Composition for improving muscular atrophy caused by antitumor drugs and improving athletic performance and application thereof

Abstract

The invention discloses a composition for improving muscular atrophy caused by antitumor drugs and improving athletic performance and application thereof. The composition comprises the following components in parts by weight: 6-30 parts of dendrobium officinale, 1-20 parts of American ginseng, 1-20 parts of rhizoma polygonati and 0.1-1 part of choline. The composition can be used for preparing pharmaceutical preparations or health-care foods for improving muscular atrophy caused by anti-tumor drugs and improving exercise performance, is used for improving the symptoms of skeletal muscle quality and function reduction of cancer patients after drug treatment, and has the effects of improving muscular tissue damage of the patients, improving exercise coordination and endurance of the patients and improving the curative effect of the patients. The exercise ability of the patient is enhanced, and the life quality of the cancer patient is improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of drugs and functional foods, and particularly relates to a composition for improving muscle atrophy caused by anti-tumor drugs and enhancing exercise performance, and its application. Background Art

[0002] Cancer is a major global public health problem. The widespread use of anti-tumor drugs is accompanied by potential side effects, such as liver and kidney damage, allergic reactions, gastrointestinal toxicity, neurotoxicity, etc. Muscle atrophy, as one of the most common side effects caused by anti-tumor drugs, can lead to a decline in muscle function and exercise ability of patients, and this symptom lasts for a long time. Some patients still do not improve after the end of treatment. The decline in exercise performance of cancer patients undergoing treatment is specifically reflected in the reduced willingness of patients to move independently and the weakness of exercise ability, which can significantly affect the daily life of patients in severe cases, interrupt treatment and shorten the survival cycle of patients. For muscle atrophy caused by anti-tumor drugs, effective intervention means are urgently needed.

[0003] The pathogenesis of anti-tumor drug-induced muscle atrophy has not been fully clarified. Physical exercise and nutritional support are mostly used to improve muscle atrophy and secondary adverse symptoms. For the symptoms of reduced exercise performance caused by anti-tumor drugs, it is clinically classified and intervened under cancer-related fatigue, and symptomatic support treatment is mostly used. Drug treatment mainly uses central stimulants (such as methylphenidate hydrochloride) and corticosteroids (such as dexamethasone). A number of studies have shown that such treatment methods have poor curative effects, and long-term use of central stimulants and corticosteroids has many adverse reactions, and sometimes it will accelerate the deterioration of the disease. Therefore, a treatment plan with better clinical effects and fewer side effects for the decline in exercise performance caused by muscle atrophy caused by anti-tumor drugs is needed.

[0004] At present, there is no special drug for improving muscle atrophy caused by anti-tumor drugs, or the drug formulations that include improving the fatigue of cancer patients within the treatment range are relatively complex, which limits their use for patients with reduced exercise performance under different pathological backgrounds; in addition, the processing methods of some functional products that improve the exercise performance of the body are complex and expensive, and they also cannot bring benefits to the majority of cancer patients. Summary of the Invention

[0005] Object of the Invention: Aiming at the problems existing in the prior art, the present invention provides a composition for improving muscle atrophy caused by anti-tumor drugs and enhancing exercise performance. The composition takes Dendrobium officinale, American ginseng, and Polygonatum sibiricum, which are both medicine and food, as the main body, and is supplemented by choline, an essential nutrient for the body. The formula is simple, and it has the effects of improving muscle tissue damage, enhancing the exercise function of patients, improving the coordination and endurance of patients' exercise, reducing muscle atrophy caused by drug treatment and enhancing exercise performance, and improving the quality of life of cancer patients.

[0006] The present invention also provides the use of the composition for improving muscle atrophy caused by anti-tumor drugs and enhancing exercise performance.

[0007] Technical solution: To achieve the above object, the present invention provides a composition for improving muscle atrophy caused by anti-tumor drugs and enhancing exercise performance, which comprises 6-30 parts by weight of Dendrobium officinale, 1-20 parts by weight of American ginseng, 1-20 parts by weight of Polygonatum sibiricum, and 0.1-1 part by weight of choline.

[0008] Among them, the composition comprises 6-10 parts by weight of Dendrobium officinale, 2-10 parts by weight of American ginseng, 2-10 parts by weight of Polygonatum sibiricum, and 0.5-1 part by weight of choline.

[0009] Among them, the composition comprises 6-10 parts by weight of Dendrobium officinale, 2-5 parts by weight of American ginseng, 2-5 parts by weight of Polygonatum sibiricum, and 1 part by weight of choline.

[0010] Preferably, the composition comprises 6 parts by weight of Dendrobium officinale, 2 parts by weight of American ginseng, 2 parts by weight of Polygonatum sibiricum, and 1 part by weight of choline.

[0011] The application of the composition of the present invention in the preparation of a pharmaceutical preparation, health food or functional food for improving muscle atrophy caused by anti-tumor drugs and enhancing exercise performance.

[0012] Among them, the pharmaceutical preparation is composed of the composition and pharmaceutically acceptable excipients or additives.

[0013] Among them, the pharmaceutical preparation is a granule, tablet, capsule, pill or oral liquid; the form of the health food or functional food is a compressed tablet candy, tea bag, instant tea or beverage.

[0014] Among them, the preparation method of the pharmaceutical preparation comprises the following steps:

[0015] (1) Drying the three medicinal materials of Dendrobium officinale, American ginseng, and Polygonatum sibiricum;

[0016] (2) Separately pulverizing the three medicinal materials, weighing them according to the weight ratio, and mixing them evenly;

[0017] (3) Adding ultrapure water, decocting and filtering, adding choline according to the weight ratio, and concentrating at low temperature to obtain a composition extract;

[0018] (4) Mixing the composition extract with excipients, granulating by wet method, sieving, drying and packaging to obtain a granule preparation of the traditional Chinese medicine compound composition.

[0019] Among them, in step (1), the three medicinal materials are dried at 55-65 °C for 5-6 h.

[0020] Among them, in step (2), the three medicinal materials are pulverized to a particle size of 1-2 mm.

[0021] Among them, in step (3), ultrapure water is added in a ratio of 1:20 - 30, decocted at 80 - 90 °C for 1 - 2 hours and then filtered; the low-temperature concentration is carried out at 50 - 60 °C until it becomes an extract.

[0022] Among them, the preparation method of the pharmaceutical preparation includes the following steps:

[0023] (1) Dry the three medicinal materials of Dendrobium officinale, American ginseng, and Polygonatum sibiricum.

[0024] (2) Crush the three medicinal materials separately, weigh them according to the weight ratio, and mix them evenly.

[0025] (3) Add ultrapure water, decoct, filter, concentrate, take the supernatant after centrifugation, and add choline to the supernatant to obtain the Shishenjing choline extract pharmaceutical preparation.

[0026] The details of the medicinal materials and nutrients selected in the present invention are as follows:

[0027] Dendrobium officinale is sweet in taste and slightly cold in nature, and belongs to the stomach and kidney meridians, with the effects of promoting the production of body fluid to quench thirst and nourishing yin to clear heat.

[0028] American ginseng is sweet in taste, slightly bitter and cool in nature, and belongs to the heart, lung, and kidney meridians, with the effects of replenishing qi and nourishing yin, clearing heat and promoting the production of body fluid.

[0029] Polygonatum sibiricum is sweet in taste and flat in nature, and belongs to the spleen, lung, and kidney meridians, with the effects of replenishing qi and nourishing yin, strengthening the spleen, moistening the lungs, and tonifying the kidneys.

[0030] Choline, a water-soluble nutrient similar to B vitamins, participates in various biochemical reaction processes in the body. Humans can synthesize a small amount of choline in the liver, but the amount is not enough to meet the body's nutritional needs and must be ingested from food and supplements.

[0031] The combination of Dendrobium officinale, American ginseng, Polygonatum sibiricum, and choline of the present invention can improve muscle atrophy caused by anti-tumor drugs and enhance exercise performance, with remarkable effects. In view of the symptoms that chemotherapy drugs and targeted drugs will exacerbate muscle tissue atrophy, lead to a decline in muscle function, and reduce the exercise performance of patients during the treatment of cancer, the present invention uses American ginseng for strengthening healthy qi and supplementing qi, Polygonatum sibiricum for nourishing yin, Dendrobium officinale for supplementing both qi and yin and regulating immune function, and choline, an essential nutrient for the body, for symptomatic treatment from multiple aspects, thus exerting remarkable curative effects. The combination has a simple compatibility and is suitable for large-scale industrial implementation; in addition, the three medicinal materials of Dendrobium officinale, American ginseng, and Polygonatum sibiricum all belong to the category of medicine and food homology, and better guarantee is obtained in terms of safety in use.

[0032] The composition of the present invention can be used to improve the symptoms of decreased skeletal muscle mass and function in cancer patients after drug treatment, and has the effects of improving muscle tissue damage in patients, enhancing the motor coordination and endurance of patients, strengthening the motor ability of patients, and improving the quality of life of cancer patients.

[0033] In fact, there is currently no therapeutic drug for the muscle atrophy symptoms caused by anti-tumor drugs, or the problem that the intervention means for muscle atrophy are not obvious. The present invention provides a drug combination to solve the muscle atrophy caused by anti-tumor drugs for the above problems.

[0034] The present invention adopts a combination of three medicaments of Dendrobium officinale, American ginseng, and ginseng, which are both medicine and food, and together with the essential choline nutrient in the body, makes the application scope of the composition wider, not limited to clinical drug preparations, and can also be eaten in daily life, facilitating the personalized treatment of muscle atrophy patients. The present invention breaks through the traditional experience of traditional Chinese medicine prescriptions, introduces nutritional supplementation as a guide, and on the basis of the three medicinal materials of Dendrobium officinale, American ginseng, and polygonatum sibiricum, plus the nutrient choline, can better improve muscle atrophy.

[0035] The present invention for the first time provides the combination of four ingredients of Dendrobium officinale, American ginseng, polygonatum sibiricum, and choline and their component ratios, and for the first time discovers that this composition can improve muscle atrophy, especially the muscle atrophy symptoms caused by anti-tumor drugs.

[0036] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0037] The present invention for the first time ingeniously combines four medicaments of Dendrobium officinale, American ginseng, polygonatum sibiricum, and choline to supplement qi and nourish yin, can improve the body's nutritional status, improve the symptoms of muscle tissue damage after anti-tumor drug treatment, resist muscle atrophy and improve motor performance. In an animal model, this composition can significantly inhibit the muscle fiber atrophy induced by 5-fluorouracil and anlotinib, enhance the grip strength of mice and improve the motor ability of mice, and its effect is better than that of the positive drug. The three medicinal materials of Dendrobium officinale, American ginseng, and polygonatum sibiricum are both medicine and food and have high safety; while choline is included in the "List of Nutritional Supplements for Health Food Ingredients (2023 Edition)" issued by the State Administration for Market Regulation, the National Health Commission, and the National Administration of Traditional Chinese Medicine, and can be promoted in the daily diet of cancer patients. Further, the present invention discloses the preparation method of the composition of Dendrobium officinale, American ginseng, polygonatum sibiricum, and choline, and this method can improve the dissolution rate of the effective substances of the composition and enhance the therapeutic effect of the composition. Description of the Drawings

[0038] Figure 1 H&E staining of the gastrocnemius muscle of the hindlimb of mice, 200×; a: blank control group, b: 5-fluorouracil group, c: Dendrobium officinale group, d: American ginseng group, e: polygonatum sibiricum group, f: choline group, g: Shishenjing choline group;

[0039] Figure 2 is the cross-sectional area of the gastrocnemius muscle fibers in the hindlimbs of mice; *: p < 0.05; **: p < 0.01; ***: p < 0.001; ****: p < 0.0001;

[0040] Figure 3 is the H&E staining of the gastrocnemius muscle in the hindlimbs of mice, 200×; a: blank control group, b: 5-fluorouracil group, c: methylphenidate hydrochloride group, d: 1.5 g / kg Shishen Jingdan group, e: 4.5 g / kg Shishen Jingdan group, f: 13.5 g / kg Shishen Jingdan group;

[0041] Figure 4 is the cross-sectional area of the gastrocnemius muscle fibers in the hindlimbs of mice; compared with the 5-fluorouracil group, *: p < 0.05; **: p < 0.01; ***: p < 0.001; ****: p < 0.0001; compared with the methylphenidate hydrochloride group, #: p < 0.05; ##: p < 0.01; : p < 0.001; #: p < 0.0001; the same below;

[0042] Figure 5 is the activity of creatine kinase in the serum of mice;

[0043] Figure 6 is the body weight growth curve of mice;

[0044] Figure 7 is the change value of body weight between D28 and D38 (before and after modeling) in mice;

[0045] Figure 8 is the grip strength change curve of mice;

[0046] Figure 9 is the grip strength difference of mice at D38;

[0047] Figure 10 is the total distance of movement of mice in the open field test;

[0048] Figure 11 is the time that mice persisted on the rotating rod in the fatigue rotating rod test (12 r / min, 180 s);

[0049] Figure 12 is the H&E staining of the gastrocnemius muscle in the hindlimbs of mice, 200×; a: blank control group, b: anlotinib group, c: methylphenidate hydrochloride group, d: 1.5 g / kg Shishen Jingdan group, e: 4.5 g / kg Shishen Jingdan group, f: 13.5 g / kg Shishen Jingdan group;

[0050] Figure 13is the cross-sectional area of the gastrocnemius muscle fibers in the hindlimbs of mice; compared with the anlotinib group, *: p < 0.05; **: p < 0.01; ***: p < 0.001; ****: p < 0.0001; compared with the methylphenidate hydrochloride group, #: p < 0.05; ##: p < 0.01; : p < 0.001; #: p < 0.0001; the same below;

[0051] Figure 14 is the activity of creatine kinase in the serum of mice;

[0052] Figure 15 is the body weight growth curve of mice;

[0053] Figure 16 is the body weight difference of mice at D28;

[0054] Figure 17 is the grip strength difference of mice at D28;

[0055] Figure 18 is the total distance of mice moving in the open field test;

[0056] Figure 19 is the time that mice persisted on the rotating rod in the fatigue rotating rod test (20 r / min, 900 s). Detailed implementation manners

[0057] The present invention will be further described below in conjunction with the embodiments and the drawings.

[0058] The experimental methods described in the embodiments are all conventional methods unless otherwise specified; the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0059] Embodiment 1

[0060] Preparation method of Shishenjing choline composition granules

[0061] By weight, Dendrobium officinale, American ginseng, Polygonatum sibiricum, and choline are 6 parts, 2 parts, 2 parts, and 1 part.

[0062] Dry the three medicinal materials of Dendrobium officinale, American ginseng, and Polygonatum sibiricum in an environment of 60 °C for 6 hours; crush the dried medicinal materials into granular form respectively, with a particle size of about 1 mm; weigh Dendrobium officinale powder, American ginseng powder, and Polygonatum sibiricum powder in a ratio of 6:2:2 by weight, mix them evenly, add 20 times the volume of ultrapure water (1 g of medicinal material corresponds to 1 mL of water), decoct at 80 °C for 2 h, filter, add 20 times the volume of ultrapure water to the filter residue, decoct at 80 °C for 2 h, filter, and combine the two filtrates; add 1 part of choline to the combined filtrate, mix well, then concentrate at 60 °C to an extract state, granulate by wet method, dry after sieving, and package to obtain Shishenjing choline composition granules.

[0063] Embodiment 2

[0064] Preparation method of composition (Shishenjing choline) extract

[0065] Dry three medicinal materials of Dendrobium officinale, American ginseng, and Polygonatum sibiricum in an environment of 60°C for 6 hours; crush the dried medicinal materials into granular form respectively, with a particle size of about 1 mm; weigh 30 g of crushed Dendrobium officinale powder, 10 g of American ginseng powder, and 10 g of Polygonatum sibiricum powder respectively, mix well, add 500 mL of ultrapure water according to a mass ratio of 1:10, and let stand for 30 min; then add 500 mL of ultrapure water to make the final ratio of drug to water 1:20; decoct at a water temperature of 80°C for 2 hours; filter and concentrate to a liquid medicine concentration of 0.125 g / mL, which is the Shishenjing extract; then set the rotation speed at 6000 rpm, centrifuge for 10 min to obtain the supernatant, and add 5 g of choline to the supernatant to obtain the composition Shishenjing choline extract.

[0066] Example 3

[0067] Pharmacodynamic comparison of Shishenjing choline composition (Shishenjing choline extract prepared in Example 2) and each single ingredient in improving chemotherapy drug-induced muscle atrophy

[0068] Use the method of multiple strikes with 5-fluorouracil to construct a chemotherapy drug-induced muscle atrophy model. Administer the composition extract in Example 2 to the medium-dose Shishenjing choline group (4.5 g / kg + 150 mg / kg), where 4.5 g / kg refers to the supernatant and 150 mg / kg refers to choline. The administration doses of the extract of each single traditional Chinese medicine ingredient are Dendrobium officinale (2.7 g / kg), American ginseng (0.9 g / kg), and Polygonatum sibiricum (0.9 g / kg). The preparation of the extract of each single traditional Chinese medicine ingredient is the same as in Example 2, and the concentration of the choline aqueous solution is 150 mg / kg. After pre-administering for 14 days, construct a muscle atrophy model caused by chemotherapy drugs, and evaluate the degree of muscle tissue damage at the end point of the model to evaluate the effects of Shishenjing choline composition and each single ingredient in improving chemotherapy drug-induced muscle atrophy.

[0069] Experimental animals: SPF-grade male C57BL / 6 mice, 6 weeks old, weighing 18 - 20 g, 56 in number, purchased from Jiangsu Jicui Yakang Biotechnology Co., Ltd.

[0070] Experimental grouping: There were 8 mice in the blank control group, and the remaining 48 mice were used to establish a muscle atrophy model induced by the chemotherapeutic drug 5-fluorouracil to evaluate the efficacy of the Shishenjing choline composition and each single ingredient. Among them, there were 8 mice in the model group, 8 mice in the Dendrobium officinale group (2.7 g / kg), 8 mice in the American ginseng group (0.9 g / kg), 8 mice in the Polygonatum sibiricum group (0.9 g / kg), 8 mice in the choline group (150 mg / kg), and 8 mice in the Shishenjing choline group (4.5 g / kg + 150 mg / kg). After pre-administering the Shishenjing choline composition and each single ingredient by drinking water for 14 days, on the 15th day, 5-fluorouracil was intraperitoneally injected to establish a chemotherapeutic drug-induced muscle atrophy model at a dose of 75 mg / kg, once every 3 days for a total of 3 times, and the model was terminated on the 25th day.

[0071] Drug preparation: The average daily water intake of mice is about 5 mL. Calculated based on a mouse weight of 20 g, the concentrations of Dendrobium officinale, American ginseng, and Polygonatum sibiricum in the drinking water of the Shishenjing choline group are C M = 18 mg / mL. Take the Shishenjing extract in Example 2, dilute it to the corresponding concentration with ultrapure water, and then add choline chloride (one form of choline supplementation) to the solution to make the concentration of choline chloride 0.8 mg / mL for administration by drinking water.

[0072] For the Dendrobium officinale group, American ginseng group, and Polygonatum sibiricum group, the drinking water concentrations are 10.8 mg / mL, 3.6 mg / mL, and 3.6 mg / mL respectively. The preparation method is the same as the preparation method of the Shishenjing extract in Example 2; the choline supplementation form is calculated based on choline chloride (molecular weight 139.63). The daily choline (molecular weight 104.17) intake of mice is calculated at 150 mg / kg, and the concentration of the choline solution should be 0.6 mg / ml, so choline chloride is prepared into a 0.8 mg / ml solution.

[0073] 5-Fluorouracil: Prepare a solution with a concentration of 7.5 mg / mL using normal saline.

[0074] Observation indicators: At the end of the model, the mice were sacrificed by cervical dislocation, and the gastrocnemius muscle tissues of the hindlimbs of the mice were separated and fixed in 4% paraformaldehyde for H&E staining to observe muscle tissue damage.

[0075] Experimental results: The results of H&E staining and the statistical results of muscle fiber cross-sectional area showed that compared with the blank control group, the muscle fiber cross-sectional area of the 5-fluorouracil group mice was significantly reduced, and obvious muscle atrophy occurred ( Figure 3 ); the muscle fiber cross-sectional area of the Shishenjing choline composition and each single ingredient was significantly increased compared with the 5-fluorouracil group mice. Among them, the Shishenjing choline group had the most obvious improvement effect on chemotherapeutic drug-induced muscle atrophy, and there was a significant difference compared with each single ingredient ( Figure 2 ).

[0076] Example 4

[0077] Efficacy verification of the Shishenjing choline composition extract (the Shishenjing choline extract prepared in Example 2) in improving chemotherapy drug-induced muscle atrophy and enhancing motor performance

[0078] A chemotherapy drug-induced muscle atrophy model was constructed by the method of multiple strikes with 5-fluorouracil. The composition extract in Example 2 was given at gradient doses. After 28 days of pre-administration, a muscle atrophy model induced by chemotherapy drugs was constructed. Methylphenidate hydrochloride (a central nervous system stimulant) was selected as the positive control drug. At the end point of the model, the degree of muscle tissue damage was investigated and evaluated, and the changes in mouse body weight, mouse grip strength, willingness for spontaneous activity, motor coordination and endurance were statistically analyzed to evaluate the effect of the composition in improving chemotherapy drug-induced muscle atrophy and enhancing motor performance.

[0079] Experimental animals: SPF-grade male C57BL / 6 mice, 5 weeks old, weighing 18 - 20 g, 48 in number, purchased from Shanghai SLAC Laboratory Animal Co., Ltd.

[0080] Experimental grouping: 8 mice in the blank control group, and the remaining 40 mice were used to construct a muscle atrophy model induced by the chemotherapy drug 5-fluorouracil to observe the pharmacodynamic effect of the Shishenjing choline composition. Among them, there were 8 mice in the model group, 8 mice in the low-dose Shishenjing choline group (1.5 g / kg + 150 mg / kg). Specifically, the composition extract was used, where 1.5 g / kg refers to the supernatant and 150 mg / kg refers to choline. There were 8 mice in the medium-dose Shishenjing choline group (4.5 g / kg + 150 mg / kg), 8 mice in the high-dose Shishenjing group (13.5 g / kg + 150 mg / kg), and 8 mice in the methylphenidate hydrochloride group (3 mg / kg). After 28 days of pre-administration of the low, medium, and high-dose Shishenjing choline composition extracts, on the 29th day, a muscle atrophy model induced by chemotherapy drugs was constructed by intraperitoneal injection of 5-fluorouracil at a dose of 75 mg / kg, once every 3 days for a total of 3 times, and the model was terminated on the 38th day. Methylphenidate hydrochloride was administered by gavage on the 29th day for 10 consecutive days.

[0081] Drug preparation: According to the literature review and previous research results, the average daily water intake of mice is about 5 mL. Calculated based on a mouse body weight of 20 g, the high concentration C H = 54 mg / mL, medium concentration C M = 18 mg / mL, and low concentration C L = 6 mg / mL of Dendrobium officinale, American ginseng, and Polygonatum sibiricum in the Shishenjing choline composition in the drinking water of mice. The Shishenjing extract in Example 2 was taken and diluted to the corresponding concentration with ultrapure water, and then choline chloride (one of the choline supplementation forms) was added to the solution to make the concentration of choline chloride 0.8 mg / mL, and it was administered by drinking water.

[0082] 5-Fluorouracil: Prepare a solution with a concentration of 7.5 mg / mL using normal saline; Methylphenidate Hydrochloride: Prepare a solution with a concentration of 0.3 mg / mL using normal saline.

[0083] Observation indicators: ① Record the body weight of mice on days 0, 7, 14, 21, 28, 30, 32, 34, 36, and 38; ② Conduct grip strength tests on mice in each group on days 0, 7, 14, 21, 28, 32, 36, and 38; ③ On day 38, terminate the model, conduct an open field test on mice in each group, observe the spontaneous activity trajectories of mice, and record the total distance traveled by mice within 300 seconds; ④ On day 38, conduct a fatigue rotarod test on mice, with the rotarod speed at 12 r / min, observe and record the time of mice on the rod (180 seconds as the termination time); ⑤ After the rotarod test, collect blood from the orbital cavities of mice in each group. After standing at room temperature for 1 hour, centrifuge at 3000 rpm for 10 minutes, and collect the serum for detecting creatine kinase activity; ⑥ After collecting blood from the orbital cavities of mice, decapitate and sacrifice the mice, separate the gastrocnemius muscle tissue of the hind limbs of mice, fix it in 4% paraformaldehyde, and use it for H&E staining to observe muscle tissue damage.

[0084] Experimental results: ① The results of H&E staining and the statistical analysis of the cross-sectional area of muscle fibers showed that compared with the blank control group, the cross-sectional area of muscle fibers in the 5-fluorouracil group of mice was significantly reduced, and obvious atrophy occurred in the muscle tissue; the cross-sectional area of muscle fibers in the mice in the Shishen Jingdan composition administration group was significantly larger than that in the 5-fluorouracil group of mice, effectively improving chemotherapy drug-induced muscle atrophy ( Figure 1 、 Figure 4 ). ② The results of detecting the serum creatine kinase levels in each group of mice showed that the activity of serum creatine kinase in the 5-fluorouracil group of mice increased significantly, and the muscle tissue was severely damaged; administering the Shishen Jingdan composition could reduce the activity level of serum creatine kinase and improve muscle tissue damage, and the effect in the high-dose group of Shishen Jingdan composition was the most significant ( Figure 9 ). ③ Compared with the blank control group, the body weight of mice in the 5-fluorouracil group decreased significantly after modeling. After administering the extract of the Shishen Jingdan composition, the loss of body weight in mice was improved, and the reversal effect of the high-dose group of the Shishen Jingdan composition on body weight loss in mice was the most significant, and the effect was better than that of the methylphenidate hydrochloride group ( Figure 7 、 Figure 8 ). ④ Compared with the blank control group, the grip strength of mice in the 5-fluorouracil group decreased significantly at the end point of the model. The grip strength of mice in the medium-dose and high-dose groups of the Shishen Jingdan composition was significantly higher than that in the 5-fluorouracil group of mice, and the effect was better than that of the methylphenidate hydrochloride group ( Figure 5 、 Figure 6)。⑤The results of the open field test showed that, compared with the blank control group, the movement distance of the mice in the 5-fluorouracil group was significantly shortened in the open field, the willingness to move decreased, and the motor ability declined; while the performance of the mice in the high-dose group of the Shishenjing choline composition was significantly improved, and the movement distance was significantly increased compared with that of the 5-fluorouracil group mice( Figure 10 )。⑥Compared with the blank control group, the time that the mice in the 5-fluorouracil group persisted on the rotating rod was significantly reduced, and the motor coordination ability decreased; after administration of the Shishenjing choline composition, the time of the mice on the rod was significantly prolonged, and the high-dose group of the Shishenjing choline composition had the best effect( Figure 11 )。

[0085] Example 5

[0086] Efficacy verification of the Shishenjing choline composition extract (the Shishenjing choline extract prepared in Example 2) in improving targeted drug-induced muscle atrophy and enhancing motor performance

[0087] Based on the method of continuously administering the targeted drug anlotinib for 14 days, a targeted drug-induced muscle atrophy model was constructed. Gradient doses of the composition extract in Example 2 were administered. After 14 days of pre-administration, 5 mg / kg anlotinib was continuously administered by gavage for 14 days to construct a targeted drug-induced muscle atrophy model. Methylphenidate hydrochloride (a central nervous system stimulant) was selected as the positive control drug. At the end of the model, the degree of muscle tissue damage was investigated and evaluated, and the body weight change, grip strength change, voluntary activity willingness, motor coordination and endurance of the mice were statistically analyzed to evaluate the efficacy of the composition in improving targeted drug-induced muscle atrophy and enhancing motor performance.

[0088] Experimental animals: SPF-grade male C57BL / 6 mice, 5 weeks old, weighing 18-20 g, 48 in number, purchased from Shanghai Slack Experimental Animal Co., Ltd.

[0089] Experimental grouping: 8 mice in the blank control group, and the remaining 40 mice were used to construct a muscle atrophy model induced by the targeted drug anlotinib to investigate the efficacy of the Shishenjing choline composition. Among them, there were 8 mice in the model group, 8 mice in the low-dose group of Shishenjing choline (1.5 g / kg + 150 mg / kg), specifically the composition extract was used, where 1.5 g / kg refers to the supernatant and 150 mg / kg refers to choline, 8 mice in the middle-dose group of Shishenjing choline (4.5 g / kg + 150 mg / kg), 8 mice in the high-dose group of Shishenjing (13.5 g / kg + 150 mg / kg), and 8 mice in the methylphenidate hydrochloride group (3 mg / kg). After 14 days of pre-administration of the low, middle and high-dose groups of the Shishenjing choline composition extract, 5 mg / kg anlotinib was administered by gavage on the 15th day until the 28th day to construct a targeted drug-induced muscle atrophy model. Methylphenidate hydrochloride was administered by gavage on the 15th day for 14 days.

[0090] Drug preparation: The preparation methods of the compound of Shishenjing choline and the positive drug methylphenidate hydrochloride are the same as those in Example 4. Anlotinib hydrochloride is prepared into a solution with a concentration of 0.5 mg / mL using normal saline.

[0091] Observation indicators: ① Record the body weight of mice on days 0, 3, 7, 10, 14, 17, 21, 24, and 28; ② Conduct a grip strength test on day 28; ③ On day 29, the model was terminated, and an open field test was performed on each group of mice to observe the spontaneous activity trajectory of the mice and record the total distance traveled by the mice within 300 seconds; ④ On day 29, a fatigue rotarod test was performed on the mice at a rotarod speed of 20 r / min, and the time the mice stayed on the rod was observed and recorded (900 seconds was the termination time); ⑤ After the rotarod test, blood was taken from the orbital cavities of each group of mice. After standing at room temperature for 1 hour, centrifuged at 3000 rpm for 10 minutes, and the serum was collected for detecting the activity of creatine kinase; ⑥ After taking blood from the orbital cavities of the mice, the mice were sacrificed by cervical dislocation, and the gastrocnemius muscle tissue of the hind limbs of the mice was separated and fixed in 4% paraformaldehyde for H&E staining to observe muscle tissue damage.

[0092] Experimental results: ① The results of H&E staining and the statistical results of the cross-sectional area of muscle fibers showed that compared with the blank control group, the cross-sectional area of muscle fibers in the anlotinib group of mice was significantly reduced, and obvious atrophy occurred in the muscle tissue; the cross-sectional area of muscle fibers in the mice in the Shishenjing choline composition administration group was increased compared with that in the anlotinib group of mice, effectively improving the muscle atrophy induced by the targeted drug ( Figure 12 、 Figure 13 ). ② The results of detecting the serum creatine kinase levels in each group of mice showed that the activity of serum creatine kinase in the anlotinib group of mice increased significantly, and the muscle tissue damage was severe; administering the Shishenjing choline composition could reduce the activity level of serum creatine kinase and improve muscle tissue damage, and the effect was most significant in the high-dose group of Shishenjing choline ( Figure 14 ). ③ Compared with the blank control group, the weight gain of the mice in the anlotinib group was significantly slowed down after modeling. After administering the extract of the Shishenjing choline composition, the weight gain of the mice was improved, and the promoting effect of the high-dose group of the Shishenjing choline composition on the weight gain of the mice was the most significant, and the effect was better than that of the methylphenidate hydrochloride group ( Figure 15 、 Figure 16 ). ④ Compared with the blank control group, the grip strength of the mice in the anlotinib group decreased significantly at the end point of the model. The grip strength of the mice in the medium-dose and high-dose groups of the Shishenjing choline composition was significantly improved compared with that in the anlotinib group of mice, and the effect was better than that of the methylphenidate hydrochloride group ( Figure 17 ). ⑤ The results of the open field test showed that compared with the blank control group, the movement distance of the mice in the anlotinib group in the open field was significantly shortened, the willingness to move decreased, and the motor ability decreased; while the performance of the mice in the medium-dose and high-dose groups of the Shishenjing choline composition in the open field test was significantly improved, and the movement distance was significantly increased compared with that of the mice in the anlotinib group ( Figure 18)。⑥Compared with the blank control group, the time that the mice in the anlotinib group persisted on the rotarod was significantly reduced, and their motor coordination ability decreased; after administration of the Shishen Jing choline composition, the time that the mice stayed on the rod increased significantly, and the medium and high dose groups of the Shishen Jing choline composition had the best effects( Figure 19 )。

[0093] In summary, the Dendrobium officinale, American ginseng, Polygonatum sibiricum, and choline composition provided by the present invention can improve muscle atrophy caused by anti-tumor drug treatment and lead to symptoms of decreased motor performance, has the effects of improving muscle tissue damage, enhancing the coordination and endurance of patients' movements, strengthening the motor function of patients, and improving the quality of life of cancer patients.

Claims

1. A composition for improving muscle atrophy caused by anti-tumor drugs and improving athletic performance, characterized in that: The composition comprises 6-30 parts of dendrobium officinale, 1-20 parts of American ginseng, 1-20 parts of polygonatum sibiricum and 0.1-1 part of choline by weight.

2. The composition for improving muscle atrophy caused by anti-tumor drugs and improving athletic performance according to claim 1, characterized in that: The composition comprises 6-10 parts of dendrobium officinale, 2-10 parts of American ginseng, 2-10 parts of polygonatum sibiricum and 0.5-1 part of choline.

3. The composition for improving muscle atrophy caused by anti-tumor drugs and improving athletic performance according to claim 1, characterized in that: The composition preferably comprises 6-10 parts of Dendrobium officinale, 2-5 parts of American ginseng, 2-5 parts of Polygonatum sibiricum and 1 part of choline.

4. Use of the composition according to any of claims 1 to 3 in the preparation of a pharmaceutical preparation, health food or functional food for improving muscle atrophy caused by anti-tumor drugs and improving athletic performance.

5. The use according to claim 4, characterized in that: The pharmaceutical preparation comprises the composition and pharmaceutically acceptable excipients or additives.

6. The use according to claim 4, characterized in that: The pharmaceutical preparation is in the form of granules, tablets, capsules, pills or oral liquids; the health food or functional food is in the form of compressed candy, tea bags, instant tea or beverages.

7. The use according to claim 6, characterized in that: The preparation method of the pharmaceutical preparation comprises the following steps: (1) Drying three medicinal materials: Dendrobium candidum, American ginseng, and Polygonatum sibiricum; (2) Grind the three medicinal materials separately, weigh them according to their weight ratio, and mix them evenly; (3) adding ultrapure water, boiling and filtering, adding choline according to weight proportion, and concentrating at low temperature to obtain a composite extract; (4) The extract of the composition is mixed with auxiliary materials, granulated by wet method, sieved, dried and packaged to obtain the granular preparation of the Chinese medicine compound composition.

8. The use according to claim 7, characterized in that: The three medicinal materials in step (1) are dried at 55-65° C. for 5-6 hours.

9. The use according to claim 7, characterized in that: In step (3), ultrapure water is added at a ratio of 1:20-30, and the mixture is boiled at 80-90° C. for 1-2 hours and then filtered; and the low-temperature concentration is concentrated at 50-60° C. to an extract.

10. The use according to claim 6, characterized in that: The preparation method of the pharmaceutical preparation comprises the following steps: (1) Drying three medicinal materials: Dendrobium candidum, American ginseng, and Polygonatum sibiricum; (2) Grind the three medicinal materials separately, weigh them according to their weight ratio, and mix them evenly; (3) adding ultrapure water, decocting, filtering, concentrating, and taking the supernatant after centrifugation, and adding choline to the supernatant to obtain the choline extract of Glehnia littoralis.

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