Granules for consolidating foundation and removing food retention for treating malignant tumors as well as preparation method and application of granules

Abstract

The invention discloses primordial qi strengthening and food retention removing granules for treating malignant tumors as well as a preparation method and application thereof, and relates to the technical field of traditional Chinese medicine preparation. The primordial qi consolidating and food retention removing granules are prepared from the following raw materials in parts by weight: 10 parts of platycodon grandiflorum, 15 parts of codonopsis pilosula, 15 parts of roasted rhizoma atractylodis macrocephalae, 15 parts of poria cocos, 10 parts of pericarpium citri reticulatae, 6 parts of ginger processed pinellia, 15 parts of thunberg fritillary bulb, 15 parts of astragalus membranaceus, 15 parts of glossy privet fruit, 10 parts of radix curcumae, 15 parts of honeysuckle stem, 15 parts of selfheal, 30 parts of roasted malt and 6 parts of raw liquorice. The primordial qi consolidating and food retention removing granules have the effect of enhancing immunity, can be used for treating lung-spleen qi deficiency and phlegm-blood stasis syndrome after radiotherapy, chemotherapy and operation of lung cancer patients, can effectively improve the life quality of the patients, and are safe and effective in clinical application.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine preparation, and in particular to Guben Xiaoji granules for treating malignant tumors and a preparation method and application thereof. Background Art

[0002] Primary lung cancer can be roughly divided into two categories: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer accounts for a large proportion. Lung cancer is one of the most aggressive malignant tumors with high morbidity and mortality. It is the main cause of cancer death in the world. Lung cancer is also the malignant tumor with the highest morbidity and mortality in my country. In the third retrospective survey on causes of death conducted in the 21st century, it was found that lung cancer has surpassed gastric cancer, esophageal cancer, liver cancer and other cancers with high mortality rates to become the leading cause of cancer death. Deaths related to lung cancer in China show an "accelerating" trend, which is higher than the global average. And lung cancer will continue to maintain an "accelerating" trend in the next 10 years. Although lung cancer is aggressive, its onset is hidden. There are no obvious symptoms in the early stage, which makes many patients have developed to the late stage when they see a doctor, and the survival rate of patients with advanced lung cancer within 5 years is very low. Today, China is facing great challenges brought to us by the aging population, and the lung cancer group accounts for a very large proportion of tumor-related deaths among the elderly. These will bring great challenges and burdens to our country's medical and health system.

[0003] At present, the treatment of lung cancer is mainly surgery and radiotherapy and chemotherapy. After surgery, the quality of life of patients is usually significantly reduced, and the recovery time is long; and radiotherapy and chemotherapy have great side effects, which significantly affect the quality of life of patients. With the deepening of research, it has been found that Chinese medicine treatment of lung cancer has shown its unique advantages in improving patients' symptoms, improving quality of life, and prolonging survival time, which has attracted the attention of a large number of scholars. According to traditional Chinese medicine, lung cancer belongs to the category of "lung accumulation", "breath bend", "polyp", etc. The internal basis of its occurrence and the key point of the evolution of the disease are deficiency syndrome, which is mainly due to the lack of positive energy in the human body, the evil energy takes advantage of the weakness to enter, stay in the lungs, and the toxic blood stasis is mutually bound, forming a mass over time, leading to lung cancer, which is the result of the combined action of internal and external factors. The lungs are blocked by "smoke poison" and other factors, and the early symptoms of patients are chronic cough and sputum. In the middle stage of lung cancer, the lungs of patients are further aggravated, and various evil toxins condense into sputum and blood stasis, causing patients to cough, sputum, hoarseness, and chest pain. Patients with advanced lung cancer have long-term illness and blood stasis, which blocks the collaterals and accumulates to form, causing patients to show symptoms such as coughing, sputum, hemoptysis, shortness of breath, and chest pain. The etiology and pathogenesis of lung cancer are related to the spleen, and the pathogenic factors are related to heat, phlegm, stasis, and spleen deficiency. Any pathogenic factor of heat, phlegm, and stasis is closely related to the spleen and stomach. In the treatment of symptoms, "strengthening the spleen and clearing the lungs" should be considered, such as strengthening the spleen and clearing heat, strengthening the spleen and removing dampness and phlegm, and strengthening the spleen and removing stasis. However, in the development of lung cancer, "heat, phlegm, and stasis" do not exist alone, so treatment must have its own emphasis, but strengthening the spleen must be carried out throughout. Although the disease is located in the lungs, because qi deficiency is the main cause of the development of lung cancer, it can cause a variety of clinical pathological changes. Qi deficiency will block the spleen qi, and then the spleen and lung qi deficiency syndrome will appear.

[0004] Based on this, in order to enable lung cancer patients to tolerate the side effects of radiotherapy and chemotherapy to a greater extent and improve their quality of life, it is very meaningful to develop Chinese medicine preparations suitable for the syndromes of lung and spleen qi deficiency and phlegm and blood stasis. Summary of the invention

[0005] In view of the above problems, the present invention provides a Guben Xiaoji granule for treating malignant tumors and a preparation method and application thereof.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows: The invention provides a Guben Xiaoji granule for treating malignant tumors. The Guben Xiaoji granule is prepared from the following raw materials in parts by weight: 10 parts of platycodon, 15 parts of codonopsis pilosula, 15 parts of stir-fried atractylodes macrocephala, 15 parts of tuckahoe, 10 parts of tangerine peel, 6 parts of ginger pinellia, 15 parts of thunbergii bulbs, 15 parts of astragalus, 15 parts of glossy privet fruit, 10 parts of curcuma, 15 parts of honeysuckle vine, 15 parts of selfheal, 30 parts of stir-fried malt and 6 parts of raw liquorice.

[0007] The present invention also provides a method for preparing the above-mentioned Guben Xiaoji granules for treating malignant tumors, comprising the following steps: S1: Weigh platycodon, codonopsis, stir-fried atractylodes, tuckahoe, tangerine peel, pinellia, fritillaria, astragalus, glossy privet, curcuma, honeysuckle, selfheal, stir-fried malt, and raw liquorice according to weight, mix, crush, and sieve to obtain drug powder; S2: placing the drug powder in a decoction container, adding water to submerge the drug material, soaking, boiling and extracting, and separating the decoction liquid; then decocting the drug residue twice in the same manner, collecting all the decoction liquid, and concentrating it by evaporation under reduced pressure to obtain a thick paste A; S3: After the thick paste A is cooled to room temperature, ethanol is added, mixed thoroughly, and allowed to stand for 24 hours. After precipitation, the supernatant is taken, and the precipitate is washed with 60% ethanol. The washing liquid is combined with the supernatant, and the ethanol is recovered and concentrated by evaporation to obtain a thick paste B; S4: Add pharmaceutical excipients to the thick paste B, mix well, and prepare granules.

[0008] Furthermore, in the step S1, the number of sieving is 60 meshes.

[0009] Furthermore, in step S2, the mass ratio of the drug powder to water is 1:12, the soaking time is 3 hours, the boiling time is 2 hours, the concentration temperature is 55°C, and the relative density of the thick paste A is 1.30-1.35.

[0010] Furthermore, in step S3, the mass ratio of thick paste A to ethanol is 1:2, the concentration temperature is 55° C., and the relative density of thick paste B is 1.0-1.1.

[0011] Furthermore, in step S4, the mass ratio of thick paste B to pharmaceutical excipients is 1:0.2.

[0012] The present invention also provides an application of the above-mentioned Guben Xiaoji granules in preparing a medicine for treating lung and spleen qi deficiency and phlegm and blood stasis syndrome in patients with lung cancer after radiotherapy, chemotherapy and surgery.

[0013] Patients after radiotherapy, chemotherapy and surgery for lung cancer have clinical symptoms such as fatigue, shortness of breath, cough and sputum, poor appetite, abdominal distension, etc., which are diagnosed as lung and spleen qi deficiency and phlegm and blood stasis syndrome according to Chinese medicine differentiation. The Guben Xiaoji granules of the present invention have the functions of strengthening the foundation and nourishing the vital energy, eliminating accumulation and dispersing stagnation, and can be used to prepare medicines for treating lung and spleen qi deficiency and phlegm and blood stasis syndrome in patients after radiotherapy, chemotherapy and surgery for lung cancer.

[0014] Insufficient spleen qi and heat evil accumulating in the lungs are important mechanisms for the formation of lung accumulation. Qi deficiency is the root of lung cancer, phlegm and heat are the symptoms of lung cancer, and lung cancer is always a syndrome of deficiency in the root and excess in the symptoms. The syndrome of spleen deficiency and lung heat is one of the common clinical syndromes. Common symptoms are coughing and expectoration, white or yellow sputum or blood in the sputum, accompanied by fatigue, shortness of breath, aggravated by activity, pale red tongue with white or yellow greasy fur, and deep, thin or stringy and slippery pulse. Therefore, for the syndrome of spleen deficiency and lung heat in lung cancer, the lung and spleen should be treated together. According to the clinical characteristics of lung cancer, the treatment principle of "strengthening the spleen and clearing the lungs" is established, and the specific treatment method is to strengthen the spleen qi and clear the lung heat. The self-prescribed Guben Xiaoji granules are used for treatment. According to the theory of the five elements of traditional Chinese medicine, the lung belongs to metal and the spleen belongs to earth. The two organs are in a mother-child relationship. The lung governs water circulation and the spleen governs transportation and transformation. Both are related to the transportation and transformation of water and moisture. The two are closely related in pathology and physiology, and the mother is strengthened and the child is strengthened, and the spleen is strengthened and the lung is benefited. The spleen is the foundation of acquired constitution, and strengthening the spleen means consolidating the foundation. Treating lung cancer by treating both the lungs and spleen is the specific manifestation and application of the method of nourishing earth to produce gold in clinical practice.

[0015] In the prescription, dried tangerine peel, codonopsis, astragalus, and glossy privet fruit strengthen the spleen and stomach, replenish qi and consolidate the foundation, and Fritillaria thunbergii clears the lungs and disperses the stagnation to treat the symptoms, which are all the main drugs; stir-fried atractylodes, poria, and ginger pinellia strengthen the spleen and replenish qi, and increase the effect of consolidating the foundation; turmeric soothes the liver and relieves depression, honeysuckle vine and self-repellent clear the lungs and disperse the stagnation, and are anti-tumor, which are all the ministerial drugs; stir-fried malt promotes the function of spleen and stomach transportation and transformation, which is an adjuvant; platycodon carries the medicine upward, and raw licorice harmonizes the various medicines, which are all the guiding drugs. The whole prescription is used together to play the role of clearing lung heat, strengthening spleen qi, and dispersing toxicity, so as to consolidate the foundation, nourish the essence, eliminate accumulation and disperse the stagnation. This prescription is composed of Erchen Decoction and Sijunzi Decoction, with the addition of self-repellent, honeysuckle vine and other lung-clearing and dispersing stagnation products. Erchen Decoction clears the lungs and resolves phlegm; Sijunzi Decoction harmonizes the lungs and spleen; Fritillaria thunbergii strengthens the effect of dispersing stagnation; astragalus and glossy privet fruit replenish qi and nourish yin, turmeric soothes the liver and relieves depression, and self-repellent clears the lungs and disperses stagnation.

[0016] The pharmacological effects of each Chinese medicinal raw material in the present invention are as follows: Platycodon grandiflorum: neutral in nature, bitter and pungent in taste. Enters the lung meridian. Has the effects of clearing the lungs and removing phlegm, relieving throat and draining pus, and can treat cough with a lot of phlegm, chest fullness, sore throat and hoarseness, and lung carbuncle with vomiting pus.

[0017] Codonopsis: It is mild in nature and sweet in taste. It enters the spleen and lung meridians. It has the effects of tonifying the middle and replenishing qi, strengthening the spleen and lungs, and is used to treat spleen and lung weakness, shortness of breath and palpitations, poor appetite and loose stools, asthma and cough, and internal heat and thirst.

[0018] Stir-fried Atractylodes macrocephala: warm in nature, sweet and bitter in taste. It enters the spleen and stomach meridians. It has the effects of strengthening the spleen, replenishing qi, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. It is used to treat weak spleen and stomach qi, loss of appetite, fatigue and shortness of breath, bloating, diarrhea, phlegm and fluid, edema, jaundice, dampness, difficulty urinating, dizziness, spontaneous sweating, and restless fetus.

[0019] Poria: neutral in nature, sweet and light in taste. It enters the heart meridian, lung meridian, spleen meridian, and kidney meridian. It has the effects of promoting diuresis and eliminating dampness, strengthening the spleen and calming the mind. It is used to treat edema, oliguria, phlegm and fluid, palpitations, spleen deficiency, poor appetite, loose stools, restlessness, palpitations and insomnia.

[0020] Tangerine peel: Spicy, bitter, warm in nature. Enters the spleen and lung meridians. Has the effects of regulating qi and appetizing, drying dampness and resolving phlegm, and treating spleen and stomach diseases. It is used to treat chest and abdominal distension, loss of appetite and vomiting, and cough with excessive phlegm.

[0021] Pinellia tuber: warm in nature, pungent in taste. Enters the lung meridian, spleen meridian, and stomach meridian. It has the effects of warming the middle and resolving phlegm, lowering adverse qi and stopping vomiting, and is used to treat phlegm and vomiting, and fullness in the stomach.

[0022] Fritillaria thunbergii: cold in nature, bitter in taste. Enters the lung meridian and heart meridian. Has the effects of clearing away heat and dispersing stagnation, resolving phlegm and relieving cough. Used to treat wind-heat cough, lung abscess, throat paralysis, scrofula, sores, swelling and poison, etc.

[0023] Astragalus: slightly warm in nature, sweet in taste. It enters the spleen and lung meridians. It has the effects of replenishing qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid and nourishing blood, relieving stagnation and relieving arthritis, expelling toxins and draining pus, and healing sores and promoting tissue regeneration. It can treat shortness of breath, palpitations, fatigue, collapse, spontaneous sweating, night sweats, physical weakness and edema, chronic nephritis, etc.

[0024] Fructus Ligustri Lucidi: cool in nature, sweet and bitter in taste. Enters the liver and kidney meridians. Has the effects of nourishing the liver and kidney, improving eyesight and darkening hair. Used to treat tinnitus, deafness, dizziness, soreness of waist and knees, premature graying of hair and beard caused by liver and kidney yin deficiency.

[0025] Curcuma: cold in nature, pungent and bitter in taste. Enters the liver meridian, heart meridian and lung meridian. It has the effects of promoting blood circulation and relieving pain, promoting qi and removing blood stasis, clearing the heart and relieving depression, promoting bile and relieving jaundice. It is used to treat amenorrhea, dysmenorrhea, coma due to febrile disease, epilepsy, jaundice, dark urine, chest and abdominal distension and pain, and tingling.

[0026] Honeysuckle: cold in nature, sweet in taste. Enters the lung meridian and stomach meridian. It has the effects of clearing away heat and detoxifying, dispersing wind and unblocking collaterals. It is used to treat fever caused by febrile diseases, dysentery caused by heat toxins, carbuncle, sore, rheumatism, and red, swollen, hot and painful joints.

[0027] Prunella Vulgaris: cold in nature, pungent and bitter in taste. It enters the liver meridian and gallbladder meridian. It has the effects of clearing heat, improving eyesight, dispersing nodules and reducing swelling. It is used to treat red and swollen eyes, night pain in the eyes, headache and dizziness, scrofula, goiter, breast abscess, goiter, lymph node tuberculosis, breast hyperplasia and hypertension.

[0028] Roasted malt: neutral in nature, sweet in taste. It enters the spleen and stomach meridians. It has the effects of promoting qi and digestion, strengthening the spleen and stimulating appetite, and relieving milk and swelling. It is used to treat indigestion, abdominal distension and pain, spleen deficiency and poor appetite, etc.

[0029] Raw licorice: neutral in nature, sweet in taste. It enters the heart meridian, stomach meridian, spleen meridian, and lung meridian. It has the effects of tonifying the spleen and replenishing qi, relieving cough and expectoration, relieving urgency and relieving pain, and harmonizing the properties of medicines. It can treat spleen and stomach weakness, insufficient qi, cough and asthma, carbuncle, acute abdominal cramps and pain, relieve the potency of drugs, and detoxify drugs.

[0030] Compared with the prior art, the present invention has the following beneficial effects: In the present invention, the combination of various drugs can achieve the effects of strengthening the body, nourishing the essence, eliminating accumulation and dispersing stagnation. The Guben Xiaoji granules of the present invention have the effect of enhancing immunity, can be used to treat lung and spleen qi deficiency and phlegm and blood stasis syndrome after radiotherapy, chemotherapy and surgery in lung cancer patients, can effectively improve the quality of life of patients, and are safe and effective in clinical application. DETAILED DESCRIPTION

[0031] In order to make the purpose and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0032] The instruments, reagents, materials, etc. involved in the following examples, unless otherwise specified, are all conventional instruments, reagents, materials, etc. in the prior art and can be obtained through regular commercial channels. The experimental methods, detection methods, etc. involved in the following examples, unless otherwise specified, are all conventional experimental methods, detection methods, etc. in the prior art.

[0033] Example 1

[0034] This embodiment provides a Guben Xiaoji granule for treating malignant tumors, which is prepared from the following raw materials by weight: 10g of Platycodon grandiflorum, 15g of Codonopsis pilosula, 15g of stir-fried Atractylodes macrocephala, 15g of Poria cocos, 10g of dried tangerine peel, 6g of Pinellia ternata, 15g of Fritillaria thunbergii, 15g of Astragalus membranaceus, 15g of Ligustrum lucidum, 10g of Curcuma aromatica, 15g of Honeysuckle vine, 15g of Prunella vulgaris, 30g of stir-fried malt, and 6g of raw licorice.

[0035] The preparation method of the Guben Xiaoji granules comprises the following steps: S1: Weigh platycodon, codonopsis, stir-fried atractylodes, poria, tangerine peel, pinellia, fritillaria, astragalus, glossy privet, curcuma, honeysuckle, selfheal, stir-fried malt, and raw liquorice by weight, mix, and grind through a 60-mesh sieve to obtain drug powder; S2: Place the drug powder in a decoction container, add 12 times the weight of water to submerge the drug material, soak for 3 hours, boil and extract for 2 hours, and separate the decoction; decoct the drug residue twice in the same way, collect all the decoction, evaporate and concentrate under reduced pressure at 55°C to obtain a thick paste A with a relative density of 1.30-1.35; S3: After the thick paste A is cooled to room temperature, add 2 times the mass of ethanol, mix thoroughly, and place for 24 hours. After precipitation, take the supernatant, wash the precipitate with 60% ethanol, combine the washing liquid with the supernatant, recover the ethanol, evaporate and concentrate at 55°C to obtain a thick paste B with a relative density of 1.0-1.1; S4: Add 0.2 times the weight of pharmaceutical excipients to the thick paste B, mix well, and prepare granules.

[0036] Experimental Example 1 Animal Experiment In this experimental example, the drugs and reagents are as follows: Guben Xiaoji Granules: Platycodon grandiflorum, Codonopsis pilosula, stir-fried Atractylodes macrocephala, Poria cocos, dried orange peel, Pinellia ternata, Fritillaria thunbergii, Astragalus, Fructus Ligustri Lucidi, Curcuma aromatica, Honeysuckle vine, Prunella vulgaris, stir-fried malt, raw licorice. Prepare a liquid with a concentration of 1g / mL.

[0037] Dexamethasone sodium phosphate injection: produced by Hubei Tianyao Pharmaceutical Co., Ltd., approval number: National Medicine Standard: H42020019, production batch number is 20230122, specifications: 1mg: 5mg.

[0038] Thymosin for injection: produced by Disai Pharmaceutical Co., Ltd., approval number: National Medicine Standard H20003905, production batch number 20241208, specification: 10mg. Functions and indications: promoting blood circulation and removing blood stasis, reducing swelling and relieving pain. Mainly used to treat occlusive cerebrovascular diseases, coronary heart disease, myocardial infarction; has an auxiliary therapeutic effect on hyperlipidemia, complications, vasculitis, irregular menstruation, rheumatoid arthritis, etc.

[0039] In this experiment, the animals and instruments are as follows: Animals: ICR mice, weighing 20-22 g, half ♀ and half ♂, provided by the Experimental Animal Center of Xi'an Jiaotong University School of Medicine, license number: SCXK (Shaanxi) 2024-001. They were kept for 3 days before the experiment, and mice with normal behavior, diet, and mental state were selected for the experiment.

[0040] Instruments: PB1502-S thousandth balance, AG285 dual-range electronic balance (Mettler-Toledo, USA); UV-265FW ultraviolet spectrophotometer (Shimadzu, Japan).

[0041] Experimental conditions: room temperature 22~24℃, relative air humidity about 50~60%, air conditioning, ventilation with exhaust fan, male and female mice fed in separate cages, kept clean, cleaned every 2~3 days, light / dark hours of 12 / 12 hours.

[0042] In this experimental example, the test dose was selected based on: The proposed clinical dosage of this formula is the proposed clinical human dosage: 10g / time, 3 times / day; that is, for a person weighing 70kg, the clinical dosage is 2.33g / (kg▪day); The dosage of the pharmacodynamic test was designed after preliminary testing: Dexamethasone 25 mg / kg, equivalent to 22 times the clinical dose (intramuscular injection: 1-8 mg once, once a day); The three dosage groups of Guben Xiaoji Granules, small, medium and large (5g / kg, 10g / kg, 15g / kg), are equivalent to 23.3 times, 46.6 times and 69.9 times the intended clinical dose.

[0043] Thymosin for injection is 10 mg / kg, which is equivalent to 35 times the clinical dose.

[0044] In this experimental example, the statistical method of the experimental results is: The experimental data are expressed as mean ± standard deviation ( ±S), and t-test was performed between groups to test the significance of the drugs.

[0045] 1. Acute toxicity test of Guben Xiaoji granules The results showed that LD could not be detected by intragastric administration 50 The drug was administered three times within 24 hours and observed for 14 days. No mice died. The maximum dose of the drug tested was 51 g / kg, which is 22 times the dose intended for clinical use.

[0046] 2. Effects of Guben Xiaoji Granules on the Weight of Immune Organs and Carbon Particle Expansion and Clearance in Mice A total of 72 ICR male mice weighing 18-22 g were randomly divided into 6 groups according to body weight, with 12 mice in each group: water control group, modeling group (dexamethasone 25 mg / kg), Guben Xiaoji granule low-dose group (5 g / kg), medium-dose group (10 g / kg), high-dose group (15 g / kg), and thymosin group (10 mg / kg). The drug groups were orally administered according to the dosage, once a day in the morning. The control group was given an equal volume of water. Except for the control group, the other 5 groups were injected with dexamethasone at the above dosage intramuscularly for 10 consecutive days. 30 minutes after the last administration, 0.1 mL / 10 g of India ink diluted 10 times with normal saline was injected through the tail vein. Then, 20 mL of blood was collected from each eye socket at 2 minutes (t1) and 10 minutes (t2) after the injection of India ink, and 1 mg / mL The Na2CO3 solution was placed in a test tube with 2 mL of Na2CO3 solution, shaken well, and placed in a UV-265FW ultraviolet spectrophotometer for colorimetry at 680 nm to measure the optical density OD. Finally, the mice were killed by cervical dislocation, and the liver, spleen, and thymus were weighed. The phagocytic index K [k = (logOD1-logOD2) / (t2-t1)] was calculated, and the liver, spleen, and thymus indexes were calculated to observe whether Guben Xiaoji Granules have an activating and enhancing effect on the phagocytic function of reticuloendothelial cells. The data of each group are expressed as mean ± standard deviation (x ± s), and t test was performed between groups to test the effect of the drug.

[0047] Table 1 Effects of Guben Xiaoji Granules on the weight of immune organs in mice ( ±S)

[0048] Note: Compared with the control group, Δ P<0.05, ΔΔ P<0.01, ΔΔΔ P<0.001 Compared with the modeling group,* P<0.05, ** P<0.01, *** P<0.001 Table 2 Effect of Guben Xiaoji Granules on the phagocytic function of macrophages ( ±S)

[0049] Note: Compared with the control group, Δ P<0.05, ΔΔ P<0.01, ΔΔΔ P<0.001 Compared with the modeling group, * P<0.05, ** P<0.01, *** P<0.001 The immune-compromised mouse model was used to study the effect of Guben Xiaoji Granules on enhancing immune function. The experimental results showed that: ① The effect on the weight of mouse immune organs: compared with the control group, the liver index, spleen index and thymus index of the model group were significantly reduced (P<0.05, P<0.001), the thymus index of the high-dose group of Guben Xiaoji Granules was significantly increased compared with the model group (P<0.05), and the thymus index of the thymosin group was also significantly increased (P<0.05). See Table 1 for details. ② The effect on the phagocytic function of macrophages: compared with the control group, the phagocytic index K value of the model group was significantly reduced (P<0.01), the phagocytic index K value of the high-dose Guben Xiaoji Granules was significantly increased compared with the model group (P<0.01), and the phagocytic index K value of the thymosin group was significantly increased compared with the model group (P<0.01). Guben Xiaoji Granules has a significant activation and enhancement effect on the phagocytic function of reticuloendothelial cells. See Table 2 for details. The results suggested that Guben Xiaoji granules significantly improved the thymus index and phagocytic function of macrophages in immunocompromised mice.

[0050] 3. Effect on the content of hemolysin in mouse serum 72 ICR male mice weighing 18-22 g were randomly divided into 6 groups according to body weight, with 12 mice in each group: water control group, modeling group (dexamethasone 25 mg / kg), Guben Xiaoji granule low-dose group (5 g / kg), medium-dose group (10 g / kg), high-dose group (15 g / kg), and thymosin group (10 mg / kg). The drug groups were given drugs by gavage according to the dose, and thymosin was injected subcutaneously according to the dose, once a day in the morning. The control group was gavaged with an equal volume of water for 10 consecutive days. On the third day of administration, each mouse was intraperitoneally injected with 5% saline chicken red blood cell suspension. Except for the control group, the other 5 groups were injected intramuscularly with dexamethasone at the above doses for modeling. Once a day in the morning for 4 consecutive days. 30 minutes after the last oral gavage or subcutaneous administration, blood was collected from the eye sockets and centrifuged. The serum was diluted 20 times with normal saline. 1 mL of the diluted serum was mixed with 0.5 mL of 5% chicken red blood cells and 0.5 mL of 10% complement. The mixture was kept in a 37°C constant temperature water bath for 30 minutes. The reaction was terminated in a 0°C refrigerator and centrifuged. The supernatant was measured at 540 nm using a UV265FW ultraviolet-visible spectrophotometer. The optical density (OD) was measured. The OD value of the diluted serum was used as an indicator for determining serum hemolysin. The data of each group were expressed as mean ± standard deviation (x ± s). t test was performed between groups to examine the effect of the drug.

[0051] Table 3 Effect of Guben Xiaoji Granules on serum hemolysin content in mice ( ±S)

[0052] Note: Compared with the control group, Δ P<0.05, ΔΔ P<0.01, ΔΔΔ P<0.001 Compared with the modeling group, * P<0.05, ** P<0.01, *** P<0.001 The immunosuppressed mouse model was used to study the effect of Guben Xiaoji granules on enhancing immune function. The experimental results showed that the optical density of the model group was significantly reduced compared with the control group (P<0.01), the optical density of the high-dose and medium-dose Guben Xiaoji granules groups was significantly increased compared with the model group (P<0.001), and the optical density of the thymosin group was significantly increased compared with the model group (P<0.001). See Table 3 for details. The results suggest that Guben Xiaoji granules significantly increase the content of serum hemolysin in immunosuppressed mice.

[0053] Conclusion: It can be seen from the animal experiment results that the Guben Xiaoji granules of the present invention have the effect of enhancing immunity.

[0054] Experimental Example 2 Clinical Experiment 1. General data: 140 patients with lung adenocarcinoma admitted to our hospital from February 2019 to March 2022 were randomly selected for the study and divided into two groups of patients by random number table method. There were 70 cases in the observation group, including 42 females and 28 males; aged 40-77 years old, with an average age of (51.23±5.61) years old. 41 cases were in stage III of TNM stage, and 29 cases were in stage IV. There were 30 cases with a history of smoking. There were 70 cases in the control group, including 40 females and 30 males; aged 41-77 years old, with an average age of (50.80±5.29) years old. 39 cases were in stage III of TNM stage, and 31 cases were in stage IV. There were 33 cases with a history of smoking. There was no statistical difference in the general data between the two groups (P>0.05). Those who signed the informed consent form; the study was approved by the Medical Ethics Committee of the hospital.

[0055] 2. Inclusion criteria: Patients who meet the diagnostic criteria of the 2015 Chinese Primary Lung Cancer Diagnosis and Treatment Guidelines; diagnosed by pathology and imaging examinations and meet the indications for chemotherapy; patients who meet the spleen and lung qi deficiency syndrome in the Practical Chinese Medicine Diagnosis; TNM stage III to IV; clear consciousness, no history of mental illness, and can communicate normally; those who have signed the informed consent form; and the study was approved by the hospital's medical ethics committee.

[0056] 3. Exclusion criteria: history of surgery, radiotherapy, chemotherapy; combined with other malignant tumors; expected survival period <3 months; pregnant or lactating women; combined with blood or immune system diseases; combined with other organ dysfunctions such as heart, liver, and kidney; allergic to study drugs.

[0057] 4. Treatment methods (1) Control group: Gefitinib alone was used for treatment. Gefitinib (AstraZeneca Pharmaceuticals Co., Ltd., National Medicine Approval No. J20180014) 250 mg was taken warm 1 hour after breakfast, once a day. The medication was continued until the patient's disease progressed, intolerance or death occurred.

[0058] (2) Observation group: combined with Guben Xiaoji granules of Example 1 (Platycodon 10g, Codonopsis pilosula 15g, stir-fried Atractylodes macrocephala 15g, Poria 15g, Tangerine peel 10g, Pinellia ternata 6g, Fritillaria thunbergii 15g, Astragalus 15g, Ligustrum lucidum 15g, Curcuma 10g, Honeysuckle 15g, Prunella vulgaris 15g, stir-fried malt 30g, Raw Licorice 6g), taken with boiled water, 1 bag (10g) at a time, 3 times a day. Continue medication until disease progression, intolerance or death.

[0059] 5. Observation indicators (1) TCM syndrome score. Before treatment and 3 months after treatment, TCM syndromes such as cough, blood in sputum, dry mouth and less drinking, fatigue, and fever in the five parts of the body were scored. Each symptom was divided into 4 levels: no symptoms (0 points), mild symptoms or occasional symptoms (1 point), severe symptoms and intermittent symptoms (2 points), and significant or continuous symptoms (3 points).

[0060] (2) Immune function. Before treatment and 3 months after treatment, 5 mL of fasting cubital venous blood was collected and centrifuged at 3000 r / min to separate serum. The Thermo Fisher Attune NxT flow cytometer was used to detect serum CD3+, CD4+, CD8+, CD19+, NK cells and other immune function-related indicators.

[0061] 6. Statistical methods SPSS 20.0 software was used for statistical analysis. The count data were expressed as n (%) and the chi-square test was used. The measurement data were expressed as mean ± standard deviation. The t-test was used to compare two samples. P < 0.05 indicated that the difference was statistically significant.

[0062] 7. Results (1) TCM syndrome score Table 4 TCM syndrome score

[0063] It can be seen from the results in Table 4 that there was no statistical difference in cough, blood in sputum, fatigue, dry mouth and less drinking, and fever in the five hearts between the two groups before intervention (P>0.05); after intervention, cough, blood in sputum, fatigue, dry mouth and less drinking, and fever in the five hearts were reduced in both groups, and the observation group had lower symptoms (P<0.05, Table 1). Conclusion: After intervention, cough, blood in sputum, fatigue, dry mouth and less drinking, and fever in the five hearts were reduced in both groups, and the observation group had lower symptoms (P<0.05).

[0064] (2) Immune function Table 5 Immune function

[0065] Note: Compared with before intervention, *P<0.05.

[0066] From the results in Table 5, it can be seen that there was no statistical difference in the levels of CD3+, CD4+, CD8+, CD19+, and NK cells between the two groups before intervention (P>0.05); after intervention, the levels of CD3+, CD4+, and NK cells in the two groups increased, and the observation group was higher, while the CD8+ level decreased, and the observation group was lower (P<0.05).

[0067] Conclusion: It can be seen from the clinical experimental results that the Guben Xiaoji granules of the present invention can effectively treat lung and spleen qi deficiency and phlegm and blood stasis syndrome in patients with lung cancer after radiotherapy, chemotherapy and surgery, improve the quality of life of patients and enhance immunity.

[0068] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A Guben Xiaoji granule for treating malignant tumors, characterized in that: The Guben Xiaoji granules are prepared from the following raw materials in parts by weight: 10 parts of Platycodon grandiflorum, 15 parts of Codonopsis pilosula, 15 parts of stir-fried Atractylodes macrocephala, 15 parts of Poria cocos, 10 parts of dried tangerine peel, 6 parts of Pinellia ternata, 15 parts of Fritillaria thunbergii, 15 parts of Astragalus membranaceus, 15 parts of Ligustrum lucidum, 10 parts of Curcuma aromatica, 15 parts of Honeysuckle vine, 15 parts of Prunella vulgaris, 30 parts of stir-fried malt, and 6 parts of raw liquorice.

2. A method for preparing the Guben Xiaoji granules for treating malignant tumors as claimed in claim 1, characterized in that: The specific steps include: S1: Weigh platycodon, codonopsis, stir-fried atractylodes, tuckahoe, tangerine peel, pinellia, fritillaria, astragalus, glossy privet, curcuma, honeysuckle, selfheal, stir-fried malt, and raw liquorice according to weight, mix, crush, and sieve to obtain drug powder; S2: placing the drug powder in a decoction container, adding water to submerge the drug material, soaking, boiling and extracting, and separating the decoction liquid; then decocting the drug residue twice in the same manner, collecting all the decoction liquid, and concentrating it by evaporation under reduced pressure to obtain a thick paste A; S3: After the thick paste A is cooled to room temperature, ethanol is added, mixed thoroughly, and allowed to stand for 24 hours. After precipitation, the supernatant is taken, and the precipitate is washed with 60% ethanol. The washing liquid is combined with the supernatant, and the ethanol is recovered and concentrated by evaporation to obtain a thick paste B; S4: Add pharmaceutical excipients to the thick paste B, mix well, and prepare granules.

3. The method for preparing the Guben Xiaoji granules for treating malignant tumors according to claim 2, characterized in that: In the step S1, the number of sieving is 60 meshes.

4. The method for preparing the Guben Xiaoji granules for treating malignant tumors according to claim 2, characterized in that: In the step S2, the mass ratio of the drug powder to water is 1:12, the soaking time is 3 hours, the boiling time is 2 hours, the concentration temperature is 55° C., and the relative density of the thick paste A is 1.30-1.

35.

5. The method for preparing the Guben Xiaoji granules for treating malignant tumors according to claim 2, characterized in that: In step S3, the mass ratio of thick paste A to ethanol is 1:2, the concentration temperature is 55° C., and the relative density of thick paste B is 1.0-1.

1.

6. The method for preparing the Guben Xiaoji granules for treating malignant tumors according to claim 2, characterized in that: In the step S4, the mass ratio of thick paste B to pharmaceutical excipients is 1:0.

2.

7. Use of the Guben Xiaoji granules for treating malignant tumors as claimed in claim 1 in the preparation of a medicine for treating lung and spleen qi deficiency and phlegm and blood stasis syndrome in patients with lung cancer after radiotherapy, chemotherapy or surgery.

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