A traditional Chinese medicine composition for treating insomnia, anxiety depression and AD, a preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating insomnia, anxiety depression and AD, a preparation method and application thereof. The traditional Chinese medicine composition adopts an ethanol extract of raw medicinal materials, and the raw medicinal materials include, by weight, 175-185 parts of polygala root, 160-170 parts of jujube seed, 90-100 parts of platycladus seed, 150-160 parts of jujube, 160-170 parts of fried licorice, 160-170 parts of astragalus, 150-160 parts of angelica, 150-160 parts of salvia miltiorrhiza, and 155-165 parts of schisandra chinensis. The raw medicinal materials in the traditional Chinese medicine composition are based on the polygala root, and are combined with the jujube seed, the platycladus seed, the jujube, the fried licorice, the astragalus, the angelica, the salvia miltiorrhiza and the schisandra chinensis. The components have a synergistic effect, can treat insomnia, anxiety depression and AD, and have the advantages of small side effect of traditional Chinese medicine and difficulty in drug resistance.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine and health products, and in particular to a traditional Chinese medicine composition for treating insomnia, anxiety, depression and Alzheimer's disease, its preparation method and application. Background Technology

[0002] Insomnia can be comorbid with anxiety and depression. Comorbid insomnia with depression or anxiety can include some symptoms of simple insomnia and depression or anxiety; it is a combination of the clinical symptoms of simple insomnia and depression or anxiety.

[0003] Insomnia is a symptom of anxiety and depression. Some symptoms of insomnia and depression overlap; for example, the decreased motivation or energy, dysphoric mood, slowed cognitive activity, impaired social functioning, and somatization symptoms associated with depression can easily be confused with daytime functional impairment caused by insomnia. Some patients with depression still experience persistent insomnia even after their mood symptoms have subsided. Compared to individuals without anxiety, those who may have anxiety or a tendency towards anxiety have a significantly increased risk of insomnia; furthermore, the presence of depression and anxiety can reinforce misconceptions about insomnia, leading to its long-term persistence.

[0004] Insomnia can trigger anxiety and depression. Insomnia manifests not only as a physiological disorder but also as a psychological one. Patients suffering from long-term insomnia are prone to developing symptoms of depression and anxiety; persistent insomnia is a risk factor for prolonged and recurrent depression.

[0005] Currently, most medications used clinically to treat insomnia are Western-style sleeping pills, such as zolpidem, triazolam, eszopiclone, lorazepam, diazepam, and quetiapine. These medications typically have sedative or hypnotic effects, helping to induce sleep and prolong sleep time. However, these medications often cause adverse reactions such as dizziness, drowsiness, dry mouth, muscle fatigue, indigestion, memory loss, weight gain, and irregular heartbeat. Western medicine only addresses the symptoms of insomnia clinically, without resolving the anxiety and depression caused by insomnia.

[0006] Alzheimer's disease (AD) is a neurodegenerative disease that primarily affects the elderly. Early symptoms include difficulty recalling recent conversations, names, or events. As the disease progresses, the brain atrophies due to the death of numerous brain cells, leading to impaired communication, confusion, behavioral changes, and poor judgment. Most people with this disease are over 65 years old, making it difficult for family members or caregivers to assist with daily activities, severely impacting the patient's quality of life and health. According to the latest data released by Alzheimer's Disease International (ADI), there are currently over 55 million people with AD worldwide, and this number is projected to surge to 139 million by 2050, with the fastest growth in developing countries. Global treatment costs for AD are estimated at $130 million, and three-quarters of patients remain undiagnosed and untreated. Therefore, AD has become a thorny health, economic, and social problem worldwide.

[0007] As of 2022, only nine drugs had been approved by the FDA. Among them, GV-971 is my country's first and the world's first new drug targeting the brain-gut axis for the treatment of Alzheimer's disease. The others, except for Memantine (an NMDA receptor antagonist), Namzaric (a multi-target inhibitor), and Aduhelm (an Aβ-targeting drug), are all cholinesterase (ChE) inhibitors. These drugs have all been shown to alleviate AD symptoms, but they cannot reverse the disease progression, have many side effects, and are prone to drug resistance. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition for treating insomnia, anxiety, depression and Alzheimer's disease and its preparation method, so that it can treat insomnia, anxiety, depression and Alzheimer's disease, with few side effects and less likely to cause drug resistance.

[0009] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0010] On one hand, the present invention provides a traditional Chinese medicine composition for treating insomnia, anxiety, depression and Alzheimer's disease, using an ethanol extract of raw materials, wherein the raw materials include, by weight: 175-185 parts of Polygala tenuifolia root, 160-170 parts of Ziziphus jujuba seed, 90-100 parts of Platycladus orientalis seed, 150-160 parts of jujube, 160-170 parts of prepared licorice root, 160-170 parts of Astragalus membranaceus, 150-160 parts of Angelica sinensis, 150-160 parts of Salvia miltiorrhiza, and 155-165 parts of Schisandra chinensis.

[0011] The main component of the above-mentioned traditional Chinese medicine composition is Polygala tenuifolia, which was first included in the 1953 edition of the Chinese Pharmacopoeia. After revisions and improvements in subsequent editions, the 2020 edition of the Chinese Pharmacopoeia records its functions and indications as calming the mind and improving intelligence, harmonizing the heart and kidneys, resolving phlegm, and reducing swelling. It is used for insomnia, dreaminess, forgetfulness, palpitations, and mental confusion caused by disharmony between the heart and kidneys, as well as cough with phlegm, sores and carbuncles, and breast swelling and pain. Polygala tenuifolia, also known as Niangmu Liang (Polygalacrotalarioides), means "mother of medicines." Other names include "Nie Liang" and "Niangmu Lai" (both transliterations). The medicinal herb is the root of Polygala tenuifolia, a perennial herbaceous plant belonging to the Polygalaceae family.

[0012] As a further improvement of the present invention, the raw materials include, by weight, the following: 175-180 parts of Polygala tenuifolia root, 160-165 parts of Ziziphus jujuba seed, 90-95 parts of Platycladus orientalis seed, 150-155 parts of jujube, 160-165 parts of prepared licorice root, 160-165 parts of Astragalus membranaceus, 150-155 parts of Angelica sinensis, 150-155 parts of Salvia miltiorrhiza, and 155-160 parts of Schisandra chinensis.

[0013] More preferably, the raw materials include, by weight: 180 parts of Polygala tenuifolia root, 165 parts of Ziziphus jujuba seed, 95 parts of Platycladus orientalis seed, 155 parts of jujube, 165 parts of prepared licorice root, 165 parts of Astragalus membranaceus, 155 parts of Angelica sinensis, 155 parts of Salvia miltiorrhiza, and 160 parts of Schisandra chinensis.

[0014] Secondly, the present invention also provides a method for preparing a traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease, comprising the following steps:

[0015] (1) Crush the raw material and sieve it for later use;

[0016] (2) After soaking in ethanol, ultrasonic-assisted extraction was performed, followed by cooling, shaking, filtration, and repeated extraction of the filter residue.

[0017] (3) Combine the filtrates, concentrate them, and obtain the ethanol extract of the traditional Chinese medicine composition.

[0018] As a further improvement of the present invention, in step (1), the sample is passed through a No. 3 sieve for later use;

[0019] In step (2), ethanol with a volume fraction of 45-75% is added at a weight-to-volume ratio of 1:(2-6), soaked for 1-3 hours, extracted with ultrasonic assistance for 4-6 hours, cooled, shaken, filtered, and the residue is extracted twice.

[0020] In step (3), the filtrates from the three filtrates are combined and concentrated to obtain an ethanol extract of the traditional Chinese medicine composition.

[0021] More preferably, in step (2), 60% ethanol is added at a weight-to-volume ratio of 1:4, soaked for 2 hours, and then extracted with ultrasound for 5 hours.

[0022] More preferably, in step (3), the ethanol extract of the traditional Chinese medicine composition is concentrated to 2-3 g / mL.

[0023] Thirdly, the present invention also provides applications of the above-mentioned traditional Chinese medicine composition and the traditional Chinese medicine composition prepared by the above-mentioned preparation method, wherein the applications are as follows:

[0024] (1) Application in the preparation of drugs or health products for treating insomnia;

[0025] and / or (2) its use in the preparation of medicines or health products for the treatment of anxiety and depression;

[0026] And / or (3) its use in the preparation of medicines or health products for the treatment of AD.

[0027] By adopting the above technical solution, the present invention has at least the following advantages:

[0028] 1. This invention uses traditional Chinese medicine to treat insomnia, anxiety, depression, and Alzheimer's disease (AD), which has the following advantages compared to Western medicine:

[0029] (1) Traditional Chinese medicine often does not have serious side effects, so it is more suitable for long-term use;

[0030] (2) Traditional Chinese medicine treatment often targets not only insomnia symptoms but also improves overall health. Sometimes, Chinese medicine is used to balance the body's energy flow and promote the health of the immune and digestive systems, thereby helping to improve sleep.

[0031] (3) Compared with some Western medicines, traditional Chinese medicine treatment has less drug dependence, which will reduce the problems of dependence and abuse.

[0032] (4) Traditional Chinese medicine often uses compound prescriptions, which can act on the body in multiple ways to provide a more comprehensive therapeutic effect. This may help treat insomnia caused by multiple factors, such as anxiety, depression, and liver qi stagnation.

[0033] 2. The raw materials in the traditional Chinese medicine composition of the present invention are based on Polygala tenuifolia root, combined with Ziziphus jujuba seed, Platycladus orientalis seed, jujube, prepared licorice root, Astragalus membranaceus, Angelica sinensis, Salvia miltiorrhiza, and Schisandra chinensis. The components work synergistically to improve sleep disorders, alleviate anxiety and depression, and significantly improve AD symptoms, providing strong technical support for further clinical application and preparation of health products and medicines. Attached Figure Description

[0034] The above is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0035] Figure 1 Typical movement trajectories of zebrafish after treatment with different concentrations of Polygala tenuifolia ethanol extract; (black line represents slow speed, green line represents medium speed, red line represents fast speed);

[0036] Figure 2 This represents the total distance the zebrafish traveled.

[0037] Figure 3 The relative expression level of the gabra1 gene in zebrafish;

[0038] Figure 4 The relative expression level of the gad2 gene in zebrafish;

[0039] Figure 5 The relative expression level of the htr2aa gene in zebrafish;

[0040] Figure 6 This represents the activity level of zebrafish monoamine oxidase.

[0041] Figure 7 The escape latency period for mice in the MWM hiding platform experiment. Detailed Implementation

[0042] Exemplary embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While exemplary embodiments of the invention are shown in the drawings, it should be understood that the invention may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the invention and to fully convey the scope of the invention to those skilled in the art.

[0043] Example 1

[0044] The raw materials, by weight, include: 180 parts of Polygala tenuifolia root, 165 parts of Ziziphus jujuba seed, 95 parts of Platycladus orientalis seed, 155 parts of jujube, 165 parts of prepared licorice root, 165 parts of Astragalus membranaceus, 155 parts of Angelica sinensis, 155 parts of Salvia miltiorrhiza, and 160 parts of Schisandra chinensis.

[0045] The above-mentioned active pharmaceutical ingredient was used to obtain an ethanol extract according to the following preparation method:

[0046] (1) Crush each of the above raw materials into powder, pass through a No. 3 sieve, and set aside;

[0047] (2) Add 60% ethanol at a material-to-liquid ratio of 1:4 (w / v), soak for 2 hours, extract with ultrasonic assistance for 5 hours (power 400W, frequency 40kHz), cool, shake well, filter, and repeat the extraction twice with the residue.

[0048] (4) Combine the three filtrates, concentrate them, and obtain the ethanol extract of the traditional Chinese medicine composition (2.5 g / mL). The subsequent experimental research is based on the ethanol extract of the traditional Chinese medicine composition in this example. When using it, dilution and other operations can be performed as needed.

[0049] Example 2

[0050] The raw materials, by weight, include: 175 parts of Polygala tenuifolia root, 160 parts of Ziziphus jujuba seed, 90 parts of Platycladus orientalis seed, 150 parts of jujube, 160 parts of prepared licorice root, 160 parts of Astragalus membranaceus, 150 parts of Angelica sinensis, 150 parts of Salvia miltiorrhiza, and 155 parts of Schisandra chinensis.

[0051] The above-mentioned active pharmaceutical ingredient was used to obtain an ethanol extract according to the following preparation method:

[0052] (1) Crush each of the above raw materials into powder, pass through a No. 3 sieve, and set aside;

[0053] (2) Add 50% ethanol at a material-to-liquid ratio of 1:3 (w / v), soak for 1.5 h, extract with ultrasonic assistance for 4 h (power 400 W, frequency 40 kHz), cool, shake well, filter, and repeat the extraction twice with the residue.

[0054] (4) Combine the three filtrates, concentrate them, and obtain the ethanol extract.

[0055] Example 3

[0056] The raw materials, by weight, include: 185 parts of Polygala tenuifolia root, 170 parts of Ziziphus jujuba seed, 100 parts of Platycladus orientalis seed, 160 parts of jujube, 170 parts of prepared licorice root, 170 parts of Astragalus membranaceus, 160 parts of Angelica sinensis, 160 parts of Salvia miltiorrhiza, and 165 parts of Schisandra chinensis.

[0057] The above-mentioned active pharmaceutical ingredients were used to prepare an ethanol extract of the traditional Chinese medicine composition using the following method:

[0058] (1) Crush each of the above raw materials into powder, pass through a No. 3 sieve, and set aside;

[0059] (2) Add 70% ethanol at a material-to-liquid ratio of 1:5 (w / v), soak for 2.5 h, extract with ultrasonic assistance for 6 h (power 400 W, frequency 40 kHz), cool, shake well, filter, and repeat the extraction twice with the residue.

[0060] (4) Combine the three filtrates, concentrate them, and obtain the ethanol extract.

[0061] The active pharmaceutical ingredients in this invention are formulated by weight. During production, the weight can be increased or decreased proportionally. For example, for large-scale production, the weight can be in kilograms or tons, while for small-scale production, it can be in grams (as in Examples 1-3 above). The weight can be increased or decreased, but the weight ratio of the active pharmaceutical ingredients among the components remains unchanged.

[0062] Example 4

[0063] This embodiment provides a research method for improving the sleep effect of a traditional Chinese medicine composition in experimental animals such as zebrafish:

[0064] Randomly selected zebrafish were placed in six-well plates, with 30 zebrafish per well and a volume of 3 mL per well. A normal control group and a pentylenetetrazole (PTZ) model control group were set up. A zebrafish insomnia model (pentylenetetrazole model) was also selected, with four treatment groups using ethanol extracts of the herbal composition at different concentrations (100, 200, 500, and 800 μg / mL), a treatment group using ethanol extracts of the remaining components without Polygala tenuifolia (concentration same as 500 μg / mL), and a positive control group using melatonin (100 μg / mL). After treatment at 28℃ for 1 day, 10 zebrafish were randomly selected from each group to collect data. The zebrafish's arousal activity (D) and total arousal time (S) were analyzed to evaluate the sleep-inducing effect of Polygala tenuifolia. The formula for calculating the sleep-inducing effect is as follows:

[0065]

[0066] Note: ER – represents the percentage (%) of the ethanol extract of Polygala tenuifolia (whole plant) that improves sleep in zebrafish.

[0067] D0 – represents the amount of arousal activity (mm) in the model group of zebrafish;

[0068] D1 – represents the level of arousal activity (mm) in the zebrafish of the treatment group.

[0069] Experimental data were analyzed using one-way ANOVA to examine differences between experimental groups. Results are expressed as mean ± standard deviation (mean ± SE). Statistical analysis was performed using GraphPad Prism 9.0 software, and p < 0.05 was considered statistically significant.

[0070] Figure 1 Typical zebrafish movement trajectories after treatment with ethanol extracts of traditional Chinese medicine compositions at different mass concentrations; where black lines represent slow speed, green lines represent medium speed, and red lines represent fast speed.

[0071] Table 1 shows the experimental results of the sleep-improving efficacy of Polygala tenuifolia ethanol extract at different mass concentrations (n=10):

[0072]

[0073] (Note: Compared with the model control group, *P<0.05, ***P<0.001)

[0074] Combination Figure 1As shown in Table 1, the study of zebrafish behavior revealed that all treatment groups using the ethanol extract of the traditional Chinese medicine composition showed varying degrees of improvement compared to the PTZ model control group. The sedative and sleep-improving effects of Polygala tenuifolia were evaluated by analyzing the zebrafish's arousal activity and total arousal time. The results showed that the positive melatonin group improved sleep by 29.79%, and the sleep-improving effects of the four treatment groups using the ethanol extract of the traditional Chinese medicine composition (100, 200, 500, and 800 μg / mL) were 8.52%, 22.54%, 35.04%, and 44.86%, respectively. The ethanol extracts of the traditional Chinese medicine composition at concentrations of 500 μg / mL and 800 μg / mL showed significantly better sleep-improving effects than the positive melatonin group. In the formulation without Polygala tenuifolia, the sleep-improving effect was 9.28%, indicating that Polygala tenuifolia (root) plays a crucial role in this formulation.

[0075] Example 5

[0076] This embodiment provides a research method for improving the anxiety and depression effects of a traditional Chinese medicine composition in experimental animals such as zebrafish.

[0077] The zebrafish were divided into three groups: a normal control group, a model control group, and a group that received an ethanol extract of a traditional Chinese medicine composition (Polygala tenuifolia ethanol extract group). The normal control group received no treatment, while the model control group and the group receiving the traditional Chinese medicine composition ingested the same amount of mCPP (mCPP was ingested by dissolving in the aquaculture water). The group receiving the Polygala tenuifolia ethanol extract group ingested the traditional Chinese medicine composition at the same time as ingesting mCPP. After taking the traditional Chinese medicine composition for a period of time, the following experiments were conducted: (1) the total movement distance of the zebrafish was analyzed; (2) the expression of anxiety-related genes was detected by q-PCR; and (3) the activity of monoamine oxidase (MAO) was detected by a kit.

[0078] (1) Behavioral Science

[0079] like Figure 2 The figure shows the total distance traveled by the zebrafish; from Figure 2 As can be seen, compared with the model control group, ***p<0.001; it can be seen that the movement distance of the group taking the traditional Chinese medicine composition (Yuanzhi ethanol extract group) was similar to that of the normal control group, and there was no significant increase in movement distance.

[0080] (2) Relative expression levels of gabra1, gad2, and htr2aa genes:

[0081] like Figure 3 As shown, this represents the relative expression level of the gabra1 gene in zebrafish. Figure 3It can be seen that, compared with the model control group, *p<0.05; it can be seen that the relative expression level of the gabra1 gene in zebrafish in the group taking the traditional Chinese medicine combination (Yuanzhi ethanol extract group) was similar to that in the normal control group, but significantly increased compared with the model control group.

[0082] like Figure 4 As shown, this represents the relative expression level of the gad2 gene in zebrafish. Figure 4 It can be seen that, compared with the model control group, *p<0.05; it can be seen that the relative expression level of gad2 gene in zebrafish in the group taking the traditional Chinese medicine combination (Yuanzhi ethanol extract group) is similar to that in the normal control group, but significantly increased compared with the model control group.

[0083] like Figure 5 The figure shows the relative expression level of the htr2aa gene in zebrafish. Figure 5 It can be seen that, compared with the model control group, **p<0.05; it can be seen that the relative expression level of htr2aa gene in zebrafish in the group taking the traditional Chinese medicine combination (Yuanzhi ethanol extract group) was similar to that in the normal control group, but significantly lower than that in the model control group.

[0084] (3) Monoamine oxidase activity:

[0085] Figure 6 The figure shows the activity level of monoamine oxidase in zebrafish, from... Figure 6 It can be seen that, compared with the model control group, *p<0.05; it can be seen that the monoamine oxidase activity of zebrafish in the group taking the traditional Chinese medicine composition (Yuanzhi ethanol extract group) was similar to that in the normal control group, but significantly lower than that in the model control group.

[0086] Zebrafish possess neural tissues and organs similar to those in humans; the hypothalamus, thalamus, basal ganglia, and limbic system are all brain regions associated with anxiety. 1-(3-chlorophenyl)piperazine hydrochloride (mCPP) is a nonspecific serotonergic (5-HT) agonist, and 5-HT is widely distributed in the aforementioned brain regions. Studies have shown that mCPP can induce anxiety by affecting the 5-HT pathway. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter widely distributed in the mammalian central nervous system; decreased GABA levels in the brain can lead to emotional problems such as depression, tension, anxiety, and insomnia. Glutamate decarboxylase (GAD) is the rate-limiting enzyme in the conversion of glutamate to GABA. Monoamine oxidase (MAO) is a single molecular enzyme with multiple binding sites, exhibiting low substrate specificity. It can oxidize and deaminate various amines, thereby affecting the metabolism of multiple neurotransmitters. Zebrafish possess only one Mao sequence, exhibiting properties similar to human MAO-A and human MAO-B, but more closely resembling human MAO-A. In most species, MAO-A degrades 5-HT. Studies have shown that locomotor activity and tacticism in zebrafish are two important indicators of anxiety. The GAD2 gene is closely related to anxiety and mood disorders. 5-HT increases anxiety-like behavior through serotonin receptor 2A (htr2aa). GABA-A receptors play an important role in the development of anxiety. Studies have shown that MAO-A / B double knockout mice have reduced 5-HT degradation and increased anxiety. Therefore, the presence of anxiety in zebrafish can be determined by detecting their behavior. Furthermore, the relative expression levels of anxiety-related genes (such as gabra1, gad2, and htr2aa genes) and MAO content can also be used to evaluate whether zebrafish experience anxiety.

[0087] The experimental data showed that, in a comparative experiment with 30 zebrafish in each group, the total movement distance, relative expression levels of gabra1, gad2, and htr2aa genes, and MAO activity of the zebrafish in the group treated with the Polygala tenuifolia extract were similar to those in the normal control group. This also confirmed that the traditional Chinese medicine combination (Polygala tenuifolia extract) has significant anti-anxiety effects.

[0088] Example 6

[0089] This embodiment provides a research method for improving the behavior of an AD model mouse using a traditional Chinese medicine composition:

[0090] The test mice (6 months old, female) were randomly divided into a normal group, an experimental group, and a model group. The experimental group and the model group were triple-transgenic AD mice (3×Tg-AD, homozygous mutant APP). SWE PS1 M146V ,and Tau P301LThree mice were placed in each group and housed in well-ventilated cages at a temperature of (23±3℃) and humidity of (55±5%), with ample food and water provided. The experimental group received a traditional Chinese medicine composition (Polygala tenuifolia extract) dissolved in physiological saline via gavage (200 mg / kg / 48h), while the other two groups received an equal volume of physiological saline. The experiment lasted for two weeks. The Morris water maze (MWM) was used to evaluate the cognitive abilities of the AD mice.

[0091] Figure 7 To determine the escape latency of mice in the MWM hiding platform experiment, from Figure 7 As can be seen, compared with the normal group, p < 0.01, the escape time of mice in the model group was significantly longer than that in the normal group, proving that the AD mouse model was successfully established; compared with the model group, p < 0.05, the escape time of mice in the experimental group was significantly shorter than that in the model group, proving that the traditional Chinese medicine composition (Yuanzhi alcohol extract formula) has a significant improvement on the learning and cognitive abilities of AD mice.

[0092] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, or alterations made by those skilled in the art using the disclosed technical content shall fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease (AD), characterized in that, The ethanol extract of the active pharmaceutical ingredients is used, and the active pharmaceutical ingredients are as follows by weight: 175-185 parts of Polygala tenuifolia root, 160-170 parts of Ziziphus jujuba seed, 90-100 parts of Platycladus orientalis seed, 150-160 parts of jujube, 160-170 parts of prepared licorice root, 160-170 parts of Astragalus membranaceus, 150-160 parts of Angelica sinensis, 150-160 parts of Salvia miltiorrhiza, and 155-165 parts of Schisandra chinensis.

2. The traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease according to claim 1, characterized in that, The raw materials are as follows by weight: 175-180 parts of Polygala tenuifolia root, 160-165 parts of Ziziphus jujuba seed, 90-95 parts of Platycladus orientalis seed, 150-155 parts of jujube, 160-165 parts of prepared licorice root, 160-165 parts of Astragalus membranaceus, 150-155 parts of Angelica sinensis, 150-155 parts of Salvia miltiorrhiza, and 155-160 parts of Schisandra chinensis.

3. The traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease according to claim 2, characterized in that, The raw materials are as follows by weight: 180 parts of Polygala tenuifolia root, 165 parts of Ziziphus jujuba seed, 95 parts of Platycladus orientalis seed, 155 parts of jujube, 165 parts of prepared licorice root, 165 parts of Astragalus membranaceus, 155 parts of Angelica sinensis, 155 parts of Salvia miltiorrhiza, and 160 parts of Schisandra chinensis.

4. A method for preparing a traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease as described in any one of claims 1-3, characterized in that, Includes the following steps: (1) Crush the raw material and sieve it for later use; (2) After soaking in ethanol, ultrasonic-assisted extraction was performed, followed by cooling, shaking, filtration, and repeated extraction of the filter residue. (3) Combine the filtrates, concentrate them, and obtain the ethanol extract of the traditional Chinese medicine composition.

5. The method for preparing the traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease according to claim 4, characterized in that: In step (1), the sample is passed through a No. 3 sieve for later use; In step (2), ethanol with a volume fraction of 45-75% is added at a weight-to-volume ratio of 1:2-6, soaked for 1-3 hours, extracted with ultrasonic assistance for 4-6 hours, cooled, shaken, filtered, and the residue is extracted twice. In step (3), the filtrates from the three filtrates are combined and concentrated to obtain an ethanol extract of the traditional Chinese medicine composition.

6. The method for preparing the traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease according to claim 5, characterized in that: In step (2), 60% ethanol is added at a weight-to-volume ratio of 1:4, soaked for 2 hours, and then extracted with ultrasound for 5 hours.

7. The method for preparing the traditional Chinese medicine composition for treating insomnia, anxiety, depression, and Alzheimer's disease according to claim 5 or 6, characterized in that: In step (3), the ethanol extract of the traditional Chinese medicine composition is concentrated to 2-3 g / mL.

8. The application of a traditional Chinese medicine composition according to any one of claims 1-3 and a traditional Chinese medicine composition prepared by the preparation method according to any one of claims 4-7, characterized in that, The application is as follows: (1) Application in the preparation of drugs for treating insomnia; and / or (2) its use in the preparation of medicines for treating anxiety and depression; And / or (3) its use in the preparation of medicaments for the treatment of AD.

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