Application of cordyceps militaris extract in preparation of medicine for resisting cancer-related fatigue

Abstract

The invention discloses application of a cordyceps militaris extract in preparation of a medicine for resisting cancer-related fatigue. The cordyceps militaris extract is a cordyceps militaris aqueous extract. The mass ratio of cordycepin to cordyceps polysaccharide in the cordyceps militaris extract is 3: (2.1-8). The cordyceps militaris extract and the composition thereof provided by the invention can be effectively used for resisting cancer-related fatigue, for example, the degree of leukocyte and platelet decline caused by cancer-related fatigue can be reduced, and the degree of swimming exhaustion time shortening caused by cancer-related fatigue can be reduced.

Description

Technical Field

[0001] The invention relates to the field of traditional Chinese medicine, and in particular to application of a Cordyceps militaris extract in preparing an anti-cancer fatigue drug. Background Art

[0002] This section merely provides background information related to the present disclosure and is not necessarily prior art.

[0003] Cancer-related fatigue is a subjective feeling of fatigue or exhaustion, including physical, emotional, and / or cognitive aspects, caused by cancer itself or cancer-related treatments. The "Clinical Practice Guidelines for Cancer-Related Fatigue" (2021, 1st edition) published by the National Comprehensive Cancer Network of the United States defines it as: a painful, persistent, subjective, physical, emotional, and / or cognitive fatigue or exhaustion that is inconsistent with recent activity levels, is related to cancer or cancer treatment, and interferes with daily life.

[0004] The specific pathogenesis of cancer-related fatigue is still unclear. Its possible mechanisms include the following aspects: (1) Inflammatory cytokine release hypothesis: The number of inflammatory cytokines in patients with cancer-related fatigue is significantly higher than that in patients with non-cancer fatigue and healthy people. The inflammatory cytokines induce anemia, malignancy, etc., which indirectly lead to the occurrence of cancer-related fatigue; (2) Hypothalamic-pituitary-adrenal disorder hypothesis: Cancer and its related treatments lead to cytokine release, 5-hydroxytryptamine imbalance, sleep disorders, and fluctuations in human hormone levels, which interfere with the hypothalamic-pituitary-adrenal axis and induce fatigue; (3) Circadian rhythm disorder hypothesis: Patients are affected by the disease and often suffer from insomnia symptoms, circadian rhythm changes, cortisol secretion rhythm disruption, decreased immune function, and increased release of tumor-related cytokines, which further lead to fatigue in cancer patients; 4) Serotonin imbalance hypothesis: 5-HT not only has the function of regulating body temperature, sleep, appetite, memory, mood, etc., but also controls hormone secretion and muscle contraction. It plays an important role in human physiological activities. Excessive or insufficient release of 5-HT in the brain of cancer patients can easily lead to central fatigue. (5) Adenosine triphosphate imbalance hypothesis: Adenosine triphosphate is mainly synthesized in mitochondria and is the energy source for cell metabolism. During cancer treatment, the structure and function of mitochondria are damaged to varying degrees, ATP synthesis is impaired, skeletal muscle energy metabolism is insufficient, and patients are very likely to experience symptoms of fatigue. (6) Vagus nerve conduction activation hypothesis: Cancer and its treatment lead to the release of peripheral neurotransmitters, etc. These cytokines activate the vagus nerve afferent pathway, reduce the patient's physical activity, and can cause continuous changes in fatigue-related central areas.

[0005] Normal fatigue is proportional to the degree of exhaustion. It is a protective regulatory mechanism of the body that can prompt the body to send out alarm signals and guide patients to take appropriate sleep and rest to promote energy recovery and fatigue relief. In contrast, cancer-related fatigue requires drug treatment or non-drug treatment. Non-drug treatments include exercise, health education, social psychology intervention, sleep therapy, bright white light therapy, nutritional management, etc. Acupuncture treatment is a traditional Chinese medicine therapy that can harmonize internal organs, dredge meridians, regulate yin and yang, and promote the normal and balanced functions of the various internal organs, meridians, tissues and organs of the human body. Among them, moxibustion, acupoint massage, Tai Chi, Tai Chi sword, Ba Duan Jin and other Chinese medicine guiding techniques can relieve cancer patients' fatigue to a certain extent. Drug treatments include central nervous system stimulants, corticosteroids, antidepressants, analgesics and other treatments to improve the senses, but they may take weeks to be effective and may cause side effects such as functional disorders. For example, erythropoietin increases the number of red blood cells to increase oxygen carrying capacity and reduce anemia-related fatigue, but may increase the risk of thrombosis and have limited effects on non-anemic patients. Sleeping pills can improve sleep quality and help restore physical strength, but may cause dependence, and long-term use reduces the effect. Analgesics can control pain and indirectly reduce fatigue caused by pain, but long-term use may lead to dependence and other side effects. Immunomodulators may improve immune system function and reduce fatigue, but may affect normal immune function and increase the risk of infection.

[0006] Traditional Chinese medicine plays a prominent role in improving physical signs and regulating sub-health. At the same time, Chinese medicine preparations have also achieved some meaningful results in improving the symptoms and quality of life of cancer patients. For example, Zhengyuan Capsule can replenish qi and spleen, nourish the kidney and replenish essence, and relieve cancer-related fatigue; Tianfoshen oral liquid has the effects of nourishing yin and qi, detoxifying and dispersing knots, and can improve the patient's immune function. Combined with chemotherapy, it can relieve the fatigue symptoms of patients with non-small cell lung cancer; Chinese medicine decoctions (such as Buzhong Yiqi Decoction) and modern Chinese medicine preparations (such as Shenqi Fuzheng Injection) also have certain effects on cancer-related fatigue. With the development of modern biomedicine and evidence-based medicine, the extraction technology of Chinese medicine active ingredients has been continuously improved. Combined with the efficacy of single Chinese medicine, according to the use concept of monarch, minister, assistant and envoy, the development of a compound of Chinese medicine extracts is of great significance for the treatment of cancer-related fatigue. For example, Cordyceps enters the lung and kidney meridians, and has the effects of storing essence, regulating bone and marrow production; ginseng extract can enhance physical strength, improve immunity, and resist fatigue; Astragalus extract replenishes Qi and strengthens the exterior, improves immunity, helps relieve fatigue and enhances physical strength; Ganoderma lucidum extract has the effects of enhancing immunity and anti-oxidation, and helps improve fatigue and overall health; Matsutake extract plays an important role in anti-cancer and immune modulation. Summary of the invention

[0007] Purpose of the invention: The technical problem to be solved by the present invention is to provide an anti-cancer fatigue drug in view of the deficiencies of the prior art.

[0008] In order to solve the above technical problems, the present invention discloses the following technical solutions:

[0009] In a first aspect, the present invention discloses the use of cordycepin in the preparation of a drug for preventing or treating cancer-related fatigue.

[0010] In some embodiments, the cordycepin is administered in combination with another pharmaceutically active agent or another anti-tumor therapy.

[0011] In some embodiments, the additional pharmaceutically active agent is a drug with anti-tumor activity.

[0012] Wherein, the tumor is selected from: gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer.

[0013] In some embodiments, the additional anti-tumor therapy is selected from surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, gene therapy, palliative care, and any combination thereof.

[0014] In some embodiments, the cancer-related fatigue is cancer-related fatigue caused by a tumor or tumor treatment; preferably, the tumor includes gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma, and ovarian cancer; the tumor treatment includes chemoradiotherapy, targeted therapy, and immunotherapy.

[0015] In a second aspect, the present invention discloses the use of Cordyceps militaris extract in the preparation of a drug for preventing or treating cancer-related fatigue.

[0016] In some embodiments, the Cordyceps militaris extract is a water extract of Cordyceps militaris; preferably, the mass ratio of cordycepin to cordyceps polysaccharide in the Cordyceps militaris extract is 3:2.1-8, preferably 3:3-6, preferably 3:4.

[0017] In some embodiments, the Cordyceps militaris extract is administered in combination with another pharmaceutically active agent or another anti-tumor therapy.

[0018] In some embodiments, the additional pharmaceutically active agent is a drug with anti-tumor activity.

[0019] Wherein, the tumor is selected from: gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer.

[0020] In some embodiments, the additional anti-tumor therapy is selected from surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, gene therapy, palliative care, and any combination thereof.

[0021] In some embodiments, the cancer-related fatigue is cancer-related fatigue caused by a tumor or tumor treatment; preferably, the tumor includes gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma, and ovarian cancer; the tumor treatment includes chemoradiotherapy, targeted therapy, and immunotherapy.

[0022] In a third aspect, the present invention discloses a composition for preventing or treating cancer-related fatigue.

[0023] In some embodiments, the active ingredients of the composition include (i) Cordyceps militaris extract, and (ii) Ganoderma lucidum extract and / or Matsutake extract; in some embodiments, the active ingredients of the composition include (i) Cordyceps militaris extract, and (ii) Ganoderma lucidum extract and Matsutake extract.

[0024] In some embodiments, the Cordyceps militaris extract in component (i) is a water extract of Cordyceps militaris; preferably, the mass ratio of cordycepin to cordyceps polysaccharide in the Cordyceps militaris extract is 3:2.1-8, preferably 3:3-6, preferably 3:4.

[0025] In some embodiments, the mass ratio of component (i) to component (ii) is 5:2.5-9.5, preferably 5:3.5-7.5, preferably 5:4.5-5.5; preferably, the mass ratio of the Cordyceps militaris extract, the Ganoderma lucidum extract and the Matsutake extract is 5:1.5-4.5:0.5-3.5, preferably 5:2-4:1-3, preferably 5:2.5-3.5:1.5-2.5.

[0026] In some embodiments, the composition further comprises other components besides the aforementioned components (i) and (ii), such as ginseng extract.

[0027] In some embodiments, the dosage form of the composition includes granules, tablets, capsules, patches, drops, pills, and sprays.

[0028] In a fourth aspect, the present invention discloses use of the composition described in the third aspect in preparing a drug for preventing or treating cancer-related fatigue.

[0029] In some embodiments, the pharmaceutical composition is administered in combination with another pharmaceutically active agent or another anti-tumor therapy.

[0030] In some embodiments, the additional pharmaceutically active agent is a drug with anti-tumor activity.

[0031] Wherein, the tumor is selected from: gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer.

[0032] In some embodiments, the additional anti-tumor therapy is selected from surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, gene therapy, palliative care, and any combination thereof.

[0033] In some embodiments, the cancer-related fatigue is cancer-related fatigue caused by a tumor or tumor treatment; preferably, the tumor includes gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma, and ovarian cancer; the tumor treatment includes chemoradiotherapy, targeted therapy, and immunotherapy.

[0034] In a fifth aspect, the present invention also discloses the use of cordycepin, Cordyceps militaris extract and a composition containing the Cordyceps militaris extract in the preparation of drugs for treating tumors.

[0035] Specifically include:

[0036] Application of cordycepin in the preparation of drugs for treating tumors.

[0037] Application of Cordyceps militaris extract in the preparation of drugs for treating tumors.

[0038] Application of a composition containing Cordyceps militaris extract in preparing a drug for treating tumors.

[0039] In some embodiments, the active ingredients of the composition include (i) Cordyceps militaris extract, and (ii) Ganoderma lucidum extract and / or Matsutake extract; in some embodiments, the active ingredients of the composition include (i) Cordyceps militaris extract, and (ii) Ganoderma lucidum extract and Matsutake extract.

[0040] In some embodiments, the Cordyceps militaris extract in component (i) is a water extract of Cordyceps militaris; preferably, the mass ratio of cordycepin to cordyceps polysaccharide in the Cordyceps militaris extract is 3:2.1-8, preferably 3:3-6, preferably 3:4.

[0041] In some embodiments, the mass ratio of component (i) to component (ii) is 5:2.5-9.5, preferably 5:3.5-7.5, preferably 5:4.5-5.5; preferably, the mass ratio of the Cordyceps militaris extract, the Ganoderma lucidum extract and the Matsutake extract is 5:1.5-4.5:0.5-3.5, preferably 5:2-4:1-3, preferably 5:2.5-3.5:1.5-2.5.

[0042] In some embodiments, the composition further comprises other components besides the aforementioned components (i) and (ii), such as ginseng extract.

[0043] In some embodiments, the dosage form of the composition includes granules, tablets, capsules, patches, drops, pills, and sprays.

[0044] Wherein, the tumor is selected from: gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer.

[0045] The Cordyceps militaris extract described in the present invention is a Cordyceps militaris water extract; in some embodiments, the Cordyceps militaris water extract, in addition to cordycepin and Cordyceps polysaccharide, also includes cordycepic acid, cordyceps adenosine, cordyceps polypeptide, amino acid, or any combination of the foregoing. In some embodiments, the mass ratio of cordycepin to cordycepic acid in the Cordyceps militaris water extract is 2.3-3.1:1, preferably 2.5-2.9:1, preferably 2.7:1; in some embodiments, the mass ratio of cordycepin to cordyceps adenosine in the Cordyceps militaris water extract is 23-31:4, preferably 25-29:4, preferably 27:4; in some embodiments, the mass ratio of cordycepin to cordyceps polypeptide in the Cordyceps militaris water extract is 23-31:5, preferably 25-29:5, preferably 27:5; in some embodiments, the mass ratio of cordycepin to amino acid in the Cordyceps militaris water extract is 3:1-3, preferably 3:1.5-2.5, preferably 3:2.

[0046] The Ganoderma lucidum extract described in the present invention is a Ganoderma lucidum water extract, which can be prepared by conventional methods in the art, such as refluxing and extracting Ganoderma lucidum in a water-soluble extract for 1-3 times, filtering, and concentrating the obtained extract to obtain an extract; it can be further dried and crushed to obtain Ganoderma lucidum water extract powder; the solid-liquid ratio of the Ganoderma lucidum to the solvent is 1g:5-20mL, such as 1g:10mL, 1g:15mL.

[0047] The pine mushroom extract described in the present invention is a pine mushroom alcohol water extract, which can be prepared by conventional methods in the art, such as refluxing the pine mushroom in an alcohol water solvent for 1-3 times, purifying the obtained extract by column chromatography or macroporous adsorption resin (such as D101 resin, AB-8 resin, etc.), and concentrating under reduced pressure to obtain an extract; it can be further dried and crushed to obtain a pine mushroom extract powder. Wherein, the alcohol includes methanol, ethanol, etc.; the volume concentration of alcohol in the alcohol water solvent is 60%-90%, such as 70%, 80%; the solid-liquid ratio of the pine mushroom to the solvent is 1g:5-20mL, such as 1g:10mL, 1g:15mL.

[0048] Each dosage form of the drug of the present invention, in addition to the Cordyceps militaris extract, also includes a pharmaceutically acceptable carrier, such as a filler, a lubricant, a sustained-release agent, a binder, a diluent, a disintegrant, a surfactant, a flavoring agent, and the like.

[0049] The present invention has no special requirements for the preparation method of each dosage form of the drug, and conventional methods in the field are all acceptable. It can be prepared according to conventional production methods in the pharmaceutical field, such as mixing the active ingredient with one or more carriers and then making it into the desired dosage form.

[0050] The term "cancer-related fatigue" in the present invention includes cancer-related fatigue caused by tumor formation and metastatic spread in gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer.

[0051] The term "prevention or treatment" in the present invention means administering the Cordyceps militaris extract described in the present application, or a composition containing the Cordyceps militaris extract and Ganoderma lucidum extract and / or Matsutake extract to prevent or treat cancer-related fatigue or one or more symptoms associated with the cancer-related fatigue, including inhibiting or reducing tumor formation and metastasis in gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer.

[0052] The term "pharmaceutically acceptable" in the present invention refers to those compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions or other problems or complications, commensurate with a reasonable benefit / risk ratio.

[0053] The term "palliative care" in the present invention refers to providing treatment and therapy to relieve patients' pain and other serious disease symptoms and improve their quality of life.

[0054] Beneficial effects:

[0055] The present invention provides a new use of Cordyceps militaris extract, which can be used for preventing and / or treating cancer-related fatigue, such as reducing the degree of decrease in leukocytes and platelets caused by cancer-related fatigue, and reducing the degree of shortening of swimming exhaustion time caused by cancer-related fatigue. DETAILED DESCRIPTION

[0056] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0057] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0058] The Cordyceps militaris extract described in the following embodiments, unless otherwise specified, comprises the following components in terms of mass ratio: 30% cordycepin, 5% cordycepic acid, 2% cordyceps adenosine, 40% cordyceps polysaccharide, 5% cordyceps polypeptide, and 15% amino acid, and can be prepared by existing methods.

[0059] The preparation method of the Ganoderma lucidum extract described in the following embodiment specifically comprises refluxing the Ganoderma lucidum in water for 2 times, each time for 1 hour, filtering, evaporating and concentrating the obtained filtrate to obtain an extract, drying, and crushing to obtain an extract; the solid-liquid ratio of the Ganoderma lucidum to water is 1g:10mL.

[0060] The preparation method of the Matsutake extract described in the following embodiment specifically includes refluxing the Matsutake in 80% ethanol (solid-liquid ratio 1g:10mL) for 2 times, each time for 1 hour; the obtained extract is purified by macroporous adsorption resin, the obtained eluate is evaporated and concentrated to obtain an extract, which is dried and crushed.

[0061] The preparation method of the ginseng extract described in the following embodiment specifically comprises soaking the ginseng in water, boiling it twice, each time for 30 minutes, evaporating and concentrating the filtrate to obtain an extract, drying, and crushing.

[0062] In the following examples, the Cordyceps militaris extract is mixed with the Ganoderma lucidum extract and / or the Tricholoma matsutake extract, suspended, and administered intragastrically.

[0063] Example 1

[0064] Group 1: Cordycepin.

[0065] Group 2: Cordyceps militaris extract, comprising the following components: cordycepin 27%, cordycepic acid 10%, cordyceps adenosine 4%, cordyceps polysaccharide 36%, cordyceps polypeptide 5%, and amino acid 18%.

[0066] Group 3: Cordyceps militaris extract, comprising the following components: cordycepin 37%, cordycepic acid 10%, cordyceps adenosine 4%, cordyceps polysaccharide 26%, cordyceps polypeptide 5%, and amino acid 18%.

[0067] Group 4: a combination of Cordyceps militaris extract (Group 3) and Ganoderma lucidum extract, with the following weight proportions: 50 parts of Cordyceps militaris extract and 30 parts of Ganoderma lucidum extract.

[0068] Group 5: A combination of Cordyceps militaris extract (Group 3) and Tricholoma matsutake extract, with the following weight proportions: 50 parts of Cordyceps militaris extract and 20 parts of Tricholoma matsutake extract.

[0069] Group 6: A combination of Cordyceps militaris extract (Group 3) with Ganoderma lucidum extract and Matsutake extract, with the following weight proportions: 50 parts of Cordyceps militaris extract, 30 parts of Ganoderma lucidum extract and 20 parts of Matsutake extract.

[0070] Group 7: A combination of Cordyceps militaris extract (Group 3) with Ganoderma lucidum extract, Matsutake extract, and ginseng extract, with the following weight proportions: 50 parts of Cordyceps militaris extract, 30 parts of Ganoderma lucidum extract, 20 parts of Matsutake extract, and 13 parts of ginseng extract.

[0071] Application Example 1 Effect on Anti-cancer Fatigue in Liver Cancer Transplantation Mouse Model

[0072] SPF mice, half male and half female, were allowed to freely consume food and water as the negative control group. Hepa-1-6 liver cancer cells were further cultured and digested at 3×10 6 The cells / mL were inoculated into the armpits of mice and the tumors were grown to 100 mm. 3 The mice were divided into groups at about 12 hours, and the grouping and dosing methods were as follows:

[0073] Model group: The model group was given the same amount of distilled water;

[0074] Cisplatin group: 4 mg / kg, once a week, intravenous injection;

[0075] Experimental group: 250 mg / kg was given to Group 1 to Group 6 in Example 1, intragastric administration once, and continued intragastric administration for 2 weeks;

[0076] Cisplatin + test group: cisplatin 4 mg / kg, once a week, intravenous injection; 250 mg / kg was given to Group 1, Group 3 and Group 6 in Example 1.

[0077] On the last day of drug administration, the mice were divided into two groups. One group was used for exhaustive swimming test to determine the anti-cancer fatigue effect of each group on the liver cancer transplanted mouse model. The mice were placed in a swimming pool. Exhaustion was determined when the mice sank below the water surface and could not float up after 10 seconds. The time from the beginning of swimming to exhaustion was recorded. If the swimming time exceeded 6 minutes, it was counted as 360 seconds. The other group took blood, measured blood routine, and killed the mice to measure the mass of the tumor.

[0078] The results are shown in Table 1. Compared with the negative control group, the tumor weight of the model group was as high as 0.87g, and the time from the start of swimming to exhaustion was significantly reduced, indicating that the model was successfully established; there was no significant change in leukocytes and platelets. Compared with the model group, the cisplatin group can significantly reduce the tumor weight, but the chemotherapy process can cause cancer-related fatigue, the time from the start of swimming to exhaustion is significantly prolonged, and the leukocytes and platelets are also significantly reduced. Compared with the model group, the test group can significantly reduce the tumor weight, and at the same time, it can also prolong the time from the start of swimming to exhaustion and increase the leukocyte content; there is no significant change in platelets. Compared with the model group, the cisplatin + test group can significantly reduce the tumor weight; compared with the cisplatin group, the cisplatin + test group can significantly increase the time from the start of swimming to exhaustion, and significantly increase the content of leukocytes and platelets, indicating that the cancer-related fatigue of mice can be reduced after drug treatment.

[0079] Table 1

[0080]

[0081] Note: Compared with the negative group, aP<0.05, aaP<0.01; compared with the model group, #P<0.05, ##P<0.01,

[0082] ###P<0.01; compared with the cisplatin group, *P<0.01, **P<0.01, ***P<0.001.

[0083] Application Example 2 Effect on Anti-cancer Fatigue in Ovarian Cancer Transplant Mouse Model

[0084] SPF mice, half male and half female, were allowed to freely access food and water. ID8 ovarian cancer cells were cultured and digested and then 3×10 6 The dosage of cells / mL was inoculated into the armpit of the mouse, and when the tumor grew to a certain volume, it was divided into groups, 8 mice in each group, namely the model group, chemotherapy group (cisplatin 4 mg / kg, once a week, intravenous injection), chemotherapy + test group (cisplatin 4 mg / kg, once a week, intravenous injection; 250 mg / kg was given to group 3-group 5 in Example 1). Blood routine was measured on the last day. The results are shown in Table 2. Compared with the model group, the cordycepin group, the Cordyceps militaris extract group and the combination group can significantly reduce the immobility time, indicating that the cancer-related fatigue of mice can be reduced after drug treatment.

[0085] Table 2

[0086] <![CDATA[White blood cells 10 9 / L]]> <![CDATA[Platelets 10 9 / L]]> Model Group 7.03±1.12 421±95.17 Chemotherapy group <![CDATA[4.56±1.11 # ]]> <![CDATA[315±84.36 ## ]]> Chemotherapy group + group 3 <![CDATA[6.65±0.95 **## ]]> <![CDATA[388±89.14 **## ]]> Chemotherapy group + group 4 <![CDATA[6.71±1.24 *## ]]> <![CDATA[402±105.67 **## ]]> Chemotherapy group + group 5 <![CDATA[6.73±1.03 **## ]]> <![CDATA[416±103.52 ***## ]]>

[0087] Note: Compared with the model group, #P<0.05, ##P<0.01; compared with the cisplatin group, *P<0.01, **P<0.01,

[0088] ***P<0.001.

[0089] Application Example 3 Effect on Anti-cancer Fatigue in Colon Cancer Transplant Mouse Model

[0090] SPF mice, half male and half female, were allowed to freely access food and water. MC-38 colon cancer cells were cultured and digested and then 3×10 6 The mice were inoculated with 10 cells / mL of the drug into the armpits. When the tumor grew to a certain volume, the mice were divided into groups, 8 mice in each group, including the model group, chemotherapy group (cisplatin 4 mg / kg, once a week, intravenous injection), and chemotherapy + test group (cisplatin 4 mg / kg, once a week, intravenous injection; 250 mg / kg was given to group 6 and group 7 in Example 1). The blood routine test was performed on the last day.

[0091] The results are shown in Table 3. Compared with the model group, the cordycepin group, the Cordyceps militaris extract group and the combination group were able to significantly reduce the immobility time, indicating that the cancer-related fatigue of mice can be reduced after drug treatment.

[0092] Table 3

[0093] <![CDATA[White blood cells 10 9 / L]]> <![CDATA[Platelet 10 9 / L]]> Model Group 6.87±1.09 440±121.61 Chemotherapy group <![CDATA[4.36±1.25 ## ]]> <![CDATA[312±105.47 ## ]]> Chemotherapy group + group 6 <![CDATA[6.75±1.04 **## ]]> <![CDATA[431±116.81 **## ]]> Chemotherapy group + group 7 <![CDATA[6.79±0.95 **## ]]> <![CDATA[436±103.54 ***## ]]>

[0094] Note: Compared with the model group, #P<0.05, ##P<0.01; compared with the chemotherapy group, *P<0.01, **P<0.01,

[0095] ***P<0.001.

[0096] Application Example 4 Effect on Anti-cancer Fatigue in Non-small Cell Lung Cancer Transplanted Mouse Model

[0097] SPF mice, half male and half female, were allowed to freely access food and water. NCI-H1048 human small cell lung cancer cells were cultured and digested and then incubated at 3×10 6 The dosage of cells / mL was inoculated under the armpit of mice, and surgery was performed after the tumor grew to a certain volume modeling success, and random groups were formed after surgery, 8 mice in each group, respectively, a control group (normal saline), a treatment group (groups 3-6 in Example 1), and oral administration began on the second day after surgery until 7 weeks after surgery. Mice were anesthetized on the last day of each week, tumor growth and metastasis were observed, and the time of metastasis was recorded to determine the disease-free survival time of each mouse, that is, the time from surgery to tumor recurrence and metastasis. After the experiment, mice were anesthetized and killed, tumor metastasis was observed, the number of lung tumor metastasis was recorded, and the inhibition rate of lung cancer cell metastasis was calculated.

[0098] The results showed that the median disease-free survival time of the control group and the treatment group (group 3-6) was 15±5.18 days, 28±4.98 days, 32±3.21 days, 30±2.53 days, and 42±5.17 days, respectively. The number of lung metastatic tumors in the control group and the treatment group (group 3-6) was 5.12±0.56, 2.67±1.25, 2.50±1.08, 2.35±0.98, and 1.95±0.51, respectively. The inhibition rates of lung cancer cell metastasis in groups 3-6 were 47.8%, 51.1%, 54.1%, and 61.9%, respectively.

[0099] Application Example 5 Effect on Anti-cancer Fatigue in Gastric Cancer Transplant Mouse Model

[0100] SPF mice, half male and half female, were allowed to freely consume food and water. Gastric cancer MFC cells were cultured and digested and then 4×10 7 Cells / mL were injected into the tail vein of mice to construct a gastric cancer metastasis model. After successful modeling, the mice were randomly divided into 8 groups, namely chemotherapy group (cisplatin group: 4 mg / kg, once a week, intravenous injection), chemotherapy + treatment group (cisplatin 4 mg / kg, once a week, intravenous injection; 250 mg / kg was given to groups 3-6 in Example 1). After the experiment, blood routine was measured, mice were anesthetized and killed, tumor metastasis was observed, the number of gastric cancer tumor metastasis was recorded, and the inhibition rate of gastric cancer cell metastasis was calculated.

[0101] The results are shown in Table 4. Compared with the model group, the cordycepin group, the Cordyceps militaris extract group and the combination group were able to significantly reduce the immobility time, indicating that the cancer-related fatigue of mice can be reduced after drug treatment.

[0102] Table 4

[0103]

[0104] Note: Compared with the model group, #P<0.05, ##P<0.01; compared with the chemotherapy group, **P<0.01, ***P<0.001.

[0106] In the above application examples, the applicant also conducted a safety study, and the results showed that the mice in groups 1 to 6 did not lose weight after taking them, and some of them even gained weight, indicating that cordycepin, Cordyceps militaris extract, and the composition containing Ganoderma lucidum extract and / or Tricholoma matsutake extract have good safety.

[0107] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. Application of Cordyceps militaris extract in the preparation of drugs for preventing or treating cancer-related fatigue.

2. The use according to claim 1, characterized in that: The Cordyceps militaris extract is a water extract of Cordyceps militaris; preferably, the mass ratio of cordycepin to cordyceps polysaccharide in the Cordyceps militaris extract is 3:2.1-8, preferably 3:3-6, and preferably 3:

4.

3. The use according to claim 1, characterized in that: The Cordyceps militaris extract is administered in combination with another pharmaceutically active agent or another anti-tumor therapy.

4. The use according to claim 3, characterized in that: The additional pharmaceutically active agent is a drug with anti-tumor activity; preferably, the tumor is selected from: gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer; preferably, the additional anti-tumor therapy is selected from: surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, gene therapy, palliative treatment and any combination thereof.

5. The use according to claim 1, characterized in that: The cancer-related fatigue is cancer-related fatigue caused by tumors or tumor treatment, preferably cancer-related fatigue caused by tumor treatment; preferably, the tumors include gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma, ovarian cancer; the tumor treatment includes radiotherapy, chemotherapy, targeted therapy, and immunotherapy.

6. A composition for preventing or treating cancer-related fatigue, characterized in that: The active ingredients of the composition include (i) Cordyceps militaris extract, and (ii) Ganoderma lucidum extract and / or Tricholoma matsutake extract.

7. The composition according to claim 6, characterized in that The Cordyceps militaris extract in component (i) is an aqueous extract of Cordyceps militaris; preferably, the mass ratio of cordycepin to cordyceps polysaccharide in the Cordyceps militaris extract is 3:2.1-8, preferably 3:3-6, preferably 3:4; preferably, the mass ratio of component (i) to component (ii) is 5:2.5-9.5, preferably 5:3.5-7.5, preferably 5:4.5-5.5; preferably, the mass ratio of the Cordyceps militaris extract, the Ganoderma lucidum extract and the Matsutake extract is 5:1.5-4.5:0.5-3.5, preferably 5:2-4:1-3, preferably 5:2.5-3.5:1.5-2.

5.

8. The composition according to claim 6, characterized in that The dosage form of the composition includes granules, tablets, capsules, patches, drops, pills and sprays.

9. Use of the composition according to any one of claims 6 to 8 in the preparation of a drug for preventing or treating cancer-related fatigue; Preferably, the pharmaceutical composition is administered in combination with another pharmaceutically active agent or another anti-tumor therapy; Preferably, the additional pharmaceutically active agent is a drug with anti-tumor activity; preferably, the tumor is selected from: gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma or ovarian cancer; Preferably, the additional anti-tumor therapy is selected from the group consisting of surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, gene therapy, palliative treatment, and any combination thereof; Preferably, the cancer-related fatigue is cancer-related fatigue caused by a tumor or tumor treatment, preferably cancer-related fatigue caused by tumor treatment; preferably, the tumor includes gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer, prostate cancer, melanoma, glioma, ovarian cancer; the tumor treatment includes radiotherapy, chemotherapy, targeted therapy, and immunotherapy.

10. Use of cordycepin in the preparation of a drug for preventing or treating cancer-related fatigue; preferably, the cordycepin is administered in combination with another pharmaceutically active agent or another anti-tumor therapy; preferably, the other pharmaceutically active agent is a drug with anti-tumor activity; preferably, the tumor is selected from: gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer prostate cancer, melanoma, glioma or ovarian cancer; the other anti-tumor therapy is selected from: surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, gene therapy, palliative therapy and any combination thereof; the cancer-related fatigue is cancer-related fatigue caused by the tumor or the treatment of the tumor, preferably cancer-related fatigue caused by the treatment of the tumor; preferably, the tumor includes gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, colorectal cancer, esophageal cancer prostate cancer, melanoma, glioma, ovarian cancer; the treatment of the tumor includes radiotherapy, chemotherapy, targeted therapy, and immunotherapy.

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