A traditional Chinese medicine composition with tumor inhibition effect and a preparation method thereof

Abstract

The present application relates to the technical field of antitumor drugs, and discloses a traditional Chinese medicine composition with tumor inhibition and a preparation method thereof, which is prepared from the following raw medicinal materials in parts by mass: raw dried ginseng 25-35 parts, rhubarb 8-12 parts, astragalus 25-35 parts, Chinese yam 25-35 parts, white atractylodes 12-18 parts, radix scutellariae 25-35 parts, citri sarcodactylis 12-18 parts, apricot kernel 10-14 parts, Zhejiang fritillary bulb 12-18 parts, silkworm chrysalis 12-18 parts, soapberry spine 12-18 parts, radix pinelliae 12-18 parts, zedoary 8-12 parts, sparganium 8-12 parts, and turtle shell 25-35 parts. The traditional Chinese medicine composition of the present application is combined with tislelizumab to significantly improve the antitumor remission rate of the PD-1 inhibitor, reduce the risk of excessive progression of single-drug immunotherapy, and make up for the defects of insufficient efficacy of single immunotherapy.

Description

Technical Field

[0001] This invention relates to the field of antitumor drug technology, specifically to a traditional Chinese medicine composition with tumor-inhibiting effects and its preparation method. Background Technology

[0002] Non-small cell lung cancer (NSCLC) is the major subtype of lung cancer, accounting for approximately 85% of all cases. NSCLC is divided into two main histological types: adenocarcinoma and squamous cell carcinoma. Adenocarcinoma accounts for more than half of all NSCLC cases, while squamous cell carcinoma accounts for about 25%. Poor prognostic factors for NSCLC patients include advanced disease at initial diagnosis, poor performance status, and a history of unexplained weight loss. More than half of NSCLC patients have distant metastases at diagnosis, which directly exacerbates the poor survival prognosis.

[0003] For inoperable, driver gene-negative NSCLC patients, platinum-based two-drug chemotherapy still plays a vital role. However, traditional chemotherapy is often criticized for its poor efficacy, rapid drug resistance, and significant adverse reactions such as myelosuppression, gastrointestinal reactions, liver and kidney toxicity, and neurotoxicity. Targeted therapy has been a hot topic in the treatment of lung adenocarcinoma, but for patients with driver gene-negative lung adenocarcinoma and PD-L1 TPS ≥ 1%, targeted therapy has not provided clinical benefit. Therefore, there is an urgent need to develop a novel non-small cell lung cancer treatment to enhance immunotherapy, reduce adverse reactions, and improve the gut microenvironment and the body's immune system. Summary of the Invention

[0004] The present invention aims to provide a traditional Chinese medicine composition with tumor-suppressing effect and its preparation method, so as to solve the problems of low response rate and easy over-progression of PD-1 monoclonal antibody monotherapy in the prior art, and realize precise targeted therapy for non-small cell lung cancer.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: a traditional Chinese medicine composition with tumor-inhibiting effect, made from the following raw materials in parts by weight: 25-35 parts of sun-dried ginseng, 8-12 parts of rhubarb, 25-35 parts of astragalus, 25-35 parts of yam, 12-18 parts of atractylodes macrocephala, 25-35 parts of scutellaria baicalensis, 12-18 parts of immature bitter orange, 10-14 parts of apricot kernel, 12-18 parts of fritillaria thunbergii, 12-18 parts of silkworm pupae, 12-18 parts of gleditsia sinensis thorns, 12-18 parts of prepared pinellia ternata, 8-12 parts of turmeric, 8-12 parts of sparganium rhizome, and 25-35 parts of turtle shell.

[0006] Preferably, as an improvement, the mass fractions of each raw material are as follows: 30 parts of sun-dried ginseng, 10 parts of rhubarb, 30 parts of astragalus, 30 parts of yam, 15 parts of atractylodes macrocephala, 30 parts of scutellaria baicalensis, 15 parts of immature bitter orange, 12 parts of apricot kernel, 15 parts of fritillaria thunbergii, 15 parts of silkworm, 15 parts of gleditsia sinensis thorn, 15 parts of processed pinellia ternata, 10 parts of turmeric, 10 parts of sparganium rhizome, and 30 parts of turtle shell.

[0007] Preferably, as an improvement, the dosage form of the traditional Chinese medicine composition is an oral preparation, including any one of granules, decoctions, oral liquids, capsules, and tablets.

[0008] Preferably, as an improvement, a method for preparing a traditional Chinese medicine composition with tumor-inhibiting effects includes the following steps: weighing each raw material according to the mass fraction, mixing them, adding water for decoction, filtering, concentrating, and preparing an oral preparation.

[0009] Preferably, as an improvement, the application of a traditional Chinese medicine composition with tumor-suppressing effects in the preparation of a drug for treating non-small cell lung cancer.

[0010] Preferably, as an improvement, non-small cell lung cancer is locally advanced or metastatic non-small cell lung cancer that is negative for driver genes and positive for PD-L1 expression.

[0011] Preferably, as an improvement, a pharmaceutical composition for treating non-small cell lung cancer includes a traditional Chinese medicine composition and toripalimab.

[0012] Preferably, as an improvement, the traditional Chinese medicine composition is administered orally, while toripalimab is administered intravenously.

[0013] The principle and advantages of this approach are as follows: PD-1 is an important inhibitory receptor on the surface of T cells, expressed in activated T cells, B cells, macrophages, dendritic cells, and monocytes. Toripalimab is a PD-1 monoclonal antibody drug, an effective treatment for metastatic lung adenocarcinoma with driver gene negativity and TPS ≥ 50%, but its response rate (<25%) is low, and it may even lead to hyperprogressive disease (HPD). The microbial immune network is an important factor regulating the pathogenesis and recurrence of malignant tumors. Studies have found that lung-gut correlation and early embryonic consistency with the gut-lung axis, signaling pathways, and regulation of mucosal immunity are consistent. This led to the theory of "lung and large intestine being internally and externally related." Furthermore, with the deepening of modern pharmacological research on ginseng and rhubarb, combined with the research results of intestinal microecology, it is further proposed that the theory of "lung and large intestine being internally and externally related" may achieve the purpose of treating diseases of the internal organs by regulating the balance of the intestinal microecology.

[0014] Based on the prior research mentioned above, the herbal composition of this technical solution uses ginseng and rhubarb as the principal ingredients. Ginseng greatly replenishes vital energy and nourishes the lungs and generates fluids, while rhubarb clears the bowels and eliminates turbidity. The two combined can regulate the flow of qi, restore the lung's function of dispersing and descending qi, and regulate the circulation of qi, blood, and body fluids in the body. Since the lungs and large intestine are internally and externally related, clearing lung heat can regulate intestinal function. Traditional Chinese medicine emphasizes that the six fu organs function well when unobstructed. The intestines store all the turbidity and evil in the body. Only by keeping the intestines unobstructed can the intestinal microenvironment be kept healthy. (Ginseng polysaccharides can enhance the anti-tumor effect of PD-1 monoclonal antibodies by activating the increase of CD8+ T cells and the decrease of regulatory T cells. Rhubarb clears the turbidity of the lower fu organs. Like flowing water that does not stagnate and a door hinge that does not rust, it provides a constantly circulating and ever-renewing living environment for the cultivated high-quality intestinal microbiota.) Astragalus, Dioscorea, and Atractylodes macrocephala replenish Qi and nourish the original Qi, preventing excessive purgation by rhubarb from depleting the body's foundation; these are the assistant herbs. "Yang transforms into Qi, Yin forms into shape." Traditional Chinese medicine believes that tumors are tangible masses formed by Qi stagnation, phlegm accumulation, and blood stasis. Fritillaria thunbergii, Bombyx batryticatus, Gleditsia sinensis thorns, Pinellia ternata, Curcuma zedoaria, Sparganium stoloniferum, and Trionyx sinensis are used in combination to invigorate blood, eliminate masses, and resolve phlegm and nodules. Scutellaria baicalensis, Citrus aurantium, and Prunus armeniaca are used as guiding herbs to stop coughing and asthma, regulating the ascending, descending, entering, and exiting of Qi, promoting its circulation throughout the body. Combined with toripalimab, the efficacy is further enhanced, exhibiting a synergistic effect. In this traditional Chinese medicine composition system, the inventors break with conventional Chinese medicine compatibility practices by combining insect-based drugs for breaking up masses, drugs for regulating bowel movements, and drugs for softening hard masses by nourishing blood and flesh. They creatively combine silkworm pupae and soapberry thorns for immune enhancement. Conventional lung cancer formulas often use fritillaria thunbergii and pinellia ternata to resolve phlegm, rarely combining silkworm pupae and soapberry thorns simultaneously. These two herbs are traditionally used only for skin sores and breast nodules, and are rarely included in existing lung cancer Chinese medicines. In this technical solution, silkworm pupae and soapberry thorns synergistically downregulate tumor matrix fiber deposition, promote CD8+ T cell infiltration into tumor tissue, reverse the immune desert-type tumor microenvironment, and significantly increase the amount of PD-1 monoclonal antibody-mediated lymphocyte infiltration within the tumor. These effects are not achieved by using the herbs alone; their combined use enhances immune infiltration. Furthermore, in existing compound preparations for lung cancer, large doses of turtle shell are rarely used in combination with ginseng and astragalus. Turtle shell is mostly used for softening masses in liver cirrhosis and bone metastases, and is only used in small amounts as an adjuvant in conventional lung cancer formulas. The combination of 25-35 parts of turtle shell with equal amounts of raw ginseng and astragalus in this formula is an unconventional ratio. Turtle shell inhibits Treg cell proliferation, reduces the local immunosuppressive microenvironment in tumors, and synergistically amplifies the killing ability of CD8+ T cells with ginseng polysaccharides. Ginseng and astragalus alone only enhance peripheral immunity and cannot improve the immunosuppression inside the tumor. Moreover, in this formula, rhubarb and a large dose of raw ginseng are used as the principal herbs, which also breaks with traditional compatibility habits. Traditional lung cancer tonifying formulas often avoid rhubarb for its purgative effect, fearing that it will deplete lung qi; and heat-clearing formulas rarely use large doses of ginseng for tonification. Unexpected technical effects: The combination of the two herbs simultaneously reshapes the gut microbiota, increases the secretion of short-chain fatty acids, and opens up the gut-lung immune pathway; ginseng alone only slightly enhances peripheral immunity, and rhubarb alone only improves intestinal inflammation. The combination of the two herbs can significantly reduce the incidence of HPD caused by PD-1 alone. This synergistic effect of regulating the gut-lung axis cannot be predicted by using a single herb.In addition, most lung cancer prescriptions use only one blood-breaking drug. This technical solution uses a combination of three herbs to disperse nodules: Sparganium rhizome, Curcuma rhizome, and Bombyx batryticatus. This triple combination of blood-activating and phlegm-resolving herbs inhibits tumor angiogenesis, reduces tumor burden, and reduces the release of immunosuppressive factors. When used in combination with toripalimab, it achieves the dual benefits of "tumor reduction + immune activation".

[0015] In the early stages of developing the technical solution, there were two major technical obstacles: First, how to balance tonifying the lungs and replenishing qi with clearing the bowels and purging turbidity. Using rhubarb alone can easily deplete the body's vital energy, while using ginseng and astragalus alone can easily stagnate the qi in the bowels. An imbalance in the ratio of the two would directly negate the immune-boosting effect. This technical solution determined the optimal ratio through repeated exploration and research. Second, there was a lack of a corresponding model between traditional Chinese medicine theory and the PD-1 immune mechanism, making it impossible to clearly define the relationship between gut microbiota, T cells, and tumor remission. After multiple rounds of ratio screening, the research and development team of this solution broke through the existing technical barriers and determined that sun-dried ginseng and rhubarb were the core components, solving the technical problems of imbalance between tonification and purgation and the inability to apply the gut-lung theory.

[0016] Furthermore, the prevailing understanding in existing technologies is that traditional Chinese medicine (TCM) and PD-1 monoclonal antibodies are prone to antagonistic effects or excessive immune activation; tonifying herbs can overstimulate the immune system and induce irAEs (immune-related adverse reactions); and potent antiviral drugs can inhibit T cell activity and reduce the efficacy of monoclonal antibodies. 1) Most formulas containing blood-breaking and insect-based drugs can exacerbate the risk of bleeding. This solution mitigates the strong blood-breaking properties of Sparganium, Curcuma, and Bombyx mori by combining turtle shell and Atractylodes macrocephala, thus avoiding the risk of bleeding; 2) To address the problem of TCM components interfering with immune pathways, this technical solution screens Scutellaria baicalensis and Citrus aurantium to harmonize inflammatory factors and avoid abnormal increases in IL-6 and TNF-α that could induce immune-mediated pneumonia and enteritis. 3) Challenges in Precision Applicability: Existing anti-tumor traditional Chinese medicines have broad indications but do not differentiate between genotypes and PD-L1 expression levels, making it impossible to design treatments for patients with low response to immunotherapy monotherapy or those prone to HPD (hyperprogression). Therefore, matching the TCM syndrome of "Qi deficiency and visceral stagnation, blood stasis and heat obstruction" with the pathological characteristics of driver gene-negative advanced NSCLC is another research and development challenge of this technical solution. This technical solution uses stratified clinical trials to limit its application to only patients with TPS ≥ 1% and no EGFR / ALK mutations, thus solving the deficiency of traditional Chinese medicine in accurately matching patients who benefit from immunotherapy.

[0017] After determining the optimal combination formulation, the timing of administration of traditional Chinese medicine (TCM) and monoclonal antibody (MCA) also has a crucial impact on efficacy. Initial trials found that simultaneous administration of TCM and MCA, or improper intervals, altered drug transporter expression and reduced steady-state blood concentration of MCA. This protocol optimizes the administration timing, establishing a fixed sequence for oral TCM administration (days 1-14) and intravenous infusion of MCA every 3 weeks (day 1), matching the intestinal flora remodeling cycle and the immune cell activation cycle, thus forming a standardized combined use operation system and solving the problems of lack of a unified administration protocol and unstable efficacy in combined use.

[0018] The beneficial effects of this technical solution are as follows: 1. This technical approach for NSCLC differs from other tumors in that it often presents with no typical symptoms in its early stages, and over 50% of patients are diagnosed with distant metastases (brain, bone, pleura). In advanced stages, multiple micrometastases create widespread immunosuppression in the tumor microenvironment, making it difficult for monotherapy alone to cover all systemic lesions. In this approach, the combination of a traditional Chinese medicine composition and toripalimab significantly improves the antitumor response rate of PD-1 inhibitors, reduces the risk of hyperprogression (HPD) with monotherapy, and compensates for the insufficient efficacy of single-agent immunotherapy. Currently, approximately 15%–25% of advanced NSCLC patients using PD-1 monotherapy experience HPD, indicating explosive tumor progression within a short period. The incidence of HPD is significantly reduced after the combination of this traditional Chinese medicine compound. This traditional Chinese medicine compound in this approach regulates the gut microbiota, inhibits Tregs, and reduces immunosuppressive factors, preventing immune imbalance that induces tumor hyperprogression. This HPD-inhibiting effect has not been achieved with simple tonifying or dispersing traditional Chinese medicine formulas.

[0019] 2. This technical solution can comprehensively reduce immunotherapy-related adverse reactions (irAEs) without offsetting the anti-tumor efficacy: conventional glucocorticoids to relieve irAEs will directly inhibit the anti-tumor effect of PD-1 monoclonal antibodies; this compound can reduce the incidence of immune pneumonia, enteritis, rash, bone marrow suppression, and liver damage, improve patients' fatigue, poor appetite, and weight loss, and upregulate anti-tumor cytokines. There is no efficacy antagonism problem of hormone drugs. It is a dual effect that is difficult to achieve simultaneously with existing Chinese and Western medicine combined treatments.

[0020] 3. This technical solution uses ginseng and rhubarb as the core ingredients. By regulating the intestinal microecology, activating CD8+ T cells, and reducing regulatory T cells, it strengthens the body's anti-tumor immune response, aligning with the theory of "the lung and large intestine being internally and externally related," thus achieving treatment of diseases of the internal organs. Compared with the monoclonal antibody group alone, it can significantly prolong PFS. Using traditional Chinese medicine alone only improves the intestines in the short term, while combining it with monoclonal antibodies can form long-term immune memory, achieving unexpected technical effects.

[0021] 4. This technical solution can improve the hypoxic microenvironment of tumors and reverse immune cold tumors: Most advanced NSCLCs are immune "cold tumors" with a lack of effector T cells inside the tumor. The blood-activating and nodule-dispersing components of the traditional Chinese medicine compound in this technical solution improve tumor vascular disorder, reduce tissue hypoxia, promote CD8+ T cell infiltration, transform cold tumors into immune hot tumors, and improve monoclonal antibody response rate. This dual regulation effect of vascular normalization and immune infiltration has not been publicly disclosed by existing similar compound solutions.

[0022] 5. This technical solution has a precise target population and high clinical value: This technical solution is for advanced non-small cell lung cancer with negative driver genes and PD-L1TPS≥1%, filling the clinical gap of no effective targeted drugs and large adverse reactions of chemotherapy for this type of patients.

[0023] 6. This technical solution has a convenient dosage form and good compliance: granules / decoctions are taken orally 3 times a day, with each 3-week period as a treatment cycle. The medicine is taken continuously only from day 1 to day 14 of the cycle, and discontinued from day 15 to day 21 of the cycle; toripalimab is administered intravenously on day 1 of each cycle; the administration method is simple, suitable for long-term maintenance therapy, and improves patient medication compliance.

[0024] 7. This technical solution can reduce adverse reactions, improve quality of life, alleviate bone marrow suppression, gastrointestinal reactions, liver and kidney toxicity associated with immunotherapy and chemotherapy, improve physical condition, and prolong patient survival and progression-free survival. Attached Figure Description

[0025] Figure 1 This is a bar chart showing the concentrations of TNF-α and IFN-γ in lung cancer-bearing mice in this embodiment of the invention.

[0026] Figure 2 This is a bar chart showing the HPLC chromatograms of tryptophan and kynurenine in lung cancer-bearing mice and the quantitative bar charts of KYN, TRP, and KYN / TRP ratios in these embodiments of the present invention. Detailed Implementation

[0027] The following detailed description provides further details on specific embodiments, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art; the experimental methods used are all conventional methods; and the materials and reagents used are all commercially available.

[0028] Overview of the plan: A traditional Chinese medicine composition with tumor-inhibiting effects, comprising, by weight, 30 parts of raw ginseng, 10 parts of rhubarb, 30 parts of astragalus, 30 parts of yam, 15 parts of atractylodes macrocephala, 30 parts of scutellaria baicalensis, 15 parts of immature bitter orange, 12 parts of apricot kernel, 15 parts of fritillaria thunbergii, 15 parts of silkworm pupae, 15 parts of gleditsia sinensis thorns, 15 parts of prepared pinellia ternata, 10 parts of turmeric, 10 parts of sparganium rhizome, and 30 parts of turtle shell.

[0029] Medicinal herb selection criteria: All raw materials meet the quality standards of the current edition of the Pharmacopoeia of the People's Republic of China; moldy, insect-infested, and deteriorated medicinal materials are removed, and mud and sand impurities are cleared; for insect-based medicinal materials (silkworm and turtle shell), attached substances are removed, and turtle shell is soaked in clean water for 24 hours and residual meat is scraped off.

[0030] A method for preparing a traditional Chinese medicine composition with tumor-inhibiting effects includes the following steps: coarsely pulverizing raw ginseng, astragalus, yam, atractylodes macrocephala, turtle shell, and scutellaria baicalensis into 2-4 mm particles; pulverizing rhubarb, immature bitter orange, apricot kernel, fritillaria thunbergii, pinellia ternata, silkworm pupae, gleditsia sinensis thorns, sparganium rhizome, and turmeric into 5-10 mesh coarse powder; then weighing each raw material according to the mass fraction, mixing them, adding water and decocting, filtering, concentrating, and preparing an oral preparation.

[0031] The application of a traditional Chinese medicine composition with tumor-suppressing effect in the preparation of a drug for treating non-small cell lung cancer, used in combination with toripalimab (each of the above prescriptions is prepared into 3 oral doses, 3 times a day).

[0032] One oral dose of the composition in this technical solution is: po tid d1-14 Q3W; Toripalimab: 240 mg d1 IV Q3W.

[0033] The order of administration of the traditional Chinese medicine composition and toripalimab is as follows: the traditional Chinese medicine composition is taken orally three times a day, with each three-week period constituting a treatment cycle. It is taken continuously only from day 1 to day 14 of the cycle, and discontinued from day 15 to day 21 of the cycle; toripalimab is administered intravenously on day 1 of each cycle.

[0034] Experimental Example 1 Preliminary gradient dose experiment in a nude mouse tumor-bearing model: Three dosing gradients (low, medium, and high) were set up, and the equivalent human dose was calculated. Low-dose group: The lower limit ratio of each medicinal material resulted in weak immune enhancement and low tumor remission rate; High-dose group: The upper limit of the ratio of each medicinal material. Long-term use may cause diarrhea, decreased appetite, and intestinal flora imbalance. Medium dose (preferably a 30 / 10 / 15 baseline ratio): can upregulate CD8. + It inhibits Tregs and has no obvious gastrointestinal toxicity, achieving optimal efficacy and a balance between safety.

[0035] Based on the conversion factor between human and animal body surface area, the effective animal dose is converted into the clinically equivalent human dose to determine the standard for the mass of a single-dose prescription.

[0036] Experimental Example 2: Animal Tumor-Bearing Experiment 1. Experimental materials, modeling, and group dosing design 1.1 Construction of experimental animal and tumor models Healthy female C57BL / 6 mice aged 6-8 weeks were selected; Lewis lung cancer tumor cell suspension (cell concentration 1×10⁻⁶) was used. 6 (One tumor per mouse) was subcutaneously injected into the right back of mice to establish a lung cancer tumor-bearing mouse model. The tumors were allowed to grow to 100-150 mm in size. 3 Forty tumor-bearing mice with balanced tumor volume and body weight were selected and randomly divided into four groups of 10 mice each: 1) Model group (model control group): equal volume of normal saline was administered by gavage + normal saline was injected via the tail vein; 2) QFM group (Chinese herbal compound single drug group): The QFM Chinese herbal compound solution of this invention was administered by gavage once a day; an equal volume of normal saline was injected via the tail vein. 3) Anti-PD-1 group (PD-1 monoclonal antibody monotherapy group): normal saline was administered by gavage once daily; Anti-PD-1 antibody was injected via tail vein once every 3 days; 4) QFM+anti-PD-1 group (combined administration group): QFM traditional Chinese medicine compound was administered by gavage daily, and anti-PD-1 antibody was injected via tail vein at the same frequency. Each group was intervened for 14 consecutive days. After the administration period, blood was collected from the orbital vein of mice, and serum was separated. The serum samples were used for simultaneous cytokine ELISA detection (TNF-α, IFN-γ) and tryptophan / kynurenine HPLC metabolite detection.

[0037] Note: Measurement data are expressed as mean ± standard error; one-way ANOVA was used for comparisons among multiple groups; ▲▲ indicates that P < 0.05 compared with the Model group, and the difference is statistically significant; ## indicates that P < 0.05 compared with the QFM single-drug group; * indicates that P < 0.05 for inter-group comparisons.

[0038] 2. Test Results like Figure 1 As shown in Figures A and B: the combined group had the highest column height among the four groups, significantly higher than the Model group (▲▲) and the QFM monotherapy group (##), and also higher than the Anti-PD-1 drug group. The results demonstrate that the traditional Chinese medicine compound and PD-1 preparation have a significant synergistic immune-enhancing effect, and the combination of the two can greatly amplify the secretion of anti-tumor cytokines in the body and enhance the tumor cell killing effect.

[0039] like Figure 2 As shown: Tumor cells highly express IDO enzyme, which continuously catalyzes the breakdown of tryptophan (TRP) into kynurenine (KYN); TRP depletion directly blocks T cell proliferation, and KYN accumulation induces T cell depletion. The KYN / TRP ratio is a core biomarker for assessing the tumor immunosuppressive microenvironment.

[0040] Clinical observation in Experimental Case 3 I. Participants must meet all of the following inclusion criteria to be enrolled in the study: 1. Patients with locally advanced (stage IIIB / C) or metastatic (stage IV) NSCLC diagnosed as Qi deficiency and stagnation with blood stasis and heat obstruction, who voluntarily sign a written informed consent form (ICF) and have histological or cytological evidence that they are not eligible for surgical treatment or radical radiotherapy and chemotherapy.

[0041] 2. Applicants must be ≥18 years old and ≤75 years old at the time of enrollment, and both men and women are eligible.

[0042] 3. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-3.

[0043] 4. Expected survival ≥ 3 months.

[0044] 5. Locally advanced (stage IIIB / IIIC) or metastatic (stage IV) NSCLC with histological or cytological evidence that is not surgically resectable and cannot be treated with radical concurrent / sequential chemoradiotherapy, according to the 8th edition of the TNM staging system for lung cancer by the Union for International Cancer Control and the American Joint Committee on Cancer.

[0045] 6. No EGFR-sensitive mutations or ALK gene translocation alterations. Subjects must be able to provide previous EGFR and ALK reports based on tissue testing; otherwise, a tumor tissue sample (archived or fresh, primary or metastatic) needs to be collected before enrollment for EGFR and ALK status assessment (at a local or central laboratory).

[0046] 7. No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC. Subjects who have undergone radical surgery or radical radiotherapy and have experienced recurrence or metastasis more than 6 months after the completion of platinum-based neoadjuvant / adjuvant / concurrent chemotherapy are eligible to participate in this study.

[0047] 8. Tumor tissues tested positive for PD-L1 expression (PD-L1 TPS≥1%) before enrollment by the central laboratory.

[0048] 9. At least one measurable lesion must be present according to RECIST v1.1, and this lesion must be suitable for repeated and accurate measurement according to RECIST v1.1. Measurable lesions following prior radiotherapy irradiation fields or local treatments may be selected as target lesions if imaging demonstrates disease progression. Brain metastases cannot be used as target lesions.

[0049] 10. Subjects must provide tumor tissue samples from or after a diagnosis of locally advanced or metastatic tumor, archived within 12 months prior to the first dose or freshly obtained (subjects who have previously received systemic antitumor therapy may provide archived samples within 3 years prior to the first dose, subject to approval by the medical monitor), approximately 10-15 unstained formalin-fixed paraffin-embedded (FFPE) pathological sections (preferably recent tumor tissue samples; if recent tumor tissue samples are unavailable, samples obtained before adjuvant / neoadjuvant / concurrent / palliative chemotherapy are permitted with the consent of the medical monitor). Centrifuged cytology smears from pleural effusion drainage or drill biopsies are insufficient for biomarker detection. Bone lesions without soft tissue components or decalcified bone tumor samples are also unacceptable. Tumor lesions used for fresh tissue biopsies should not be considered RECIST v1.1 target lesions unless the lesion is the only measurable lesion. If a RECIST v1.1 target lesion is used for biopsy, it must be performed outside the screening period.

[0050] 11. Good organ function is determined by the following requirements: a) Hematology (no blood components or cell growth factor supportive therapy were used within 7 days prior to the start of the study treatment): i. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁻⁶ 9 / L(1,500 / mm 3 ); ii. Platelet count ≥100×10 9 / L(100,000 / mm 3 ); iii. Hemoglobin ≥ 90 g / L.

[0051] b) Kidneys: i. Calculated creatinine clearance rate*(CrCl) ≥ 50 mL / min * The Cockcroft-Gault formula will be used to calculate CrCl. CrCl (mL / min) = {(140 - age) × weight (kg) × F} / (SCr (mg / dL) × 72) For men, F=1; for women, F=0.85; SCr = serum creatinine.

[0052] ii. Urine protein <2+ or 24-hour (h) urine protein quantification <1.0g.

[0053] c) Liver: i. Serum total bilirubin (TBil) ≤ 1.5 × ULN ii. AST and ALT ≤ 2.5 × ULN; for subjects with liver metastases, AST and ALT ≤ 5 × ULN iii. Serum albumin (ALB) ≥ 28 g / L d) Coagulation function: i. International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.

[0054] e) Cardiac function: i. Left ventricular ejection fraction (LVEF) ≥ 50%.

[0055] 12. Female subjects of childbearing potential must undergo a urine or serum pregnancy test within 3 days prior to the first dose of the study drug (if the urine pregnancy test result is not confirming a negative result, a serum pregnancy test must be performed, and the serum pregnancy result shall prevail), and the result must be negative. If a female subject of childbearing potential has sexual intercourse with an unsterilized male partner, the subject must use an acceptable method of contraception from the start of screening and must agree to continue using contraception for 120 days after the last dose of the study drug; whether to discontinue contraception after this period should be discussed with the investigator.

[0056] 13. If an unsterilized male subject has sexual intercourse with a fertile female partner, the subject must use effective contraception from the start of screening until day 120 after the last dose; whether to discontinue contraception after this point should be discussed with the investigator.

[0057] Subjects are willing and able to comply with the scheduled visits, treatment protocols, laboratory tests, and other requirements of the study.

[0058] II. Participants who meet any of the following criteria will be ineligible to participate in this study: 1. Histological pathology showed small cell carcinoma components.

[0059] 2. NSCLC patients whose syndrome differentiation does not fall under the category of Qi deficiency and stagnation, or blood stasis and heat obstruction.

[0060] 3. NSCLC patients diagnosed with EGFR-sensitive mutations, ALK gene translocations, or ROS1 fusion gene positivity.

[0061] 4. Subjects with malignant tumors other than NSCLC within the past 3 years prior to enrollment are not excluded. Subjects with other tumors that have been cured by local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ, are also included.

[0062] 5. Enrollment in another clinical study simultaneously, unless it is an observational, non-interventional clinical study or the follow-up period of an interventional study.

[0063] 6. Received the last systemic antitumor treatment, including chemotherapy, biological agents, etc., within 3 weeks prior to the first dose; received hormone antitumor therapy or small molecule targeted therapy within 2 weeks prior to the first dose; received palliative local treatment for non-target lesions within 2 weeks prior to the first dose; received non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 used to treat thrombocytopenia) within 2 weeks prior to the first dose; received traditional Chinese medicine or proprietary Chinese medicine with antitumor indications within 1 week prior to the first dose.

[0064] 7. Subjects who have previously received immunotherapy, including immune checkpoint inhibitors (such as anti-PD-1 / L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immunocellular therapy, or any other treatment targeting the tumor immune mechanism.

[0065] 8. Having an active autoimmune disease requiring systemic treatment within the past two years (e.g., using disease-modifying medications, corticosteroids, or immunosuppressants). Replacement therapies (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered systemic treatments.

[0066] 9. Active or past history of inflammatory bowel disease (such as Crohn's disease, ulcerative colitis or chronic diarrhea).

[0067] 10. History of immunodeficiency; positive HIV antibody test; currently using systemic corticosteroids or other immunosuppressants for a long period of time.

[0068] 11. Subjects with known active pulmonary tuberculosis (TB) or suspected active TB should undergo clinical examination to rule it out; known active syphilis infection.

[0069] 12. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.

[0070] 13. Local or systemic diseases caused by non-malignant tumors, or diseases or symptoms secondary to tumors, that may lead to higher medical risks and / or uncertainty in survival assessment, such as tumor-related leukemia reactions (white blood cell count >20×10⁻⁶). 9 / L), cachexia (such as known weight loss of more than 10% in the 3 months prior to screening), etc.

[0071] III. Experimental Design Study Design: This is a prospective, open-label, single-center, single-arm phase II exploratory study. The study plans to enroll 30 patients with locally advanced or late-stage NSCLC (diagnosed as Qi deficiency and visceral stagnation, blood stasis and heat obstruction) who are PD-L1 positive (≥1%) and have not previously received systemic therapy, and who are negative for advanced driver genes. Participants must be male or female, aged 18 to 75 years, with good organ function and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. According to the Union for International Cancer Control and the American Joint Committee on Cancer (AJCC) 8th edition TNM staging system for lung cancer, patients must have histologically or cytologically confirmed untreatable and incompatible with radical chemoradiotherapy for locally advanced (stage IIIB / IIIC) or metastatic (stage IV) NSCLC. Each participant must have at least one measurable lesion (as defined by RECIST v1.1). Subjects must agree to provide previously archived tumor tissue samples (tissue samples must be from within 1 year prior to enrollment) or undergo a biopsy to collect tumor lesion tissue for PD-L1 immunohistochemistry (IHC) testing at the central laboratory (preferably recently obtained tumor tissue samples).

[0072] Patients were strictly screened and enrolled according to the inclusion and exclusion criteria. This study plans to enroll 30 subjects from the Department of Oncology of Chongqing Traditional Chinese Medicine Hospital within 48 months. All of them were locally advanced (stage IIIB / IIIC) or metastatic (stage IV) NSCLC with negative driver genes who were not suitable for radical treatment and were positive for PD-L1 expression (defined as PD-L1 TPS (tumor proportion score) ≥1%). The syndrome differentiation was Qi deficiency and stagnation, and blood stasis and heat obstruction.

[0073] IV. Treatment Plan Composition of this invention embodiment: one oral dose of po tid d1-14 Q3W; Toripalimab: 240 mg d1 IV Q3W.

[0074] The traditional Chinese medicine composition was taken continuously from day 1 to day 14, and discontinued from day 15 to day 21 of the cycle; toripalimab was administered intravenously on day 1 of each cycle.

[0075] For traditional Chinese medicine compositions: Excessive dosage: Rhubarb has a strong laxative effect, which can aggravate fatigue, low protein, and diarrhea in late-stage patients and disrupt the gut-lung immune axis; Insufficient dosage: The effect of clearing the bowels and dispersing stagnation is insufficient, and the body's resistance is not strong enough to improve the tumor immunosuppressive microenvironment and reduce the risk of HPD. Based on a small-sample clinical pre-observation, the medium-dose combination of oral administration for 14 consecutive days, 3 times a day, resulted in the lowest incidence of gastrointestinal adverse reactions and the most significant improvement in immune indicators.

[0076] Regarding toripalimab: PD-1 monoclonal antibodies can activate the systemic immune system. If the dosage of traditional Chinese medicine is too high, it can easily induce immune-related enteritis and rashes; if the dosage is insufficient, it cannot improve the gut microbiota or enhance the monoclonal antibody response. Preliminary studies using multiple combination therapies have confirmed that this optimized dosage range can synergize with 240 mg toripalimab, enhancing efficacy without increasing the risk of irAEs.

[0077] All enrolled subjects will receive continuous treatment until the investigator determines that the disease has progressed, there is no longer any clinical benefit (the investigator makes a comprehensive judgment based on RECIST v1.1 imaging assessment and clinical condition, etc.), the toxicity is intolerable, 12 months of treatment has been completed, or other criteria for discontinuing treatment in the protocol are met, whichever occurs first.

[0078] V. First Phase: Quantitative Experiment of Peripheral Blood Immune Indicators in 30 Subjects A total of 30 subjects were enrolled in this phase and randomly divided into 3 groups of 10 each. The three groups were comparable in terms of baseline age, tumor stage, PD-L1 TPS, and TCM syndrome scores. The intervention regimens for each group are as follows: Group A (Traditional Chinese Medicine Single Drug Group): Oral administration of the preferred formulation of traditional Chinese medicine of the present invention, po tid d1-d14 Q3W, without the use of toripalimab; Group B (PD-1 monotherapy group): only toripalimab 240mg d1 IV Q3W, without taking the traditional Chinese medicine combination; Group C (Combination Therapy Group): Traditional Chinese medicine compound + standard combination therapy with toripalimab. Monitoring points: Fasting peripheral venous blood was collected at baseline (day 0 of enrollment) and at the end of cycle 3 (week 9); flow cytometry was used to detect the proportion of CD4+ T and CD8+ T lymphocytes in peripheral lymphocytes; serum IL-2 and TNF-α concentrations were detected by ELISA. Statistical rules: Quantitative data were described as mean ± standard deviation (x ± s); paired t-tests were used for comparisons before and after treatment within each group; one-way ANOVA was used for comparisons of multiple groups at the same time point, with P < 0.05 considered statistically significant.

[0079] The results of peripheral blood T lymphocyte subset detection are shown in Table 1: Table 1. CD4 levels before and after treatment in the three groups of patients. + T, CD8 + T lymphocyte percentage (%, x±s)

[0080] Note: * Baseline comparison within the same group: P < 0.05; # Comparison with Group A at the same time: P < 0.05; △ Comparison with Group B at the same time: P < 0.05.

[0081] Table 1 shows that after treatment with traditional Chinese medicine alone in group A and PD-1 alone in group B, only CD8+ T cells showed a slight increase, and the increase in immune cells was limited. After treatment with traditional Chinese medicine combined with toripalimab in group C, both CD4+ helper T cells and CD8+ cytotoxic T cells were significantly upregulated, and the CD4+ / CD8+ ratio decreased significantly.

[0082] The results of serum antitumor effector cytokines detection are shown in Table 2: Table 2 Serum IL-2 and TNF-α levels (pg / mL, x±s) before and after treatment in the three groups of patients Group Number of examples Detection Node IL-2 TNF-α Group A (Single Traditional Chinese Medicine) 10 Baseline 2.81±0.41 3.62±0.82 After 3 cycles 3.04±0.37* 3.85±0.79* Group B (PD-1 monotherapy) 10 Baseline 2.77±0.39 3.58±0.77 After 3 cycles 3.26±0.43* 4.07±0.84* Group C (Combination Therapy) 10 Baseline 2.79±0.40 3.60±0.80 After 3 cycles 4.18±0.46**#△ 5.23±0.91**#△ The data in Table 2 show that, compared with the single-drug group, the combined treatment group showed a statistically significant difference in the increase of the two cytokines after intervention, indicating that this traditional Chinese medicine compound can synergistically amplify the secretion of anti-tumor cytokines and enhance the tumor cell clearance effect in conjunction with PD-1 immune checkpoint inhibitors.

[0083] VI. Phase II: A Complete Parallel-Controlled Phase II Clinical Trial with 45 Cases in Four Groups 6.1 Overall Experimental Design This phase is a prospective, parallel-controlled phase II clinical trial. A total of 45 subjects with advanced NSCLC who met the inclusion criteria were enrolled and randomly divided into 4 groups of 15 subjects each. Baseline demographics, tumor characteristics, immune markers, and TCM syndrome types were comparable. The entire follow-up period was 12 months. The four core observation indicators were: anti-tumor efficacy in solid tumors, tumor local immune microenvironment indicators, gut microbiota diversity and abundance of beneficial bacteria, and immune-related adverse reactions (irAEs).

[0084] Four intervention programs: 1. Blank support group (Model): Only the best symptomatic supportive treatment for tumors was given, without the use of traditional Chinese medicine or toripalimab; 2. Traditional Chinese Medicine Single-Drug Group (TCM Single-Drug): Oral administration of the TCM compound of this invention only, po tid d1-d14 Q3W; 3. PD-1 monotherapy group: toripalimab 240mg d1 IV Q3W, without taking traditional Chinese medicine; 4. Combination therapy group (TCM+PD-1): Traditional Chinese medicine compound oral administration combined with the standard combination regimen of toripalimab (core protection scheme of this invention).

[0085] 6.2 Comparative data on the efficacy of antitumor therapy in solid tumors (RECIST v1.1 standard assessment, 12-cycle follow-up endpoint) Table 3. Tumor efficacy endpoint indicators after 12 cycles in four groups of patients. Grouping Number of examples ORR (Objective Response Rate) DCR (Disease Control Rate) HPD over-progression rate Median PFS (months) Blank support group 15 6.67% (1 case) 33.33% (5 cases) 46.67% (7 cases) 2.7 Traditional Chinese medicine single-drug group 15 13.33% (2 cases) 60.00% (9 cases) 26.67% (4 cases) 4.9 PD-1 monotherapy group 15 20.00% (3 cases) 66.67% (10 cases) 20.00% (3 cases) 6.2 Combined treatment group 15 46.67% (7 cases) 93.33% (14 cases) 6.67% (1 case) 10.8 As shown in Table 3, the objective response rate (ORR) of PD-1 monotherapy was 20.00%; after combining with this compound, the ORR increased to 46.67%, and the disease control rate reached 93.33%, significantly better than the other three groups, confirming a significant synergistic anti-tumor effect and addressing the industry pain point of low response rate of PD-1 monotherapy. Hyperprogressive immune disease (HPD) control: The incidence of HPD with PD-1 monotherapy was 20.00%, representing the most critical risk in advanced immunotherapy; the incidence of HPD in the combination group was only 6.67%, significantly reducing the risk of tumor progression. Thanks to the use of ginseng and rhubarb as the principal herbs in this formula, which simultaneously regulate the gut-lung axis and stabilize systemic immune homeostasis, this HPD inhibition effect cannot be achieved by traditional Chinese medicine or PD-1 monotherapy alone, representing an unexpected technical effect of this invention. Survival benefits: The median progression-free survival in the combination group was 10.8 months, which was 4.6 months longer than that in the PD-1 monotherapy group and 8.1 months longer than that in the blank support group. It can stably control the tumor burden in the long term and significantly improve the long-term survival prognosis of patients.

[0086] 6.3 Complete set of immune markers in the local tumor microenvironment (CD8) + (T, Treg, IFN-γ, measured after 3 cycles of treatment) Table 4. Tumor-infiltrating immune cells and core cytokines in four groups (x±s) Grouping Tumor infiltration CD8+ T (%) Treg regulatory T cells (%) IFN-γ (pg / ml) Blank support group 4.12±0.75 12.36±1.42 1.24±0.28 Traditional Chinese medicine single-drug group 7.86±1.03 9.15±1.16 1.89±0.35 PD-1 monotherapy group 10.24±1.31 7.63±0.98 2.67±0.41 Combined treatment group 19.73±1.68 3.82±0.74 4.72±0.56 As shown in Table 4, the proportion of CD8+ T cell infiltration in the tumor of the combined treatment group was nearly twice that of PD-1 monotherapy, and the level of Treg cells was significantly downregulated. IFN-γ is a core killing mediator of CD8+ T cells, and the IFN-γ concentration in the combined treatment group was significantly higher than that in the other three groups. These three local tumor immune indicators jointly confirmed that the traditional Chinese medicine compound and PD-1 monoclonal antibody had a significant synergistic effect, and monotherapy could not achieve the same immune remodeling effect.

[0087] 6.4 Intestinal microbial diversity and abundance of beneficial bacteria producing short-chain fatty acids Fecal samples were collected from subjects in each group after 3 treatment cycles. 16S rRNA high-throughput sequencing was used to analyze the gut microbiota. The Shannon index was used to evaluate the overall diversity of the microbiota, and the relative abundance of beneficial bacteria that produce short-chain fatty acids, such as Faecalibacterium and Parabacterium, was statistically analyzed.

[0088] Table 5. Results of gut microbiota detection in four groups (x±s) Grouping Shannon Index Relative abundance (%) of beneficial bacteria producing short-chain fatty acids Blank support group 2.14±0.23 11.37±1.486 Traditional Chinese medicine single-drug group 2.76±0.29 24.62±2.71 PD-1 monotherapy group 2.21±0.25 13.15±2.04 Combined treatment group 3.48±0.34 42.83±3.26 As shown in Table 5, there was no significant difference in Shannon index and beneficial bacteria abundance between the PD-1 monotherapy group and the blank support group, proving that immunosuppressants alone cannot improve the gut microbiota. Traditional Chinese medicine monotherapy can only slightly improve gut microbiota diversity and beneficial bacteria abundance, with limited improvement. When ginseng and rhubarb were combined with PD-1, the gut microbiota diversity index and short-chain fatty acid-producing bacteria abundance were significantly improved. The two drugs worked together to reshape the healthy gut microbiota and open up the gut-lung immune pathway.

[0089] 6.5 Safety verification of immune-related adverse reactions (irAEs) We statistically analyzed all immune-related adverse reactions (irAEs) over 12 treatment cycles, including immune-related pneumonia, immune-related enteritis, rash, bone marrow suppression, and drug-induced liver injury, and differentiated the overall incidence of irAEs and the proportion of grade 3 or higher severe irAEs.

[0090] Table 6. Occurrence of four groups of immune-related adverse reactions (irAEs) Grouping Total incidence of irAE Percentage of severe irAEs of level 3 and above Incidence of immune pneumonia Incidence of immune enteritis Blank support group 13.33% 0% 0% 6.67% Traditional Chinese medicine single-drug group 20.00% 0% 0% 13.33% PD-1 monotherapy group 53.33% 20.00% 20.00% 26.67% Combined treatment group 26.67% 6.67% 6.67% 13.33% As shown in Table 6, the overall incidence of adverse events (irAEs) with PD-1 monotherapy was as high as 53.33%, which decreased to 26.67% after combining with this combination therapy, nearly halving the incidence of adverse reactions; the incidence of severe grade 3 or higher irAEs decreased from 20% to 6.67%, significantly reducing the risk of severe immunotoxicity. Immune pneumonia and immune enteritis are the two most dangerous types of irAEs in PD-1 treatment, and the incidence of both types of toxicity in the combination group was significantly lower than that in the PD-1 monotherapy group.

[0091] The experimental case study includes four parts showcasing the therapeutic effects of actual samples: Sample ZWK: Left lung squamous cell carcinoma with mediastinal lymph node metastasis and left pleural effusion, making surgery impossible. First diagnosis at the Second Affiliated Hospital of Chongqing Medical University in December 2016. From February to July 2017, he underwent 6 cycles of palliative chemotherapy combined with radiotherapy. After treatment, residual lesions were still visible on CT, so he has been taking traditional Chinese medicine orally ever since. He has regular CT scans every year, and the lesions have been fluctuating within a stable range (RECISIT 1.1 SD).

[0092] Sample LYH: First visit on June 12, 2014 at Daping Hospital of the Third Military Medical University of the People's Liberation Army, hospital number 755654, right lung adenocarcinoma T2N1M1 stage IV. No Western medicine treatment was used from beginning to end. From 2014 to 2019, the Chinese medicine of this invention was taken orally. CT evaluation showed that the tumor was shrinking continuously.

[0093] Sample STQ: Hospitalization No. 20145605, right lung squamous cell carcinoma with mediastinal lymph node metastasis, diagnosed in April 2020. After completing radiotherapy, chemotherapy and immunotherapy from May to October 2020, a standard follow-up CT scan was performed. In April 2021, signs of lesion enlargement and recurrence were found. Oral treatment with the traditional Chinese medicine of this invention was started. Follow-up examinations in July and October 2021 showed that the lesion had shrunk and the solid component had decreased.

[0094] Sample TJM: First visit to Chongqing Traditional Chinese Medicine Hospital on December 23, 2019, diagnosed with stage IV endometrial cancer with multiple intraperitoneal metastases and lung metastases. After palliative surgery of the uterus and adnexa, there were still metastatic lesions in the lungs and intraperitoneal cavity. From April 2020 to August 2020, she underwent 5 cycles of palliative chemotherapy combined with targeted therapy. On December 8, 2020, tumor lesions were still present. From this point onwards, she began oral treatment with the traditional Chinese medicine of this invention. Follow-up examinations were conducted on June 22, 2021, September 24, 2021, and December 28, 2021, and the tumor lesions were stable.

[0095] Sample ZWF: Initially diagnosed at the First Affiliated Hospital of Chongqing Medical University (hospital number 1024817), diagnosed with right submandibular follicular lymphoma. Surgical resection was performed on February 20, 2013. Postoperative PET-CT showed increased metabolic activity in the parapharyngeal, cervical, infraclavicular, mediastinal, retroperitoneal, and groin areas, suggestive of lymphoma infiltration. Four cycles of chemotherapy were administered. A follow-up CT scan at Chongqing Traditional Chinese Medicine Hospital on October 12, 2017, revealed enlarged lymph nodes throughout the body, suggesting recurrence and metastasis. Treatment with the traditional Chinese medicine of this invention began thereafter, with annual CT scans showing a gradual reduction in tumor size.

[0096] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A traditional Chinese medicine composition with tumor-suppressive effects, characterized in that: It is made from the following raw materials in parts by weight: 25-35 parts of sun-dried ginseng, 8-12 parts of rhubarb, 25-35 parts of astragalus, 25-35 parts of yam, 12-18 parts of atractylodes macrocephala, 25-35 parts of scutellaria baicalensis, 12-18 parts of immature bitter orange, 10-14 parts of apricot kernel, 12-18 parts of fritillaria thunbergii, 12-18 parts of silkworm, 12-18 parts of gleditsia sinensis thorns, 12-18 parts of processed pinellia ternata, 8-12 parts of turmeric, 8-12 parts of sparganium rhizome, and 25-35 parts of turtle shell.

2. The traditional Chinese medicine composition with tumor-suppressing effect according to claim 1, characterized in that: The mass fractions of each raw material are as follows: 30 parts of sun-dried ginseng, 10 parts of rhubarb, 30 parts of astragalus, 30 parts of yam, 15 parts of atractylodes macrocephala, 30 parts of scutellaria baicalensis, 15 parts of immature bitter orange, 12 parts of apricot kernel, 15 parts of fritillaria thunbergii, 15 parts of silkworm, 15 parts of gleditsia sinensis thorn, 15 parts of prepared pinellia ternata, 10 parts of turmeric, 10 parts of sparganium rhizome, and 30 parts of turtle shell.

3. The traditional Chinese medicine composition with tumor-suppressing effect according to claim 2, characterized in that: The dosage form of the traditional Chinese medicine composition is an oral preparation, including any one of granules, decoctions, oral liquids, capsules, and tablets.

4. A method for preparing a traditional Chinese medicine composition with tumor-suppressing effect according to any one of claims 1 to 3, characterized in that: The process includes the following steps: weighing each raw material according to its mass percentage, mixing them, adding water and decocting, filtering, concentrating, and preparing an oral preparation.

5. The use of a traditional Chinese medicine composition with tumor-inhibiting effect according to any one of claims 1 to 3 in the preparation of a drug for treating non-small cell lung cancer.

6. The application of the traditional Chinese medicine composition with tumor-suppressing effect according to claim 5 in the preparation of a drug for treating non-small cell lung cancer, characterized in that: The non-small cell lung cancer referred to is locally advanced or metastatic non-small cell lung cancer that is negative for driver genes and positive for PD-L1 expression.

7. A pharmaceutical composition for treating non-small cell lung cancer, characterized in that: Includes the traditional Chinese medicine composition according to any one of claims 1 to 3 and toripalimab.

8. The pharmaceutical composition for treating non-small cell lung cancer according to claim 7, characterized in that: The traditional Chinese medicine composition was administered orally, while toripalimab was administered intravenously.

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