Traditional Chinese medicine composition for adjuvant treatment of phlegm-heat obstructing lung type advanced non-small cell lung cancer

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition for adjuvant treatment of phlegm-heat obstructing lung type advanced non-small cell lung cancer (NCSLC). The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials in parts by weight: 15-30 parts of rheum officinale, 15-30 parts of fructus trichosanthis, 15-30 parts of fried Chinese waxgourd seeds, 15-30 parts of coix seeds, 15-30 parts of fried fructus aurantii, 15-30 parts of ginger processed cortex magnoliae officinalis, 15-30 parts of fried semen raphani, 10-15 parts of radix curcumae, 10-15 parts of rhizoma curcumae longae, 10-15 parts of oldenlandia diffusa and 10-15 parts of radix ranunculi ternati. The invention further provides a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition is used for treating the phlegm-heat obstructing lung type advanced NCSLC, the main symptoms include cough, expectoration, phlegm blood, chest pain, inappetence, nausea and vomiting, constipation and the like, and the traditional Chinese medicine composition can be used for long-term treatment of patients with the advanced NCSLC by being matched with a traditional Chinese medicine preparation for strengthening the body resistance. The traditional Chinese medicine composition has a good curative effect on phlegm-heat obstructing lung type advanced NCSLC, and is reasonable in formula, free of toxic and side effects and safe and reliable in curative effect.

Description

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for adjuvant treatment of advanced non-small cell lung cancer with phlegm-heat obstructing the lung. Background Art

[0002] In clinical diagnosis and treatment, for patients with advanced non-small cell lung cancer, the treatment plan is relatively single, the survival period is short, and the prognosis is poor. Western medicine treatment has large toxic and side effects and a high recurrence rate, seriously affecting the quality of life of patients. Patients with advanced NSCLC with phlegm-heat obstructing the lung are mostly complicated with pulmonary infections. In this case, the condition is more serious and the mortality rate is high. Traditional Chinese medicine theory has a profound accumulation and rich practical experience in the treatment of tumors. Traditional Chinese medicine believes that the formation of tumors is due to the deficiency of healthy qi, and the condensation of pathological products such as phlegm, stasis, toxin, and turbidity. The concept of treating cancer in traditional Chinese medicine emphasizes grasping the relationship between eliminating pathogenic factors and strengthening healthy qi, attacking and tonifying repeatedly, and achieving balance. Purging the lower energizer to promote defecation is an important method for the ancients to treat tumors. For example, "Collection of Medical Formulas" states: "For those who treat tumors, drugs that promote rapid defecation must first dredge the qi of the lower energizer." "Rumen Shiqin" says: "For large accumulations and aggregations, serious constipation... Laxatives are tonics." And modern research shows that many traditional Chinese medicines with specific purgative effects have good anti-tumor effects. Based on this, through long-term clinical practice on patients with advanced NSCLC with phlegm-heat obstructing the lung, our team found that the method of purging the lower energizer to promote defecation has good therapeutic effects, especially for patients with advanced NSCLC with phlegm-heat obstructing the lung, presenting symptoms such as cough, expectoration, hemoptysis, chest pain, loss of appetite, nausea and vomiting, constipation, etc. Therefore, our team summarized a traditional Chinese medicine composition for adjuvant treatment of advanced non-small cell lung cancer with phlegm-heat obstructing the lung in order to improve the quality of life of patients with advanced NSCLC with phlegm-heat obstructing the lung. Summary of the Invention

[0003] (1) Technical Problems to be Solved

[0004] To solve the treatment dilemma of advanced non-small cell lung cancer with phlegm-heat obstructing the lung, the present invention provides a traditional Chinese medicine composition.

[0005] (2) Technical Solution

[0006] The technical solution adopted by the present invention is: a traditional Chinese medicine composition for adjuvant treatment of advanced non-small cell lung cancer with phlegm-heat obstructing the lung. Calculated by weight, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 15 - 30 parts of rhubarb, 15 - 30 parts of Trichosanthis Fruit, 15 - 30 parts of stir-fried winter melon seeds, 15 - 30 parts of coix seed, 15 - 30 parts of stir-fried Fructus Aurantii, 15 - 30 parts of Magnolia Officinalis with Ginger Juice, 15 - 30 parts of stir-fried Semen Raphani, 10 - 15 parts of Curcuma aromatica Salisb., 10 - 15 parts of Curcuma longa L., 10 - 15 parts of Hedyotis diffusa Willd., 10 - 15 parts of Ranunculus ternatus Thunb.

[0007] The prescription of this Chinese medicine composition is explained as follows: the rhubarb, trichosanthes and radish seeds in this composition can clear the bowels and eliminate turbidity, remove rot and promote new growth, and rhubarb has the power to dissipate blood stasis, and trichosanthes and radish seeds have the function of removing phlegm; wax gourd seeds can dissipate phlegm and resolve nodules, clear the lungs and discharge pus, and together with coix seeds, they have the effect of clearing heat and discharging pus; turmeric and turmeric can promote blood circulation and dissipate blood stasis, promote the circulation of blood and qi, and improve the state of phlegm and blood stasis; oldenlandia diffusa and cat's claw can clear away heat and detoxify, and relieve inflammatory reactions; coix seeds can strengthen the spleen and transport dampness, implying that a healthy spleen will eliminate phlegm; Citrus aurantium and Magnolia officinalis can relax the middle and lower qi, implying that phlegm will be eliminated if qi flows. Since cancer patients often suffer from insufficient vital energy, they often suffer from deficiency of both qi and yin or deficiency of both qi and blood after the phlegm-heat is eliminated. At this time, they can be used with herbs that can replenish qi and produce body fluid, such as astragalus, pseudostellaria, ophiopogon, and schisandra, or herbs that can invigorate qi and nourish blood, such as astragalus, codonopsis, angelica, and white peony, to improve the patient's deficiency of vital energy and prolong their survival time.

[0008] The pharmacology of the raw materials contained in this Chinese medicine composition is as follows:

[0009] Rhubarb: The dried root and rhizome of Rheum palmatum, Rheum tangutum or Rheum officinale of the Polygonaceae family. Medicinal properties: bitter, cold. Enters the spleen, stomach, large intestine, liver, and pericardium meridians. Efficacy: purgative, clearing away heat and purging fire, cooling blood and detoxifying, stopping bleeding, removing blood stasis and dredging menstruation, removing dampness and relieving jaundice. Modern research: promotes defecation, resists infection, and promotes bile and stomach function. In addition, it also has the effects of stopping bleeding, protecting the liver, lowering blood pressure, and lowering serum cholesterol.

[0010] Whole Trichosanthes: This product is the dried mature fruit of the plant Trichosanthes or Trichosanthes sibiricum of the Cucurbitaceae family. Medicinal properties: sweet, slightly bitter, cold. Enter the lung, stomach, and large intestine meridians. Efficacy: clearing heat and removing phlegm, relieving chest congestion, moistening and lubricating the intestines. Modern research: expectorant, immune regulation, anti-infection, coronary artery dilation, increase coronary flow, anti-tumor and other effects.

[0011] Winter melon seeds: This product is the dried mature seeds of winter melon, a plant of the Cucurbitaceae family. It is sweet and slightly cold in nature and enters the lung, spleen and small intestine meridians. It has the functions of clearing heat and resolving phlegm, discharging pus and promoting dampness. It is suitable for cough with phlegm heat, lung abscess, intestinal abscess, leucorrhea and leukorrhea. Coix seed: This product is the dried mature seed kernel of the Gramineae plant Coix. Medicinal properties: sweet, light and cool. It enters the spleen, stomach and lung meridians. Efficacy: promoting water and dampness, strengthening the spleen and stopping diarrhea, removing numbness, discharging pus, detoxifying and dispersing nodules. Modern research: Coix seed decoction, alcohol and acetone extracts have a significant inhibitory effect on cancer cells. Coix lactone has an inhibitory effect on the small intestine. Its fatty oil can reduce serum calcium and blood sugar levels, and has antipyretic, sedative, analgesic, immune-regulating effects. Citrus aurantium: This product is the dried immature fruit of the Rutaceae plant sour orange and its cultivated varieties. The nature, flavor, and meridians of this drug are the same as those of Zhishi, but its effects are milder. It has the functions of regulating qi, relieving fullness, and relieving stagnation and swelling. It is used for qi stagnation in the chest and flanks, fullness and pain, indigestion, phlegm and fluid retention, and sagging of internal organs.

[0012] Magnolia officinalis: This product is the dried trunk bark, root bark and branch bark of Magnolia officinalis Rehd. et Wils. or Magnolia officinalis Rehd. et Wils. var. biloba Rehd. et Wils. of the Magnoliaceae family. Medicinal properties: Bitter, pungent, warm. It acts on the spleen, stomach, lung and large intestine meridians. Efficacy: Dry dampness, promote qi movement, eliminate accumulation, resolve phlegm and relieve asthma. Modern research: Anti-infection, central muscle relaxation, prevention and treatment of gastric ulcers, blood pressure lowering, etc.

[0013] Semen Raphani: This product is the dried ripe seeds of Raphanus sativus L. of the Brassicaceae family. Medicinal properties: Pungent, sweet, neutral. It acts on the spleen, stomach and lung meridians. Efficacy: Promote digestion and relieve distension, lower qi and resolve phlegm. Modern research: Semen Raphani can enhance the rhythmic contraction of isolated rabbit ileum and inhibit gastric emptying in mice. It also has effects such as resolving phlegm, relieving cough, relieving asthma, improving urination function, lowering cholesterol and preventing arteriosclerosis.

[0014] Radix Curcumae: This product is the dried tuberous roots of Curcuma wenyujin Y. H. Chen et C. Ling, Curcuma longa L., Curcuma kwangsiensis S. G. Lee et C. F. Liang or Curcuma phaeocaulis Valeton of the Zingiberaceae family. Medicinal properties: Pungent, bitter, cold; it acts on the liver, gallbladder, heart and lung meridians. Efficacy: Promote blood circulation to relieve pain, promote qi movement to relieve depression, clear the heart and cool the blood, promote bile drainage and remove jaundice. Modern research: Promote bile secretion and excretion, reduce whole blood viscosity, inhibit platelet aggregation, anti-arrhythmia, anti-infection, anti-inflammatory and analgesic, anti-early pregnancy, etc.

[0015] Rhizoma Curcumae Longae: The dried rhizomes of Curcuma longa L. of the Zingiberaceae family. Medicinal properties: Pungent, bitter, warm. It acts on the liver and spleen meridians. Efficacy: Promote blood circulation and qi movement, dredge meridians and relieve pain. Modern research: Curcumin can inhibit platelet aggregation, reduce plasma viscosity and whole blood viscosity; it can have anti-inflammatory, antioxidant, lipid-lowering, blood pressure-lowering effects; protect gastric mucosa, protect liver cells, and have neuroprotective effects. Turmeric extract, curcumin, volatile oil, etc. can all promote bile secretion. In addition, turmeric powder and extract have anti-early pregnancy and anti-tumor effects.

[0016] Hedyotis diffusa: This product is the dried whole herb of Hedyotis diffusa Willd. of the Rubiaceae family. Medicinal properties: Slightly bitter, sweet, cold. It acts on the stomach, large intestine and small intestine meridians. Efficacy: Clear heat and detoxify, promote diuresis and relieve stranguria. Modern research: This product has anti-tumor effects. Its antibacterial effect in vitro is not significant, and high-concentration decoction has a weak inhibitory effect on Staphylococcus aureus and Shigella dysenteriae; in vivo, it can enhance the phagocytic ability of white blood cells and has an anti-inflammatory effect. It also has the effects of inhibiting spermatogenesis ability and protecting the liver and promoting bile secretion.

[0017] Radix Ranunculi Ternati: This product is the dried tuberous roots of Ranunculus ternatus Thunb. of the Ranunculaceae family. Medicinal properties: Sweet, pungent, warm. It acts on the liver and lung meridians. Efficacy: Resolve phlegm and dissipate nodules, detoxify and reduce swelling. Modern research: The water extract of this product has inhibitory effects on Staphylococcus aureus, Staphylococcus albus, Shigella dysenteriae, etc., and can also inhibit drug-resistant Mycobacterium tuberculosis. In addition, it also has effects such as relieving cough, resolving phlegm, anti-tumor, and enhancing immunity.

[0018] Preparation method:

[0019] Step 1: Cut 15 - 30 parts of rhubarb into pieces and soak for half an hour. Cut 15 - 30 parts of Trichosanthis Fruit, 15 - 30 parts of stir - fried Winter Melon Seeds, 15 - 30 parts of Coix Seeds, 15 - 30 parts of stir - fried Fructus Aurantii, 15 - 30 parts of Magnolia Officinalis with Ginger, 15 - 30 parts of stir - fried Raphanus Sativus Seeds, 10 - 15 parts of Curcuma aromatica Salisb., 10 - 15 parts of Curcuma longa L., 10 - 15 parts of Hedyotis diffusa Willd., and 10 - 15 parts of Ranunculus ternatus Thunb. into pieces and soak in warm water for half an hour.

[0020] Step 2: Add water to cover all the medicinal residues for the 11 kinds of decoction pieces such as Trichosanthis Fruit and stir - fried Winter Melon Seeds and their soaking solutions. Bring to a boil over high heat and then continue to decoct over low heat for 20 minutes. Add the rhubarb decoction pieces and their soaking solutions and continue to decoct for 10 minutes. Filter out the medicinal residues to obtain the first decoction.

[0021] Step 3: Add water to cover all the filtered medicinal residues. Bring to a boil over high heat and then continue to decoct over low heat for 30 minutes. Filter out the medicinal residues to obtain the second decoction. Repeat this process 2 - 3 times. After the decocting is completed, filter through an 80 - mesh sieve, collect the medicinal liquid in a storage tank, combine the extracted filtrates, and let it stand for 6 hours.

[0022] Step 4: Concentrate and collect the extract. Concentrate the medicinal liquid after standing. Start the concentrator, filter and transfer the supernatant liquid into the concentrator for double - effect concentration. The vacuum degree of the first effect is controlled at - 0.04 Mpa to - 0.06 Mpa, and the temperature is 70 - 80 °C; the vacuum degree of the second effect is controlled at - 0.06 Mpa to - 0.08 Mpa, and the temperature is 60 - 70 °C. During the concentration process, check and record the concentration temperature and vacuum degree at any time. When the concentration reaches an appropriate amount, transfer it to a single - effect concentrator for combined liquid concentration. After concentrating to the calibrated liquid level, transfer it to a spherical concentrator for concentrating and collecting the extract, with the temperature controlled at 70 - 80 °C. Check and record the temperature during the concentration process at any time. When the concentration reaches twice the amount of the total medicinal herb decoction pieces, transfer it to the extract collection room, filter through a 200 - mesh sieve to collect the extract. Take an appropriate amount of clear extract to measure the dry extract rate, put the qualified clear extract into a sealed container, weigh it, attach a status label, and store it in the intermediate product warehouse.

[0023] Step 5: Granulation process (1) Spray granulation: Weigh the dextrin and extract respectively. Put the dextrin into the spray granulator, adjust the flow rate and temperature, and spray the clear extract to make granules. Collect the dry granule powder for subsequent dry granulation. (2) Dry granulation: Weigh the dextrin and dry granule powder respectively, mix them evenly, and then prepare the granules by dry pressing granulation method for all the mixed granule powders. Collect the dry granules in a vortex vibrating sieve and screen them with 10 - mesh and 40 - mesh sieves to obtain granules with the required particle size.

[0024] Step 6: Packaging and storage. Carry out inner packaging and outer packaging for the prepared granules to ensure the tightness and stability of the granules. The packaged granules should be stored in a dry, cool, and ventilated place, avoiding direct sunlight and high temperature. Clinical Observation on the Treatment of Advanced Non - small Cell Lung Cancer of Phlegm - Heat Obstructing the Lung Type by the Method of Promoting Defecation and Removing Turbidity

[0025] 1 Case source

[0026] The 110 cases selected in this study were all advanced NSCLC patients with phlegm-heat obstructing the lung type who were treated in the inpatient department of the Oncology Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 1, 2019 to October 31, 2023.

[0027] 2 Diagnostic criteria

[0028] 2.1 Western medicine diagnostic criteria

[0029] The western medicine diagnostic criteria for NSCLC refer to the "Diagnosis and Treatment Guidelines for Primary Lung Cancer (2022 Edition)".

[0030] 2.2 Clinical staging criteria

[0031] The clinical staging adopts the eighth edition of the TNM staging criteria for lung cancer of the International Association for the Study of Lung Cancer (IASLC).

[0032] 2.3 Traditional Chinese medicine diagnostic criteria

[0033] The traditional Chinese medicine syndrome differentiation criteria for lung cancer refer to "Diagnostics of Traditional Chinese Medicine" and the traditional Chinese medicine diagnosis and treatment plan for lung cancer in our department. Syndrome of phlegm-heat obstructing the lung: (1) Main symptoms: cough with expectoration, expectoration of yellow and thick phlegm, shortness of breath, chest tightness, constipation or sticky stools. (2) Secondary symptoms: blood in sputum, chest pain, fever, thirst, short and red urine. (3) Tongue and pulse manifestations: red tongue with yellow coating, slippery or slippery and rapid pulse.

[0034] 3 Inclusion criteria

[0035] (1) Advanced NSCLC patients diagnosed by pathological and imaging examinations.

[0036] (2) Patients who are chemotherapy-intolerant or refuse chemotherapy.

[0037] (3) Those who conform to the syndrome of phlegm-heat obstructing the lung type in traditional Chinese medicine syndrome differentiation.

[0038] (4) Karnofsky performance status score (KPS score) ≥ 60 points.

[0039] (5) Aged 18 - 80 years old, regardless of gender and race.

[0040] (6) Those with detailed medical records (CT examinations of measurable tumor lesions are performed every two treatment cycles during hospitalization, and blood cell analysis, comprehensive biochemical tests, tumor markers, D-dimer, absolute count of lymphocyte subsets, etc. are examined before and after each anti-tumor treatment), contact information and address.

[0041] 4 Exclusion criteria

[0042] (1) Those with concomitant primary malignant tumors in other parts.

[0043] (2) Those with active autoimmune diseases receiving systemic glucocorticoid or immunosuppressive therapy.

[0044] (3) Those with mental disorders or unable to cooperate with the treatment.

[0045] (4) Pregnant or lactating women.

[0046] (5) Those with severe heart, liver, or kidney damage, or other severe complications.

[0047] (6) Those in whom the lack of original data affects the researchers.

[0048] 5 Grouping method

[0049] Through a retrospective study method, 110 patients with advanced NSCLC of the phlegm-heat obstructing the lung type were divided into an observation group and a control group. The observation group was treated with the prescription of promoting defecation and removing turbidity as the basic formula (Rheum officinale 15 - 30 g, Trichosanthes kirilowii Maxim. 15 - 30 g, Semen Benincasae 15 - 30 g, Coix lacryma-jobi L. 15 - 30 g, Fructus Aurantii 15 - 30 g, Magnolia officinalis Rehd. et Wils. 15 - 30 g, Semen Raphani 15 - 30 g, Curcuma aromatica Salisb. 10 - 15 g, Curcuma longa L. 10 - 15 g, Hedyotis diffusa Willd. 10 - 15 g, Radix Ranunculi Ternati 10 - 15 g), and the control group was treated with other treatment methods as the basic formula. Other traditional Chinese medicine regimens included prescriptions using a small dose of drugs for promoting defecation and removing turbidity but without achieving the effect of promoting defecation and removing turbidity (that is, no spontaneous defecation occurred after the patients took the drugs continuously for 3 days) and prescriptions using other treatment methods except the method of promoting defecation and removing turbidity. The traditional Chinese medicine decoction pieces were all sourced from the traditional Chinese medicine hall of our hospital and were decocted by the decoction pharmacy of our hospital on behalf. All patients took 3 weeks as 1 cycle, and the curative effect was evaluated in both groups after 2 cycles. Follow-up was conducted once every 2 months until the patients died or were lost to follow-up.

[0050] 6 Observation indicators

[0051] 6.1 General information

[0052] Age, gender, height, weight, smoking status, drinking status, family history, pathological type, clinical stage, metastasis status, comorbidities, treatment regimen, etc.

[0053] 6.2 Observation indicators

[0054] 6.2.1 Main observation indicators

[0055] The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard was adopted for efficacy evaluation. Complete remission (CR) was defined as the disappearance of all target lesions; the short diameter of all pathological lymph nodes was < 10 mm. Partial remission (PR) was defined as a reduction of at least 30% in the sum of the diameters of all target lesions compared to the baseline. Stable disease (SD) was defined as not achieving PR or PD and lasting for at least 8 weeks. Progressive disease (PD) was defined as an increase of at least 20% in the sum of the diameters of all target lesions, and the absolute value of the sum of the diameters must increase by at least 5 mm.

[0056] (1) Overall survival (OS): The time from the start of treatment to death. (2) Progression-free survival (PFS): The time from the start of treatment to disease progression or death. (3) Objective response rate (ORR): Including CR and PR. (4) Disease control rate (DCR): Including CR, PR, and SD.

[0057] 6.2.2 Secondary observation indicators

[0058] (1) Traditional Chinese medicine (TCM) syndrome score: It was evaluated with reference to the evaluation criteria for TCM symptoms of lung cancer in the "Guiding Principles for Clinical Research of New TCM Drugs" (2002 edition). Common symptoms of lung cancer such as cough, expectoration, hemoptysis, chest pain, fatigue, loss of appetite, nausea and vomiting, constipation, etc. were selected as observation indicators. According to the standard, the above symptoms were divided into 4 grades: none, mild, moderate, and severe, and were assigned 0 - 3 points from none to severe accordingly.

[0059] Symptom score improvement rate = [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%; Evaluation criteria for TCM syndrome efficacy: Marked effect: The symptom score improvement rate decreased by 70%; Effective: 30% < the symptom score improvement rate decreased < 70%; Ineffective: The symptom score improvement rate decreased < 30%.

[0060] (2) Quality of life evaluation: Refer to the Functional Assessment of Cancer Therapy - Lung (FACT - L) 4.0, including five aspects: physical condition, social / family condition, emotional condition, functional condition, and additional concerns, and were assigned 0 - 4 points from none to very accordingly.

[0061] (3) Karnofsky Performance Status (KPS) score: The quality of life of the two groups of patients before and after treatment was evaluated according to the KPS score table. The score was 0 - 100 points, and the higher the score, the higher the quality of life of the patient.

[0062] (4) Tumor markers: Changes in carcinoembryonic antigen (CEA), ferritin (FER), squamous cell carcinoma antigen assay (SCC), and cytokeratin 19 fragment (CYFRA21 - 1).

[0063] (5) Safety indicators: Blood routine, liver function, kidney function, D - dimer, etc.

[0064] 7 Safety evaluation

[0065] Referring to the WHO standards for the manifestations and gradings of acute and subacute toxic and side reactions of anti-cancer drugs, the adverse reactions are divided into grades 0, I, II, III, and IV (see Appendix), and the occurrence of ICIs-related adverse reactions was observed. The main evaluation indicators were clinical manifestations, laboratory tests, and imaging examinations.

[0066] 8 Results

[0067] 8.1 Baseline situation

[0068]

[0069]

[0070] All the cases selected in this study were patients with advanced NSCLC of the phlegm-heat obstructing the lung type who were admitted to the inpatient department of the Oncology Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 1, 2019, to October 31, 2023. A total of 110 advanced NSCLC patients who met the inclusion and exclusion criteria were collected, with 52 cases in the observation group and 58 cases in the control group. Statistical analysis was performed on the data of each group, and the results showed that there were no significant differences in general data such as gender, age, BMI, and pathological classification before treatment, as well as TCM symptom scores and Karnofsky scores between the two groups (P>0.05), indicating comparability.

[0071] 8.2 Efficacy evaluation

[0072] 8.2.1 Survival period

[0073] Table 2-1 PFS of the two groups

[0074]

[0075] Table 2-2 OS of the two groups

[0076]

[0077] The mPFS of the patients in the observation group was 3.3 months (95% CI: 2.7 - 3.9 months), and the mPFS of the patients in the control group was 2.0 months (95% CI: 1.8 - 2.2 months). The PFS of the patients in the observation group was prolonged by 1.3 months compared with that in the control group (HR = 0.49, 95% CI: 0.33 - 0.73, P<0.0001) (Table 2-1, Figure 1 ). The mOS of the patients in the observation group and the control group were 8.0 months vs. 6.0 months (HR = 0.79, 95% CI: 0.49 - 1.26), respectively. The OS survival curve of the observation group showed a trend of benefit, but it was not statistically significant (P = 0.2602) (Table 2-2, Figure 2 ).

[0078] 8.2.2 Remission Rate

[0079] Table 2-3 Disease Remission Conditions in Two Groups [Number of Cases (%)]

[0080]

[0081] Note: The number of remissions includes complete remission and partial remission

[0082] As shown in Table 2-3, Figure 3 the ORR of the observation group was 59.6%, and the ORR of the control group was 39.6%. The chi-square test showed that χ2 = 6.162, P = 0.046 (<0.05), which was statistically significant; the DCR of the observation group was 84.6%, and the DCR of the control group was 65.5%. The chi-square test showed that χ2 = 5.270, P = 0.022 (<0.05), which was statistically significant. The above results indicated that the ORR and DCR of the observation group were superior to those of the control group.

[0083] 8.2.3 TCM Symptom Scores

[0084] Table 2-4 Comparison of TCM Symptom Scores in Two Groups Before and After Treatment

[0085]

[0086] Note: The above did not conform to the normal distribution and was expressed as M(25%, 75%).

[0087] Before and after treatment in the observation group and the control group, the TCM syndrome scores decreased. After the rank sum test, P < 0.05, which was statistically significant. After treatment, the rank sum test of the TCM syndrome scores in the two groups showed that Z = -4.805, P < 0.05, indicating that there was a statistically significant difference in the TCM symptom scores after treatment in the two groups (Table 2-4, Figure 4 ); after treatment, the chi-square test of the effective rates of TCM clinical symptoms in the two groups showed that χ2 = 6.128, P = 0.047 (<0.05) (Table 2-5, Figure 5 ), indicating that there was a statistically significant difference between the two groups. The above results showed that the improvement of TCM symptoms in the observation group was better than that in the control group, indicating that the method of purging the bowels and removing turbidity could better relieve the clinical symptoms of patients and reduce the pain of patients compared with other treatment methods.

[0088] Table 2-5 Comparison of the Curative Effects of TCM Clinical Symptoms in Two Groups Before and After Treatment [Number of Cases (%)]

[0089]

[0090]

[0091] 8.2.4 FACT-L 4.0 Scale Scores

[0092] Comparison of FACT-L 4.0 Scale Scores between Two Groups before and after Treatment

[0093]

[0094] Note: The above does not conform to the normal distribution and is expressed as M(25%, 75%).

[0095] As shown in Table 2-6, Figure 6 before and after treatment in the observation group and the control group, the scores in the five aspects of physical condition, emotional condition, additional concerns, social / family situation, and functional status all decreased. After the rank sum test, P < 0.005, which was statistically significant. After treatment, the rank sum test of the scores of each part of the two groups showed that the score of physical condition Z = -2.651, P = 0.008 (P < 0.05); the score of social / family situation Z = -0.205, P = 0.837 (P > 0.05); the score of emotional condition Z = -2.875, P = 0.004 (P < 0.05); the score of functional status Z = -0.794, P = 0.427 (P > 0.05); the score of additional concerns Z = -2.479, P = 0.013 (P < 0.05). The above results suggest that after treatment, the improvement of the scores of physical condition, emotional condition, and additional concerns in the observation group is better than that in the control group; there is no significant difference in the improvement of the scores of social / family situation and functional status between the two groups.

[0096] 8.2.5 Karnofsky Score

[0097] Karnofsky Score of Two Groups before and after Treatment

[0098]

[0099] Comparison of Karnofsky Scores between Two Groups before and after Treatment [Number of Cases (%)]

[0100]

[0101] As shown in Table 2-8, Figure 7 after treatment, the Karnofsky scores of both groups improved. Among the 52 cases in the observation group, 30 cases had an increased Karnofsky score, accounting for 57.7%; 19 cases were stable, accounting for 36.5%; 3 cases decreased, accounting for 5.8%. Among the 58 cases in the control group, 19 cases had an increased score, accounting for 32.8%; 32 cases were stable, accounting for 55.2%, and 7 cases decreased, accounting for 12.1%. After the chi-square test, χ2 = 7.077, P < 0.05, and the difference was statistically significant. The improvement of the Karnofsky score in the observation group was better than that in the control group.

[0102] 8.2.6 Tumor Markers

[0103] Values of Tumor Markers of Two Groups before and after Treatment

[0104]

[0105] Note: The above data does not conform to the normal distribution and is expressed as M(25%, 75%).

[0106] As shown in Table 2-9, Figure 8 as shown, before treatment, carcinoembryonic antigen, ferritin, and cytokeratin 19 fragment in the two groups of patients were tested by the rank sum test, and P>0.05, indicating no statistical difference. After treatment, carcinoembryonic antigen and cytokeratin 19 fragment in the two groups were tested by the rank sum test, and P>0.05, showing no statistical difference; ferritin was tested by the rank sum test, Z=-2.054, P=0.04 (P<0.05), with statistical difference. After the rank sum test of the two groups before and after treatment, it was found that there was no significant change in ferritin in the observation group, Z=-0.195, P=0.845 (P>0.05), and the ferritin in the control group increased as a whole, Z=-2.179, P=0.029 (P<0.05), indicating that the observation group had a certain advantage over the control group in inhibiting the increase of ferritin value.

[0107] 8.2.7 D-dimer

[0108] Table 2-10 D-dimer conditions of the two groups before and after treatment [number of cases (%)]

[0109]

[0110] Table 2-11 D-dimer value conditions of the two groups before and after treatment

[0111]

[0112] Note: The above data does not conform to the normal distribution and is expressed as M(25%, 75%)

[0113] Before treatment, there was no statistical difference between the two groups by chi-square test, χ2=0.510, P=0.822 (>0.05); after treatment, it was found that there was a statistical difference between the two groups by chi-square test, χ2=4.362, P=0.037 (P<0.05) (Table 23), indicating that the observation group could improve the abnormal situation of D-dimer compared with the control group. After the rank sum test of the two groups before and after treatment, it was found that there was no significant change in D-dimer in the observation group, Z=-0.923, P=0.356 (P>0.05), and the D-dimer in the control group increased as a whole, Z=-2.314, P=0.021 (P<0.05) (Table 2-11, Figure 9 ), indicating that the observation group could inhibit the increase of D-dimer in tumor patients to a certain extent compared with the control group.

[0114] 9 Safety evaluation

[0115] Table 2-12 Comparison of Adverse Reactions between Two Groups before and after Treatment (cases)

[0116]

[0117] Continued Table 2-12

[0118]

[0119] Note: α refers to before and after treatment

[0120] As shown in Table 2-12, the hemoglobin, white blood cells, platelets, ALT, AST, GGT, creatinine, and urea nitrogen of the two groups before treatment showed P>0.05 by the rank sum test, indicating no statistical difference. After treatment, the hemoglobin, ALT, AST, GGT, and urea nitrogen showed P>0.05 by the rank sum test, indicating no statistical difference. The results of the rank sum test for white blood cells, platelets, and creatinine in the two groups showed that the Z values were -3.341, -2.839, and -2.077 respectively, and the P values were 0.001, 0.005, and 0.038 (P<0.05) respectively, indicating statistical differences. By comparing the ranks, it was found that the observation group had advantages over the control group in increasing the levels of white blood cells and platelets and decreasing the level of creatinine. In addition, no adverse reactions above grade III were found in the observation group after treatment, and 2 cases of grade IV adverse reactions occurred in the control group.

[0121] 10 Beneficial Effects

[0122] This traditional Chinese medicine composition has the effects of purging the bowels to remove turbidity and detoxifying and anti-cancer, and is applicable to advanced NSCLC of the phlegm-heat obstructing the lung type, with clinical manifestations of: coughing and expectorating phlegm, the phlegm is sticky and difficult to expectorate, or there is blood in the phlegm, chest tightness, shortness of breath, poor appetite and sleep, constipation or sticky stools, normal or short and red urine, red tongue with yellow coating, and deep, string-like, slippery and rapid pulse. This important composition can effectively improve the clinical symptoms of patients with advanced NSCLC of the phlegm-heat obstructing the lung type. When used in combination with the traditional Chinese medicine preparation for strengthening the healthy qi for a long time, it can improve the objective remission rate of patients with advanced NSCLC, prolong the survival period of patients, and improve the quality of life of patients. Description of the Drawings

[0123] Figure 1 It is a diagram of the PFS analysis of the observation group and the control group;

[0124] Figure 2 It is a diagram of the OS analysis of the observation group and the control group;

[0125] Figure 3 It is a diagram of the remission rate ratio of the observation group and the control group;

[0126] Figure 4 Distribution diagram of the TCM syndrome scores of the observation group and the control group;

[0127] Figure 5It is a comparison chart of the curative effects of traditional Chinese medicine clinical symptoms before and after treatment in the observation group and the control group;

[0128] Figure 6 It is a comparison chart of the scores of the FACT-L 4.0 scale before and after treatment in the observation group and the control group;

[0129] Figure 7 It is a chart showing the proportion of the improvement level of Karnofsky score in the observation group and the control group;

[0130] Figure 8 It is a chart of the changes in ferritin before and after treatment in the observation group and the control group;

[0131] Figure 9 It is a chart of the changes in D-dimer before and after treatment in the observation group and the control group;

[0132] Figure 3 、 Figure 5 、 Figure 7 In the left figures of Specific implementation method

[0133] , the left figure is the observation group and the right figure is the control group. The composition is made into granules as follows:

[0134] First step: Cut 15 - 30 parts of rhubarb into pieces, soak for half an hour, and cut 15 - 30 parts of Trichosanthis Fruit, 15 - 30 parts of stir-fried Winter Melon Seeds, 15 - 30 parts of Coix Seed, 15 - 30 parts of stir-fried Fructus Aurantii, 15 - 30 parts of Magnolia Officinalis with Ginger, 15 - 30 parts of stir-fried Raphanus Sativus Seed, 10 - 15 parts of Curcuma aromatica Salisb., 10 - 15 parts of Curcuma longa L., 10 - 15 parts of Hedyotis diffusa Willd., and 10 - 15 parts of Ranunculus ternatus Thunb. into pieces, and soak in warm water for half an hour.

[0135] Second step: Add water to the 11 kinds of decoction pieces such as Trichosanthis Fruit and stir-fried Winter Melon Seeds and the soaking solution to cover all the medicinal residues. Bring to a boil over high heat, then simmer for 20 minutes. Add the rhubarb decoction pieces and the soaking solution and continue to simmer for 10 minutes. Filter the medicinal residues to obtain the first decoction.

[0136] Third step: Add water to the filtered medicinal residues to cover all the medicinal residues. Bring to a boil over high heat, then simmer for 30 minutes. Filter the medicinal residues to obtain the second decoction. Repeat this process 2 - 3 times. After the decocting is completed, filter with an 80 - mesh sieve, collect the medicinal liquid in a storage tank, combine the extracted filtrates, and let it stand for 6 hours.

[0137] Step 4: Concentration and paste collection. Concentrate the settled liquid medicine. Start the concentrator, filter and collect the supernatant and pump it into the concentrator for double-effect concentration. The vacuum degree of the first effect is controlled at -0.04 Mpa to -0.06 Mpa, and the temperature is 70 - 80 °C; the vacuum degree of the second effect is controlled at -0.06 Mpa to -0.08 Mpa, and the temperature is 60 - 70 °C. During the concentration process, check and record the concentration temperature and vacuum degree at any time. When the concentration reaches an appropriate amount, transfer it to a single-effect concentrator for combined liquid concentration. After concentrating to the calibrated liquid level, transfer it to a spherical concentrator for paste collection, with the temperature controlled at 70 - 80 °C. Check and record the temperature at any time during the concentration process. When the concentration reaches twice the amount of the total medicinal herb slices in liquid form, transfer it to the paste collection room and filter and collect the paste through a 200-mesh sieve. Take an appropriate amount of clear paste to measure the dry paste rate. Pack the qualified clear paste in a sealed container, weigh it, attach a status label, and store it in the intermediate product warehouse.

[0138] Step 5: Granulation process (1) Spray granulation: Weigh the dextrin and extract obtained respectively. Put the dextrin into the spray granulator, adjust the flow rate and temperature, and spray the clear paste to make granules. Collect the dried granule powder for subsequent dry granulation. (2) Dry granulation: Weigh the dextrin and the dried granule powder obtained respectively, mix them evenly, and then prepare the granules by dry pressing granulation for all the mixed granule powder. Collect the dried granules in a vortex shaker and screen them with 10-mesh and 40-mesh sieves to obtain granules with the required particle size.

[0139] Step 6: Packaging and storage. Carry out inner packaging and outer packaging for the obtained granules to ensure the sealing and stability of the granules. The packaged granules should be stored in a dry, cool and ventilated place, avoiding direct sunlight and high temperature.

Claims

1. A Chinese medicine composition, processed from Chinese herbal medicine pieces, characterized in that: In parts by weight, the Chinese medicine composition is composed of the following raw materials: The composition includes: 15-30 parts of rhubarb, 15-30 parts of whole trichosanthes, 15-30 parts of stir-fried wax gourd seeds, 15-30 parts of coix seeds, 15-30 parts of stir-fried fructus aurantii, 15-30 parts of ginger magnolia bark, 15-30 parts of stir-fried radish seeds, 10-15 parts of curcuma, 10-15 parts of turmeric, 10-15 parts of oldenlandia diffusa, and 10-15 parts of cat's claw. It is suitable for people with advanced non-small cell lung cancer of the phlegm-heat obstructing lung type.

2. The Chinese medicine composition as described in claim 1, characterized in that: The Chinese medicine composition can be prepared into decoction, granules, pills, etc., preferably granules.

3. The Chinese medicine composition as described in claim 1, characterized in that: It can be used in combination with tonic Chinese medicine preparations for the long-term treatment of patients with advanced non-small cell lung cancer.

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