Licorice polysaccharide for treating cancer-related fatigue and its pharmaceutical preparation

Abstract

The present invention discloses a licorice polysaccharide for treating cancer-related fatigue and a pharmaceutical preparation thereof. The licorice polysaccharide pharmaceutical preparation is prepared by compounding licorice polysaccharides. Compared with the prior art, the licorice polysaccharide pharmaceutical preparation prepared by the present invention has a significant effect on improving immune function, can improve the patient's physical condition, and has certain efficacy in the areas of physical, role, emotional, and social function, fatigue, pain, fatigue, cough and sputum, shortness of breath, pale complexion, spontaneous sweating, poor appetite, abdominal distension, shortness of breath, weak bowel movements, and abnormal bowel movements, without obvious toxic and side effects.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a licorice polysaccharide for treating cancer-related fatigue and a pharmaceutical preparation thereof. Background Art

[0002] Cancer-related fatigue (CRF) is one of the most distressing symptoms associated with cancer and cancer treatment that plagues cancer patients. Compared to other symptoms, it is more common and difficult to effectively control with medication. Patients with CRF may experience pain, anxiety, depression, nausea, chest tightness, and poor sleep, severely impacting their quality of life, physical and mental health, and even personal and social functioning, reducing their satisfaction with their quality of life. Glaus et al., in a study of 499 patients with various cancer types, found that lung cancer patients experience the highest levels of CRF. The underlying mechanisms of CRF remain unclear. Some have suggested possible causes, including abnormal accumulation of muscle metabolites, impaired cytokine metabolism, neuromuscular metabolic disorders, abnormal gene control and expression, insufficient adenosine triphosphate synthesis, serotonin imbalance, abnormal excitability of vagal afferents, neurotransmitter imbalances, hypothalamic-pituitary-adrenal axis function, circadian rhythms, and cytokine dysregulation. However, insufficient evidence has yet to confirm these hypotheses. Western medicine uses both pharmacological and non-drug therapies. Pharmacological treatments often include erythropoietin; antidepressants such as serotonin reuptake inhibitors (paroxetine); psychostimulants such as methylphenidate; and modafinil, a wakefulness-enhancing, non-amphetamine psychostimulant. Studies have shown that these medications have some efficacy in treating cancer-related fatigue, but their therapeutic mechanisms and adverse reactions require further investigation. Therefore, Traditional Chinese Medicine (TCM) is increasingly effective in treating this condition. Zhang Chunyang, Xu Hui, and others investigated the distribution of TCM syndromes and clinical characteristics of patients with lung cancer-related fatigue and found that lung and spleen qi deficiency is the most common type of cancer-related fatigue. Therefore, developing a TCM preparation that can effectively treat cancer-related fatigue is crucial.

[0003] Invention patent application CN109820908A discloses a traditional Chinese medicine composition for treating cancer-related fatigue in patients with malignant tumors, which is composed of the following components: astragalus, codonopsis or ginseng, stir-fried atractylodes, roasted licorice, angelica, tangerine peel, cimicifuga, bupleurum, rhodiola and agrimony. The invention's Rhodiola rosea strengthens the body, replenishes Qi and nourishes blood, and has anti-fatigue and antioxidant effects. Herba Agrimoniae can treat blood syndromes and coughs caused by tumors, and is effective for long-term physical weakness and qi deficiency in tumor patients. The combination of Rhodiola rosea and Herba Agrimoniae has the effect of relieving fatigue. Adding Codonopsis pilosula or ginseng replenishes Qi and strengthens the spleen, supplementing the body's vital Qi. Roasted Licorice root treats fatigue and weakness. Stir-fried Atractylodes macrocephala strengthens the spleen and eliminates dampness, promoting proper transportation and blood circulation. Astragalus root and stir-fried Atractylodes macrocephala can replenish the spleen, and when combined with Angelica sinensis, can replenish Qi and generate blood. Cimicifuga heracleifolia and Bupleurum chinense soothe the liver and relieve depression, while Tangerine peel regulates Qi and strengthens the spleen. The combination of these herbs treats both the liver and spleen, taking into account both Qi and blood. With careful medication, it can treat cancer-related fatigue in patients with malignant tumors. However, the traditional Chinese medicine composition prepared by the invention suffers from poor efficacy. Summary of the Invention

[0004] In view of the shortcomings of the prior art in treating cancer-related fatigue that are poorly effective, the technical problem to be solved by the present invention is to provide a licorice polysaccharide with good effect for treating cancer-related fatigue and a pharmaceutical preparation thereof.

[0005] Licorice polysaccharide is a water-soluble polysaccharide compound in the traditional Chinese medicine licorice. Its molecular weight is 70,000 to 120,000 and it is one of the important medicinal ingredients in licorice.

[0006] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical solutions:

[0007] A glycyrrhiza polysaccharide capsule comprises the following raw materials: glycyrrhiza polysaccharide, a filler, a stabilizer, and a disintegrant.

[0008] Preferably, the glycyrrhiza polysaccharide capsule comprises the following raw materials in weight percentage: glycyrrhiza polysaccharide 60-80%, filler 10-30%, stabilizer 1-3%, disintegrant 1-10%.

[0009] The invention also discloses a preparation method of the liquorice polysaccharide medicinal capsule.

[0010] A preparation method of licorice polysaccharide capsules is as follows:

[0011] Step 1: Weigh the raw materials according to weight percentage, sieve the stabilizer, sieve the glycyrrhizic polysaccharide, filler and disintegrant, and set aside;

[0012] Step 2: Mix and stir the glycyrrhizic acid polysaccharide, filler and disintegrant, moisten with ethanol aqueous solution to prepare a soft material, and sieve and granulate to obtain wet granules;

[0013] Step 3: Dry the wet granules and sieve them to obtain dry granules;

[0014] Step 4: Add the stabilizer to the dry particles, stir, and then fill them into capsule shells to obtain the licorice polysaccharide capsules.

[0015] Preferably, the preparation method of the licorice polysaccharide capsule is as follows:

[0016] Step 1, weighing the raw materials according to weight percentage, passing the stabilizer through a 100-120 mesh sieve, and passing the glycyrrhizic polysaccharide, filler and disintegrant through a 50-70 mesh sieve, and set aside;

[0017] Step 2, mixing the glycyrrhizic polysaccharide, filler and disintegrant for 10 to 40 minutes at a stirring speed of 100 to 500 rpm to obtain a mixture, moistening the mixture with a 20 to 40 wt% ethanol aqueous solution to prepare a soft material, and granulating the mixture through a 20 to 40 mesh sieve to obtain wet granules;

[0018] Step 3, drying the wet granules at 35°C to 60°C, and passing through a 20-50 mesh sieve to obtain dry granules;

[0019] Step 4: Add the stabilizer to the dry particles, stir for 10 to 40 minutes at a stirring speed of 100 to 500 rpm, and then fill them into capsule shells. The filling amount of each capsule shell is 0.3 to 0.5 g, thereby obtaining the licorice polysaccharide drug capsules.

[0020] The preparation method of the licorice polysaccharide is as follows:

[0021] Z1. Wash licorice with water, dry it, and then grind it through a 40-100 mesh sieve to obtain licorice raw material;

[0022] Z2, adding water to the licorice raw material prepared in step Z1 and decocting 2 to 4 times, adding 7 to 9 times the weight of the licorice raw material water for the first time and decocting for 2 to 4 hours, adding 5 to 7 times the weight of the licorice raw material water for the second time and decocting for 2 to 4 hours, and adding 4 to 6 times the weight of the licorice raw material water for the third time and decocting for 1 to 3 hours, combining the decoctions to obtain a licorice extract;

[0023] Z3, vacuum concentrate the liquorice extract prepared in step Z2 to a relative density of 1.05-1.07 g / cm at 25°C. 3 , to obtain a concentrated solution;

[0024] Z4. Add 3 times the mass of 90-98 wt% ethanol aqueous solution to the concentrated solution prepared in step Z3, let it stand for 20-48 hours, and collect the precipitate;

[0025] Z5. Spray drying the precipitate prepared in step Z4 at an air inlet temperature of 160-180° C. and an air outlet temperature of 70-90° C. to obtain a dried product;

[0026] Z6. Grind the dried product prepared in step Z5 and pass it through a 60-100 mesh sieve to obtain glycyrrhiza polysaccharide.

[0027] Preferably, the filler is selected from at least one of starch, microcrystalline cellulose and powdered sugar.

[0028] Preferably, the stabilizer is selected from at least one of talc and sodium lauryl sulfate.

[0029] Preferably, the disintegrant is selected from at least one of hydroxypropyl cellulose and sodium carboxymethyl starch.

[0030] Preferably, the ethanol aqueous solution is 20 to 40 wt% of the mass of the mixture.

[0031] The invention relates to an application of the liquorice polysaccharide pharmaceutical preparation in treating cancer-related fatigue.

[0032] This study took patients with cancer-related fatigue caused by malignant tumors as the subjects, observed the effects of licorice polysaccharide capsules on cancer-related fatigue, biochemical indicators, and immune function, as well as the safety of licorice polysaccharide capsules in treating cancer-related fatigue in patients with malignant tumors, so as to explore the role, efficacy and safety of licorice polysaccharide capsules on cancer-related fatigue in malignant tumors, provide some theoretical basis and clinical data support for the treatment of cancer-related fatigue with traditional Chinese medicine, provide reference data for further randomized, double-blind, placebo-controlled clinical studies in the future, and provide ideas for the clinical treatment of CRF.

[0033] Licorice polysaccharide preparations are primarily composed of licorice polysaccharides. In traditional Chinese medicine, licorice is known to "tonify qi and replenish the middle, clear away heat and detoxify, eliminate phlegm and relieve cough, relieve acute pain, and harmonize medicinal properties." Preclinical pharmacological studies have shown that licorice polysaccharide preparations significantly enhance humoral, cellular, and nonspecific immune functions, while also providing a certain degree of resistance to bacterial and viral infections. Toxicology tests have shown that licorice polysaccharide preparations have no significant toxic or side effects.

[0034] The invention also discloses a method for preparing the glycyrrhiza polysaccharide tablets.

[0035] A preparation method of a glycyrrhiza polysaccharide tablet is as follows, in parts by weight:

[0036] 80-100 parts of allose, 1-5 parts of octenyl succinate starch, 1-5 parts of silicon dioxide and 1-5 parts of kaolin are dried and crushed together, and then passed through a 0.5-2 mm sieve. Then, 700-900 parts of glycyrrhizic acid polysaccharide and 80-150 parts of water are added and mixed evenly. A 5-10×10-30 mm punch is used in a tableting device to prepare glycyrrhizic acid polysaccharide tablets with a weight of 0.5-2 parts.

[0037] The invention also discloses a preparation method of the glycyrrhiza polysaccharide medicinal granules.

[0038] A preparation method of a glycyrrhiza polysaccharide medicinal granule is as follows, in parts by weight:

[0039] 40-60 parts of glycyrrhizic acid polysaccharide and 80-120 parts of beta-cyclodextrin are mixed and ground into powder; 400-600 parts of lactose are added to the above-mentioned micro-powder, and the mixture is further ground into powder. The mixture is passed through a 100-300 mesh sieve to obtain a mixed powder; 5-20 parts of low-substituted hydroxypropyl cellulose are passed through a 50-200 mesh sieve and then added to the mixed powder; 0.1-0.3 parts of stevia are added and the mixture is uniformly mixed; 250-350 parts of a 40-80 wt% ethanol aqueous solution are added to prepare a soft material; the mixture is granulated through a 10-30 mesh sieve; the mixture is dried at 50-80° C.; and the mixture is passed through a 40-60 mesh sieve to obtain a glycyrrhizic acid polysaccharide medicinal granule.

[0040] The invention also discloses a preparation method of the liquorice polysaccharide oral liquid.

[0041] A preparation method of a licorice polysaccharide oral liquid is as follows, in parts by weight:

[0042] Add 40-50 parts of sucrose, 10-30 parts of pectin, 10-20 parts of seaweed polysaccharide and 40-60 parts of licorice polysaccharide to 300-500 parts of water, perform ultrasonic vibration at 50-70°C for 2-5 hours, with an ultrasonic power of 200-400W and an ultrasonic frequency of 40-60kHz, cool to 5-15°C overnight to obtain a mixed oral liquid for later use; add 3-8 parts of multivitamins, 1-5 parts of multiminerals and 0.5-2 parts of lemon juice to the mixed oral liquid, mix well, add 100-300 parts of water, fill, and sterilize at 120-150°C for 10-50 minutes to obtain the licorice polysaccharide oral liquid.

[0043] Further preferably, the preparation method of the licorice polysaccharide capsule is as follows, in parts by weight:

[0044] Step 1: Pass 1 to 3 parts of talc powder through a 100-120 mesh sieve, and pass 60 to 80 parts of glycyrrhiza polysaccharide, 5 to 10 parts of hydroxypropyl cellulose and 15 to 25 parts of modified filler through a 50-70 mesh sieve for later use;

[0045] Step 2: mixing the glycyrrhiza polysaccharide, modified filler and hydroxypropyl cellulose for 10 to 40 minutes at a stirring speed of 100 to 500 rpm, moistening the mixture with 20 to 40 parts of a 20 to 40 wt% ethanol aqueous solution to form a soft material, and granulating the mixture through a 20 to 40 mesh sieve to obtain wet granules;

[0046] Step 3, drying the wet granules at 35°C to 60°C, and passing through a 20-50 mesh sieve to obtain dry granules;

[0047] Step 4: add the talcum powder sieved in step 1 to the dry particles, stir for 10 to 40 minutes at a stirring speed of 100 to 500 rpm, and then fill into capsule shells. The filling amount of each capsule shell is 0.3 to 0.5 g, thereby obtaining licorice polysaccharide capsules.

[0048] The preparation method of the modified filler is as follows, in parts by weight:

[0049] S1. Add 0.5-2 parts of sodium hydroxide, 5-15 parts of corn starch and 3-8 parts of 3-chloro-2-hydroxypropyltrimethylammonium chloride to 4-8 parts of water, stir at 2-6°C for 5-15 minutes, then heat to 70-90°C and maintain for 2-6 hours, add 15-25 parts of 70-85wt% ethanol aqueous solution to terminate the reaction, collect the precipitate by centrifugation, wash 1-3 times with 70-85wt% ethanol aqueous solution, and dry at 40-70°C for 4-8 hours to obtain a pretreated material;

[0050] S2, adding 3 to 8 parts of edible bentonite to 200 to 300 parts of water, adding 0.5 to 2 parts of the pretreated material prepared in step S1 under stirring at 100 to 300 rpm, maintaining at 40 to 70 ° C for 2 to 6 hours, centrifuging at 12000 to 18000 rpm for 3 to 8 minutes, collecting the solid, washing it with water 1 to 3 times, drying it at 40 to 70 ° C to a constant weight, grinding it, and sieving it through a 120 to 180 μm sieve to obtain a post-treated material;

[0051] S3, adding the post-treated product prepared in step S2 to 40-60 parts of water, adding 1-3 parts of sodium alginate while stirring at 100-300 rpm, continuing to stir for 5-15 minutes to form a mixture, and adding the mixture dropwise into 80-120 parts of 0.2-0.8 mol / L calcium chloride aqueous solution, stirring at 100-500 rpm for 10-50 minutes to obtain a mixed solution;

[0052] S4. The mixed solution is subjected to freeze / thaw treatment for 2 to 8 cycles. After final thawing, the mixed solution is centrifuged at 12,000 to 18,000 rpm for 3 to 8 minutes. The solid is collected, rinsed with water, and then freeze-dried at -10 to -30°C to obtain a modified filler.

[0053] Compared with the prior art, the present invention has the following beneficial effects:

[0054] 1) The present invention prepares a licorice polysaccharide pharmaceutical preparation by compounding licorice polysaccharides, which significantly improves humoral immunity, cellular immunity, and nonspecific immunity, while also having a certain ability to resist bacterial and viral infections. Toxicology tests show that the licorice polysaccharide pharmaceutical preparation has no obvious toxic and side effects.

[0055] 2) The licorice polysaccharide pharmaceutical preparation prepared by the present invention can improve the patient's physical condition.

[0056] 3) The licorice polysaccharide pharmaceutical preparation prepared by the present invention can significantly improve the patients' symptoms of lung and spleen deficiency, such as fatigue, cough and sputum, shortness of breath and laziness to speak, pale complexion, spontaneous sweating, poor appetite, abdominal distension, shortness of breath, weak defecation, and abnormal stool in the process of treating patients with cancer-related fatigue (lung and spleen deficiency syndrome), especially showing significant statistical differences in improving the patients' symptoms of fatigue, shortness of breath and laziness to speak, pale complexion, spontaneous sweating, and shortness of breath.

[0057] 4) The licorice polysaccharide pharmaceutical preparation prepared by the present invention can regulate the expression level of immune cells, increase the body's immune capacity, and thus improve the patient's fatigue symptoms.

[0058] 5) The licorice polysaccharide pharmaceutical preparation prepared by the present invention has a significant effect on improving the fatigue symptoms of tumor patients and the symptoms of lung and spleen deficiency in traditional Chinese medicine. It has certain effects on the physical, role, emotional, and social functions, fatigue, pain, fatigue, cough and sputum, shortness of breath, pale complexion, spontaneous sweating, poor appetite, abdominal distension, shortness of breath, weak defecation, and abnormal stool.

[0059] 6) The modified filler prepared by the present invention is beneficial to the filling and coating of glycyrrhiza polysaccharide, and increases the stability and embedding rate of glycyrrhiza polysaccharide drug capsules. DETAILED DESCRIPTION

[0060] Main sources of substances:

[0061] Licorice polysaccharide: Huapeptide Biotechnology (Shaanxi) Co., Ltd., product number: HTSW-DT0193, content ≥80%.

[0062] Low-substituted hydroxypropyl cellulose: Henan Linfan Biotechnology Co., Ltd., model: SH-LH22.

[0063] Multivitamin: Henan Hanyue Biotechnology Co., Ltd., model: food grade, item number: O445.

[0064] Composite minerals: Shandong Chuangtian Biotechnology Co., Ltd., item number: 5016, model: food grade.

[0065] Capsule shell: Ningbo Jiananjin Biotechnology Co., Ltd., model: 0#.

[0066] Edible bentonite: Shijiazhuang Jinhong Mineral Products Co., Ltd., item number: 633-6.

[0067] Example 1

[0068] A preparation method of licorice polysaccharide capsules is as follows:

[0069] Step 1: Pass 2 kg of talc powder through a 100-mesh sieve, and pass 70 kg of liquorice polysaccharide, 8 kg of hydroxypropyl cellulose, and 20 kg of corn starch through a 60-mesh sieve for later use;

[0070] Step 2: Glycyrrhiza polysaccharide, starch and hydroxypropyl cellulose were mixed and stirred for 30 minutes at a stirring speed of 300 rpm, moistened with 30 kg of 30 wt% ethanol aqueous solution to form a soft material, and granulated through a 30-mesh sieve to obtain wet granules;

[0071] Step 3, drying the wet granules at 40°C and passing through a 30-mesh sieve to obtain dry granules;

[0072] Step 4: add the talcum powder sieved in step 1 to the dry particles, stir for 30 minutes at a stirring speed of 300 rpm, and then fill into capsule shells. The filling amount of each capsule shell is 0.4 g, thereby obtaining licorice polysaccharide drug capsules.

[0073] The preparation method of the licorice polysaccharide is as follows:

[0074] Z1. Wash licorice with water, dry it, and then grind it through a 50-mesh sieve to obtain a licorice raw material;

[0075] Z2, adding water to the licorice raw material prepared in step Z1 and decocting three times, adding 8 times the weight of the licorice raw material water for the first time and decocting for 3 hours, adding 6 times the weight of the licorice raw material water for the second time and decocting for 3 hours, and adding 5 times the weight of the licorice raw material water for the third time and decocting for 2 hours, combining the three decoctions to obtain a licorice extract;

[0076] Z3, vacuum concentrate the liquorice extract prepared in step Z2 to a relative density of 1.06 g / cm at 25 °C. 3 , to obtain a concentrated solution;

[0077] Z4. Add 3 times the mass of 95 wt% ethanol aqueous solution to the concentrated solution prepared in step Z3, let it stand for 24 hours, and collect the precipitate;

[0078] Z5. The precipitate prepared in step Z4 is spray dried at an air inlet temperature of 170° C. and an air outlet temperature of 80° C. to obtain a dried product;

[0079] Z6. Grind the dried product prepared in step Z5 and pass it through an 80-mesh sieve to obtain glycyrrhiza polysaccharide.

[0080] Test Examples 1 to 9 were tested using the glycyrrhiza polysaccharide capsules prepared in Example 1 of the present invention.

[0081] Test Example 1

[0082] Routine blood test

[0083] Among the 33 CRF patients included in this study, 23 were female and 10 were male, including 15 patients aged 55-65 years, 11 patients aged 65-75 years, 3 patients aged 35-45 years, and 4 patients aged 45-55 years. Among them, there were 11 patients with breast cancer, 6 patients with colorectal cancer, 5 patients with lung cancer, 2 patients each with cervical cancer, kidney cancer, endometrial cancer, and bladder cancer, and 1 patient each with B-cell lymphoma, multiple myeloma, and acute leukemia.

[0084] All patients were orally administered the licorice polysaccharide pharmaceutical preparation prepared by the present invention. 4 capsules each time, twice a day, half an hour before breakfast and dinner. Basic symptomatic treatment was given according to the patient's general condition, and symptomatic treatment such as anti-inflammatory, analgesic, expectorant, and antiemetic treatment was given when necessary. The patients were observed for 4 weeks after taking the medication (observed and recorded before and after 4 weeks of treatment).

[0085] Blood test: Serum was collected from patients before and after treatment for routine blood tests. Changes in WBC, RBC, HGB, HCT, MCV, cortisol, liver and kidney function, myocardial enzymes, and stool routine were observed before and after treatment. The test results are shown in Table 1.

[0086] Table 1: Blood test results

[0087]

[0088] Platelet count (PLT) before treatment was (216.24±54.249)×10 9 / L, and PLT after treatment was (222.48±59.535)×10 9 / L; the difference did not conform to the normal distribution. Using the Wilcoxon signed rank test, Z = -0.917, P = 0.359 (P>0.05), the difference was not statistically significant. Before treatment, the red blood cell (RBC) was (4.47 ± 0.317) × 10 12 / L, and RBC after treatment was (4.51±0.301)×10 12 / L; the difference did not conform to the normal distribution, and the Wilcoxon signed rank test was used, Z = -0.643, P = 0.520 (P> 0.05), and the difference was not statistically significant. Hemoglobin (HGB) before treatment was (135.39 ± 10.000) g / L, and HGB after treatment was (136.48 ± 9.994) g / L; the paired sample T test was used, t (32) = 0.867, P = 0.392 (P> 0.05), and the difference was not statistically significant. Lymphocyte count (LY) before and after treatment did not conform to the normal distribution, and was described by M (P25, P75), that is, LY before treatment was 1.65 (1.405, 2.100) × 109 / L, and LY after treatment was 1.82 (1.520, 2.185) × 10 9 / L; the difference did not conform to the normal distribution. The Wilcoxon signed rank test showed Z = -2.136, P = 0.033 (P < 0.05), and the difference was statistically significant. Before treatment, the white blood cell (WBC) count was 5.77 (4.765, 6.58) × 10 9 / L, WBC after treatment was 5.81 (4.855, 7.155) × 10 9 / L; the difference did not conform to the normal distribution, and the Wilcoxon signed rank test was used, Z = -1.841, P = 0.066 (P>0.05), and the difference was not statistically significant

[0089] Test Example 2

[0090] C-reactive protein (CRP) test

[0091] The serum of the patients before and after treatment was tested for C-reactive protein (CRP). The test results are shown in Table 2.

[0092] Table 2: C-reactive protein (CRP) test results

[0093]

[0094] C-reactive protein (CRP) levels before and after treatment did not conform to a normal distribution and were described using M (P25, P75). That is, the CRP before treatment was 3.36 (1.485, 5.425) mg / L, and the CRP after treatment was 3.18 (2.160, 5.420) mg / L. The difference did not conform to a normal distribution and was tested using the Wilcoxon signed-rank test, Z = -0.670, P = 0.503 (P > 0.05), indicating no statistically significant difference.

[0095] Test Example 3

[0096] Immunity testing

[0097] Sera from patients before and after treatment were collected for immune testing to observe changes in serum levels of total T cells, CD3+, CD4+, CD8+, and other lymphocyte subsets before and after treatment, and to calculate changes in the CD4+ / CD8+ ratio before and after treatment. The test results are shown in Table 3.

[0098] Table 3: Immunity test results

[0099]

[0100]

[0101] The absolute number of total T lymphocytes before treatment (CD3 + #) was (902.33±308.394) / μL, and CD3 +The absolute number of lymphocytes (Lym#) before treatment was (1258.70±366.188) / μL, and the Lym# after treatment was (1364.97±362.763) / μL; the difference did not conform to the normal distribution, and the Wilcoxon signed-rank test was used, Z=-2.001, P=0.045 (P<0.05), and the difference was statistically significant. The absolute number of helper T lymphocytes (CD4 + #) was (513.88±196.431) / μL, and CD4 + # was (553.82±199.609) / μL; the difference did not conform to the normal distribution. The Wilcoxon signed rank test showed that Z=-1.867, P=0.062 (P>0.05), indicating no statistically significant difference. + %) was (30.15±9.304)%,CD8 + The difference did not conform to the normal distribution. The Wilcoxon signed rank test showed that Z = -0.170, P = 0.865 (P>0.05), indicating that the difference was not statistically significant. + %) was (41.49±11.813)%, and CD4% after treatment was (41.24±11.375)%; the difference was in accordance with normal distribution, and the paired sample T test was used: t(32)=0.363, P=0.719 (P>0.05), indicating no statistically significant difference. + %) did not conform to the normal distribution and were described by M(P25, P75), that is, CD3 + % was 74.11 (62.77, 81.61), CD3 + The percentage was 73.74 (64.39, 80.24); the Wilcoxon signed rank test showed that Z = -0.608, P = 0.544 (P>0.05), and the difference was not statistically significant. + #) was 336 (274, 446.5) / μL, and CD8 + # was 376 (285, 496.5) / μL; Wilcoxon signed rank test, Z = -1.412, P = 0.158 (P>0.05), the difference was not statistically significant. + / CD8 + ) was 1.32 (0.945, 1.835), and CD4 + / CD8 + was 1.36 (1.065, 1.805); using the Wilcoxon signed-rank test, Z = -0.161, P = 0.872 (P>0.05), the difference was not statistically significant.

[0102] Test Example 4

[0103] Piper score change test before and after treatment

[0104] The Piper Fatigue Scale (PFS), developed by Piper in 1982 based on the original scale, is specifically designed for patients with CRF and has high reliability and validity. This 22-item scale encompasses four dimensions: behavioral, physical, emotional, and cognitive fatigue. Each dimension is scored on a scale of 0 to 10: 0 for no fatigue; 1 to 3 for mild fatigue; 4 to 6 for moderate fatigue; and 7 to 10 for severe fatigue. The scores for the four dimensions are summed to form a total score, with higher scores indicating greater CRF severity. Records were taken before and after treatment. The test results are shown in Table 4.

[0105] Table 4: Piper scores before and after treatment

[0106] index Before treatment After treatment Z / t value P-value Behavioral Dimension 23(12，31.5) 12(7，22.5) -3.932 0.000 Emotional dimension 23.55±12.610 16.73±11.796 -3.988 0.000 sensory dimension 25.67±11.776 18.21±11.008 -4.110 0.000 Cognitive Dimension 28.76±12.450 20.58±11.982 -3.848 0.000 Total score (points) 101.70±45.047 71.18±41.724 -4.277 0.000

[0107] The Piper score results in this study showed that the total score before treatment was (101.70±45.047) points, and the total score after treatment was (71.18±41.724) points. The total score after treatment was lower than that before treatment, and the difference was statistically significant (P<0.05). The scores of each dimension are as follows: in the behavioral dimension, the score decreased after treatment compared with that before treatment, and the difference was statistically significant (P<0.05); the emotional dimension score was (23.55±12.610) points before treatment and (16.73±11.796) points after treatment, and the score decreased after treatment compared with that before treatment, and the difference was statistically significant (P<0.05); the sensory dimension score was (25.67±11.776) points before treatment and (18.21±11.008) points after treatment, and the score decreased after treatment compared with that before treatment, and the difference was statistically significant (P<0.05); the cognitive dimension score was (28.76±12.450) points before treatment and (20.58±11.982) points after treatment, and the score decreased after treatment compared with that before treatment, and the difference was statistically significant (P<0.05).

[0108] Test Example 5

[0109] KPS score and distribution test before and after treatment

[0110] The Karnofsky (KPS) functional status scale (using a percentage scale) is used to categorize patients into 11 levels based on their ability to perform normal activities, their condition, and their ability to care for themselves. Each level is 10 points, and the level of functional status decreases from high to low. Higher scores indicate better health, while lower scores indicate worse health. Data were recorded before and after treatment. The results are shown in Tables 5 and 6.

[0111] Table 5: Distribution of KPS scores before and after treatment (examples)

[0112] Time / Rating 60-69 70-79 80-89 90-100 Before treatment (case) 5 5 5 18 After treatment (case) 3 2 4 24

[0113] Table 6: Distribution of KPS scores before and after treatment (examples)

[0114] Before treatment After treatment Z / t P-value Score (points) 90(70，90) 90(80，90) -2.547 0.011

[0115] Before treatment, the KPS scores of CRF in the 33 patients were (60-69) in 5, (70-79) in 5, (80-89) in 5, and (90-100) in 18. After treatment, the KPS scores were (60-69) in 3, (70-79) in 2, (80-89) in 4, and (90-100) in 24, as shown in Table 5. A comparison of the KPS scores before and after treatment showed that the scores were 90 (70, 90) before treatment and 90 (80, 90) after treatment. The KPS scores of the patients increased after treatment, and the difference was statistically significant (P < 0.05), as shown in Table 6.

[0116] Test Example 6

[0117] BFI scores before and after treatment

[0118] The BFI (Brain Fatigue Index) was designed by Mendoza et al. and consists of nine items. It uses a linear scoring system with 0 (none) and 10 (maximum severity). Patients are asked to mark the corresponding number based on their individual fatigue. Scoring criteria are: 1-3 for mild fatigue, 4-6 for moderate fatigue, and 7-10 for severe fatigue. The first three items assess the patient's current fatigue level, the average fatigue level over the past 24 hours, and the most severe fatigue level. The last six items assess the impact of fatigue on the patient's daily life. The results are shown in Table 7.

[0119] Table 7: Distribution of KPS scores before and after treatment (examples)

[0120]

[0121] The BFI total score was (38.33±19.176) before treatment and (26.27±18.250) after treatment. The difference did not conform to a normal distribution. The Wilcoxon signed-rank test showed a statistically significant difference: Z = -4.079, P = 0.000 (P < 0.05). Item 1 (patient's current fatigue level): The score was 5 (3, 7) before treatment and 3 (1, 5) after treatment. The difference did not conform to a normal distribution. The Wilcoxon signed-rank test showed a statistically significant difference: Z = -4.083, P = 0.000 (P < 0.05). Item 2 (general fatigue level in the past 24 hours): 5 (3, 7) points before treatment and 3 (1.5, 4.5) points after treatment; the difference did not conform to a normal distribution, and the Wilcoxon signed-rank test showed a statistically significant difference: Z = -4.202, P = 0.000 (P < 0.05). Item 3 (maximum fatigue level in the past 24 hours): 5.18 ± 2.430 points before treatment and 3.52 ± 2.502 points after treatment; the difference did not conform to a normal distribution, and the Wilcoxon signed-rank test showed a statistically significant difference: Z = -3.980, P = 0.000 (P < 0.05). Item 4 (the impact of fatigue on the patient's daily activities, mood, walking ability, etc. in the past 24 hours): 20 (11.5, 30.5) points before treatment and 12 (8, 25) points after treatment; the difference did not conform to the normal distribution, and the Wilcoxon signed-rank test was used: Z = -3.713, P = 0.000 (P < 0.05), indicating a statistically significant difference.

[0122] Test Example 7

[0123] Cancer Quality of Life Questionnaire (QLQ-C30) scores before and after treatment

[0124] The EORTC QLQ-C30 is a core scale developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess the quality of life of cancer patients. This 30-item questionnaire includes five functional scales (physical functioning, role functioning, cognitive functioning, emotional functioning, and social functioning) and an overall quality of life scale. Three of these items (whether you needed to rest in the past week; whether you felt very weak; and whether you felt very tired) are used to measure fatigue. Each item is scored on a four-point scale, with "not at all" receiving 1 point and "very much" receiving 4 points. Higher scores indicate greater fatigue. The test results are shown in Table 8.

[0125] Table 8: Distribution of KPS scores before and after treatment (examples)

[0126]

[0127]

[0128] In terms of functional domains, the SW normality test for all five functional domains showed no normal distribution before and after treatment (P < 0.05). Therefore, a paired-sample rank-sum test was performed on the pre- and post-treatment data. The test showed statistically significant differences in physical, role, emotional, and social functioning (P < 0.05); there was no statistically significant difference in cognitive function (P > 0.05). In terms of major symptom domains, the SW normality test for all three major symptom domains showed no normal distribution before and after treatment (P < 0.05). Therefore, a paired-sample rank-sum test was performed on the pre- and post-treatment data. The test showed statistically significant differences in fatigue and pain (P < 0.05), but no statistically significant difference in nausea and vomiting (P > 0.05). In terms of individual symptom domains, the SW normality test for all six individual symptom domains before and after treatment showed no normal distribution (P < 0.05). Therefore, a paired sample rank sum test was performed on the pre- and post-treatment data. This test showed statistically significant differences in dyspnea, insomnia, loss of appetite, constipation, diarrhea, and financial difficulties (P < 0.05). In terms of overall quality of life, the difference in pre- and post-treatment scores did not show a normal distribution (P < 0.05). Therefore, a paired sample rank sum test was performed on the pre- and post-treatment data. This difference was statistically significant (P < 0.05).

[0129] Test Example 8

[0130] Medical syndrome scoring

[0131] Based on the 2002 edition of the People's Medical Publishing House's "Diagnostics of Traditional Chinese Medicine" and the 2014 edition of the People's Medical Publishing House's "Guidelines for the Diagnosis and Treatment of Malignant Tumors in Traditional Chinese Medicine," and in conjunction with the opinions of experts from the Department of Respiratory Medicine and the Department of Oncology at the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, the following symptoms of lung and spleen qi deficiency were included: fatigue, cough and sputum, or thin sputum, shortness of breath and laziness to speak, pale or sallow complexion, spontaneous perspiration, poor appetite, abdominal distension, shortness of breath, edema, weak bowel movements, abnormal bowel movements, pale and fat tongue, or teeth marks on the edges of the tongue, thin white fur, weak pulse, or deep and thready pulse, weak pulse, or deep and slow pulse. Records were taken once before and after medication. Based on the above common symptoms and signs of lung and spleen qi deficiency, the condition was divided into three levels: mild, moderate, and severe (referring to the Ministry of Health's "Guiding Principles for Clinical Research of New Chinese Medicines," 2002 edition). Mild, moderate, and severe levels were scored as +, ++, and +++, respectively, with (+) scored as 1 and no symptoms scored as 0. The test results are shown in Table 9.

[0132] Table 9: Distribution of KPS scores before and after treatment (examples)

[0133] symptom Number of cases Before treatment After treatment Z value P-value Fatigue 33 2(1，2) 1(1，1) -4.185 0.000 Cough and sputum 33 1(0，1) 0(0，1) -2.714 0.007 Short temper and lazy 33 1(1，1) 1(0，1) -3.606 0.000 Pale complexion 33 2(1，2) 1(1，1) -4.690 0.000 spontaneous sweating 33 1(1，2) 1(0，1) -4.082 0.000 Na Shao 33 1(0，1) 0(0，1) -2.673 0.008 abdominal distension 33 0(0，1) 0(0，1) -2.517 0.012 shortness of breath 33 1(1，2) 1(0，1) -4.025 0.000 Weak bowel movements 33 0(0，1) 0(0，0) -2.121 0.034 Abnormal bowel movements 33 0(0，1) 0(0，0) -2.530 0.011 nausea and vomiting 33 0(0，0) 0(0，0) -0.577 0.564 edema 33 0(0，1) 0(0，1) -1.000 0.317 Total score 33 12(10，15.5) 8(6，10) -4.951 0.000

[0134] The differences in the total symptom score and individual symptom scores (fatigue, cough and sputum, shortness of breath and laziness, pale complexion, spontaneous sweating, poor appetite, abdominal distension, shortness of breath, weak bowel movements, abnormal bowel movements, nausea and vomiting, and edema) before and after treatment were tested by Swimming Pool Test (SWT) and all showed no normal distribution (P < 0.05). Paired rank sum tests showed that the total symptom score and individual symptom scores decreased after treatment compared with those before treatment. Significant differences were found in fatigue, cough and sputum, shortness of breath and laziness, pale complexion, spontaneous sweating, poor appetite, abdominal distension, shortness of breath, weak bowel movements, and abnormal bowel movements (P < 0.05). There were no significant differences in nausea and vomiting or edema (P > 0.05).

[0135] Test Example 9

[0136] Safety Assessment

[0137] No serious adverse events were observed during this study. Monitoring of electrocardiogram, blood, stool, routine, liver and kidney function were all normal with no significant changes.

[0138] In summary, in this study, Piper, BFI, and QLQ-C30 scores were significantly lower after treatment than before treatment, and the differences were statistically significant (P<0.05), indicating that licorice polysaccharides can effectively improve fatigue symptoms in cancer patients.

[0139] The KPS score is the patient's physical condition score; the higher the score, the better the physical condition. In this study, after four weeks of treatment, the KPS score was significantly higher than before treatment, with a statistically significant difference (P < 0.05). The results show that Licorice Polysaccharide Capsules can improve patients' physical condition.

[0140] Compared with before treatment, the TCM lung and spleen deficiency syndrome score after treatment was improved, and the difference was statistically significant (P<0.05), indicating that in the process of treating patients with cancer-related fatigue (lung and spleen deficiency syndrome), licorice polysaccharide can significantly improve the patients' symptoms of lung and spleen deficiency, such as fatigue, cough and sputum, shortness of breath, pale complexion, spontaneous sweating, poor appetite, abdominal distension, shortness of breath, weak defecation, and abnormal stool, especially in improving the symptoms of fatigue, shortness of breath, pale complexion, spontaneous sweating, and shortness of breath.

[0141] After treatment, the lymphocyte (LY) count in routine blood tests (P=0.033), the absolute number of total T lymphocytes CD3+# (P=0.045) and the absolute number of lymphocytes Lym# (P=0.047) in immune indicators were all improved compared with those before treatment, and the differences were statistically significant (P<0.05), indicating that Licorice Polysaccharide Capsules can regulate the expression level of immune cells, increase the body's immune ability, and thus improve patients' fatigue symptoms.

[0142] In traditional Chinese medicine, licorice root is known to "tonify qi and replenish the middle, clear away heat and detoxify, eliminate phlegm and relieve cough, relieve acute pain, and harmonize medicinal properties." Modern pharmacology has demonstrated that licorice polysaccharides can enhance immunity. Small-scale clinical observational trials have shown significant effects in improving fatigue and lung and spleen deficiency symptoms in cancer patients. Further large-scale, multicenter, randomized, double-blind trials are needed to validate and discuss this effect.

[0143] Example 2

[0144] A preparation method of a glycyrrhiza polysaccharide tablet is as follows:

[0145] 91g of allose, 3g of octenyl succinate starch, 3g of silicon dioxide and 3g of white clay were dried and crushed together and passed through a 1mm sieve. Then, 800g of glycyrrhizic acid polysaccharide and 100g of water were added and mixed evenly. A 9×20mm punch was used in a tableting device to prepare glycyrrhizic acid polysaccharide tablets weighing 1000mg.

[0146] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0147] Example 3

[0148] A preparation method of glycyrrhiza polysaccharide medicinal granules is as follows:

[0149] 50 g of glycyrrhiza polysaccharide and 100 g of β-cyclodextrin were mixed and ground into powder. 500 g of lactose was added to the above-mentioned micropowder, and the mixture was further ground into powder. The mixture was passed through a 200-mesh sieve to obtain a mixed powder. 10 g of low-substituted hydroxypropyl cellulose was passed through a 100-mesh sieve and then added to the mixed powder. 0.2 g of stevia was then added and mixed uniformly. 300 g of a 50 wt% ethanol aqueous solution was added to prepare a soft material. The mixture was granulated with a 20-mesh sieve, dried at 70° C., and passed through a 50-mesh sieve to obtain glycyrrhiza polysaccharide pharmaceutical granules.

[0150] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0151] Example 4

[0152] A preparation method of licorice polysaccharide oral liquid is as follows:

[0153] Add 45g of sucrose, 20g of pectin, 15g of seaweed polysaccharide and 50g of licorice polysaccharide to 400g of water, and ultrasonically vibrate at 60°C for 3h with an ultrasonic power of 300W and an ultrasonic frequency of 50kHz. Cool to 10°C overnight to obtain a mixed oral liquid for later use. Add 5g of multivitamins, 3g of multiminerals and 1g of lemon juice to the mixed oral liquid, mix well, add 200g of water, fill, and sterilize at 145°C for 40min to obtain a licorice polysaccharide oral liquid.

[0154] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0155] Example 5

[0156] A preparation method of liquorice polysaccharide capsules is as follows:

[0157] Step 1: Pass 2 kg of talc powder through a 100-mesh sieve, and pass 70 kg of liquorice polysaccharide, 8 kg of hydroxypropyl cellulose, and 20 kg of modified filler through a 60-mesh sieve for later use;

[0158] Step 2: Glycyrrhiza polysaccharide, modified filler and hydroxypropyl cellulose were mixed and stirred for 30 minutes at a stirring speed of 300 rpm, moistened with 30 kg of 30 wt% ethanol aqueous solution to form a soft material, and granulated through a 30-mesh sieve to obtain wet granules;

[0159] Step 3, drying the wet granules at 40°C and passing through a 30-mesh sieve to obtain dry granules;

[0160] Step 4: add the talcum powder sieved in step 1 to the dry particles, stir for 30 minutes at a stirring speed of 300 rpm, and then fill into capsule shells. The filling amount of each capsule shell is 0.4 g, thereby obtaining licorice polysaccharide drug capsules.

[0161] The preparation method of the modified filler is as follows:

[0162] S1. Add 1 g of sodium hydroxide, 10 g of corn starch and 5 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride to 6 g of water, stir at 4 ° C for 10 min, then heat to 80 ° C and maintain for 4 h, add 20 g of 80 wt% ethanol aqueous solution to terminate the reaction, collect the precipitate by centrifugation, wash three times with 80 wt% ethanol aqueous solution, and dry at 60 ° C for 6 h to obtain a pretreated material;

[0163] S2. Add 5 g of edible bentonite to 250 g of water, add 1 g of the pretreated material prepared in step S1 under stirring at 200 rpm, maintain at 60° C. for 4 h, centrifuge at 15,000 rpm for 5 min, collect the solid, wash twice with water, dry at 60° C. to a constant weight, grind, and sieve through a 150 μm sieve to obtain a post-treated material;

[0164] S3, the post-treated product prepared in step S2 was added to 50 g of water, 2 g of sodium alginate was added under stirring at 200 rpm, and stirring was continued for 10 min to form a mixture, and the mixture was dropped into 100 g of 0.5 mol / L calcium chloride aqueous solution, and stirred at 300 rpm for 30 min to obtain a mixed solution;

[0165] S4. The mixture was subjected to freeze / thaw treatment for 5 cycles. After final thawing, the mixture was centrifuged at 15,000 rpm for 5 minutes. The solid was collected, rinsed with water, and then freeze-dried at -20°C to obtain a modified filler.

[0166] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0167] Example 6

[0168] The preparation method of a liquorice polysaccharide capsule is basically the same as that of Example 1, with the only difference being that the preparation method of the modified filler is different.

[0169] The preparation method of the modified filler is as follows:

[0170] S1. Add 1 g of sodium hydroxide, 10 g of corn starch and 5 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride to 6 g of water, stir at 4 ° C for 10 min, then heat to 80 ° C and maintain for 4 h, add 20 g of 80 wt% ethanol aqueous solution to terminate the reaction, collect the precipitate by centrifugation, wash three times with 80 wt% ethanol aqueous solution, and dry at 60 ° C for 6 h to obtain a pretreated material;

[0171] S2. Add 1 g of the pretreated product prepared in step S1 to 250 g of water, maintain at 60° C. for 4 h, centrifuge at 15,000 rpm for 5 min, collect the solid, wash it twice with water, dry it at 60° C. to a constant weight, grind it, and sieve it through a 150 μm sieve to obtain a post-treated product;

[0172] S3, the post-treated product prepared in step S2 was added to 50 g of water, 2 g of sodium alginate was added under stirring at 200 rpm, and stirring was continued for 10 min to form a mixture, and the mixture was dropped into 100 g of 0.5 mol / L calcium chloride aqueous solution, and stirred at 300 rpm for 30 min to obtain a mixed solution;

[0173] S4. The mixture was subjected to freeze / thaw treatment for 5 cycles. After final thawing, the mixture was centrifuged at 15,000 rpm for 5 minutes. The solid was collected, rinsed with water, and then freeze-dried at -20°C to obtain a modified filler.

[0174] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0175] Example 7

[0176] The preparation method of a liquorice polysaccharide capsule is basically the same as that of Example 1, with the only difference being that the preparation method of the modified filler is different.

[0177] The preparation method of the modified filler is as follows:

[0178] S1. Add 1 g of sodium hydroxide, 10 g of corn starch and 5 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride to 6 g of water, stir at 4 ° C for 10 min, then heat to 80 ° C and maintain for 4 h, add 20 g of 80 wt% ethanol aqueous solution to terminate the reaction, collect the precipitate by centrifugation, wash three times with 80 wt% ethanol aqueous solution, and dry at 60 ° C for 6 h to obtain a pretreated material;

[0179] S2. Add 5 g of edible bentonite to 250 g of water, add 1 g of the pretreated material prepared in step S1 under stirring at 200 rpm, maintain at 60° C. for 4 h, centrifuge at 15,000 rpm for 5 min, collect the solid, wash twice with water, dry at 60° C. to a constant weight, grind, and sieve through a 150 μm sieve to obtain a post-treated material;

[0180] S3, adding the post-treated product prepared in step S2 to 50 g of water, stirring at 200 rpm for 10 min to form a mixture, and adding the mixture dropwise into 100 g of 0.5 mol / L calcium chloride aqueous solution, stirring at 300 rpm for 30 min to obtain a mixed solution;

[0181] S4. The mixture was subjected to freeze / thaw treatment for 5 cycles. After final thawing, the mixture was centrifuged at 15,000 rpm for 5 minutes. The solid was collected, rinsed with water, and then freeze-dried at -20°C to obtain a modified filler.

[0182] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0183] Example 8

[0184] The preparation method of a liquorice polysaccharide capsule is basically the same as that of Example 1, with the only difference being that the preparation method of the modified filler is different.

[0185] The preparation method of the modified filler is as follows:

[0186] S1. Add 1 g of sodium hydroxide, 10 g of corn starch and 5 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride to 6 g of water, stir at 4 ° C for 10 min, then heat to 80 ° C and maintain for 4 h, add 20 g of 80 wt% ethanol aqueous solution to terminate the reaction, collect the precipitate by centrifugation, wash three times with 80 wt% ethanol aqueous solution, and dry at 60 ° C for 6 h to obtain a pretreated material;

[0187] S2. Add 5 g of edible bentonite to 250 g of water, add 1 g of the pretreated material prepared in step S1 under stirring at 200 rpm, maintain at 60° C. for 4 h, centrifuge at 15,000 rpm for 5 min, collect the solid, wash twice with water, dry at 60° C. to a constant weight, grind, and sieve through a 150 μm sieve to obtain a post-treated material;

[0188] S3, the post-treated product prepared in step S2 was added to 50 g of water, 2 g of sodium alginate was added under stirring at 200 rpm, and stirring was continued for 10 min to form a mixture, and the mixture was dropped into 100 g of 0.5 mol / L calcium chloride aqueous solution, and stirred at 300 rpm for 30 min to obtain a mixed solution;

[0189] S4. Centrifuge the mixed solution at 15,000 rpm for 5 minutes, collect the solid, rinse with water, and then freeze-dry at -20°C to obtain a modified filler.

[0190] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0191] Comparative Example 1

[0192] The preparation method of a liquorice polysaccharide capsule is basically the same as that of Example 1, with the only difference being that the preparation method of the modified filler is different.

[0193] The preparation method of the modified filler is as follows:

[0194] S1. Add 1 g of sodium hydroxide, 10 g of corn starch and 5 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride to 6 g of water, stir at 4 ° C for 10 min, then heat to 80 ° C and maintain for 4 h, add 20 g of 80 wt% ethanol aqueous solution to terminate the reaction, collect the precipitate by centrifugation, wash three times with 80 wt% ethanol aqueous solution, and dry at 60 ° C for 6 h to obtain a pretreated material;

[0195] S2. Add 1 g of the pretreated product prepared in step S1 to 250 g of water, maintain at 60° C. for 4 h, centrifuge at 15,000 rpm for 5 min, collect the solid, wash it twice with water, dry it at 60° C. to a constant weight, grind it, and sieve it through a 150 μm sieve to obtain a post-treated product;

[0196] S3, adding the post-treated product prepared in step S2 to 50 g of water, stirring at 200 rpm for 10 min to form a mixture, and adding the mixture dropwise into 100 g of 0.5 mol / L calcium chloride aqueous solution, stirring at 300 rpm for 30 min to obtain a mixed solution;

[0197] S4. The mixed solution was centrifuged at 15000 rpm for 5 min, the solid was collected, washed with water, and then freeze-dried at -20°C to obtain a modified filler.

[0198] The preparation method of the licorice polysaccharide is the same as that in Example 1.

[0199] Test Example 10

[0200] Stability testing

[0201] Storage stability: Glycyrrhiza polysaccharide capsules prepared in Example 1, Examples 5-8, and Comparative Example 1 were stored at 40°C for 60 days. The retention of glycyrrhiza polysaccharide was evaluated by ultraviolet light absorption measurement at a wavelength of 488 nm. The average of three measurements was used as the result. The test results are shown in Table 10.

[0202] Table 10: Stability test results

[0203] Trial plan Retention rate / % Example 1 84.42 Example 5 98.35 Example 6 93.12 Example 7 93.83 Example 8 91.59 Comparative Example 1 88.51

[0204] Test Example 11

[0205] Embedding efficiency test

[0206] The glycyrrhiza polysaccharide capsules prepared in Example 1, Examples 5-8, and Comparative Example 1 were thoroughly rinsed with 10 mL of anhydrous ethanol and centrifuged at 4000 rpm for 3 min. The surface unencapsulated glycyrrhiza polysaccharide content (W1) was measured. The glycyrrhiza polysaccharide capsules prepared in Example 1, Examples 5-8, and Comparative Example 1 were weighed, 10 mL of water was added, and the capsules were thoroughly ground in a mortar. The volume was then adjusted to 20 mL with anhydrous ethanol, and the glycyrrhiza polysaccharide content (W2) was measured.

[0207] Licorice polysaccharide capsule embedding rate λ=(W2-W1) / W2

[0208] The average value of three measurements was taken as the result. The test results are shown in Table 11.

[0209] Table 11: Embedment efficiency test results

[0210] Trial plan Embedding rate λ / % Example 1 73.71 Example 5 88.53 Example 6 84.52 Example 7 82.05 Example 8 80.94 Comparative Example 1 75.01

[0211] From the results of Test Examples 10 and 11, it can be seen that Example 5 has the highest retention rate and embedding rate. The possible reason is that starch is a polysaccharide and edible bentonite has a very weak affinity for organic matter. This is because the cations adsorbed on the surface of edible bentonite compensate for the negative charge generated by isostructural substitution under strong hydration, but the binding of starch reduces the adsorption of cations. The abundant methyl and methylene groups on the starch polymer chain also serve as hydrophobic binding sites for glycyrrhizic polysaccharides, resulting in an increase in adsorption enthalpy, entropy and free energy, and can serve as a carrier for glycyrrhizic polysaccharides. Edible bentonite nanosheets are electrostatically attracted to alginate after binding to the cations on the surface of the starch polymer chain, thereby improving dispersibility and increasing affinity with glycyrrhizic polysaccharides. Edible bentonite is organically modified with cationic starch and 3-chloro-2-hydroxypropyltrimethylammonium chloride. Adding alginate is a feasible method for preparing a diffusion release dosage form. The freeze-thaw method is conducive to the formation of pores in the modified filler, which is further conducive to the filling and coating of glycyrrhizic polysaccharides and increases stability.

Claims

1. A use of licorice polysaccharide in the preparation of a drug for treating cancer-related fatigue, characterized in that: Cancer-related fatigue refers to fatigue caused by cancer or cancer treatment; The drug for treating cancer-related fatigue comprises 60-80 wt% of licorice polysaccharide; The drug for treating cancer-related fatigue is in the form of capsules; The capsule is a licorice polysaccharide capsule; The preparation method of the licorice polysaccharide capsule is as follows, in parts by weight: Step 1: Pass 1 to 3 parts of talc powder through a 100-120 mesh sieve, and pass 60 to 80 parts of glycyrrhiza polysaccharide, 5 to 10 parts of hydroxypropyl cellulose and 15 to 25 parts of modified filler through a 50-70 mesh sieve for later use; Step 2: mixing the glycyrrhiza polysaccharide, modified filler and hydroxypropyl cellulose for 10 to 40 minutes at a stirring speed of 100 to 500 rpm, moistening the mixture with 20 to 40 parts of a 20 to 40 wt% ethanol aqueous solution to form a soft material, and granulating the mixture through a 20 to 40 mesh sieve to obtain wet granules; Step 3, drying the wet granules at 35°C to 60°C, and passing through a 20-50 mesh sieve to obtain dry granules; Step 4: adding the talc powder sieved in step 1 to the dried granules, stirring for 10 to 40 minutes at a stirring speed of 100 to 500 rpm, and then filling into capsule shells, with the filling amount of each capsule shell being 0.3 to 0.5 g, to obtain glycyrrhizic polysaccharide capsules; The preparation method of the modified filler is as follows, in parts by weight: S1. Add 0.5-2 parts of sodium hydroxide, 5-15 parts of corn starch and 3-8 parts of 3-chloro-2-hydroxypropyltrimethylammonium chloride to 4-8 parts of water, stir at 2-6°C for 5-15 minutes, then heat to 70-90°C and maintain for 2-6 hours, add 15-25 parts of 70-85wt% ethanol aqueous solution to terminate the reaction, collect the precipitate by centrifugation, wash 1-3 times with 70-85wt% ethanol aqueous solution, and dry at 40-70°C for 4-8 hours to obtain a pretreated material; S2, adding 3 to 8 parts of edible bentonite to 200 to 300 parts of water, adding 0.5 to 2 parts of the pretreated material prepared in step S1 under stirring at 100 to 300 rpm, maintaining at 40 to 70 ° C for 2 to 6 hours, centrifuging at 12000 to 18000 rpm for 3 to 8 minutes, collecting the solid, washing it with water 1 to 3 times, drying it at 40 to 70 ° C to a constant weight, grinding it, and sieving it through a 120 to 180 μm sieve to obtain a post-treated material; S3, adding the post-treated product prepared in step S2 to 40-60 parts of water, adding 1-3 parts of sodium alginate while stirring at 100-300 rpm, continuing to stir for 5-15 minutes to form a mixture, and adding the mixture dropwise into 80-120 parts of 0.2-0.8 mol / L calcium chloride aqueous solution, stirring at 100-500 rpm for 10-50 minutes to obtain a mixed solution; S4. The mixed solution is subjected to freeze / thaw treatment for 2 to 8 cycles. After final thawing, the mixed solution is centrifuged at 12,000 to 18,000 rpm for 3 to 8 minutes. The solid is collected, rinsed with water, and then freeze-dried at -10 to -30°C to obtain a modified filler.

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