Traditional Chinese medicine composition for tonifying kidney and spleen, clearing heat and softening hardness to dissipate stagnation as well as pharmaceutical preparation and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine compound preparation for tonifying kidney and spleen, clearing heat and softening hardness to dissipate stagnation and application thereof.The traditional Chinese medicine compound preparation is composed of morinda officinalis, semen cuscutae, raw radix astragali, roasted rhizoma atractylodis macrocephalae, herba lycopi, wenyujin concisum, abrus cantoniensis hance, pseudobulbus cremastrae seu pleiones, curcuma zedoary and pericarpium citri reticulatae viride and has the effects of tonifying kidney and spleen, clearing heat and softening hardness to dissipate stagnation. The traditional Chinese medicine composition disclosed by the invention has the advantages of exact curative effect, no toxic or side effect, low cost and convenience in popularization and application, and has a better clinical curative effect on treating liver cancer and large nodular cirrhosis through clinical application and observation and analysis for many years.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for tonifying the kidney and spleen, clearing away heat, softening hard masses and dispersing lumps, as well as a pharmaceutical preparation and use thereof. Background Art

[0002] Primary liver cancer is a malignant tumor with a high morbidity and mortality rate. It is a common malignant tumor and cause of death from cancer worldwide. It is currently believed that liver cancer has a relatively long subclinical period. Due to its insidious onset, 70% to 80% of cases are already in the middle and late stages when discovered, and the opportunity for radical surgical treatment is often lost. For patients with middle and late stage (BCLC B / C) liver cancer, the current treatment methods mainly include TACE, radiotherapy and systemic therapy. Systemic treatment is mainly targeted therapy and immunotherapy, but it has no significant effect on prolonging the survival of patients with middle and late stage liver cancer. The occurrence of liver cancer is a long, multi-link, and multi-factorial process, but most liver cancer patients progress from cirrhosis. Cirrhosis is also a common cause of death worldwide, seriously damaging the quality of life of patients.

[0003] In recent years, Traditional Chinese Medicine (TCM), a crucial component of comprehensive cancer prevention and control systems, has become an indispensable component of liver cancer treatment. Traditional Chinese Medicine (TCM) believes that liver cancer is caused by the invasion of damp-heat, epidemic toxins by the pathogenic factors of dampness. Its fundamental pathogenesis is the entanglement of pathogenic factors with the deficiency of vital energy, with Qi deficiency and blood stasis as the root cause and the difficulty in clearing the remaining damp-heat, epidemic toxins as the symptom. TCM offers unique advantages in anti-tumor treatment through multiple levels, targets, and pathways. Clinical studies have shown that TCM treatment can improve clinical symptoms in patients with liver cancer, enhance the body's immune system, mitigate the adverse effects of chemotherapy and radiotherapy, slow the progression of liver cirrhosis, promote hepatocyte regeneration, regulate immunity, alleviate complications of cirrhosis, reduce mortality, and improve patients' quality of life. In line with the fundamental pathogenesis of liver cirrhosis, strengthening vital energy and eliminating pathogenic factors is often the core treatment approach, with the integration of symptoms and signs as the primary TCM diagnosis and treatment model. TCM differentiation and treatment are based on the foundation of disease management. However, there are currently no specific and effective drugs for the treatment of this disease. Summary of the Invention

[0004] The present invention aims to provide a traditional Chinese medicine composition for tonifying the kidney and spleen, clearing heat, softening hard masses, and dispersing nodules, as well as its pharmaceutical preparation and use. Through long-term clinical practice, the present invention has discovered that the fundamental pathogenesis of liver cancer is a mixture of deficiency and excess, with underlying symptoms primarily characterized by spleen and kidney deficiency, and pathology primarily characterized by damp-heat, qi stagnation, and blood stasis. To address these pathogenesis, the fundamental principles of treatment are tonifying the kidney and spleen, clearing heat, softening hard masses, and dispersing nodules.

[0005] The first aspect of the present invention provides a traditional Chinese medicine composition for nourishing the kidney and strengthening the spleen, clearing away heat, softening and dispersing nodules, which is composed of the following raw materials in parts by weight: 10-20 parts of Morinda officinalis, 10-20 parts of Cuscuta australis, 15-45 parts of raw Astragalus, 10-20 parts of stir-fried Atractylodes macrocephala, 10-20 parts of Eupatorium fortunei, 10-20 parts of Curcuma longa, 10-20 parts of Gastrodia elata, 3-9 parts of Psoralea corylifolia, 3-9 parts of Curcuma zedoaria, and 3-9 parts of Citrus aurantium.

[0006] Furthermore, the traditional Chinese medicine composition is composed of the following raw medicines in parts by weight: 12-18 parts of Morinda officinalis, 12-18 parts of Cuscuta australis, 25-35 parts of raw Astragalus, 12-18 parts of stir-fried Atractylodes macrocephala, 12-18 parts of Zedoariae rhizome, 12-18 parts of Curcuma longa, 12-18 parts of Glechoma longifolia, 5-7 parts of Trillium gracile, 5-7 parts of Curcuma zedoaria, and 5-7 parts of Citrus aurantium.

[0007] Furthermore, the Chinese medicine composition is composed of the following raw medicines in parts by weight: 15 parts of Morinda officinalis, 15 parts of Cuscuta australis, 30 parts of raw Astragalus membranaceus, 15 parts of stir-fried Atractylodes macrocephala, 15 parts of Zedoariae rhizome, 15 parts of Curcuma longa, 15 parts of Glechoma longifolia, 6 parts of Trillium gracile, 6 parts of Curcuma zedoaria, and 9 parts of Citrus aurantium.

[0008] The second aspect of the present invention provides a pharmaceutical preparation having the above-mentioned traditional Chinese medicine composition as an active ingredient, wherein the pharmaceutical preparation is prepared into a commonly used dosage form in pharmacy by conventional preparation methods in the art.

[0009] Furthermore, the pharmaceutical preparation is a decoction, tablet, capsule, granule, pill, oral liquid or syrup.

[0010] Furthermore, the pharmaceutical preparation also includes pharmaceutically acceptable excipients.

[0011] Furthermore, the pharmaceutical preparation can be prepared by the following method: (A) weighing the medicinal components, mixing them, and obtaining a mixture; (B) adding a pharmaceutically acceptable carrier to the mixture and preparing the mixture by conventional preparation methods in the art.

[0012] The third aspect of the present invention provides a use of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament for treating liver cancer and macronodular cirrhosis.

[0013] A fourth aspect of the present invention provides a use of the pharmaceutical preparation described above in the preparation of a drug for treating liver cancer and macronodular cirrhosis.

[0014] Furthermore, the liver cancer is primary liver cancer.

[0015] Furthermore, the criteria for determining macronodular cirrhosis refer to the criteria in Liang Kuohuan's "Hepatology": nodules are large and uneven in size, generally >3 mm in diameter and up to several centimeters in size, with irregular fibrous septa and the prevalence of regenerative nodules. These nodules can be considered precancerous lesions of the liver, and pathological diagnoses include regenerative nodules, dysplastic foci, and dysplastic nodules.

[0016] The traditional Chinese medicine composition of the present invention can reduce the disease progression rate, prolong progression-free survival, and increase the progression-free survival rate in patients with macronodular compensated hepatitis B cirrhosis. It can also improve patients' elastic ultrasound liver stiffness (LSM) values ​​and improve Traditional Chinese Medicine (TCM) symptoms, demonstrating significant therapeutic effects for patients with macronodular cirrhosis. The traditional Chinese medicine composition of the present invention can also reduce the postoperative recurrence rate and prolong postoperative disease-free survival in patients with primary liver cancer, demonstrating significant therapeutic effects for patients undergoing liver cancer surgery.

[0017] Liver cancer and macronodular cirrhosis, as used in this invention, are modern medical disease names. In traditional Chinese medicine, they fall under the category of "accumulation." Based on the patient's relevant clinical symptoms, they can also be categorized as "flank pain," "dampness," "jaundice," and other disease names. The term "accumulation" was first mentioned in the Neijing (Inner Canon of Medicine), which explores its formation and pathogenesis. Lingshu (Lingshu) states in its Five Changes: "People are prone to intestinal accumulation. How can this be predicted? Shao Yu answers: Thin, dull skin, and loose, soft, moist flesh. This indicates intestinal distress. Distress leads to the retention of pathogenic qi, which causes damage. Between the spleen and stomach, the flow of cold and heat is inconsistent. When pathogenic qi arrives, it accumulates and lingers, leading to a major accumulation." The Difficult Classic provides a detailed distinction between accumulation and congestion syndromes, and outlines the clinical symptoms of accumulation in the five internal organs. "Liver accumulation is called 'fat qi,' which is located under the left rib, like an inverted cup, with a head and feet. If it persists for a long time, it can cause coughs, lumps, and malaria, which can persist for years." The Jingyue Complete Works summarizes the application of attack-and-tonify methods to treat accumulations: "In summary, there are no more than four methods: attack, dissipate, disperse, and tonify." Exposure to cold and dampness, emotional depression, excessive drinking and eating, and prolonged illnesses such as jaundice, insect poisoning, and malaria are the primary pathogenic factors for the formation of accumulations, while deficiency of vital energy is an intrinsic factor. The fundamental pathogenesis is the entanglement of pathogenic factors with deficiency of vital energy, with qi stagnation and blood stasis as the root cause, and dampness, toxicity, and heat retention in the blood as the secondary cause.

[0018] The Chinese medicine composition of the present invention is formulated with careful selection of herbs based on years of clinical practice and guided by traditional Chinese medicine theory. Morinda officinalis and Cuscuta chinensis warm and tonify the kidney yang, nourishing the innate foundation, and serve as the main herbs; Astragalus membranaceus and Atractylodes macrocephala invigorate the spleen and replenish qi, and protect the acquired foundation, and serve as the assistant herbs; Herba Glechomae Atractylodis Macrocephalae clears heat and detoxifies, soothes the liver and reduces jaundice; Trillium gracile clears heat and detoxifies and disperses stagnation; Herba Eupatorii promotes blood circulation and promotes diuresis; and Curcuma longa and Atractylodes lancea promote blood circulation and qi circulation; Citrus aurantium soothes the liver and regulates qi, and guides the herbs into the liver meridian; the combination of herbs achieves the effects of tonifying the kidney and strengthening the spleen, clearing heat, softening hard masses, and dispersing stagnation, strengthening the body's resistance without hindering the evil, and dispelling the evil without harming the body's resistance. It can be used to treat patients with spleen and kidney deficiency and incomplete damp-heat syndrome, and is in line with the core pathogenesis of liver cancer and macronodular cirrhosis.

[0019] The weight ratio of the raw materials of the traditional Chinese medicine compound preparation of the present invention is obtained by the inventor through long-term clinical practice in combination with traditional Chinese medicine syndrome differentiation and formulation, and good therapeutic effects can be achieved within this ratio range.

[0020] The advantages of the present invention are:

[0021] 1. The inventors, based on their own understanding of the core pathogenesis of liver cancer and nodular cirrhosis (spleen and kidney deficiency as the root cause, and qi stagnation, blood stasis, and difficulty in clearing away residual pathogenic factors such as damp-heat and toxicity as the symptoms), have provided a traditional Chinese medicine composition with the effects of tonifying the kidney and spleen, clearing away heat, softening hard masses and dispersing nodules. After years of clinical application, observation and analysis, and pharmacological research, it has been confirmed that the composition can be used to improve patients' clinical symptoms, reduce the recurrence rate of patients after surgery for primary liver cancer, reduce the incidence of liver cancer in patients with nodular cirrhosis, and improve the quality of life. It can be used to treat liver cancer and nodular cirrhosis with definite and significant efficacy.

[0022] 2. The raw materials of the Chinese medicine composition of the present invention are low in cost, easy to prepare, and suitable for popularization and application;

[0023] 3. The Chinese medicine composition of the present invention is made of pure Chinese medicine and has no toxic or side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Effect of 48 weeks of treatment on disease-free survival in patients with liver cancer after surgery DETAILED DESCRIPTION

[0025] The specific implementation methods provided by the present invention are described in detail below with reference to the examples.

[0026] Example 1: Chinese medicine composition of the present invention

[0027] The invention is composed of the following raw medicines in parts by weight: 10 parts of Morinda officinalis, 10 parts of Cuscuta seeds, 15 parts of raw Astragalus, 10 parts of stir-fried Atractylodes macrocephala, 10 parts of Zedoariae rhizome, 10 parts of Curcuma longa slices, 10 parts of Herba Eupatorii, 5 parts of Trillium gracile, 5 parts of Curcuma zedoariae and 3 parts of Citrus aurantium.

[0028] Example 2: Chinese medicine composition of the present invention

[0029] The invention is composed of the following raw materials in parts by weight: 20 parts of Morinda officinalis, 12 parts of Cuscuta seeds, 25 parts of raw Astragalus, 20 parts of stir-fried Atractylodes macrocephala, 20 parts of Zedoariae rhizome, 20 parts of Curcuma longa slices, 20 parts of Herba Eupatorii, 9 parts of Psoralea corylifolia, 9 parts of Curcuma zedoariae and 6 parts of Citrus aurantium.

[0030] Example 3: Chinese medicine composition of the present invention

[0031] The invention is composed of the following raw medicines in parts by weight: 12 parts of Morinda officinalis, 18 parts of Cuscuta seeds, 35 parts of raw Astragalus, 12 parts of stir-fried Atractylodes macrocephala, 12 parts of Zedoariae rhizome, 12 parts of Curcuma longa slices, 12 parts of Herba Eupatorii, 3 parts of Psoralea corylifolia, 3 parts of Curcuma zedoariae and 7 parts of Citrus aurantium.

[0032] Example 4: Chinese medicine composition of the present invention

[0033] The invention is composed of the following raw materials in parts by weight: 18 parts of Morinda officinalis, 20 parts of Cuscuta seeds, 45 parts of raw Astragalus, 18 parts of stir-fried Atractylodes macrocephala, 18 parts of Zedoariae rhizome, 18 parts of Curcuma longa slices, 18 parts of Herba Eupatorii, 7 parts of Psoralea corylifolia, 7 parts of Curcuma zedoariae and 5 parts of Citrus aurantium.

[0034] Example 5: Chinese medicine composition of the present invention

[0035] The drug is composed of the following raw materials in parts by weight: 15 parts of Morinda officinalis, 15 parts of Cuscuta australis, 30 parts of raw Astragalus, 15 parts of stir-fried Atractylodes macrocephala, 15 parts of Zedoariae rhizome, 15 parts of Curcuma longa, 15 parts of Herba Eupatorii, 6 parts of Trillium gracile, 6 parts of Curcuma zedoariae and 9 parts of Citrus aurantium.

[0036] Example 6: Preparation of decoction

[0037] A conventional method for preparing a Chinese herbal decoction is adopted, that is, the Chinese herbal composition described in any one of Examples 1-5 is weighed, added with water and boiled into a decoction.

[0038] Example 7: Preparation of tablets / capsules

[0039] Weigh any one of the Chinese medicine compositions described in Examples 1-5, grind them into powder, decoct them, and concentrate them under reduced pressure to obtain an extract. Dry and crush the extract to form granules, add pharmaceutical excipients, and press them into tablets or fill them into capsules.

[0040] Example 8: Preparation of granules

[0041] The Chinese medicine composition described in any one of Examples 1-5 was weighed, ground into powder, decocted, and concentrated under reduced pressure to obtain an extract, which was then dried and crushed to prepare granules.

[0042] Example 9: Preparation of pills / oral liquids / syrups

[0043] Weigh any one of the Chinese medicine compositions described in Examples 1-5, grind them into powder, decoct them, take the supernatant, and concentrate it into a thick extract; add appropriate pharmaceutical excipients (such as sugar, honey, benzopropionic acid or ethylparaben) to prepare pills, oral liquids or syrups.

[0044] Example 10: Pharmacodynamics Experiment 1 of the Chinese Medicine Composition of the Present Invention

[0045] (1) Case source: The cases were collected from 111 patients with compensated hepatitis B cirrhosis who visited the outpatient clinic of the Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between April 1, 2019 and October 31, 2021, and whose imaging examinations showed intrahepatic nodules >3 mm (regenerative nodules, abnormal hyperplastic nodules), with informed consent.

[0046] (II) Inclusion Criteria: Patients were diagnosed according to the criteria for compensated cirrhosis in the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 Edition). The criteria for macronodular cirrhosis were based on the criteria in the Journal of Hepatology: The nodules were large and uneven in size, generally >3 mm in diameter and up to several centimeters in size, with irregular fibrous septa and frequent regenerative nodules. Ultrasound, CT, or MRI imaging revealed nodules >3 mm in diameter; the patients were aged 18-70 years, regardless of gender; and signed informed consent.

[0047] (3) Exclusion criteria: patients with cirrhosis caused by other hepatotropic viral infections or other liver diseases; patients with or suspected primary liver cancer on ultrasound, CT or MRI examination; patients with Child-Pugh score > 12, or patients with decompensated cirrhosis within the past 6 months; patients with serious primary diseases of other important organs or severe mental illness; pregnant or lactating women, or those who intend to have children in the near future; and legally disabled persons.

[0048] (IV) Research Methods

[0049] 1. Baseline Data: 120 patients were randomly divided into a treatment group (TCM + basic treatment) and a control group (basic treatment), with 60 patients in each group. At the end of the treatment course, 55 patients in the treatment group completed follow-up, while 56 patients in the control group completed follow-up, with a total of 9 patients dropping out. There were no statistically significant differences between the two groups in terms of gender, age, smoking history, alcohol consumption history, family history, baseline liver-related scores (Child-Pugh score, MELD score, APRI score, FIB-4 score), liver function (ALT, AST, ALP, γ-GT, ALB, TBiL), blood routine (WBC, PLT), prothrombin time, virological indicators (HBsAg, HBV DNA positivity rate), LSM, and TCM syndrome score (P>0.05), indicating that the baseline data between the two groups were balanced and comparable.

[0050] 2. Medication Instructions: The treatment group (the group treated with the Chinese herbal medicine composition of the present invention) received an oral decoction consisting of 15g of Morinda officinalis, 15g of Cuscuta australis, 30g of raw Astragalus membranaceus, 15g of stir-fried Atractylodes macrocephala, 15g of Herba Eupatorii, 15g of Curcuma longa, 15g of Herba Glechomae seu Herba Eupatorii, 6g of Psoralea corylifolia, 6g of Curcuma zedoariae, and 9g of Citrus aurantium (Green Peel), one dose daily, taken warm twice a day, morning and evening. Basic antiviral therapy was also administered. The control group received basic antiviral therapy. Both groups received a 96-week treatment course.

[0051] (V) Observation indicators:

[0052] The clinical efficacy of the two groups was observed. The incidence of disease progression, including the incidence of primary liver cancer, the incidence of decompensated cirrhosis, and the mortality rate, was observed in the treatment group and the control group. The changes in liver stiffness (LSM) and the improvement of TCM symptoms were compared between the two groups before and after treatment.

[0053] (VI) Criteria for determining efficacy:

[0054] Refer to the relevant standards for evaluating the efficacy of cirrhosis. (1) Compare the disease progression rate of the two groups of patients (including the incidence of primary liver cancer, the incidence of decompensated cirrhosis, and the mortality rate). (2) Improvement in imaging: After treatment, the LSM of Fibroscan examination decreased compared with before. (3) Improvement of TCM symptoms: Refer to the "Guidelines for Clinical Research of New Chinese Medicines (Trial)", and calculate according to the nimodipine method: [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%. The criteria for judging the efficacy of symptoms are as follows: Clinical cure: symptoms disappear or basically disappear, and the symptom score decreases by ≥95%; marked effect: symptoms are significantly improved, and the symptom score decreases by ≥70%; effective: all symptoms are improved, and the symptom score decreases by ≥30%; ineffective: all symptoms are not significantly improved, or even worsen, and the symptom score is less than 30%.

[0055] (VII) Data Analysis

[0056] Data were analyzed using SPSS 27.0 statistical software. P ≤ 0.05 was considered statistically significant. When data did not follow a normal distribution, medians and interquartile ranges were used to describe the results, and nonparametric tests were used for statistical inference. Count data were described using frequency and rate statistics, and chi-square tests were used for statistical inference. Rank-sum tests were used for statistical inference of rank data. Progression-free survival was calculated using the life table method, and the Kaplan-Meier method was used to calculate progression-free survival rates, and survival curves were drawn.

[0057] (8) Results:

[0058] 1. Comparison of disease progression between the two groups of patients:

[0059] Compared with the control group, the disease progression rate of the treatment group was significantly improved (94.5% vs 82.1%), and the difference was statistically significant (χ 2 =4.128, P=0.042). The results are shown in Table 1.

[0060] Table 1 Comparison of disease progression in the treatment group and the control group

[0061]

[0062] The 55 patients in the treatment group survived for 23.4 months (95% CI = 22.52-24.21), with 6-month, 12-month, and 24-month survival rates of 96%, 96%, and 95%, respectively. The 56 patients in the control group survived for 22.3 months (95% CI = 21.16-23.44), with 6-month, 12-month, and 24-month survival rates of 96%, 86%, and 82%, respectively. The survival rates of the two groups at each follow-up point were compared, and the survival time and survival rate of the treatment group were longer than those of the control group, and the differences were statistically significant (Log-Rank test, χ 2 =4.041, P=0.044), (see Table 2).

[0063] Table 2 Comparison of survival time (months) and survival rate (%) between the two groups

[0064]

[0065] Among the 55 patients in the treatment group, 3 patients developed liver cancer, and the incidence of liver cancer was 5.5%. Compared with the control group (12.5%), the incidence of liver cancer was lower, but the difference was not statistically significant (χ 2 =1.680, P=0.195), the results are shown in Table 3. Among the 55 patients in the treatment group, no patient progressed to the decompensated stage of liver cirrhosis, while the incidence of decompensated liver cirrhosis in the 56 patients in the control group was 5.4%, and the difference was statistically significant (χ 2 =4.187, P=0.041), the results are shown in Table 4. Among the 55 patients in the treatment group, no patient died, while the mortality rate of the 56 patients in the control group was 3.6%, and the difference was not statistically significant (χ 2 =2.773, P=0.096), the results are shown in Table 5.

[0066] Table 3 Comparison of the incidence of liver cancer in the treatment group and the control group

[0067]

[0068] Table 4 Comparison of the incidence of decompensated cirrhosis in the treatment group and the control group

[0069]

[0070] Table 5 Comparison of mortality rates between the treatment group and the control group

[0071]

[0072] 2. Imaging improvement of the two groups of patients: The LSM of the patients in the treatment group was lower than that before treatment, and the LSM of the patients in the treatment group was lower than that in the control group after treatment, and the differences were statistically significant (P < 0.05); the difference in LSM before and after treatment in the treatment group was significantly greater than that in the control group, and the difference was statistically significant (P < 0.05), see Table 6.

[0073] Table 6 Comparison of LSM (kPa) before and after treatment between the two groups of patients [P50 (P25, P75)]

[0074]

[0075] 3. Improvement of TCM symptoms in the two groups of patients: The total TCM symptoms scores of the treatment group and the control group were lower after treatment than those before treatment, and the differences were statistically significant (P < 0.05); the difference in the total TCM symptoms scores of the treatment group was higher than that of the control group after treatment, and the difference was statistically significant (P < 0.05). The results are shown in Table 7.

[0076] Table 7 Comparison of total TCM syndrome scores between the two groups before and after treatment [P50 (P25, P75)]

[0077]

[0078] Clinical efficacy observations show that the Chinese medicine composition of the present invention can reduce the disease progression rate of patients with macronodular compensated hepatitis B cirrhosis, prolong the disease progression-free survival time, and improve the disease progression-free survival rate; it can improve the patient's elastic ultrasound liver stiffness LSM value and improve traditional Chinese medicine symptoms, and has a significant therapeutic effect on patients with macronodular cirrhosis.

[0079] Example 11: Pharmacodynamics Experiment 2 of the Chinese Medicine Composition of the Present Invention

[0080] (I) Case sources: A total of 228 patients who underwent surgery for primary liver cancer and visited the Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March 1, 2019 to March 1, 2022, with informed consent were retrospectively collected.

[0081] (2) Inclusion criteria: Patients were diagnosed according to the "Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)", met relevant pathological or clinical diagnostic criteria, had undergone radical hepatocellular carcinoma resection, were older than 18 years old, and had no gender restrictions.

[0082] (3) Exclusion criteria: patients with other tumors or metastatic liver cancer; patients with distant metastasis; patients with other systemic serious complications or mental illness; pregnant or lactating women; patients with incomplete medical records.

[0083] (IV) Research Methods

[0084] 1. Baseline Data: All patients undergoing surgery for primary liver cancer who met the inclusion and exclusion criteria were enrolled. A treatment group (139 patients) received the traditional Chinese medicine composition of the present invention plus basic treatment, while a control group (89 patients) received basic treatment alone. No significant differences were found in baseline data (P>0.05) such as gender, age, presence of hepatitis B / cirrhosis, liver function, blood count, renal function, and alpha-fetoprotein, indicating that baseline data were well-balanced and comparable between the two groups.

[0085] 2. Medication method: Treatment group (treatment group with the Chinese medicine composition of the present invention): oral administration of a decoction prepared by boiling 15g of Morinda officinalis, 15g of Cuscuta australis, 30g of raw Astragalus membranaceus, 15g of stir-fried Atractylodes macrocephala, 15g of Herba Eupatorii, 15g of Curcuma longa, 15g of Herba Glechomae Aconiti Lateralis Preparata, 6g of Psoralea corylifolia, 6g of Curcuma zedoariae, and 9g of Citrus aurantium, 1 dose per day, taken warm twice a day in the morning and evening; and basic treatment was also given; control group: basic treatment was given; the treatment course for both groups of patients was 48 weeks.

[0086] (V) Observation indicators:

[0087] The clinical efficacy of the two groups was observed. The postoperative recurrence rate and disease-free survival time of the treatment group and the control group were observed and compared.

[0088] (6) Data Analysis

[0089] SPSS 24.0 statistical software was used for data processing. The data were expressed as % and compared between groups using t test or rank sum test; the enumeration data were expressed as rate (%) and compared between groups using χ test. 2 P<0.05 was considered statistically significant.

[0090] (8) Results:

[0091] 1. Comparison of postoperative recurrence rates in patients with liver cancer: After treatment, 26 patients in the control group relapsed, while 23 patients in the treatment group relapsed. The postoperative recurrence rate in the treatment group was significantly lower than that in the control group, and the difference was statistically significant (29.2% vs 16.5%, P = 0.023), as shown in Table 8.

[0092] Table 8 Relapse of patients in the two groups after 48 weeks of treatment (cases, %)

[0093]

[0094] Note: Compared with the control group, *P<0.05.

[0095] 2. Comparison of disease-free survival after surgery in patients with liver cancer: After treatment, the average disease-free survival time in the control group was 10.87 months, while the average disease-free survival time in the treatment group was 11.58 months. The disease-free survival time in the treatment group was significantly longer than that in the control group, and the difference was statistically significant (HR = 1.924, 95% CI = 1.077-3.436, Log Rank P = 0.018). Figure 1 .

[0096] Clinical efficacy observations show that the Chinese medicine composition of the present invention can reduce the postoperative recurrence rate of patients with primary liver cancer and prolong the postoperative disease-free survival time of patients, and has a significant therapeutic effect on patients after surgery for liver cancer.

[0097] The preferred embodiments of the present invention have been specifically described above, but the present invention is not limited to the described embodiments. Those skilled in the art may make various equivalent modifications or substitutions without departing from the spirit of the present invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of this application.

Claims

1. A Chinese medicine composition for tonifying the kidney and spleen, clearing away heat, softening hard masses and dispersing nodules, characterized in that: The invention is composed of the following raw materials in parts by weight: 10-20 parts of Morinda officinalis, 10-20 parts of Cuscuta australis, 15-45 parts of raw Astragalus, 10-20 parts of stir-fried Atractylodes macrocephala, 10-20 parts of Zedoariae rhizome, 10-20 parts of Curcuma longa slices, 10-20 parts of Aconitum carmichaelii, 3-9 parts of Trillium gracile, 3-9 parts of Curcuma zedoariae and 3-9 parts of Citrus aurantium.

2. The Chinese medicine composition for tonifying the kidney and spleen, clearing away heat, softening hard masses and dispersing nodules according to claim 1, characterized in that: The drug is composed of the following raw materials in parts by weight: 12-18 parts of Morinda officinalis, 12-18 parts of Cuscuta australis, 25-35 parts of raw Astragalus, 12-18 parts of stir-fried Atractylodes macrocephala, 12-18 parts of Zedoariae rhizome, 12-18 parts of Curcuma longa slices, 12-18 parts of Aconitum carmichaelii, 5-7 parts of Trillium gracile, 5-7 parts of Curcuma zedoariae and 5-7 parts of Citrus aurantium.

3. The Chinese medicine composition for tonifying the kidney and spleen, clearing away heat, softening hard masses and dispersing nodules according to claim 1, characterized in that: The drug composition is composed of the following raw materials in parts by weight: 15 parts of Morinda officinalis, 15 parts of Cuscuta australis, 30 parts of raw Astragalus, 15 parts of stir-fried Atractylodes macrocephala, 15 parts of Zedoariae rhizome, 15 parts of Curcuma longa slices, 15 parts of Glechoma longituba, 6 parts of Trillium gracile, 6 parts of Curcuma zedoariae, and 9 parts of Citrus aurantium.

4. A pharmaceutical preparation comprising the Chinese medicine composition for invigorating the kidney and spleen, clearing away heat, softening hard masses and dispersing nodules as claimed in any one of claims 1 to 3 as an active ingredient, characterized in that: The pharmaceutical preparation is prepared into a common dosage form in pharmacy by conventional preparation methods in the art.

5. The pharmaceutical preparation according to claim 4, characterized in that The pharmaceutical preparation is a decoction, tablet, capsule, granule, pill, oral liquid or syrup.

6. The pharmaceutical preparation according to claim 4, characterized in that The pharmaceutical preparation also includes pharmaceutically acceptable excipients.

7. Use of the Chinese medicinal composition for tonifying the kidney and spleen, clearing away heat, softening hard masses and dispersing nodules as claimed in any one of claims 1 to 3 in the preparation of a medicament for treating liver cancer and macronodular cirrhosis.

8. Use of the pharmaceutical preparation according to any one of claims 4 to 6 in the preparation of drugs for treating liver cancer and macronodular cirrhosis.

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