Traditional Chinese medicine composition for improving cancer-related fatigue as well as preparation method and application of traditional Chinese medicine composition

Abstract

The traditional Chinese medicine composition is characterized by being prepared by extracting the following traditional Chinese medicinal materials in parts by weight: 10-20 parts of radix astragali preparata, 10-20 parts of oldenlandia diffusa, 10-14 parts of radix pseudostellariae, 10-14 parts of roasted rhizoma atractylodis macrocephalae, 10-14 parts of poria cocos, 5-10 parts of albizia flower, 6-12 parts of radix ophiopogonis, 3-9 parts of paris polyphylla, 6-12 parts of processed rhizoma arisaematis, 6-12 parts of vinegar-processed curcuma zedoary and 2-4 parts of honey-fried licorice root. The traditional Chinese medicine composition has the effects of strengthening the body resistance and eliminating evil, combining purgation and tonification and treating both symptoms and root causes, has the effects of strengthening the body resistance and strengthening the spleen, resolving depression and relieving restlessness, and eliminating cancer and detoxifying, and is beneficial to improving various clinical symptoms of cancer fatigue patients.

Description

Technical Field

[0001] The present invention relates to the medical field, and in particular to a Chinese medicinal composition for improving cancer-related fatigue, which is prepared from Chinese medicinal materials as raw materials, and a preparation method and application thereof. Background Art

[0002] Cancer-related fatigue, also known as cancer-related fatigue, is one of the common clinical symptoms of patients with malignant tumors. It is closely related to the tumor itself or the treatment process. Unlike ordinary fatigue, cancer-related fatigue is more severe, disproportionate to the amount of activity or energy consumption, cannot be relieved by rest or sleep, and lasts for a long time. Cancer-related fatigue is a subjective experience involving multiple dimensions of physiology, psychology, function and society, which seriously affects the patient's physical condition, mental health, social function and quality of life. It mainly manifests in three aspects: ① physical fatigue: weakness and inability to complete the work that was originally competent; ② emotional fatigue: lack of passion, depression, and lack of energy; ③ cognitive fatigue: difficulty concentrating and unclear thinking. At present, the effect of Western medicine in the treatment of cancer-related fatigue is still unclear. In terms of alleviating clinical symptoms, traditional Chinese medicine shows certain advantages and characteristics. According to traditional Chinese medicine theory, cancer-related fatigue belongs to the category of "deficiency". The name of "Xulao" was first mentioned in "Golden Chamber Synopsis: Blood Bi and Deficiency Disease Pulse and Treatment" by Zhang Zhongjing, a famous doctor in the Eastern Han Dynasty. The article records: "The five labors are extremely weak and thin, and the abdomen is full and cannot eat." The so-called "Xulao", also known as "Xu Shang", refers to the deficiency of qi, blood, yin, and yang, as well as the damage of the five internal organs. Its main causes include long-term illness and physical weakness, or damage to the vital energy caused by chemotherapy, radiotherapy and surgery. Traditional Chinese medicine believes that the kidney is the foundation of the innate and the spleen is the foundation of the acquired. Cancer and its related treatments often cause damage to the foundation of the acquired and acquired at the same time, and both qi, blood, yin and yang are deficient. In the context of the lack of clear drug treatment options for cancer-related fatigue, alternative compensatory therapies, including traditional Chinese medicine treatment options, have been identified as one of the important means. Studies have shown that the incidence of cancer-related fatigue is as high as 40% when cancer is diagnosed, but it is more likely to occur in patients with active cancer and those undergoing anti-tumor treatment. At the same time, fatigue is a common adverse reaction, affecting up to 90% of patients receiving radiotherapy and up to 80% of patients receiving chemotherapy. Professor Wu Mianhua, a famous Chinese medicine doctor in China, pointed out that the pathogenesis of cancer-related fatigue is fundamentally due to spleen deficiency and internal cancer toxins based on the characteristics of the disease and the theory of cancer toxin pathogenesis. The root cause lies in the primary disease itself. Fatigue is an external manifestation. Deficiency of vital energy and accumulation of cancer toxins are the root causes of the disease. Therefore, in addition to strengthening the vital energy, eliminating the evil is equally important in treatment. The functional activities of the limbs are closely related to the spleen, so it is necessary to strengthen the spleen. Professor Wu believes that cancer toxins often attach to phlegm, blood stasis, heat and other evils to cause diseases, and then form complex pathological factors such as phlegm toxins, blood stasis toxins, and heat toxins. Therefore, in the diagnosis and treatment of cancer-related fatigue, Professor Wu does not forget to use products that regulate qi and resolve phlegm, resolve blood stasis and detoxify. However, cancer toxins linger, and over time, they damage body fluids and qi, and chemotherapy damages vital energy. Patients have both qi, blood, yin and yang deficiency, and need to be matched with products that replenish qi, nourish blood, and nourish yin according to individual differences of patients. Cancer patients suffer from prolonged illness and are often accompanied by cognitive impairment and depression over time. This is not only due to the pathological products of the malignant tumor process (phlegm, heat, blood stasis, etc.), but also because the patients lose confidence due to the long-term inability to cure the disease. Treatment still requires soothing the liver and relieving depression, which is also an extremely important part of the treatment process for cancer patients.The invention not only emphasizes strengthening the body and eliminating evil, but also plays the role of strengthening the spleen, eliminating cancer and detoxifying, and can also relieve depression and relieve restlessness. This treatment method runs through the entire disease, stabilizes the body, resists tumors, and regulates emotions. Summary of the invention

[0003] The invention provides a traditional Chinese medicine composition for improving cancer fatigue and a preparation method thereof.

[0004] The present invention adopts the following technical scheme: a traditional Chinese medicine composition for improving cancer fatigue, which is prepared by extracting the following traditional Chinese medicines in parts by weight: 10-20 parts of roasted astragalus, 10-20 parts of oldenlandia diffusa, 10-14 parts of pseudostellaria, 10-14 parts of stir-fried atractylodes, 10-14 parts of poria, 5-10 parts of julibrissin, 6-12 parts of ophiopogon, 3-9 parts of parsley, 6-12 parts of processed arisaema, 6-12 parts of vinegar-curcuma, and 2-4 parts of roasted liquorice.

[0005] The Chinese medicine composition for improving cancer fatigue is prepared by extracting the following Chinese medicinal materials in parts by weight: 15 parts of roasted Astragalus, 15 parts of Oldenlandia Diffusa, 12 parts of Pseudostellariae Radix, 12 parts of stir-fried Atractylodes macrocephala, 12 parts of Poria, 12 parts of Flos Albiziae, 12 parts of Ophiopogon japonicus, 9 parts of Paris polyphylla, 9 parts of processed Arisaema, 9 parts of Curcuma zedoariae with vinegar, and 3 parts of roasted Licorice root.

[0006] The preparation method of the Chinese medicine composition for improving cancer-related fatigue comprises the following steps: weighing the above medicinal materials by weight, adding 10-20 times the weight of water, soaking for 2 hours, heating to boiling, decocting twice, each time for 2-3 hours, combining the decoctions, filtering, evaporating and concentrating to a relative density of 1.2-1.3 at 25° C., adding 85-90% ethanol to adjust the ethanol concentration to 65-75% after cooling, precipitating with alcohol, fully mixing, leaving overnight, taking the supernatant, recovering ethanol under reduced pressure to obtain an extract, spray drying, sieving, adding appropriate amount of auxiliary materials and preparing the preparation.

[0007] The Chinese medicine composition for improving cancer-related fatigue is in the form of granules, tablets, capsules, powders, pills, oral liquids or pastes.

[0008] The application of the traditional Chinese medicine composition for improving cancer-related fatigue in the preparation of medicines for improving cancer-related fatigue.

[0009] Formula basis and beneficial effects

[0010] The present invention provides a Chinese medicine for treating cancer-related fatigue, which can be used for the entire illness cycle of patients with malignant tumors, and takes into account strengthening the body, anti-cancer, relieving depression and strengthening the spleen, and a preparation method thereof, especially for patients with "spleen deficiency and internal cancer toxins" after surgery, radiotherapy and chemotherapy. At present, there is no clear treatment plan for cancer-related fatigue, and most of them are symptomatic treatments. Guidelines often recommend alternative complementary therapies including traditional Chinese medicine treatment plans. Cancer-related fatigue occurs at all stages, and the characteristics of the disease at the current stage often need to be taken into account during the treatment process, while playing the roles of anti-cancer, enhancing efficacy and reducing toxicity, preventing recurrence and preventing metastasis. The purpose of the present invention is to solve the technical problems of existing Western medicines with single efficacy, large toxicity and side effects, and inability to be taken for a long time.

[0011] Theoretical basis and beneficial effects: Professor Wu Mianhua pointed out in his long-term clinical practice that the pathogenesis of cancer-related fatigue is fundamentally due to the spleen's dysfunction. The functional activities of the limbs are closely related to the spleen. "Suwen·Jingmai Bielun" says: "Drink enters the stomach, overflows with essence and qi, and is transported to the spleen. The spleen disperses the essence and returns to the lungs, regulates the water channels, and transports it to the bladder. The water essence is distributed in all directions, and the five meridians run in parallel." The spleen distributes the clear yang qi of water and grain to nourish the limbs and internal organs. If the spleen is deficient and the acquired essence is insufficient, the limbs will be weak and tired, just as "Suwen·Taiyinyangming Lun" says: "The limbs all receive qi from the stomach, but cannot reach the meridians. They must be due to the spleen, and then they can receive it." When diagnosing and treating cancer-related fatigue, Professor Wu Mianhua not only emphasizes "root deficiency", but also attaches importance to "symptom excess", attaches equal importance to strengthening the body and eliminating evil, and takes both attack and supplement into account, and takes both the symptoms and the root into account. Professor Wu Mianhua pointed out based on his many years of clinical experience that the condition of cancer patients is often a mixture of deficiency and excess. If only nourishing and strengthening products are given, there is a risk of accelerating the progression of the tumor. The cancer toxicity pathogenesis theory believes that cancer toxicity is a specific cause of malignant tumors, and cancer toxicity often attaches to phlegm, blood stasis, heat and other evils to cause diseases, and then forms complex pathological factors such as phlegm toxicity, blood stasis toxicity, and heat toxicity. Different detoxification treatment methods such as heat-clearing and detoxification method, blood stasis softening method, and phlegm-resolving and knot-dispersing method are used. Therefore, when distinguishing and treating cancer-related fatigue, Professor Wu Mianhua did not forget anti-tumor treatment and added products for regulating qi and resolving phlegm, removing blood stasis and detoxification. After cancer patients are diagnosed, due to mental stress and the pain caused by the disease itself, the mental burden increases, so Professor Wu Mianhua often lists the method of soothing the liver and relieving depression as a necessary means of treating cancer-related fatigue.

[0012] In the present invention, roasted Astragalus membranaceus can invigorate the middle qi, and Hedyotis diffusa can clear away heat and toxic substances, and the two can strengthen the body and eliminate evil as the main medicine. Radix Pseudostellariae, stir-fried Atractylodes macrocephala, and Poria cocos all enter the spleen meridian, making the spleen strong and vigorous, transmitting the essence and micro-organisms, thereby nourishing the five internal organs and irrigating the surroundings; Radix Ophiopogonis is sweet, cold and moist in nature, good at clearing and nourishing the yin of the lungs and stomach and moistening dryness, and can also clear the heat of the heart meridian and eliminate restlessness, nourishing and clearing, and is matched with the effect of Flos Albizziae to relieve depression and calm the mind, and the two can relieve depression and eliminate restlessness. The above are all ministerial medicines to help the main medicine to strengthen the body and resist evil. Paris polyphylla, processed Arisaema confusa, and Curcuma zedoaria assist the main medicine in resolving phlegm, softening hard masses, removing blood stasis and eliminating tumors; roasted Licorice root can invigorate the spleen and invigorate qi, clear away heat and toxic substances, and harmonize various medicines as the guiding medicine. Strengthening the body and eliminating evil are given equal importance, attacking and replenishing are applied simultaneously, and both the symptoms and the root causes are taken into consideration, and the effects of strengthening the body and invigorating the spleen, relieving depression and eliminating restlessness, and eliminating cancer and detoxification are played together, which is conducive to improving many clinical symptoms of patients with cancer-related fatigue.

[0013] The main feature of this invention that is different from other Chinese herbal compound prescriptions for cancer-related fatigue is that currently most Chinese herbal prescriptions for improving cancer-related fatigue use tonic drugs such as astragalus and Ligustrum lucidum to replenish qi and nourish yin, but ignore the negative impact of the primary disease on the patient and only play a symptomatic treatment role, which does not meet the basic condition of cancer-related fatigue, and ignores the mental stress of patients after cancer diagnosis. Negative emotions cannot be effectively channeled, and the resulting fear, depression, frustration, anxiety, sleep disorders, sadness, pain, etc. may aggravate the patient's condition. Therefore, the prescription is based on a series of qi-invigorating, spleen-strengthening and yin-nourishing drugs such as astragalus, pseudostellaria, stir-fried white atractylodes, poria, and ophiopogon, and is combined with parsley, processed arisaema, and curcuma to play the roles of clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, resolving phlegm and softening hard masses, so as to eliminate pathological products such as heat toxins, phlegm toxins, and blood stasis toxins, and limit the progression of the primary disease; the combination of julibrissin flowers and ophiopogon to relieve depression and restlessness can effectively relieve the patient's mental stress. The liver is responsible for the regulation of qi and is the general's official. When the liver qi is relieved, the patient's whole body will feel comfortable, and qi, blood, and body fluids will flow smoothly, further alleviating toxic evils such as dampness, heat, phlegm, and blood stasis. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Changes in pathological morphology of tumor tissue in mice with colorectal cancer (HE, 200X)

[0015] Figure 2 Observation of CT 26 cell morphology

[0016] Figure 3 Observation of RKO cell morphology

[0017] Figure 4 Gender comparison between the two groups (x±S)

[0018] Figure 5 Comparison of the two groups' age (years, )

[0019] Figure 6 Comparison of tumor types between the two groups (cases)

[0020] Figure 7Comparison of Piper fatigue scores between groups before treatment

[0021] Figure 8 Comparison of Piper fatigue scores between groups after treatment

[0022] Fig. 9 Comparison of Piper fatigue scores before and after treatment in the treatment groups

[0023] Fig.10 Comparison of Piper fatigue scores in the control group before and after treatment

[0024] Fig.11 Comparison of spleen qi deficiency syndrome scores between groups before treatment

[0025] Fig.12 Comparison of spleen qi deficiency syndrome scores among groups after treatment

[0026] Fig.13 Comparison of spleen qi deficiency syndrome scores before and after treatment in the treatment groups

[0027] Fig.14 Comparison of spleen qi deficiency syndrome scores before and after treatment in the control group

[0028] Fig.15 Comparison of therapeutic effects of spleen qi deficiency syndrome between two groups

[0029] Fig.16 Comparison of KPS scores between the two groups before and after treatment

[0030] Fig.17 Comparison of quality of life scores between the two groups before and after treatment

[0031] Fig.18 Comparison of red blood cell values ​​between the two groups before and after treatment

[0032] Fig.19 Comparison of white blood cell counts between the two groups before and after treatment

[0033] Fig. 20 Comparison of hemoglobin values ​​between the two groups before and after treatment

[0034] Fig.21 Comparison of platelet counts between the two groups before and after treatment

[0035] Fig. 22 Comparison of AST values ​​between the two groups before and after treatment

[0036] Fig.23 Comparison of ALT between the two groups before and after treatment

[0037] Fig.24 Comparison of SCR values ​​between the two groups before and after treatment

[0038] Fig.25 Comparison of BUN values ​​between the two groups before and after treatment DETAILED DESCRIPTION

[0039] The present invention is further described below in conjunction with embodiments, but the present invention is not limited to these specific examples.

[0040] Example 1

[0041] Take 150g of roasted Astragalus, 150g of Hedyotis diffusa, 120g of Radix Pseudostellariae, 120g of stir-fried Atractylodes, 120g of Poria, 120g of Flos Albiziae, 120g of Radix Ophiopogonis, 60g of Paris polyphylla, 90g of processed Arisaema, 90g of Curcuma zedoariae and 30g of roasted Licorice. The preparation method comprises the following steps: weigh the above medicinal materials according to the dosage, add 15 times the weight of water, soak for 2 hours, heat to boiling, decoct twice, each time for 2 hours, combine the decoctions, filter, evaporate and concentrate to a relative density of 1.25 at 25°C, cool, add 90% ethanol to adjust the ethanol concentration to 65%, precipitate with alcohol, mix thoroughly, leave overnight, take the supernatant, recover the ethanol under reduced pressure to obtain an extract, spray dry, sieve, add dextrin and prepare granules.

[0042] Example 2

[0043] Take 100g of roasted Astragalus, 200g of Hedyotis diffusa, 100g of Radix Pseudostellariae, 140g of stir-fried Atractylodes, 100g of Poria, 100g of Flos Albiziae, 100g of Radix Ophiopogonis, 90g of Rhizoma Paris, 120g of processed Arisaema, 120g of Rhizoma Curcumae, and 20g of roasted Licorice. The preparation method comprises the following steps: weigh the above medicinal materials according to the dosage, add 20 times the weight of water, soak for 2 hours, heat to boiling, decoct twice, each time for 2 hours, combine the decoctions, filter, evaporate and concentrate to a relative density of 1.3 at 25°C, cool, add 85% ethanol to adjust the ethanol concentration to 75%, precipitate with alcohol, mix thoroughly, place overnight, take the supernatant, recover the ethanol under reduced pressure to obtain an extract, spray dry, sieve, add an appropriate amount of starch and make tablets.

[0044] Example 3

[0045] Take 200g of roasted Astragalus, 100g of Hedyotis diffusa, 140g of Pseudostellariae Radix, 140g of stir-fried Atractylodes macrocephala, 140g of Poria, 140g of Albizzia julibrissin, 140g of Radix Ophiopogonis, 60g of Paris polyphylla, 60g of processed Arisaema, 120g of Curcuma zedoariae and 40g of roasted Licorice root. The preparation method comprises the following steps: weigh the above medicinal materials according to the dosage, add 10 times the weight of water, soak for 2 hours, heat to boiling, decoct twice, each time for 3 hours, combine the decoctions, filter, evaporate and concentrate to a relative density of 1.2 at 25°C, cool, add 90% ethanol to adjust the ethanol concentration to 65%, precipitate with alcohol, mix thoroughly, leave overnight, take the supernatant, recover the ethanol under reduced pressure to obtain an extract, spray dry, sieve, add microcrystalline cellulose and prepare capsules.

[0046] Example 4

[0047] Take 150g of roasted Astragalus, 150g of Hedyotis diffusa, 120g of Radix Pseudostellariae, 120g of stir-fried Atractylodes macrocephala, 120g of Poria, 120g of Flos Albiziae, 120g of Radix Ophiopogonis, 90g of Paris polyphylla, 90g of processed Arisaema, 90g of Curcuma zedoariae and 30g of roasted Licorice root. The preparation method comprises the following steps: weigh the above medicinal materials according to the dosage, add 10-20 times the weight of water, soak for 2 hours, heat to boiling, decoct twice, each time for 2-3 hours, combine the decoctions, filter, evaporate and concentrate to a relative density of 1.2-1.3 at 25°C, cool, add ethanol with a concentration of 85-90% to adjust the ethanol concentration to 65-75%, precipitate with alcohol, mix thoroughly, place overnight, take the supernatant, recover the ethanol under reduced pressure to obtain an extract, and add a flavoring agent to prepare an oral solution.

[0048] Example 5 In vivo pharmacodynamics of the present invention against CRC

[0049] 1. Animal Experiments

[0050] In order to study the anti-colorectal cancer effect of the Chinese medicine composition of the present invention in vivo, 24 male BALB / c mice aged 6 to 8 weeks were fed adaptively for 1 week and 1×10 7 CT-26 cells with a concentration of 1 cell / mL were subcutaneously injected into the right groin of BALB / c mice to establish a colorectal cancer tumor-bearing mouse model. When a mass with a long diameter of 3-5 mm grew on the right back of the mouse, it indicated that the transplanted tumor model was successfully established. On the 7th day of modeling, the mice were divided into a model group, a 5-FU group, an AZKLF high-dose group (AZKLF-H), and an AZKLF low-dose group (AZKLF-L) according to the tumor volume of the mice. The drugs in the AZKLF high-dose group and the AZKLF low-dose group were all taken from the granules prepared in Example 1 above. Six BALB / c mice of the same period were taken as the normal group. The concentration was based on the commonly used dose for clinical adults (70 kg), and the mouse dosing concentration was calculated according to the formula for the equivalent dose ratio of human and animal administration. The AZKLF-H dosing concentration was twice the commonly used clinical dose. Both groups of animals were administered from the 7th day of modeling, and the dosing volume was 0.2 mL·10 g -1 , once a day for 21 days. The 5-FU group was injected intraperitoneally with 5-FU (3.57*10 -4 g·kg -1 ), the intraperitoneal injection volume was 0.1 mL·10 g -1 , once every 3 days for 21 days. Within 21 days of administration, mice were weighed once every 3 days, and the long diameter and short neck of transplanted tumors in each group were measured and recorded with a vernier caliper, and the tumor volume was calculated. After the tumor tissue was peeled off, it was fixed with 4% paraformaldehyde solution, dehydrated, embedded, sectioned, and then routine HE staining was performed and observed under a microscope.

[0051] Effect of AZKLF treatment on tumor volume in colorectal cancer mice

[0052] By observing the changes in tumor volume in Table 1, it was found that compared with the model group, the growth of transplanted tumors in the 5-FU group, the high-dose AZKLF group, and the low-dose AZKLF group of mice was relatively slow, and on the 27th day of inoculation, the transplanted tumor volume of mice in the 5-FU group, the high-dose AZKLF group, and the low-dose AZKLF group was significantly smaller than that in the model group (P<0.001). At the same time, as shown in Table 2, compared with the model group, there was no significant difference in the body weight of mice in the 5-FU group, the high-dose AZKLF group, and the low-dose AZKLF group, and the difference was not statistically significant (all P>0.05).

[0053] Table 1 Effect of AZKLF treatment on tumor volume in colorectal cancer mice

[0054]

[0055] Note: Compared with the model group, ***P<0.001, **P<0.01, *P<0.05

[0056] Table 2 Effect of AZKLF treatment on body weight of mice with colorectal cancer

[0057]

[0058] Effect of AZKLF treatment on tumor tissue morphology in colorectal cancer mice

[0059] HE pathological staining results Figure 1 The results showed that the tumor cells in the model group were closely arranged, with deep nuclei, uneven cell sizes and irregular shapes, and frequent nuclear division, indicating that the tumor cells were in a rapid proliferation stage. Compared with the model group, the necrosis area in the tumor tissue of the 5-FU group and the high-dose AZKLF group increased, the cell arrangement became sparse, and the nuclear division figures decreased, indicating that AZKLF has an inhibitory effect on the growth of tumors in colorectal cancer mice. Figure 1 Note: A: model group, B: 5-FU group, C: AZKLF-H, D: AZKLF-L.

[0060] 2. Cell experiments

[0061] 2.1 Experimental procedures

[0062] 2.1.1 Recovery and culture of colorectal cancer CT-26 cells

[0063] Mouse colorectal cancer CT-26 cells frozen in liquid nitrogen were quickly rewarmed in a water bath at 37°C, added to RPMI-1640 medium containing 10% FBS and 1% penicillin-streptomycin, and incubated in an incubator at 37°C and 5% CO2. Cell experiments were performed when the cells reached the logarithmic growth phase.

[0064] 2.1.2 CCK8 detection of cell proliferation

[0065] CT-26 cells and RKO cells in logarithmic growth phase were cultured at 5×10 3 and 8×10 3 Inoculate in 96-well plates. After the cells adhere to the wall, low, medium and high concentrations of AZKLF lyophilized powder (preparation method: combine the two drug solutions according to the steps of Example 1, filter and concentrate to obtain AZKLF decoction, freeze at -80°C for 48 hours, quickly transfer to a freeze dryer, and obtain AZKLF lyophilized powder after vacuum drying) culture medium were added to each well, 3 replicate wells were set for each group, CCK8 solution was added after 48 hours of culture, and the culture medium was discarded after another 4 hours of incubation, 100 μL of CCK8 working solution was added to each well, and the absorbance value at 450 nm of each group was detected by an enzyme marker.

[0066] 2.1.3 Cell morphology observation

[0067] The cells were divided into a blank control group (Control), a 5-FU group, and low-, medium-, and high-dose AZKLF groups. The colorectal cancer cells were treated with interventions, and the cell morphology and density of each group were recorded by photographing 48 hours after the intervention.

[0068] 3. Experimental results

[0069] 3.1CCK8

[0070] As the concentration of AZKLF increased, the inhibition rate of colorectal cancer cell CT-26 proliferation gradually increased, indicating that AZKLF can effectively inhibit the proliferation of colorectal cancer cell CT-26. Cell proliferation in the 5-FU group was also significantly inhibited, and its inhibition rate was roughly similar to that in the AZKLF-M group (see Table 3 for details).

[0071] Table 3 Effect of AZKLF treatment on the proliferation of colorectal cancer cell CT-26

[0072]

[0073] As the concentration of AZKLF increased, the inhibition rate of colorectal cancer cell RKO proliferation gradually increased, indicating that AZKLF can effectively inhibit the proliferation of colorectal cancer cell RKO. The cell proliferation of the 5-FU group was also significantly inhibited, and its inhibition rate was roughly similar to that of AZKLF-M (see Table 4 for details).

[0074] Table 4 Effect of AZKLF treatment on the proliferation of colorectal cancer cells RKO

[0075]

[0076] Compared with the blank control group, **P<0.01

[0077] 2.2 Cell morphology observation

[0078] Observation under a 10× microscope revealed that the cells in the blank control group of CT-26 cells were completely attached to the wall, with good cell morphology and state, and the cells were polygonal, spindle-shaped or triangular; while after 48 hours of exposure to AZKLF in each dose group and the positive drug group, the cell morphology changed, some cells were round, the volume was reduced, the gaps between cells became larger, the cells were sparsely distributed, and the number of cells decreased (see Figure 2 ).

[0079] Observation under a 10× microscope revealed that the blank control group of RKO cells were completely attached to the wall, with good cell morphology and state, polygonal and rhombic cells, and closely connected to each other; compared with the blank control group, the number of cells in the AZKLF groups and the positive drug group gradually decreased after 48 hours of action, and the cells were obviously wrinkled and rounded (see Figure 3 ).

[0080] Example 6: Clinical study of the present invention

[0081] This study used AZKLF as a treatment method to conduct a clinical study on its effectiveness and safety in treating cancer-related fatigue in cancer patients. A total of 60 patients with cancer-related fatigue from Professor Wu Mianhua's outpatient clinic and the Department of Oncology of Jiangsu Provincial Hospital of Traditional Chinese Medicine were selected and divided into a treatment group and a control group with 30 cases in each group. The course of treatment was 4 weeks. The results showed that the treatment group was better than the control group in terms of Piper fatigue score, spleen deficiency syndrome score, KPS score, quality of life measurement score, decrease in ALT level, and increase in red blood cells and hemoglobin. There were statistical differences between the two groups after treatment (P < 0.05). However, there was no statistically significant improvement in chlorosis of the face by AZKLF compared with the control group (P > 0.05), and the efficacy of the two groups was equivalent. No obvious abnormalities were found in the safety indicators such as liver and kidney function in the two groups, and no adverse reactions of the test drugs were observed in the experiment. The results of the clinical trial showed that the application of AZKLF in the treatment of spleen deficiency-type cancer-related fatigue was safe and effective, and the efficacy was better than that of the control group.

[0082] 1. Clinical research

[0083] 1. Case selection criteria

[0084] The 60 cancer patients with cancer-related fatigue in this study were selected from Professor Wu Mianhua's outpatient clinic and the Oncology Department of Jiangsu Provincial Hospital of Traditional Chinese Medicine from October 2022 to January 2024. Their ages ranged from 18 to 80 years old. All cases met the diagnostic criteria of this study and were qualified after screening based on the inclusion and exclusion criteria.

[0085] 1.1 Case diagnosis criteria

[0086] 1.1.1 Diagnostic criteria for malignant tumors

[0087] All cases were confirmed to be malignant tumors by pathology. The staging criteria for malignant tumors refer to the staging method established in the eighth edition of the AJCC Tumor Staging Manual.

[0088] 1.1.2 Diagnostic criteria for cancer-related fatigue

[0089] The 10th edition of the International Classification of Diseases standard is used: subjective fatigue symptoms that persist for more than 2 weeks recur repeatedly and are difficult to relieve through normal rest, and are accompanied by at least 5 of the following discomfort symptoms:

[0090] ① Feeling weak or limp;

[0091] ②Unable to concentrate on daily tasks;

[0092] ③ Lack of passion, depression, and listlessness;

[0093] ④ Sleep disorders, difficulty sleeping all night or difficulty falling asleep after waking up or drowsiness;

[0094] ⑤ The feeling of fatigue does not disappear after sleep or rest;

[0095] ⑥ Reduced mobility and limited exercise;

[0096] ⑦ Prone to negative emotions such as sadness, depression, panic or anxiety;

[0097] ⑧It is difficult to complete the work that you were previously capable of doing;

[0098] ⑨Decrease in short-term memory;

[0099] ⑩ Fatigue worsens after activity, and fatigue symptoms are still difficult to relieve after rest.

[0100] 1.1.3 TCM syndrome diagnostic criteria

[0101] According to the relevant provisions of the "Guidelines for Clinical Research of New Chinese Medicines (Trial)" issued by the Drug Authorization Bureau of the Ministry of Health in 2002, and combined with the corresponding symptoms and signs of clinical spleen deficiency syndrome, the syndrome diagnostic criteria for spleen deficiency syndrome are formulated:

[0102] Main symptoms: ① poor appetite; ② abdominal distension; ③ loose stools.

[0103] Secondary symptoms: ① Pale complexion; ② Dull pain in the abdomen; ③ Fatigue and laziness; ④ Nausea and vomiting.

[0104] Tongue and pulse: The tongue is pale with a thin white coating, the tongue is enlarged or there are teeth marks on the edge of the tongue; the pulse is weak and powerless.

[0105] The diagnosis can be made if the above-mentioned tongue and pulse are met and 2 main symptoms are present; or 1 main symptom plus 2 secondary symptoms are present.

[0106] 1.2 Case inclusion criteria:

[0107] ① Patients diagnosed with malignant tumors;

[0108] ②Those who meet the diagnostic criteria of spleen deficiency syndrome in traditional Chinese medicine;

[0109] ③Those who meet the diagnostic criteria for CRF and have fatigue symptoms detected by the scale score;

[0110] ④ Those aged between 18 and 80;

[0111] ⑤ Those with Karnofsky score ≥ 60 and estimated survival period of more than 3 months;

[0112] ⑥ Those with hemoglobin ≥ 90g / L and no serious damage to heart, liver or kidney function;

[0113] ⑦ No use of traditional Chinese medicine containing qi-tonifying, blood-nourishing, or marrow-tonifying drugs or other drugs that may affect the efficacy evaluation within 1 week before enrollment, and during the observation period;

[0114] ⑧ Those with good compliance, who can actively cooperate with the treatment as required, voluntarily join the study and sign the informed consent.

[0115] If any of the above items are not met, they will not be included.

[0116] 1.3 Case Exclusion Criteria:

[0117] ① Those who have been allergic to Chinese medicine in the past;

[0118] ② Patients receiving hormones or psychostimulants at the same time;

[0119] ③ Pregnant or breastfeeding women and patients with mental illness;

[0120] ④ Fatigue can be explained by other primary diseases;

[0121] ⑤ Those who cannot take oral medications.

[0122] If any of the above items are met, they will not be included.

[0123] 1.4 Case exclusion criteria:

[0124] ① Although the initial screening meets the inclusion criteria of this drug trial, the patient voluntarily stops taking the drug, switches to other drugs, or fails to take the drug according to the regulations during the trial, thus affecting the reliability and safety of the study;

[0125] ② Those who fail to provide true and detailed personal information or conceal their medical history;

[0126] ③ Cases with incomplete clinical data records after medication.

[0127] 1.5 Case termination criteria:

[0128] ① Subjects who experience severe adverse reactions, worsening of their condition, or life-threatening organ metastasis during the trial and cannot continue to be observed;

[0129] ② The research subjects regret to join the trial and withdraw from the trial on their own.

[0130] 1.6 Case dropout criteria:

[0131] ① Those who voluntarily quit or lost contact during medication;

[0132] ② Those who were lost to follow-up due to accidental death during treatment or follow-up;

[0133] ③ Patients who need to take other intervention plans due to their medical condition during the trial.

[0134] 1.7 Piper Fatigue Scale Revised (see Table 5)

[0135] Table 5 Piper Fatigue Scale-Revised-Chinese Version

[0136]

[0137]

[0138] 1.8 TCM spleen deficiency syndrome score (see Table 6) Table 6 TCM spleen deficiency syndrome score

[0139]

[0140] 1.9 Quality of life measurement scale (see Table 7) Table 7 Quality of life measurement scale

[0141]

[0142] 1.10KPS score table (see Table 8)

[0143] Table 8 KPS score table

[0144]

[0145] 2 Research Methods

[0146] A total of 60 patients with cancer-related fatigue were expected to be included in this study and divided into a treatment group (30 cases, Chinese medicine) and a control group (30 cases) by random number grouping.

[0147] 2.1 Treatment groups

[0148] On the basis of conventional symptomatic treatment in the control group, patients were given oral Chinese medicine decoction of AZKLF plus or minus.

[0149] 2.1.1 Dosage and Usage

[0150] The dosage of the above Chinese medicine is controlled according to the patient's age and condition, decocted in water, one dose per day, warm after meals in the morning and evening. The granules prepared by the method of the above embodiment 1 are taken three times a day, one pack each time, and the daily dosage is: 15g of roasted Astragalus, 15g of Hedyotis diffusa, 12g of Pseudostellariae Radix, 12g of stir-fried Atractylodes macrocephala, 12g of Poria, 12g of Albizzia julibrissin, 12g of Ophiopogon japonicus, 6g of Paris polyphylla, 9g of processed Arisaema, 9g of vinegar Curcuma, and 3g of roasted Licorice root.

[0151] 2.1.2 Application of addition and subtraction

[0152] If the patient has poor appetite, add Amomum villosum, fried Coix seeds, Chinese yam, and scorched hawthorn fruit; if the patient has constipation, add fried Citrus aurantium, Trichosanthes seeds, and Cannabis sativa seeds; if the patient has noisy stomach, sour vomiting, and hiccups, add Coptis chinensis, Evodia rutaecarpa, and Iron fern seeds; if the patient has pleural effusion, add Red safflower seeds, Zedoaria, and Polyporus umbellatus; if the patient has cough, add Houttuynia cordata, Fagopyrum scabra, etc.; if the patient has poor sleep at night, add Polygonum multiflorum and Ziziphus jujuba seeds, etc.

[0153] 2.2 Control group

[0154] Routine symptomatic treatment is given according to the patient's condition, including fluid replacement, maintenance of water and electrolyte balance, nutritional support, analgesia, antiemetics, laxatives, etc. At the same time, the patient is guided to have a reasonable work and rest schedule, engage in appropriate exercise activities, and provide corresponding psychological counseling when necessary.

[0155] 2.3 Observation time

[0156] Before treatment and 4 weeks after treatment.

[0157] 2.4 Observation indicators

[0158] Piper fatigue score, TCM spleen deficiency syndrome score, Karnofsky score (KPS), quality of life measurement score. Blood routine (red blood cells, white blood cells, hemoglobin, platelets), liver and kidney function (ALT, AST, BUN, SCR) were observed as safety indicators, and adverse reactions were recorded during the observation period.

[0159] 2.5 Efficacy evaluation criteria

[0160] Formulated with reference to the "Guidelines for Clinical Research of New Chinese Medicines" and combined with clinical practice

[0161] Clinical recovery: TCM clinical symptoms and signs basically disappear, and the symptom score decreases by ≥90%;

[0162] Markedly effective: Clinical symptoms of traditional Chinese medicine are significantly relieved, and the symptom score is reduced by ≥70%;

[0163] Effective: TCM clinical symptoms are relieved, and the symptom score is reduced by ≥30%;

[0164] Ineffective: TCM clinical symptoms were not significantly relieved or even aggravated, and the symptom score decreased by <30%.

[0165] Note: (symptom score before treatment - symptom score after treatment) / symptom score before treatment × 100%.

[0166] 2.6 Statistical methods

[0167] All data were summarized, and corresponding databases were established as needed. SPSS26.0 statistical software was used for processing. The chi-square test was used for counting data, and the t-test and Wilcoxon rank sum test were used for measurement data depending on whether they met the normal distribution.

[0168] 3 General data analysis

[0169] 3.1 Comparison of relevant data between the two groups of patients

[0170] 3.1.1 Gender comparison between the two groups

[0171] The number of male and female patients in the two groups was counted separately. 2 Test, P = 1.000 > 0.05, it can be seen that there is no statistically significant difference in gender between the two groups, and they are comparable, as shown in Table 9, Figure 4 shown.

[0172] Table 9 Gender comparison between the two groups (examples)

[0173]

[0174] 3.1.2 Comparison of age between the two groups

[0175] The treatment group finally included 30 patients, aged between 30 and 77 years old; the control group finally included 30 patients, aged between 45 and 73 years old. According to the independent sample t test, P = 0.12 > 0.05, there was no statistically significant difference in age between the two groups, and they were comparable, as shown in Table 10, Figure 5 shown.

[0176] Table 10 Comparison of age between the two groups (years old, )

[0177]

[0178] 3.1.3 Comparison of tumor types between the two groups

[0179] The tumor types and number of patients in the two groups were counted respectively. 2 Test, P = 0.733 > 0.05, indicating that there was no statistically significant difference in tumor types between the two groups of patients, and they were comparable, as shown in Table 11, Figure 6 shown.

[0180] Table 11 Comparison of tumor types between the two groups (cases)

[0181]

[0182] 4 Efficacy data analysis

[0183] 4.1 Piper Fatigue Scale Score

[0184] 4.1.1 Comparison between groups

[0185] (1) An independent sample t-test was performed on the scores of the four dimensions of Piper fatigue (behavioral dimension, emotional dimension, sensory dimension, and cognitive dimension) and the total average score of the treatment group and the control group before treatment. The P values ​​were all greater than 0.05, indicating that the differences were not statistically significant. The data of the two groups before treatment were balanced and comparable. The results are shown in Table 12. Figure 7 shown.

[0186] (2) Independent sample t-test was used to compare the Piper fatigue scores and total mean scores after treatment in the two groups. The P values ​​were all < 0.05, indicating that the differences between the two groups after treatment were statistically significant. The treatment group had a better improvement effect on cancer-related fatigue than the control group. The results are shown in Table 12. Figure 8 shown.

[0187] Table 12 Comparison of Piper fatigue scores before and after treatment (between groups)

[0188]

[0189] 4.1.2 Intra-group comparison

[0190] (1) The Piper fatigue scores of the four dimensions and the total average scores of the treatment group before and after treatment were tested with paired sample t-tests. The P values ​​were all < 0.05. There were statistically significant differences in the treatment group before and after treatment. The results are shown in Table 13. Fig. 9 shown.

[0191] (2) The Piper Fatigue Scale scores of the control group before and after treatment were subjected to paired sample t-test. Except for the score of the sensory dimension, P = 0.022 < 0.05, the difference was statistically significant. The P values ​​of the other dimensions were all > 0.05, indicating no statistical difference, as shown in Table 13. Fig.10shown.

[0192] Table 13 Comparison of Piper fatigue scores before and after treatment (within group)

[0193]

[0194] 4.2 Spleen Qi Deficiency Syndrome Score

[0195] 4.2.1 Comparison between groups

[0196] (1) The scores of spleen deficiency symptoms (poor appetite, abdominal distension, loose stools, sallow complexion, dull abdominal pain, fatigue, laziness, nausea and vomiting) and the total scores of the treatment group and the control group before treatment were tested by independent sample t-test. The P values ​​were all greater than 0.05. There was no statistically significant difference between the two groups. The data of the two groups before treatment were balanced and comparable. The results are shown in Table 14. Fig.11 shown.

[0197] (2) After treatment, the scores of spleen deficiency syndrome and total score of the two groups were tested by independent sample t test. Except for the sallow complexion (P=0.074>0.05), which was not statistically significant, the other P values ​​were all <0.05, which were statistically significant. The results are shown in Table 14. Fig.12 shown.

[0198] Table 14 Comparison of spleen qi deficiency syndrome scores before and after treatment (between groups)

[0199]

[0200] 4.2.2 Intra-group comparison

[0201] (1) The spleen qi deficiency syndrome scores of the treatment group before and after treatment were tested by paired sample t-test, and the P values ​​were all < 0.05, which was statistically significant, indicating that this study had a significant effect in improving spleen qi deficiency. The results are shown in Table 15. Fig.13 shown.

[0202] (2) The paired sample t-test showed that the spleen deficiency syndrome scores of the control group before and after treatment showed no statistically significant differences except for loose stools, sallow complexion, and total score (P<0.05). The other P values ​​were all >0.05, indicating no statistically significant differences. The results are shown in Table 15. Fig.14 shown.

[0203] Table 15 Comparison of spleen qi deficiency syndrome scores before and after treatment (within the group)

[0204]

[0205]

[0206] 4.2.3 Evaluation of the therapeutic effect of spleen qi deficiency syndrome

[0207] The number of cases of efficacy after treatment in the treatment group and the control group was tested by independent sample rank sum test, and the P value was <0.05, indicating that there was a statistical difference between the control group and the treatment group. The results are shown in Table 16. Fig.15 shown.

[0208] Table 16 Comparison of the therapeutic effects of spleen qi deficiency syndrome between two groups (examples)

[0209]

[0210] 4.3 KPS score changes

[0211] 4.3.1 Comparison between groups

[0212] (1) The KPS scores of the treatment group and the control group before treatment were tested by independent sample rank sum test, P value = 0.073> 0.05, and the difference between the two groups was not statistically significant. The data of the two groups before treatment were balanced and comparable. (2) The KPS scores between the two groups after treatment were tested by independent sample rank sum test, P value < 0.05, indicating that the difference in KPS scores between the two groups after treatment was statistically significant, and the improvement effect of the treatment group was better than that of the control group. The results are shown in Table 17, Fig.16 shown.

[0213] Table 17 Comparison of KPS scores between the two groups before and after treatment (between groups) [M (Q25, Q75)]

[0214]

[0215] 4.3.2 Intra-group comparison

[0216] (1) The KPS scores of the treatment group before and after treatment were tested by the paired design Wilcoxon rank sum test, P value <0.05, and the difference was statistically significant compared with before treatment. (2) The KPS scores of the control group before and after treatment were tested by the paired design Wilcoxon rank sum test, P value = 0.033 <0.05, and the difference was statistically significant. The results are shown in Table 18. Fig.16 shown.

[0217] Table 18 Comparison of KPS scores between the two groups before and after treatment (within the group) [M (Q25, Q75)]

[0218]

[0219] 4.4 Changes in quality of life assessment scores

[0220] 4.4.1 Comparison between groups

[0221] (1) An independent sample t-test was performed on the quality of life scores of the treatment group and the control group before treatment. The P value was 0.658>0.05. There was no statistically significant difference between the two groups. The data of the two groups before treatment were comparable. (2) An independent sample t-test was performed on the quality of life scores of the two groups after treatment. The P value was <0.05. The difference was statistically significant, indicating that the improvement effect of the treatment group was better than that of the control group. The results are shown in Table 19. Fig.17 shown.

[0222] Table 19 Comparison of life quality scores before and after treatment (between groups)

[0223]

[0224] 4.4.2 Intra-group comparison

[0225] (1) The quality of life scores of the treatment group before and after treatment were tested by paired sample t test, P value <0.05, and the difference was statistically significant, indicating that this study had a significant effect in improving the quality of life scores. (2) The quality of life scores of the control group before and after treatment were tested by paired sample t test, P value = 0.293 > 0.05, and there was no statistically significant difference. The results are shown in Table 20. Fig.17 shown.

[0226] Table 20 Comparison of the quality of life scores between the two groups before and after treatment (within the group)

[0227]

[0228] 5 Safety evaluation

[0229] 5.1 Routine blood test (red blood cells, white blood cells, hemoglobin, platelets)

[0230] 5.1.1 Red blood cells

[0231] 5.1.1.1 Comparison between groups

[0232] (1) The red blood cell counts between the two groups before treatment were tested by independent sample t test, P value = 0.239> 0.05, there was no statistically significant difference between the two groups, and the numbers of the two groups before treatment were comparable. (2) The red blood cell counts between the two groups after treatment were tested by independent sample t test, P < 0.05, and the difference was statistically significant. The results are shown in Table 13. Fig.15 shown.

[0233] Table 21 Comparison of red blood cell values ​​before and after treatment (between groups)

[0234]

[0235] 5.1.1.2 Intra-group comparison

[0236] (1) The paired sample t test showed that the red blood cell count of the treatment group after treatment was P = 0.002 < 0.05, and the difference was statistically significant. (2) The paired sample t test showed that the control group after treatment was P = 0.068 > 0.05, and the difference was not statistically significant. The results are shown in Table 22. Fig.18 shown.

[0237] Table 22 Comparison of red blood cell values ​​before and after treatment (within the group) between the two groups

[0238]

[0239] 5.1.2 Leukocytes

[0240] 5.1.2.1 Comparison between groups

[0241] (1) The white blood cell counts before treatment between the two groups were tested by independent sample t test, P value = 0.485 > 0.05, and there was no statistically significant difference. (2) The white blood cell counts after treatment between the two groups were tested by independent sample t test, P = 0.319 > 0.05, and there was no statistically significant difference. The results are shown in Table 23. Fig.19 shown.

[0242] Table 23 Comparison of white blood cell values ​​before and after treatment (between groups)

[0243]

[0244] 5.1.2.2 Intra-group comparison

[0245] (1) After treatment, the white blood cell count of the treatment group was tested by paired sample t test, P value = 0.037 < 0.05, and the difference was statistically significant. (2) After treatment, the white blood cell count of the control group was tested by paired sample t test, P value = 0.924 > 0.05, and the difference was not statistically significant. The results are shown in Table 24. Fig. 20 shown.

[0246] Table 24 Comparison of white blood cell values ​​before and after treatment (within the group) between the two groups

[0247]

[0248] 5.1.3 Hemoglobin

[0249] 5.1.3.1 Comparison between groups

[0250] (1) The hemoglobin values ​​between the two groups before treatment were tested by independent sample t test, P = 0.047 < 0.05, and the difference was statistically significant. (2) The hemoglobin values ​​between the two groups after treatment were tested by independent sample t test, P = 0.004 < 0.05, and the difference was statistically significant. The results are shown in Table 25. Fig. 20 shown.

[0251] Table 25 Comparison of hemoglobin values ​​before and after treatment (between groups)

[0252]

[0253] 5.1.3.1 Intra-group comparison

[0254] (1) The hemoglobin values ​​of the treatment group after treatment were tested by paired sample t test, P value = 0.062 > 0.05, and there was no statistically significant difference. (2) The hemoglobin values ​​of the control group after treatment were tested by paired sample t test, P value = 0.331 > 0.05, and there was no statistically significant difference. The results are shown in Table 26. Fig. 20 shown.

[0255] Table 26 Comparison of hemoglobin values ​​before and after treatment (within group) between the two groups

[0256]

[0257] 5.1.4 Platelets

[0258] 5.1.4.1 Comparison between groups

[0259] (1) The platelet counts before treatment between the two groups were tested by independent sample t test, P = 0.959 > 0.05, with no statistically significant difference. (2) The platelet counts after treatment between the two groups were tested by independent sample t test, P = 0.847 > 0.05, with no statistically significant difference. The results are shown in Table 27. Fig.21 shown.

[0260] Table 27 Comparison of platelet values ​​between the two groups before and after treatment (between groups)

[0261]

[0262] 5.1.4.2 Intra-group comparison

[0263] (1) After treatment, the platelet count in the treatment group was tested by the paired Wilcoxon rank sum test, P value = 0.430 > 0.05, and there was no statistically significant difference. (2) After treatment, the platelet count in the control group was tested by the paired Wilcoxon rank sum test, P value = 0.334 > 0.05, and there was no statistically significant difference. The results are shown in Table 28. Fig.21 shown.

[0264] Table 28 Comparison of platelet values ​​before and after treatment (within group) between the two groups [M (Q25, Q75)]

[0265]

[0266] 5.2 Liver and kidney function (AST, ALT, SCR, BUN)

[0267] 5.2.1AST Aspartate aminotransferase

[0268] 5.2.1.1 Comparison between groups

[0269] (1) The AST values ​​between the two groups before treatment were tested by independent sample t test, P = 0.001 < 0.05, and the difference was statistically significant. (2) The AST values ​​between the two groups after treatment were tested by independent sample t test, P = 0.108 > 0.05, and there was no statistically significant difference. The results are shown in Table 29, Fig. 22 shown.

[0270] Table 29 Comparison of AST values ​​before and after treatment (between groups)

[0271]

[0272] 5.2.1.2 Intra-group comparison

[0273] (1) The AST values ​​of the treatment group after treatment were tested by paired sample t test, P value = 0.048 < 0.05, and the difference was statistically significant. (2) The AST values ​​of the control group after treatment were tested by paired sample t test, P value = 0.478 > 0.05, and the difference was not statistically significant. The results are shown in Table 30, Fig. 22 shown.

[0274] Table 30 Comparison of AST values ​​before and after treatment between the two groups (within the group)

[0275]

[0276] 5.2.2 ALT Alanine aminotransferase

[0277] 5.2.2.1 Comparison between groups

[0278] (1) The ALT values ​​before treatment between the two groups were tested by independent sample t test, P < 0.05, and the difference was statistically significant. (2) The ALT values ​​after treatment between the two groups were tested by independent sample t test, P = 0.003 < 0.05, and the difference was statistically significant. The results are shown in Table 31. Fig.23 shown.

[0279] Table 31 Comparison of ALT values ​​before and after treatment between the two groups (between groups)

[0280]

[0281] 5.2.2.2 Intra-group comparison

[0282] (1) After treatment, the ALT value of the treatment group was tested by paired sample t test, P value = 0.177 > 0.05, and the difference was not statistically significant. (2) After treatment, the control group was tested by paired sample t test, P value = 0.121 > 0.05, and the difference was not statistically significant. The results are shown in Table 32. Fig.23 shown.

[0283] Table 32 Comparison of ALT values ​​before and after treatment between the two groups (within the group)

[0284]

[0285] 5.2.3 SCR creatinine

[0286] 5.2.3.1 Comparison between groups

[0287] (1) The SCR values ​​before treatment between the two groups were tested by independent sample t test, P = 0.405 > 0.05, and there was no statistically significant difference. (2) The SCR values ​​after treatment between the two groups were tested by independent sample t test, P = 0.512 > 0.05, and there was no statistically significant difference. The results are shown in Table 33. Fig.24 shown.

[0288] Table 33 Comparison of SCR values ​​before and after treatment (between groups)

[0289]

[0290] 5.2.3.2 Intra-group comparison

[0291] (1) The SCR values ​​of the treatment group after treatment were tested by paired sample t test, P value = 0.906 > 0.05, and there was no statistically significant difference. (2) The SCR values ​​of the control group after treatment were tested by paired sample t test, P value = 0.713 > 0.05, and there was no statistically significant difference. The results are shown in Table 34. Fig.24 shown.

[0292] Table 34 Comparison of SCR values ​​before and after treatment between the two groups (within the group)

[0293]

[0294] 5.2.4BUN

[0295] 5.2.4.1 Comparison between groups

[0296] (1) The BUN values ​​before treatment between the two groups were tested by independent sample t test, P = 0.621 > 0.05, and there was no statistically significant difference. (2) The BUN values ​​after treatment between the two groups were tested by independent sample t test, P = 0.860 > 0.05, and there was no statistically significant difference. The results are shown in Table 35. Fig.25 shown.

[0297] Table 35 Comparison of BUN values ​​before and after treatment between the two groups (between groups)

[0298]

[0299] 5.2.4.2 Intra-group comparison

[0300] (1) The BUN value of the treatment group after treatment was tested by paired sample t test, P value = 0.748 > 0.05, and there was no statistically significant difference. (2) The BUN value of the control group after treatment was tested by paired sample t test, P value = 0.358 > 0.05, and there was no statistically significant difference. The results are shown in Table 36. Fig.25 Shown

[0301] Table 36 Comparison of BUN values ​​before and after treatment between the two groups (within the group)

[0302]

[0303] 5 Adverse Reactions

[0304] No patient experienced obvious adverse reactions or drug allergies during the treatment.

[0305] 2. Discussion of research results

[0306] 1 General Information

[0307] There was no statistically significant difference in gender, age, and tumor type between the two groups of patients, and they were comparable.

[0308] 2. Efficacy score

[0309] 2.1 Piper Fatigue Score

[0310] The differences in the scores and total average scores of the four dimensions (behavioral dimension, emotional dimension, sensory dimension, and cognitive dimension) of Piper fatigue between the two groups before treatment were all greater than 0.05, which was not statistically significant. The data of the two groups were balanced and comparable. The P values ​​of the scores and total average scores of the four dimensions before and after treatment in the treatment group were all less than 0.05, which were statistically significant, indicating that AZKLF has a certain effect on improving cancer-related fatigue. In the control group, except for the score of the sensory dimension (P=0.022<0.05), the P values ​​of the other dimensions were all greater than 0.05, which were not statistically significant, indicating that symptomatic treatment has an improvement effect on the patient's sensory dimension, but has no obvious effect on other aspects. The P values ​​of the scores and total average scores of the four dimensions of Piper fatigue in the two groups after treatment were all less than 0.05, which were statistically significant, indicating that the combined use of AZKLF has a better effect on improving cancer-related fatigue than symptomatic supportive treatment alone.

[0311] 2.2 Spleen Qi Deficiency Syndrome Score

[0312] The differences in the scores and total scores of the spleen deficiency syndrome (poor appetite, abdominal distension, loose stools, sallow complexion, dull abdominal pain, fatigue, laziness, nausea and vomiting) before treatment between the two groups of patients were all greater than 0.05, which was not statistically significant, and the data of the two groups were balanced and comparable. After treatment, the P values ​​of the treatment group were all less than 0.05, and the differences were statistically significant, indicating that this prescription had a significant effect on improving the spleen deficiency syndrome. In the control group, except for loose stools, sallow complexion, and total score P < 0.05, which were statistically significant, the other P values ​​were all greater than 0.05, with no statistical differences, indicating that symptomatic treatment had a certain improvement effect on the loose stools and sallow complexion of patients, but did not significantly improve other symptoms of spleen deficiency. After treatment, except for sallow complexion (P=0.074>0.05, which was not statistically significant, the other P values ​​were all <0.05, which was statistically significant, indicating that the combined use of AZKLF was equivalent to symptomatic treatment alone in improving sallow complexion in the two groups, but had significant advantages in improving other symptoms of spleen deficiency such as poor appetite and abdominal distension. According to the nimodipine formula, 6 cases were effective and 2 cases were ineffective in the control group, and 3 cases were markedly effective, 25 cases were effective, and 2 cases were ineffective in the treatment group. The efficacy of the two groups was tested, and the P value was <0.05, which was statistically significant, indicating that the treatment group had a better effect on improving spleen deficiency than the control group.

[0313] 2.3KPS Rating

[0314] The KPS score P value of the two groups of patients before treatment was greater than 0.05, which was not statistically significant and comparable. The KPS score P values ​​of the treatment group and the control group before and after treatment were both less than 0.05, and the difference was statistically significant, indicating that the physical condition of the two groups of patients was improved compared with before treatment. The KPS score P value of the two groups after treatment was less than 0.05, and the difference was statistically significant. The treatment group had a better improvement effect on the KPS score than the control group.

[0315] 2.4 Quality of life assessment score

[0316] The P value of the quality of life measurement score before treatment in the two groups of patients was greater than 0.05, which was not statistically significant and comparable. The P value of the quality of life measurement score before and after treatment in the treatment group was less than 0.05, which was statistically significant. The use of AZKLF to improve the quality of life measurement score was effective, and the quality of life of patients was improved compared with before treatment. The P value of the quality of life measurement score before and after treatment in the control group was greater than 0.05, with no statistically significant difference, and the therapeutic effect was not good. The P value of the quality of life measurement score after treatment in the two groups was less than 0.01, and the difference was statistically significant, indicating that the therapeutic effect of the treatment group was significant compared with that of the control group.

[0317] 3 Safety indicators

[0318] 3.1 Blood routine examination

[0319] Before treatment, the P values ​​of red blood cells, white blood cells, and platelets between the two groups were greater than 0.05, with no statistically significant difference, and they were comparable. The P value of hemoglobin was less than 0.05, which was not comparable. After treatment, the P values ​​of red blood cells and white blood cells in the treatment group were less than 0.05, which were statistically significant, and the P values ​​of hemoglobin and platelets were greater than 0.05, with no statistically significant difference, indicating that the treatment group can increase the levels of red blood cells and white blood cells to a certain extent. After treatment, the P values ​​of various blood routine indicators in the control group were greater than 0.05, with no statistically significant difference, and the control group had no significant improvement effect on various blood routine indicators. After treatment, the P values ​​of red blood cells and hemoglobin in the two groups were less than 0.05, which were statistically significant, and the P values ​​of white blood cells and platelets were greater than 0.05, with no statistically significant difference, indicating that the treatment group had a more significant improvement effect on anemia than the control group.

[0320] 3.2 Liver and kidney function

[0321] Before treatment, the P values ​​of SCR and BUN between the two groups were greater than 0.05, with no statistically significant difference and comparability. The P values ​​of AST and ALT were less than 0.05, which were not comparable. After treatment, except for the P value of AST in the treatment group which was less than 0.05, which was statistically significant, the P values ​​of the other items were all greater than 0.05, with no statistically significant difference, indicating that the treatment group could reduce the AST level to a certain extent. After treatment, the P values ​​of various liver and kidney function indicators in the control group were greater than 0.05, with no statistically significant difference, indicating that the control group had no significant effect on improving the various liver and kidney function indicators. After treatment, except for the P value of ALT which was less than 0.05, which was statistically significant, the P values ​​of the other items were all greater than 0.05, with no statistically significant difference, indicating that the effect of reducing glutamic acid in the treatment group was more significant than that in the control group.

[0322] 3.3 Safety evaluation

[0323] No adverse events related to this prescription were found during the study. This prescription has good safety and can be widely used in clinical practice.

Claims

1. A Chinese medicine composition for improving cancer-related fatigue, characterized in that: The invention is prepared by extracting the following Chinese medicinal materials in parts by weight: 10-20 parts of roasted astragalus, 10-20 parts of oldenlandia diffusa, 10-14 parts of pseudoginseng, 10-14 parts of stir-fried atractylodes, 10-14 parts of poria, 5-10 parts of julibrissin flowers, 6-12 parts of ophiopogon, 3-9 parts of parsley, 6-12 parts of processed arisaema, 6-12 parts of vinegar-curcuma and 2-4 parts of roasted liquorice.

2. The Chinese medicine composition for improving cancer-related fatigue according to claim 1, characterized in that: The product is extracted from the following Chinese medicinal materials in parts by weight: 15 parts of roasted astragalus, 15 parts of oldenlandia diffusa, 12 parts of pseudoginseng, 12 parts of stir-fried atractylodes, 12 parts of tuckahoe, 12 parts of lily of the valley, 12 parts of ophiopogon, 6 parts of parsley, 9 parts of processed arisaema, 9 parts of vinegar-curcuma, and 3 parts of roasted liquorice.

3. The Chinese medicine composition for improving cancer-related fatigue according to claim 1, characterized in that: The preparation method comprises the following steps: weighing the above medicinal materials by weight, adding 10-20 times the weight of water, soaking for 2 hours, heating to boiling, decocting twice, each time for 2-3 hours, combining the decoctions, filtering, evaporating and concentrating to a relative density of 1.2-1.3 at 25°C, cooling, adding 85-90% ethanol to adjust the ethanol concentration to 65-75%, precipitating with alcohol, fully mixing, leaving overnight, taking the supernatant, recovering ethanol under reduced pressure to obtain an extract, spray drying, sieving, adding a proper amount of auxiliary materials and preparing the preparation.

4. The Chinese medicinal composition for improving cancer-related fatigue according to claim 1, characterized in that: The dosage form of the preparation is one of granules, tablets, capsules, powders, pills, oral liquids or paste prescriptions.

5. Use of the traditional Chinese medicine composition for improving cancer-related fatigue as claimed in claim 1 in the preparation of medicines for improving cancer-related fatigue.

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