Traditional Chinese medicine composition for treating insomnia as well as preparation method and application thereof

Abstract

The invention belongs to the field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition for treating insomnia and a preparation method and application thereof. The traditional Chinese medicine composition for treating insomnia disclosed by the invention is derived from a classic famous prescription combination, and provides an effective prescription for solving the problem of insomnia of marine navigation personnel, so that the health guarantee ability of people such as navy long-voyage and underwater navigation officers and soldiers, marine exploration personnel, fishermen and ocean crew in China is improved.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and relates to a traditional Chinese medicine composition for treating insomnia, its preparation method and application, and particularly relates to a traditional Chinese medicine composition for treating insomnia of long-distance navigation personnel, its preparation method and application. Background Art

[0002] Long-distance navigation personnel refer to those who are at sea for a long time. Long-distance navigation insomnia refers to the sleep disorder caused by the special living environment, strict management system, high-intensity training and various military emergency operations that officers and soldiers bear. During long-term navigation operations, long-distance navigation personnel need to face situations such as narrow working and living spaces, noise, sea bumps, loneliness, and the change of circadian rhythm caused by the watch-keeping system. Compared with ordinary people, long-distance navigation personnel are more prone to insomnia.

[0003] Insomnia can lead to negative emotions such as negativity and depression in long-distance navigation officers and soldiers or seafarers, resulting in problems related to cognitive abilities such as memory decline and decreased analytical and decision-making abilities. Lack of sleep can also lead to decreased activity ability.

[0004] To improve the sleep of long-distance navigation officers and soldiers or seafarers during long-distance navigation military activities, the reported intervention measures currently include non-drug and drug treatments. Non-drug therapies include: 1) Music therapy: The tissues and cells of the human body can resonate with the frequency sound pressure of music sound waves, thereby affecting the heart rate, respiration, and brain waves of people, improving the cardiovascular system, respiratory system, nervous system, etc., so as to relax the body and mind. 2) Relaxation therapy: ① Chewing therapy: Officers and soldiers relax by chewing 1 piece of chewing gum 1-2 hours after meals. ② Relaxation therapy: Relax through the reciprocal breathing method. 3) External treatment of traditional Chinese medicine: Treat insomnia through methods such as auricular points, acupuncture, and massage: For example, the insomnia condition of some officers and soldiers in "XX Mission-2017" improved after using moxibustion, auricular points, etc. 4) Psychotherapy: Including cognitive behavioral therapy, psychological counseling, psychological suggestion, etc. Drug treatments include: ① Modern drug treatment: Including benzodiazepines, non-benzodiazepines, antidepressants, melatonin, orexin antagonists, etc. ② Traditional Chinese medicine treatment: For example, Zhang Wenguang et al. used Guipi Decoction combined with music therapy to improve the sleep condition and related symptoms of long-distance navigation officers and soldiers or seafarers. Currently, relevant studies have proved that traditional Chinese medicine can improve insomnia in long-distance navigation personnel, but there are not many cases of using traditional Chinese medicine to treat insomnia in long-distance navigation personnel at present, and there is still a lack of a traditional Chinese medicine treatment plan for long-distance navigation insomnia with complete traditional Chinese medicine theory.

[0005] There is little research on seafarers' insomnia at home and abroad, and most of the research on the insomnia mechanism focuses on the level of neurotransmitter regulation, and there has been no in-depth exploration of the synergistic relationship between neuropeptides and flora. In view of the close relationship between the disorder of BGMA network regulation and the onset of this disease, it is necessary to focus the research on the linkage regulation mechanism of neuropeptides and flora in the pathway. Summary of the invention

[0006] In order to solve the above technical problems, the applicant found in the early stage of the long-distance personnel's symptoms that their common symptoms include: shortness of breath, laziness, depression, irritability, fatigue, muscle soreness, forgetfulness, etc. By classifying the symptoms, it was found that they are closely related to the liver and spleen. At the same time, the team members conducted an epidemiological survey on 1,216 patients with insomnia in different maritime occupational groups and found that the TCM syndromes of long-distance insomnia attacks mostly involve the liver, spleen, and heart. Among them, 62.42% of the TCM pathogenesis of insomnia patients at sea is related to the liver and spleen, which provides an important basis for the TCM theoretical framework and formula establishment of the Chinese medicine composition of the present invention. Therefore, based on the previous nearly 10 years of research, the applicant found that "the imbalance of neuropeptides related to the GABA pathway of the brain-gut-bacteria axis network and the regulation of intestinal flora is the pathological mechanism of repeated insomnia attacks in maritime professionals", providing a Chinese medicine composition for the treatment of insomnia and its preparation method and application.

[0007] Specifically, the Chinese medicine composition for treating insomnia provided by the present invention comprises: bupleurum, white peony root, immature bitter orange, roasted liquorice, stir-fried spiny jujube seed, anemarrhena, tuckahoe, and ligusticum chuanxiong.

[0008] The Chinese medicine composition of the present invention is also called "Chaishao Zaoren Decoction", which is composed of the original prescriptions of "Sini San" and "Suanzaoren Decoction" of the Han Dynasty. "Sini San" comes from "Treatise on Febrile Diseases", and its efficacy focuses on soothing the liver and regulating the spleen. In the prescription, Bupleurum is the main ingredient for soothing the liver and relieving depression, and promoting yang qi; white peony is the minister for astringing yin, nourishing blood and softening the liver. The combination of the two medicines can regulate liver qi, astringe yin and harmonize yang; Zhishi is the smooth flow of spleen and stomach qi, and licorice harmonizes the spleen and stomach. "Suanzaoren Decoction" is recorded in "Golden Chamber" for "deficiency, restlessness and insomnia", and its symptoms are consistent with this disease. In the prescription, Suanzaoren nourishes blood, nourishes the liver and calms the mind, Poria calms the mind and calms the mind, Anemarrhena clears stomach heat and reduces fire, nourishes yin and eliminates restlessness, and Chuanxiong promotes blood circulation and promotes qi. Therefore, the combination of the two has the efficacy of "soothing the liver and strengthening the spleen, regulating yin and yang, and treating both the mind and body".

[0009] Preferably, the above-mentioned traditional Chinese medicine composition for treating insomnia comprises, by weight: 4-16 parts of bupleurum, 4-16 parts of white peony root, 4-16 parts of immature bitter orange, 3-12 parts of roasted liquorice, 7-28 parts of stir-fried spiny jujube seeds, 3-12 parts of anemarrhena, 4-16 parts of poria, and 3-12 parts of ligusticum chuanxiong.

[0010] Further preferably, the above-mentioned traditional Chinese medicine composition for treating insomnia comprises, by weight: 10-15 parts of bupleurum, 12-16 parts of white peony root, 12-16 parts of immature bitter orange, 10-12 parts of roasted liquorice, 20-28 parts of stir-fried spiny jujube seeds, 10-12 parts of anemarrhena, 12-16 parts of poria, and 10-12 parts of ligusticum chuanxiong.

[0011] More preferably, the traditional Chinese medicine composition for treating insomnia comprises the following components in parts by weight: prescription: 16 parts of Bupleuri Radix, 16 parts of Paeoniae Radix Alba, 16 parts of Aurantii Fructus Immaturus, 12 parts of Glycyrrhizae Radix Preparata, 28 parts of Ziziphi Spinosae Semen, 12 parts of Anemarrhenae Rhizoma, 16 parts of Poria, 12 parts of Chuanxiong Rhizoma.

[0012] Preferably, the insomnia is that of seafarers during sea voyages.

[0013] On the other hand, the present invention also provides a preparation method of the above-mentioned traditional Chinese medicine composition for treating insomnia, comprising: soaking the compatibility combination prescription in water and then decocting, filtering the medicinal residues with a gauze, repeating the above operations 3 times as before, and then heating and concentrating the filtered medicinal liquid into a powder and storing it sealed.

[0014] On yet another hand, the present invention also provides a drug for treating insomnia, which comprises the above-mentioned traditional Chinese medicine composition for treating insomnia.

[0015] Preferably, the above-mentioned drug for treating insomnia further comprises a pharmaceutically acceptable excipient.

[0016] Preferably, the dosage form of the above-mentioned drug for treating insomnia is: oral liquid, capsule, tablet, pill, granule, powder, decoction or ointment, and more preferably traditional Chinese medicine instant granules.

[0017] On still another hand, the present invention also provides the application of the above-mentioned traditional Chinese medicine composition for treating insomnia in the preparation of drugs for treating insomnia.

[0018] The technical solution of the present invention has the following beneficial effects:

[0019] (1) The traditional Chinese medicine composition for treating insomnia of the present invention is derived from a classic famous prescription combination, providing an effective prescription for solving the insomnia problem of seafarers during sea voyages, thereby improving the health protection ability of officers and soldiers on long sea voyages and submarine voyages of the Chinese Navy, as well as people such as offshore exploration personnel, fishermen, and ocean crew members;

[0020] (2) The traditional Chinese medicine composition for treating insomnia of the present invention can improve the sleep situation of rats with long voyage insomnia, as well as negative emotions, cognitive impairment, decreased spontaneous activity ability, etc. caused by insomnia by means of different doses, and can be taken by people with long voyage insomnia to improve the sleep condition of people with long voyage insomnia and relieve the harm caused by insomnia;

[0021] (3) The traditional Chinese medicine composition for treating insomnia of the present invention can regulate the Glu - GABA system (NR1, CAMK2, GABAARα1, GAT - 1) and brain - gut peptides NT, NPY of rats with long voyage insomnia and promote sleep;

[0022] (4) The traditional Chinese medicine composition for treating insomnia of the present invention can increase the diversity of intestinal flora in rats and relieve the insomnia condition of long voyage rats by changing the intestinal flora composition of rats with long voyage insomnia. Brief Description of the Drawings

[0023] By reading the following detailed description of the preferred embodiments, various other advantages and benefits will become clear to those of ordinary skill in the art. The drawings are only for the purpose of showing the preferred embodiments and are not considered to be a limitation of the present invention.

[0024] Figure 1 It consists of a shaker;

[0025] Figure 2 It is a schematic diagram of the overall structure of the shaker;

[0026] Figure 3 It is a schematic diagram of the standing box for the small water environment platform;

[0027] Figure 4 It is a line graph of the body weight changes of each group of rats during the modeling period (n = 10);

[0028] Figure 5 It is a bar graph of the hanging immobile time values of each group of rats (n = 5); compared with the blank group, **P < 0.01, compared with the model group, △△P < 0.01;

[0029] Figure 6 It is a bar graph of the sleep latency and sleep duration of each group of rats (n = 5); compared with the blank group, *** P < 0.001, compared with the model group, △ P < 0.05, △△△ P < 0.001;

[0030] Figure 7 It is a bar graph of the spontaneous alternation rate and total number of arm entries of each group of rats (n = 5); compared with the blank group, * P < 0.05, *** P < 0.001, compared with the model group, △ P < 0.05, △△ P < 0.01, △△△ P < 0.001;

[0031] Figure 8 It is a bar graph of the number of rears, rear time, grooming times, and grooming time of each group of rats in the open field (n = 5); compared with the blank group, *** P < 0.001, compared with the model group, △ P < 0.05, △△ P < 0.01, △△△ P < 0.001;

[0032] Figure 9Bar graphs of the residence time in the central area, the percentage of the number of grid crossings in the central area, the total movement distance, and the total number of grid crossings (n = 5) for each group of rats; compared with the blank group, * P < 0.05, ** P < 0.01, *** P < 0.001, compared with the model group, △△ P < 0.01 △△△ P < 0.001;

[0033] Figure 10 The movement trajectories of rats in each group in the open field test;

[0034] Figure 11 Bar graphs of the relative expression levels of GABAARα1, GAT-1, and NPY proteins in the hypothalamus of rats in each group; compared with the blank group, * P < 0.05, *** P < 0.001, compared with the model group, △△ P < 0.01, △△△ P < 0.001;

[0035] Figure 12 Bar graphs of the expression levels of GABAARα1, GAT-1, and NPY mRNAs in the hypothalamus of rats in each group; compared with the blank group, compared with the blank group, ** P < 0.01, *** P < 0.001, compared with the model group, △ P < 0.05, △△ P < 0.01;

[0036] Figure 13 Bar graphs of the expression levels of NT, NR1, and CAMK2 mRNAs in the hypothalamus of rats in each group;

[0037] Figure 14 Bar graphs of the expression levels of NT, NR1, and CAMK2 proteins in the hypothalamus of rats in each group;

[0038] Figure 15 Comparison of the intestinal microbial diversity of rats in different groups;

[0039] Figure 16 PCoA analysis based on microorganisms;

[0040] Figure 17 Bar graphs of the comparison of species composition at the phylum level;

[0041] Figure 18 Box plots of the comparison of species composition at the phylum level;

[0042] Figure 19 Bar graphs of the comparison of species composition at the genus level;

[0043] Figure 20 It is a box plot for comparing species composition at the genus level;

[0044] Figure 21 It is a bar chart for species composition at the species level;

[0045] Figure 22 It is a heat map of differential species at the species level. Detailed implementation manners

[0046] In order to fully understand the purpose, features and effects of the present invention, the present invention will be described in detail through the following specific implementation manners. Except for the following content, the process methods of the present invention all adopt conventional methods or devices in the art. Unless otherwise specified, the following terms have the meanings commonly understood by those skilled in the art.

[0047] Example 1

[0048] Formulation: 16 parts of Bupleurum chinense, 16 parts of Paeonia lactiflora, 16 parts of Fructus Aurantii Immaturus, 12 parts of roasted Glycyrrhiza uralensis, 28 parts of Semen Ziziphi Spinosae, 12 parts of Anemarrhena asphodeloides, 16 parts of Poria cocos, 12 parts of Ligusticum wallichii.

[0049] Preparation method: This compatibility combination medicine recipe is soaked in water and then decocted, and the medicinal residues are filtered out with gauze. The above operations are repeated 3 times, and then the filtered medicinal liquid is heated and concentrated into a powder, and stored sealed.

[0050] Example 2

[0051] Formulation: 14 parts of Bupleurum chinense, 14 parts of Paeonia lactiflora, 14 parts of Fructus Aurantii Immaturus, 10 parts of roasted Glycyrrhiza uralensis, 22 parts of Semen Ziziphi Spinosae, 10 parts of Anemarrhena asphodeloides, 12 parts of Poria cocos, 10 parts of Ligusticum wallichii.

[0052] Preparation method: This compatibility combination medicine recipe is soaked in water and then decocted, and the medicinal residues are filtered out with gauze. The above operations are repeated 3 times, and then the filtered medicinal liquid is heated and concentrated into a powder, and stored sealed.

[0053] Example 3

[0054] Formulation: 12 parts of Bupleurum chinense, 10 parts of Paeonia lactiflora, 10 parts of Fructus Aurantii Immaturus, 8 parts of roasted Glycyrrhiza uralensis, 18 parts of Semen Ziziphi Spinosae, 8 parts of Anemarrhena asphodeloides, 10 parts of Poria cocos, 8 parts of Ligusticum wallichii.

[0055] Preparation method: This compatibility combination medicine recipe is soaked in water and then decocted, and the medicinal residues are filtered out with gauze. The above operations are repeated 3 times, and then the filtered medicinal liquid is heated and concentrated into a powder, and stored sealed.

[0056] Example 4

[0057] Formulation: 8 parts of Bupleurum chinense, 8 parts of Paeonia lactiflora, 8 parts of Fructus Aurantii Immaturus, 6 parts of roasted Glycyrrhiza uralensis, 14 parts of Semen Ziziphi Spinosae, 6 parts of Anemarrhena asphodeloides, 8 parts of Poria cocos, 6 parts of Ligusticum wallichii.

[0058] Preparation method: For this combined prescription, soak it in water and then decoct it. Filter the medicinal residues with a gauze. Repeat the operation 3 times as before. Then heat and concentrate the filtered medicinal liquid into a powder and store it sealed.

[0059] Example 5

[0060] Composition: 4 parts of Bupleurum chinense, 4 parts of Paeonia lactiflora, 4 parts of Aurantii Fructus Immaturus, 3 parts of roasted Glycyrrhiza uralensis, 7 parts of Semen Ziziphi Spinosae, 3 parts of Anemarrhena asphodeloides, 4 parts of Poria cocos, 3 parts of Ligusticum chuanxiong.

[0061] Preparation method: For this combined prescription, soak it in water and then decoct it. Filter the medicinal residues with a gauze. Repeat the operation 3 times as before. Then heat and concentrate the filtered medicinal liquid into a powder and store it sealed.

[0062] Animal experiment

[0063] 1 Preparation of experimental drugs

[0064] Prepare the Chai Shao Zao Ren Decoction for animal experiments according to the method of Example 1. The dose of the high-dose group of Chai Shao Zao Ren Decoction is twice that of the medium-dose group, and the medium-dose group is twice that of the low-dose group. All drugs are purchased from Beijing Kangrentang Pharmaceutical Co., Ltd., and the dosage form is Chinese patent medicine instant granules.

[0065] 2 Experimental methods

[0066] 2.1 Model replication

[0067] Randomly divide 60 rats in the model group into a blank group, a model group, a low-dose group of Chai Shao Zao Ren Decoction (2.99 g·kg -1 ·d -1 ), a low-medium-dose group of Chai Shao Zao Ren Decoction (5.98 g·kg -1 ·d -1 ), a high-dose group of Chai Shao Zao Ren Decoction (11.96 g·kg -1 ·d -1 ), and an estazolam group (western medicine group 0.089 mg·kg -1 ·d -1 ) according to the random number table method, with 10 rats in each group.

[0068] Place the rats on the floating platform of the water surface shaking platform instrument at 8:00 every morning for 6 hours, with the speed of the wave maker at 85 revolutions / min, and then place them in the static small platform standing box in the water environment for 6 hours. Model for 12 hours every day for 14 consecutive days. During the modeling period, water and food are suspended in the gap above the model to ensure that the rats can eat and drink normally.

[0069] 2.1.1 Rat water surface shaking platform instrument

[0070] To ensure that the rats can stand normally on the floating platform in the water environment and shake within a certain range, as Figure 1As shown in the figure, the device is mainly composed of four parts: a floating platform A, a test chamber B, a limit frame C, and a wave maker D.

[0071] ① Floating platform: As Figure 1 shown in A, to ensure the floating feeling of the rat platform, the platform is composed of a hollow cylinder or frustum (the upper bottom surface is smaller than the lower bottom surface) that can move freely. The buoyancy it receives can float normally while bearing the weight of the experimental rats.

[0072] ② Test chamber: As Figure 1 shown in B, its main function is to provide environmental conditions for experimental modeling and prevent rats from escaping, etc.

[0073] ③ Limit frame: As Figure 1 shown in C, it is a triangular bracket. Its main function is to make the floating platform shake within a certain range, preventing the floating platform from floating and colliding randomly due to water waves or tipping over due to bumps during the modeling process.

[0074] ④ Wave maker: As Figure 1 shown in D, it is used to generate waves to simulate the wind and wave environment of navigation.

[0075] Twelve floating cylinders (d = 85 mm, H = 165 mm) are evenly arranged around the inner wall of a circular water tank (d = 1000 cm, H = 400 cm), and the brackets are suspended (as Figure 2 shown).

[0076] 2.1.2 Standing box on a small platform in the water environment

[0077] Figure 3 It is a water tank with dimensions of 110 cm * 60 cm * 40 cm (length * width * height). There are 15 small platforms fixed inside the tank. The platforms are circular platforms with a diameter of 6.5 cm and a height of 10 cm. The interval between platforms is 15 cm. Water is injected around the platforms, and the water temperature is maintained at 30 - 32 °C. The water surface is about 6 cm away from the platforms. One animal is placed on each platform. The water tank is covered with a mesh lid to prevent animals from escaping, and a feeding cage is suspended on the lid. Rats can eat freely. When rats enter the sleep state, the muscle strength of their whole body decreases, causing them to touch the water surface or fall into the water, resulting in awakening, and standing for a long time causes fatigue.

[0078] 2.2 Administration method

[0079] All experimental drugs are converted into the equivalent dose of rats as the crude drug amount according to the human drug dosage. The conversion formula is: crude drug amount per kilogram of rats = adult drug dosage g / adult body weight (70 kg) × 6.25. The administration volume is prepared with deionized water according to the gastric capacity of 10 ml / kg of rats, and the drug dosage is adjusted according to the rat body weight. Starting from the first day of modeling, at 7:00 am every day, the blank group and the model group are given distilled water by gavage, and the low-dose group of Chaihu Shaoren Decoction (2.99 g·kg -1·d -1 )、The low and medium dose groups of Chaihu Shaoyao Zaoren Decoction (5.98 g·kg -1 ·d -1 ), the high dose group of Chaihu Shaoyao Zaoren Decoction (11.96 g·kg -1 ·d -1 ) were given intragastric administration of the prepared formula component solution, and the western medicine group was given estazolam (0.089 mg·kg -1 ·d -1 ). The administration volume was 10 ml / kg, and the administration was continuous for 14 days.

[0080] Animal experiment 1: Efficacy evaluation

[0081] 1 Experimental method

[0082] 1.1 Observe the animal model every day, observing the rats from general conditions and body weight.

[0083] 1.2 Behavioral evaluation: On the 14th day of modeling, the tail suspension test, Y-maze test, pentobarbital sodium synergistic test, and open field test were conducted.

[0084] 2. Experimental results

[0085] 2.1 General conditions of rats

[0086] During the modeling period, the general state of the rats was observed and found that: the fur of the rats in the normal group was shiny, the mental state was good, the feces were formed, neither dry nor thin. The rats in the model group showed states of liver depression and spleen deficiency such as being nervous and vigilant, increased aggression, belligerence, liking to huddle together, decreased activity, not liking to clean the hair, the hair being messy, yellowish and dry, and the stools being loose and irregular. Compared with the rats in the model group, the overall conditions of the rats in the estazolam group, the medium dose Chaihu Shaoyao Zaoren Decoction group, and the high dose Chaihu Shaoyao Zaoren Decoction group improved.

[0087] 2.2 Changes in rat body weight

[0088] As Figure 4 shown, on the 7th and 14th days of modeling, compared with the blank group, there were significant differences in the body weights of the rats in the model group, the medium dose Chaihu Shaoyao Zaoren Decoction group, the high dose Chaihu Shaoyao Zaoren Decoction group, and the estazolam group (P<0.01), as detailed in Table 1.

[0089] Table 1 Changes in rat body weight during modeling (g; n = 10)

[0090]

[0091]

[0092] Note: Compared with the blank group, * P<0.05, **P < 0.01.

[0093] 2.3 Depression mood evaluation: Tail suspension test in rats

[0094] As Figure 5 shown, compared with the blank group, the immobile time of rats in the model group was significantly prolonged, with significant statistical difference (P < 0.01). Compared with the model group, the immobile time of rats in the estazolam group and the medium-dose group did not improve significantly, and the difference was not statistically significant, indicating that western medicine and the medium-dose Chaishao Zaoren Decoction have no obvious effect in relieving depression. Compared with the model group, the immobile time of rats in the high-dose group was significantly shortened, with significant statistical difference (P < 0.01). It is indicated that the high-dose Chaishao Zaoren Decoction can relieve the depression mood of rats in the long-term insomnia model to a certain extent. See Table 2 for details.

[0095] Table 2 Immobile time of rats in each group ([[]] n = 5)

[0096]

[0097] Note: Compared with the blank group, ** P < 0.01, compared with the model group, △△ P < 0.01

[0098] 2.4 Sleep status evaluation experiment: Pentobarbital sodium synergistic experiment

[0099] As Figure 6 shown, from the observation of sleep latency, compared with the blank group: the sleep latency of the model group was significantly increased, with extremely significant statistical difference (P < 0.001). Compared with the model group: the sleep latency of the medium-dose group decreased, with statistical difference (P < 0.05), and the sleep latency of the estazolam group and the high-dose group was significantly shortened, with extremely significant statistical difference (P < 0.001).

[0100] From the observation of sleep duration, compared with the blank group: the sleep duration of the model group was significantly decreased, with extremely significant statistical difference (P < 0.001). Compared with the model group: the sleep duration of the medium-dose group increased, with statistical difference (P < 0.05), and the sleep duration of the estazolam group and the high-dose group increased significantly, with extremely significant statistical difference (P < 0.001). See Table 3 for details.

[0101] Table 3 Sleep latency and sleep duration of rats n = 5)

[0102]

[0103] Note: Compared with the blank group, ***P < 0.001, compared with the model group, △ P < 0.05, △△△ P < 0.001

[0104] 2.5 Evaluation experiments on recognition ability, memory ability and activity ability: Y-maze alternation test

[0105] As Figure 7 shown, from the study of the spontaneous alternation rate of rats in each group of the Y-maze, it was found that compared with the blank group, the spontaneous alternation rate of the model group decreased significantly, with extremely significant statistical differences (P < 0.001). Compared with the model group, the spontaneous alternation rates of the medium-dose group, high-dose group, and western medicine group were significantly higher than that of the model group (P < 0.05, P < 0.01, P < 0.001).

[0106] From the study of the total number of arm entries of rats in each group of the Y-maze, it was found that compared with the blank group, the total number of arm entries of rats in the model group decreased, with statistical differences (P < 0.05). Compared with the model group, the total number of arm entries of rats in the high-dose group increased significantly (P < 0.01). There was no significant difference between the medium-dose group and the estazolam group and the model group, but it could be seen that the total number of arm entries of rats in the medium-dose group and the estazolam group had an increasing trend. See Table 4 for details.

[0107] Table 4 Spontaneous alternation rate and total number of arm entries of rats ( n = 5)

[0108]

[0109] Note: Compared with the blank group, * P < 0.05, *** P < 0.001, compared with the model group, △ P < 0.05, △△ P < 0.01, △△△ P < 0.001

[0110] 2.6 Emotion evaluation experiment: Open field test

[0111] 2.6.1 Vertical movement

[0112] As Figure 8As shown, compared with the blank group, the number of rearing times, standing time, grooming times, and grooming time in the model group all decreased extremely significantly (P<0.001). Compared with the model group, the number of rearing times, standing time, grooming times, and grooming time in the medium-dose group all increased extremely significantly (P<0.001). Compared with the model group, the number of rearing times, standing time, and grooming time in the high-dose group all increased extremely significantly (P<0.001), and the grooming times increased significantly (P<0.01). Compared with the model group, the grooming time and grooming times in the estazolam group increased extremely significantly (P<0.001), the number of rearing times and standing time increased, and there was a statistical difference (P<0.05). See Table 5 for details.

[0113] Table 5 Numerical values of vertical movement-related indicators in the open field test of rats ( n = 5)

[0114]

[0115] Note: Compared with the blank group, *** P<0.001, compared with the model group, △ P<0.05, △△ P<0.01, △△△ P<0.001

[0116] 2.6.2 Horizontal movement

[0117] As Figure 9 shown, the horizontal movement indicators of rats recorded in the open field test mainly include the residence time in the central square, the total movement distance, the percentage of the number of grid crossings in the central area, and the number of grid crossings. Compared with the blank group, the residence time in the central area, the percentage of the number of grid crossings in the central area, and the total number of grid crossings of rats in the model group decreased significantly (P<0.01, P<0.001), and the total movement distance decreased (P<0.05), with a statistical difference. Compared with the model group, the percentage of the number of grid crossings in the central area and the total number of grid crossings in the medium-dose group increased significantly (P<0.001), the percentage of the number of grid crossings in the central area, the total movement distance, and the total number of grid crossings in the high-dose group increased significantly (P<0.01, P<0.001), and the percentage of the number of grid crossings in the central area and the total number of grid crossings in the estazolam group increased significantly (P<0.001). See Table 6 for details.

[0118] Table 6 Numerical values of horizontal movement-related indicators in the open field test of rats ( n = 5)

[0119]

[0120] Note: Compared with the blank group, * P<0.05, ** P<0.01, *** P<0.001, compared with the model group,△△ P < 0.01, △△△ P < 0.001

[0121] 2.6.3 Open-field test: Movement trajectories of rats in each group

[0122] As Figure 10 shown, compared with the blank group, the rats in the model group explored the edge and the frequency and distance of entering the central area were significantly reduced, indicating a decline in the exploratory and autonomous activity ability of the rats in the model group. After intervention with medium-dose Chaishao Zaoren Decoction, high-dose Chaishao Zaoren Decoction, and estazolam, the situation improved compared with that of the rats in the model group.

[0123] Animal experiment 2: Mechanism evaluation

[0124] Experiment 1

[0125] Determination of related indexes of GABA pathway in the hypothalamus of rats (GABAARα1, GAT-1), protein blotting, and gene expression of insomnia-related brain-gut peptide (NPY).

[0126] 1. Experimental results

[0127] 1.1 Experimental results of protein expression

[0128] As Figure 11 shown, compared with the blank group, the relative protein expressions of GABAARα1 and NPY in the model group were significantly decreased (P < 0.001), and the relative protein expression of GAT-1 in the model group was increased (P < 0.05). Compared with the model group, the relative protein expressions of NPY and GABAARα1 in the medium-dose group, high-dose group, and estazolam group were significantly increased (P < 0.05, P < 0.01, P < 0.001). There was no significant statistical difference in the relative protein expression of GAT-1 in the medium-dose group, high-dose group, and estazolam group, but there was a downward trend. See Table 7 for details.

[0129] Table 7 Relative protein expression levels of GABAARα1, GAT-1, and NPY in the hypothalamus of rats in each group ( n = 3)

[0130]

[0131] Note: Compared with the blank group, * P < 0.05, *** P < 0.001, compared with the model group, △ P < 0.05, △△ P < 0.01, △△△ P < 0.001

[0132] 1.2 Experimental results of gene expression:

[0133] As Figure 12 shown, compared with the blank group, the expression levels of GABAARα1 and NPY mRNA in the model group of rats were significantly decreased (P<0.01, P<0.001), and the expression level of GAT-1mRNA was significantly increased (P<0.01). Compared with the model group, the medium-dose Zaishao Zaoren Decoction could down-regulate the expression level of GAT-1mRNA (P<0.01). Although there was no significant statistical difference in the expression levels of NPY mRNA and GABAARα1mRNA in the medium-dose group, there was an upward trend. The high-dose Zaishao Zaoren Decoction group could up-regulate the expression level of GABAARα1 (P<0.05) and down-regulate the expression level of GAT-1mRNA (P<0.01). Although there was no significant statistical difference in the expression level of NPY mRNA in the high-dose group, there was an upward trend. The estazolam group could up-regulate the expression levels of GABAARα1 and NPY mRNA (P<0.01, P<0.05). Although there was no significant statistical difference in the expression level of GAT-1mRNA in the estazolam group, there was a downward trend. See Table 8 for details.

[0134] Table 8 Expression levels of GABAARα1, GAT-1, and NPY mRNA in the hypothalamus of rats in each group ( n = 6)

[0135]

[0136] Note: Compared with the blank group, compared with the blank group, ** P<0.01, *** P<0.001, compared with the model group, △ P<0.05, △△ P<0.01

[0137] Experiment 2

[0138] Determination of related indexes (NR1, CAMK2) of the Glu pathway, protein blotting, and gene expression of insomnia-related brain-gut peptide (NT) in the hypothalamus of rats.

[0139] 2.1 Gene expression results:

[0140] Table 9 Expression levels of NT, NR1, and CAMK2 mRNA in the hypothalamus of rats in each group ( n = 6)

[0141]

[0142] Note: Compared with the blank group, compared with the blank group, **P<0.01, ***P<0.001, compared with the model group, △P<0.05, △△P<0.01

[0143] like Figure 13 As shown in the figure, compared with the blank group, the mRNA expression of NT, NR1, and CAMK2 in the model group rats was significantly decreased (P<0.001). Compared with the model group, the medium dose, high dose, and estazolam of Chaishaozaoren decoction could upregulate the mRNA expression of NT, NR1, and CAMK2 (P<0.05, P<0.01). Among them, the increase in NR1 was the most obvious, and NT could be increased slightly. The effect of the medium dose group of Chaishaozaoren decoction on the increase of NT, NR1, and CAMK2 mRNA expression in rats was more significant than that of the medium dose and estazolam.

[0144] 2.2 Protein expression results:

[0145] Table 10 Relative expression of NT, NR1 and CAMK2 proteins in the hypothalamus of rats in each group ( n=3)

[0146]

[0147]

[0148] Note: Compared with the blank group, *P<0.05, ***P<0.001, compared with the model group, △P<0.05, △△P<0.01, △△△P<0.001

[0149] like Figure 14 As shown in the figure, compared with the blank group, the expression of NT, NR1, and CAMK2 proteins in the model group rats was significantly decreased (P<0.001). Compared with the model group, the medium dose, high dose, and estazolam of Chaishaozaoren decoction could upregulate the expression of NT, NR1, and CAMK2 proteins (P<0.05, P<0.01), but the medium dose group had no significant increase in the expression of NR1 and CAMK2 proteins. The most obvious increase among the three indicators was in the high dose group (P<0.001), and the expression of CAMK2 protein was increased to a level close to that of the normal group.

[0150] Animal experiment 3: Evaluation of intestinal flora

[0151] 1 Experimental methods

[0152] Gut microbiota metagenomic sequencing.

[0153] 2 Experimental results

[0154] In this experiment, a total of 50 rat feces samples were sent for double-end 150bp sequencing, and the average sequencing depth was 9Gbase.

[0155] Table 11 Rat feces metagenomic sequencing

[0156]

[0157] 2.1 Alpha diversity comparison

[0158] The abscissa of the rarefaction curve represents the number of samples drawn; the ordinate represents the number of genes in the sample combinations drawn. Starting from the abundance table of genes in each sample, the number of species in each sample can be obtained. By randomly drawing different numbers of samples, the number of species among different combinations of samples can be obtained, and thus the rarefaction curve can be constructed and plotted. The box plots are the Shannon diversity and Simpson index respectively, and the abscissa represents different groups.

[0159] As Figure 15 shown, the rarefaction curve analysis results show that with the increase in the number of samples, although the number of detected species is still increasing and not tending to level off, it can still be found that compared with the blank group, the number of detectable microbial species in the intestinal tract of rats in the model group decreases. Compared with the model group, the number of detectable microbial species in the intestinal tract of rats in the estazolam group, the medium-dose Chaishao Zaoren Decoction group, and the high-dose Chaishao Zaoren Decoction group increases. Both the Shannon diversity and Simpson diversity indices indicate that the intestinal microbial diversity of rats in the estazolam group and the high-dose Chaishao Zaoren Decoction group is higher than that in the model group.

[0160] 2.2 Beta diversity comparison

[0161] Points of different colors or shapes represent samples of different groups; Principal Component 2 (CAP2) and Principal Component 3 (CAP3) are the second and third largest differential features of the partitioned samples, and the percentage form reflects the explanatory power of the principal components. The closer the spatial distance of the samples, the more similar the species composition structure of the samples

[0162] Permutational multivariate analysis of variance (PERMANOVA, Adonis) is a variance analysis based on the F statistic, a non-parametric multivariate variance analysis method for decomposing the total variance based on the distance matrix. The basic steps are to calculate the Bray-curtis distance between samples based on the relative abundance table of species, and then generate the results through adonis analysis. As Figure 16 shown, the Adonis results show that there are significant differences in the bacterial composition among these 5 groups of samples (pvalue = 0.001, R2 = 26.7%). Distance-based redundancy analysis (dbRDA) based on the Bray-Curtis distance shows that there are differences in the bacterial community composition between the blank group and the model group. Compared with the model group, the bacterial community composition in the intestinal tract of rats intervened with the medium-dose Chaishao Zaoren Decoction, high-dose Chaishao Zaoren Decoction, and estazolam is closer to that of the normal group.

[0163] 2.3 Comparison of species composition differences at the phylum level

[0164] As Figure 17 shown, the vertical axis of the bar chart represents the percentage relative content, the horizontal axis represents the samples, each color represents a type of species, the abundance in the legend decreases from top to bottom, and only the top 10 species with the highest average relative content are shown in the figure, and the remaining species are all classified as other. As Figure 18 shown, the box plot shows the prominent species with significant differences in abundance at the phylum level among groups. The box represents the interquartile range between the first and third quartiles and the median (inner line). The whiskers above and below the box represent the lowest and highest values within 1.5 times the first and third quartile ranges respectively, and each point represents a sample. * P < 0.05, ** P < 0.01, *** P < 0.001.

[0165] At the phylum level of species composition, the intestinal microbiota of rats is mainly composed of Bacteroidetes and Firmicutes. Compared with the blank group: the Bacteroidetes in the intestinal tract of rats in the model group increased significantly (P < 0.01), while the Firmicutes and Actinobacteria decreased significantly (P < 0.01, P < 0.001). Compared with the model group: there was no significant difference in the content of Firmicutes in the intestinal tract of rats in the medium-dose group, high-dose group, and estazolam group, but there was an upward trend in the content of Firmicutes in high-dose rats compared with the model group; there was no significant difference in the content of Actinobacteria in the intestinal tract of rats in the medium-dose group, high-dose group, and estazolam group, but there was an upward trend in the content of Actinobacteria in the western medicine group and medium-dose group; there was no significant difference in the content of Bacteroidetes in the intestinal tract of rats in the medium-dose group and high-dose group, and after intervention with estazolam, the increase was more obvious (P < 0.05).

[0166] 2.4 Comparison of differences in species composition at the genus level

[0167] As Figure 19 shown, the vertical axis of the bar chart represents the percentage relative content, the horizontal axis represents the samples, each color represents a type of species, the abundance in the legend decreases from top to bottom, and only the top 15 species with the highest average relative content are shown in the figure, and the remaining species are all classified as other. As Figure 20 shown, the box plot shows the prominent species with significant differences in abundance at the genus level among groups. The box represents the interquartile range between the first and third quartiles and the median (inner line). The whiskers above and below the box represent the lowest and highest values within 1.5 times the first and third quartile ranges respectively, and each point represents a sample. * P < 0.05, ** P < 0.01, *** P < 0.001

[0168] At the genus level, the intestinal microbiota of rats was mainly composed of *Blautia*, *Ligilactobacillus*, *Lactobacillus*, *Prevotella*, and *Bacteroides*. Compared with the blank group, the genera *Parabacteroides* and *Anaerofustis* in the intestinal tract of rats in the model group were significantly increased (P<0.01, P<0.001), while the genera *Lactobacillus* and *Limosilactobacillus* were significantly decreased (P<0.01, P<0.001). Compared with the model group: the genus *Anaerofustis* in the medium-dose group and high-dose group was significantly decreased (P<0.05); there was no significant statistical difference in the genus *Parabacteroides* in the intestinal tract of rats in the medium-dose group and high-dose group compared with the model group, but there was a downward trend in the genus *Parabacteroides* in the intestinal tract of the medium-dose group and high-dose group; there was a significant decrease in the genus *Lactobacillus* in the intestinal tract of rats in the western medicine group and medium-dose group (P<0.5, P<0.01), and there was no significant statistical difference between the high-dose group and the model group, but there was an upward trend; there was no significant statistical difference in the genus *Limosilactobacillus* in the intestinal tract of the western medicine group, medium-dose group, and high-dose group compared with the model group.

[0169] 2. Comparison of species composition differences at the phylum level

[0170] As Figure 21 shown, the vertical coordinate of the bar chart represents the percentage relative content, the horizontal coordinate represents the samples, each color represents a class of species, and the abundance in the legend decreases from top to bottom. Only the top 15 species with the average relative content are shown in the figure, and the remaining species are all classified as other.

[0171] As Figure 22 shown, the heat map only shows the species that are different between the normal group and the model group. Each row represents a species, each column represents a sample, and the relative content ranges from light to dark from low to high. Because the relative content of species varies greatly among different samples, we standardized the relative content of each species in all samples so that their variance is 1 and the mean is 0.

[0172] The intestinal microbiota of normal rats at the species level mainly consists of Blautia wexlerae (no Chinese translation), Lactobacillus johnsonii, Lactobacillus intestinalis, and Limosilactobacillus reuteri. At the species level, after performing a rank-sum test on the relative abundances of species in the model group and the normal group, we found that there were 54 species with differences (P<0.05). Among them, 31 were significantly decreased in the model group, including Lactobacillus intestinalis, Lactobacillus johnsonii, and Limosilactobacillus reuteri, and 23 were significantly increased in the model group, including Bacteroidales bacterium, Parabacteroides distasonis, Anaerofustis stercorihominis, and Bacteroides caccae. In the drug intervention group, compared with the other two groups, the relative abundances of Limosilactobacillus reuteri and Lactobacillus intestinalis in the intestinal tract of rats in the high-dose Zaishao Zaoren Decoction group were closer to those in the normal group.

[0173] Conclusions of animal experiments

[0174] 1.1 The tail suspension test indicated that long-term insomnia rats showed depressive mood. The pentobarbital sodium synergistic test found that the sleep latency of long-term insomnia rats increased and the sleep duration decreased. The Y-maze alternation test found that the recognition ability, memory ability, and activity ability of long-term insomnia rats decreased. The open field test indicated that long-term insomnia rats showed negative emotions such as anxiety and depression, and the exploratory desire and spontaneous activity ability decreased. Zaishao Zaoren Decoction could effectively improve the above conditions. It was proved that long-term insomnia rats met the syndrome of liver depression and spleen deficiency through behavioral observation research and drug counterevidence.

[0175] 1.2 Molecular biology experimental observations found that the GABA system of long-term insomnia rats was inhibited and the level of the brain-gut peptide NPY with a sleep-promoting effect decreased. Zaishao Zaoren Decoction could promote sleep by regulating the GABA system and the brain-gut peptide NPY in long-term insomnia rats.

[0176] 1.3 Metagenomic sequencing found that the intestinal microbiota diversity of long-term insomnia rats decreased. Zaishao Zaoren Decoction could increase the intestinal microbiota diversity of rats, and Zaishao Zaoren Decoction could change the intestinal microbiota composition of long-term insomnia rats to relieve the insomnia condition of long-term rats.

[0177] 1.4 The present invention established a long-term insomnia model, and proved the establishment of the liver depression and spleen deficiency model through behavioral studies and drug counter-evidence. By observing the behavior of rats with long-term insomnia, it was found that the negative emotions of rats with long-term insomnia were aggravated, and their exploratory desire and autonomous activity ability decreased. Molecular biology experiments found that the levels of GABAARα1 and neuropeptide Y (NPY) secreted by the brain of rats with long-term insomnia decreased, while the transporter GAT-1 increased; detecting the intestinal flora of rats with long-term insomnia found that the diversity of intestinal flora decreased and the composition of intestinal flora changed. A series of changes occurred in the intestinal flora-gut-brain axis of rats with long-term insomnia. It can be speculated that the pathogenesis of long-term insomnia may be closely related to the intestinal flora-gut-brain axis. After intervention with Chaishao Zaoren Decoction, it can change the related indexes of brain-gut peptides and GABA pathway and the composition of intestinal flora in rats with long-term insomnia, increase the diversity of intestinal flora and relieve the insomnia condition of rats with long-term insomnia.

[0178] Effect research of Implementation Cases 2 - 5

[0179] The curative effect of Chaishao Zaoren Decoction showed advantages in multiple indexes, and some indexes were comparable to those of the positive drug estazolam. Among them, in the Glu pathway, it could up-regulate the expression levels of NT, NR1, and CAMK2. In the GABA pathway, it could up-regulate GABAARα1 and down-regulate GAT-1 to enhance the inhibitory effect of GABA; at the same time, it up-regulated NPY to promote sleep.

[0180] Administration method

[0181] All experimental drugs were converted into the equivalent dose for rats as the crude drug amount according to the human drug dosage. The conversion formula was: crude drug amount per kilogram of rats = adult drug dosage g / adult body weight (70 kg) × 6.25. The administration volume was prepared with deionized water according to the gastric capacity of rats at 10 ml / kg, and the drug dosage was adjusted according to the body weight of rats. Starting from the first day of modeling, the blank group and the model group were given distilled water by gavage at 7:00 am every day.

[0182] Low-dose group of Chaishao Zaoren Decoction: The drug composition of Implementation Case 5 was given by gavage with the prepared formula component solution;

[0183] Medium-dose group of Chaishao Zaoren Decoction: The drug composition of Implementation Case 4 was given by gavage with the prepared formula component solution;

[0184] High-dose group of Chaishao Zaoren Decoction: The drug composition of Implementation Case 1 was given by gavage with the prepared formula component solution;

[0185] The western medicine group was given estazolam (0.089 mg·kg -1 ·d -1 ) by gavage. The administration volume was 10 ml / kg for all, and the drug was administered continuously for 14 days.

[0186] From the observation of sleep duration, compared with the blank group: the sleep duration of the model group was significantly reduced, with a statistically significant difference (P<0.001). Compared with the model group: the sleep duration of the medium-dose group increased, with a statistically significant difference (P<0.05), and the sleep duration of the estazolam group and the high-dose group increased significantly, with a statistically significant difference (P<0.001).

[0187] Table 12 Sleep latency and sleep duration of rats ( n=5)

[0188]

[0189] Note: Compared with the blank group, *** P<0.001, compared with the model group, △ P<0.05, △△△ P<0.001 Comparative study on the effect of implementation plan and Suanzaoren decoction and Sinisan

[0190] Results of pentobarbital sodium reversal test

[0191] Dosage

[0192] The experimental drugs were converted into rat equivalent doses according to the human dosage as the raw drug dosage. The conversion formula was: raw drug dosage per kg rat = adult dosage g / adult weight (70kg) × 6.25. The dosage volume was prepared with deionized water according to the rat stomach capacity of 10ml / kg, and the dosage was adjusted according to the rat weight. Starting from the first day of modeling, the blank group and the model group were gavaged with distilled water at 7:00 am every day.

[0193] Chaishaozaoren decoction group: the drug composition of implementation case 1 was administered by intragastric administration;

[0194] Suanzaoren decoction group: the drug composition of the implementation case (formula: 30 parts of stir-fried jujube seeds, 12 parts of roasted licorice, 10 parts of rhizoma anemarrhenae, 16 parts of poria, 12 parts of rhizoma chuanxiong) was administered by intragastric administration;

[0195] Sinisan group: the drug composition of the implementation case (formula: 15 parts of Bupleurum, 16 parts of White Peony Root, 16 parts of Citrus Aurantium, 12 parts of Radix Glycyrrhizae) was administered intragastrically with the prepared formula solution;

[0196] The positive drug group was treated with estazolam (0.089 mg kg -1 ·d -1 ) were intragastrically administered at a volume of 10 ml / kg for 14 consecutive days.

[0197] Study Results

[0198] In the pentobarbital sodium righting test after drug intervention, the inter-group differences in the sleep latency of rats were very significant (P<0.01). Compared with the normal group, the sleep latency of rats in the model group was significantly prolonged (P<0.01); compared with the model group, the sleep latency of rats in the Sinisan group, Suanzaoren Decoction group, and positive drug group was significantly shortened (P<0.05), and the sleep latency of rats in the combined prescription group was significantly shortened (P<0.01).

[0199] There were significant differences in the sleep duration of rats among the groups (P<0.05). Compared with the normal group, the sleep duration of rats in the model group was significantly reduced (P<0.05). Compared with the model group, the sleep duration of rats in the positive drug group, Suanzaoren Decoction group, and Chaishaozaoren Decoction group was significantly increased (P<0.05), and the sleep duration of rats in the Sinisan group was very significantly increased (P<0.01), as shown in Table 13.

[0200] Table 13 Pentobarbital sodium righting test results

[0201]

[0202] Note: Compared with the Chaishaozaoren decoction group, #P<0.05, ##P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0203] The present invention has been disclosed above with preferred embodiments, but those skilled in the art should understand that these embodiments are only used to describe the present invention and should not be understood as limiting the scope of the present invention. It should be noted that all changes and substitutions equivalent to these embodiments should be deemed to be included in the scope of the claims of the present invention. Therefore, the scope of protection of the present invention should be based on the scope defined in the claims.

Claims

1. A traditional Chinese medicine composition for treating insomnia, characterized in that, Comprising: Bupleurum chinense, Paeonia lactiflora Pall., Fructus Aurantii Immaturus, Radix Glycyrrhizae Praeparata, Semen Ziziphi Spinosae Praeparata, Anemarrhena asphodeloides Bge., Poria cocos (Schw.) Wolf, Rhizoma Chuanxiong.

2. The traditional Chinese medicine composition for treating insomnia according to claim 1, characterized in that, By weight parts, comprising: 4 - 16 parts of Bupleurum chinense, 4 - 16 parts of Paeonia lactiflora Pall., 4 - 16 parts of Fructus Aurantii Immaturus, 3 - 12 parts of Radix Glycyrrhizae Praeparata, 7 - 28 parts of Semen Ziziphi Spinosae Praeparata, 3 - 12 parts of Anemarrhena asphodeloides Bge., 4 - 16 parts of Poria cocos (Schw.) Wolf, 3 - 12 parts of Rhizoma Chuanxiong.

3. The traditional Chinese medicine composition for treating insomnia according to claim 2, characterized in that, By weight parts, comprising: 10 - 15 parts of Bupleurum chinense, 12 - 16 parts of Paeonia lactiflora Pall., 12 - 16 parts of Fructus Aurantii Immaturus, 10 - 12 parts of Radix Glycyrrhizae Praeparata, 20 - 28 parts of Semen Ziziphi Spinosae Praeparata, 10 - 12 parts of Anemarrhena asphodeloides Bge., 12 - 16 parts of Poria cocos (Schw.) Wolf, 10 - 12 parts of Rhizoma Chuanxiong.

4. The traditional Chinese medicine composition for treating insomnia according to claim 3, characterized in that, By weight parts, comprising: 16 parts of Bupleurum chinense, 16 parts of Paeonia lactiflora Pall., 16 parts of Fructus Aurantii Immaturus, 12 parts of Radix Glycyrrhizae Praeparata, 28 parts of Semen Ziziphi Spinosae Praeparata, 12 parts of Anemarrhena asphodeloides Bge., 16 parts of Poria cocos (Schw.) Wolf, 12 parts of Rhizoma Chuanxiong.

5. The traditional Chinese medicine composition for treating insomnia according to any one of claims 1-4, characterized in that, The insomnia is that of seafarers.

6. A drug for treating insomnia, characterized in that, Comprising the traditional Chinese medicine composition for treating insomnia according to any one of claims 1 - 5.

7. The drug for treating insomnia according to claim 6, characterized in that, Further comprising pharmaceutically acceptable excipients.

8. The drug for treating insomnia according to claim 6, characterized in that, The dosage form of the drug is: oral liquid, capsule, tablet, pill, granule, powder, decoction or ointment.

9. The drug for treating insomnia according to claim 8, characterized in that, The dosage form of the drug is: traditional Chinese medicine instant granule.

10. Use of the traditional Chinese medicine composition for treating insomnia according to any one of claims 1-5 in the preparation of a drug for treating insomnia.

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