A traditional Chinese medicine composition, a preparation method thereof, and an application thereof in the preparation of a drug for preventing and treating stress insomnia

Abstract

The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition, a preparation method thereof, and an application thereof in the preparation of a drug for preventing and treating stress insomnia. The composition provided by the present invention is composed of Cyperus rotundus L. var. aromaticus Rehd., Pericarpium Citri Reticulatae Viride, Pinellia ternata (Thunb.) Breit., Poria, Salvia miltiorrhiza Bunge, Panax ginseng C. A. Mey., Acorus tatarinowii Schott, Margarita nuda, Os Draconis, and Zingiber officinale Rosc. Through a multi-target and multi-pathway regulation mechanism, combined with the significant regulatory effects of GO function enrichment and KEGG signal pathways, the composition demonstrates its comprehensive advantages in the treatment of stress insomnia. This multi-level mechanism of action provides unique therapeutic potential for this formula, especially in dealing with complex stress responses and neurological disorders, and has important clinical application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition, a preparation method thereof, and an application thereof in the preparation of a drug for preventing and treating stress-induced insomnia. Background Art

[0002] Stress-induced insomnia, as a common sleep disorder induced by sudden or continuous stress events, is mainly clinically manifested as difficulty in falling asleep, frequent night awakenings, early awakening, and decreased sleep quality. Epidemiological studies have shown that the incidence of stress-induced insomnia is on the rise in modern society, especially in high-pressure work environments and fast-paced lives. Its social impacts are mainly manifested in the long-term negative effects on individual health, including memory loss, emotional instability, reduced work efficiency, and other health problems such as cardiovascular diseases and diabetes that may be induced.

[0003] Currently, the methods for treating stress-induced insomnia are mainly divided into two categories: drug treatment and non-drug treatment. In terms of drug treatment, benzodiazepines and non-benzodiazepines, as commonly used hypnotics, although they have a rapid onset and significant efficacy, long-term use may lead to adverse reactions such as drug dependence, drug resistance, and daytime sleepiness. In addition, certain antidepressants and anti-anxiety drugs are also used to improve sleep, but these drugs may cause side effects such as cognitive decline and emotional out-of-control, especially in the elderly population. In traditional Chinese medicine theory, stress-induced insomnia is often related to factors such as liver depression and spleen deficiency, and heart and spleen deficiency. For stress-induced insomnia, especially the liver depression and spleen deficiency type, common traditional Chinese patent medicines include: Tianwang Buxin Dan, which has the effect of nourishing the heart and calming the mind, and is suitable for insomnia caused by qi and blood deficiency and restlessness of the mind; Guipi Wan, which is applicable to palpitations and insomnia caused by spleen deficiency, and can invigorate the spleen, nourish the heart, and calm the mind; Suanzaoren Decoction, which nourishes yin and calms the mind, and is commonly used for insomnia of the type of hyperactivity of fire due to yin deficiency; Chaihu Shugan Powder, which is specifically used to regulate the liver qi and relieve liver depression, and can relieve insomnia caused by emotional depression. Although the above traditional Chinese patent medicines can relieve symptoms to a certain extent, they also have some limitations: 1. Stress-induced insomnia often belongs to the types of liver depression and spleen deficiency, and heart and spleen deficiency. Patients often have manifestations such as emotional discomfort and anxiety. Even if traditional Chinese patent medicines for calming the mind are used, the curative effect may not be effective due to the failure to effectively dredge emotional factors. 2. The components of many traditional Chinese patent medicines are relatively single. For insomnia of the type of combined liver depression and spleen deficiency and heart and spleen deficiency, they may not be able to provide comprehensive conditioning, resulting in no significant improvement in symptoms. 3. Individual differences in drug efficacy: Different patients have large differences in their responses to traditional Chinese patent medicines. Some patients may be sensitive to certain traditional Chinese patent medicines, but have poor responses to others, resulting in uneven treatment effects. In summary, for stress-induced insomnia, traditional Chinese patent medicines can play a certain role in conditioning and relieving symptoms, but their effects are affected by various factors, and the clinical effects are always unstable.

[0004] It can be seen that the limitations of traditional Chinese medicine (TCM) treatment lie in its complex mechanism of action, slow onset of effect, and difficulty in standardization, which pose certain challenges to clinical application and efficacy evaluation. In addition, TCM has diverse components and may interact with other drugs, so special attention is needed when using it. Non-drug treatment methods such as cognitive behavioral therapy for insomnia (CBT-I) and sleep hygiene education, although avoiding the problem of drug dependence, have a slow onset of efficacy and require long-term adherence by patients to achieve the desired effect.

[0005] In summary, the existing means for treating stress-induced insomnia have significant limitations. It is difficult to avoid the side effects and dependence problems of drugs, and it is also impossible to achieve good efficacy through non-drug treatment in the short term. Therefore, it is particularly crucial to develop a safe, effective, and long-term applicable treatment method, which is also the unique advantage of the TCM formula in the treatment of stress-induced insomnia. Summary of the Invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition, its preparation method, and its application in the preparation of drugs for preventing and treating stress-induced insomnia.

[0007] The raw materials of the traditional Chinese medicine composition provided by the present invention include: Cyperus rotundus L. var. aromaticus Rehd., Pericarpium Citri Reticulatae Viride, Pinellia ternata (Thunb.) Breit., Poria cum Radice Pini, Salvia miltiorrhiza Bunge, Panax ginseng C. A. Mey., Acorus tatarinowii Schott, Margarita nuda, Os Draconis, and Zingiber officinale Rosc.

[0008] Based on long-term clinical practice, the present invention has optimized the drug components to obtain a traditional Chinese medicine composition capable of treating insomnia, especially stress-induced insomnia. In this drug, Cyperus rotundus L. var. aromaticus Rehd. and Acorus tatarinowii Schott are used as the monarch drugs, acting together on the pathological state of liver depression and spleen deficiency. Pericarpium Citri Reticulatae Viride, Pinellia ternata (Thunb.) Breit., and Poria cum Radice Pini are used as the ministerial drugs, further enhancing the effects of soothing the liver and relieving depression, and strengthening the spleen and nourishing the heart, which are particularly effective in treating insomnia symptoms caused by emotional fluctuations and indigestion. Salvia miltiorrhiza Bunge, Panax ginseng C. A. Mey., Margarita nuda, and Os Draconis are used as the adjuvant drugs, jointly enhancing the sedative effect of the prescription. Zingiber officinale Rosc. is used as the guiding drug, harmonizing all the drugs, reducing the side effects of the drugs, and enhancing the drug efficacy.

[0009] Experiments show that the component composition of the composition in the present invention is reasonable. Replacing some of its components will lead to a decline in the drug effect. For example, the decline in the relevant protein expression level is inhibited. In other words, the compatibility of the medicinal flavors of the composition in the present invention is more reasonable, so that the drug combination in the present invention can effectively relieve the symptoms of stress-induced insomnia and achieve the therapeutic purpose.

[0010] Furthermore, the present invention has optimized the dosage of each component in the traditional Chinese medicine composition. Compared with other dosage ratios, the following ratio can bring better effects in improving insomnia.

[0011] In the present invention, the traditional Chinese medicine composition is made from the following raw materials in parts by mass: 12-18 parts of Cyperus rotundus L. prepared with vinegar, 12-16 parts of Pericarpium Citri Reticulatae Viride, 12-20 parts of Pinellia ternata (Thunb.) Breit., 12-18 parts of Poria cum Radix Pini, 12-19 parts of Salvia miltiorrhiza Bunge, 8-12 parts of Panax ginseng C. A. Mey., 10-18 parts of Acorus tatarinowii Schott, 20-30 parts of Margarita nuda, 25-35 parts of Os Draconis, and 3-6 parts of Zingiber officinale Rosc.

[0012] In some embodiments, the traditional Chinese medicine composition is made from the following raw materials in parts by mass: 12 parts of Cyperus rotundus L. prepared with vinegar, 15 parts of Pericarpium Citri Reticulatae Viride, 12 parts of Pinellia ternata (Thunb.) Breit., 15 parts of Poria cum Radix Pini, 15 parts of Salvia miltiorrhiza Bunge, 9 parts of Panax ginseng C. A. Mey., 15 parts of Acorus tatarinowii Schott, 30 parts of Margarita nuda, 30 parts of Os Draconis, and 5 parts of Zingiber officinale Rosc.

[0013] In some other embodiments, the traditional Chinese medicine composition is made from the following raw materials in parts by mass: 18 parts of Cyperus rotundus L. prepared with vinegar, 12 parts of Pericarpium Citri Reticulatae Viride, 20 parts of Pinellia ternata (Thunb.) Breit., 12 parts of Poria cum Radix Pini, 19 parts of Salvia miltiorrhiza Bunge, 8 parts of Panax ginseng C. A. Mey., 18 parts of Acorus tatarinowii Schott, 20 parts of Margarita nuda, 35 parts of Os Draconis, and 3 parts of Zingiber officinale Rosc.

[0014] In some other embodiments, the traditional Chinese medicine composition is made from the following raw materials in parts by mass: 15 parts of Cyperus rotundus L. prepared with vinegar, 16 parts of Pericarpium Citri Reticulatae Viride, 15 parts of Pinellia ternata (Thunb.) Breit., 18 parts of Poria cum Radix Pini, 12 parts of Salvia miltiorrhiza Bunge, 12 parts of Panax ginseng C. A. Mey., 10 parts of Acorus tatarinowii Schott, 30 parts of Margarita nuda, 25 parts of Os Draconis, and 6 parts of Zingiber officinale Rosc.

[0015] Furthermore, the present invention also provides an extract, which is prepared from the traditional Chinese medicine composition as described above.

[0016] The methods used in the extraction of the extract of the present invention include, but are not limited to, percolation method, decoction method, heating reflux extraction, maceration extraction, ultrasonic-assisted extraction, supercritical fluid extraction, microwave-assisted extraction, sublimation extraction, steam distillation extraction, or enzymatic-assisted extraction.

[0017] The solvents used in the extraction of the extract of the present invention include at least one of water, ethanol or its aqueous solution, propylene glycol or its aqueous solution, glycerol or its aqueous solution, acetic acid or its aqueous solution.

[0018] Even further, the present invention also provides a preparation method of the extract as described above, which includes soaking the traditional Chinese medicine composition as described above in water and then performing decoction extraction, and concentrating and drying the decoction liquid to obtain the extract.

[0019] Preferably, the number of times of decoction extraction is 2 times, each time for 1.5-2 h. For the first time, the amount of water added is 8-15 times the mass of the medicinal materials, and for the second time, the amount of water added is 6-12 times the mass of the medicinal materials.

[0020] Preferably, it is concentrated to a relative density of 1.25-1.40 (50-60 °C). The drying is carried out by vacuum drying, and the temperature of the vacuum drying is 60-80 °C.

[0021] Furthermore, the present invention also provides the use of the Chinese medicine composition as described above, the extract as described above or the extract prepared by the preparation method as described above in the preparation of a drug for preventing and treating stress-induced insomnia.

[0022] In the present invention, the treatment includes regulating the expression level of proteins and / or targets, prolonging sleep latency, and prolonging sleep duration.

[0023] In some embodiments, the proteins include at least one of FOS, PLA2G4A, ELK1, and IL1B.

[0024] In some embodiments, the targets include at least one of the MAPK signaling pathway, IL-17 signaling pathway, NF-kappaB signaling pathway, Th17 cell differentiation, VEGF signaling pathway, calcium signaling pathway, regulation of TRP channels by inflammatory mediators, cholinergic synapses, relaxin signaling pathway, apoptosis, p53 signaling pathway, necroptosis, B cell receptor signaling pathway, cGMP-PKG signaling pathway, antifolate resistance, Th1 and Th2 cell differentiation, GnRH signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, or T cell receptor signaling pathway.

[0025] The present invention also provides a drug for preventing and treating stress-induced insomnia, which includes a pharmaceutically acceptable excipient and the Chinese medicine composition as described above, the extract as described above or the extract prepared by the preparation method as described above.

[0026] The dosage forms of the drug of the present invention include, but are not limited to, granules, ointments, oral liquids, pellets, dripping pills, honey pills, water pills, tablets, decoctions, granules, capsules, tinctures, syrups, suppositories, gels, and / or sprays.

[0027] The pharmaceutically acceptable excipients include fillers, diluents, lubricants, suspending agents, emulsifiers, disintegrants, plasticizers, preservatives, flavoring agents, edible flavors, sweeteners, acidulants, and edible pigments, one or a mixture of two or more of the above.

[0028] The drug of the present invention may also include other drugs for treating insomnia, and the other drugs for treating insomnia include at least one of diazepam, estazolam, alprazolam, triazolam, clonazepam, lorazepam, oxazepam, zopiclone, eszopiclone, zaleplon, eszopiclone, melatonin, ramelteon, agomelatine, or doxepin.

[0029] In the present invention, in the drug, the Chinese medicine composition and other therapeutic agents may exist independently of each other or may be mixed, and the present invention does not make any limitation thereto.

[0030] Furthermore, the present invention also provides a method for preventing and treating insomnia, which includes administering the drug as described above.

[0031] The administration methods of the drug include but are not limited to oral administration, chewing, swallowing, sublingual administration, oral mucosal administration, nasal feeding, gastric tube administration, duodenal administration, jejunostomy administration, colostomy administration, rectal administration, enema, suppository insertion, anal drip, rectal foam agent administration, and rectal gel administration. Preferably, the administration method is oral administration.

[0032] In the present invention, the objects to be prevented and treated are humans or mammals, and the mammals include equidae, bovidae, suidae, ovidae, canidae, felidae, primates or rodents.

[0033] The present invention provides a composition that can be composed of Cyperus rotundus L. vinegar processed, Pericarpium Citri Reticulatae Viride, Pinellia ternata, Poria, Salvia miltiorrhiza, Panax ginseng, Acorus tatarinowii, Margaritifera usta, Os Draconis and Zingiber officinale, which has the effect of preventing and treating stress-induced insomnia. Experiments show that this traditional Chinese medicine formula demonstrates its comprehensive advantages in the treatment of stress-induced insomnia through a multi-target and multi-pathway regulation mechanism, combined with the significant regulatory effects of GO function enrichment and KEGG signaling pathways. This multi-level mechanism of action provides unique therapeutic potential for this formula, especially in dealing with complex stress responses and neurological disorders, and has important clinical application prospects. Brief Description of the Drawings

[0034] Figure 1 Showing differentially expressed genes related to insomnia, and different columns in Figure b represent the gene expression of tissues of different samples;

[0035] Figure 2 Showing potential targets for the treatment of stress-induced insomnia by the traditional Chinese medicine combination;

[0036] Figure 3 Showing the "protein-protein interaction" network diagram of potential targets for the treatment of insomnia by the traditional Chinese medicine combination;

[0037] Figure 4 Showing the functional enrichment clustering diagram of potential targets for the treatment of insomnia by the traditional Chinese medicine combination;

[0038] Figure 5 Showing the effects of each prescription on the sleep latency and sleep duration of animals;

[0039] Figure 6 Showing the protein band diagrams of FOS, PLA2G4A, ELK1, and IL1B in the hippocampus of mice in each group, where A is the blank group; B is the model group; C is the traditional Chinese medicine group;

[0040] Figure 7The protein band diagrams of FOS, PLA2G4A, ELK1, and IL1B in the hippocampus of each group of mice are shown, where: A is the blank group; B is the model group; C is Prescription 2 group; D is Prescription 3 group. Detailed implementation mode

[0041] The present invention provides a traditional Chinese medicine composition, its preparation method, and its application in the preparation of drugs for preventing and treating stress-induced insomnia. Those skilled in the art can draw on the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The methods and applications of the present invention have been described through preferred embodiments, and relevant personnel can obviously make changes or appropriate alterations and combinations to the methods and applications in this article without departing from the content, spirit, and scope of the present invention to implement and apply the technology of the present invention.

[0042] The test materials used in the present invention are all ordinary commercially available products and can be purchased in the market.

[0043] The medicinal materials involved in the present invention include:

[0044] Cyperus rotundus processed with vinegar: Cyperus rotundus is the dried rhizome of the Cyperus rotundus L. plant of the Cyperaceae family. The processed product obtained by vinegar roasting or vinegar boiling is Cyperus rotundus processed with vinegar.

[0045] Pericarpium Citri Reticulatae Viride is the dried pericarp of the young fruits or immature fruits of the Citrus reticulata Blanco plant of the Rutaceae family and its cultivated varieties.

[0046] Pinellia ternata is the dried tuber of the Pinellia ternata (Thunb.) Breit. plant of the Araceae family.

[0047] Poria cum Radix Pini is the part of the Poria cocos sclerotium that holds the pine root or fine pinewood core in the middle (white Poria cocos).

[0048] Salvia miltiorrhiza is the dried root and rhizome of the Salvia miltiorrhiza Bunge. plant of the Lamiaceae family.

[0049] Ginseng is the root of the Panax ginseng C. A. Mey. [P. schin-seng Nees] plant of the Araliaceae family of the genus Panax.

[0050] Acorus tatarinowii is the dried rhizome of the Acorus tatarinowii Schott plant of the Araceae family.

[0051] Margarita is the nacre layer of the shells of Pteria margaritifera, Pinctada martensii, or several species of freshwater mussels of the Unionidae family.

[0052] Dragon bones are skeletal fossils of ancient mammals such as elephants, rhinos, and three-toed horses.

[0053] Ginger is the fresh rhizome of Zingiber officinale Rosc., a plant of the ginger family.

[0054] TCM pathogenesis of stress-induced insomnia:

[0055] Stress insomnia refers to insomnia caused by factors such as psychological pressure and mood swings, which is often manifested as symptoms such as difficulty falling asleep, easy awakening, and dreaminess. In traditional Chinese medicine theory, liver depression and spleen deficiency combined with deficiency of both heart and spleen are the main pathological mechanisms leading to stress insomnia. The liver governs the release of qi and regulates emotions. If the liver qi is stagnant, the mood is easily volatile and the mind is restless, leading to insomnia. The spleen governs transportation and transformation, which is the source of qi and blood biochemical transformation. If the spleen is weak, the qi and blood biochemical transformation is insufficient, and the mind is not nourished, which can also cause insomnia. The heart governs the mind. If the heart and spleen are both deficient, the mind is not nourished, and the spirit is not at home, thereby causing symptoms such as difficulty falling asleep, easy awakening, and dreaminess. Therefore, the present invention aims to relieve liver depression, strengthen the spleen and nourish the heart through reasonable compatibility of Chinese medicines, thereby achieving the purpose of treating stress insomnia.

[0056] Pharmacological action: The present invention is derived from the empirical prescription of the inventor's long-term clinical practice. Vinegar-scented Cyperus has the effects of soothing the liver and relieving depression, regulating menstruation and relieving pain, while Acorus calamus can open the mind and calm the heart, eliminate dampness and soothe the stomach. The two are the main drugs and work together on the pathological state of liver depression and spleen deficiency. Qingpi, Pinellia, and Poria are the ministerial drugs. Qingpi is warm in nature, bitter and pungent in taste, and enters the liver and stomach meridians. It is good at soothing the liver and regulating qi, eliminating accumulation and removing stagnation; Pinellia is warm in nature, pungent in taste, and enters the spleen and stomach meridians. It has the effects of drying dampness and resolving phlegm, and descending adverse vomiting; Poria is flat in nature, sweet and light in taste, and enters the heart, spleen, and kidney meridians, and can strengthen the spleen and eliminate dampness, calm the heart and tranquilize the mind. The combination of these three drugs further strengthens the effects of soothing the liver and relieving depression and strengthening the spleen and nourishing the heart, and is particularly effective for treating insomnia symptoms caused by mood swings and indigestion. The liver-soothing effect of the green peel is combined with the phlegm-removing and adverse-relief effect of the pinellia tuber, which can effectively relieve the discomfort symptoms such as chest tightness and nausea, while the spleen-strengthening and dampness-removing effect of Poria cocos helps to improve the function of the digestive system, thereby providing support for improving sleep quality. The three complement each other and strengthen the effects of soothing the liver and relieving depression and strengthening the spleen and nourishing the heart. Salvia miltiorrhiza, ginseng, mother-of-pearl, and dragon bone are used as adjuvants. Salvia miltiorrhiza promotes blood circulation and removes blood stasis, calms the nerves and calms the mind, ginseng greatly replenishes vital energy, invigorates the spleen and benefits the lungs, mother-of-pearl calms the nerves, clears the liver and improves eyesight, and dragon bone calms the nerves and calms the liver and suppresses yang, and they jointly enhance the calming effect of the prescription. Ginger, as a messenger, harmonizes all medicines, alleviates the side effects of drugs, and enhances drug efficacy. Through this compatibility, the drug combination of the present invention can effectively alleviate the symptoms of stress-induced insomnia and achieve therapeutic purposes.

[0057] Drug pair analysis:

[0058] ①The compatibility of Cyperus rotundus L. vinegar processed and Acorus tatarinowii Schott is based on the principle of "the liver governing dispersion and the spleen governing transportation and transformation" in traditional Chinese medicine theory. Cyperus rotundus L. vinegar processed is warm in nature, pungent and bitter in taste, and belongs to the liver and spleen meridians, with the functions of soothing the liver and relieving depression, regulating menstruation and alleviating pain. Acorus tatarinowii Schott is pungent in taste, warm in nature, and belongs to the heart and stomach meridians, capable of opening orifices and calming the mind, promoting digestion and removing dampness. The combination of the two can play a synergistic role in targeting the pathological state of liver depression and spleen deficiency, thus effectively relieving the symptoms of stress-induced insomnia. The combination of the liver-soothing effect of Cyperus rotundus L. vinegar processed and the mind-calming effect of Acorus tatarinowii Schott can not only improve mood but also regulate the function of the spleen and stomach, enhancing the overall anti-stress ability.

[0059] ②Pinellia ternata (Thunb.) Breit. and Acorus tatarinowii Schott: Pinellia ternata (Thunb.) Breit. is warm in nature, pungent and bitter in taste, and belongs to the spleen, stomach and lung meridians, with the effects of drying dampness and resolving phlegm, descending adverse qi and stopping vomiting, dissipating binds and resolving masses. Acorus tatarinowii Schott is pungent in taste, warm in nature, and belongs to the heart and stomach meridians, capable of opening orifices and calming the mind, promoting digestion and removing dampness. The compatibility of the two can play a synergistic role in targeting the pathological state of phlegm-dampness obstruction and restlessness of the mind, thus effectively relieving the symptoms of stress-induced insomnia. The combination of the phlegm-resolving effect of Pinellia ternata (Thunb.) Breit. and the mind-calming effect of Acorus tatarinowii Schott can not only improve sleep quality but also regulate the function of the spleen and stomach, enhancing the overall anti-stress ability.

[0060] ③Ginseng and Margarita: Ginseng is sweet and slightly bitter in taste, slightly warm in nature, and belongs to the spleen, lung and heart meridians, with the effects of greatly tonifying primordial qi, invigorating the spleen and benefiting the lung, promoting fluid production and quenching thirst, calming the mind and improving intelligence. Margarita is salty in taste, cold in nature, and belongs to the liver and heart meridians, with the functions of suppressing the hyperactive liver-yang, clearing the liver and improving eyesight, calming the mind and tranquilizing the spirit. The compatibility of the two can play a synergistic role in targeting the pathological state of deficiency of both the heart and spleen and hyperactivity of the liver-yang, thus effectively relieving the symptoms of stress-induced insomnia. The combination of the qi-tonifying effect of ginseng and the mind-calming effect of Margarita can not only improve sleep quality but also regulate the function of the heart and spleen, enhancing the overall anti-stress ability.

[0061] ④Poria cum Radice Pini and Salvia miltiorrhiza Bunge: Poria cum Radice Pini is sweet in taste, neutral in nature, and belongs to the heart and spleen meridians, with the effects of calming the mind and tranquilizing the spirit, strengthening the spleen and promoting diuresis. Salvia miltiorrhiza Bunge is bitter in taste, slightly cold in nature, and belongs to the heart and liver meridians, with the functions of promoting blood circulation to remove blood stasis, clearing the heart and relieving vexation. The compatibility of the two can play a synergistic role in targeting the pathological state of deficiency of both the heart and spleen and blood stasis obstruction, thus effectively relieving the symptoms of stress-induced insomnia. The combination of the mind-calming effect of Poria cum Radice Pini and the blood-activating and stasis-removing effect of Salvia miltiorrhiza Bunge can not only improve sleep quality but also regulate the function of the heart and spleen, enhancing the overall anti-stress ability.

[0062] Through the analysis of medicinal pairs, it can be seen that the different medicinal flavors in the traditional Chinese medicine composition provided by the present invention are irreplaceable, and their mutual interaction produces good curative effects on stress-induced insomnia.

[0063] The numerical ranges and parameters involved in the present invention have been presented as precisely as possible in the specific embodiments. However, any numerical value inherently inevitably contains standard deviations caused by individual testing methods. Therefore, unless otherwise clearly stated, it should be understood that all numerical ranges or specific data used in this disclosure may have certain reasonable deviations within a certain range, for example: within ±10%, ±5%, ±1% or ±0.5%. The present invention will be further described below in conjunction with the embodiments:

[0064] Example 1

[0065] Prescription 1: 12 g of Cyperus rotundus L. vinegar processed, 15 g of Pericarpium Citri Reticulatae Viride, 12 g of Pinellia ternata (Thunb.) Breit., 15 g of Poria cum Radix Pini, 15 g of Salvia miltiorrhiza Bunge, 9 g of Ginseng Radix et Rhizoma, 15 g of Acorus tatarinowii Schott, 30 g of Concha Margaritifera Usta, 30 g of Os Draconis, 5 g of Ginger Rhizome.

[0066] Take the first 10 herbs as mentioned above, soak them in water for 0.5 - 2 h, decoct them twice, each time for 1.5 - 2 hours. Add 8 - 15 times the amount of water for the first decoction and 6 - 12 times the amount of water for the second decoction. Filter, combine the two decoction liquids, concentrate them under reduced pressure to a thick paste with a relative density of 1.25 - 1.4 (50 - 60 °C), and dry them under reduced pressure (60 - 80 °C) to obtain a dry paste for standby. Mix the above dry paste, an appropriate amount of dextrin and medicinal powder, pulverize them, and pass through a 60 - mesh sieve for standby.

[0067] Example 2

[0068] Prescription 2: 12 g of Cyperus rotundus L. vinegar processed, 15 g of Pericarpium Citri Reticulatae, 12 g of Pinellia ternata (Thunb.) Breit., 15 g of Poria cum Radix Pini, 15 g of Salvia miltiorrhiza Bunge, 9 g of Ginseng Radix et Rhizoma, 15 g of Atractylodes macrocephala Koidz., 30 g of Concha Margaritifera Usta, 30 g of Os Draconis recens, 5 g of Ginger Rhizome.

[0069] The preparation method is the same as that of Example 1.

[0070] Example 3

[0071] Prescription 3: 12 g of Aucklandia lappa Decne., 15 g of Pericarpium Citri Reticulatae Viride, 12 g of Pinellia ternata (Thunb.) Breit., 15 g of Poria cum Radix Pini, 15 g of Salvia miltiorrhiza Bunge, 9 g of Codonopsis pilosula (Franch.) Nannf., 15 g of Acorus tatarinowii Schott, 30 g of Concha Margaritifera Usta, 30 g of Os Draconis recens, 5 g of Ginger Rhizome.

[0072] The preparation method is the same as that of Example 1.

[0073] Efficacy verification:

[0074] 1. Screening targets and predicting pathways by network pharmacology:

[0075] (1) Therapeutic advantages of traditional Chinese medicine formulas with multiple targets and multiple pathways

[0076] This traditional Chinese medicine formula acts on 226 targets in the human body. By comparing with the transcriptome detection data of stress - induced insomnia collected clinically, it is found that there are 3655 related expressed genes in stress - induced insomnia ( Figure 1). Using a Venn diagram to draw the drug-disease target map, it was found that this traditional Chinese medicine formula could act on 40 disease targets ( Figure 2 ), suggesting that this traditional Chinese medicine formula has the characteristics of multi-target action.

[0077] (2) Protein-Protein Interaction network diagram of the targets of the traditional Chinese medicine formula for treating stress-induced insomnia

[0078] In the STRING database, we first set the species to "Homo sapiens", and then input the 40 targets of this traditional Chinese medicine formula for treating stress-induced insomnia to obtain a Protein-Protein Interaction (PPI) network diagram ( Figure 3 in a), involving 40 nodes and 85 edges. The TSV file obtained from the STRING online analysis tool was imported into Cytoscape 3.7.1 for visualization and analysis ( Figure 3 in b). The results showed that the interaction relationship among the above 40 action targets was good, with potential effects on treating stress-induced insomnia.

[0079] (3) Functional enrichment of the targets of the traditional Chinese medicine formula for treating stress-induced insomnia

[0080] GO and KEGG are important tools in enrichment analysis, mainly used to explore the biological processes and signaling pathways involved in the treatment of diseases by clinical drugs, as well as the key genes in this process. Through the ClusterProfiler package, we performed GO analysis on the 40 targets of the traditional Chinese medicine formula for treating stress-induced insomnia, and a total of 831 items (adjusted P < 0.05) were obtained, including 795 biological processes (BP), 35 molecular functions (MF), and 78 KEGG. By combining the up-regulated and down-regulated expression of the 40 target genes in the clinical transcriptome, we respectively drew circular diagrams of the top 18 BP ( Figure 4 in a), MF ( Figure 4 in b), and KEGG ( Figure 4 in c) to intuitively understand the biological processes and signaling pathways of the traditional Chinese medicine formula for treating stress-induced insomnia. The top 20 KEGG signaling pathways of the traditional Chinese medicine formula for treating stress-induced insomnia are shown in Table 1.

[0081] Table 1 The top 20 KEGG signaling pathways

[0082]

[0083] 2. Regulatory effect of the traditional Chinese medicine formula on the FOS / PLA2G4A / ELK1 signaling pathway in stress-induced insomnia model mice

[0084] (1) Verification pathway selection

[0085] According to the top 20 KEGG signaling pathways obtained by enrichment analysis, the MAPK signaling pathway was significantly involved in the regulation of treating stress-induced insomnia with traditional Chinese medicine formula. Therefore, we selected the downstream protein targets FOS / PLA2G4A / ELK1 signaling pathway of this signaling pathway to carry out animal experiment verification based on stress-induced insomnia model mice.

[0086] Animal grouping and modeling method:

[0087] A. Animal grouping:

[0088] Thirty SPF-grade C57BL / 6J healthy male mice, 6 - 8 weeks old, weighing 18 - 22 g, were purchased from Beijing Huafukang Biotechnology Co., Ltd. During the experiment, the mice had free access to food and water, the room temperature was 18 - 26°C, the relative humidity was 50% - 70%, and there was a 12h / 12h light-dark cycle.

[0089] After 1 week of adaptive feeding of the mice, the 30 mice were divided into 5 groups according to their spontaneous activity and body weight, namely the blank group, the model group, Prescription 1 group, Prescription 2 group, and Prescription 3 group, with 6 mice in each group.

[0090] B. Preparation of stress-induced insomnia mouse model (using PCPA intraperitoneal injection + modified multi-platform water environment method): According to relevant literature, a stress-induced insomnia mouse model was prepared. At 8:00 - 9:00 every day, PCPA was intraperitoneally injected at 350 mg / kg, once a day for 3 consecutive days. At the same time, a stress-induced insomnia mouse model was prepared using the modified multi-platform water environment method: Prepare a water tank (60 cm × 35 cm × 20 cm), and fill the water tank with water about 0.2 cm deep under the platform. For the mice in the blank group, 6 large platforms (12 cm in diameter, 5 cm high, with a diameter spacing of 15 cm between platforms) were placed in the water tank, and wire meshes were placed on the platforms to allow the mice to sleep without falling into the water. For the mice in the remaining groups, 18 circular platforms (3 cm in diameter, 5 cm high at the bottom, with a diameter spacing of about 6.5 cm between platforms) were placed in the water tank. The mice could drink water and move freely on the platforms. During rapid eye movement sleep, when the abdominal muscle muscle tension of the mice decreased, the mice would fall into the water or wake up when touching the water surface, resulting in sleep deprivation of the mice. During the modeling period, the mice could freely access the food pellets and water bottles at the top of the water tank. Breeding environment: 12h / 12h light-dark cycle, with light starting at 8:00, constant temperature (22 ± 2)°C, and the water in the water tank was changed 2 times a day during the entire sleep deprivation period. To reduce stress, the experiment was carried out after each mouse was familiar with the environment for 3 days. The mice were sleep deprived for 24 h every day for 3 days.

[0091] C. Verification of whether the model was successfully established:

[0092] Twenty-four hours after the establishment of the model, the sleep latency and sleep duration of the righting experiment were used to evaluate the model. The disappearance of the righting reflex in the animal for more than 1 minute was used as the sleep onset criterion, and the sleep onset time was recorded; the flipping reaching 3 times within 1 minute was used as the sleep end criterion, and the sleep end time was recorded. Compared with the blank group, the sleep latency of the model group, prescription 1, 2, and 3 groups was prolonged (P < 0.05), and the sleep duration was shortened (P < 0.05), indicating that the stress-induced insomnia model mice were successfully modeled. See Figure 5 。

[0093] (2) Operating steps of Western blot experiment

[0094] Take the hippocampal tissues of the stress-induced insomnia model mice in each group (blank group, model group, prescription 1 group, prescription 2 group, prescription 3 group). After rapid freezing with liquid nitrogen, cut the hippocampal region for subsequent Western blot experiment detection and analysis. To avoid sample degradation, the frozen samples need to be quickly frozen in liquid nitrogen and then transferred to a -80°C refrigerator for storage.

[0095] Take out the hippocampi of the mice in each group from the refrigerator, homogenize the tissues with RIPA lysis buffer. After homogenization, place the samples on ice and let them stand for 30 minutes to ensure sufficient cell lysis and protein release. Remove cell debris by centrifugation (12,000 rpm, 4°C, 10 minutes), and collect the supernatant as the total protein sample. Subsequently, use the BCA method to measure the protein concentration to ensure that the protein content in each group of samples is consistent. According to the molecular weight of the target protein, select an appropriate SDS-PAGE separating gel. Mix the protein sample (20 μg) with the loading buffer and boil for 10 minutes to denature the protein. Then load the sample onto the gel and perform protein separation by electrophoresis (120 V, 2 hours). After electrophoresis, transfer the protein from the gel to the PVDF membrane by wet transfer method for 2 hours, and set the voltage to 100 V.

[0096] After transfer, block the membrane with 5% non-fat milk solution at room temperature for 1 hour. After blocking, incubate the membrane with the diluted primary antibodies (FOS, PLA2G4A, ELK1 antibodies) overnight at 4°C. The next day, wash the membrane 3 times with TBST for 5 minutes each time, and incubate the membrane with the secondary antibody for 1 hour. After incubation, wash the membrane with TBST 3 times again, and finally develop the image with ECL chemiluminescent substrate.

[0097] After obtaining the images of the protein bands through the imaging system, use the ImageJ analysis software to quantitatively analyze the optical density of each band. Measure the optical density value of the band by the software and normalize it with the optical density of the internal reference protein β-actin. Finally, calculate the relative changes in the protein expression levels between each group and perform statistical analysis to compare the differences between each group.

[0098] (3) Results of Western blot

[0099] Results of Western blot showed that (Table 2, Figure 6 ) compared with the blank group, the protein expressions of FOS, PLA2G4A, ELK1, and IL1B in the stress-induced insomnia model mice were significantly increased (P < 0.01); compared with the model group, the protein expressions of FOS, PLA2G4A, ELK1, and IL1B in the traditional Chinese medicine formula group were significantly decreased (P < 0.01). It is suggested that this traditional Chinese medicine formula can treat stress-induced insomnia by participating in the regulation of the FOS / PLA2G4A / ELK1 signaling pathway.

[0100] Table 2 Comparison of the protein expression levels of FOS, PLA2G4A, ELK1, and IL1B in the hippocampus of mice in each group (n = 6, ±s)

[0101]

[0102] Note: a Compared with the blank group, P < 0.01; b Compared with the model group, P < 0.01.

[0103] 3. Drug component conversion experiment:

[0104] Meanwhile, the traditional Chinese medicine group in Example 1 was set as Prescription 1 group: Cyperus rotundus L. 12g, Pericarpium Citri Reticulatae Viride 15g, Pinellia ternata 12g, Poria cum Radix Pini 15g, Salvia miltiorrhiza 15g, Ginseng 9g, Acorus tatarinowii 15g, Concha Margaritifera Usta 30g, Os Draconis 30g, Zingiber officinale 5g. Another Prescription 2 group and Prescription 3 group in Examples 2 - 3 were set as parallel controls. The formulas of Prescription 2 and Prescription 3 are as follows (the preparation methods of the formula granules of Prescription 2 and 3 are the same as those of Prescription 1 group):

[0105] Prescription Two: Cyperus rotundus L. 12g, Pericarpium Citri Reticulatae 15g, Pinellia ternata 12, Poria cum Radix Pini 15g, Salvia miltiorrhiza 15g, Ginseng 9g, Atractylodes macrocephala 15g, Concha Margaritifera Usta 30g, Os Draconis 30, Zingiber officinale 5g (Pericarpium Citri Reticulatae Viride and Acorus tatarinowii are changed to Pericarpium Citri Reticulatae and Atractylodes macrocephala)

[0106] Prescription Three: Aucklandia lappa Decne. 12g, Pericarpium Citri Reticulatae Viride 15g, Pinellia ternata 12g, Poria cum Radix Pini 15g, Salvia miltiorrhiza 15g, Codonopsis pilosula 9g, Acorus tatarinowii 15g, Concha Margaritifera Usta 30g, Os Draconis 30g, Zingiber officinale 5g (Cyperus rotundus L. and Ginseng are changed to Aucklandia lappa Decne. and Codonopsis pilosula)

[0107] Results of Western blot showed that (Table 3, Table 4, Figure 7), compared with the prescription 1 group, the protein expressions of FOS, PLA2G4A, ELK1, and IL1B in the prescription 2 group were all significantly increased (P < 0.01), indicating that the curative effect of the prescription 1 group was better than that of the prescription 2 group; compared with the prescription 1 group, the protein expressions of FOS, PLA2G4A, ELK1, and IL1B in the prescription 3 group were all significantly increased (P < 0.01), indicating that the curative effect of the prescription 1 group was better than that of the prescription 3 group.

[0108] Table 3 Comparison of the protein expression levels of FOS, PLA2G4A, ELK1, and IL1B in the hippocampus of mice in each group

[0109] (n = 6, ±s)

[0110]

[0111] Note: a Compared with the prescription 1 group, P < 0.01.

[0112] Table 4 Comparison of the protein expression levels of FOS, PLA2G4A, ELK1, and IL1B in the hippocampus of mice in each group

[0113] (n = 6, ±s)

[0114]

[0115] Note: a Compared with the prescription 1 group, P < 0.01.

[0116] The above results show that the traditional Chinese medicine formula (Example 1, i.e., the prescription 1 group) can treat stress-induced insomnia by participating in the regulation of the FOS / PLA2G4A / ELK1 signaling pathway, and its curative effect is better than that of the prescription 1 group and the prescription 2 group.

[0117] Conclusion: The traditional Chinese medicine formula of Example 1 demonstrates its comprehensive advantages in the treatment of stress-induced insomnia through a multi-target and multi-pathway regulation mechanism, combined with the significant regulatory effects of GO function enrichment and KEGG signaling pathways. This multi-level mechanism of action provides unique therapeutic potential for this formula, especially in dealing with complex stress responses and neurological disorders, and has important clinical application prospects.

[0118] 4. Efficacy of the traditional Chinese medicine formula on patients with stress-induced insomnia intolerant to electromagnetic radiation

[0119] 4.1. Research objects:

[0120] 120 patients with stress-induced insomnia intolerant to electromagnetic radiation who met the diagnostic criteria were selected. The SPSS statistical software was used to generate a unified random number table, and the patients were assigned to the treatment group 1, treatment group 2, and western medicine group in the order of their medical visits.

[0121] 4.2. Diagnostic criteria:

[0122] Refer to the diagnostic criteria in the "Classification and Diagnostic Criteria of Mental Disorders in China" (CCMD-3).

[0123] 4.3. Inclusion criteria:

[0124] (1) Those who meet the above diagnostic criteria;

[0125] (2) Aged 18 to 55 years old;

[0126] (3) Those with a PSQI score ranging from 11 to 15;

[0127] (4) Long-term exposure to a complex electromagnetic environment, with a total electromagnetic radiation time of ≥ 3 months

[0128] (5) Those who voluntarily participate in this study and sign the informed consent form.

[0129] 4.4. Exclusion criteria:

[0130] (1) Those who have participated in other clinical trials within the past 3 months;

[0131] (2) Those who are unwilling to cooperate.

[0132] 4.5. Criterion for exclusion from the study:

[0133] (1) Those who do not meet the inclusion criteria after being included in the study;

[0134] (2) Those who do not take medications according to the study protocol after being included in the study.

[0135] 4.6. Criterion for termination of the study:

[0136] (1) Those who experience serious adverse events and are not suitable to continue with the study protocol;

[0137] (2) Those who develop certain sudden diseases and are not suitable to continue with the study protocol;

[0138] (3) Those with poor compliance of the subjects, who fail to complete the study according to the study protocol.

[0139] 4.7. Estimation of sample size and randomization method:

[0140] (1) Estimation of sample size: Referring to the literature reports, previous clinical experience, and research basis, and consulting a statistical expert, using the SPSS statistical software, setting the significance level α = 0.05 (one-sided), the power of the test 1-β = 0.90, the first overall rate (estimated) π1 = 60%, the second overall rate (estimated value) π2 = 85%. From this, the sample size of each group n = 36. Adding 10% of the dropout cases, the total sample size of the two groups N = 80.

[0141] (2) Randomization method: The SPSS statistical software was used to generate a unified random number table, and the patients were assigned to the traditional Chinese medicine group and the western medicine group according to the order of their visits.

[0142] 4.8. Treatment plan

[0143] Treatment group 1: Drug composition: 10 g of Pinellia ternata (processed with ginger), 20 g of Coix lacryma-jobi, 15 g of Ziziphus jujuba var. spinosa (fried), 15 g of Acorus tatarinowii, 15 g of Atractylodes macrocephala, 20 g of Poria, 15 g of Polygala tenuifolia (processed with honey), 20 g of Semen platycladi, and 6 g of Glycyrrhiza uralensis. One dose of the drug was made into 2 bags of granules (produced by Tianjin Xinjingtang Traditional Chinese Medicine Clinic Co., Ltd., batch number: 20230801), each bag weighing 7 g. Take 1 bag each time, twice a day, 30 minutes after breakfast and dinner.

[0144] Treatment group 2: Drug composition: 12 g of Cyperus rotundus (processed with vinegar), 15 g of Citrus reticulata Blanco var. austera, 12 g of Pinellia ternata, 15 g of Poria, 15 g of Salvia miltiorrhiza, 9 g of Panax ginseng, 15 g of Acorus tatarinowii, 30 g of Margarita nuda, 30 g of Os draconis, and 5 g of Zingiber officinale. One dose of the drug was made into 2 bags of granules (produced by Tianjin Xinjingtang Traditional Chinese Medicine Clinic Co., Ltd., batch number: 202301003), each bag weighing 7 g. Take 1 bag each time, twice a day, 30 minutes after breakfast and dinner.

[0145] Positive control group: Oral zolpidem tartrate tablets [Sanofi (Hangzhou) Pharmaceutical Co., Ltd., import drug registration number: H20181237, 10 mg per tablet], 10 mg each time, once a day, taken before going to bed. The treatment period for both groups was 4 weeks, and no other sedative and hypnotic drugs were taken during the treatment.

[0146] 4.9. Observation items:

[0147] (1) General observation items: Include name, gender, age, marital status, occupation, contact information, etc. This part of the information belongs to the personal privacy confidentiality part and cannot be leaked and is only for the use of this study.

[0148] (2) Quantification items: Total sleep duration before and after treatment

[0149] (3) Scale measurement: Sleep parameters (sleep efficiency, sleep structure, arousal index), sleep quality (PSQI score), and quality of life (SGRQ score).

[0150] 4.10. Efficacy evaluation:

[0151] (1) Improvement of sleep duration: Compare the recorded sleep duration before and after treatment.

[0152] (2) Improvement of sleep parameters: Compare the levels of each quantified component of sleep efficiency, sleep structure, and arousal index before and after treatment.

[0153] (3) Improvement in sleep quality: Compare the total scores of the PSQI scale before and after treatment.

[0154] (4) Improvement in quality of life: Compare the total scores of the SGRQ scale before and after treatment.

[0155] 4.11. Efficacy determination:

[0156] The clinical efficacy was determined by the reduction rate of the total PSQI score. The reduction rate of the total PSQI score = (total PSQI score before treatment - total PSQI score after treatment) / total PSQI score before treatment × 100%. Cure: Insomnia completely disappeared, and the reduction rate of the total PSQI score ≥ 80%; Marked effect: Insomnia almost completely disappeared, and the reduction rate of the total PSQI score ≥ 50% but < 80%; Improvement: Insomnia was significantly reduced, and the reduction rate of the total PSQI score ≥ 30% but < 50%; Ineffective: Insomnia had no improvement, and the reduction rate of the total PSQI score < 30%. Total effective = Cure + Marked effect + Improvement.

[0157] The curative effect of traditional Chinese medicine syndromes was determined by the reduction rate of the traditional Chinese medicine syndrome scores. The reduction rate of the traditional Chinese medicine syndrome scores = (traditional Chinese medicine syndrome scores before treatment - traditional Chinese medicine syndrome scores after treatment) / traditional Chinese medicine syndrome scores before treatment × 100%. Clinical recovery: Clinical symptoms and signs disappeared or basically disappeared, and the reduction rate of the traditional Chinese medicine syndrome scores ≥ 95%; Marked effect: Clinical symptoms and signs were significantly improved, and the reduction rate of the traditional Chinese medicine syndrome scores ≥ 70% but < 95%; Improvement: Clinical symptoms and signs were both improved, and the reduction rate of the traditional Chinese medicine syndrome scores ≥ 30% but < 70%; Ineffective: Symptoms and signs were not significantly improved or worsened, and the reduction rate of the traditional Chinese medicine syndrome scores < 30%. Total effective = Clinical recovery + Marked effect + Improvement.

[0158] 4.12. Statistical method: The data were processed using SPSS 22.0 software. Measurement data were expressed as (x±s) and analyzed by t-test; Count data were analyzed by chi-square test using rate (%). P < 0.05 was considered statistically significant.

[0159] 4.13. Experimental results

[0160] 4.13.1 Treatment results

[0161] 4.13.1.1 Comparing the PSQI scores and efficacy of the two groups of patients before and after treatment, the results are shown in Table 5:

[0162] Table 5 Comparison of PSQI item scores of the treatment group and the control group before and after treatment (x±s)

[0163]

[0164] Note: Compared with before treatment, *: P < 0.05, compared with the control group, #: P < 0.05.

[0165] Conclusion:

[0166] By comparing various indicators of the treatment group and the control group, it can be clearly seen that the treatment group has significant improvements in aspects such as sleep quality, sleep onset time, sleep duration, sleep efficiency, sleep disorders, and daytime dysfunction. Specifically, the indicators of the treatment group were significantly lower after treatment than before treatment, and compared with the control group, the differences were statistically significant (P < 0.05). This indicates that this treatment method has a significant effect on improving the sleep status of patients with stress insomnia. In addition, although the control group also had certain improvements, the effects were not as obvious as those of the treatment group.

[0167] 4.13.2 Comparison of the curative effects of traditional Chinese medicine syndromes between the two groups of patients

[0168] The total effective rate of the curative effect of traditional Chinese medicine syndromes in the treatment group was 96%, and that in the control group was 70%. The treatment group was superior to the control group (χ 2 = 12.43, P < 0.01).

[0169] Table 6 Comparison of the curative effects of traditional Chinese medicine syndromes between male patients with stress insomnia in the two groups [cases (%)]

[0170]

[0171] 4.13.3 Comparison of traditional Chinese medicine syndromes between the two groups of patients with stress insomnia

[0172]

[0173] By comparing the changes in various traditional Chinese medicine syndrome indicators of the treatment group and the control group, it can be seen that the improvement degree of the treatment group in aspects such as abdominal distension, irritability, fatigue, and mental fatigue is significantly higher than that of the control group. Specifically, the median values of the indicators after treatment decreased significantly, and statistical analysis showed that the differences were extremely significant (p < 0.001). This indicates that the traditional Chinese medicine formula has a significant curative effect on improving the traditional Chinese medicine syndromes of patients with stress insomnia. The overall symptom improvement range of the treatment group is relatively large, suggesting that this treatment plan has high application value in clinical practice.

[0174] The above are only the preferred implementation manners of the present invention. It should be noted that for those of ordinary skill in the art in this technical field, without departing from the principle of the present invention, several improvements and refinements can still be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition is made from raw materials in the following parts by mass: 12-18 parts of Cyperus rotundus L. var. rotundus treated with vinegar, 12-16 parts of Pericarpium Citri Reticulatae Viride, 12-20 parts of Pinellia ternata (Thunb.) Breit., 12-18 parts of Poria cum Radix Pini, 12-19 parts of Salvia miltiorrhiza Bunge, 8-12 parts of Ginseng Radix et Rhizoma, 10-18 parts of Acorus tatarinowii Schott, 20-30 parts of Concha Margaritifera Usta, 25-35 parts of Os Draconis, and 3-6 parts of Zingiber officinale Rosc.

2. The traditional Chinese medicine composition according to claim 1, characterized in that is made from raw materials in the following parts by mass: 12 parts of Cyperus rotundus L. var. rotundus treated with vinegar, 15 parts of Pericarpium Citri Reticulatae Viride, 12 parts of Pinellia ternata (Thunb.) Breit., 15 parts of Poria cum Radix Pini, 15 parts of Salvia miltiorrhiza Bunge, 9 parts of Ginseng Radix et Rhizoma, 15 parts of Acorus tatarinowii Schott, 30 parts of Concha Margaritifera Usta, 30 parts of Os Draconis, and 5 parts of Zingiber officinale Rosc.

3. An extract prepared by extracting the traditional Chinese medicine composition described in claim 1 or 2.

4. A preparation method of the extract described in claim 3, comprising soaking the traditional Chinese medicine composition described in claim 1 or 2 in water and then performing water decoction extraction, and concentrating and drying the decoction to obtain the extract.

5. The preparation method according to claim 4, characterized in that, The number of times of the water decoction extraction is 2 times, 1.5-2 h each time. For the first time, add water at 8-15 times the mass of the medicinal materials, and for the second time, add water at 6-12 times the mass of the medicinal materials.

6. The preparation method according to claim 4, characterized in that, Concentrate to a relative density of 1.25-1.

40.

7. Use of the traditional Chinese medicine composition described in claim 1 or 2, or the extract described in claim 3, or the extract prepared by the preparation method described in any one of claims 4-6 in the preparation of a drug for preventing and treating stress-induced insomnia.

8. The application according to claim 7, wherein The prevention and treatment include regulating the expression level of proteins and / or targets, prolonging the sleep latency, and prolonging the sleep duration; The proteins include at least one of FOS, PLA2G4A, ELK1, and IL1B.

9. A drug for preventing and treating stress-induced insomnia, which comprises a pharmaceutically acceptable excipient and the traditional Chinese medicine composition described in any one of claims 1 or 2, or the extract described in claim 3, or the extract prepared by the preparation method described in any one of claims 4-6.

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