Traditional Chinese medicine composition for adjuvant therapy of tumors as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for adjuvant therapy of tumors as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition comprises the following components in parts by mass: 1-10 parts of ginseng, 1-10 parts of dendrobe, 1-15 parts of fructus amomi and 1-20 parts of coix seeds. The traditional Chinese medicine composition disclosed by the invention has an effect of relieving toxic and side effects caused by chemotherapy, such as weight loss, lifetime shortening, serum kidney injury index increase and the like. The traditional Chinese medicine composition is prepared from pure medicinal and edible traditional Chinese medicines, and is remarkable in medicine effect and few in side effect. The traditional Chinese medicine composition disclosed by the invention is rich in raw materials, simple in preparation process and low in cost, is an innovation in medicines for improving tumor malignant fluid and relieving toxic and side effects of chemotherapy medicines, and has a very good market prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for adjuvant treatment of tumors, and a preparation method and application thereof. Background Art

[0002] Malignant tumors are one of the diseases with the highest mortality rates in the world. In recent years, the incidence rate has continued to rise, posing a serious threat to human health (Mao JJ, et al. Integrative oncology: Addressing the global challenges of cancer prevention and treatment. CA Cancer J Clin. 2022 Mar; 72(2): 144-164; Shi X, et al. Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives. Signal Transduct Target Ther. 2024 Aug 2; 9(1): 192). As the tumor worsens, the body's stress state and the continuous proliferation of tumor tissue will lead to the continuous consumption of nutrients in the body, presenting a multifactorial syndrome characterized by continuous skeletal muscle loss with or without loss of adipose tissue. Conventional nutritional therapy cannot completely alleviate this syndrome, ultimately leading to progressive functional impairment, also known as cancer cachexia (Cancer cachexia: involvement of an expanding macroenvironment. Cancer Cell, 2023 Mar 13; 41(3): 581-584). Cancer cachexia has a high incidence rate and is a common complication of various advanced malignant tumors. Approximately 60% to 80% of patients with progressive malignant tumors may develop cachexia, and approximately 20% of cancer patients die from cachexia (Cachexia: A systemic consequence of progressive, unresolved disease. Cell, 2023Apr27;186(9):1824-1845). Cancer patients with cancer cachexia often experience fatigue, pain, loss of appetite, and decreased body function. They are more likely to experience grade III and IV radiotherapy toxicity and side effects, and physical discomfort may lead to interruption of the radiotherapy and chemotherapy process, affecting the patient's prognosis. In addition, while killing tumor cells, the commonly used broad-spectrum chemotherapy drugs in clinical practice also show indiscriminate inhibitory or killing effects on normal cells with active growth and metabolism. Therefore, during radiotherapy and chemotherapy, a variety of toxic and side effects are often induced, including gastrointestinal reactions, gastrointestinal mucosal damage, and bone marrow suppression. These toxic and side effects not only affect the patient's quality of life, but also seriously hinder the treatment process of cancer patients, which may lead to interruption or delay of treatment.

[0003] According to the CSCO Guidelines for the Diagnosis and Treatment of Cancer Cachexia (2021), the best approach to treating cancer cachexia may involve single or combined strategies, including targeted drugs, nutritional support, and exercise. Currently, the U.S. Food and Drug Administration has not approved any drugs for the treatment of cancer cachexia. It has been reported that in some clinical trials, nutritional counseling and dietary guidance can increase weight to a certain extent, but clinical evidence is still limited. However, for patients with advanced malignancies, nutritional intervention alone does not bring survival benefits. In the absence of stronger evidence, no specific drug intervention can be recommended as a standard of care. Therefore, clinicians may choose to prescribe drugs that are not specifically used to treat cancer cachexia. For example, clinicians can provide patients with loss of appetite and / or weight loss with drug interventions including short-term trials of progesterone analogs or corticosteroids. The choice of agent and course of treatment depends on the treatment goals and the risk-benefit assessment. A phase II clinical trial involving multiple cancer types showed that the appetite enhancer mirtazapine improved appetite and weight gain in approximately one-third of patients, but information on the impact of cancer treatment is lacking (Novel investigational biologics for the treatment of cancer cachexia. Expert Opin Biol Ther 14:1113-1120, 2014). Although current pharmacological interventions associated with improving appetite and / or weight include progesterone analogs and corticosteroids, other evaluated interventions either had no benefit or insufficient evidence of benefit to draw conclusions about their efficacy.

[0004] Through holistic conditioning and syndrome differentiation, Chinese medicine can enhance the patient's immunity, improve physical fitness, and alleviate the discomfort caused by chemotherapy. For example, Chinese medicine can effectively alleviate the toxic and side effects of chemotherapy such as gastrointestinal reactions, bone marrow suppression, and immune dysfunction by replenishing qi and blood, strengthening the spleen and stomach, and alleviate cachexia symptoms (He Linqiao, Zeng Borong. Clinical Observation on the Treatment of Cancer Cachexia with Fuzheng Oral Liquid [J]. Journal of Traditional Chinese Medicine, 2017, 23(6):3; Song Na et al. "Observation on the Clinical Efficacy of Modified Tiaowei Xingpi Recipe in Improving Cachexia Symptoms in Advanced Cancer Patients." World Traditional Chinese Medicine 9(2016):6.); On the other hand, it can synergize with chemotherapy drugs to enhance the inhibitory and killing effects on tumor cells, thereby improving the effectiveness of tumor treatment (Qin Weifu, He Juqiao. "Clinical Observation on the Effect of Yiqi Fuyuan Decoction on Reducing Toxicity and Increasing Efficacy of Chemotherapy in Patients with Postoperative Colorectal Cancer." Liaoning Journal of Traditional Chinese Medicine 38.2(2011):2; Xie Yuanyuan, Deng Yanan, Xu Yu, & Sun Xiao. Effect of Shenqi Fuzheng Injection Combined with Sintilimab on the Enhancement and Reduction of Toxicity in Patients with Advanced Gastric Cancer Chemotherapy. Hainan Medicine, 2024, 35(11), 1549-1554.). Based on existing research results and clinical practice experience, it is undeniable that TCM adjuvant therapy has a certain positive effect on reducing the toxic side effects of chemotherapy and improving tumor cachexia. Summary of the Invention

[0005] The purpose of the present invention is to overcome the shortcomings and deficiencies of the prior art and to provide a Chinese medicine composition for adjuvant treatment of tumors. The present invention selects several Chinese medicines that are both medicinal and edible, and according to the characteristics of their nature, flavor, meridians, efficacy and main indications, follows the principle of compatibility of monarch, minister, assistant and envoy to finely formulate the prescription, and innovates a Chinese medicine composition for reducing toxicity and increasing efficacy of tumor chemotherapy. It is hoped that by comprehensively adjusting the overall function of the body, it can exert its effects from multiple targets, multiple links and multiple pathways, effectively alleviate the toxic and side effects caused by chemotherapy, such as gastrointestinal reactions, bone marrow suppression, and immune dysfunction, improve cachexia, improve the effectiveness of tumor treatment and the quality of life of patients, provide innovative ideas and strategic support for the optimization of comprehensive treatment plans for tumor chemotherapy, and open up new paths and possibilities for the optimization of treatment and rehabilitation of patients undergoing tumor chemotherapy.

[0006] Another object of the present invention is to provide a method for preparing the above-mentioned traditional Chinese medicine composition for adjuvant treatment of tumors.

[0007] Another object of the present invention is to provide an application of the above-mentioned traditional Chinese medicine composition for adjuvant treatment of tumors.

[0008] The purpose of the present invention is achieved through the following technical solutions:

[0009] A traditional Chinese medicine composition for adjuvant treatment of tumors comprises the following components: ginseng, dendrobium, amomum villosum and coix seed.

[0010] Furthermore, the traditional Chinese medicine composition comprises the following components in parts by weight: 1 to 10 parts of ginseng, 1 to 10 parts of dendrobium, 1 to 15 parts of amomum villosum, and 1 to 20 parts of coix seed.

[0011] Furthermore, the traditional Chinese medicine composition is composed of the following components in parts by mass: 1 to 10 parts of ginseng, 1 to 10 parts of dendrobium, 1 to 15 parts of amomum villosum, and 1 to 20 parts of coix seed.

[0012] Furthermore, the traditional Chinese medicine composition is composed of the following components in parts by mass: 1 to 3 parts of ginseng, 1 to 3 parts of dendrobium, 2 to 4 parts of amomum villosum, and 3 to 9 parts of coix seed.

[0013] Furthermore, the traditional Chinese medicine composition is composed of the following components in parts by mass: 1 part of ginseng, 1 part of dendrobium, 2 parts of amomum villosum, and 3 parts of coix seed.

[0014] Furthermore, the Chinese medicine composition consists of an effective ingredient or an effective ingredient and a pharmaceutically acceptable carrier.

[0015] Furthermore, the dosage form of the Chinese medicine composition includes an oral preparation or a transdermal absorption preparation;

[0016] Furthermore, the oral preparation includes granules, powders, tablets, pills, oral liquids, capsules or soft capsules.

[0017] The preparation method of the above-mentioned traditional Chinese medicine composition for adjuvant tumor treatment is to take each component by mass, crush it to obtain powder, break the wall, and grind it into fine powder; or take each component by mass, add water to decoct, and combine the decoction.

[0018] Furthermore, the crushing is achieved by an ultra-micro nano-crushing machine.

[0019] Furthermore, the cell wall breaking is carried out at 0-4°C.

[0020] Furthermore, before use, the obtained fine powder is dissolved and mixed with physiological saline, and then broken into a suspension using an ultrasonic instrument after mixing.

[0021] Furthermore, the water-adding decoction is as follows: ginseng is decocted separately, first soaked for 30 to 60 minutes, and then decocted slowly for 2 to 3 hours at a material-liquid ratio of 1:5 to obtain ginseng decoction; dendrobium is decocted separately, first soaked for 60 minutes, and then decocted slowly for 2 to 3 hours at a material-liquid ratio of 1:5 to obtain dendrobium decoction; coix seed is decocted in the same conventional manner, first soaked for 30 minutes, and then decocted for the first time at a material-liquid ratio of 1:2, then boiled on low heat for 20 to 30 minutes, and decocted for the second time for 40 minutes to obtain coix seed decoction; amomum villosum is added 5 to 10 minutes before the end of the first decoction, and maintained on low heat for 5 to 10 minutes after boiling to obtain amomum villosum decoction.

[0022] The application of the above-mentioned Chinese medicine composition for adjuvant tumor treatment includes at least one of the following applications:

[0023] (1) Application in the preparation of drugs for adjuvant treatment of tumors;

[0024] (2) Application of combined chemotherapy drugs in the preparation of anti-tumor drugs.

[0025] Furthermore, the tumor preferably includes any one or more of brain glioma, oral cancer, nasopharyngeal cancer, esophageal cancer, gastric cancer, small intestine cancer, colorectal cancer, liver cancer, pancreatic cancer, breast cancer, lung cancer, prostate cancer, melanoma, osteosarcoma, leukemia, cervical cancer, ovarian cancer, bladder cancer, thyroid cancer, non-Hodgkin's lymphoma, etc., and their metastases.

[0026] Furthermore, the drugs used in the chemotherapy include any one or more of CAPEOX chemotherapy regimen, FOLFIRINOX chemotherapy regimen, FOLFOX chemotherapy regimen, GP chemotherapy regimen, docetaxel, paclitaxel, irinotecan, cisplatin, carboplatin-paclitaxel, epirubicin, doxorubicin, fluorouracil and its derivatives, and gemcitabine.

[0027] Furthermore, the CAPEOX chemotherapy regimen includes drugs capecitabine and oxaliplatin.

[0028] Furthermore, the FOLFIRINOX chemotherapy regimen includes the drugs 5-fluorouracil, folinate, oxaliplatin, and irinotecan;

[0029] Furthermore, the FOLFOX chemotherapy regimen includes drugs 5-fluorouracil, folinic acid, and oxaliplatin.

[0030] Furthermore, the GP chemotherapy regimen includes drugs gemcitabine and cisplatin.

[0031] Furthermore, the medicine also includes other pharmaceutically acceptable carriers or excipients.

[0032] Furthermore, the drug is administered by any one or more of oral administration, oral gavage, intraperitoneal injection, intramuscular injection, and intravenous injection.

[0033] The principle of the present invention is as follows: the early clinical diagnosis of most malignant tumors is difficult, and most cancer patients are already in the middle and late stages when they are diagnosed. Patients with middle and late stage tumors have been suffering from the disease for a long time, and the evil qi is deep and the righteous qi is weak. Patients will experience symptoms of spleen weakness such as loss of appetite, loose stools, weakness in the limbs, pale tongue and weak pulse. It is advisable to strengthen the spleen, replenish deficiency, promote qi and harmonize the stomach; patients with middle and late stage tumors need to undergo some radiotherapy and chemotherapy, and these treatment methods usually cause certain side effects that lead to extreme weakness of the patient's body. Symptoms such as poor appetite, weakness in the limbs, mental fatigue, thick tongue coating, diarrhea, and loose stools may also occur. In addition, the damage caused by radiotherapy in patients with middle and late stage tumors falls into the category of fire evil and heat toxicity in traditional Chinese medicine, and is an exogenous fire toxicity. It is advisable to clear away heat and nourish the stomach at the beginning, and then nourish yin and tonify the kidney; the digestive system damage and bone marrow suppression symptoms caused by chemotherapy cause spleen and kidney yin deficiency symptoms, and the treatment first recommends strengthening the spleen, tonifying the kidney and nourishing yin. In this prescription, ginseng is the main ingredient, tonifying vital energy, nourishing the spleen and lungs, promoting fluid production, nourishing blood, and calming the mind. It can be used to alleviate symptoms such as limb fatigue, spontaneous perspiration, wheezing and coughing due to lung deficiency, poor appetite and loose stools, insomnia, and memory loss. It is a crucial remedy for those in critical condition, treating all deficiency symptoms in men and women and a premier remedy for internal injuries caused by consumptive fatigue. Dendrobium is the auxiliary ingredient, nourishing the stomach and promoting fluid production, nourishing yin, clearing heat, and tonifying the kidneys. It is particularly suitable for cancer patients experiencing symptoms of yin deficiency, internal heat, and qi deficiency after chemotherapy, such as dry mouth and throat, loss of appetite, and fatigue. The combination of the two tonifies both qi and yin, strengthening the body's resistance to disease, and reducing fatigue and the risk of infection. They also nourish yin, tonify the lungs, nourish the stomach and promote fluid production, and calm the mind and improve intelligence. Coix seed is a mild, penetrating, and nourishing herb. It strengthens the spleen and dispels dampness, while also stopping diarrhea, eliminating numbness, clearing heat and discharging pus. It promotes diuresis without damaging the body's vital energy, and tonifies the spleen without causing greasy indigestion. It is commonly used as an adjuvant for lung and intestinal abscesses. Amomum villosum not only invigorates the spleen but also harmonizes the stomach and resolves stagnation, with anti-vomiting and antidiarrheal benefits, making it an adjuvant. The slightly cold Dendrobium and slightly warming ginseng in this formula avoid damaging Yang with either cold or warming herbs alone, thereby maintaining a dynamic balance between Yin and Yang. The combination of Amomum villosum and Coix seed, with their pungent and warm properties and sweet and cool properties, eliminates dampness without damaging Yin and dissipates dampness without hindering the spleen, effectively alleviating symptoms such as diarrhea and loss of appetite. The entire formula, when used together, replenishes Qi, benefits the stomach, promotes fluid production, nourishes Yin, clears heat, strengthens the spleen, and nourishes the stomach. It dissipates dampness and turbidity, promotes Qi circulation, and promotes the flow of Qi, eliminating dampness. This prescription has the functions of regulating the spleen and stomach, consolidating stomach qi, preserving body fluids, protecting the spirit, draining away dampness and stopping diarrhea. It is used for cancer patients who have indigestion, chest and abdominal distension, intestinal rumbling and diarrhea, limb fatigue, weight loss, sallow complexion, etc. after radiotherapy and chemotherapy. It can not only relieve the pain of patients, but also improve their quality of life and prolong their survival.

[0034] The present invention has the following advantages and effects compared to the prior art:

[0035] The four Chinese medicinal herbs in the composition of the present invention are all medicinal and edible herbs with mild medicinal properties. The prescription is used to strengthen the spleen and eliminate dampness, taking into account both the positive and negative effects, and is nourishing without stagnation, and promoting benefits without harshness. Adverse reactions are rarely seen after long-term use.

[0036] This prescription can be used to treat spleen and stomach qi deficiency, poor digestion and absorption, intestinal rumbling and diarrhea; abnormal ascending and descending, anorexia due to malnutrition; and shortness of breath and cough due to spleen and lung qi deficiency, dampness and phlegm. Modern research has confirmed that the composition of this invention has pharmacological effects such as regulating gastrointestinal motility, resisting fatigue, resisting stress, regulating immunity, and regulating blood lipids.

[0037] The composition of the present invention is composed of pure traditional Chinese medicine, has significant efficacy and few side effects, and the traditional Chinese medicine of the present invention has abundant raw materials, simple preparation process and low cost. It is an innovation in alleviating the toxic and side effects of chemotherapy drugs and has good market prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The figures are the experimental results of Example 3; wherein, A shows the effect of compound RSH and RSH-J on prolonging the survival of mice receiving CAPEOX chemotherapy, B shows the effect of compound RSH and RSH-J on improving the body weight of mice receiving CAPEOX chemotherapy, C shows the effect of compound RSH and RSH-J on improving tumor cachexia (muscle, fat, and energy consumption at rest) receiving CAPEOX chemotherapy, and D shows the effect of compound RSH and RSH-J on improving the serum kidney damage index Cre, inflammatory indicators interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and tumor progression indicator C-reactive protein (CRP) in mice receiving CAPEOX chemotherapy.

[0039] Figure 2 The figures are the experimental results of Example 4; wherein, A shows the effect of compound RSH and RSH-J on prolonging the survival of mice receiving FOLFIRINOX chemotherapy, B shows the effect of compound RSH and RSH-J on improving the body weight of mice receiving FOLFIRINOX chemotherapy, C shows the effect of compound RSH and RSH-J on improving tumor cachexia (muscle, fat, and energy consumption at rest) receiving FOLFIRINOX chemotherapy, and D shows the effect of compound RSH and RSH-J on improving serum Cre, IL-6, TNF-α, and CRP in mice receiving FOLFIRINOX chemotherapy.

[0040] Figure 3 The figures are the experimental results of Example 5; wherein, A represents the effect of compound RSH and RSH-J on prolonging the survival of mice receiving docetaxel chemotherapy, B represents the effect of compound RSH and RSH-J on improving the body weight of mice receiving docetaxel chemotherapy, C represents the effect of compound RSH and RSH-J on improving tumor cachexia (muscle, fat, and energy consumption at rest) of mice receiving docetaxel chemotherapy, and D represents the effect of compound RSH and RSH-J on improving serum Cre, IL-6, TNF-α, and CRP of mice receiving docetaxel chemotherapy.

[0041] Figure 4 The figures are the experimental results of Example 6; wherein, A represents the effect of compound RSH and RSH-J on prolonging the survival of mice receiving paclitaxel chemotherapy, B represents the effect of compound RSH and RSH-J on improving the body weight of mice receiving paclitaxel chemotherapy, C represents the effect of compound RSH and RSH-J on improving tumor cachexia (muscle, fat, and energy consumption at rest) of mice receiving paclitaxel chemotherapy, and D represents the effect of compound RSH and RSH-J on improving serum Cre, IL-6, TNF-α, and CRP of mice receiving paclitaxel chemotherapy.

[0042] Figure 5 The figures are the experimental results of Example 7; wherein, A represents the effect of compound RSH and RSH-J on prolonging the survival of mice receiving irinotecan chemotherapy, B represents the effect of compound RSH and RSH-J on improving the body weight of mice receiving irinotecan chemotherapy, C represents the effect of compound RSH and RSH-J on improving tumor cachexia (muscle, fat, and energy consumption at rest) of mice receiving irinotecan chemotherapy, and D represents the effect of compound RSH and RSH-J on improving serum Cre, IL-6, TNF-α, and CRP of mice receiving irinotecan chemotherapy.

[0043] Figure 6 The figures are the experimental results of Example 8; wherein, A represents the effect of compound RSH and RSH-J on prolonging the survival of mice receiving GP chemotherapy, B represents the effect of compound RSH and RSH-J on improving the body weight of mice receiving GP chemotherapy, C represents the effect of compound RSH and RSH-J on improving tumor cachexia (muscle, fat, and energy consumption at rest) of mice receiving GP chemotherapy, and D represents the effect of compound RSH-1, RSH-2, RSH-3, and RSH-J on improving serum Cre, IL-6, TNF-α, and CRP of mice receiving GP chemotherapy.

[0044] Figure 7 The figures are the experimental results of Example 9; wherein, A shows the effect of compound RSH and RSH-J on prolonging the survival of mice receiving FOLFOX chemotherapy, B shows the effect of compound RSH and RSH-J on improving the body weight of mice receiving FOLFOX chemotherapy, C shows the effect of compound RSH and RSH-J on improving the body weight of mice receiving FOLFOX chemotherapy, and D shows the effect of compound RSH and RSH-J on improving the serum levels of Cre, IL-6, TNF-α, and CRP in mice receiving FOLFOX chemotherapy.

[0045] Figure 8This is the test result of compound RSH and RSH-J in alleviating the toxic and side effects of FOLFOX chemotherapy on the liver, spleen, kidney, lung and intestine (H&E staining of mouse organs). DETAILED DESCRIPTION

[0046] The present invention will be further described in detail below with reference to the examples and accompanying drawings, but the embodiments of the present invention are not limited thereto. In a preferred embodiment, the Chinese medicine composition comprises the following Chinese medicine components in parts by weight: 1-10 parts of ginseng, 1-10 parts of dendrobium, 1-10 parts of amomum, and 1-10 parts of coix seed.

[0047] In the specific implementation process, the formula of the Chinese medicine composition is: 1 part of Dendrobium, 1 part of Ginseng, 2 parts of Amomum villosum, and 3 parts of Coix seed.

[0048] Example 1

[0049] A traditional Chinese medicine composition (RSH compound) for adjuvant tumor treatment with the effect of nourishing and strengthening the spleen, comprising the following raw materials in parts by weight: 1 part of dendrobium, 1 part of ginseng, 2 parts of amomum villosum, and 3 parts of coix seed.

[0050] The preparation method is as follows: weigh each raw material drug by weight, prepare powder by ultrafine nano powder crusher, break the wall at low temperature, grind into fine powder, add corresponding volume of physiological saline to dilute according to the dosage before use, and crush into suspension by ultrasonic instrument.

[0051] Example 2

[0052] A traditional Chinese medicine composition (RSH-J compound) for auxiliary treatment of tumors with the effects of nourishing and strengthening the spleen comprises the following raw materials in parts by weight: 1 part of dendrobium, 1 part of ginseng, 2 parts of amomum villosum, and 3 parts of coix seed.

[0053] The preparation method is as follows: weigh each raw material medicine according to weight, decoct according to the method in Table 1, and combine the decoctions.

[0054] Table 1. Decoction methods

[0055]

[0056] Example 3

[0057] The experiment used male C57BL / 6J mice, 6 weeks old, weighing 20-22g, and inoculated MC38 cells in the colon to establish an orthotopic colorectal cancer model. The C57BL / 6J mice were divided into 7 groups, namely:

[0058] CTL group (n=10)

[0059] CAPEOX group (capecitabine 100 mg / kg / time; oxaliplatin 10 mg / kg / time, n=10)

[0060] CAPEOX + RSH (0.75 g / kg / day, n=10)

[0061] CAPEOX+RSH-J (0.2 mL, n=10)

[0062] CAPEOX+reduced glutathione (40 mg / kg / day, n=10).

[0063] Mice were given RSH and the RSH-J combination for prophylaxis starting 3 days after inoculation. After tumor formation, mice were treated with CAPEOX chemotherapy once a week, depending on the mice's condition. Following chemotherapy, the combination was administered daily via gavage. Reduced glutathione was used as a positive agent, administered intraperitoneally daily at the same frequency as the combination. RSH, RSH-J, and reduced glutathione were administered continuously for 30 days. Mouse body weight and survival were recorded daily.

[0064] Mouse survival monitoring: Compared with the control group and CAPEOX group, the CAPEOX+RSH group and CAPEOX+RSH-J group prolonged the mouse survival, among which the CAPEOX+RSH group had the best effect on the mouse survival ( Figure 1 Middle A).

[0065] Body weight test: Compared with the control group, the body weight of mice in the CAPEOX group was significantly decreased; compared with the CAPEOX group, the body weight of mice in the CAPEOX+RSH and CAPEOX+RSH-J groups was significantly increased ( Figure 1 Middle B).

[0066] Tumor cachexia detection indicators Muscle and fat weight detection: Compared with the control group, the gastrocnemius muscle and fat weight of mice in the CAPEOX group were significantly decreased; compared with the CAPEOX group, the gastrocnemius muscle and fat weight of mice in the CAPEOX+RSH and CAPEOX+RSH-J groups were significantly increased ( Figure 1 Middle C).

[0067] Metabolic index detection of mice: The resting energy expenditure (REE) of mice was measured by indirect calorimetry system. It was found that compared with the control group, the REE of mice in the CAPEOX group increased; the REE of mice in the CAPEOX+RSH and CAPEOX+RSH-J groups decreased ( Figure 1 Middle C).

[0068] Serum biochemical index detection of mice: Compared with the control group, the levels of blood Cre, IL-6, TNF-α and CRP in the CAPEOX group were significantly increased; compared with the CAPEOX group, the levels of blood Cre, CRP, IL-6 and TNF-α in the CAPEOX+RSH and CAPEOX+RSH-J groups were decreased ( Figure 1 Middle D).

[0069] Note: ### P < 0.001 vs control group; * P<0.05, ** P<0.01, *** P<0.001VS CAPEOX group.

[0070] Example 4

[0071] The experiment used male C57BL / 6J mice, 6 weeks old, weighing 20-22g, and inoculated PanC02 cells orthotopically in the pancreas to establish an orthotopic pancreatic cancer model. The C57BL / 6J mice were divided into 7 groups, namely:

[0072] CTL group (n=10)

[0073] FOLFIRINOX (5-FU 50 mg / kg / time; folinate 50 mg / kg / time; oxaliplatin 10 mg / kg / time, irinotecan 20 mg / kg / time, n=10)

[0074] FOLFIRINOX+RSH (0.75g / kg / day, n=10)

[0075] FOLFIRINOX+RSH-J (0.2mL, n=10)

[0076] FOLFIRINOX+reduced glutathione (40 mg / kg / day, n=10).

[0077] Mice were given RSH and RSH-J prophylaxis starting three days after inoculation. After tumor formation, mice were treated with FOLFIRINOX chemotherapy once a week, depending on the mice's condition. Following chemotherapy, mice were gavaged with RSH and RSH-J daily. Reduced glutathione was used as a positive agent, administered intraperitoneally daily at the same frequency as the compound. RSH, RSH-J, and reduced glutathione were administered continuously for 30 days. Mouse body weight and survival were recorded daily.

[0078] Mouse survival monitoring: Compared with the control group and FOLFIRINOX group, the FOLFIRINOX+RSH and FOLFIRINOX+RSH-J groups prolonged the survival of mice, among which the FOLFIRINOX+RSH group had the best effect on the survival of mice ( Figure 2 Middle A).

[0079] Body weight test: Compared with the control group, the body weight of mice in the FOLFIRINOX group was significantly decreased; compared with the FOLFIRINOX group, the body weight of mice in the FOLFIRINOX+RSH and FOLFIRINOX+RSH-J groups was significantly increased ( Figure 2 Middle B).

[0080] Muscle and fat weight detection: Compared with the control group, the gastrocnemius muscle and fat weight of mice in the FOLFIRINOX group were significantly decreased; compared with the FOLFIRINOX group, the gastrocnemius muscle and fat weight of mice in the FOLFIRINOX+RSH and FOLFIRINOX+RSH-J groups were significantly increased ( Figure 2 Middle C).

[0081] Metabolic index detection of mice: The resting energy expenditure (REE) of mice was measured by indirect calorimetry system. It was found that compared with the control group, the REE of mice in the FOLFIRINOX group increased; the REE of mice in the FOLFIRINOX+RSH and FOLFIRINOX+RSH-J groups decreased ( Figure 2 Middle C).

[0082] Serum biochemical indexes of mice were detected: compared with the control group, the levels of Cre, IL-6, TNF-α and CRP in the FOLFIRINOX group were increased; compared with the FOLFIRINOX group, the levels of Cre, IL-6, TNF-α and CRP in the FOLFIRINOX+RSH and FOLFIRINOX+RSH-J groups were decreased ( Figure 2 Middle D).

[0083] Note: ### P < 0.001 vs control group; * P<0.05, ** P<0.01, *** P<0.001VS FOLFIRINOX group.

[0084] Example 5

[0085] Female C57BL / 6J mice, 6 weeks old and weighing 20-22g, were inoculated with 4T1 cells orthotopically in the mammary gland to establish an orthotopic breast cancer model. The C57BL / 6J mice were divided into 7 groups:

[0086] CTL group (n=10)

[0087] Docetaxel group (20 mg / kg, intraperitoneal injection, twice a week, n=10)

[0088] Docetaxel+RSH group (0.75 g / kg / day, n=10)

[0089] Docetaxel+RSH-J group (0.2 mL, n=10)

[0090] Docetaxel + recombinant human granulocyte-stimulating factor injection (15 μg / kg / day, subcutaneous injection, n=10).

[0091] Mice were given prophylactic doses of RSH and RSH-J starting three days after inoculation. After tumor formation, mice were treated with Docetaxel chemotherapy once a week, depending on the mice's condition. Following chemotherapy, mice were gavaged daily with RSH and RSH-J. Reduced glutathione was used as a positive agent, administered intraperitoneally daily at the same frequency as the compound. RSH, RSH-J, and reduced glutathione were administered continuously for 30 days. Mouse body weight and survival were recorded daily.

[0092] Mouse survival monitoring: Compared with the control group, Docetaxel group and positive drug group, Docetaxel+RSH and Docetaxel+RSH-J groups prolonged the survival of mice, among which the Docetaxel+RSH group had the best effect on the survival of mice ( Figure 3 Middle A).

[0093] Body weight test: Compared with the control group, the body weight of mice in the Docetaxel group was significantly decreased; compared with the Docetaxel group, the body weight of mice in the Docetaxel+RSH and Docetaxel+RSH-J groups was significantly increased ( Figure 3 Middle B).

[0094] Muscle and fat weight detection: Compared with the control group, the weight of gastrocnemius muscle and fat of mice in the Docetaxel group was significantly decreased; compared with the Docetaxel group, the weight of mice in the Docetaxel+RSH and Docetaxel+RSH-J groups was significantly increased ( Figure 3 Middle C).

[0095] Metabolic index detection of mice: The resting energy expenditure (REE) of mice was measured by indirect calorimetry system. It was found that compared with the control group, the REE of mice in the Docetaxel group increased; the REE of mice in the Docetaxel+RSH and Docetaxel+RSH-J groups decreased ( Figure 3 Middle C).

[0096] Serum biochemical index detection of mice: Compared with the control group, the levels of blood Cre, IL-6, TNF-α and CRP in the Docetaxel group increased; compared with the Docetaxel group, the levels of blood Cre, IL-6, TNF-α and CRP in the Docetaxel+RSH and Docetaxel+RSH-J groups decreased (P<0.001)( Figure 3 Middle D).

[0097] Note: ###P < 0.001 vs control group; * P<0.05, ** P<0.01, *** P<0.001VSDocetaxel group.

[0098] Example 6

[0099] In this experiment, male C57BL / 6J mice, 6 weeks old and weighing 20-22g, were inoculated with LLC cells in situ in their lungs to establish an orthotopic lung cancer model. The C57BL / 6J mice were divided into 7 groups:

[0100] CTL group (n=10)

[0101] Paclitaxel group (30 mg / kg / time, n=10)

[0102] Paclitaxel+RSH group (0.75 g / kg / day, n=10)

[0103] Paclitaxel+RSH-J group (0.2 mL, n=10)

[0104] Paclitaxel + recombinant human granulocyte-stimulating factor injection (15 μg / kg / day, subcutaneous injection, n=10)

[0105] Mice were given prophylactic doses of RSH and RSH-J starting 3 days after inoculation. After tumor formation, mice were treated with paclitaxel chemotherapy once a week, depending on the mice's condition. Following chemotherapy, mice were gavaged with RSH and RSH-J daily. Recombinant human granulocyte-stimulating factor injection was used as the active agent, administered subcutaneously daily at the same frequency as the compound. RSH, RSH-J, and recombinant human granulocyte-stimulating factor injection were all administered continuously for 30 days. Mouse body weight and survival were recorded daily.

[0106] Survival monitoring of mice: Compared with the control group, Paclitaxel group and positive drug group, the Paclitaxel+RSH group and Paclitaxel+RSH-J group prolonged the survival of mice, among which the Paclitaxel+RSH group had the best effect on the survival of mice ( Figure 4 Middle A).

[0107] Body weight test: Compared with the control group, the body weight of mice in the Paclitaxel group was significantly decreased; compared with the Paclitaxel group, the body weight of mice in the Paclitaxel+RSH and Paclitaxel+RSH-J groups was significantly increased ( Figure 4 Middle B).

[0108] Muscle and fat weight detection: Compared with the control group, the weight of gastrocnemius muscle and fat of mice in the Paclitaxel group was significantly decreased; compared with the Paclitaxel group, the weight of mice in the Paclitaxel+RSH and Paclitaxel+RSH-J groups was significantly increased ( Figure 4 Middle C).

[0109] Metabolic index detection of mice: The resting energy expenditure (REE) of mice was measured by indirect calorimetry system. It was found that compared with the control group, the REE of mice in the Paclitaxel group increased; the REE of mice in the Paclitaxel+RSH and Paclitaxel+RSH-J groups decreased ( Figure 4 Middle C).

[0110] Serum biochemical index detection of mice: Compared with the control group, the blood Cre content, CRP, IL-6, and TNF-α levels in the Paclitaxel group increased; compared with the Paclitaxel group, the blood Cre content, CRP, IL-6, and TNF-α levels in the Paclitaxel+RSH and Paclitaxel+RSH-J groups decreased ( Figure 4 Middle D).

[0111] Note: ### P < 0.001 vs control group; * P<0.05, ** P<0.01, *** P<0.001VS Paclitaxel group.

[0112] Example 7

[0113] The experiment used male C57BL / 6J mice, 6 weeks old, weighing 20-22g, and inoculated MC38 cells in the colon to establish an orthotopic colorectal cancer model. The C57 mice were divided into 7 groups, namely:

[0114] CTL group (n=10)

[0115] Irinotecan group (120 mg / kg / time, n=10)

[0116] Irinotecan+RSH group (0.75 g / kg / day, n=10)

[0117] Irinotecan+RSH-J group (0.2 mL, n=10)

[0118] Irinotecan + loperamide (8 mg / kg / day, n=10).

[0119] Three days after inoculation, mice received prophylactic administration of RSH and RSH-J. Once tumors had formed, Irinotecan was administered every four days, depending on the mice's weight. Loperamide, a positive agent, was administered after Irinotecan administration. If diarrhea occurred, loperamide was administered again, with the frequency depending on the severity of the diarrhea. Following chemotherapy, mice received daily oral administration of RSH and RSH-J for 30 days. During the dosing period, the mice's weight and survival were recorded daily.

[0120] Survival observation: Compared with the Irinotecan group, the Irinotecan+RSH and Irinotecan+RSH-J compound groups can effectively prolong the survival of mice, among which the Irinotecan+RSH compound group is more effective. The mice treated with Irinotecan alone died earlier, and the mice treated with Irinotecan+RSH and Irinotecan+RSH-J compound groups died later than the mice treated with Irinotecan alone ( Figure 5 Middle A).

[0121] Body weight test: Compared with the control group, the body weight of mice in the Irinotecan group was significantly decreased; compared with the Irinotecan group, the body weight of mice in the Irinotecan+RSH and Irinotecan+RSH-J compound groups was significantly increased ( Figure 5 Middle B).

[0122] Muscle and fat weight detection: Compared with the control group, the weight of gastrocnemius muscle and fat of mice in the Irinotecan group was significantly decreased; compared with the Irinotecan group, the weight of mice in the Irinotecan+RSH and Irinotecan+RSH-J groups was significantly increased ( Figure 5 Middle C).

[0123] Metabolic index detection of mice: The resting energy expenditure (REE) of mice was measured by indirect calorimetry system. It was found that compared with the control group, the REE of mice in the Irinotecan group increased; the REE of mice in the Irinotecan+RSH and Irinotecan+RSH-J groups decreased ( Figure 5 Middle C).

[0124] Serum biochemical index detection of mice: Compared with the control group, the blood Cre content, CRP, IL-6, and TNF-α levels in the Irinotecan group increased; compared with the Irinotecan group, the blood Cre content, CRP, IL-6, and TNF-α levels in the Irinotecan+RSH and Irinotecan+RSH-J groups decreased ( Figure 5 Middle D).

[0125] Note: ### P < 0.001 vs control group; * P<0.05, ** P<0.01, *** P<0.001VS Irinotecan group.

[0126] Example 8

[0127] The experiment used female BALB / c mice, 6 weeks old and weighing 20-22g, and injected 4T1 cells into the tail vein to simulate the process of tumor cells metastasizing to the lungs through the blood, thus establishing a breast cancer lung metastasis model. The BALB / c mice were divided into 7 groups, namely:

[0128] CTL group (n=10)

[0129] GP group (GP regimen: gemcitabine 200 mg / kg / time + cisplatin 1 mg / kg / time, n=10)

[0130] GP+RSH group (0.75 g / kg / day, n=10)

[0131] GP+RSH-J group (0.2 mL, n=10)

[0132] GP + reduced glutathione (40 mg / kg / day, n=10).

[0133] Mice were given prophylactic doses of RSH and RSH-J starting 3 days after inoculation. After tumor formation, mice were treated with GP chemotherapy once a week, depending on the mice's condition. Following chemotherapy, mice were gavaged daily with RSH and RSH-J. Reduced glutathione was used as a positive agent, administered intraperitoneally daily at the same frequency as the compound. RSH, RSH-J, and reduced glutathione were administered continuously for 30 days. Mouse body weight and survival were recorded daily.

[0134] Mouse survival monitoring: Compared with the control group, GP group and positive drug group, GP+RSH and GP+RSH-J groups prolonged the survival of mice, among which GP+RSH group had the best effect on the survival of mice ( Figure 6 Middle A).

[0135] Body weight test: Compared with the control group, the body weight of mice in the GP group decreased significantly; compared with the GP group, the body weight of mice in the GP+RSH and GP+RSH-J groups increased significantly ( Figure 6 Middle B).

[0136] Muscle and fat weight detection: Compared with the control group, the weight of gastrocnemius muscle and fat of mice in the GP group was significantly decreased; compared with the GP group, the weight of mice in the GP+RSH and GP+RSH-J groups was significantly increased ( Figure 6 Middle C).

[0137] Metabolic index detection of mice: The resting energy expenditure (REE) of mice was measured by indirect calorimetry system. It was found that compared with the control group, the REE of mice in the GP group increased; the REE of mice in the GP+RSH and GP+RSH-J groups decreased ( Figure 6 Middle C).

[0138] Serum biochemical index detection of mice: compared with the control group, the levels of blood Cre, IL-6, TNF-α and CRP in the GP group increased; compared with the GP group, the levels of blood Cre, IL-6, TNF-α and CRP in the GP+RSH and GP+RSH-J groups decreased ( Figure 6 Middle D).

[0139] Note: ### P < 0.001 vs control group; * P<0.05, ** P<0.01, *** P<0.001VS GP group.

[0140] Example 9

[0141] Male BALB / c mice, 6 weeks old and weighing 20-22 g, were injected with CT26 cells into the spleen to establish a colorectal cancer liver metastasis model. The BALB / c mice were divided into 7 groups:

[0142] CTL group (n=10)

[0143] FOLFOX group (5-FU 50 mg / kg / time; folinate 90 mg / kg / time; oxaliplatin 10 mg / kg / time, n=10)

[0144] FOLFOX+RSH group (0.75 g / kg / day, n=10)

[0145] FOLFOX+RSH-J group (0.2 mL, n=10)

[0146] FOLFOX+reduced glutathione (40 mg / kg / day, n=10).

[0147] Mice were given RSH and RSH-J prophylaxis starting 3 days after inoculation. After tumor formation, mice were treated with FOLFOX chemotherapy once a week, depending on the mice's condition. Following chemotherapy, mice were gavaged with RSH and RSH-J daily. Reduced glutathione was used as a positive agent, administered intraperitoneally daily at the same frequency as the compound. RSH, RSH-J, and reduced glutathione were administered continuously for 30 days. Mouse body weight and survival were recorded daily.

[0148] After 30 days, the mice were sacrificed, and the liver, kidney, spleen, jejunum, colon, and tumor were collected and fixed in 4% paraformaldehyde for at least 24 hours. Tissues were dehydrated, paraffin-embedded, and sectioned for H&E staining, and tissue damage was observed under a microscope.

[0149] Mouse survival monitoring: Compared with the control group, FOLFOX group and positive drug group, FOLFOX+RSH and FOLFOX+RSH-J groups prolonged the survival of mice, among which FOLFOX+RSH group had the best effect on the survival of mice ( Figure 7 Middle A).

[0150] Body weight test: Compared with the control group, the body weight of mice in the FOLFOX group was significantly decreased; compared with the FOLFOX group, the body weight of mice in the FOLFOX+RSH and FOLFOX+RSH-J groups was significantly increased ( Figure 7 Middle B).

[0151] Muscle and fat weight detection: Compared with the control group, the weight of gastrocnemius muscle and fat of mice in the FOLFOX group was significantly decreased; compared with the FOLFOX group, the weight of mice in the FOLFOX+RSH and FOLFOX+RSH-J groups was significantly increased ( Figure 7 Middle C).

[0152] Metabolic index detection of mice: The resting energy expenditure (REE) of mice was measured by indirect calorimetry system. It was found that compared with the control group, the REE of mice in the FOLFOX group increased; the REE of mice in the FOLFOX+RSH and FOLFOX+RSH-J groups decreased ( Figure 7 Middle C).

[0153] Serum biochemical index detection of mice: The results showed that compared with the control group, the levels of Cre, IL-6, TNF-α and CRP in the FOLFOX group increased; compared with the FOLFOX group, the levels of Cre, IL-6, TNF-α and CRP in the FOLFOX+RSH and FOLFOX+RSH-J groups decreased ( Figure 7 Middle D).

[0154] Note: ### P < 0.001 vs control group; * P<0.05, ** P<0.01, *** P<0.001VS FOLFOX group.

[0155] Mouse H&E pathological sections: Compared with the control group, the boundary between the white pulp and red pulp of the spleen in the model group was blurred, the white pulp was smaller, the villi of the small intestine were shortened, and the lamina propria was thickened. The boundary between the white pulp and red pulp of the spleen in the FOLFOX+RSH and FOLFOX+RSH-J groups was clear, the white pulp was larger, the villi of the small intestine were longer, and the lamina propria was thinner. Figure 8 ).

[0156] The results of the above in vivo experiments show that the compound of the present invention has an alleviating effect on the toxic side effects caused by chemotherapy, such as weight loss, shortened survival, and increased serum kidney damage indicators. In addition, the compound of the present invention also enhances the efficacy of chemotherapy, such as enhancing the killing effect of tumor cells.

[0157] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be considered as equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for adjuvant treatment of tumors, characterized in that: The traditional Chinese medicine composition comprises the following components: ginseng, dendrobium, amomum villosum and coix seed.

2. The Chinese medicine composition for adjuvant tumor treatment according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 1 to 10 parts of ginseng, 1 to 10 parts of dendrobium, 1 to 15 parts of amomum villosum, and 1 to 20 parts of coix seed.

3. The Chinese medicine composition for adjuvant tumor treatment according to claim 1 or 2, characterized in that: 1-3 parts of ginseng, 1-3 parts of dendrobium, 2-4 parts of amomum villosum, and 3-9 parts of coix seed.

4. The Chinese medicine composition for adjuvant tumor treatment according to claim 1 or 2, characterized in that: The Chinese medicine composition is composed of an active ingredient or an active ingredient and a pharmaceutically acceptable carrier or excipient; The dosage form of the Chinese medicine composition includes oral preparations or transdermal absorption preparations; The oral preparations include granules, powders, tablets, pills, oral liquids, capsules or soft capsules.

5. A method for preparing the Chinese medicine composition for adjuvant tumor treatment according to any one of claims 1 to 4, characterized in that: Take each component by weight, crush it to obtain powder, break the wall, and grind it into fine powder; or take each component by weight, add water and boil, and combine the decoction; The crushing is achieved by an ultra-fine nano-crushing machine; The cell wall breaking is carried out at 0-4°C.

6. The use of the traditional Chinese medicine composition for adjuvant tumor treatment according to any one of claims 1 to 4, comprising at least one of the following uses: (1) Application in the preparation of drugs for adjuvant treatment of tumors; (2) Application of combined chemotherapy drugs in the preparation of anti-tumor drugs.

7. The use according to claim 6, characterized in that: The tumors include any one or more of colorectal cancer, brain glioma, oral cancer, nasopharyngeal cancer, esophageal cancer, gastric cancer, small intestinal cancer, colorectal cancer, liver cancer, pancreatic cancer, breast cancer, lung cancer, prostate cancer, melanoma, osteosarcoma, leukemia, cervical cancer, ovarian cancer, bladder cancer, thyroid cancer, non-Hodgkin's lymphoma, etc., and their metastases.

8. The use according to claim 6, characterized in that: The drugs used in the chemotherapy include any one or more of CAPEOX chemotherapy regimen, FOLFIRINOX chemotherapy regimen, FOLFOX chemotherapy regimen, GP chemotherapy regimen, docetaxel, paclitaxel, irinotecan, cisplatin, carboplatin-paclitaxel, epirubicin, doxorubicin, fluorouracil and its derivatives, and gemcitabine.

9. The use according to claim 8, characterized in that: The CAPEOX chemotherapy regimen includes the drugs capecitabine and oxaliplatin; The FOLFIRINOX chemotherapy regimen includes the drugs 5-fluorouracil, folinic acid, oxaliplatin, and irinotecan; The FOLFOX chemotherapy regimen includes the drugs 5-fluorouracil, folinic acid, and oxaliplatin; The GP chemotherapy regimen includes the drugs gemcitabine and cisplatin.

10. The use according to any one of claims 6 to 9, characterized in that: The medicine also includes other pharmaceutically acceptable carriers or excipients; The drug can be administered orally, orally, by gavage, intraperitoneally, intramuscularly, or intravenously.

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