Traditional Chinese medicine composition with anti-tumor function and application thereof

Abstract

The invention provides a traditional Chinese medicine composition with an anti-tumor function and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 8-12 parts of radix scutellariae, 12-18 parts of radix paeoniae alba, 8-12 parts of ginger processed cortex magnoliae officinalis, 8-12 parts of fructus aurantii, 8-12 parts of pericarpium citri reticulatae, 8-12 parts of radix puerariae, 8-12 parts of radix bupleuri, 8-12 parts of liquorice, 12-18 parts of codonopsis pilosula, 25-35 parts of radix astragali, 25-35 parts of actinidia valvata, 25-35 parts of oldenlandia diffusa, 25-35 parts of radix actinidiae chinensis, 25-35 parts of herba patriniae and 25-35 parts of semen coicis. The traditional Chinese medicine composition has direct anti-tumor activity, can significantly enhance the treatment effect of chemotherapeutic drugs and / or immune checkpoint inhibitors, and provides an effective means for comprehensive treatment of tumors.

Description

Technical Field

[0001] This application belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition with anti-tumor function and its application. Background Technology

[0002] Malignant tumors are among the most serious diseases threatening human health. Currently, the main treatment methods in modern medicine include surgery, radiotherapy, chemotherapy, and immunotherapy. Chemotherapy and immunotherapy have become core treatment options for mid-to-late-stage tumors. However, chemotherapy drugs suffer from poor selectivity, significant toxic side effects (such as bone marrow suppression, gastrointestinal reactions, and liver and kidney damage), and a high risk of drug resistance, severely impacting patients' quality of life and treatment adherence. In recent years, while immunotherapy, represented by immune checkpoint inhibitors, has made breakthrough progress, its overall response rate is limited, and it may induce immune-related adverse reactions, with some patients developing primary or secondary drug resistance. Faced with these challenges, traditional Chinese medicine (TCM) has demonstrated unique advantages in the comprehensive treatment of tumors. Numerous clinical practices have shown that combining TCM with chemotherapy and immunotherapy can potentially achieve a synergistic effect of "reducing toxicity and increasing efficacy," that is, mitigating the toxic side effects of Western medicine treatments while enhancing their anti-tumor efficacy.

[0003] Huangqin Houpu Decoction, first recorded in the ancient and modern medical text *Gujin Yiche*, is a traditional Chinese medicine formula composed of eight herbs: Scutellaria baicalensis, Paeonia lactiflora (bran), Magnolia officinalis (ginger), Citrus aurantium (bran), Citrus reticulata (tangerine peel), Pueraria lobata (kudzu root), Bupleurum chinense (bupleurum), and Glycyrrhiza uralensis (prepared). To date, no reports have documented the use of modified Huangqin Houpu Decoction in the preparation of anti-tumor drugs or in enhancing the efficacy of tumor treatment. Summary of the Invention

[0004] The purpose of this application is to provide a traditional Chinese medicine composition with anti-tumor function, which not only has strong anti-tumor activity, but also has a synergistic effect with conventional therapies in anti-tumor treatment.

[0005] This invention provides a traditional Chinese medicine composition comprising the following raw materials in parts by weight: 8-12 parts of Scutellaria baicalensis, 12-18 parts of Paeonia lactiflora, 8-12 parts of Magnolia officinalis, 8-12 parts of Citrus aurantium, 8-12 parts of Citrus reticulata peel, 8-12 parts of Pueraria lobata, 8-12 parts of Bupleurum chinense, 8-12 parts of Glycyrrhiza uralensis, 12-18 parts of Codonopsis pilosula, 25-35 parts of Astragalus membranaceus, 25-35 parts of Panax ginseng, 25-35 parts of Hedyotis diffusa, 25-35 parts of Actinidia chinensis root, 25-35 parts of Patrinia scabiosaefolia, and 25-35 parts of Coix lacryma-jobi.

[0006] Preferably, the ingredients are made from the following parts by weight: 9-11 parts of Scutellaria baicalensis, 13-16 parts of Paeonia lactiflora, 9-11 parts of Magnolia officinalis, 9-11 parts of Citrus aurantium, 9-11 parts of Citrus reticulata, 9-11 parts of Pueraria lobata, 9-11 parts of Bupleurum chinense, 9-11 parts of Glycyrrhiza uralensis, 13-16 parts of Codonopsis pilosula, 28-33 parts of Astragalus membranaceus, 28-33 parts of Panax ginseng, 28-33 parts of Hedyotis diffusa, 28-32 parts of Actinidia chinensis root, 28-32 parts of Patrinia scabiosaefolia, and 28-32 parts of Coix lacryma-jobi.

[0007] Preferably, it is made from the following raw materials in parts by weight: 10 parts Scutellaria baicalensis, 15 parts Paeonia lactiflora, 10 parts Magnolia officinalis, 10 parts Citrus aurantium, 10 parts Citrus reticulata, 10 parts Pueraria lobata, 10 parts Bupleurum chinense, 10 parts Glycyrrhiza uralensis, 15 parts Codonopsis pilosula, 30 parts Astragalus membranaceus, 30 parts Panax quinquefolius, 30 parts Hedyotis diffusa, 30 parts Actinidia chinensis root, 30 parts Patrinia scabiosaefolia, and 30 parts Coix lacryma-jobi.

[0008] This invention provides a method for preparing the traditional Chinese medicine composition, wherein the raw materials are mixed and then subjected to reflux extraction, and the extract is collected to obtain the traditional Chinese medicine composition.

[0009] Preferably, the solvent used for heating and reflux extraction includes water or an aqueous solution of 70 vol% to 99 vol% ethanol; The water extraction temperature is 92~102℃; The extraction temperature of the 70 vol%–99 vol% ethanol aqueous solution is 98℃–102℃ or 78℃–90℃. This invention provides the application of the traditional Chinese medicine composition, the traditional Chinese medicine composition prepared by the preparation method, or the traditional Chinese medicine composition combined with chemotherapy drugs and / or immune checkpoint inhibitors in the preparation of antitumor drugs.

[0010] This invention provides the application of the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method in the preparation of drugs that enhance the anti-tumor efficacy of chemotherapy drugs and / or immune checkpoint inhibitors.

[0011] Preferably, the tumor is selected from at least one of colorectal cancer, lung cancer, stomach cancer, liver cancer, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, kidney cancer, bladder cancer, esophageal cancer, glioma, melanoma, nasopharyngeal carcinoma, thyroid cancer, osteosarcoma, gallbladder cancer, and soft tissue sarcoma.

[0012] This invention provides an antitumor drug, the active ingredient of which includes the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method.

[0013] This invention provides a traditional Chinese medicine composition comprising the following raw materials in parts by weight: 8-12 parts Scutellaria baicalensis, 12-18 parts Paeonia lactiflora, 8-12 parts Magnolia officinalis, 8-12 parts Citrus aurantium, 8-12 parts Citrus reticulata, 8-12 parts Pueraria lobata, 8-12 parts Bupleurum chinense, 8-12 parts Glycyrrhiza uralensis, 12-18 parts Codonopsis pilosula, 25-35 parts Astragalus membranaceus, 25-35 parts Panax quinquefolius, 25-35 parts Hedyotis diffusa, 25-35 parts Actinidia chinensis root, 25-35 parts Patrinia scabiosaefolia, and 25-35 parts Coix lacryma-jobi. This traditional Chinese medicine composition is an optimized and improved version of the classic formula Huangqin Houpu Decoction. Results show that this composition has a significant advantage over Huangqin Houpu Decoction in inhibiting the proliferation of colorectal cancer tumors. Experiments show that the tumor inhibition rate of Huangqin Houpu Decoction at medium concentration is 30.1%, and at high concentration it is 52.7%. The traditional Chinese medicine composition exhibits a tumor inhibition rate of 69.9% at medium concentrations and 79.4% at high concentrations. Simultaneously, the composition significantly enhances the inhibitory effect of chemotherapy regimens on colorectal cancer tumors, demonstrating a synergistic effect (CI value 1.39). Furthermore, it significantly enhances the tumor inhibition effect of immune checkpoint inhibitors, also exhibiting a synergistic effect (CI value 1.59). Therefore, the traditional Chinese medicine composition of this invention demonstrates excellent anti-tumor activity and a synergistic sensitizing effect with chemotherapeutic drugs and / or immune checkpoint inhibitors, significantly enhancing the anti-tumor efficacy of the aforementioned therapies. This indicates that the traditional Chinese medicine composition can not only serve as a direct anti-tumor drug but also as a highly promising chemotherapeutic and immunotherapeutic sensitizer, providing an innovative solution for the comprehensive treatment of colorectal cancer. Attached Figure Description

[0014] Figure 1 The results show the comparative effects of different concentrations of traditional Chinese medicine compositions on inhibiting tumor growth in the MC38 subcutaneous xenograft model of colorectal cancer; A shows the results of traditional Chinese medicine composition 1 prepared in Comparative Example 1, and B shows the results of traditional Chinese medicine composition 2 prepared in Example 1. Figure 2 The graphs show the tumor growth in two colorectal cancer tumor models: the blank group and the group with different concentrations of traditional Chinese medicine composition. A is the HCT116 nude mouse subcutaneous xenograft model, and B is the MC38 black mouse subcutaneous xenograft model. Figure 3 The tumor growth pattern of the FOLFOX chemotherapy regimen enhanced by the Chinese herbal combination (MC38 black mouse subcutaneous xenograft model). Figure 4 This image shows the tumor growth of the immune checkpoint inhibitor PD-1 enhanced by a traditional Chinese medicine composition (MC38 black mouse subcutaneous xenograft model). Detailed Implementation

[0015] This invention provides a traditional Chinese medicine composition comprising the following raw materials in parts by weight: 8-12 parts of Scutellaria baicalensis, 12-18 parts of Paeonia lactiflora, 8-12 parts of Magnolia officinalis, 8-12 parts of Citrus aurantium, 8-12 parts of Citrus reticulata peel, 8-12 parts of Pueraria lobata, 8-12 parts of Bupleurum chinense, 8-12 parts of Glycyrrhiza uralensis, 12-18 parts of Codonopsis pilosula, 25-35 parts of Astragalus membranaceus, 25-35 parts of Panax ginseng, 25-35 parts of Hedyotis diffusa, 25-35 parts of Actinidia chinensis root, 25-35 parts of Patrinia scabiosaefolia, and 25-35 parts of Coix lacryma-jobi.

[0016] In this invention, the traditional Chinese medicine composition is an optimized and improved version of the classic formula Huangqin Houpu Decoction. The herbal composition described herein is based on the principle of supporting the body's resistance and eliminating pathogenic factors. The specific relationships between the principal, assistant, and adjuvant herbs are as follows: The principal herbs, Astragalus membranaceus and Codonopsis pilosula, greatly replenish vital energy and strengthen the body's resistance, enhancing the body's disease-fighting ability and immune reserves. Simultaneously, Codonopsis pilosula, Hedyotis diffusa, and Actinidia chinensis root clear heat and detoxify, dispersing nodules and attacking toxins, directly targeting "cancer toxins" and laying the foundation for "supporting the body's resistance and eliminating pathogenic factors." The assistant herbs, Patrinia scabiosaefolia, Coix lacryma-jobi, and Scutellaria baicalensis, clear heat and eliminate dampness, resolving the damp-heat internal environment conducive to tumor growth. Magnolia officinalis promotes qi circulation, relieves fullness, and unblocks the middle jiao, clearing obstacles for treatment. The adjuvant herbs, Citrus aurantium and Citrus reticulata peel, regulate qi and relieve bloating; Bupleurum chinense and Paeonia lactiflora harmonize the liver and spleen to relieve pain and soothe emotions; and Pueraria lobata promotes qi circulation and stops diarrhea to protect the spleen and stomach, comprehensively improving the patient's symptoms and quality of life. The guiding herb, Glycyrrhiza uralensis, harmonizes the other herbs, replenishes qi, and detoxifies, ensuring synergistic effects and a balanced approach to both attacking and tonifying. The entire formula integrates immune support, direct anti-tumor action, and improvement of the internal environment.

[0017] In this invention, the traditional Chinese medicine composition preferably comprises the following raw materials in parts by weight: 9-11 parts of Scutellaria baicalensis, 13-16 parts of Paeonia lactiflora, 9-11 parts of Magnolia officinalis, 9-11 parts of Citrus aurantium, 9-11 parts of Citrus reticulata peel, 9-11 parts of Pueraria lobata, 9-11 parts of Bupleurum chinense, 9-11 parts of Glycyrrhiza uralensis, 13-16 parts of Codonopsis pilosula, 28-33 parts of Astragalus membranaceus, 28-33 parts of Panax quinquefolius, 28-33 parts of Hedyotis diffusa, and 2 parts of Actinidia chinensis root. The herbal composition comprises 8-32 parts of *Patrinia scabiosaefolia*, 28-32 parts of *Patrinia scabiosaefolia*, and 28-32 parts of *Coix lacryma-jobi*. It may also be prepared from the following raw materials in parts by weight: 10 parts of *Scutellaria baicalensis*, 15 parts of *Paeonia lactiflora*, 10 parts of *Magnolia officinalis*, 10 parts of *Citrus aurantium*, 10 parts of *Citrus reticulata*, 10 parts of *Pueraria lobata*, 10 parts of *Bupleurum chinense*, 10 parts of *Glycyrrhiza uralensis*, 15 parts of *Codonopsis pilosula*, 30 parts of *Astragalus membranaceus*, 30 parts of *Panax notoginseng*, 30 parts of *Hedyotis diffusa*, 30 parts of *Actinidia chinensis* root, 30 parts of *Patrinia scabiosaefolia*, and 30 parts of *Coix lacryma-jobi*. This invention does not impose any particular limitation on the preparation method of the herbal composition; any herbal raw materials well-known in the art can be used.

[0018] This invention provides a method for preparing the traditional Chinese medicine composition, wherein the raw materials are mixed and then subjected to reflux extraction, and the extract is collected to obtain the traditional Chinese medicine composition.

[0019] In this invention, the solvent used for the heating reflux extraction preferably includes water or a 70 vol% to 99 vol% aqueous ethanol solution. The extraction temperature of the water is 92 to 102°C, and can be 100°C. The extraction temperature of the 70 vol% to 99 vol% aqueous ethanol solution is 98°C to 102°C or 78°C to 90°C, and can be 78°C to 90°C. The concentration of the aqueous ethanol solution is preferably 75% to 85%. The number of extractions is preferably 1 to 5 times, and can be 2 to 4 times, or can be 3 times. The extraction time for each extraction is preferably 0.5 to 3 hours, and can be 1 to 2 hours, or can be 1.5 hours. During the heating reflux extraction, the preferred ratio of the total mass of the solvent to the total mass of the raw material is 3 to 15:1, and can be 4 to 6:1. The raw material is preferably pulverized to below 20 mesh before extraction to ensure sufficient extraction of the active ingredients.

[0020] In this invention, after extraction, the extracts are collected, combined, concentrated, and dried.

[0021] This invention provides the application of the traditional Chinese medicine composition, the traditional Chinese medicine composition prepared by the preparation method, or the traditional Chinese medicine composition combined with chemotherapy drugs and / or immune checkpoint inhibitors in the preparation of antitumor drugs.

[0022] This invention provides the application of the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method in the preparation of drugs that enhance the anti-tumor efficacy of chemotherapy drugs and / or immune checkpoint inhibitors.

[0023] In this invention, the tumor preferably includes one or more of the following: colorectal cancer, lung cancer, stomach cancer, liver cancer, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, kidney cancer, bladder cancer, esophageal cancer, glioma, melanoma, nasopharyngeal carcinoma, thyroid cancer, osteosarcoma, gallbladder cancer, and soft tissue sarcoma. The colorectal cancer may be colon cancer.

[0024] In this invention, the chemotherapeutic drugs preferably include at least one of the following: platinum-based drugs, fluorouracil-based drugs, taxane-based drugs, topoisomerase inhibitors, or alkylating agents, which may be oxaliplatin or fluorouracil. The immune checkpoint inhibitors are preferably antibody drugs targeting PD-1, PD-L1, or CTLA-4.

[0025] This invention provides an antitumor drug, the active ingredient of which includes the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method.

[0026] In this invention, the active ingredient of the antitumor drug preferably further includes chemotherapeutic drugs and / or immune checkpoint inhibitors. In this invention, the antitumor drug also comprises pharmaceutically acceptable excipients selected from one or more of fillers, disintegrants, binders, lubricants, flow aids, coating materials, solvents, solubilizers, emulsifiers, thickeners, stabilizers, preservatives, flavoring agents, colorants, and pH adjusters.

[0027] The present invention does not limit the dosage form of the drug, which includes compressed tablets, dispersible tablets, enteric-coated tablets, capsules, granules, pills, drop pills, emulsions, nanoparticles, liposomes, powders, oral liquids, or injections.

[0028] The following detailed description, in conjunction with embodiments, illustrates a traditional Chinese medicine composition with anti-tumor function provided by the present invention and its application, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0029] Comparative Example 1 A method for preparing a traditional Chinese medicine composition (Huang Qin Hou Po Tang). Accurately weigh the following Chinese medicinal materials: Scutellaria baicalensis, Paeonia lactiflora, Citrus reticulata peel, Bupleurum chinense, Magnolia officinalis, Citrus aurantium, Pueraria lobata, and Glycyrrhiza uralensis in a mass ratio of 7:5:5:4:5:5:5:3, wherein the mass of Scutellaria baicalensis is 21g. Mix the above medicinal materials and extract them three times by heating and reflux with water. The water added each time was 42.4kg, 42.4kg, and 31.8kg respectively, and the extraction time was 1.5 hours, 1.5 hours, and 1 hour respectively. Combine the three extracts, concentrate, and dry to obtain Chinese medicinal composition 1.

[0030] Example 1 A method for preparing a traditional Chinese medicine composition The following herbs were mixed in a mass ratio of 1:1.5:1:1:1:1:1:1:1:1:1.5:3:3:3:3, with 10g of Scutellaria baicalensis. The mixture was heated under reflux with water for three extractions, with water additions of 42.4kg, 42.4kg, and 31.8kg respectively, and extraction times of 1.5 hours, 1.5 hours, and 1 hour respectively. The three extracts were combined, concentrated, and dried to obtain herbal composition 2.

[0031] Example 2 Preparation method of traditional Chinese medicine composition The following herbs were mixed in a mass ratio of 1:1.5:1:1:1:1:1:1:1:1:1.5:3:3:3:3, with 10g of Scutellaria baicalensis. The mixture was extracted twice with 95% vol% ethanol aqueous solution under reflux, using 42.4kg of solvent each time for 2 hours. The two extracts were combined, concentrated, and dried to obtain the herbal composition 3.

[0032] Example 3 Preparation method of traditional Chinese medicine composition Scutellaria baicalensis, Paeonia lactiflora, Magnolia officinalis, Citrus aurantium, Citrus reticulata, Pueraria lobata, Bupleurum chinense, Glycyrrhiza uralensis, Codonopsis pilosula, Astragalus membranaceus, Panax quinquefolius, Hedyotis diffusa, Actinidia chinensis root, Patrinia scabiosaefolia, and Coix lacryma-jobi were mixed in a mass ratio of 1:1.5:1:1:1:1:1:1:1:1.5:3:3:3:3:3, with Scutellaria baicalensis weighing 10g. The herbs were pulverized separately until the particle size was less than 20 mesh, then mixed evenly to obtain the aforementioned traditional Chinese medicine composition 4.

[0033] Experiment Example 4 1. Experimental Materials 1.1 Reagents Comparative Example 1, the traditional Chinese medicine composition 1, was prepared by adding water to prepare medicinal solutions with raw drug concentrations of 1.521 g / ml (medium concentration) and 3.042 g / ml (high concentration).

[0034] The traditional Chinese medicine composition 2 of Example 1 was prepared into medicinal solutions with raw drug concentrations of 1.82 g / ml (low concentration), 3.64 g / ml (medium concentration), and 7.28 g / ml (high concentration) by adding water.

[0035] Each mouse was given 0.2 ml of the solution once a day via gavage.

[0036] 1.2 Cell lines HCT116 and MC38 cell lines were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences.

[0037] 1.3 Experimental Animals The experimental animals were 5-week-old female BALB / c nude mice and C57BL / 6 black mice, weighing 20±2g, purchased from Jiangsu Jicui Pharmaceutical Co., Ltd. All animal handling and research were conducted at the Animal Center of Hangzhou Normal University, and all procedures met the standards of the Animal Ethics Committee. The environment for animal husbandry and management met the requirements of SPF-grade animal experimental facilities, and the animals had free access to water and food.

[0038] 2. Establishment of animal models 2.1 Culture of HCT116 and MC38 colorectal cancer cells HCT116 cells were added to 5A culture medium and placed in a 5% CO2 solution. 2 The cells were cultured in a 37°C incubator, with culture medium 5A containing 10% fetal bovine serum, 100 U / ml sodium penicillin, and 100 U / ml streptomycin. When the HCT116 cells reached approximately 80% confluence, they were digested with 0.25% trypsin containing 0.02% EDTA for 2 minutes. The reaction was terminated with culture medium containing serum. After centrifugation, the cells were passaged at a 1:3 ratio twice a week. HCT116 cells in the logarithmic growth phase were cultured to obtain HCT116 colon cancer cells for later use.

[0039] MC38 cells were added to DMEM culture medium and placed in a container containing 5% CO2. 2 The cells were cultured in a 37°C incubator with DMEM medium containing 10% fetal bovine serum, 100 U / ml sodium penicillin, and 100 U / ml streptomycin. When the MC38 cells reached approximately 80% confluence, they were digested with 0.25% trypsin containing 0.02% EDTA for 2 minutes. The reaction was terminated with culture medium containing serum. After centrifugation, the cells were passaged at a 1:3 ratio twice a week. MC38 cells in the logarithmic growth phase were cultured to obtain MC38 colon cancer cells for later use.

[0040] 2.2 Establishment of nude mouse and black mouse models of colorectal cancer Forty female BALB / c nude mice weighing 15–17 g were selected, and each mouse was subcutaneously injected with 1×10 g of chlorine solution via the lateral ventral region of the forearm. 6 HCT116 colon cancer cells were collected per mouse, and the mice were given a normal diet and water. The growth of subcutaneous tumors in the nude mice was observed visually every day. Tumor formation was observed from the 5th day after modeling, indicating that the colon cancer nude mouse model was successfully established.

[0041] Forty female C57BL / 6 black mice weighing 15–17 g were selected, and each mouse was subcutaneously injected with 5 × 10 g of solution via the lateral ventral region of the forearm. 5 / MC38 colon cancer suspension cells were extracted from each mouse, and then the mice were given a normal diet and water. The growth of subcutaneous tumors in the mice was observed by the naked eye every day. Tumor formation was observed from the third day of modeling, indicating that the colon cancer mouse model was successfully established.

[0042] 2.3 Grouping and Collection of Experimental Animals 2.3.1 Animal Experiments on the Anti-cancer Effects of Traditional Chinese Medicine Compositions: Nude or black mice with intestinal cancer were randomly divided into the following groups: blank group, low-concentration group of traditional Chinese medicine composition 1, medium-concentration group of traditional Chinese medicine composition 1, low-concentration group of traditional Chinese medicine composition 2, medium-concentration group of traditional Chinese medicine composition 2, high-concentration group of traditional Chinese medicine composition 1, and high-concentration group of traditional Chinese medicine composition 2. Drug administration began from the observation of tumor formation (day 5 or 3 of modeling). The blank group was given physiological saline, while the mice in each traditional Chinese medicine composition group were given the corresponding traditional Chinese medicine composition continuously. Two hours after the last administration, the nude or black mice with intestinal cancer in each group were sacrificed, and tumor tissue was collected. A portion of the tumor tissue from each group was then aliquoted into liquid nitrogen and frozen at -80℃. Another portion of the tumor tissue from each group was fixed in formalin for later use.

[0043] 2.3.2 Animal experiment on the synergistic effect of traditional Chinese medicine composition on chemotherapy: Black mice with colorectal cancer were randomly divided into 6 groups, namely blank group, medium concentration group of traditional Chinese medicine composition, FOLFIRI group, FOLFOX group, medium concentration group of traditional Chinese medicine composition + FOLFIRI group and medium concentration group of traditional Chinese medicine composition + FOLFOX group. Drug administration began from the observation of tumor formation (day 3 of modeling). The blank group was given normal saline. The traditional Chinese medicine composition group was given traditional Chinese medicine composition 2 of Example 1, administered by gavage once a day for continuous administration. FOLFIRI group: 5-FU (22.5 mg / kg), calcium levofolinate (33.75 mg / kg) were administered on days 1 and 8, and irinotecan (15 mg / kg) were administered on days 2 and 9. FOLFOX group: 5-FU (22.5 mg / kg), calcium levofolinate (33.75 mg / kg) were administered on days 21 and 8, and oxaliplatin (9.375 mg / kg) were administered from days 2 to 9. Two hours after the last administration, the black mice with intestinal cancer in each group were sacrificed and tumor tissues were collected. Then, a portion of the tumor tissue from each group was aliquoted into liquid nitrogen and frozen at -80°C. Another portion of the tumor tissue from each group was fixed in formalin for later use.

[0044] 2.3.3 Animal experiment on the efficacy of traditional Chinese medicine composition in enhancing immunotherapy: Black mice with colorectal cancer were randomly divided into 4 groups: blank group, medium concentration group of traditional Chinese medicine composition, anti-PD-1 group, and medium concentration group of traditional Chinese medicine composition + anti-PD-1 group. Drug administration began from the observation of tumor formation (day 3 of modeling). The blank group was given physiological saline; the traditional Chinese medicine composition group was given traditional Chinese medicine composition 2 from Example 1, administered by gavage once daily for continuous administration; the anti-PD-1 group was injected intraperitoneally every 3 days (50 μg / mouse).

[0045] 3. Experimental Methods 3.1 Tumor volume measurement On the first day of administration, the average tumor size was measured and recorded using calipers, and then measured and recorded every two days thereafter.

[0046] 3.2 Statistical Analysis All data are expressed as mean ± SD. P <0.05 was considered statistically significant. All data were analyzed using the Prism9 statistical software package.

[0047] 4. Experimental Results: This invention established nude and black mouse models of colorectal cancer using HCT116 and MC38 cancer cells. The above experiments evaluated whether the traditional Chinese medicine composition possesses anti-tumor effects and enhances the effects of chemotherapy and immunotherapy. Experimental results are shown below. Figures 1-4 .

[0048] Tumor suppression test results as follows Figure 1 As shown in Figures A and B, the tumor inhibition rate of the medium-concentration traditional Chinese medicine composition 1 was 30.1%, and that of the high-concentration composition was 52.7%. The tumor inhibition rate of the medium-concentration traditional Chinese medicine composition 2 was 69.9%, and that of the high-concentration composition was 79.4%, demonstrating that the optimized traditional Chinese medicine compositions had a higher tumor inhibition rate.

[0049] The tumor-inhibiting results of different concentrations of traditional Chinese medicine composition 2 are as follows: Figure 2 As shown in Figures A and B, compared with the blank group, the traditional Chinese medicine composition 2 of the present invention can significantly inhibit the proliferation of colorectal cancer tumors.

[0050] Animal experiments demonstrating the synergistic effect of traditional Chinese medicine combinations on chemotherapy efficacy, such as... Figure 3 As shown, the traditional Chinese medicine composition 2 of the present invention can significantly enhance the inhibitory effect of the chemotherapy regimen FOLFOX on colorectal cancer tumors and has a synergistic effect, with a CI value of 1.39.

[0051] Animal experiments demonstrating the synergistic effect of traditional Chinese medicine combinations on immunotherapy, such as... Figure 4 As shown, the traditional Chinese medicine composition 2 of the present invention can significantly enhance the inhibitory effect of the immune checkpoint inhibitor PD-1 on colorectal cancer tumors and has a synergistic effect, with a CI value of 1.59.

[0052] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, It is made from the following ingredients in parts by weight: Scutellaria baicalensis 8-12 parts, Paeonia lactiflora 12-18 parts, Magnolia officinalis 8-12 parts, Citrus aurantium 8-12 parts, Citrus reticulata 8-12 parts, Pueraria lobata 8-12 parts, Bupleurum chinense 8-12 parts, Glycyrrhiza uralensis 8-12 parts, Codonopsis pilosula 12-18 parts, Astragalus membranaceus 25-35 parts, Panax ginseng 25-35 parts, Hedyotis diffusa 25-35 parts, Actinidia chinensis root 25-35 parts, Patrinia scabiosaefolia 25-35 parts, and Coix lacryma-jobi 25-35 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, It is made from the following ingredients in parts by weight: Scutellaria baicalensis 9-11 parts, Paeonia lactiflora 13-16 parts, Magnolia officinalis 9-11 parts, Citrus aurantium 9-11 parts, Citrus reticulata 9-11 parts, Pueraria lobata 9-11 parts, Bupleurum chinense 9-11 parts, Glycyrrhiza uralensis 9-11 parts, Codonopsis pilosula 13-16 parts, Astragalus membranaceus 28-33 parts, Panax ginseng 28-33 parts, Hedyotis diffusa 28-33 parts, Actinidia chinensis root 28-32 parts, Patrinia scabiosaefolia 28-32 parts, and Coix lacryma-jobi 28-32 parts.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, It is made from the following ingredients in parts by weight: 10 parts Scutellaria baicalensis, 15 parts Paeonia lactiflora, 10 parts Magnolia officinalis, 10 parts Citrus aurantium, 10 parts Citrus reticulata, 10 parts Pueraria lobata, 10 parts Bupleurum chinense, 10 parts Glycyrrhiza uralensis, 15 parts Codonopsis pilosula, 30 parts Astragalus membranaceus, 30 parts Panax quinquefolius, 30 parts Hedyotis diffusa, 30 parts Actinidia chinensis root, 30 parts Patrinia scabiosaefolia, and 30 parts Coix lacryma-jobi.

4. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The raw materials are mixed and then heated under reflux for extraction. The extract is collected to obtain the traditional Chinese medicine composition.

5. The preparation method according to claim 4, characterized in that, The solvent used for heating and reflux extraction includes water or an aqueous solution of 70 vol% to 99 vol% ethanol; The water extraction temperature is 92~102℃; The extraction temperature of the 70 vol% to 99 vol% ethanol aqueous solution is 98℃ to 102℃ or 78℃ to 90℃.

6. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3, the traditional Chinese medicine composition prepared by the preparation method according to claim 4 or 5, or the traditional Chinese medicine composition in combination with chemotherapy drugs and / or immune checkpoint inhibitors in the preparation of antitumor drugs.

7. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine composition prepared by the preparation method according to claim 4 or 5 in the preparation of a drug for improving the anti-tumor efficacy of chemotherapeutic drugs and / or immune checkpoint inhibitors.

8. The application according to claim 6 or 7, characterized in that, The tumor is selected from at least one of the following: colorectal cancer, lung cancer, stomach cancer, liver cancer, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, kidney cancer, bladder cancer, esophageal cancer, glioma, melanoma, nasopharyngeal carcinoma, thyroid cancer, osteosarcoma, gallbladder cancer, and soft tissue sarcoma.

9. An antitumor drug composition, characterized in that, The active ingredients include the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine composition prepared by the preparation method according to claim 4 or 5.

10. The antitumor pharmaceutical composition according to claim 9, characterized in that, The active ingredients also include chemotherapy drugs and / or immune checkpoint inhibitors.

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