Traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer and application thereof. The traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer provided by the invention is prepared from the following components in parts by weight: 15-20 parts of raw radix astragali, 15-20 parts of lucid ganoderma, 10-20 parts of rhizoma polygonati, 15-20 parts of roasted rhizoma atractylodis macrocephalae, 15-20 parts of semen cuscutae, 8-15 parts of prepared rhizoma cyperi, 10-15 parts of rhizoma curcumae, 10-15 parts of sculellaria barbata and 5-10 parts of bombyx batryticatus. The traditional Chinese medicine composition has the effects of building middle energizer, detoxifying, harmonizing pivot and regulating primordial qi, and can improve the clinical effective rate of advanced gastric cancer, relieve clinical symptoms of patients, reduce the expression level of tumor invasion and metastasis indexes, improve the immunity of the patients and relieve adverse reactions related to chemotherapy by being combined with XELOX chemotherapy, so that the traditional Chinese medicine composition and chemotherapy drugs synergistically generate the effects of reducing toxicity and enhancing efficacy.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition for adjuvant treatment of advanced gastric cancer and application thereof. BACKGROUND

[0002] Gastric cancer is a common malignant tumor in the digestive tract, and its morbidity and mortality have been high. According to statistics, gastric cancer is the fifth most common cancer in the world and the third leading cause of cancer death (SMYTH E C, NILSSON M, GRABSCH H I, et al. Gastric cancer [J]. Lancet (London, England), 2020, 396(10251): 635-48). Due to the high cost of early screening of gastric cancer, combined with the fact that the early symptoms of gastric cancer are not typical and the development process is relatively insidious, it is easy to cause missed diagnosis and misdiagnosis. More than 60% of gastric cancer patients are in the advanced or locally advanced stage when they seek medical treatment, and the mortality rate also increases linearly.

[0003] The main treatment for early gastric cancer is endoscopic resection, and the treatment principle for advanced gastric cancer is comprehensive treatment with chemotherapy combined with immunotherapy. The current commonly used chemotherapy regimens include FOLFOX (oxaliplatin + calcium folinate + fluorouracil), once every 2 weeks, and XELOX (oxaliplatin + capecitabine), once every 3 weeks, among which the latter is the more commonly used treatment regimen (LIU J, YUAN Q, GUO H, et al. Deciphering drug resistance in gastric cancer: Potential mechanisms and future perspectives [J]. Biomed Pharmacother, 2024, 173: 116310). Even if chemotherapy drugs are used, the median survival of advanced patients is less than 1 year (SMYTH E C, NILSSON M, GRABSCH H I, et al. Gastric cancer [J]. Lancet (London, England), 2020, 396(10251): 635-48). In addition, patients receiving chemotherapy will have problems such as nausea, vomiting, loss of appetite, gastrointestinal symptoms, and hematologic toxicity; the most common grade 3 or higher treatment-related adverse events include thrombocytopenia, neutropenia, and anemia (XU J, JIANG H, PAN Y, et al. Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial [J]. Jama, 2023, 330(21): 2064-74). Peripheral neuropathy and hypersensitivity reactions are also very common adverse reactions of the XELOX regimen, with an incidence rate of up to about 20% (MAURI G, GORI V, BONAZZINA E, et al. Oxaliplatin retreatment in metastatic colorectal cancer: Systematic review and future research opportunities [J]. Cancer Treat Rev, 2020, 91: 102112).Chemotherapy resistance and chemotherapy-related adverse reactions limit its clinical efficacy, seriously affecting the quality of life and treatment compliance of patients (FERRO Y, MAUROTTIS, TARSITANO M G, et al. Therapeutic Fasting in Reducing Chemotherapy Side Effects in Cancer Patients: A Systematic Review and Meta-Analysis [J]. Nutrients, 2023, 15(12)).

[0004] The 2025 version of NCCN gastric cancer guidelines points out that for patients with advanced unresectable gastric cancer, chemotherapy can be used in combination with the best supportive treatment for symptoms to relieve symptoms and delay disease progression (AJANI J A, D'AMICO T A, BENTREM D J, et al. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology [J]. J Natl Compr Canc Netw, 2025, 23(5): 169-91). Traditional Chinese medicine compound combined with chemotherapy drugs in clinical anticancer treatment is increasingly widely used.

[0005] Gastric cancer can be attributed to "stomach pain", "dysphagia" and other categories in traditional Chinese medicine. Traditional Chinese medicine believes that the occurrence of gastric cancer is mostly due to congenital deficiency, improper diet, emotional disorders, etc., leading to spleen deficiency, accumulation of toxic evil. Professor Fang Shengquan believes that spleen deficiency and toxic accumulation are the core pathogenesis of gastric cancer. Spleen and stomach deficiency cannot transport water and nutrient essence, and the production of qi and blood is reduced, leading to deficiency of qi and blood, deficiency of vital qi, and deficiency of qi, which can promote blood flow, and the evil is vigorous, which can block the qi movement, causing blood stasis; long-term stagnation of qi and blood can produce toxic evil, phlegm, and turbidity, which can accumulate and develop into cancer, forming gastric cancer. Gastric cancer should be treated from spleen deficiency and toxic accumulation. Spleen deficiency includes spleen qi deficiency, spleen yin deficiency and spleen yang deficiency, and toxic accumulation is the mutual inclusion of pathogenic factors such as qi stagnation, blood stasis, phlegm turbidity, dampness and cancer poison. Clinically, the methods of invigorating the spleen and tonifying qi, promoting blood circulation and removing blood stasis, resolving turbidity and detoxifying are used to balance yin and yang.

[0006] Therefore, it is still an important problem to be solved in the treatment of advanced gastric cancer to provide a traditional Chinese medicine composition that can reduce chemotherapy resistance and chemotherapy-related adverse reactions. SUMMARY

[0007] To solve the above problems, the object of the present application is to provide a traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer and its application. The traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer provided by the present application is also called Qiling Tiaoyuan Drink, which has the effects of building the middle and detoxifying, and coordinating the pivot and the essence, and can improve the clinical effective rate of advanced gastric cancer, reduce the clinical symptoms of patients, reduce the expression level of tumor invasion and metastasis indexes, improve the immunity of patients, and relieve the adverse reactions related to chemotherapy, thereby producing the effects of reducing toxicity and increasing efficacy in cooperation with the chemotherapeutic drugs.

[0008] The object of the present application can be achieved by the following technical solutions:

[0009] The first object of the present application is to provide a traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer, which is composed of the following components by weight:

[0010] 15-20 parts of raw astragalus, 15-20 parts of ganoderma lucidum, 10-20 parts of polygonatum, 15-20 parts of fried atractylodes, 15-20 parts of semen cuscutae, 8-15 parts of prepared cyperus, 10-15 parts of curcuma zedoaria, 10-15 parts of hemparis handeliana, and 5-10 parts of silkworm chrysalis.

[0011] Preferably, the traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer is composed of the following components by weight:

[0012] 15-20 parts of raw astragalus, 15-20 parts of ganoderma lucidum, 10-15 parts of polygonatum, 15-18 parts of fried atractylodes, 15-18 parts of semen cuscutae, 8-12 parts of prepared cyperus, 10-12 parts of curcuma zedoaria, 12-15 parts of hemparis handeliana, and 8-10 parts of silkworm chrysalis.

[0013] More preferably, the traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer is composed of the following components by weight:

[0014] 15 parts of raw astragalus, 18 parts of ganoderma lucidum, 12 parts of polygonatum, 18 parts of fried atractylodes, 15 parts of semen cuscutae, 9 parts of prepared cyperus, 12 parts of curcuma zedoaria, 15 parts of hemparis handeliana, and 9 parts of silkworm chrysalis.

[0015] In the traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer, astragalus and ganoderma lucidum are the monarch drugs, astragalus invigorates the spleen and replenishes qi, and ganoderma lucidum invigorates the liver and kidney, strengthens the innate and replenishes the acquired, promotes the running of qi and blood, and at the same time, helps the toxin to go out, supports the healthy qi and does not stagnate the pathogenic factor. Polygonatum, atractylodes, and semen cuscutae are the ministerial drugs, which tonify the spleen and kidney, and strengthen the therapeutic effect of the monarch drugs. Prepared cyperus and curcuma zedoaria are the auxiliary drugs, prepared cyperus soothes the liver and regulates qi, and curcuma zedoaria moves qi, breaks blood stasis, and resolves mass, and the two drugs are combined to enhance the effect of regulating qi and activating blood. Hemparis handeliana and silkworm chrysalis are the ministerial drugs, hemparis handeliana clears heat and resolves toxin, and silkworm chrysalis resolves phlegm and resolves mass, and the two drugs are combined to disperse the mass in the body. The present application mainly invigorates the healthy qi, invigorates the spleen and kidney, moves qi and activates blood, resolves mass and eliminates tumor, and the composition is combined with tonification and elimination, and the primary and secondary are considered, which can invigorate the essence, relieve weakness, restore the running of qi, release heat, resolve water and dampness, disperse blood stasis, and eliminate the secondary symptoms.

[0016] The second object of the present application is to provide an application of the traditional Chinese medicine composition for assisting in treating advanced gastric cancer in preparing a traditional Chinese medicine preparation.

[0017] The third object of the present application is to provide a traditional Chinese medicine preparation containing the traditional Chinese medicine composition for assisting in treating advanced gastric cancer.

[0018] In an embodiment of the present application, the traditional Chinese medicine preparation is an oral preparation.

[0019] In an embodiment of the present application, the dosage form of the oral preparation is a decoction, a syrup, a dripping pill, a tablet, a capsule, a pill, or a granule.

[0020] In an embodiment of the present application, the traditional Chinese medicine preparation comprises a pharmaceutically acceptable excipient.

[0021] In an embodiment of the present application, the pharmaceutically acceptable excipient comprises any one or more of amino acids and mannitol.

[0022] The fourth object of the present application is to provide a preparation method of a traditional Chinese medicine preparation, comprising the following steps:

[0023] The raw astragalus, ganoderma lucidum, polygonatum, fried atractylodes, cuscuta, prepared cyperus rotundus, zedoary, kadsura japonica, and silkworm chrysalis are weighed by weight parts, decocted, and filtered to obtain the traditional Chinese medicine preparation.

[0024] In an embodiment of the present application, the filtrate obtained after filtration is compounded with a pharmaceutically acceptable excipient to prepare the traditional Chinese medicine preparation in any dosage form.

[0025] Compared with the prior art, the present application has the following beneficial effects:

[0026] Compared with the chemotherapy drug treatment, the traditional Chinese medicine composition for assisting in treating advanced gastric cancer provided by the present application, i.e., Qiling Tiaoyuan Drink combined with XELOX chemotherapy drugs, can improve the clinical effective rate of advanced gastric cancer, relieve the clinical symptoms of patients with advanced gastric cancer, increase the physical function of patients, reduce the expression level of inflammatory indexes, inhibit the malignant progression of gastric cancer to a certain extent, and reduce the adverse reactions related to chemotherapy, thereby producing a synergistic effect of attenuation and potentiation with the chemotherapy drugs. DETAILED DESCRIPTION

[0027] The present application provides a traditional Chinese medicine composition for assisting in treating advanced gastric cancer, which is composed of the following components by weight:

[0028] 15-20 parts of raw astragalus, 15-20 parts of ganoderma lucidum, 10-20 parts of polygonatum, 15-20 parts of fried atractylodes, 15-20 parts of cuscuta, 8-15 parts of prepared cyperus rotundus, 10-15 parts of zedoary, 10-15 parts of kadsura japonica, and 5-10 parts of silkworm chrysalis.

[0029] Preferably, the following weight parts of each component are included:

[0030] 15-20 parts of raw Radix Astragali, 15-20 parts of Ganoderma lucidum, 10-15 parts of Polygonatum, 15-18 parts of fried Atractylodes, 15-18 parts of Semen Trichosanthis, 8-12 parts of prepared Cyperus, 10-12 parts of Curcuma, 12-15 parts of Huperzia, and 8-10 parts of Bombyx Batryticatus.

[0031] More preferably, the following weight parts of each component are included:

[0032] 15 parts of raw Radix Astragali, 18 parts of Ganoderma lucidum, 12 parts of Polygonatum, 18 parts of fried Atractylodes, 15 parts of Semen Trichosanthis, 9 parts of prepared Cyperus, 12 parts of Curcuma, 15 parts of Huperzia, and 9 parts of Bombyx Batryticatus.

[0033] In the Chinese medicine composition for assisting in the treatment of advanced gastric cancer, Radix Astragali and Ganoderma lucidum are the monarch drugs, Radix Astragali invigorates the spleen and replenishes qi, Ganoderma lucidum invigorates the liver and kidney, strengthens the innate and replenishes the acquired, promotes the running of qi and blood, and at the same time, expels toxins and supports the healthy qi without stagnating the pathogenic qi. Polygonatum, Atractylodes, and Semen Trichosanthis are the ministerial drugs, which tonify the spleen and kidney and strengthen the therapeutic effect of the monarch drugs. Prepared Cyperus and Curcuma are the auxiliary drugs, prepared Cyperus soothes the liver and regulates qi, and Curcuma moves qi, breaks blood stasis, and resolves masses, and the two drugs are combined to promote the movement of qi and blood. Huperzia and Bombyx Batryticatus are the ministerial drugs, Huperzia clears heat and resolves toxins, and Bombyx Batryticatus resolves phlegm and resolves masses, and the two drugs are combined to disperse the masses in the body. The present application mainly invigorates the healthy qi, invigorates the spleen and kidney, moves qi and invigorates blood, resolves masses and eliminates tumors, and the composition is tonifying and eliminating, and balances the primary and secondary, which can invigorate the vital energy, relieve weakness, restore the movement of qi, release stagnation and heat, dredge water and dampness, disperse blood stasis, and eliminate the risk of secondary symptoms.

[0034] The present application provides an application of a Chinese medicine composition for assisting in the treatment of advanced gastric cancer in the preparation of a Chinese medicine preparation.

[0035] The present application provides a Chinese medicine preparation containing the Chinese medicine composition for assisting in the treatment of advanced gastric cancer.

[0036] In an embodiment of the present application, the Chinese medicine preparation is an oral preparation.

[0037] In an embodiment of the present application, the dosage form of the oral preparation is a decoction, a syrup, a dripping pill, a tablet, a capsule, a pill, or a granule.

[0038] In an embodiment of the present application, the Chinese medicine preparation includes a pharmaceutically acceptable excipient.

[0039] In an embodiment of the present application, the pharmaceutically acceptable excipient includes any one or more of amino acids and mannitol.

[0040] The present application provides a preparation method of a Chinese medicine preparation, including the following steps:

[0041] The raw radix astragali, lucid ganoderma, polygonatum, fried atractylodes, cuscuta, prepared cyperus rotundus, zedoary, kyllinga and silkworm chrysalis are taken by weight parts, decocted and filtered to obtain the traditional Chinese medicine preparation.

[0042] In one embodiment of the application, the filtrate obtained after filtration is compounded with a pharmaceutically acceptable excipient to prepare a traditional Chinese medicine preparation in any dosage form.

[0043] The application will be described in detail below in combination with specific examples.

[0044] In the following examples, the research subjects are selected from patients with advanced gastric cancer hospitalized in the Department of Digestive Medicine and Oncology of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine from February 2023 to February 2025.

[0045] 1. The diagnostic criteria are as follows:

[0046] 1) Western medicine diagnostic criteria for gastric cancer: gastric cancer is diagnosed according to histopathological typing, and the 2022 edition of the gastric cancer diagnosis and treatment guidelines is referred to. The clinical pathological stage of gastric cancer is based on the 8th edition of the TNM stage of the International Union Against Cancer (UICC) / American Joint Committee on Cancer (AJCC).

[0047] 2) Traditional Chinese medicine diagnostic criteria for gastric cancer: the 2023 edition of the Guidelines for the Diagnosis and Treatment of Gastric Cancer in Combination with Traditional Chinese and Western Medicine and the 2014 edition of the Guidelines for the Diagnosis and Treatment of Malignant Tumors in Traditional Chinese Medicine are referred to for the diagnosis of traditional Chinese medicine syndrome types of gastric cancer. The main symptoms of spleen deficiency and blood stasis syndrome are: ① lassitude and fatigue; ② loss of appetite; ③ diarrhea and intestinal rumbling; ④ abdominal pain; secondary symptoms are: ① sallow complexion; ② postprandial fullness; ③ epigastric pain; ④ dry and rough skin; tongue and pulse: dark tongue, white and slippery or thin white fur, tortuous sublingual collateral, thin and astringent pulse. Key points of syndrome differentiation: those who have 2 or more of the above main symptoms and 1 or 2 of the secondary symptoms, and whose tongue and pulse are consistent, can be diagnosed.

[0048] 2. The inclusion and exclusion criteria are as follows:

[0049] 1) Inclusion criteria: subjects must meet all the following criteria to be included in the study: ① patients aged 18-75 years, gender unrestricted; ② histologically confirmed HER2-negative, unresectable, advanced or recurrent gastric cancer or gastroesophageal junction adenocarcinoma; ③ meet the spleen deficiency and blood stasis syndrome of the traditional Chinese medicine diagnostic criteria for gastric cancer; ④ patients who meet the conditions have not received chemotherapy for locally advanced or metastatic disease, and have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria); ⑤ Eastern Cooperative Oncology Group (ECOG) physical status score (PS) 0-2; ⑥ KPS score ≥60 points, and survival period >3 months; ⑦ no serious underlying diseases, and no significant abnormalities in blood routine, heart, liver and kidney function, etc.

[0050] 2) Exclusion criteria: anyone with one or more of the following cannot be selected for this study: ① has received chemotherapy for advanced gastric cancer in the past, except for adjuvant therapy that ended > 6 months before the start of the study; ② received any experimental drugs or antitumor drugs within 4 weeks before enrollment; ③ has an adverse reaction to previous treatment (except alopecia) that has not recovered to I degree or above; ④ is HER2 positive (HER2 IHC 3+ or IHC 2+ and FISH+) and is prepared to use Herceptin as first-line therapy; ⑤ is receiving other experimental drugs or antitumor drugs simultaneously; ⑥ has a history of other tumors; ⑦ is pregnant or lactating; ⑧ is addicted to alcohol or drugs, or is allergic to drugs; ⑨ has significant organ dysfunction or other serious history of neurological or psychiatric disease.

[0051] 3. Exclusion and discontinuation criteria are as follows:

[0052] ① does not take the required medication or takes other drugs that affect the study. ② cannot cooperate with the researcher to fill out the scale. ③ has a serious adverse event or adverse reaction during the study. ④ has enrolled but not completed the clinical observation, including self-withdrawal, loss to follow-up, poor compliance, etc. ⑤ the clinician believes that there are other factors that should be discontinued.

[0053] 4. Randomization method is as follows:

[0054] An open, prospective, randomized controlled clinical trial was designed according to evidence-based medicine. Random numbers were generated using SPSS 27.0, and all eligible cases were randomly divided into test and control groups in a 1:1 ratio according to the generated random numbers.

[0055] 5. Observation indicators are as follows:

[0056] 1) Efficacy evaluation indicators

[0057] ① Primary efficacy endpoint: objective response rate (ORR) ② Secondary efficacy endpoints: disease control rate (DCR), TCM symptom score, TCM syndrome efficacy, KPS score, KPS score efficacy. ③ Changes in T lymphocytes before and after treatment were detected by flow cytometry, and CD3 + , CD4 + , CD8 + , CD4 + / CD8 + cell ratios were observed and recorded. This indicator was detected and completed by the hospital laboratory.

[0058] 2) Safety evaluation

[0059] Blood routine, liver and kidney function were used as clinical safety evaluation indicators, and adverse reactions such as nausea, vomiting, diarrhea, constipation, peripheral nerve toxicity, etc. that occurred during the observation period were recorded.

[0060] 6. The efficacy evaluation criteria are as follows:

[0061] 1) Objective response rate (ORR)

[0062] The objective response of tumor is evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria). The subjects must have measurable tumor lesions at baseline. The efficacy evaluation criteria are divided into complete remission (CR): all tumor lesions disappear and maintain for 4 weeks, partial remission (PR): the sum of the longest diameters of target lesions is reduced by ≥30% and maintain for 4 weeks, stable disease (SD): the sum of the longest diameters of target lesions is reduced or increased within the range between PR and PD, and progressive disease (PD): the sum of the longest diameters of target lesions is increased by ≥20%. ORR refers to the proportion of patients whose tumors are reduced to a certain amount and maintained for a certain period of time, including CR and PR cases. That is, ORR = (CR + PR / CR + PR + SD + PD) * 100%.

[0063] 2) Disease control rate (DCR)

[0064] DCR is the proportion of patients who achieve remission (PR + CR) and stable disease (SD) after treatment, that is, DCR = (CR + PR + SD / CR + PR + SD + PD) * 100%.

[0065] 3) TCM symptom score

[0066] The TCM symptom quantification grading score table is formulated according to the Guiding Principles for Clinical Research on New Drugs of Traditional Chinese Medicine. According to whether the patient has clinical symptoms and their degree, it is divided into four levels: no symptoms, mild, moderate and severe. No symptoms means that the patient has never had such symptoms; mild means that the symptoms occur occasionally, less than once a day or occasionally, and do not affect work and rest; moderate means that the symptoms occur 1 to 3 times a day or occasionally; severe means that the symptoms occur more than 3 times a day or frequently, affecting work and rest. The main symptoms (languor, loss of appetite, diarrhea and intestinal rumbling, abdominal pain) are scored as 0, 1, 2 and 3 for no, mild, moderate and severe, respectively; the secondary symptoms (pale complexion, postprandial fullness, stomach pain, and skin and nail disorders) are scored as 0, 1, 2 and 3 for no, mild, moderate and severe, respectively. The higher the score, the more severe the clinical symptoms.

[0067] 4) TCM syndrome efficacy

[0068] Cure: clinical symptoms and signs disappear or basically disappear, and the symptom score after treatment is reduced by ≥95% compared with that before treatment;

[0069] Marked effect: clinical symptoms and signs are significantly improved, and the symptom score after treatment is reduced by ≥70% compared with that before treatment;

[0070] Effective: improvement of clinical symptoms and signs, the symptom score after treatment decreased by ≥30% compared with that before treatment;

[0071] Invalid: no improvement of clinical symptoms and signs, the symptom score after treatment decreased by <30% compared with that before treatment;

[0072] Total effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases x 100%.

[0073] Calculation formula (nimodipine method): efficacy index = [(pre-treatment score - post-treatment score) / pre-treatment score] x 100%

[0074] 5) KPS score evaluation criteria

[0075] Improvement: KPS score after treatment increased by ≥10 points compared with that before treatment;

[0076] Stable: KPS score after treatment = 0 compared with that before treatment;

[0077] Decrease: KPS score after treatment decreased by ≥10 points compared with that before treatment.

[0078] KPS score effective rate is the number of cases improved after treatment.

[0079] 7. Statistical method

[0080] SPSS 27 statistical software was used for data analysis. Shapiro-Wilk (S-W) method was used for normality test of measurement data. If it met the normal distribution and the variance was equal, the mean ± standard deviation (X ± S) was used, and the paired t test was used for comparison within groups, and the two independent sample t test was used for comparison between groups; if it did not have the characteristics of normal distribution, the median M (P25, P75) was used, and the rank sum test was used for comparison between two groups. Rank sum test was used for comparison of ordinal data, and χ 2 test (sample size > 40) or Fisher's exact probability method (sample size < 40) was used for comparison. The test standard was α = 0.05, P < 0.05 (two-sided) indicated statistical significance, and P < 0.01 indicated extremely significant difference (two-sided).

[0081] Unless otherwise specified, all reagents used are commercially available reagents, and all detection means and methods are detection means and methods in the art.

[0082] Example 1

[0083] This example provides a traditional Chinese medicine composition for adjuvant treatment of advanced gastric cancer, as follows:

[0084] The control group is XELOX treatment plan, specifically: injection of oxaliplatin (Jiangsu O'Shea Pharmaceutical Co., Ltd., GMP H20064296, specifications: 50mg / bottle), according to 130mg / m 2 The injection amount is calculated, and intravenous infusion is performed on the first day of each course, and is repeated every 21 days; capecitabine 1000mg / m 2 (Shanghai Roche Pharmaceutical Co., Ltd., GMP H20073024, specifications: 500mg*30 tablets / box) is taken twice a day from the first to the 14th day, and is repeated every 21 days, according to 1000mg / m 2 The oral dose is calculated, 2 times / day, taken orally on the first day of each course, and stopped for 7 days after continuous oral administration for 14 days, repeated every 21 days; 21 days as a course, a total of 2 courses.

[0085] The Qiling Tiaoyuan Drink used in this embodiment is as follows:

[0086] Put raw astragalus 15g, ganoderma 18g, 12g of huangji, fried atractylodes 18g, cuscuta 15g, prepared cyperus 9g, curcuma 12g, 15g of half branch lotus, 9g of canthydia, into the decoction container, immerse the surface of the medicinal materials with cold water, and carry out the first decoction treatment (boil and continue to decoct for 20 minutes), filter to obtain the first medicinal juice;

[0087] The filtered residue is subjected to a second decoction treatment (boil and continue to decoct for 30 minutes), and then filtered to obtain the second medicinal juice;

[0088] Mix the first medicinal juice and the second medicinal juice evenly, and you get Qiling Tiaoyuan Drink (200mL in total).

[0089] The test group is added with Qiling Tiaoyuan Drink on the basis of the control group, 100mL each time, 2 times / day, taken before and after breakfast, 21 days as a course, a total of 2 courses.

[0090] Results analysis:

[0091] A total of 78 inpatients were screened for the study, 8 of which were excluded, including 5 who did not meet the inclusion criteria and 3 who refused. Finally, 70 patients were included in the trial, 35 in the control group (XELOX chemotherapy group) and 35 in the test group (Qiling Tiaoyuan Drink combined with XELOX chemotherapy group). Both groups of patients were inpatients, and the patients had good compliance. During the clinical treatment, patients cooperated with filling out the scale and blood tests in time, and there were no cases of dropout or missing.

[0092] (1) Analysis of baseline data of patients in the two groups

[0093] Among the 70 subjects finally included in the per-protocol set, 35 were in the control group and 35 in the test group. Of the total subjects, 50 were male and 20 were female. The mean age of the subjects in the control group was 65.83 ± 6.31 years, of which 8 were < 65 years old, 27 were ≥ 65 years old, the youngest was 35 years old, and the oldest was 73 years old. The mean age of the subjects in the test group was 66.14 ± 6.71 years, of which 10 were < 65 years old, 25 were ≥ 65 years old, the youngest was 36 years old, and the oldest was 74 years old. In the ECOG performance status score, the scores of the patients in both groups were mostly 1, indicating that they could engage in light physical activity. In terms of pathological type, both groups of patients were mainly gastric adenocarcinoma. In terms of clinical stage, most of the patients with advanced gastric cancer in both groups were distributed in stage IVA, with a total of 45 cases, and 25 cases in stage IVB. The main metastatic sites were peritoneum and omentum, of which 5 cases had liver metastasis, 15 cases had peritoneal and omentum metastasis, and 5 cases had metastasis to other sites. The distribution of the patients in both groups was relatively balanced in terms of gender, age, ECOG performance status, pathological type, clinical stage, and metastatic site, and the differences were not statistically significant (P > 0.05). See Table 1 below.

[0094] Table 1 Comparison of baseline data of patients in both groups (%)

[0095]

[0096]

[0097] (2) Comparison of objective response rate and disease control rate of patients in both groups

[0098] After 2 cycles of treatment, neither group of patients achieved complete remission, i.e., the tumor lesions did not disappear completely, but 3 cases in the control group achieved partial remission, while 5 cases in the test group achieved partial remission. In the control group, 14 patients had progression, while in the test group, only 6 patients had progression. The chi-square test showed that the difference in ORR between the two groups of patients was not statistically significant (P > 0.05), of which the ORR in the control group was 8.6%, and in the test group was 14.3%. The difference in DCR between the two groups was statistically significant (P < 0.05), of which the DCR in the control group was 60%, and in the test group was 82.9%. See Table 2.

[0099] Table 2 Comparison of objective response rate and disease control rate of patients in both groups (%)

[0100]

[0101]

[0102] (3) Comparison of TCM symptom scores of patients in both groups

[0103] The normality test of TCM symptom score showed P<0.05, the data was skewed distribution, so the two independent sample rank sum test was used for comparison between groups, and the paired sample rank sum test was used for comparison within groups. The results showed that there was no statistical significance in TCM symptom score before treatment in the control group and the test group (P>0.05), and the two groups could be compared. The control group could reduce the TCM symptom scores of loss of appetite, diarrhea and intestinal sound, abdominal pain, postprandial fullness, stomach and chest pain, etc. (P<0.05), but the TCM symptom score of skin and nails was significantly increased (P<0.01). The test group could reduce the TCM symptom scores of fatigue, loss of appetite, diarrhea and intestinal sound, abdominal pain, pale, postprandial fullness, stomach and chest pain, skin and nails, etc. (P<0.05), and compared with the control group, the test group had lower scores in fatigue, loss of appetite, diarrhea and intestinal sound, postprandial fullness, stomach and chest pain, skin and nails, etc. (P<0.05). See Table 3.

[0104] Table 3 Comparison of TCM symptom scores of patients in two groups before and after treatment (points, M (P25, P75))

[0105]

[0106]

[0107] Note: comparison within groups * P<0.05, ** P<0.01, comparison between groups # P<0.05, ## P<0.01

[0108] The normality test of TCM symptom total score showed P<0.05, the data was skewed distribution, so the two independent sample rank sum test was used for comparison between groups, and the paired sample rank sum test was used for comparison within groups. After rank sum test, there was no statistical difference in TCM symptom total score of patients in two groups before treatment (P>0.05), and the two groups could be compared; the TCM symptom total scores of the control group and the test group were improved after treatment (P<0.001), but the TCM symptom total score of the test group was significantly lower than that of the control group (P<0.05). See Table 4.

[0109] Table 4 Comparison of TCM symptom total scores of patients in two groups before and after treatment (points, M (P25, P75))

[0110]

[0111] (4) Comparison of clinical efficacy of patients in two groups

[0112] After treatment, the number of ineffective cases in the control group was 9, and that in the test group was 3. The total effective rate of the test group was significantly higher than that of the control group (91.4% vs 74.3%) (P<0.01). See Table 5.

[0113] Table 5 Comparison of TCM syndrome efficacy between the two groups of patients (%)

[0114]

[0115] (5) Comparison of KPS scores between the two groups of patients

[0116] The KPS scores of the two groups of patients before and after treatment were subjected to normality test, and it was found that P<0.05, the data were skewed, so the comparison between the two groups was subjected to two independent sample rank sum test, and the comparison within the group was subjected to paired sample rank sum test. The KPS scores of the two groups of patients before treatment had no statistical significance (P>0.05), and the two groups could be compared. After treatment, the KPS score of the test group was significantly increased compared with the control group (P<0.05), and the KPS scores of the control group and the test group after treatment were significantly increased compared with those before treatment (P<0.01). See Table 6.

[0117] Table 6 Comparison of KPS scores between the two groups of patients before and after treatment (points, M (P25, P75))

[0118]

[0119] (6) Comparison of KPS scores between the two groups of patients

[0120] After treatment, 12 cases in the control group had improved KPS scores, 15 cases had stable KPS scores, and 8 cases had decreased KPS scores, and the effective rate was 32.4%. In the test group, 25 cases had improved KPS scores, 7 cases had stable KPS scores, and 3 cases had decreased KPS scores, and the effective rate was 67.6%. The effective rate of the test group was better than that of the control group (P<0.01) by chi-square test. See Table 7.

[0121] Table 7 Comparison of KPS scores between the two groups of patients after treatment (cases)

[0122]

[0123] (7) Comparison of immunological indexes between the two groups of patients

[0124] CD3 + , CD4 + , CD8 + , CD4 + / CD8 +The proportion of cells was changed, and the normality test of each index between the two groups was performed. It was found that P>0.05, the variance was equal, and the data overall presented normal distribution. The two independent sample T test was used for comparison between groups, and the paired sample T test was used for comparison within groups. The results showed that the CD3 + , CD4 + , CD4 + / CD8 + cell proportions in the control group and the test group after treatment were significantly increased, and CD8 + was reduced (P<0.01). The CD3 + , CD4 + , CD4 + / CD8 + cell proportions in the test group after treatment were significantly increased, and CD8 + was significantly decreased (P<0.01). See Table 8.

[0125] Table 8 Comparison of immunological indexes of patients in two groups before and after treatment (X±S)

[0126]

[0127] Note: Comparison within groups * P<0.05, ** P<0.01

[0128] (8) Comparison of adverse reactions of patients in two groups

[0129] After 2 cycles of treatment, the patients in the two groups all had certain degree of chemotherapy-related adverse reactions. The incidence of adverse reactions such as nausea and vomiting, liver and kidney function reduction, constipation, fatigue, dry mouth and throat, loss of appetite, peripheral nerve toxicity, etc. in the test group was significantly lower than that in the control group (P<0.05). In addition, the number of cases of adverse reactions such as leukopenia, neutropenia, hemoglobin reduction, thrombocytopenia, diarrhea, etc. in the test group was lower than that in the control group, but the difference was not statistically significant (P>0.05). See Table 9.

[0130] Table 9 Comparison of chemotherapy-related adverse reactions of patients in two groups (unit: cases (%))

[0131]

[0132]

[0133] Note: Comparison between groups * P<0.05, ** P<0.01

[0134] In summary, the traditional Chinese medicine composition provided by the application can improve the clinical effective rate of advanced gastric cancer in combination with a chemotherapy regimen, alleviate the clinical symptoms of advanced patients, improve physical function, reduce chemotherapy-related adverse reactions, and achieve the purpose of reducing toxicity and increasing efficacy in cooperation with chemotherapy drugs, thereby further suppressing the progression of gastric cancer.

[0135] The foregoing description of the embodiments is to enable a person having ordinary skill in the art to understand and use the application. It will be apparent to a person skilled in the art that various modifications can be made to the embodiments and the general principles described herein can be applied to other embodiments without departing from the scope of the application. Therefore, the application is not limited to the above-described embodiments, and improvements and modifications made by those skilled in the art based on the description of the application without departing from the scope of the application should be within the scope of protection of the application.

Claims

1. A traditional Chinese medicine composition for adjuvant treatment of advanced gastric cancer, characterized in that, consists of the following components by weight parts: 15-20 parts of raw Radix Astragali, 15-20 parts of Ganoderma lucidum, 10-20 parts of Polygonatum sibiricum, 15-20 parts of fried Atractylodes, 15-20 parts of Semen Nelumbinis, 8-15 parts of prepared Cyperus rotundus, 10-15 parts of Curcuma zedoaria, 10-15 parts of Kadsura japonica, 5-10 parts of Bombyx Batryticatus.

2. The traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer according to claim 1, characterized in that, consists of the following components by weight parts: 15-20 parts of raw Radix Astragali, 15-20 parts of Ganoderma lucidum, 10-15 parts of Polygonatum sibiricum, 15-18 parts of fried Atractylodes, 15-18 parts of Semen Nelumbinis, 8-12 parts of prepared Cyperus rotundus, 10-12 parts of Curcuma zedoaria, 12-15 parts of Kadsura japonica, 8-10 parts of Bombyx Batryticatus.

3. The traditional Chinese medicine composition for adjuvant therapy of advanced gastric cancer according to claim 1, characterized in that, consists of the following components by weight parts: 15 parts of raw Radix Astragali, 18 parts of Ganoderma lucidum, 12 parts of Polygonatum sibiricum, 18 parts of fried Atractylodes, 15 parts of Semen Nelumbinis, 9 parts of prepared Cyperus rotundus, 12 parts of Curcuma zedoaria, 15 parts of Kadsura japonica, 9 parts of Bombyx Batryticatus.

4. The use of the traditional Chinese medicine composition for adjuvant treatment of advanced gastric cancer according to any one of claims 1-3 in the preparation of a traditional Chinese medicine preparation.

5. A traditional Chinese medicine preparation, characterized in that, The traditional Chinese medicine composition for adjuvant treatment of advanced gastric cancer according to any one of claims 1-3.

6. The traditional Chinese medicine preparation according to claim 5, characterized in that, The traditional Chinese medicine preparation is an oral preparation.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, The dosage form of the oral preparation is a decoction, a syrup, a dripping pill, a tablet, a capsule, a pill, or a granule.

8. The traditional Chinese medicine preparation of claim 5, characterized in that, The traditional Chinese medicine preparation includes a pharmaceutically acceptable excipient.

9. The preparation method of the traditional Chinese medicine preparation according to claim 5, characterized in that, The method comprises the following steps: Raw Radix Astragali, Ganoderma lucidum, Polygonatum sibiricum, fried Atractylodes, Semen Nelumbinis, prepared Cyperus rotundus, Curcuma zedoaria, Kadsura japonica, and Bombyx Batryticatus are weighed by weight parts, decocted, and filtered to obtain a traditional Chinese medicine preparation.

10. The preparation method of the traditional Chinese medicine preparation according to claim 9, characterized in that, The filtrate obtained after filtration is compounded with a pharmaceutically acceptable excipient to prepare a traditional Chinese medicine preparation in any dosage form.

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