Traditional Chinese medicine preparation for treating chronic fatigue syndrome

Abstract

The invention discloses a traditional Chinese medicine preparation for treating chronic fatigue syndrome, which is prepared from the following raw material medicines in parts by mass: 10-15 parts of prepared rehmannia root, 12-25 parts of radix pseudostellariae, 6-12 parts of bighead atractylodes rhizome, 6-15 parts of oriental wormwood, 3-10 parts of fingered citron, 3-10 parts of platycladi seed and pharmaceutically acceptable auxiliary materials, and is prepared into water decoction, decocted extract, pills, granules, tablets, capsules or oral liquid. The traditional Chinese medicine preparation makes up the deficiency limitation of current chronic fatigue syndrome medicines and non-medicine treatment to a certain extent, can improve the symptoms of patients to a certain extent, is safe to take, does not have obvious toxic or side effects, and is worthy of clinical popularization and application.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine preparation for treating chronic fatigue syndrome. BACKGROUND

[0002] Chronic fatigue syndrome (CFS) is a common systemic syndrome in the modern high-pace and high-pressure social environment, with persistent and difficult-to-relieve fatigue as the core feature, often accompanied by multiple system dysfunction. The pathogenesis of the disease is complex, involving the interaction of genetic susceptibility, environmental factors, pathogen infection, immune dysfunction and neuroendocrine regulation imbalance. Patients have diverse clinical manifestations, such as decreased neurological function (e.g., memory loss, lack of concentration), reduced exercise tolerance, digestive dysfunction, urinary abnormalities and sensory hypersensitivity, etc., showing long-term mental and physical debilitation, which cannot be effectively improved after rest. It is worth noting that although CFS patients have obvious complaints, routine physical examination and laboratory indicators are often not specific, which brings certain difficulties to the clinical diagnosis.

[0003] In modern society, especially among young people, the risk of CFS is significantly increasing. Fast-paced work and lifestyle, continuous psychological stress, and unhealthy eating habits such as caffeine beverages further exacerbate the body's sub-health state. Currently, patients often rely on physical therapies such as massage and acupuncture to relieve fatigue, but such methods often have slow effects, limited efficacy, and are prone to psychological dependence, making it difficult to fundamentally improve the condition.

[0004] According to epidemiological investigations, the global prevalence of CFS is about 0.89%, with a peak age of 30-50 years old, and the incidence is increasing year by year. Although China has not established a national CFS epidemiological database, regional studies suggest that the prevalence of the disease in China is gradually expanding, and it has become an important public health problem. CFS not only seriously affects the quality of life of patients, but also leads to decreased work efficiency, weakened social participation, and may induce emotional disorders, increasing the individual and social medical burden. The U.S. Centers for Disease Control and Prevention (CDC) has listed it as one of the diseases that may pose a major challenge to human health in the 21st century.

[0005] Currently, the treatment of CFS in Western medicine is mainly symptomatic support, and there is a lack of radical means. For example, fludrocortisone, beta-blockers and the like are used to improve orthostatic intolerance; trazodone, benzodiazepines and the like are used to relieve sleep disorders; modafinil and the like are used as central stimulants for cognitive function improvement; gabapentin, duloxetine and the like are used to control pain symptoms; and rifaximin and the like are used to regulate intestinal microecology. Although the above-mentioned drugs can alleviate certain symptoms to a certain extent, they all have different degrees of side effects, poor treatment compliance, and are prone to disease recurrence, and lack of systematic and individualized comprehensive management strategies.

[0006] Although traditional Chinese medicine does not have the disease name of "chronic fatigue syndrome", it has a systematic understanding and rich discussion of the symptoms related to "fatigue". There are many descriptions such as "lazy", "sleeping", "limbs do not want to move" and the like in Huangdi Neijing, which points out that "prolonged vision damages blood, prolonged lying damages qi, prolonged sitting damages flesh, prolonged standing damages bones, and prolonged walking damages tendons, which is called five labor injuries" (Suwen Xuanming Wugi Chapter), emphasizing that excessive fatigue can damage the functions of five zang organs. The Labor Injury is further classified in Yi Jia Si Yao Yi Liao Lun as follows: "operating the mechanism of the spirit will cause mental fatigue, exhausting the mind will cause liver fatigue, unexpected overthinking will cause spleen fatigue, worrying about future events will cause lung fatigue, and excessive desire for color will cause kidney fatigue". In addition, external invasion of six evils is also a pathogenic factor, as Wu Cheng of the Qing Dynasty said in "Buju Ji": "The symptoms of deficiency and damage are not only caused by internal injury, but also by external invasion", thinking that wind, cold, heat, dampness, dryness and fire can all cause deficiency and labor. Therefore, the pathogenesis of CFS in traditional Chinese medicine can be summarized as deficiency of zang-fu and blood, dysfunction, combined with phlegm and blood stasis, and real evil such as fire, forming a complex syndrome of deficiency and excess.

[0007] Under the current medical background, fully exerting the advantages of overall regulation and multi-target intervention of traditional Chinese medicine, developing safe and effective traditional Chinese medicine preparations for chronic fatigue syndrome has important clinical significance for improving the clinical symptoms of patients, preventing serious complications such as cardiovascular and cerebrovascular events, and improving the overall quality of life. SUMMARY

[0008] The technical problem to be solved by the present application is to provide a traditional Chinese medicine preparation for treating chronic fatigue syndrome, which can to some extent make up for the deficiency that the current clinical application of chronic fatigue syndrome drugs and non-drug treatment is limited.

[0009] In order to solve the above technical problems, the technical scheme adopted by the present application is: a traditional Chinese medicine preparation for treating chronic fatigue syndrome is prepared from the following raw materials in parts by mass: radix rehmanniae preparata 10-15 parts, radix pseudostellariae 12-25 parts, atractylodes 6-12 parts, artemisia 6-15 parts, bergamot 3-10 parts, and platycladus 3-10 parts.

[0010] Preferably, it is prepared from the following raw materials in parts by mass: radix rehmanniae preparata 15 parts, radix pseudostellariae 15 parts, atractylodes 12 parts, artemisia 15 parts, bergamot 10 parts, and platycladus 10 parts.

[0011] The Chinese medicine preparation for treating chronic fatigue syndrome also comprises pharmaceutically acceptable adjuvants, and is prepared into water decoction, decoction, pill, granule, tablet, capsule or oral liquid.

[0012] The Chinese medicine preparation for treating chronic fatigue syndrome has the advantages of making up for the deficiency of current chronic fatigue syndrome drugs and non-drug treatment, which are limited in clinical application due to adverse reactions or complications, improving the clinical symptoms of patients to a certain extent, being safe in taking, having no obvious toxic side effects, and being worthy of clinical popularization and application. BRIEF DESCRIPTION OF DRAWINGS

[0013] Figure 1 is a statistical chart of total movement distance and target quadrant distance of chronic fatigue syndrome rats ## P <0.01 vs. blank control group; ** P <0.01 vs. model group; n=5).

[0014] Figure 2 is a statistical chart of exhaustive swimming time of chronic fatigue syndrome rats ## P <0.01 vs. blank control group; ** P <0.01 vs. model group; n=5).

[0015] Figure 3 is a statistical chart of myocardial injury markers of chronic fatigue syndrome rats ## P <0.01 vs. blank control group; ** P <0.01 vs. model group; n=5).

[0016] Figure 4 is an immunohistochemical chart of chronic fatigue syndrome rats. DETAILED DESCRIPTION

[0017] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the embodiments of the present application; obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments of the present application, and all other embodiments obtained by those skilled in the art without creative labor on the basis of the embodiments in the present application belong to the protection scope of the present application.

[0018] The Chinese medicine preparation for treating chronic fatigue syndrome comprises the following raw materials in mass fraction: Radix Rehmanniae Preparata 10-15 parts, Radix Pseudostellariae 12-25 parts, Rhizoma Atractylodis Macrocephalae 6-12 parts, Herba Artemisiae Scopariae 6-15 parts, Citrus Bergamia 3-10 parts, and Semen Platycladi 3-10 parts.

[0019] Preferably, the raw materials are prepared in the following mass fractions: Radix Rehmanniae Preparata 15 parts, Radix Pseudostellariae 15 parts, Rhizoma Atractylodis Macrocephalae 12 parts, Herba Artemisiae Scopariae 15 parts, Fructus Citri Medicae 10 parts, Semen Platycladi 10 parts.

[0020] The traditional Chinese medicine preparation for treating chronic fatigue syndrome also comprises a pharmaceutically acceptable excipient, and is prepared into a decoction, a decocted paste, a pill, a granule, a tablet, a capsule or an oral liquid.

[0021] The method of taking is as follows: 2-3 times a day, among which the decoction and the decocted paste are taken 2 times a day, in the morning and evening on an empty stomach; the pill, the granule, the tablet, the capsule and the oral liquid are taken 3 times a day, half an hour after breakfast, lunch and dinner. The course of treatment is at least one week. During the medication, it is forbidden to drink strong tea and to eat cold, spicy and stimulating food.

[0022] The traditional Chinese medicine used in the application is as follows: Radix Rehmanniae Preparata: sweet, slightly warm, and belongs to the heart, liver and kidney channels. It has the effects of tonifying blood and nourishing yin. Zhang Jiebin said in "Ben Cao Zheng": "Radix Rehmanniae Preparata is flat and pure, so it can tonify the true yin of five zang organs, and is most important for the blood-rich organs. It is not a spleen and stomach channel medicine, and it is the reason why human beings have blood, that is, qi and blood." Modern pharmacological research has found that there are about 70 kinds of single compounds in Radix Rehmanniae Preparata, including iridoid, monoterpene, glycoside, glucose, galactose, fructose, amino acid, organic acid and trace element, etc., most of which are terpenoids, such as catalpol, dihydroxyphenyl ethanol, and other polysaccharides, radix rehmanniae glycoside D and mullein glycoside.

[0023] Radix Pseudostellariae: sweet and slightly bitter, flat, and belongs to the spleen and lung channels. It has the effects of benefiting qi and invigorating the spleen, producing saliva and moistening the lung. Its anti-fatigue effect is closely related to the regulation of energy metabolism, and the polysaccharides in Radix Pseudostellariae can promote the utilization of energy in the body by regulating the signal pathways closely related to energy metabolism such as PI3K / Akt and AMPK / PGC-1α, thereby improving exercise endurance and anti-fatigue ability. Research has also confirmed that Radix Pseudostellariae has immune regulation activity, and its polysaccharides and saponins can help to consolidate the body's immunity, and has an improving effect on the low immune function commonly seen in CFS patients. It is worth noting that the tonic medicine like Radix Pseudostellariae is widely used in the treatment of CFS, and its effect of "invigorating the spleen and benefiting qi" is in line with the core pathogenesis of CFS, which is deficiency in the root and excess in the branches, and can fundamentally supplement energy and improve the source of qi and blood.

[0024] Baizhu: sweet, bitter, warm, spleen, stomach meridian. Effect of spleen and qi, dry wet water. Baizhu contains sesquiterpenes (such as atractylenolide I, II, III), polyacetylene and polysaccharides and other ingredients. Studies have shown that atractylenolide I and polyacetylene compounds can effectively inhibit TNF-α, IL-6 and other inflammatory factors, and block the TLR4 / NF-κB inflammatory pathway. In addition, Baizhu can also improve the overall energy metabolism of the body by activating key enzymes of energy metabolism, providing a material basis for relieving the fatigue symptoms of CFS from the "spleen and stomach".

[0025] Yinchen: bitter, pungent, slightly cold, spleen, stomach, liver, gallbladder meridian. Effect of traditional use for clearing and draining damp heat, bile and yellow. Modern pharmacological research has found that it is rich in coumarins (such as binchotan lactone), flavonoids and organic acids (such as chlorogenic acid) and other ingredients, with significant anti-inflammatory and antioxidant activity. In the treatment of CFS, these components can effectively remove excess reactive oxygen species (ROS) in the body, reduce the damage of oxidative stress to cells. Studies have confirmed that Yinchen extract can inhibit the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and other pro-inflammatory factors by regulating TLR4 / NF-κB and other signaling pathways, and improve the chronic low-grade inflammation often accompanied by CFS. In addition, its active ingredient binchotan lactone showed the ability to prolong sleep time and enhance δ wave brain activity in sleep regulation experiments, which was achieved by regulating GABAA and 5-HT1A receptors, and had potential value for relieving sleep disorders in CFS patients.

[0026] Foshou: bitter, pungent, sour, warm, liver, spleen, stomach, lung meridian. Effect of soothing liver and regulating qi, harmonizing stomach and relieving pain, drying dampness and reducing phlegm. The pathogenesis of CFS is closely related to liver qi stagnation caused by emotional internal injury. Foshou is not directly invigorating, but its volatile oil (such as limonene) and flavonoids (such as hesperidin) have central nervous system regulation, which can help relieve anxiety, depression and other negative emotions and sleep disorders accompanied by CFS. Its "soothing liver and regulating qi" effect can regulate the unsmooth qi movement caused by "liver depression", and its "harmonizing stomach and relieving pain" effect can improve the gastrointestinal dysfunction of CFS patients caused by "liver qi invading the spleen", such as abdominal distension, loss of appetite, etc. The use of Foshou embodies the overall thinking of TCM in the treatment of CFS, that is, regulating qi movement to restore the function of zang-fu organs.

[0027] Semen Platycladi: sweet, flat, heart, kidney, large intestine. Nourishing heart, soothing the nerves, moistening the intestines and relieving constipation. CFS patients often have severe sleep disorders, and the heart-nourishing and nerve-soothing effects of Platycladi Semen are just for this. Its fatty oil (rich in linoleic acid, oleic acid) and Platycladi Semen polysaccharides and other ingredients have a calming effect. Studies have shown that these ingredients can help improve sleep speed and prolong deep sleep time by regulating neurotransmitters. By improving sleep quality, it helps to restore energy and physical strength, directly relieving fatigue. In addition, the effect of Platycladi Semen on moistening the intestines and relieving constipation can improve the constipation problem of CFS patients, especially those who are often under long-term mental stress or blood deficiency. Its rich unsaturated fatty acids also have a certain regulating effect on blood lipids, which helps to improve the overall condition of CFS patients in many ways.

[0028] The traditional Chinese medicine preparation of the present application is based on the core idea of regulating liver and spleen, tonifying qi and nourishing yin, and invigorating spleen and tranquilizing the mind. Huangdi's Internal Classic says, "At the age of forty, the yin energy is half, and the living is declining". With the increase of age, the body's yin energy is gradually depleted, and the deficiency of both qi and yin is the core pathogenesis of aging. The prepared rehmannia and prince seng are the monarchs in the present application. The prepared rehmannia is sweet and slightly warm, and is a yin-tonifying medicinal herb. The prince seng is sweet and flat, and can tonify qi and invigorate the spleen, moisten the lungs and produce saliva. The combination of the two can tonify both qi and yin, nourish blood to fill essence, and tonify qi to circulate blood. The white atractylodes is the minister, which can assist the prince seng to strengthen the function of the spleen and stomach, and can also prevent the prepared rehmannia from causing greasy and stomach-stuffy due to its dampness-eliminating property. The Suwen of Canon of Internal Classic says, "The liver is the origin of extreme, …… the abode of the soul". The liver governs blood and is responsible for the dispersion, and can regulate the distribution of qi and blood in the whole body, which is the basis of the body's endurance and fatigue relief. The deficiency of liver blood or the stagnation of liver qi and the abnormal dispersion can easily cause fatigue. At the same time, the abode of the soul indicates that the liver is closely related to sleep and emotion, so chronic fatigue patients often have emotional problems such as depression, anxiety, irritability, insomnia and dreaminess. Therefore, the other minister of the present application is the wormwood, which is bitter and slightly cold, and can soothe the liver and clear damp-heat. The wormwood is used together with the prepared rehmannia and the prince seng to make the tonification unobstructed and the tonification without stagnation, and to regulate the liver and spleen. The bergamot is the assistant, which is sour and warm. On the one hand, it can soothe the liver and regulate the liver qi, and enhance the effect of the wormwood on soothing the liver. On the other hand, it can regulate qi and stomach, so that the prepared rehmannia and the white atractylodes can tonify without greasiness, and promote the absorption of the spleen and stomach. The bergamot is warm, and does not hurt yin. Modern research shows that the active ingredients of the bergamot can reduce the expression of inflammatory factors IL-6 and TNF-α, reduce the senescence-associated secretory phenotype (SASP) factor, and delay the aging of osteoarthritis chondrocytes. The core component of the bergamot, bergamottin, can inhibit the inflammatory signaling pathway such as MAPK, reduce nerve inflammation, and improve the memory disorder of Alzheimer's disease model animals, and has good anti-aging effect. The platycladus seed is the auxiliary medicine, which is sweet and flat, and can nourish the heart and tranquilize the mind, and moisten the intestines and defecate. On the one hand, it can directly improve the symptoms such as insomnia, palpitation and forgetfulness caused by chronic fatigue. On the other hand, it can moisten the intestines and defecate, make the turbid qi descend, and relieve the burden of the spleen and stomach of the patients with chronic fatigue syndrome. In summary, the combination of the above-mentioned medicines can regulate the liver and spleen, tonify both qi and yin, eliminate dampness and stomach, and calm the heart and mind.

[0029] The drug raw materials and the dosage of the present application are obtained through a large amount of groping and summarizing by the inventors. The present application can be prepared into conventional oral preparations such as water decoction, decoction paste, pill, granule, tablet, capsule or oral liquid by using the conventional method of traditional Chinese medicine preparation, and the related preparation methods are as follows:

[0030] The prepared rehmannia 10-15 parts, the prince seng 12-25 parts, the white atractylodes 6-12 parts, the wormwood 6-15 parts, the bergamot 3-10 parts, and the platycladus seed 3-10 parts.

[0031] 1. The preferred preparation method of the present application is water decoction, which comprises the following steps: after the raw materials are weighed according to the above proportioning, they are put into a disposable non-woven fabric medicine bag, 3-5 cm of water higher than the medicine level is added, and soaked for 20-40 minutes; the medicine is first decocted in a medicine decocting vessel (such as a sand pot), boiled with a large fire, then turned to small fire for decocting for 30-40 minutes, filtered out after decocting, and 20000 ml of medicine liquid is obtained; when decocting for the second time, an appropriate amount of water is added (preferably to cover the medicine residue), boiled with a large fire, then turned to small fire for decocting for about 20 minutes, filtered, and 10000 ml of medicine liquid is obtained; the two medicine liquids are mixed, and 30000 ml of medicine liquid is obtained. Each 150 ml is vacuum compressed and packaged as one bag.

[0032] Method of taking: 1 bag each time, 2 times a day, taken on an empty stomach in the morning and evening.

[0033] 2. The specific preparation method of decocted paste is as follows: after the raw materials are weighed according to the above proportioning, they are put into a disposable non-woven fabric medicine bag, soaked with an appropriate amount of water, and allowed to fully absorb and swell, then water is added to about 10 cm higher, and soaked for 12 hours; the soaked medicine is put into a medicine decocting pot, 15 cm of water higher than the medicine level is added, boiled with a large fire first, then boiled with a small fire for 1 hour, turned to a micro fire to a degree of boiling, filtered out the first medicine juice with gauze, then added clean water to soak the original medicine residue, and boiled and decocted with fire, the decocting method is the same as before, this is the second decocting, when decocting for the third time, the medicine juice is filtered out, and the medicine residue is discarded. The medicine juice obtained by the first three decoctings is mixed together, and after standing, it is precipitated and filtered, the less the medicine residue, the better; the obtained medicine juice is poured into a pot for concentration, boiled and decocted with a large fire first, accelerates the evaporation of water, and removes the floating scum in time, allows the medicine juice to slowly become thick, then changes to a small fire for further concentration, stirs constantly during the period, to a degree that the medicine juice does not spread when dropped on paper, stops boiling and decocting, and gets thick paste, which is reserved for use; then 3.5 kg of honey is poured into the thick paste reserved for use and continues to be heated on a small fire, constantly stirs and removes the foam on the liquid surface, until it can be pulled into a flag or forms beads when water is dropped, then the paste is obtained (diabetic patients or patients with high blood sugar can omit this step); then the paste is quickly poured into a glass bottle (200 ml per bottle) which has been cleaned and disinfected in advance while hot, and is cooled and placed to obtain the product.

[0034] Method of taking: 1 small spoon (about 10 ml) each time, 2 times a day, taken on an empty stomach in the morning and evening.

[0035] 3. The specific preparation method of the pill is as follows: the raw medicine is weighed according to the above proportion, put into a disposable non-woven fabric medicine bag, put into a medicine soaking barrel, add appropriate water to soak the raw material, let it absorb and swell, then add water to 10 cm higher, soak for 12 hours; put the soaked medicine into a medicine pot, add water 15 cm higher than the medicine surface, boil with large fire first, then cook with small fire for about 1 hour, turn to micro fire, filter the first medicine juice with gauze, add clean water to soak the original medicine residue, then boil and cook, the method is the same as before, this is the second decoction, when the third decoction, filter the medicine juice, then discard the medicine residue. Mix the medicine juice of the first three decoctions together, stand and then filter the sediment, the less residue the better; pour the obtained medicine juice into a pot for concentration, first boil with large fire to speed up water evaporation, and remove the floating scum in time, let the medicine juice become thick slowly, then change to small fire for further concentration, stir constantly during the process, until the medicine juice drops on paper without spreading, then stop boiling to get thick paste, reserve for use; then spray dry the thick paste, add 4 kg of refined honey, mix well, make pill blocks, then send to an automatic pill making machine to make pills, each pill is 0.1 g.

[0036] The taking method is as follows: 60 pills each time, 3 times a day, half an hour after breakfast, lunch and dinner.

[0037] 4. The specific preparation method of the granules is as follows: the raw medicine is weighed according to the above proportion, put into a disposable non-woven fabric medicine bag, put into a medicine soaking barrel, add appropriate water to soak the raw material, let it absorb and swell, then add water to 10 cm higher, soak for 12 hours; put the soaked medicine into a medicine pot, add water 15 cm higher than the medicine surface, boil with large fire first, then cook with small fire for about 1 hour, turn to micro fire, filter the first medicine juice with gauze, add clean water to soak the original medicine residue, then boil and cook, the method is the same as before, this is the second decoction, when the third decoction, filter the medicine juice, then discard the medicine residue. Mix the medicine juice of the first three decoctions together, stand and then filter the sediment, the less residue the better; pour the obtained medicine juice into a pot for concentration, first boil with large fire to speed up water evaporation, and remove the floating scum in time, let the medicine juice become thick slowly, then change to small fire for further concentration, stir constantly during the process, until the medicine juice drops on paper without spreading, then stop boiling to get thick paste, reserve for use; then spray dry the thick paste, add 4 kg of refined honey, mix well, make pill blocks, then send to an automatic pill making machine to make pills, each pill is 0.1 g.

[0038] The taking method is as follows: 60 pills each time, 3 times a day, half an hour after breakfast, lunch and dinner.

[0039] 5. The specific preparation method of tablets is as follows: After weighing the raw materials according to the above proportions, put them into a disposable non-woven fabric medicine bag and place it in a soaking bucket. Add an appropriate amount of water to soak the raw materials, allowing them to fully absorb and expand. Then add water to a level 10 cm above the raw materials and soak for 12 hours. Put the soaked medicine into a decoction vessel, add water to a level 15 cm above the medicine, bring to a boil over high heat, then simmer over low heat for 1 hour. Turn to a simmer and let it boil. Filter the first decoction through gauze. Add water to moisten the original dregs and then decoct over a fire. The decoction method is the same as before. This is the second decoction. When it comes to the third decoction, filter the decoction and discard the dregs. Mix the decoctions obtained from the first three decoctions together, let them stand, and then filter them after sedimentation, aiming for minimal residue. Pour the resulting decoction into a pot for concentration. First, boil it over high heat to accelerate water evaporation, skimming off any foam as needed, allowing the decoction to gradually thicken. Then, reduce the heat to low and concentrate it further, stirring constantly until the decoction drips onto paper without spreading. Stop boiling to obtain a thick paste, which is then set aside for later use. The paste is then spray-dried, and 500g of sodium carboxymethyl starch and 100g of magnesium stearate are added and mixed thoroughly. The mixture is then wet-granulated, dried, sized, compressed, and coated to form tablets, each weighing 0.5g.

[0040] Dosage: Take 3 tablets 3 times a day, half an hour after breakfast, lunch and dinner.

[0041] 6. The specific preparation method of the capsules is as follows: After weighing the raw materials according to the above proportions, put them into a disposable non-woven fabric medicine bag and place it in a soaking bucket. Add an appropriate amount of water to soak the raw materials, allowing them to fully absorb and expand. Then add water to a level 10 cm above the raw materials and soak for 12 hours. Put the soaked medicine into a decoction pot, add water to a level 15 cm above the medicine, bring it to a boil over high heat, then simmer over low heat for about 1 hour. Turn to a simmer and let it boil. Filter the first decoction with gauze. Add water to moisten the original dregs and then decoct over a fire. The decoction method is the same as before. This is the second decoction. When it comes to the third decoction, filter the decoction and discard the dregs. Mix the decoctions obtained from the first three decoctions together, let them stand, and then filter them after sedimentation, aiming for as little residue as possible. Pour the resulting decoction into a pot for concentration. First, boil it over high heat to accelerate water evaporation, skimming off any foam as needed, allowing the decoction to gradually thicken. Then, reduce the heat to low and concentrate it further, stirring constantly until the decoction drips onto paper without spreading. Stop boiling to obtain a thick paste, which is then set aside for later use. Finally, spray-dry the paste, pulverize it into a fine powder, and encapsulate it to make capsules, each weighing 0.5g.

[0042] Dosage: Take 3 capsules 3 times a day, half an hour after breakfast, lunch and dinner.

[0043] 7. The specific preparation method of the oral liquid is as follows: After weighing the raw materials according to the above weight ratio, put them into a disposable non-woven medicine bag and place it in a medicine soaking bucket. Add an appropriate amount of water to soak the raw materials, allowing them to fully absorb and expand. Then add water again to a height 10 cm higher, and soak for 12 hours. Put the soaked medicinal materials into a decocting pot, add water 15 cm higher than the plane of the medicinal materials, first bring to a boil over high heat, then simmer for 1 hour, and turn to low heat to keep boiling. Then filter out the first decoction with a gauze. Add clear water to moisten the original medicinal residues and then heat it up for decocting. The decocting method is the same as before. This is the second decoction. When it comes to the third decoction, after filtering out the medicinal juice, discard the medicinal residues. Mix the medicinal juices obtained from the first three decoctions together, let it stand and then precipitate and filter. The less the medicinal residues, the better. Pour the obtained medicinal juice into a pot for concentration. First, decoct over high heat to accelerate the evaporation of water, and constantly skim off the floating foam. Let the medicinal juice slowly become thick. Then switch to low heat for further concentration, and keep stirring during this period until the medicinal juice drops onto the paper and does not spread out. Stop decocting to obtain a thick paste and reserve it for later use. Then add 1 kg of simple syrup to the thick paste, mix well, cool it, add distilled water to 6000 ml, let it stand and then filter, and fill and seal to obtain the oral liquid, 20 ml per bottle.

[0044] Dosage method: Take it 3 times a day, 20 ml each time, half an hour after breakfast, lunch, and dinner.

[0045] The medicine of the present invention is precise in formulation, rigorous in compatibility, and has remarkable curative effects. It is a traditional Chinese medicine preparation for treating chronic fatigue syndrome. This traditional Chinese medicine preparation has certain curative effects in improving the clinical symptoms of patients, preventing the occurrence of stroke and malignant complications, and improving the quality of life. To further elaborate and verify the remarkable effects of the present invention, relevant basic experiments and clinical studies are carried out.

[0046] 1. Experimental animals Purchase 20 SPF-grade Sprague-Dawley (SD) rats at 6 weeks old from Beijing Vital River Laboratory Animal Technology Co., Ltd. [SCXK (Beijing) 2021-0006], with 10 males and 10 females, and the average body weight is (200 ± 20) g. All experimental animals are raised in the Animal Center of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences [SYXK (Tianjin) 2019-0002]. The raising temperature is 20 - 25 °C, the humidity is 55 - 65%, and there is a 12-hour day-night alternating cycle lighting. During the raising period, ensure that the rats can drink water and eat normally. All experimental animal operations follow the requirements of the Experimental Animal Ethics Committee of the Institute of Radiation Medicine, Chinese Academy of Chinese Medical Sciences, and the ethics number is IRM-DWLL-2023238.

[0047] Experimental drug 2.1 Chinese medicine preparation formula: the drug ratio is 15 g of Radix Rehmanniae Preparata, 15 g of Radix Pseudoginseng, 12 g of Rhizoma Atractylodis Macrocephalae, 15 g of Herba Artemisiae Scopariae, 10 g of Fructus Citri Sarcodactylis, and 10 g of Semen Platycladi. The formula is purchased as a decoction granule from the pharmacy of Zhejiang Provincial Hospital of Traditional Chinese Medicine. According to the dose conversion method of human and rat body surface area, the rat dose of the Chinese medicine preparation formula is calculated to be 6.93 g of crude drug / kg. A water decoction is selected for this experiment.

[0048] 2.2 Positive drug: Buzhong Yiqi Wan (Zhongjing Wanxi Pharmaceutical Co., Ltd.), 8 pills equivalent to 3 g of crude drug, the rat gavage amount is calculated to be 0.81 g / kg / d. The pills are made into a powder and dissolved in pure water to form a suspension, which is the gavage solvent.

[0049] 3 Experimental grouping and modeling The SD rats are randomly divided into 4 groups by computer: blank control group, model group, Chinese medicine compound group, and positive drug group, 5 rats in each group. After 3 days of adaptive feeding, modeling is performed. The CFS rat model is established by a combined stress method of chronic restraint and exhaustive swimming. The modeling period is 21 days. Except for the blank control group, the rats in the other groups are fixed in a self-made restraint cylinder for 3 hours every day to limit their activity. After the restraint is over, the rats are immediately put into a swimming tank with water temperature of (20±2) °C and water depth of about 35 cm to perform exhaustive swimming. The exhaustive swimming standard is that the rat cannot float out of the water by itself when the head is submerged in the water for more than 10 seconds, or the body is in an angle of arching. When the rat is floating in the water, it is slightly disturbed to continue moving. During the whole modeling period, the rats are fed quantitatively (50 g of standard feed per rat per day) and drink water freely.

[0050] After the modeling is completed, the model is evaluated by general behavior observation (such as listless appearance, disheveled hair, and slow reaction) and Morris water maze experiment. The rats that meet the above behavior change characteristics are determined to be successfully modeled and used for subsequent experiments.

[0051] 4 Animal administration 4.1 Blank control group: gavage with pure water 10 mL / kg, continuous gavage for 14 days, 1 time / day.

[0052] 4.2 Model group: gavage with pure water 10 mL / kg, continuous gavage for 14 days, 1 time / day.

[0053] 4.3 Chinese medicine compound group: gavage with Chinese medicine compound solution 10 mL / kg, continuous gavage for 14 days, 1 time / day.

[0054] 4.4 Positive drug group: gavage with Buzhong Yiqi Tang 10 mL / kg, continuous gavage for 14 days, 1 time / day.

[0055] 5 Behavioral detection 5.1 Morris water maze experiment The 150 cm x 70 cm circular pool was equally divided into 4 quadrants, marked as 1, 2, 3, 4 quadrants, and the platform was immersed in water by 1 cm as the 5th quadrant. After the modeling was completed, the rats were trained to adapt to the water from different quadrants, and after each training was completed, the rats were quickly wiped clean with a clean towel and returned to the cage. After the treatment was completed, the total distance and target quadrant distance of each group of rats were recorded continuously.

[0056] 5.2 Exhaustive swimming experiment The rats were forced to swim in a water tank with a water temperature of (25±2) °C and a water depth of more than 45 cm, with a weight of 3% of their own weight tied to their tails, until they reached the exhausted state. The standard for exhaustion was that the rats could not continue to swim due to disordered movement, and their mouth and nose were submerged in water and could not float up for more than 10 seconds. The time from the start of swimming to the standard for exhaustion was recorded.

[0057] 6 Biochemical detection Serum sample collection and preparation: After the observation after the modeling was completed, the abdominal aorta was taken. After blood collection, the labeled blood collection tube was straightened and stood for 30 min, and centrifuged at 3000 rpm for 15 min, and the supernatant was taken.

[0058] Machine detection: According to the instructions of the biochemical kit, the levels of creatine kinase-MB (CKMB) and lactate dehydrogenase (LDH) in serum were detected using a fully automatic biochemical analyzer.

[0059] 7 Immunohistochemical detection of PGC-1α index Myocardial tissue of 3 rats in each group was fixed in 4% paraformaldehyde for 72 h, then inserted into the dehydration basket, set the dehydration machine program, and started the automatic closed dehydration treatment, then soaked in melted paraffin, and embedded. Three 4 μm tissue sections were taken from each wax block, deparaffinated to water, washed with PBS for 3 times, dropped with 3% H2O2 (80% methanol), and incubated at room temperature for 10 min, washed with PBS for 3 times, and then boiled in sodium citrate antigen repair solution for 10 min for antigen heat repair. After cooling to room temperature, wash with PBS for 3 times, drop goat serum blocking solution, and incubate at room temperature for 20 min. Remove the blocking solution, drop PGC-1α antibody, incubate at 4 °C for 12 h, and then incubate at room temperature for 45 min. Wash with PBS for 3 times, incubate with secondary antibody at room temperature for 1 h, wash with PBS for 3 times, and develop color with DAB. Then perform hematoxylin re-staining, pure water washing, and 1% hydrochloric acid alcohol differentiation, and dehydrate, transparent, and mount.

[0060] 8 Statistical analysis The data analysis in this experiment was performed using IBM SPSS Statistics 26.0 software. Quantitative data were expressed as mean ± standard deviation and compared using one-way ANOVA. If the variances were homogeneous, the LSD (Least Significant Difference) test was used; otherwise, Tamhane's test was used. The significance level was set at α = 0.05. P <0.05 indicates statistical significance); categorical data were analyzed using the chi-square test, with both tails taken. P <0.05 is considered statistically significant. Graphs were created using GraphPad Prism 9.0.0.

[0061] 9 Experimental Results 9.1 Total distance traveled by CFS rats After 14 days of administration, compared with the blank control group, the total distance traveled and the target quadrant distance of rats in the model group were significantly reduced (P<0.01). Compared with the model group, the total distance traveled and the target quadrant distance of the traditional Chinese medicine group and the positive control group were significantly increased (P<0.01). There was no statistically significant difference in the total distance traveled and the target quadrant distance between the positive control group and the traditional Chinese medicine group (P>0.05, see...). Figure 1 ).

[0062] 9.2 Exhaustion swimming time in CFS rats After 14 days of administration, compared with the blank control group, the exhaustive swimming time of mice in the model group was significantly shortened (P < 0.01). Compared with the model group, the exhaustive swimming time of rats in the traditional Chinese medicine compound group and the positive control group was significantly prolonged (P < 0.01), while there was no statistically significant difference in exhaustive swimming time between the positive control group and the traditional Chinese medicine group (P > 0.05), indicating that the traditional Chinese medicine compound can improve the fatigue state of CFS rats (see...). Figure 2 ).

[0063] 9.3 Results of myocardial injury markers in CFS rats Fourteen days after administration, myocardial injury markers in rats from each group were compared. Compared with the blank control group, the model group rats showed significantly increased levels of CKMB and LDH. P <0.01), compared with the model group, the CKMD and LDH levels in rats in the traditional Chinese medicine group and the positive drug group were significantly reduced ( P <0.01), indicating that the traditional Chinese medicine compound can improve myocardial injury in CFS rats, and there was no statistically significant difference between the traditional Chinese medicine group and the positive drug group. P >0.05, see Figure 3 ).

[0064] 9.4 Immunohistochemical staining results Immunohistochemistry showed that the positive expression area of myocardial PGC-1a in the model group was significantly reduced compared with the blank control group. Compared with the model group, the positive expression area of myocardial PGC-1a in the traditional Chinese medicine group and the positive drug group was significantly increased (P<0.01, see Figure 4 ).

[0065] The following typical cases 1 and 2 of treating chronic fatigue syndrome by the present application further illustrate the remarkable effect of the present application.

[0066] Example 1 Li, female, 53 years old, on August 17, 2025, complained of persistent fatigue and inattention for more than 3 years, and aggravated for 6 months. Present illness: The patient has been experiencing whole-body fatigue and weakness since 2020 without any obvious inducement. She feels tired in the morning, and her work energy has decreased significantly. She also has memory loss and difficulty concentrating. She underwent a comprehensive physical examination at a local hospital, and blood routine, liver and kidney function, and thyroid function tests showed no obvious abnormalities. In the past 6 months, she has been feeling tired even after 8-9 hours of sleep every day, and she needs to rest for a long time after light physical activity. She also has insomnia, poor appetite, abdominal distension, and loose stools. She has tried exercise therapy, nutritional supplements, and psychological counseling, but the effect is not significant. Past medical history: No special disease history. Physical examination: spiritless, pale complexion, pale tongue, thin white fur, and weak pulse. Auxiliary examination: fatigue severity scale (FSS) score 58; Hamilton depression scale (HAMD) score 16; Hamilton anxiety scale (HAMA) score 14. Diagnosis: chronic fatigue syndrome (TCM syndrome: spleen and kidney deficiency, heart and spirit deficiency). Treatment process: the present application of traditional Chinese medicine preparation (granules) is used, and the prescription composition is: Radix Rehmanniae Preparata 15g, Radix Notoginseng 15g, Herba Artemisiae Scopariae 15g, Rhizoma Atractylodis Macrocephalae 12g, Fructus Citri Sarcodactylis 10g, Semen Platycladi 10g. 1 bag each time, 3 times a day, after meals. Efficacy observation: after 2 weeks of treatment, the patient felt that her energy had improved, her daytime drowsiness had decreased, and her appetite had improved. After 4 weeks of treatment, her energy was significantly improved, she could complete her daily office work, her attention span was extended, and her sleep quality was improved. After 8 weeks of treatment, the FSS score was reduced to 32, the HAMD score was reduced to 8, and the HAMA score was reduced to 7. Continue taking for 4 weeks to consolidate the effect, and follow up for 3 months, the disease is stable, and the daily life and work ability are basically restored.

[0067] Example 2 Gao Mou, male, 37 years old, November 23, 2024, the main reason for "repeated fatigue, muscle soreness for 2 years, accompanied by cognitive dysfunction for 1 year." Visit Zhejiang Province A hospital. Present history: The patient is an IT engineer, who has been under great work pressure for a long time. Two years ago, he began to have persistent fatigue, which worsened after exercise and recovered slowly, accompanied by muscle soreness and joint discomfort all over the body. In the past year, he has experienced significant thinking slowness and short-term memory loss, which has severely affected his work efficiency. He also has irritability, night sweats, dry mouth, and dry throat. He has been treated in the departments of neurology and rheumatology and immunology, and has been ruled out of fibromyalgia and autoimmune diseases. Past history: No special. Physical examination: Thin body, tongue tip red, little moss, pulse thin and rapid. Auxiliary examination: FSS score 62; Montreal Cognitive Assessment (MoCA) score 24; serum cortisol rhythm is abnormal (morning is low, night is high). Diagnosis: Chronic fatigue syndrome. Treatment process: The patient is given a traditional Chinese medicine preparation (capsule) according to the present application, the prescription composition of which is: Radix Rehmanniae Preparata 20g, Radix Pseudostellariae 15g, Herba Artemisiae Scopariae 15g, Rhizoma Atractylodis Macrocephalae 15g, Fructus Citri Sarcodactylis 10g, Semen Platycladi 12g. Take 3 capsules 3 times a day after meals. After 1 week of treatment, the patient felt that the depth of sleep had improved and the night sweats had decreased. After 3 weeks of treatment, muscle soreness was significantly reduced and thinking clarity was improved. After 6 weeks of treatment, fatigue was significantly improved, daily work endurance was improved, and mood was stable. After 12 weeks of treatment, the FSS score was reduced to 35 and the MoCA score was increased to 28. After 4 weeks of continued maintenance treatment, the patient was able to adapt to normal work intensity and cognitive function was basically restored to normal.

[0068] The above-described embodiments are only used to illustrate the technical ideas and characteristics of the present application, and the purpose is to enable those skilled in the art to understand the present application and implement it, and cannot be limited to the patent scope of the present application by the above-described embodiments, i.e. any equivalent changes or modifications made according to the spirit disclosed by the present application still fall within the patent scope of the present application.

Claims

1. A traditional Chinese medicine preparation for treating chronic fatigue syndrome, characterized in that, It is made of the following raw medicinal materials in mass fraction: Radix Rehmanniae Preparata 10-15 parts, Radix Pseudostellariae 12-25 parts, Rhizoma Atractylodis Macrocephalae 6-12 parts, Herba Artemisiae Scopariae 6-15 parts, Citrus Bergamia 3-10 parts, Semen Platycladi 3-10 parts.

2. The traditional Chinese medicine preparation for treating chronic fatigue syndrome according to claim 1, characterized in that, It is made of the following raw medicinal materials in mass fraction: Radix Rehmanniae Preparata 15 parts, Radix Pseudostellariae 15 parts, Rhizoma Atractylodis Macrocephalae 12 parts, Herba Artemisiae Scopariae 15 parts, Citrus Bergamia 10 parts, Semen Platycladi 10 parts.

3. The traditional Chinese medicine preparation for treating chronic fatigue syndrome according to claim 1, characterized in that, It also comprises pharmaceutically acceptable adjuvants, and is prepared into water decoction, decoction paste, pill, granule, tablet, capsule or oral liquid.

Images