Traditional Chinese medicine composition for treating nutritional state decline after chemotherapy and application of traditional Chinese medicine composition

Abstract

The invention relates to a traditional Chinese medicine composition for treating nutritional state decline after chemotherapy and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 9-40 parts of codonopsis pilosula, 6-30 parts of fried rhizoma atractylodis macrocephalae, 6-30 parts of poria cocos, 6-20 parts of processed rhizoma pinelliae, 6-12 parts of pericarpium citri reticulatae, 6-40 parts of fried hawthorn, 6-40 parts of fried medicated leaven, 6-40 parts of fried grain malt, 6-40 parts of caulis spatholobi, 6-40 parts of pyrrosia lingua, 6-40 parts of hairyvein agrimony, 3-15 parts of honey-fried licorice root and 6-30 parts of Chinese date. Compared with the prior art, the traditional Chinese medicine composition disclosed by the invention not only can relieve gastrointestinal symptoms during chemotherapy and effectively improve delayed nausea and vomiting, but also can inhibit weight loss caused by chemotherapy, improve myelosuppression after chemotherapy and the nutritional state of a patient and improve the living quality of the patient.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and in particular relates to a traditional Chinese medicine composition for treating the decline of nutritional status after chemotherapy and its application. Background Art

[0002] Chemotherapy is the main means for treating malignant tumors. Although it has significant effects, it has many adverse reactions. The more common ones are myelosuppression, gastrointestinal reactions, peripheral neuropathy, etc. Digestive tract adverse reactions are the most common and one of the earliest adverse reactions in cancer patients during chemotherapy. The incidence of chemotherapy-induced gastrointestinal symptoms can be as high as 80-90%. Approximately 67% of patients receiving high-dose cisplatin chemotherapy experience diarrhea, 70-80% of patients suffer from vomiting, and about 50% of chemotherapy patients have varying degrees of nausea symptoms.

[0003] Currently, Western medicine is mostly used to relieve the related symptoms of gastrointestinal reactions caused by chemotherapy, but most Western medicines have adverse reactions to varying degrees. For example, the most common adverse reactions of 5-HT3 receptor antagonists are headache and asymptomatic prolongation of electrocardiogram intervals; the most common side effects of NK-1 receptor antagonists are fatigue, hiccups and indigestion; corticosteroids are also commonly used clinically to treat chemotherapy-induced nausea and vomiting (CINV). After use, acne, hypokalemia, hypertension, hyperglycemia, pituitary-pituitary-adrenal axis suppression, osteonecrosis and immune deficiency are likely to occur.

[0004] In terms of oral traditional Chinese medicine, the main pathogenesis of nausea and vomiting caused by chemotherapy is the disorder of qi movement and transformation. Harmonizing the stomach and suppressing reverse flow to stop vomiting is the basic principle of treatment, and it is necessary to take into account the pathological basis of drug toxicity damage and spleen and stomach weakness. Among classical prescriptions, the representative prescription of "pungent opening and bitter descending", Banxia Xiexin Decoction, can significantly improve chemotherapy-related nausea and vomiting. Among them, banxia alkaloids are the main components for banxia to exert its antiemetic effect. Zhang Qilong et al. found that banxia alkaloids have a certain blocking effect on 5-HT receptors and NK-1 receptors on the ileum, which may be one of the important mechanisms for banxia to prevent and treat CINV. Liujunzi Decoction has also been found to have an antiemetic effect. Its mechanism is to improve gastric emptying by blocking the 5-HT3 receptor pathway. At the same time, atractylodes polysaccharide contained in atractylodes in the prescription can improve the antioxidant capacity of gastric mucosa and play a role in protecting the stomach. The high-frequency core traditional Chinese medicines for improving CINV mainly include licorice, pinellia, poria, atractylodes and tangerine peel, and their effects are mainly to tonify deficiency and resolve phlegm. "Tangye Bencao" records: "Sweet can tonify the spleen and can soothe it, so it is used in decoctions to strengthen the middle energizer", and "Compendium of Materia Medica" records: "Licorice, tonifies the spleen and stomach".

[0005] However, currently, traditional Chinese medicines are mostly used to improve gastrointestinal reactions after chemotherapy. In "The Effect of Zhizhu Liujunzi Decoction in Treating Lung Cancer Patients with Qi Deficiency Syndrome during Chemotherapy and Its Influence on Tongue Coating Thickness and Gastrointestinal Reactions", the incidence of gastrointestinal reactions was used to evaluate the improvement of gastrointestinal reactions and quality of life in lung cancer patients with qi deficiency syndrome by Zhizhu Liujunzi Decoction (including ginseng, atractylodes macrocephala, poria cocos, pinellia ternata, citrus reticulata, fructus aurantii, etc.). The results showed that the incidence of gastrointestinal reactions in the treatment group was: decreased appetite (24.44%), nausea (13.33%), vomiting (8.89%), diarrhea (6.67%), constipation (13.33%); the incidence of gastrointestinal reactions in the control group was: decreased appetite (60.00%), nausea (37.78%), vomiting (31.11%), diarrhea (26.67%), constipation (42.22%), proving that relevant traditional Chinese medicines can effectively improve gastrointestinal reactions after chemotherapy. However, the above-mentioned Zhizhu Liujunzi Decoction can only relieve some gastrointestinal reactions, and the problem of decreased nutritional status after chemotherapy still needs to be solved. Summary of the Invention

[0006] The object of the present invention is to provide a traditional Chinese medicine composition for treating decreased nutritional status after chemotherapy and its application, in order to overcome the defect that existing traditional Chinese medicine compositions are difficult to balance the improvement of gastrointestinal reactions after chemotherapy and the improvement of the patient's nutritional status.

[0007] The object of the present invention can be achieved by the following technical solutions:

[0008] The present invention first provides a traditional Chinese medicine composition for treating decreased nutritional status after chemotherapy, which is characterized in that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 9 - 40 parts of codonopsis pilosula, 6 - 30 parts of stir-fried atractylodes macrocephala, 6 - 30 parts of poria cocos, 6 - 20 parts of processed pinellia ternata, 6 - 12 parts of citrus reticulata, 6 - 40 parts of stir-fried fructus crataegi, 6 - 40 parts of stir-fried medicated leaven, 6 - 40 parts of stir-fried fructus hordei germinatus and fructus malt, 6 - 40 parts of millettia reticulata, 6 - 40 parts of pyrrosia lingua, 6 - 40 parts of agrimonia pilosa, 3 - 15 parts of roasted licorice root, and 6 - 30 parts of Chinese dates.

[0009] Further, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 15 - 32 parts of codonopsis pilosula, 10 - 15 parts of stir-fried atractylodes macrocephala, 14 - 16 parts of poria cocos, 6 - 10 parts of processed pinellia ternata, 6 - 10 parts of citrus reticulata, 13 - 30 parts of stir-fried fructus crataegi, 13 - 30 parts of stir-fried medicated leaven, 28 - 30 parts of stir-fried fructus hordei germinatus and fructus malt, 28 - 32 parts of millettia reticulata, 28 - 32 parts of pyrrosia lingua, 28 - 32 parts of agrimonia pilosa, 5 - 7 parts of roasted licorice root, and 12 - 18 parts of Chinese dates.

[0010] Still further, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 30 parts of codonopsis pilosula, 12 parts of stir-fried atractylodes macrocephala, 15 parts of poria cocos, 9 parts of processed pinellia ternata, 9 parts of citrus reticulata, 15 parts of stir-fried fructus crataegi, 15 parts of stir-fried medicated leaven, 15 parts of stir-fried fructus hordei germinatus and fructus malt, 30 parts of millettia reticulata, 30 parts of pyrrosia lingua, 30 parts of agrimonia pilosa, 6 parts of roasted licorice root, and 15 parts of Chinese dates.

[0011] In the traditional Chinese medicine formula of the present invention, Codonopsis pilosula is the main ingredient for strengthening the spleen and lungs, nourishing blood and promoting the production of body fluids; Atractylodes macrocephala is the auxiliary ingredient for strengthening the spleen and replenishing qi, consolidating the exterior and stopping sweating, and removing dampness and promoting diuresis. The Atractylodes macrocephala polysaccharide can improve the antioxidant capacity of the gastric mucosa and play a role in protecting the stomach; Poria cocos is the auxiliary ingredient for promoting diuresis and removing dampness, strengthening the spleen and calming the mind; Tangerine peel is sweet and bitter in taste, warm in nature, and enters the spleen and lung meridians, and has the effects of regulating qi and strengthening the spleen, removing dampness and resolving phlegm; Pinellia ternata has anti-inflammatory, anti-aging, and sedative effects, and the alkaloids in Pinellia ternata can inhibit the central nervous system and have an antiemetic effect. These five herbs are taken from the important components of Liujunzi Decoction, and their combined use can strengthen the spleen and replenish qi, remove dampness and resolve phlegm; and Radix Glycyrrhizae Preparata and Chinese Dates are used to harmonize the other herbs.

[0012] At the same time, hawthorn charcoal, Shenqu charcoal, fried barley sprouts, and fried malt can strengthen the spleen and appetite, help digestion and eliminate abdominal distension.

[0013] In addition, the folks call it "weakness grass". It can replenish qi and blood, improve fatigue and weakness. It is especially suitable for those who are weak due to long-term illness, or those who have qi and blood deficiency after surgery or radiotherapy and chemotherapy. Modern research shows that its polysaccharide components can enhance immunity and alleviate the weak state after radiotherapy and chemotherapy.

[0014] Millettia reticulata is warm in nature, bitter and slightly sweet in flavor, and specifically affects the liver and kidney meridians. The "Supplement to Compendium of Materia Medica" states that it "greatly replenishes qi and blood, strengthens bones and muscles, and unclogs the meridians." Modern research confirms that it can significantly promote the proliferation of bone marrow hematopoietic stem cells and increase hemoglobin levels by stimulating the secretion of erythropoietin.

[0015] Selaginella ternata is slightly cold in nature, bitter and sweet in flavor, and primarily enters the lung and bladder meridians. The Shennong Bencao Jing states that it "expels fatigue and heat, and promotes urination." Modern pharmacology reveals that it can activate granulocyte colony-stimulating factor, promoting the production of white blood cells, particularly neutrophils, and is effective for treating leukopenia after radiotherapy and chemotherapy. The combination of Millettia reticulata and Selaginella ternata creates a potent combination of warming and cooling properties, regulating both Qi and blood, and forming a "biochemical barrier between Qi and blood," effectively tonifying Qi and blood.

[0016] The present invention also provides an application of a traditional Chinese medicine composition in the preparation of a drug for treating decreased nutritional status after chemotherapy. The drug is an oral preparation, including any one of granules, lyophilized powder, decoction, tablets, capsules, pills, oral liquid or syrup.

[0017] Furthermore, the medicine also includes pharmaceutically acceptable conventional excipients.

[0018] Furthermore, the drug is preferably in the form of granules, which are prepared by the following method:

[0019] S1. Extraction: Weigh the corresponding Chinese medicinal raw materials, add water and boil them for primary extraction, filter to obtain a first filtrate and a filter residue: add water to the filter residue and perform a secondary heating extraction, filter and combine the two filtrates;

[0020] S2. Concentration: Heat and concentrate the filtrate obtained in S1.

[0021] S3. Spray drying: Spray dry the concentrated filtrate in S2 to obtain dry paste powder.

[0022] S4. Sieving and granulation: Sieve and mix the dry paste powder obtained in S3, and then prepare the final granule by dry granulation.

[0023] Further, in step S1, the ratio of the medicinal liquids for the two heating extractions is 1:(6 - 10).

[0024] Further, in step S1, the heating extraction time is 1 - 2 h.

[0025] Further, in step S2, heat and concentrate until the specific gravity is 1.08 - 1.10.

[0026] Further, in step S2, the heating temperature is 60 - 70 °C.

[0027] Further, in step S3, the inlet air temperature for the spray drying is 165 - 195 °C, and the outlet air temperature is 80 - 105 °C.

[0028] Further, in step S4, the mesh number for sieving is 70 - 90 meshes, and the mesh number of the finally prepared granule is 12 - 30 meshes.

[0029] Further, the usage method of the granule is as follows: Pause on the day of chemotherapy. Start taking the Hewei Yangxue Granule from the first day after chemotherapy, 2 times a day, 2 packs each time, each pack is 12 g, and take it with 150 ml of warm boiled water.

[0030] Further, the drug is used to relieve gastrointestinal symptoms during chemotherapy, improve delayed nausea and vomiting, and inhibit weight loss caused by chemotherapy.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] (1) The traditional Chinese medicine composition of the present invention can not only relieve gastrointestinal symptoms during chemotherapy, effectively improve delayed nausea and vomiting, but also inhibit weight loss caused by chemotherapy, improve myelosuppression (WBC, NE) after chemotherapy and the nutritional status of patients, and improve the quality of life of patients.

[0033] (2) The traditional Chinese medicine composition of the present invention is properly formulated. Codonopsis pilosula is used as the monarch drug to invigorate the spleen and lungs, nourish blood and promote fluid production; Atractylodes macrocephala is used as the minister drug to invigorate the spleen and replenish qi, secure the exterior and stop sweating, dry dampness and promote diuresis; Poria cocos is used as the assistant drug, which is good at promoting diuresis and percolating dampness, strengthening the spleen and calming the mind; Tangerine peel is sweet, bitter and warm in nature, and belongs to the spleen and lung meridians, with the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm; The alkaloids in Pinellia ternata can stop vomiting by inhibiting the central nervous system. These five drugs are taken from the important components of Liujunzi Decoction, and when used together, they can strengthen the spleen and replenish qi, dry dampness and resolve phlegm; Prepared Licorice Root and Jujube are used as the guiding drugs to harmonize various drugs. In addition, Carbonized Hawthorn Fruit, Carbonized Medicated Leaven, Stir-fried Fructus Setariae Germinatus and Stir-fried Fructus Hordei Germinatus in the prescription can also strengthen the spleen and promote appetite, promote digestion and eliminate mass; Agrimonia pilosa can replenish qi and nourish blood, and improve weakness due to consumptive disease; The combination of Spatholobus suberectus and Pyrrosia lingua forms a wonderful combination of mutually restraining cold and heat, and regulating qi and blood, and jointly constructs a "qi and blood biotransformation barrier", achieving the effect of supplementing qi and nourishing blood together. Through the reasonable drug ratio in the above formula, it can relieve gastrointestinal symptoms and improve the nutritional status of patients.

[0034] (3) The traditional Chinese medicine composition of the present invention has mild medication and is not likely to cause gastrointestinal reactions during treatment. After taking it for 28 days, it can better improve myelosuppression (WBC, NE) after chemotherapy and reduce the toxic and side effects of non-small cell lung cancer patients undergoing chemotherapy.

[0035] (4) The traditional Chinese medicine composition of the present invention can be prepared into granule drugs, which are convenient to carry and easy for patients to brew and take, without the need for daily decocting. Description of the Drawings

[0036] Figure 1 It is a comparison chart of body weight before and after treatment of the present invention. *P < 0.05, **P < 0.01, ***P < 0.001.

[0037] Figure 2 It is a measurement result chart of white blood cells and neutrophils before and after treatment and during treatment of the present invention. *P < 0.05, **P < 0.01, ***P < 0.001.

[0038] Figure 3 It is a change chart of scores of various symptoms of the spleen and stomach system before and after treatment of the present invention. *P < 0.05, **P < 0.01, ***P < 0.001.

[0039] Figure 4 It is a comparison chart of the degree of delayed nausea of the present invention. *P < 0.05, **P < 0.01, ***P < 0.001. Detailed Embodiments

[0040] The present invention will be described in detail below with reference to the drawings and specific embodiments. This embodiment is implemented on the premise of the technical solution of the present invention, and gives detailed implementation methods and specific operation processes, but the protection scope of the present invention is not limited to the following embodiments.

[0041] Unless otherwise specified, the reagents, methods, instruments, and equipment used in the present invention are conventional reagents, methods, instruments, and equipment in the art. Unless otherwise specified, the reagents and materials used in the following examples are all commercially available.

[0042] Example 1:

[0043] This example provides a traditional Chinese medicine composition for treating the decline in nutritional status after chemotherapy. The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 30 parts of Codonopsis pilosula, 12 parts of stir-fried Atractylodes macrocephala, 15 parts of Poria cocos, 9 parts of processed Pinellia ternata, 9 parts of Citrus reticulata Blanco, 15 parts of stir-fried Crataegus pinnatifida, 15 parts of stir-fried Medicago sativa, 15 parts of stir-fried Setaria italica Beauv. var. germanica (Mill.) Schred. and Hordeum vulgare L. var. nudum Hook. f., 30 parts of Spatholobus suberectus Dunn, 30 parts of Pyrrosia lingua (Thunb.) Farw., 30 parts of Agrimonia pilosa Ledeb., 6 parts of roasted Glycyrrhiza uralensis Fisch., and 15 parts of Chinese date.

[0044] In this example, the above traditional Chinese medicine composition is prepared into a granule drug for treating the decline in nutritional status after chemotherapy, namely Hewei Yangxue Granules. The production process is carried out in an environment meeting GMP requirements. The specific preparation method is as follows:

[0045] S1: Extraction process:

[0046] 1) Extraction: Add 10 times the amount of water for the first decoction, heat to boiling, maintain gentle boiling for 2 hours, and perform suction filtration (200 mesh); add 8 times the amount of water for the second decoction, heat to boiling, maintain gentle boiling for 1 hour, and perform suction filtration (200 mesh), and combine the filtrates.

[0047] 2) Concentration: Concentrate the filtrate under reduced pressure by heating to a specific gravity of 1.08 - 1.10, and the heating temperature is 60 - 70 °C). Quality requirements for the clear paste: There should be no medicinal residues or scorched chips in the clear paste.

[0048] 3) Spray drying: Process parameters: Inlet air temperature: 165 - 195 °C; outlet air temperature: 80 - 105 °C. Quality requirements for the dry extract powder: There should be no scorched chips or soft lumps.

[0049] 4) Sieving and mixing: Sieve the obtained dry extract powder (80 mesh) and mix evenly.

[0050] S2: Granule packaging:

[0051] 1) Granulation: Place the dry extract powder in a dry granulator and granulate it into 12 - 30 mesh granules by dry granulation;

[0052] 2) Inkjet coding: Use a blank aluminum foil bag for inkjet printing and packaging;

[0053] 3) Inner packaging: Pack the granules into small aluminum foil bags as required;

[0054] 4) Outer packaging: Perform outer packaging as required.

[0055] S3: Inspection: The inspection items for the finished product granules include appearance, solubility, moisture content, particle size, difference in filled quantity, microbial limit, etc. (The inspection is based on the fourth part of the Chinese Pharmacopoeia (2020 Edition)).

[0056] Example 2:

[0057] This example provides a traditional Chinese medicine composition for treating the decline in nutritional status after chemotherapy. The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 25 parts of Codonopsis pilosula, 12 parts of stir-fried Atractylodes macrocephala, 12 parts of Poria cocos, 8 parts of processed Pinellia ternata, 11 parts of Citrus reticulata Blanco, 20 parts of stir-fried Crataegus pinnatifida, 20 parts of stir-fried Medicago sativa, 25 parts of stir-fried Setaria italica and Hordeum vulgare, 25 parts of Spatholobus suberectus, 25 parts of Pyrrosia lingua, 35 parts of Agrimonia pilosa Ledeb., 5 parts of honey-fried Glycyrrhiza uralensis Fisch., and 10 parts of Chinese date.

[0058] In this example, the above traditional Chinese medicine composition is prepared into a granule drug for treating the decline in nutritional status after chemotherapy, namely Hewei Yangxue Granules. The specific preparation method refers to Example 1.

[0059] Example 3:

[0060] This example provides a traditional Chinese medicine composition for treating the decline in nutritional status after chemotherapy. The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 35 parts of Codonopsis pilosula, 15 parts of stir-fried Atractylodes macrocephala, 18 parts of Poria cocos, 10 parts of processed Pinellia ternata, 7 parts of Citrus reticulata Blanco, 10 parts of stir-fried Crataegus pinnatifida, 10 parts of stir-fried Medicago sativa, 35 parts of stir-fried Setaria italica and Hordeum vulgare, 35 parts of Spatholobus suberectus, 35 parts of Pyrrosia lingua, 25 parts of Agrimonia pilosa Ledeb., 10 parts of honey-fried Glycyrrhiza uralensis Fisch., and 20 parts of Chinese date.

[0061] In this example, the above traditional Chinese medicine composition is prepared into a granule drug for treating the decline in nutritional status after chemotherapy, namely Hewei Yangxue Granules. The specific preparation method refers to Example 1.

[0062] Taking the Hewei Yangxue Granules prepared in Example 1 as an example, the present invention conducts clinical trials to prove, and the specific process is as follows:

[0063] A randomized controlled study was conducted on non-small cell lung cancer patients who received outpatient or inpatient treatment in the First Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine from April 2024 to January 2025. The treatment group received chemotherapy + Hewei Yangxue Fang granules, and the control group received chemotherapy + placebo granules. The drugs used for chemotherapy were administered according to the recommended regimens in the 2024 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer, including pemetrexed monotherapy, docetaxel monotherapy, platinum-containing doublet chemotherapy regimens, etc. The placebo was prepared according to the method of pure placebo, achieving similarity in color, odor, taste, and appearance to traditional Chinese medicine granules, without drug ingredients and therapeutic effects. Preparation method: Take maltodextrin, lemon yellow pigment, sunset yellow pigment, caramel pigment, bitter agent, and lactose, mix them evenly, then granulate the mixture by dry granulation to make 12 - 30 mesh granules, and finally package the granules into small aluminum foil bags as required. A total of 81 patients were finally included in the analysis, with 55 in the treatment group and 26 in the control group. For the 55 cases in the oral Hewei Yangxue Fang treatment group, the specific conventional usage method of Hewei Yangxue Fang was to suspend Hewei Yangxue granules on the day of chemotherapy. Start taking Hewei Yangxue granules on the first day after chemotherapy. Take it twice a day, 2 packs each time, with each pack being 12 g, and take it with 150 ml of warm boiled water.

[0064] The treatment duration was 2 chemotherapy cycles, and the weight changes, spleen and stomach system symptoms, and evaluation of nausea and vomiting symptoms were observed in both groups. In the following result analysis, C1 represents the first chemotherapy cycle, and C2 represents the second chemotherapy cycle. T0 is the first day of the first chemotherapy cycle, denoted as C1 - 1d, and T1, T2, T3, T4, T5, T6 refer to T0, representing C1 - d7, C1 - d14, C2 - 1d, C2 - d7, C2 - d14, and C2 - d21 in sequence, and will not be elaborated further hereafter. In statistical analysis, *P < 0.05, **P < 0.01, ***P < 0.001, and will not be elaborated further hereafter.

[0065] The results are as follows:

[0066] (1) Weight changes

[0067] As Figure 1 shown, it was found that there was no statistical difference in the weight between the two groups of patients before treatment (P > 0.05). After treatment, when comparing the weights of the two groups of patients before and after treatment within the group, it was found that there were statistical differences in the weight changes within the group of patients in the oral Hewei Yangxue Fang treatment group (63.87 ± 9.07 vs. 65.06 ± 9.42, P < 0.05) and the placebo control group (64.48 ± 8.34 vs. 63.45 ± 8.45, P < 0.05). Moreover, the weight increased in the treatment group after treatment, while it decreased in the control group.

[0068] In addition, the mental state of the treatment group was improved compared with that of the control group. After treatment, fatigue was alleviated, appetite was enhanced, and mood was improved. At the same time, the complexions of some patients in the treatment group changed from sallow to rosy, and the pale white tongue improved, which was in line with the manifestation of "abundant qi and blood" in traditional Chinese medicine.

[0069] In traditional Chinese medicine theory, malnutrition mostly belongs to the categories of "consumptive fatigue", "sallow complexion", "infantile malnutrition", etc. Chemotherapy drugs are of cold nature and mostly damage the spleen and stomach. It is mentioned in "Plain Questions: The Secret Classic of the Spiritual Orchid" that "the spleen and stomach are the officials in charge of the granary, from which the five flavors come out." This shows that the spleen and stomach are the foundation of acquired constitution and the source of qi and blood production. If the spleen and stomach are weak, the essence of water and grains cannot be normally transported and transformed, leading to poor nutritional status. "Internal injury of the spleen and stomach gives rise to all diseases." "Plain Questions: Theory of Flaccidity" in "Huangdi Neijing" states that "Yangming is the sea of the five zang-organs and six fu-organs, and it is responsible for moistening the tendons. The tendons are responsible for binding the bones and facilitating the movement of joints." It points out that the stomach is the sea of water and grains and the source of qi and blood production. When the qi and blood of the Yangming meridian are abundant, the joints can move freely. The spleen ascends and the stomach descends. The spleen is responsible for ascending the clear and the stomach is responsible for descending the turbid. When the spleen and stomach ascend and descend normally and the qi mechanism is smooth, the qi and blood of the whole body are abundant. Otherwise, there will be malnutrition states such as emaciation of muscles and difficulty in limb movement. In the Hewei Yangxue Decoction, the Licorice Root is removed from the Four Gentlemen Decoction, and Chenpi and Pinellia ternata are added to the Six Gentlemen Decoction to strengthen the spleen and replenish qi, and dry dampness and resolve phlegm. The spleen is the official in charge of the granary, preferring dryness to dampness. When the spleen and stomach function normally, it can effectively improve the nutritional status of NSCLC chemotherapy patients.

[0070] (2) Determination of white blood cells and neutrophils

[0071] As Figure 2 shown, the determination results of WBC (white blood cells) and NE (neutrophils) before treatment showed no significant statistical differences between the two groups (6.44±1.50 vs. 6.50±2.37, P>0.05; 4.21±1.31 vs. 4.83±2.59, P>0.05). However, at C2-d7 in the second chemotherapy cycle, there were statistical differences in the comparison of WBC and NE determination results between the two groups (5.32±2.76 vs. 3.62±1.22, P<0.05; 3.45±2.45 vs. 2.19±1.03, P<0.05); at C2-d21, there was a statistical difference in the comparison of WBC determination results between the two groups (6.70±2.42 vs. 5.60±2.00, P<0.05).

[0072] Therefore, the Hewei Yangxue Decoction granules of the present invention can better improve the levels of WBC and NE in chemotherapy patients. This may be related to the fact that Pyrrosia lingua in the formula enhances the function of the mononuclear-macrophage system and improves the immune ability by bidirectionally regulating the immune-related signaling pathway, thereby promoting the generation of white blood cells.

[0073] (3) Symptoms related to the spleen and stomach system

[0074] As Figure 3As shown, the total scores of the symptoms of the spleen and stomach system (nausea, loss of appetite, vomiting, constipation, bitter taste in the mouth, diarrhea) before the first treatment (C1-1d) and after the second treatment (C2-d14) of the patients were compared statistically between groups. It was found that there was no statistical difference in the total scores of the symptoms of the spleen and stomach system between the two groups before treatment (P>0.05). The scores of each symptom before treatment were compared between groups, and it was found that there was no statistical difference (P>0.05). After treatment, there were statistical differences in the total scores of the symptoms of the spleen and stomach system (0.88±1.02 vs. 3.77±3.21, P<0.05), nausea (0.10±0.30 vs. 0.77±1.27, P<0.05), vomiting (0.00±0.00 vs. 0.41±0.91, P<0.05), and bitter taste in the mouth (0.02±0.14 vs. 0.41±1.05, P<0.05) between groups.

[0075] At the same time, there were statistical differences in the total scores of the symptoms of the spleen and stomach system between groups at C1-d14, C2-1d, and C2-d7 during the treatment period (P<0.05); further comparing the between-group scores of nausea, loss of appetite, vomiting, constipation, bitter taste in the mouth, and diarrhea at each time point during the treatment period, there was a statistical difference in the score of constipation between groups at C1-d7 (0.94±1.60 vs. 1.65±1.57, P<0.05), and there were statistical differences in the scores of nausea and constipation between the two groups at C1-d14 (0.16±0.50 vs. 0.70±1.26, P<0.05; 0.18±0.48 vs. 0.55±0.76, P<0.05). At C2-d7, there were statistical differences between the two groups in nausea, loss of appetite, and vomiting (P<0.05).

[0076] Traditional Chinese medicine believes that the pathogenesis of tumors mainly lies in the deficiency of healthy qi and the imbalance of yin and yang in the zang-fu organs. Although chemotherapy can inhibit tumors, it may further damage healthy qi, especially the function of the spleen and stomach, resulting in insufficient production of qi and blood, and more deficiency of healthy qi. Cheng Zhongling mentioned in "Medical Insights": "Nausea is due to the upward reversal of stomach qi, either caused by cold, heat, phlegm-fluid retention, or food stagnation." It points out that the upward reversal of stomach qi is the core pathogenesis of nausea. "The Spiritual Pivot" mentions that "the meridian of the foot-taiyin... when there is abnormal movement of its qi, it will cause a stiff tongue root and vomiting during eating", indicating that when the qi of this meridian undergoes abnormal changes, such as disharmony between the spleen and stomach, it may lead to vomiting. The toxic pathogens of chemotherapy drugs accumulate and stagnate in the gastrointestinal tract, resulting in adverse rising and falling of the qi movement in the gastrointestinal tract. The turbid qi does not descend but instead reverses upward, inducing vomiting reactions; the spleen and stomach are weak, turbid pathogens accumulate and stagnate, the qi movement of the fu-organs is not smooth, the qi mechanism is chaotic, and the main focus is on smoothing the qi movement. The stomach is one of the six fu-organs and follows the principle of descending and regulating. "When the qi movement of the fu-organs is smooth, the qi movement of the zang-organs will be peaceful." The results show that after 14 days of treatment with the formula for regulating the stomach and nourishing blood, the symptoms related to the spleen and stomach of the patients were significantly improved. Among them, 7 days after chemotherapy, due to receiving 5-HT3 receptor antagonist antiemetics such as ondansetron and tropisetron, the most common adverse reaction of the patients was constipation, and the constipation symptoms in the treatment group were significantly alleviated compared with the control group. After treatment, the rising and falling of the spleen and stomach returned to normal, so the symptoms of nausea could be effectively improved. The transportation and transformation of the spleen and stomach are abnormal, phlegm-dampness is generated internally, and over time it overflows to the mouth, so bitter taste in the mouth can be seen. 21 days after taking the medicine in the treatment group, the transportation and transformation functions of the spleen and stomach had basically recovered, while those of the control group had not recovered. Therefore, there was a statistical difference in the bitter taste symptoms between the two groups (P<0.05). Since the chemotherapy regimens involved in this study did not contain common drugs that are likely to cause chemotherapy-related diarrhea, such as irinotecan and capecitabine, there was no statistical difference in the diarrhea symptoms between the two groups.

[0077] (4) Delayed nausea and vomiting

[0078] As Figure 4 shown, 4 days after the end of chemotherapy, the situation of nausea and vomiting in the patients from 24 hours after the end of chemotherapy to the 4th day after the end of chemotherapy was evaluated. The number of cases and severity of delayed nausea and vomiting in the treatment group and the control group were statistically compared. It was found that in the first chemotherapy cycle, the number of patients who had nausea 24 hours after treatment in the treatment group was 28, and in the control group was 21. There was a statistical difference in the comparison of the degree of nausea between the groups (1.13±1.32 vs. 2.69±2.17, P<0.05). In the second chemotherapy cycle, the number of patients who had nausea 24 hours after treatment in the treatment group was 21 (38.18%), and in the control group was 19 (73.08%). There was a statistical difference in the comparison of the degree of nausea between the groups (0.64±0.93 vs. 2.65±2.06, P<0.05). At the same time, the degree of delayed nausea in the first and second chemotherapy cycles was compared within the groups. It was found that there was a statistical difference in the within-group comparison of the treatment group (P<0.05), while there was no statistical difference in the control group (P>0.05).

[0079] Nausea is mostly caused by weakness of the spleen and stomach and upward adverse flow of stomach qi. The spleen and stomach are the sources for the production of qi and blood. If the spleen and stomach are weak, transportation and transformation will fail, and upward adverse flow of stomach qi will be induced, leading to nausea. When the spleen and stomach fail to function healthily, phlegm-dampness will accumulate internally, blocking qi movement and causing disharmony of the stomach in descending. By strengthening the spleen and stomach, resolving phlegm and suppressing adverse flow, the ascending and descending functions of the spleen and stomach can be restored, qi movement can be dredged, and thus nausea can be improved.

[0080] In summary, the traditional Chinese medicine composition of the present invention can not only relieve gastrointestinal symptoms during chemotherapy, improve delayed nausea and vomiting, but also inhibit weight loss caused by chemotherapy, improve myelosuppression (WBC, NE) after chemotherapy and the nutritional status of patients, and improve the quality of life of patients.

[0081] The above description of the embodiments is to enable those of ordinary skill in the art to understand and use the invention. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative efforts. Therefore, the present invention is not limited to the above embodiments, and all improvements and modifications made by those skilled in the art without departing from the scope of the present invention according to the disclosure of the present invention should be within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating the decline of nutritional status after chemotherapy, characterized in that, The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 9-40 parts of Codonopsis pilosula, 6-30 parts of stir-fried Atractylodes macrocephala, 6-30 parts of Poria cocos, 6-20 parts of processed Pinellia ternata, 6-12 parts of Citrus reticulata Blanco, 6-40 parts of stir-fried Crataegus pinnatifida, 6-40 parts of stir-fried Medicago sativa, 6-40 parts of stir-fried Setaria italica and Hordeum vulgare, 6-40 parts of Spatholobus suberectus, 6-40 parts of Pyrrosia lingua, 6-40 parts of Agrimonia pilosa Ledeb., 3-15 parts of honey-fried Glycyrrhiza uralensis Fisch., and 6-30 parts of Chinese date.

2. The traditional Chinese medicine composition for treating the decline of nutritional status after chemotherapy according to claim 1, wherein, The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 15-32 parts of Codonopsis pilosula, 10-15 parts of stir-fried Atractylodes macrocephala, 14-16 parts of Poria cocos, 6-10 parts of processed Pinellia ternata, 6-10 parts of Citrus reticulata Blanco, 13-30 parts of stir-fried Crataegus pinnatifida, 13-30 parts of stir-fried Medicago sativa, 28-30 parts of stir-fried Setaria italica and Hordeum vulgare, 28-32 parts of Spatholobus suberectus, 28-32 parts of Pyrrosia lingua, 28-32 parts of Agrimonia pilosa Ledeb., 5-7 parts of honey-fried Glycyrrhiza uralensis Fisch., and 12-18 parts of Chinese date.

3. A traditional Chinese medicine composition for treating the decline of nutritional status after chemotherapy according to claim 1, characterized in that, The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 30 parts of Codonopsis pilosula, 12 parts of stir-fried Atractylodes macrocephala, 15 parts of Poria cocos, 9 parts of processed Pinellia ternata, 9 parts of Citrus reticulata Blanco, 15 parts of stir-fried Crataegus pinnatifida, 15 parts of stir-fried Medicago sativa, 15 parts of stir-fried Setaria italica and Hordeum vulgare, 30 parts of Spatholobus suberectus, 30 parts of Pyrrosia lingua, 30 parts of Agrimonia pilosa Ledeb., 6 parts of honey-fried Glycyrrhiza uralensis Fisch., and 15 parts of Chinese date.

4. Use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for treating decreased nutritional status after chemotherapy, characterized in that, The drug is an oral preparation, which includes any one of granules, freeze-dried powder, decoction, tablets, capsules, pills, oral liquid or syrup.

5. Use of the traditional Chinese medicine composition according to claim 4 in the preparation of a medicament for treating decreased nutritional status after chemotherapy, characterized in that, The granules are prepared by the following method: S1. Extraction: Weigh the corresponding traditional Chinese medicine raw materials, boil them in water for primary extraction, filter to obtain the first filtrate and residue; add water to the residue for secondary heating extraction, and filter and combine the two filtrates. S2. Concentration: Heat and concentrate the filtrate obtained in S1. S3. Spray drying: Spray dry the filtrate concentrated in S2 to obtain dry extract powder. S4. Sieving and granulation: Sieve and mix the dry extract powder obtained in S3, and then prepare the final granules by dry granulation.

6. Use of the traditional Chinese medicine composition according to claim 5 in the preparation of a medicament for treating decreased nutritional status after chemotherapy, characterized in that, In step S1, the liquid ratio of the two heating extractions is 1:(6-10), and the heating extraction time is 1-2 h.

7. Use of the traditional Chinese medicine composition according to claim 5 in the preparation of a medicament for treating the decline of nutritional status after chemotherapy, characterized in that, In step S2, heat and concentrate to a specific gravity of 1.08-1.10, and the heating temperature is 60-70 °C.

8. Use of the traditional Chinese medicine composition according to claim 5 in the preparation of a medicament for treating the decline of nutritional status after chemotherapy, characterized in that, In step S3, the inlet air temperature of the spray drying is 165-195 °C, and the outlet air temperature is 80-105 °C.

9. Use of the traditional Chinese medicine composition according to claim 5 in the preparation of a medicament for treating the decline of nutritional status after chemotherapy, characterized in that, In step S4, the mesh number of the sieving is 70-90 mesh, and the mesh number of the finally prepared granules is 12-30 mesh.

10. Use of the traditional Chinese medicine composition according to claim 4 in the preparation of a medicament for treating decreased nutritional status after chemotherapy, characterized in that, The drug is used to relieve gastrointestinal symptoms during chemotherapy, improve delayed nausea and vomiting, and inhibit weight loss caused by chemotherapy.

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