A traditional Chinese medicine composition for preventing recurrence and metastasis after gastrointestinal cancer surgery and application thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a traditional Chinese medicine composition for preventing postoperative recurrence and metastasis of gastrointestinal cancer and application thereof. The traditional Chinese medicine composition for preventing postoperative recurrence and metastasis of gastrointestinal cancer provided by the present application has the effects of nourishing blood, activating blood, invigorating spleen and warming yang, and can effectively prevent postoperative recurrence and metastasis of gastrointestinal cancer. The traditional Chinese medicine composition of the present application takes prepared rehmannia and radix codonopsis as monarch drugs, prepared rehmannia nourishes liver and kidney yin, liver and kidney are homologous, essence and blood are born from each other, radix codonopsis invigorates spleen and replenishes qi, and strengthens the functions of transportation, qi movement, ascending and descending; white peony root, angelica, chuanxiong rhizome and blood charcoal, which are all minister drugs, soothe liver and nourish blood, activate blood and resolve stasis, and yin yam enters liver and kidney meridians, supplements kidney and assists yang to generate and develop, yiyi- ren detoxifies and removes dampness; pericarpium citri reticulatae and amomum cardamomum regulate qi and resolve phlegm, and zanthoxylum pepper warms middle, which are all auxiliary drugs; licorice root supplements spleen and replenishes qi, and adjusts all drugs as auxiliary and minister drugs. In the prescription, qi, blood, yin and yang are supplemented, the qi movement is regulated, the whole body qi and blood are circulated, the liver, kidney and spleen are considered, the postoperative body function is recovered, the body resistance is strengthened, the evil is expelled, the cancer progression is prevented.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, and particularly relates to a traditional Chinese medicine composition for preventing postoperative recurrence and metastasis of gastrointestinal cancer and application thereof. BACKGROUND

[0002] Gastric cancer is one of the most common malignant tumors of the digestive tract, with high incidence and poor prognosis. At present, radical resection is the main treatment for gastric cancer. Except for 30% to 40% of patients with advanced gastric cancer who have no surgical opportunity, the rest can receive surgical treatment. Gastric cancer patients often relapse within 3 years after surgery. The recurrence rate of early gastric cancer is relatively low, about 12.56%. The recurrence rate of locally advanced gastric cancer patients is high, which can reach 50% to 80%. Gastric cancer has a high recurrence and metastasis rate. The main distant metastasis sites are liver, followed by lung, bone, brain and other organs, which seriously reduces the survival period. The recurrence and metastasis rates of gastric cancer after radical surgery are 19.1%, 35.0% and 39.2% in 1 year, 2 years and 3 years, respectively. The median disease-free survival is about 16.8 months (

Huake Lei, Yingkun Ren, Yong Li, et al. Value of Cancer Nodule Status Nomogram Model in Predicting Postoperative Recurrence of TNM Stage Ⅱ / Ⅲ Gastric Cancer Patients [J]. Chinese Journal of Practical Diagnosis and Treatment, 2023, 37(04): 357-362.

Xiao-Yan Xu. Analysis of Recurrence Time, Recurrence Mode and Prognosis after Radical Surgery for Gastric Cancer [D]. Nanjing Medical University, 2021.

[0003] Colorectal cancer is one of the most common malignant tumors of the intestine. Radical surgery is the first choice for the vast majority of patients with resectable colorectal cancer. Although conventional Western medicine treatments such as postoperative radiotherapy and chemotherapy reduce the recurrence and metastasis rate, there is still a 20% to 50% risk of recurrence and metastasis. Postoperative recurrence is also a major cause of shortened survival time and decreased quality of life for patients. For patients with stage II to III cancer, the rate of recurrence or metastasis after surgery reaches 50%, of which 20% to 30% experience local recurrence and metastasis, and as many as 50% to 80% experience distant metastasis. The liver is the most common site of colorectal cancer metastasis, followed by the lungs, lymph nodes, peritoneum, bone, and brain. The recurrence and metastasis rates at 1, 2, 3, 4, and 5 years after radical resection for stage II and III colorectal cancer were 11.7%, 22.9%, 27.9%, 32.5%, and 34.0%, respectively. The average disease-free survival after colorectal cancer surgery was 30.1 months. (Xu Y, Mao JJ, Sun LY, et al. Association between use of traditional Chinese medicine herbal therapy and survival outcomes in patients with stage II and III colorectal cancer: A multicenter prospective cohort study. JNCI Monographs, 2017, 2017(52): lgx015. , Peng Xia. Survival analysis of stage II and III colorectal cancer patients after surgery combined with staged syndrome differentiation and treatment and adjuvant chemotherapy [D]. Gansu University of Traditional Chinese Medicine, 2020.)

[0004] Despite adequate postoperative radiotherapy and chemotherapy, gastrointestinal cancer still suffers from high recurrence and metastasis rates. Developing new adjuvant therapies to prevent metastasis and recurrence and improve survival rates is of great clinical significance. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a traditional Chinese medicine composition for preventing postoperative recurrence and metastasis of gastrointestinal cancer and its application. The traditional Chinese medicine composition for preventing postoperative recurrence and metastasis of gastrointestinal cancer provided by this invention has the effects of nourishing blood and promoting blood circulation, strengthening the spleen and warming yang, and can effectively prevent postoperative recurrence and metastasis of gastrointestinal cancer.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] This invention provides a traditional Chinese medicine composition comprising the following components in parts by weight: 15-30 parts of Rehmannia glutinosa (processed), 10-30 parts of Angelica sinensis, 10-30 parts of Paeonia lactiflora, 5-15 parts of Ligusticum chuanxiong, 10-20 parts of Epimedium brevicornu, 10-20 parts of carbonized human hair, 20-30 parts of Codonopsis pilosula, 10-20 parts of Citrus reticulata peel, 5-10 parts of Zanthoxylum bungeanum, 10-30 parts of Coix lacryma-jobi, 5-10 parts of Amomum villosum, and 10-15 parts of Glycyrrhiza uralensis.

[0008] Preferably, the components include the following parts by weight: 15 parts Rehmannia glutinosa, 12 parts Angelica sinensis, 15 parts Paeonia lactiflora, 9 parts Ligusticum chuanxiong, 10 parts Epimedium, 10 parts carbonized human hair, 20 parts Codonopsis pilosula, 10 parts Citrus reticulata peel, 6 parts Zanthoxylum bungeanum, 30 parts Coix lacryma-jobi, 6 parts Amomum villosum, and 10 parts Glycyrrhiza uralensis.

[0009] This invention provides the application of the traditional Chinese medicine composition described above in the preparation of a drug for preventing postoperative recurrence and metastasis of cancer, including gastric cancer and / or intestinal cancer.

[0010] This invention provides a drug for preventing postoperative recurrence and metastasis of cancer, including gastric cancer and / or intestinal cancer, and the raw materials for preparing the drug include the traditional Chinese medicine composition described in the above technical solution.

[0011] Preferably, the drug also includes medically acceptable excipients.

[0012] Preferably, the medically acceptable excipients include sucrose and / or dextrin.

[0013] Preferably, the dosage form of the drug includes decoction, tablet, capsule, granule, oral liquid or drop pill.

[0014] This invention provides a method for preparing the drug described in the above technical solution, comprising the following steps:

[0015] The traditional Chinese medicine composition described in the above technical solution is decocted to obtain a medicinal liquid.

[0016] Preferably, when the dosage form of the drug is granules, the preparation method further includes the following steps:

[0017] The drug solution was concentrated and then mixed with dextrin to obtain a mixture;

[0018] The mixture is then mixed with an ethanol solution to obtain a soft material;

[0019] The soft material is sieved and then dried to obtain the granules.

[0020] This invention provides the application of the drug described in the above-described technical solution or the drug prepared by the preparation method described in the above-described technical solution in the preparation of products for preventing postoperative recurrence and metastasis of cancer, wherein the cancer includes gastric cancer and / or colorectal cancer.

[0021] Beneficial effects:

[0022] The traditional Chinese medicine composition for preventing postoperative recurrence and metastasis of gastrointestinal cancer provided by this invention has the effects of nourishing blood and promoting blood circulation, strengthening the spleen and warming yang, and can effectively prevent postoperative recurrence and metastasis of gastrointestinal cancer. The composition uses Rehmannia glutinosa and Codonopsis pilosula as the principal herbs. Rehmannia glutinosa nourishes the yin of the liver and kidneys, as the liver and kidneys share the same origin and mutually generate essence and blood. Codonopsis pilosula strengthens the spleen and replenishes qi, enhancing digestion and regulating qi circulation. Paeonia lactiflora, Angelica sinensis, Ligusticum chuanxiong, and carbonized human hair soothe the liver, nourish blood, promote blood circulation, and remove blood stasis. Epimedium enters the liver and kidney meridians, tonifying the kidneys and assisting the generation of yang qi. Coix lacryma-jobi detoxifies and resolves dampness. These are the assistant herbs. Citrus reticulata and Amomum villosum regulate qi and resolve phlegm. Zanthoxylum bungeanum warms the middle jiao. These are the adjuvant herbs. Glycyrrhiza uralensis tonifies the spleen and replenishes qi, harmonizing the other herbs. The formula nourishes qi, blood, yin, and yang simultaneously, using the regulation of qi as the pivot to circulate qi and blood throughout the body, while also considering the liver, kidneys, and spleen, to restore postoperative bodily functions, support the body's resistance, eliminate pathogenic factors, and prevent cancer progression. As can be seen from the data recorded in the examples, after taking the traditional Chinese medicine composition provided by the present invention, the median disease-free survival of 20 patients after gastric cancer surgery was 25 months, the 1-year recurrence and metastasis rate was 10%, and the 2-year recurrence and metastasis rate was 30%; the median survival of 20 patients after colorectal cancer surgery was 33 months, the 1-year recurrence and metastasis rate was 10%, and the 2-year recurrence and metastasis rate was 15%. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0024] Figure 1 The results of a retrospective study of 20 postoperative gastric cancer patients who took the drug of the present invention;

[0025] Figure 2 This is a retrospective study of the results of 20 postoperative colorectal cancer patients who took the medicine according to the embodiments of the present invention;

[0026] Figure 3 This represents the intersection of the target points of the traditional Chinese medicine composition provided by the present invention for the action of gastrointestinal cancer.

[0027] Figure 4 The prediction results of the core targets of the effective components of the traditional Chinese medicine composition provided by the present invention;

[0028] Figure 5 Results of gene ontology GO enrichment analysis and KEGG analysis;

[0029] Figure 6 Results for the number of cancerous nodules on the liver surface;

[0030] Figure 7 The results show the weight of the liver bearing tumor. Detailed Implementation

[0031] This invention provides a traditional Chinese medicine composition comprising the following components in parts by weight: 15-30 parts of Rehmannia glutinosa (processed), 10-30 parts of Angelica sinensis, 10-30 parts of Paeonia lactiflora, 5-15 parts of Ligusticum chuanxiong, 10-20 parts of Epimedium brevicornu, 10-20 parts of carbonized human hair, 20-30 parts of Codonopsis pilosula, 10-20 parts of Citrus reticulata peel, 5-10 parts of Zanthoxylum bungeanum, 10-30 parts of Coix lacryma-jobi, 5-10 parts of Amomum villosum, and 10-15 parts of Glycyrrhiza uralensis.

[0032] The present invention does not have any special requirements on the source of each component of the traditional Chinese medicine composition; commercially available products known to those skilled in the art can be used.

[0033] The traditional Chinese medicine composition of the present invention comprises 15-30 parts of Rehmannia glutinosa (processed), preferably 15-20 parts, and more preferably 15 parts, by weight. The Rehmannia glutinosa described in this invention is sweet and slightly warm in nature, and enters the liver and kidney meridians, possessing the effects of nourishing blood and yin, and replenishing essence and marrow.

[0034] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 10-30 parts of Angelica sinensis, preferably 11-15 parts, and more preferably 12 parts. The Angelica sinensis of this invention is the dried root of Angelica sinensis (Oliv.) Diels, a plant of the Apiaceae family. It is sweet, pungent, and warm in nature. It enters the liver, heart, and spleen meridians.

[0035] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 10-30 parts of white peony root, preferably 12-20 parts, and more preferably 15 parts. The white peony root of this invention is the dried root of Paeonia lactiflora Pall., a plant of the Ranunculaceae family. It is bitter, sour, and slightly cold in nature. It enters the liver and spleen meridians.

[0036] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 5-15 parts of Ligusticum chuanxiong, preferably 7-12 parts, and more preferably 9 parts. The Ligusticum chuanxiong described in this invention is the dried rhizome of Ligusticum chuanxiong Hort., a plant of the Apiaceae family. It is pungent and warm in nature. It enters the liver, gallbladder, and pericardium meridians.

[0037] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 10-20 parts of Epimedium, preferably 10-15 parts, and more preferably 10 parts. The Epimedium of this invention is the dried leaf of Epimedium brevicornu Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium pubescens Maxim., or Epimedium pubescens Maxim., all belonging to the Berberidaceae family. It is pungent, sweet, and warm in nature. It enters the liver and kidney meridians.

[0038] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 10-20 parts of carbonized human hair, preferably 10-15 parts, and more preferably 10 parts. The carbonized human hair of this invention is a carbonized product made from human hair. It is bitter and neutral in nature. It enters the liver and stomach meridians.

[0039] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 20-30 parts of Codonopsis pilosula, preferably 20-25 parts, and more preferably 20 parts. The Codonopsis pilosula of this invention is the dried root of Codonopsis pilosula (Franch.) Nannf., Codonopsis pilosula Nannf. var. modesta (Nannf.) L. Shen, or Codonopsis tangshen Oliv. It is sweet and neutral in nature, and enters the spleen and lung meridians.

[0040] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 10-20 parts of dried tangerine peel, preferably 10-15 parts, and more preferably 10 parts. The dried tangerine peel of this invention is the dried, mature peel of Citrus reticulata Blanco and its cultivated varieties, belonging to the Rutaceae family. It is bitter, pungent, and warm in nature. It enters the lung and spleen meridians.

[0041] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 5-10 parts of Sichuan pepper, preferably 5-8 parts, and more preferably 6 parts. The Sichuan pepper mentioned in this invention is the dried, mature pericarp of *Zanthoxylum schinifolium* Sieb. et Zucc. or *Zanthoxylum bungeanum* Maxim., both belonging to the Rutaceae family. It is pungent and warm in nature, and enters the spleen, stomach, and kidney meridians.

[0042] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 10-30 parts of Coix seed, preferably 20-30 parts, and more preferably 30 parts. The Coix seed of this invention is the dried, mature seed kernel of the grass Coix lacryma-jobi L. var. ma-yuen (Roman.) Stapf. It is sweet, bland, and cool in nature. It enters the spleen, stomach, and lung meridians.

[0043] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 5-10 parts of Amomum villosum, preferably 5-8 parts, and more preferably 6 parts. The Amomum villosum mentioned in this invention is the dried, mature fruit of Amomum villosum Lour., Amomum villosum Lour. var. xanthioides TLWu et Senjen, or Amomum longiligulare TLWu, all belonging to the ginger family. It is pungent and warm in nature. It enters the spleen, stomach, and kidney meridians.

[0044] Based on the mass fraction of the prepared Rehmannia root, the traditional Chinese medicine composition of this invention includes 10-15 parts of licorice root, preferably 10-12 parts, and more preferably 10 parts. The licorice root of this invention is the dried root and rhizome of the legumes *Glycyrrhiza uralensis* Fisch., *Glycyrrhiza inflata* Bat., or *Glycyrrhiza glabra* L. It is sweet and neutral in nature, and enters the heart, lung, spleen, and stomach meridians.

[0045] The traditional Chinese medicine composition for postoperative prevention of gastrointestinal cancer provided by this invention is formulated based on the theory of traditional Chinese medicine and the mechanism of postoperative metastasis. The proportions of each component are strictly controlled, balancing the effects of pathogenic factors and the body's resistance, and working synergistically to nourish blood, promote blood circulation, strengthen the spleen, and warm the yang. The traditional Chinese medicine composition provided by this invention is mild in nature, highly safe, and can reduce the recurrence and metastasis rate of gastrointestinal cancer, and prolong disease-free survival.

[0046] The present invention also provides the application of the traditional Chinese medicine composition described above in the preparation of a drug for preventing postoperative recurrence and metastasis of cancer, wherein the cancer includes gastric cancer and / or intestinal cancer.

[0047] The present invention also provides a drug for preventing postoperative recurrence and metastasis of cancer, including gastric cancer and / or intestinal cancer, and the raw materials for preparing the drug include the traditional Chinese medicine composition described in the above technical solution.

[0048] In this invention, the drug preferably further includes medically acceptable excipients; the medically acceptable excipients preferably include sucrose and / or dextrin; the dosage form of the drug preferably includes decoction, tablet, capsule, granule, oral liquid or drop pill.

[0049] The present invention also provides a method for preparing the drug described in the above technical solution, comprising the following steps:

[0050] The traditional Chinese medicine composition described in the above technical solution is decocted to obtain a medicinal liquid.

[0051] The present invention preferably involves mixing the traditional Chinese medicine composition described in the above technical solution according to the specified ratio, soaking it in 8 to 10 times the amount of water for 60 to 120 minutes, then decocting it for 0.5 to 1 hour, filtering it, and obtaining the medicinal liquid.

[0052] In this invention, when the dosage form of the drug is granules, the preparation method preferably further includes the following steps:

[0053] The drug solution was concentrated and then mixed with dextrin to obtain a mixture;

[0054] The mixture is then mixed with an ethanol solution to obtain a soft material;

[0055] The soft material is sieved and then dried to obtain the granules.

[0056] In this invention, the dextrin preferably includes maltodextrin; the volume concentration of the ethanol solution is preferably 90%.

[0057] The drug for postoperative prevention of gastrointestinal cancer provided by this invention is simple to prepare, environmentally friendly, and low in cost. It can also be prepared into various dosage forms with pharmaceutically acceptable carriers, which is convenient for clinical use and reduces hospitalization costs and economic burden.

[0058] The present invention also provides the application of the drug described in the above technical solution or the drug prepared by the preparation method described in the above technical solution in the preparation of products for preventing postoperative recurrence and metastasis of cancer, wherein the cancer includes gastric cancer and / or intestinal cancer.

[0059] To further illustrate the present invention, the following detailed description, in conjunction with the accompanying drawings and embodiments, describes a traditional Chinese medicine composition for preventing postoperative recurrence and metastasis of gastrointestinal cancer and its application, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0060] Example 1

[0061] A granule preparation for preventing postoperative recurrence and metastasis of gastrointestinal cancer is prepared according to the following parts by weight: 15 parts Rehmannia glutinosa, 12 parts Angelica sinensis, 15 parts Paeonia lactiflora, 9 parts Ligusticum chuanxiong, 10 parts Epimedium brevicornu, 10 parts carbonized human hair, 20 parts Codonopsis pilosula, 10 parts Citrus reticulata peel, 6 parts Zanthoxylum bungeanum, 30 parts Coix lacryma-jobi, 6 parts Amomum villosum, and 10 parts Glycyrrhiza uralensis.

[0062] The preparation method is as follows:

[0063] The raw medicinal materials are mixed according to the formula, soaked in 8 times the weight of water for 60 minutes, then decocted for 1 hour, filtered, and the filtrate is concentrated under reduced pressure to obtain a thick extract (relative density 1.30-1.35). Maltodextrin is added to the thick extract, and then spray-dried to obtain a dry extract. The mass ratio of the thick extract to maltodextrin is 1:1.

[0064] Next, maltodextrin is added to the dry extract at a mass ratio of 1:1 to obtain a mixed powder; then, 90% ethanol-water solution is added to the mixed powder to make a soft material, which is then sieved to obtain wet granules.

[0065] Finally, the wet granules are dried to obtain the granules for preventing postoperative recurrence and metastasis of gastrointestinal cancer. The granules are then packaged into packets of approximately 10g each for easy clinical use and administration.

[0066] Example 2

[0067] The traditional Chinese medicine decoction for preventing postoperative recurrence and metastasis of gastrointestinal cancer in this embodiment is prepared from the following raw materials: 15 parts Rehmannia glutinosa, 12 parts Angelica sinensis, 15 parts Paeonia lactiflora, 9 parts Ligusticum chuanxiong, 10 parts Epimedium brevicornu, 10 parts carbonized human hair, 20 parts Codonopsis pilosula, 10 parts Citrus reticulata peel, 6 parts Zanthoxylum bungeanum, 30 parts Coix lacryma-jobi, 6 parts Amomum villosum, and 10 parts Glycyrrhiza uralensis.

[0068] First decoction: Simmer under low pressure and maintain boiling; stop heating and collect the decoction while it is still hot, squeezing out the herbs until there is no residue. Store the decoction separately.

[0069] Second decoction with water: Measure the temperature of the medicinal materials, add purified water at a temperature not lower than the measured temperature to the medicinal materials until it exceeds the surface of the medicinal materials; Second decoction: Decoction under normal pressure and maintain boiling, stop heating and collect the liquid while hot, squeeze the medicinal materials until there is no residual liquid, combine the two decoctions and mix them evenly; Using paeoniflorin in white peony root and ferulic acid in angelica root as quality control indicator components, perform peak matching according to UPLC-Q-TOF-MS to detect the content. Each batch of indicator components is stable within M±20%. If qualified, it is packaged in doses; if unqualified, it is concentrated until the content of the medicine is qualified.

[0070] Example 3

[0071] The traditional Chinese medicine decoction for preventing postoperative recurrence and metastasis of gastrointestinal cancer in this embodiment is prepared from the following raw materials: 15 parts Rehmannia glutinosa, 12 parts Angelica sinensis, 15 parts Paeonia lactiflora, 9 parts Ligusticum chuanxiong, 10 parts Epimedium brevicornu, 10 parts carbonized human hair, 20 parts Codonopsis pilosula, 10 parts Citrus reticulata peel, 6 parts Zanthoxylum bungeanum, 30 parts Coix lacryma-jobi, 6 parts Amomum villosum, and 10 parts Glycyrrhiza uralensis.

[0072] Clean the herbs, soak them together for 30-120 minutes, add three times the amount of purified water and boil. After boiling, reduce the decoction to half its original volume, filter, and concentrate to 400ml. Divide into two portions for easy morning and evening consumption.

[0073] Example 4

[0074] In clinical practice, a retrospective study was conducted on the prognostic data of 40 patients with gastrointestinal cancer who received one dose of the granules prepared in Example 1 once a day after surgery (10 cases) and the decoction prepared in Example 3 once a day (30 cases).

[0075] Inclusion criteria:

[0076] (1) Patients with stage II-III gastrointestinal cancer confirmed by histology or cytopathology;

[0077] (2) Perform radical resection and complete at least 4 cycles of standard adjuvant chemoradiotherapy;

[0078] (3) ECOG score: 0-2 points;

[0079] (4) Age 18-75 years old;

[0080] (5) Taking the drug of the present invention for more than 8 weeks.

[0081] Exclusion criteria:

[0082] (1) Patients with concurrent acute or chronic infectious diseases;

[0083] (3) Those with severe impairment of vital organs such as the heart, liver, brain, and kidneys;

[0084] (4) Those with a history of other malignant tumors;

[0085] (5) Patients with mental illness, pregnant women and breastfeeding women.

[0086] Medication administration method:

[0087] The granules prepared in Example 1 are taken once a day, 10g each time, twice a day, morning and evening; the decoction prepared in Example 3 is taken once a day, 200ml each time, twice a day, morning and evening.

[0088] Observation indicators:

[0089] (1) Disease-free survival (DFS): refers to the time from surgery to the first tumor recurrence and metastasis, or to the patient's death due to any cause.

[0090] (2) 1-year and 2-year recurrence and metastasis rate: refers to the proportion of patients who relapse or metastasize or die (for any reason) within 1 year and 2 years after surgery.

[0091] Main results:

[0092] This invention includes 40 patients who underwent surgery for stage II-III gastrointestinal cancer. Among them, 20 patients underwent surgery for gastric cancer. The median disease-free survival was 25 months, the 1-year recurrence and metastasis rate was 10%, and the 2-year recurrence and metastasis rate was 30% (see results). Figure 1The data (where the horizontal axis represents the patient number and the vertical axis represents time in months) is superior to the data reported in the literature [Hua Kelei, Ren Yingkun, Li Yong, et al. Value of cancer nodule status nomogram model in predicting postoperative recurrence in patients with TNM stage II / III gastric cancer [J]. Chinese Journal of Practical Diagnosis and Treatment, 2023, 37(04):357-362.] and [Xu Xiaoyan. Study on recurrence time, recurrence pattern and prognosis analysis after radical gastrectomy for gastric cancer [D]. Nanjing Medical University, 2021.] (the recurrence and metastasis rates at 1, 2 and 3 years after radical gastrectomy for gastric cancer were 19.1%, 35.0% and 39.2%, respectively, and the median disease-free survival was approximately 16.8 months).

[0093] The median survival of 20 patients with colorectal cancer after surgery was 33 months, the 1-year recurrence and metastasis rate was 10%, and the 2-year recurrence and metastasis rate was 15% (see results). Figure 2 The data is superior to those reported in the literature [XuY,MaoJJ,SunLY, et al. Association between use of traditional Chinese medicine herbal therapy and survival outcomes in patients with stage II and III colorectal cancer: A multicenter prospective cohort study. JNCI Monographs, 2017, 2017(52):lgx015.] and [PengXia. Survival analysis of patients with stage II and III colorectal cancer after surgery combined with adjuvant chemotherapy [D]. Gansu University of Traditional Chinese Medicine, 2020.] (the recurrence and metastasis rates at 1, 2, 3, 4 and 5 years after radical resection of stage II and III colorectal cancer were 11.7%, 22.9%, 27.9%, 32.5% and 34.0%, respectively, and the average disease-free survival after colorectal cancer surgery was 30.1 months).

[0094] Some specific cases are as follows:

[0095] Case G7: Patient Cui, male, 70 years old, experienced abdominal distension and vomiting after eating in July 2015. Gastroscopy confirmed poorly differentiated adenocarcinoma. On August 14, 2015, he underwent a subtotal gastrectomy with gastrojejunostomy-Bismuth submucosal resection. Postoperatively, he received 6 cycles of tegafur + oxaliplatin chemotherapy. After adjuvant chemotherapy, he received the granules prepared in Example 1 of this invention for one year. He reported no discomfort, his appetite and sleep were normal, bowel movements were regular, and regular follow-up examinations showed no recurrence or metastasis.

[0096] Case C1: Patient Li, male, 67 years old, developed melena without obvious cause in January 2018. Colonoscopy confirmed sigmoid colon cancer. He underwent radical sigmoid colectomy in February 2018 and received 6 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine. He also received the granules prepared in Example 1 of this invention intermittently for 1 year postoperatively. His symptoms of fatigue and cold intolerance improved significantly. He underwent regular follow-up examinations thereafter. In May 2021, a follow-up examination revealed a suspicious patchy slightly low-density lesion in the right lobe of the liver, measuring 5*4cm, considered to be liver metastasis. The patient's disease-free survival reached 40 months.

[0097] Example 5

[0098] The main active ingredients and targets of action of the traditional Chinese medicine composition for the prevention of gastrointestinal cancer of this invention were screened.

[0099] A total of 247 effective components of the traditional Chinese medicine composition of this invention for preventing recurrence and metastasis of gastrointestinal cancer were identified, as shown in Table 1. An interaction network between the components and their targets was constructed, including 12 traditional Chinese medicines and 578 potential target genes.

[0100] To identify the target genes of the traditional Chinese medicine composition of this invention that have an impact on gastrointestinal cancer, 896 gastrointestinal cancer-related genes were screened and compared with 578 target genes of the active ingredients of the traditional Chinese medicine composition. 77 common target genes were found. (See below) Figure 3 The PPI network was visualized using Cytoscape software, and topological analysis was performed using the CytoNCA plugin. Using "median centrality (BC), proximity centrality (CC), and degree centrality (DC) greater than the median" as screening criteria, nine core target genes were identified: TP53 (Degree=53), TNF (Degree=50), STAT3 (Degree=49), AKT1 (Degree=53), IL6 (Degree=49), PTGS2 (Degree=48), IL1B (Degree=48), CASP3 (Degree=51), and EGFR (Degree=51). See [link to relevant documentation]. Figure 4 .

[0101] Gene Ontology GO enrichment analysis revealed that the biological processes by which traditional Chinese medicine compositions affect gastrointestinal cancer mainly include cellular responses to chemical stress, responses to lipopolysaccharides, regulation of small molecule metabolic processes, and responses to bacterial molecules. Molecular functions primarily include cytokine receptor binding, protease binding, cytokine activity, receptor ligand activity, and signal receptor activator activity. Cellular composition mainly includes membrane rafts and membrane microdomains. KEGG enrichment analysis showed that the composition was primarily involved in various viral infection-related pathways, lipid and atherosclerosis pathways, the AGE-RAGE pathway, the TNF pathway, and other pathways closely related to gastrointestinal cancer. Figure 5 .

[0102] Table 1 Effective components of traditional Chinese medicine compositions

[0103]

[0104]

[0105]

[0106]

[0107] Example 6

[0108] This embodiment demonstrates the effective effect of the traditional Chinese medicine composition of the present invention in preventing gastrointestinal cancer metastasis. According to literature reports, the liver is the most common organ for distant metastasis of gastrointestinal cancer, with an incidence of approximately 50%. Therefore, a mouse model of gastrointestinal cancer with liver metastasis was constructed by intrasplenic injection to study the preventive value of the traditional Chinese medicine composition.

[0109] SPF-grade male BALB / c mice, 6–8 weeks old and weighing 18–20 g, were acclimatized for one week. A spleen-preserving injection model was established using the "splenic injection method." CT26-luc cells were slowly injected subcapsularly into the spleen. After confirming hemostasis, the spleen was carefully pushed back into the abdominal cavity, and the abdomen was closed layer by layer. The mice were then placed on a heating pad for rewarming. CT26-luc cells returned to the liver via the portal vein and gradually formed liver metastases.

[0110] Two groups were set up for the experiment: a model group and a traditional Chinese medicine composition group, with 5 mice in each group. After modeling, the mice in the traditional Chinese medicine composition group were given 60 mg of the granules prepared in Example 1 by gavage once daily, while the mice in the model group were given an equal volume of physiological saline. The mice were observed for 28 days before tissue collection. The number of cancerous nodules on the liver surface and the tumor-bearing weight of the liver were measured. The results are shown in the table below. Figure 6 and Figure 7 , where * indicates P < 0.05.

[0111] Depend on Figure 6 and Figure 7 It is evident that the herbal composition of this invention can significantly reduce the number of cancerous nodules on the liver surface and reduce the tumor weight of the liver, indicating that this invention can effectively prevent liver metastasis and is a compound with definite curative effect in preventing gastrointestinal cancer metastasis.

[0112] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, It is made from the following components in parts by weight: 15-30 parts Rehmannia glutinosa, 10-30 parts Angelica sinensis, 10-30 parts Paeonia lactiflora, 5-15 parts Ligusticum chuanxiong, 10-20 parts Epimedium brevicornu, 10-20 parts carbonized human hair, 20-30 parts Codonopsis pilosula, 10-20 parts Citrus reticulata peel, 5-10 parts Zanthoxylum bungeanum, 10-30 parts Coix lacryma-jobi, 5-10 parts Amomum villosum, and 10-15 parts Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, It is made from the following components in parts by weight: 15 parts Rehmannia glutinosa, 12 parts Angelica sinensis, 15 parts Paeonia lactiflora, 9 parts Ligusticum chuanxiong, 10 parts Epimedium, 10 parts carbonized human hair, 20 parts Codonopsis pilosula, 10 parts Citrus reticulata peel, 6 parts Zanthoxylum bungeanum, 30 parts Coix lacryma-jobi, 6 parts Amomum villosum, and 10 parts Glycyrrhiza uralensis.

3. The use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicament for preventing postoperative recurrence and metastasis of cancer, wherein the cancer is gastric cancer and / or intestinal cancer.

4. A drug for preventing postoperative recurrence and metastasis of cancer, wherein the cancer is gastric cancer and / or intestinal cancer, characterized in that, The raw materials for preparing the drug include the traditional Chinese medicine composition as described in claim 1 or 2.

5. The drug according to claim 4, characterized in that, The drug also includes pharmaceutically acceptable excipients.

6. The drug according to claim 4, characterized in that, Pharmaceutically acceptable excipients include sucrose and / or dextrin.

7. The drug according to claim 4, characterized in that, The dosage forms of the drug include decoctions, tablets, capsules, granules, oral liquids, or pills.

8. A method for preparing the drug according to any one of claims 4 to 7, characterized in that, Includes the following steps: The traditional Chinese medicine composition according to claim 1 or 2 is decocted to obtain a medicinal liquid.

9. The preparation method according to claim 8, characterized in that, When the dosage form of the drug is granules, the preparation method further includes the following steps: The drug solution was concentrated and then mixed with dextrin to obtain a mixture; The mixture is then mixed with an ethanol solution to obtain a soft material; The soft material is sieved and then dried to obtain the granules.

10. The use of the drug according to any one of claims 4 to 7 or the drug prepared by the preparation method according to claim 8 or 9 in the preparation of a product for preventing postoperative recurrence and metastasis of cancer, wherein the cancer is gastric cancer and / or intestinal cancer.

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