A traditional Chinese medicine composition for treating insomnia, its preparation and application

Abstract

This invention relates to the field of traditional Chinese medicine, specifically to a traditional Chinese medicine composition for treating insomnia, characterized by being made from the following raw materials in parts by weight: 5-45 parts of stir-fried jujube seed, 3-35 parts of cypress seed, 5-30 parts of poria cocos, 5-30 parts of mulberry, 3-18 parts of dried plum, 1-10 parts of costus root, 3-18 parts of privet fruit, 2-16 parts of lycium chinense root bark, and 2-16 parts of fleeceflower stem. This invention also provides a traditional Chinese medicine compound preparation for treating insomnia and its application.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically, it relates to a traditional Chinese medicine composition for treating insomnia, its preparation and application. Background Technology

[0002] Insomnia refers to a persistent state of unsatisfactory sleep quality or quantity, also known as a sleep disorder. Clinical manifestations include difficulty falling asleep, shallow sleep, frequent awakenings, early awakenings, vivid dreams, fatigue upon waking, or lack of alertness, as well as changes in alertness, energy, cognitive function, behavior, and mood. Long-term sleep disorders often lead to weakened immunity, mental irritability, and can also easily trigger hypertension, neurasthenia, cardiovascular accidents, and mental illnesses, even causing sudden death. The threats that sleep disorders pose to daily work and life are also quite serious. Statistics show that 30-50% of accidents are caused by drowsiness. Furthermore, the economic and non-economic costs associated with insomnia are enormous. In Australia, the total cost of sleep deprivation in 2016-2017 was estimated at US$45.21 billion, of which the estimated total economic cost was US$17.88 billion, accounting for 1.55% of Australia's GDP, and the non-economic cost was US$27.33 billion, accounting for 4.60% of the total disease burden. Clearly, insomnia seriously affects people's normal lives and work. Summary of the Invention

[0003] The purpose of this invention is to provide a traditional Chinese medicine composition for treating insomnia, its preparation, and its application.

[0004] The first aspect of the present invention is to provide a traditional Chinese medicine composition for treating insomnia, which is made from the following raw materials in parts by weight: 5-45 parts of stir-fried jujube seed, 3-35 parts of cypress seed, 5-30 parts of poria cocos, 5-30 parts of mulberry, 3-18 parts of dried plum, 1-10 parts of costus root, 3-18 parts of privet fruit, 2-16 parts of lycium chinense root bark, and 2-16 parts of fleeceflower stem.

[0005] In a preferred embodiment, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 8-43 parts of stir-fried jujube seed, 7-30 parts of cypress seed, 6-29 parts of poria cocos, 10-25 parts of mulberry, 6-17 parts of dried plum, 2-9 parts of costus root, 6-17 parts of privet fruit, 4-15 parts of lycium bark, and 5-14 parts of fleeceflower stem.

[0006] In another preferred embodiment, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 12-40 parts of stir-fried jujube seed, 9-27 parts of cypress seed, 11-28 parts of poria cocos, 11-23 parts of mulberry, 7-15 parts of dried plum, 3-8 parts of costus root, 7-15 parts of privet fruit, 5-14 parts of lycium bark, and 6-13 parts of fleeceflower stem.

[0007] In another preferred embodiment, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of stir-fried jujube seed, 11 parts of cypress seed, 11 parts of poria cocos, 11 parts of mulberry, 7 parts of dried plum, 4 parts of costus root, 7 parts of privet fruit, 6 parts of lycium bark, and 6 parts of fleeceflower stem.

[0008] A second aspect of the present invention is to provide a traditional Chinese medicine compound preparation for treating insomnia, wherein the traditional Chinese medicine compound preparation is a decoction, granules, powder, capsule, tablet or oral liquid with the above-mentioned traditional Chinese medicine composition as the active ingredient.

[0009] In a preferred embodiment, the traditional Chinese medicine compound preparation is a decoction.

[0010] The present invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating insomnia.

[0011] Details of various aspects of the invention will be described in detail in the following sections. The features, objects, and advantages of the invention will become more apparent from the following description and the claims. Detailed Implementation

[0012] The sources of the Chinese medicinal materials used by the inventors in preparing the Chinese medicine composition of the present invention are as follows:

[0013] Sour jujube seed (fried) is the dried, mature seed of the sour jujube plant (Ziziphus jujuba), belonging to the Rhamnaceae family. It is sweet and neutral in nature, and enters the heart, spleen, liver, and gallbladder meridians. It nourishes the heart and liver, calms the mind and soothes the nerves, and astringes sweat and promotes the production of body fluids. It is a commonly used heart-nourishing and mind-calming herb in traditional Chinese medicine for treating insomnia. Sour jujube seed mainly contains triterpenoids, flavonoids, and fatty oils, among other bioactive components. Pharmacological experiments have confirmed that the compounds that mainly affect the central nervous system are flavonoids and saponins, which can inhibit the central nervous system and have a sedative effect. Its mechanism of action may be through reducing monoamine neurotransmitters in the brain.

[0014] Arborvitae seed kernel is the dried, mature seed kernel of the Arborvitae plant (Platycladus orientalis), belonging to the Cupressaceae family. It is sweet and neutral in nature, and enters the heart, kidney, and large intestine meridians. It has the effects of nourishing the heart and calming the mind, moistening the intestines and promoting bowel movements, and stopping sweating. Arborvitae seed kernel contains various chemical components, including total terpenoids, flavonoids, glycosides, and steroidal compounds, among other bioactive components. Pharmacological experiments have confirmed that saponins and terpenoids in arborvitae seed kernel have certain antidepressant effects. Studies have shown that saponins in arborvitae seed kernel have a certain ameliorative effect on Alzheimer's disease, and its mechanism of action may be through regulating malondialdehyde, glutathione, and superoxide dismutase in the hippocampus.

[0015] Poria cocos is the dried sclerotium of the fungus Poria cocos (family Polyporaceae). It is sweet and bland in nature, and has the effects of promoting diuresis and eliminating dampness, strengthening the spleen and calming the mind. The main chemical components of Poria cocos are triterpenoids, diterpenoids, sterols, polysaccharides, and other compounds, among which triterpenoids and polysaccharides are the most studied. Modern pharmacological studies indicate that Poria cocos has numerous pharmacological activities, including lowering blood sugar and blood lipids, protecting the liver, anti-tumor activity, immunomodulation, anti-inflammation, sedation and hypnosis, anti-oxidation, and anti-aging. Studies have shown that the aqueous decoction of Poria cocos has a synergistic central inhibitory effect with sodium pentobarbital, further verifying the sedative and hypnotic effect of the decoction. Simultaneously, the high, medium, and low doses of Poria cocos polysaccharides, in synergistic effect with phenobarbital, all increased the sleep duration and anticonvulsant rate in mice to varying degrees, indicating that Poria cocos polysaccharides have a significant sedative and hypnotic effect on mice.

[0016] Mulberry is the dried fruit spike of the mulberry tree (Morus alba), a plant in the Moraceae family. It has the effects of nourishing yin and blood, promoting body fluid production and moistening dryness, and is often used to treat symptoms such as liver and kidney yin deficiency, dizziness and tinnitus, palpitations and insomnia, premature graying of hair, thirst due to fluid depletion, internal heat and thirst, and constipation due to intestinal dryness. The main chemical components of mulberry include flavonoids, anthocyanins, phenolic acids, and polysaccharides. Modern pharmacological studies have shown that it has hepatoprotective, antioxidant, anti-inflammatory, anti-cancer, and blood pressure-lowering effects. Research has found that pressure treatment reduces the content of total phenolic acids, total flavonoids, and anthocyanins in mulberry juice, while also reducing its ability to reduce iron ions and scavenge DPPH free radicals, preliminarily indicating that total phenolic acids, total flavonoids, and anthocyanins have antioxidant capabilities.

[0017] Ume (dried plum) is the nearly mature fruit of the plum tree (Prunus mume) in the Rosaceae family. It has a sour and astringent taste, is neutral in nature, and enters the lung, liver, spleen, and large intestine meridians. It has the effects of astringing the lungs, astringing the intestines, promoting body fluid production, and expelling roundworms. The chemical composition of ume is complex and diverse, mainly including organic acids, terpenes, sterols, sugars, amino acids, alkaloids, lipids, flavonoids, and volatile components. Modern pharmacological studies have shown that ume has sedative, anticonvulsant, antitumor, antioxidant stress, and antibacterial effects. Research has found that a decoction of ume can increase the subthreshold dose of sodium pentobarbital in mice, prolong sleep time in mice, and reduce the latency of convulsions in mice induced by nikethamide.

[0018] Costus root is the dried root of the Aucklandia lappa plant (family Asteraceae). It has a pungent and bitter taste, is warm in nature, and enters the spleen, stomach, large intestine, triple burner, and gallbladder meridians. Its main functions are to regulate qi and relieve pain, strengthen the spleen and promote digestion. It is often used for pain caused by qi stagnation due to various reasons. Costus root contains various chemical components, such as volatile oils, resins, costine, and inulin. Modern pharmacological studies have shown that costus root has anti-inflammatory, hepatoprotective, cardiac function regulating, anti-tumor, and antiviral effects. Research has found that costunolactone in costus root has smooth muscle relaxant and antispasmodic effects.

[0019] Privet fruit is the dried, ripe fruit of the privet plant (Ligustrum lucidum), belonging to the Oleaceae family. It has a sweet and bitter taste, is cool in nature, and enters the liver and kidney meridians. It nourishes the liver and kidneys, improves eyesight, and darkens hair. It is mainly used to treat symptoms such as liver and kidney yin deficiency, dizziness, tinnitus, lower back and knee weakness, premature graying of hair, blurred vision, internal heat and thirst, and night sweats. Privet fruit contains various active ingredients, such as triterpenoids, iridoids, phenylethyl alcohol, flavonoids, volatile oils, sugars, amino acids, and sterols. Modern pharmacological studies have shown that privet fruit has various pharmacological effects, including immunomodulation, anti-aging, liver protection, anti-inflammatory, antibacterial, antiviral, antitumor, anti-osteoporosis, hypoglycemic, and hypolipidemic effects. Research has found that water extract of privet fruit significantly inhibited acetic acid-induced writhing, formalin-induced pain, and foot edema. Its mechanism of action is mainly related to increasing the activity of liver antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase, and reducing inducible nitric oxide synthase and cyclooxygenase-2.

[0020] Lycium bark is the dried root bark of *Lycium chinense* or *Lycium ningpoensis*, both belonging to the Solanaceae family. It is sweet and cold in nature, and enters the lung, liver, and kidney meridians. It has the effects of cooling the blood and relieving fever, clearing the lungs and reducing heat. It is mainly used for symptoms such as yin deficiency with tidal fever, night sweats, lung heat cough, hemoptysis, and internal heat with thirst. Lycium bark contains alkaloids, phenylpropanoids, organic acids and their esters, anthraquinones, and sterols. Modern pharmacological studies have shown that Lycium bark has pharmacological effects such as lowering blood pressure, regulating blood lipids, lowering blood sugar, antibacterial, antiviral, antipyretic, and analgesic properties.

[0021] Polygonum multiflorum vine is the dried stem of the Polygonum multiflorum plant (Polygonaceae family). It has a sweet taste and neutral properties, and enters the heart and liver meridians. It nourishes the heart and calms the mind, unblocks the meridians and dispels wind, and is commonly used for symptoms such as insomnia, excessive dreaming, and rheumatic pain. The main components of Polygonum multiflorum vine include quinones, flavonoids, and glycosides, as well as steroids, stilbene derivatives, benzene derivatives, anthocyanins, and volatile components. Modern pharmacological studies have shown that Polygonum multiflorum vine has sedative-hypnotic, hypoglycemic, hypolipidemic, anti-inflammatory, antioxidant, and immunomodulatory pharmacological effects. Studies have found that a compound oral liquid containing Polygonum multiflorum vine as the main component effectively treats neurasthenia-related insomnia with a total efficacy rate of over 87%, showing no significant difference in effect compared to the control group taking diazepam. The mechanism may be related to Polygonum multiflorum vine improving the ultrastructure of mitochondria and increasing Na+. + -K + -ATPase and Ca 2+ -Mg 2+ The level of ATPase is associated with improving insomnia.

[0022] By analyzing the pharmacological properties of various Chinese medicinal herbs and comprehensively considering the multiple composite syndromes of insomnia in traditional Chinese medicine syndromes, and aiming at the characteristics of various syndromes of insomnia, such as hyperactivity of fire due to yin deficiency, spleen deficiency with liver depression, loss of nourishment of the heart spirit, and upward disturbance of heart fire, in the formula, wild jujube seed is sour in taste and enters the heart and liver meridians, which can nourish the heart, tonify the liver, calm the mind and soothe the nerves; semen platycladi is sweet in taste, moist in nature, and mild in medicinal properties, mainly entering the heart meridian, and is used in combination with wild jujube seed to calm the mind and soothe the nerves. The two are used as a medicinal pair and have a good sedative and hypnotic effect, so they are重用 as the monarch drug. Poria cocos is sweet in taste and neutral in nature, which can tonify the heart and spleen and calm the mind and soothe the nerves; mulberry fruit is sweet in taste and cold in nature, which can enter the liver meridian and nourish the liver blood; smoked plum is sour in taste and enters the liver, and is good at promoting the production of body fluids and relieving vexation and thirst, and can treat internal disturbance of deficiency fire. The three together are the ministerial drugs. Aucklandiae radix has a thin, pungent and fragrant smell, can regulate qi and arouse the spleen to promote digestion, prevent the herbs from being greasy and obstructing the stomach, so that the tonics are not stagnant, and can regulate qi movement smoothly; glossy privet fruit is sweet in taste and cool in nature, which can nourish the liver and kidney and also clear away deficiency heat. It is combined with cortex lycii radicis to better achieve the effect of clearing away deficiency heat and is the assistant drug. Caulis polygoni multiflori, also known as "caulis polygoni multiflori noctis", enters the liver meridian. In addition to nourishing the heart and calming the mind, it can also lead all the herbs to achieve the effect of harmony between yin and yang and is the guiding drug. The whole formula has a reasonable structure and precise compatibility, and together they achieve the effects of nourishing blood, tonifying blood, calming the mind and soothe the nerves.

[0023] Semen platycladi, Poria cocos, mulberry fruit, smoked plum, Aucklandiae radix, glossy privet fruit, and Caulis polygoni multiflori in the traditional Chinese medicine composition of the present invention are all purchased from Shanghai Wanshicheng Chinese Medicine Products Co., Ltd.; stir-fried wild jujube seed and cortex lycii radicis are purchased from Shanghai Kangqiao Chinese Herbal Pieces Co., Ltd. The traditional Chinese medicine composition of the present invention can be prepared by conventional methods in the art. For example: Take the nine herbs of stir-fried wild jujube seed, semen platycladi, Poria cocos, mulberry fruit, smoked plum, Aucklandiae radix, glossy privet fruit, cortex lycii radicis, and Caulis polygoni multiflori, add 12 times the total weight of water, decoct twice, each time for 50 - 70 minutes, combine the two decoction extracts, filter, take the filtrate, and concentrate it into an extract with a relative density of 1.15 - 1.25 (70 - 85 °C) for standby.

[0024] It has been confirmed by the research of the present inventor that the traditional Chinese medicine composition, its preparation, and application of the present invention have a reasonable overall structure, precise compatibility, no obvious toxic and side effects, and have effects in aspects such as calming the mind and soothe the nerves, clearing away heart-fire and relieving vexation, and improving sleep.

[0025] The following further elaborates the present invention in combination with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions noted in the following embodiments are usually carried out under conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise specified, all percentages, ratios, proportions, or parts are by weight.

[0026] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the method of the present invention. The preferred methods and materials described herein are only for demonstration purposes.

[0027] The features mentioned above in this invention, or the features mentioned in the embodiments, can be combined arbitrarily. All features disclosed in this patent specification can be used in any compositional form, and each feature disclosed in the specification can be replaced by any alternative feature that provides the same, equivalent, or similar purpose. Therefore, unless otherwise specified, the disclosed features are merely general examples of equivalent or similar features.

[0028] Example 1

[0029] Take 5g of stir-fried jujube seed, 3g of cypress seed, 5g of poria cocos, 5g of mulberry, 3g of dried plum, 1g of costus root, 3g of privet fruit, 2g of lycium bark, and 2g of fleeceflower stem.

[0030] The preparation method is as follows:

[0031] Take the above nine herbs, add 12 times their total weight of water, decoct twice, each time for 50-70 minutes, combine the extracts from the two decoctions and filter, take the filtrate and concentrate it into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0032] The administration method is as follows: Take the extract, dissolve it in water, and administer orally.

[0033] Example 2

[0034] Take 8g of stir-fried jujube seed, 9g of cypress seed, 12g of poria cocos, 14g of mulberry, 7g of dried plum, 6g of costus root, 8g of privet fruit, 5g of lycium bark, and 7g of fleeceflower stem.

[0035] The preparation and administration methods are the same as in Example 1.

[0036] Example 3

[0037] Take 12g of stir-fried jujube seed, 7g of cypress seed, 12g of poria cocos, 12g of mulberry, 6g of dried plum, 2g of costus root, 9g of privet fruit, 4g of lycium bark, and 6g of fleeceflower stem.

[0038] The preparation and administration methods are the same as in Example 1.

[0039] Example 4

[0040] Take 15g of stir-fried jujube seeds, 10g of cypress seeds, 6g of poria cocos, 10g of mulberry, 6g of dried plum, 3g of costus root, 6g of privet fruit, 5g of lycium bark, and 5g of fleeceflower stem.

[0041] The preparation and administration methods are the same as in Example 1.

[0042] Example 5

[0043] 15g of stir-fried jujube seeds, 11g of cypress seeds, 11g of poria cocos, 11g of mulberry, 7g of dried plum, 4g of costus root, 7g of privet fruit, 6g of lycium bark, and 6g of fleeceflower stem.

[0044] The preparation and administration methods are the same as in Example 1.

[0045] Example 6

[0046] Take 18g of stir-fried jujube seeds, 10g of cypress seeds, 12g of poria cocos, 15g of mulberry, 8g of dried plum, 3g of costus root, 12g of privet fruit, 6g of lycium bark, and 9g of fleeceflower stem.

[0047] The preparation and administration methods are the same as in Example 1.

[0048] Example 7

[0049] Take 25g of stir-fried jujube seeds, 19g of cypress seeds, 17g of poria cocos, 17g of mulberry, 11g of dried plum, 6g of costus root, 11g of privet fruit, 9g of lycium bark, and 9g of fleeceflower stem.

[0050] The preparation and administration methods are the same as in Example 1.

[0051] Example 8

[0052] Take 29g of stir-fried jujube seeds, 20g of cypress seeds, 25g of poria cocos, 30g of mulberry, 15g of dried plum, 5g of costus root, 17g of privet fruit, 10g of lycium bark, and 14g of fleeceflower stem.

[0053] The preparation and administration methods are the same as in Example 1.

[0054] Example 9

[0055] Take 35g of stir-fried jujube seeds, 27g of cypress seeds, 23g of poria cocos, 23g of mulberry, 15g of dried plum, 8g of costus root, 15g of privet fruit, 13g of lycium bark, and 13g of fleeceflower stem.

[0056] The preparation and administration methods are the same as in Example 1.

[0057] Example 10

[0058] Take 40g of stir-fried jujube seeds, 22g of cypress seeds, 28g of poria cocos, 35g of mulberry, 17g of dried plum, 8g of costus root, 11g of privet fruit, 14g of lycium bark, and 16g of fleeceflower stem.

[0059] The preparation and administration methods are the same as in Example 1.

[0060] Example 11

[0061] Take 43g of stir-fried jujube seeds, 30g of cypress seeds, 29g of poria cocos, 30g of mulberry, 18g of dried plum, 9g of costus root, 13g of privet fruit, 15g of lycium bark, and 16g of fleeceflower stem.

[0062] The preparation and administration methods are the same as in Example 1.

[0063] Example 12

[0064] Take 45 g of stir-fried Semen Ziziphi Spinosae, 35 g of Semen Platycladi, 30 g of Poria, 30 g of Fructus Mori, 18 g of Fructus Mume, 10 g of Aucklandiae Radix, 18 g of Fructus Ligustri Lucidi, 16 g of Cortex Lycii, and 16 g of Caulis Polygoni Multiflori.

[0065] The preparation method and administration method are the same as those in Example 1.

[0066] Example 13 Comparative study of the traditional Chinese medicine composition of the present invention with the literature formula

[0067] Experimental drug: The traditional Chinese medicine composition of the present invention is prepared according to Example 5. The composition of the literature formula Zaoren Ningxin Capsule is: Semen Ziziphi Spinosae, Concha Margaritifera, Bulbus Lilii, Radix Curcumae, Poria, Caulis Polygoni Multiflori, Radix Pseudostellariae, Radix Salviae Miltiorrhizae, Fructus Mume, Cortex Albiziae, Radix Glycyrrhizae, Radix Panacis Quinquefolii. This formula uses Semen Ziziphi Spinosae, Poria, and Radix Curcumae as the main drugs, and is assisted by Concha Margaritifera, Bulbus Lilii, Caulis Polygoni Multiflori, Radix Pseudostellariae, Radix Salviae Miltiorrhizae, Fructus Mume, Cortex Albiziae, Radix Glycyrrhizae, etc. The whole formula invigorates the spleen, soothes the liver, nourishes the heart, and calms the mind (He Furong, He Juan, Tong Liguo, Feng Mali. Experimental study on the sedative and hypnotic effects of traditional Chinese medicine Zaoren Ningshen Capsule [J]. Ningxia Medical Journal, 2015, 37(8): 706-707; Li Xiaojun, Shi Na. Clinical study on the treatment of insomnia with spleen deficiency and liver depression and loss of nourishment of the heart by Zaoren Ningshen Capsule [J]. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease, 2021, 19(16): 2823-2826.). Preparation of the drug in the literature formula: Take Zaoren Ningxin Capsule (prepared by the preparation room of Shanxi Traditional Chinese Medicine Hospital), and prepare it into a solution containing 2 g / mL of capsule powder. Prepared according to the method disclosed in the literature.

[0068] Experimental animals: SPF-grade ICR male mice, weighing 18.0-22.0 g, provided by Shanghai Slake Experimental Animal Co., Ltd., certificate number SCXK (Shanghai) 2022-0004. The mice were housed in the barrier breeding room of the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine, with an environmental temperature of 20-25 °C, a relative humidity of 40%-70%, a light of 12 h light and 12 h dark, and free access to food and water.

[0069] Experimental method: 1. Direct sleep experiment: 30 mice weighing 18.0-22.0 g were randomly divided into a control group, a literature formula group, and a traditional Chinese medicine composition group of the present invention, with 10 mice in each group. The control group was given normal saline (0.1 mL / 10 g) by gavage every day, and the literature formula group and the traditional Chinese medicine composition group of the present invention were given 0.1 mL / 10 g once a day for 30 consecutive days by gavage. 20 minutes after the last administration, observe whether the mice in each group showed sleep phenomena, and record the number of sleeping animals and the sleep time.

[0070] 2. Pentobarbital Sodium Sleep Time Prolongation Experiment: Thirty mice weighing 18.0–22.0 g were randomly divided into a control group, a literature-based formula group, and a traditional Chinese medicine composition group of the present invention, with 10 mice in each group. The control group was administered physiological saline (0.1 mL / 10 g) by gavage daily, while the literature-based formula group and the traditional Chinese medicine composition group received 0.1 mL / 10 g once daily for 30 consecutive days. Twenty minutes after the last administration, each group of animals was injected intraperitoneally with 60 mg / kg of pentobarbital sodium (0.1 mL / 10 g). The disappearance of the righting reflex was used as an indicator to observe whether the test substance could prolong pentobarbital sodium sleep time. The experimental results were statistically analyzed using analysis of variance. If the sleep time of the experimental group mice was significantly longer than that of the negative control group, the experimental result was considered positive.

[0071] 3. Subthreshold dose hypnotic experiment of sodium pentobarbital: Thirty mice weighing 18.0–22.0 g were randomly divided into a control group, a literature-prepared formula group, and a traditional Chinese medicine composition group of the present invention, with 10 mice in each group. The control group was given physiological saline (0.1 mL / 10 g) by gavage daily, while the literature-prepared formula group and the traditional Chinese medicine composition group received 0.1 mL / 10 g once daily for 30 consecutive days. Twenty minutes after the last administration, each group of animals was injected intraperitoneally with sodium pentobarbital 40 mg / kg, at a dose of 0.1 mL / 10 g. The number of animals falling asleep within 30 minutes was recorded, and the incidence of falling asleep was calculated.

[0072] 4. Sodium barbital sleep latency test: Thirty mice weighing 18.0–22.0 g were randomly divided into a control group, a literature-based formula group, and a traditional Chinese medicine composition group of the present invention, with 10 mice in each group. The control group was administered physiological saline (0.1 mL / 10 g) by gavage daily, while the literature-based formula group and the traditional Chinese medicine composition group received 0.1 mL / 10 g once daily for 30 consecutive days. Twenty minutes after the last administration, each group of animals was intraperitoneally injected with sodium barbital at a dose of 285 mg / kg (0.1 mL / 10 g). The disappearance of the righting reflex was used as an indicator to observe whether the test substance could shorten the sodium barbital sleep latency. The experimental results were statistically analyzed using analysis of variance. If the sleep latency of the experimental group mice was shorter than that of the negative control group and the difference was statistically significant, the experimental result was considered positive.

[0073] 5. Statistical Methods

[0074] Statistical analysis of the data was performed using one-way ANOVA in SPSS 25.0 software for mean comparison. Except for the incidence of animals falling asleep, which was tested using the chi-square test, all other indicators were compared using the t-test between groups.

[0075] The results are as follows:

[0076] Table 1. Effects of the herbal composition of the present invention and the literature formula on direct sleep in mice. n=10)

[0077]

[0078]

[0079] Note: Compared with the normal group, *P<0.05.

[0080] Experimental Results: As shown in Table 1, the animals in the control group exhibited normal behavior and movement, with no abnormal postures or gaits, and no salivation or muscle tremors. Compared with the control group, the herbal composition of this invention and the prescription from the literature, administered to mice by gavage for 30 consecutive days, showed no obvious drowsiness except for a few animals exhibiting reduced activity. There were no significant differences in the number of animals falling asleep or the duration of sleep (P > 0.05), indicating that the herbal composition of this invention and the prescription from the literature have no direct sleep-inducing effect on mice, and the results of this experiment are negative.

[0081] Table 2. Effects of the traditional Chinese medicine composition of the present invention and the literature formula on prolonging the sleep time of sodium pentobarbital ( n=10)

[0082]

[0083] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the literature group, △ P < 0.05 △△ P < 0.01, △△△ P < 0.001.

[0084] Experimental Results: As shown in Table 2, compared with the normal group, both the herbal composition group of this invention and the prescription group in the literature significantly advanced the time it took for normal mice to fall asleep, and also prolonged the average sleep time of the mice, significantly improving sleep with statistical differences (P < 0.01). Furthermore, the improvement effect of the herbal composition of this invention was significantly better than that of the prescription in the literature, with a statistical difference (P < 0.05), indicating that the herbal composition of this invention and the prescription in the literature have a sleep-aiding effect on mice, and the results of this experiment are positive.

[0085] Table 3. Effects of the traditional Chinese medicine composition of the present invention and the literature formula on the incidence of sleep at subthreshold doses of pentobarbital sodium ( n=10)

[0086]

[0087] Note: Compared with the normal group, *P<0.05.

[0088] Experimental Results: As shown in Table 3, compared with the normal group, both the herbal composition group of this invention and the literature prescription group improved the sleep rate of normal mice, but the herbal composition group of this invention showed a statistically significant difference (P < 0.05). Furthermore, the improvement effect of the herbal composition of this invention was significantly better than that of the literature prescription. This indicates that the literature prescription did not significantly improve the sleep rate of mice, and the experimental result was negative. The herbal composition of this invention has a sleep-aiding effect on mice, and the experimental result of this experiment is positive.

[0089] Table 4. Effects of the traditional Chinese medicine composition of the present invention and the literature formula on the sleep latency of sodium barbital ( n=10)

[0090]

[0091] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the literature group, △ P < 0.05 △△ P < 0.01, △△△ P < 0.001.

[0092] Experimental results: As shown in Table 4, compared with the normal group, the sleep latency of the herbal composition group of the present invention and the literature prescription group were significantly different from those of the control group (P<0.001), and the improvement effect of the herbal composition of the present invention was significantly better than that of the literature prescription (P<0.01), and the experimental results were positive.

[0093] Example 14: Comparative Study of the Traditional Chinese Medicine Composition and Individual Formulas of the Present Invention

[0094] The decoction of the traditional Chinese medicine composition of the present invention, as described in Example 5, was prepared as follows: 15g of stir-fried jujube seed, 11g of cypress seed, 11g of poria cocos, 11g of mulberry, 7g of dried plum, 4g of costus root, 7g of privet fruit, 6g of lycium bark, and 6g of fleeceflower stem. Add 12 times the total weight of water (792mL), decoct twice, each time for 50-70 minutes. Combine the extracts from the two decoctions, filter, and concentrate the filtrate into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0095] Formula 1: Ingredients: 10g of Platycladus orientalis seed, 6g of Poria cocos, 10g of mulberry, 6g of dried plum, 3g of costus root, 6g of privet fruit, 5g of Lycium chinense root bark, and 5g of Polygonum multiflorum vine. Add 12 times the total weight of water (612mL), decoct twice, each time for 50-70 minutes. Combine the two decoctions and filter. Take the filtrate and concentrate it into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0096] Formula 2 consists of the following ingredients: 15g of stir-fried jujube seed, 6g of Poria cocos, 10g of mulberry, 6g of dried plum, 3g of costus root, 6g of privet fruit, 5g of lycium bark, and 5g of fleeceflower stem. Add 12 times the total weight of water (672mL), decoct twice, each time for 50-70 minutes. Combine the two decoctions and filter. Take the filtrate and concentrate it into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0097] Formula 3 consists of the following ingredients: 15g of stir-fried jujube seed, 10g of cypress seed, 10g of mulberry, 6g of dried plum, 3g of costus root, 6g of privet fruit, 5g of lycium root bark, and 5g of fleeceflower stem. Add 12 times the total weight of water (720mL), decoct twice, each time for 50-70 minutes. Combine the two decoctions and filter. Take the filtrate and concentrate it into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0098] Formula 4 consists of the following ingredients: 15g of stir-fried jujube seed, 10g of cypress seed, 6g of poria cocos, 6g of dried plum, 3g of costus root, 6g of privet fruit, 5g of lycium bark, and 5g of fleeceflower stem. Add 12 times the total weight of water (672mL), decoct twice, each time for 50-70 minutes. Combine the two decoctions and filter. Take the filtrate and concentrate it into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0099] Formula 5 consists of the following ingredients: 15g of stir-fried jujube seed, 10g of cypress seed, 6g of poria cocos, 10g of mulberry fruit, 3g of costus root, 6g of privet fruit, 5g of lycium bark, and 5g of fleeceflower stem. Add 12 times the total weight of water (720mL), decoct twice, each time for 50-70 minutes. Combine the two decoctions and filter. Take the filtrate and concentrate it into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0100] Formula 6 consists of the following ingredients: 15g of stir-fried jujube seed, 10g of cypress seed, 6g of poria cocos, 10g of mulberry, 6g of dried plum, 6g of privet fruit, 5g of lycium bark, and 5g of fleeceflower stem. Add 12 times the total weight of water (756mL), decoct twice, each time for 50-70 minutes. Combine the extracts from the two decoctions, filter, and concentrate the filtrate into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0101] Formula 7 consists of the following ingredients: 15g of stir-fried jujube seed, 10g of cypress seed, 6g of poria cocos, 10g of mulberry, 6g of dried plum, 3g of costus root, 5g of lycium bark, and 5g of fleeceflower stem. Add 12 times the total weight of water (720mL), decoct twice, each time for 50-70 minutes. Combine the two decoctions and filter. Take the filtrate and concentrate it into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0102] Formula 8 consists of the following ingredients: 15g of stir-fried jujube seed, 10g of cypress seed, 6g of poria cocos, 10g of mulberry, 6g of dried plum, 3g of costus root, 6g of privet fruit, and 5g of fleeceflower stem. Add 12 times the total weight of water (732mL), decoct twice, each time for 50-70 minutes. Combine the extracts from the two decoctions, filter, and concentrate the filtrate into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0103] Formula 9 consists of the following ingredients: 15g of stir-fried jujube seed, 10g of cypress seed, 6g of poria cocos, 10g of mulberry, 6g of dried plum, 3g of costus root, 6g of privet fruit, and 5g of lycium root bark. Add 12 times the total weight of water (732mL), decoct twice, each time for 50-70 minutes. Combine the extracts from the two decoctions, filter, and concentrate the filtrate into an extract with a relative density of 1.15-1.25 (70-85℃) for later use.

[0104] Preparation method of the disassembled drug: It was prepared according to the method in Example 5.

[0105] Experimental animals: Same as those in Example 13.

[0106] Experimental Methods: 110 mice weighing 18.0–22.0 g were randomly divided into a control group, each component group, and the herbal composition group of the present invention, with 10 mice in each group. The control group was administered physiological saline (0.1 mL / 10 g) by gavage daily, while the herbal composition and each component group of the present invention were administered 0.1 mL / 10 g once daily for 30 consecutive days. After the 30th day of administration, experiments were conducted on the effects of direct sleep, prolonged pentobarbital sodium sleep time, the effect of subthreshold doses of pentobarbital sodium on sleep incidence, and the effect of barbital sodium latency, using the same methods as in Example 13.

[0107] Table 5. Effects of the herbal composition and its components of the present invention on direct sleep in mice. n=10)

[0108]

[0109] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001

[0110] Experimental Results: As shown in Table 5, the animals in the normal group exhibited normal behavior and movement, with no abnormal postures or gaits, and no salivation or muscle tremors. Compared with the normal group, the mice in the herbal composition group and each component group of this invention, after being administered the medicine by gavage for 30 consecutive days, showed no obvious drowsiness, except for a few animals exhibiting reduced activity. There were no significant differences in the number of animals falling asleep or the duration of sleep (P > 0.05).

[0111] Table 6. Effects of the traditional Chinese medicine composition and its components of the present invention on prolonging the sleep time of sodium pentobarbital (Table 6) n=10)

[0112]

[0113] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the traditional Chinese medicine composition group of the present invention, △ P < 0.05 △△ P < 0.01.

[0114] Experimental results: As shown in Table 6, compared with the normal group, the time for mice to fall asleep was significantly shortened and the average sleep time was significantly prolonged in the herbal composition group and each component group of the present invention (P<0.01 or P<0.001), which significantly improved sleep. However, the therapeutic effect of any component group with one less herb was not as good as that of the composition of the present invention, and the difference was statistically significant (P<0.01). The experimental result was positive.

[0115] Table 7. Effects of the traditional Chinese medicine composition and its components of the present invention on the incidence of sleep at subthreshold doses of pentobarbital sodium. n=10)

[0116]

[0117]

[0118] Note: Compared with the normal group, *P<0.05, **P<0.01; compared with the traditional Chinese medicine composition group of the present invention, △ P < 0.05 △△ P < 0.01.

[0119] Experimental Results: As shown in Table 7, compared with the normal group, the traditional Chinese medicine composition group and each component group of the present invention improved the sleep rate of normal mice. However, the traditional Chinese medicine composition group of the present invention showed a statistically significant difference (P<0.05 or P<0.01). The experimental result was positive. However, the sleep improvement effect of any component group with one less herb was not as good as that of the traditional Chinese medicine composition of the present invention, and the difference was statistically significant (P<0.05).

[0120] Table 8. Effects of the traditional Chinese medicine composition and its components of the present invention on the sleep latency of sodium barbital ( n=10)

[0121]

[0122] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the traditional Chinese medicine composition group of the present invention, △ P < 0.05 △△ P < 0.01, △△△ P < 0.001.

[0123] Experimental results: As shown in Table 8, compared with the normal group, the sleep latency of the herbal composition group and each decomposed group of the present invention was significantly different from that of the control group (P<0.001), and the experimental results were positive. However, the sleep improvement effect of any decomposed group with one less herb was not as good as that of the herbal composition of the present invention, and the difference was statistically significant (P<0.05).

[0124] Example 15 Experimental study on the effect of the traditional Chinese medicine composition and its preparation and application of the present invention on improving sleep function.

[0125] Experimental drug: The traditional Chinese medicine composition of the present invention was prepared according to Example 5.

[0126] Experimental animals: Same as those in Example 13.

[0127] Experimental Methods: Forty mice weighing 18.0–22.0 g were randomly divided into a control group and low, medium, and high dose groups of the traditional Chinese medicine composition of this invention, with 10 mice in each group. The control group was administered physiological saline (0.1 mL / 10 g) by gavage daily, while the low, medium, and high dose groups of the traditional Chinese medicine composition of this invention were administered 0.1 mL / 10 g once daily for 30 consecutive days. After the 30th day of administration, experiments were conducted on the effects of direct sleep, prolonged pentobarbital sodium sleep time, the effect of subthreshold dose pentobarbital sodium on sleep incidence, and the effect of barbital sodium latency. The experimental methods were consistent with those in Example 13.

[0128] Statistical methods: Data were analyzed using one-way ANOVA in SPSS 25.0 software for mean comparison. Except for the incidence of animals falling asleep, which was tested using the chi-square test, all other indicators were compared using the t-test between groups.

[0129] The results are as follows:

[0130] Table 9. Effects of the herbal composition of the present invention on direct sleep in mice ( n=10)

[0131]

[0132] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001

[0133] Experimental Results: As shown in Table 9, the animals in the control group exhibited normal behavior and movement, with no abnormal postures or gaits, and no salivation or muscle tremors. Compared with the control group, the mice in the low, medium, and high dose groups of the herbal composition of this invention, after being administered by gavage for 30 consecutive days, showed no obvious drowsiness except for a few animals exhibiting reduced activity. There were no significant differences in the number of animals falling asleep or the duration of sleep (P > 0.05).

[0134] Table 10. Effects of the traditional Chinese medicine composition of the present invention on prolonging the sleep time of sodium pentobarbital () n=10)

[0135]

[0136] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001

[0137] Experimental Results: As shown in Table 10, compared with the control group, the time to fall asleep and the average sleep time were significantly shortened in the medium and high dose (3.30, 4.95 g / mL) groups of the traditional Chinese medicine composition of the present invention (P < 0.01 or P < 0.001). There were no significant differences in the time to fall asleep and the average sleep time between the low dose (1.65 g / mL) group and the control group (P > 0.05). This indicates that the medium and high doses of the traditional Chinese medicine composition of the present invention can prolong the sleep time induced by sodium pentobarbital in mice, and the experimental results are positive.

[0138] Table 11. Effect of the traditional Chinese medicine composition of the present invention on the incidence of sleep at subthreshold doses of pentobarbital sodium ( n=10)

[0139]

[0140]

[0141] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001

[0142] Experimental Results: As shown in Table 11, compared with the control group, the incidence of sleep in mice in the medium and high dose (3.30, 4.95 g / mL) groups of the traditional Chinese medicine composition of the present invention was significantly increased (P < 0.05 or P < 0.01), while the incidence of sleep in the low dose (1.65 g / mL) group was not significantly different from that in the control group (P > 0.05). This indicates that the medium and high doses of the traditional Chinese medicine composition of the present invention can increase the incidence of sleep in mice with subthreshold sodium pentobarbital, and the experimental results are positive.

[0143] Table 12. Effects of the traditional Chinese medicine composition of the present invention on the sleep latency of sodium barbital ( n=10)

[0144]

[0145] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001

[0146] Experimental results: As shown in Table 12, compared with the control group, the sleep latency of mice in each dose group of sodium barbital decreased with increasing dose, and the sleep latency of each dose group was significantly different from that of the control group (P<0.001), indicating a positive experimental result.

[0147] The various aspects of this invention have been described above. However, it should be understood that, without departing from the spirit of this invention, those skilled in the art can make equivalent changes and modifications, which also fall within the scope of the appended claims.

Claims

1. A traditional Chinese medicine composition for treating insomnia, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 12-40 parts of stir-fried jujube seed, 9-27 parts of cypress seed, 11-28 parts of poria cocos, 11-23 parts of mulberry, 7-15 parts of dried plum, 3-8 parts of costus root, 7-15 parts of privet fruit, 5-14 parts of lycium bark, and 6-13 parts of fleeceflower stem.

2. The traditional Chinese medicine composition of claim 1, wherein, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of stir-fried jujube seed, 11 parts of cypress seed, 11 parts of poria cocos, 11 parts of mulberry, 7 parts of dried plum, 4 parts of costus root, 7 parts of privet fruit, 6 parts of lycium bark, and 6 parts of fleeceflower stem.

3. A traditional Chinese medicine compound preparation for treating insomnia, characterized in that, The traditional Chinese medicine compound preparations described herein are decoctions, granules, powders, capsules, tablets or oral liquids with the traditional Chinese medicine composition described in claim 1 or 2 as the active ingredient.

4. The traditional Chinese medicine compound preparation as described in claim 3, characterized in that, The traditional Chinese medicine compound preparation is a decoction.

5. The use of the traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of a medicament for treating insomnia.

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