator for continued culture for 48 hours.

[0040] MTT assay: After 48 hours of drug treatment, 20 μL of MTT solution (5 mg / mL) was carefully added to each well and incubated for an additional 4 hours. The culture was terminated, and the supernatant in the wells was carefully aspirated. 150 μL of DMSO was added to each well and placed on a shaker for low-speed oscillation for 10 minutes to fully dissolve the purple formazan crystals.

[0041] Absorbance detection and data analysis: The absorbance values (OD values) of each well were measured at a wavelength of 490 nm using an enzyme-labeled instrument. The data was recorded and the cell proliferation inhibition rate was calculated according to the following formula:

[0042] Cell proliferation inhibition rate (%) = [1 - (OD experimental group - OD blank group) / (OD negative control group - OD blank group)] × 100% Using GraphPad Prism 8.0 software, with the drug concentration as the abscissa and the inhibition rate as the ordinate, non-linear regression fitting was performed to calculate the IC50 value. One-way ANOVA was used for comparison between groups, and P < ۰.۰۵ was considered statistically significant.

[0043] Experimental results: As shown in Table 1, the drug of the present invention showed a significant concentration-dependent inhibitory effect on the proliferation of HepG2 cells. At a concentration of 200 μg / mL, the inhibition rate was over 90%. After calculation, its IC50 value was 68.5 μg / mL. The inhibition rate of the positive control drug 5-FU (20 μg / mL) was 78.3%. The results showed that the drug of the present invention had definite anti-human liver cancer cell activity in vitro.

[0044] Table 1: Inhibition rate of the drug of the present invention on the proliferation of HepG2 cells (n = 6, X ± SD) Table 1 Test Example 2: In vivo anti-hepatocarcinoma pharmacodynamic study (H22 tumor-bearing mouse model) Experimental purpose: Verify the inhibitory effect of the drug of the present invention on the growth of liver cancer in vivo at the animal level, and preliminarily evaluate its effect on liver function and safety.

[0045] Experimental materials: Animals: Healthy ICR mice, male, SPF grade, weighing 18 - 22 g, provided by the Experimental Animal Center of a certain university [License number: SCXK (Shanghai) 2018 - 0004]. All animal experiments were conducted in accordance with the national regulations on the welfare and ethics of experimental animals and approved by the Animal Ethics Committee of our unit.

[0046] Tumor strain: Mouse H22 liver cancer ascites tumor strain, donated by a certain research institute.

[0047] Test drug: Drug of the present application, Example 1 (low dose formulation) and Example 2 (high dose formulation).

[0048] Positive control drug: Sorafenib, prepared into suspension with 0.5% sodium carboxymethyl cellulose solution.

[0049] Main reagent: ALT, AST detection kit.

[0050] Main instrument: Electronic analytical balance, tissue homogenizer, automatic biochemical analyzer.

[0051] Experimental method: Tumor preparation and animal model establishment: Take H22 ascitic tumor mice with good growth after 7 days of inoculation, and kill them by cervical dislocation, and extract the milky white ascites under sterile operation. Dilute with sterile normal saline, and count the viable cell number by trypan blue exclusion method > 95%. Adjust the cell concentration to 1×10^7 cells / mL. Inoculate 0.2 mL of cell suspension subcutaneously in the right anterior axillary of each mouse.

[0052] Grouping and administration: 24 hours after inoculation, the tumor-bearing mice were randomly divided into 4 groups, 10 in each group.

[0053] Model control group: Intragastrically administered with the same volume of normal saline.

[0054] Positive control group: Intragastrically administered with sorafenib (30 mg / kg / d).

[0055] Low-dose group of the drug of the present application: Intragastrically administered with the liquid of Example 1 (5 mL / kg / d).

[0056] High-dose group of the drug of the present application: Intragastrically administered with the liquid of Example 2 (10 mL / kg / d).

[0057] Administer once a day, continuously for 14 days. Measure the body weight and tumor diameter (vernier caliper) of the mice every 3 days.

[0058] Specimen collection and processing: Tumor weighing: 24 hours after the last administration, weigh the mice, kill the mice by cervical dislocation, completely strip the tumor tissue, weigh the tumor, and calculate the tumor inhibition rate.

[0059] Tumor inhibition rate (%) = (1 - experimental group average tumor weight / model group average tumor weight) × 100% Serum preparation and liver function detection: Enucleate the eyeball to take blood, and after the blood is left to stand for 30 minutes, centrifuge at 3000 rpm for 15 minutes to separate the serum. Strictly follow the kit instructions to operate, and detect the serum ALT and AST activity on the automatic biochemical analyzer.

[0060] Survival observation: Another batch of tumor-bearing mice was divided into groups according to the above method, and was not killed, and the natural survival time was continuously observed and recorded, the survival curve was drawn, and the median survival time was calculated.

[0061] Statistical analysis: All data were expressed as mean ± standard deviation, one-way ANOVA was used for statistical analysis by SPSS 22.0 software, and LSD-t test was used for comparison between groups. P<0.05 was considered statistically significant.

[0062] Experimental results: General state observation: The mice in the model control group showed signs of cachexia such as decreased activity, arching back and dull fur in the later stage. The mice in each drug group, especially the drug group of the application, showed lighter signs, and the mental state and activity were relatively better.

[0063] Effect on body weight: During the experiment, the body weight of the mice in the model control group increased slowly. The body weight of the mice in the positive control group and the drug group of the application increased steadily, and there was no significant difference compared with the model group, indicating that the drug did not show obvious systemic toxicity under the experimental period and dose.

[0064] Tumor inhibition effect: As shown in Table 2, compared with the model control group, the positive control group and the low and high dose groups of the drug of the application could significantly inhibit tumor growth, and the tumor inhibition rates were 56.6%, 36.0% and 48.1% respectively, and the difference was extremely statistically significant (P<0.01).

[0065] Effect on liver function: As shown in Table 2, the serum ALT and AST levels of the mice in the model control group were significantly increased, indicating that the liver cancer load caused obvious liver damage. Compared with the model group, the ALT and AST levels of each drug group were significantly decreased (P<0.05 or P<0.01), and the protective effect of the high dose group of the drug of the application was particularly obvious, even better than that of the positive control group, indicating that the drug of the application had a significant protective effect on liver function while inhibiting tumors.

[0066] Effect on survival time: Survival analysis showed that the median survival time of the mice in the model control group was 28 days. The median survival times of the mice in the positive control group, the low and high dose groups of the drug of the application were 38 days, 35 days and 41 days respectively. Compared with the model group, each drug group could significantly prolong the survival time of tumor-bearing mice.

[0067] Table 2: Tumor inhibition effect and liver function of the drug of the application on H22 tumor-bearing mice (n=10, X ± SD) Note: Compared with the model control group, P<0.05, *P<0.01.

[0068] Table 2 Test Example 3: Preliminary evaluation of drug safety and typical medical cases Safety observation: In the in vivo experiment of Test Example 2, the mice in each administration group were observed daily, and their fur color, activity, and diet were normal, and their body weight increased steadily, without any acute toxicity reactions such as death or convulsions, which preliminarily indicated that the drug had good safety at the experimental dose.

[0069] Typical medical cases (examples): Case 1: Mr. Zhou, 52 years old, was diagnosed with advanced primary liver cancer in 2019. He could not tolerate conventional chemotherapy due to poor liver function. Under the guidance of the doctor, he orally took 300 milliliters of the pharmaceutical liquid prepared according to Example 3 of the present application (in two doses) every day. After three months of reexamination, CT showed that the liver tumor had shrunk by about 30%, the serum AFP level had decreased significantly, and symptoms such as fatigue and poor appetite had improved significantly.

[0070] Case 2: Ms. Sun, 48 years old, was diagnosed with liver cancer with lung metastasis in 2020. While using supportive treatment, she also took the pharmaceutical liquid prepared according to Example 2 of the present application (reduced to 200 milliliters per day). After six months of reexamination, the liver lesions were stable, some lung metastatic lesions were slightly reduced, the quality of life was maintained, and she is still alive with the tumor.

[0071] Case 3: Mr. Zhao, 61 years old, was diagnosed with liver cancer recurrence after surgery in 2018. To prevent recurrence, he has been taking the pharmaceutical liquid prepared according to Example 1 of the present application for a long time, 150 milliliters per day. Regular reexamination has been carried out for more than three years, and no new lesions have been found, and the liver function indicators have been maintained within the normal range.

[0072] Note: The above medical cases are only individual case observations, and there are individual differences, which do not represent the universal therapeutic effect.

[0073] Obviously, those skilled in the art can make various modifications and variations to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application fall within the scope of the claims of the present application and their equivalents, the present application also intends to include these modifications and variations.

Claims

1. A broad-spectrum combination drug for treating liver cancer, characterized in that, The ingredients include the following components by weight: 100 parts purified water, 38-90 parts Tripterygium wilfordii alkaloids, 38-90 parts Kunming Mountain crabapple alkaloids, 28-85 parts Euphorbia fischeriana alkaloids, 28-85 parts Gelsemium elegans alkaloids, 28-85 parts Zanthoxylum bungeanum alkaloids, 16-80 parts Osthol, 16-80 parts Sophora flavescens alkaloids, 16-80 parts Lonicera japonica chlorogenic acid, 16-80 parts Tanshinone, 16-80 parts Curcumin, 16-80 parts Paeoniflorin, 16-80 parts Adenophora stricta Zanthoxylum bungeanum alkaloids, 16-80 parts Rehmannia glutinosa flavonoids, 16-80 parts Rosa rugosa florida flavonoids, and rose petals. Volatile oil 16-80 parts, milk thistle organic acid 16-80 parts, Cyperus rotundus volatile oil 16-80 parts, Prunella vulgaris alkaloids 16-80 parts, Scutellaria barbata alkaloids 16-80 parts, Selaginella tamariscina alkaloids 16-80 parts, rhein 16-80 parts, Ganoderma lucidum polysaccharide 16-80 parts, Spatholobus suberectin 16-80 parts, Angelica sinensis volatile oil 16-80 parts, Psoralea corylifolia volatile oil 16-80 parts, Astragalus membranaceus saponins 16-80 parts, Aucklandia lappa volatile oil 16-80 parts, Magnolia officinalis alkaloids 16-80 parts, Areca catechu alkaloids 16-80 parts, Sturgeon sterol 1 6-80 parts, Atractylodes macrocephala volatile oil 16-80 parts, Ophiopogon japonicus glucose 16-80 parts, Dioscorea opposita germanium 16-80 parts, Cassia seed extract 16-80 parts, Citrus reticulata flavonoids 16-80 parts, Lycium barbarum betaine 16-80 parts, Lygodium japonicum chlorogenic acid 16-80 parts, Panax notoginseng saponins 16-80 parts, Aucklandia lappa lactone 16-80 parts, Amomum villosum volatile oil 16-80 parts, Cistanche deserticola minerals 16-80 parts, Azadirachtin 16-80 parts, Pharbitis nil alkaloids 16-80 parts, Safflower glycoside 16-80 parts, Cynanchum paniculatum phenylacetone 16-80 parts, Pinellia ternata sitosterol 1 6-80 parts, Piper longum volatile oil 16-80 parts, menthol 16-80 parts, Leonurus japonicus trace elements 16-80 parts, Gentiana macrophylla alkaloids 16-80 parts, taraxasterol 16-80 parts, hawthorn flavonoids 16-80 parts, bergamot alcohol 16-80 parts, phytolacca saponins 16-80 parts, and strychnine 16-80 parts; also includes folic acid 0.4-0.8 parts, vitamins 0.05-0.08 parts, copper sulfate 2-10 parts, zinc sulfate 10-16 parts, manganese sulfate 5-10 parts, glutenin 2-8 parts, and sodium penicillin 0.01-0.08 parts.

2. The broad-spectrum combination drug for treating liver cancer as described in claim 1, characterized in that, The vitamins mentioned include vitamin B1, vitamin B2, vitamin B6, and vitamin B12.

3. The method of claim 1, wherein the preparation of the broad-spectrum combined medicine for treating liver cancer is characterized in that, Includes the following steps: a. To provide each component in the weight proportions described in claim 1; b. Dissolve the folic acid, vitamins, copper sulfate, zinc sulfate, manganese sulfate, digestive enzymes, and sodium penicillin in a portion of the purified water to obtain solution A; c. Mix all other components except those used in step b with the remaining purified water, and then disperse and homogenize to obtain suspension B; d. Mix solution A with suspension B, stir well, adjust the pH, and bring to a final volume; e. Sterilize the drug solution obtained in step d and dispense it into unit dosage forms.

4. The method of claim 3, wherein the preparation of the broad-spectrum combined medicine for treating liver cancer is characterized in that, The dispersion homogenization treatment in the step c is carried out by using a high-speed shearing emulsifier, the rotating speed is 8000-12000 rpm, and the time is 3-10 minutes; the sterilization treatment in the step e is carried out by filtering sterilization.

5. The broad-spectrum combination drug for treating liver cancer as described in claim 1, characterized in that, It is applied to oral administration, and is taken half an hour before meal every day, and the total treatment course is 3-8 months.

6. The broad-spectrum combination drug for treating liver cancer as described in claim 1, characterized in that, The application relates to a medicine preparation for treating liver cancer.

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