A traditional Chinese medicine composition for treating insomnia with fatigue and application thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine composition, and particularly relates to a traditional Chinese medicine composition for treating insomnia with lassitude and application thereof.The traditional Chinese medicine composition provided by the present application comprises the following raw medicinal materials by weight or is prepared from the following raw medicinal materials by weight: fried gardenia 2-10 parts, radix sophorae tonkinensis 2-10 parts, lophatheri herba 2-10 parts, fried semen ziziphi spinosae 5-20 parts, citrus medica 2-10 parts, citrus aurantium 2-10 parts, longan arillus 3-17 parts and poria cocos 3-17 parts.The traditional Chinese medicine composition can effectively relieve the difficulty in falling asleep, easy wake-up, short sleep duration and lassitude caused by insomnia, and can be used for treating insomnia, significantly shortening sleep latency, prolonging sleep duration, and reducing lassitude and other symptoms, and has a good application prospect in improving and treating insomnia.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a traditional Chinese medicine composition for treating insomnia accompanied by fatigue and its application. Background Technology

[0002] Sleep is an essential physiological process for maintaining bodily health. With the accelerating pace of life and increasing work pressure, sleep disorders have become common, seriously affecting patients' physical and mental health. Insomnia is a sleep disorder characterized by frequent and persistent difficulty falling asleep and / or maintaining sleep. In recent years, the incidence of insomnia has been increasing year by year, and the severity of insomnia is positively correlated with age. Insomnia can also cause symptoms such as general weakness, anxiety, and depression, and is closely related to hypertension and cardiovascular and cerebrovascular diseases.

[0003] Currently, there is still considerable international debate regarding the long-term use of hypnotics for insomnia patients. Due to the risks of drug dependence and potential adverse consequences such as work-related errors or serious accidents after medication use, most scholars do not advocate for long-term use of hypnotics. Furthermore, the effectiveness of cognitive behavioral therapy, a first-line treatment for insomnia, is also quite limited. Therefore, insomnia is a significant public health problem, and actively exploring new and effective treatments to provide effective intervention methods for insomnia patients is of great importance to improving the overall health of the population. Developing a traditional Chinese medicine composition that can effectively treat difficulty falling asleep, frequent awakenings, and short sleep duration in insomnia patients is a pressing technical problem that needs to be solved. Summary of the Invention

[0004] This invention provides a traditional Chinese medicine composition for treating insomnia accompanied by fatigue and its application, which addresses the shortcomings of existing traditional Chinese medicine compositions in terms of therapeutic efficacy and achieves a more effective effect in improving insomnia.

[0005] Specifically, the present invention provides the following technical solutions.

[0006] In a first aspect, the present invention provides a traditional Chinese medicine composition comprising or prepared from the following raw materials in parts by weight: 2-10 parts of stir-fried gardenia, 2-10 parts of fermented soybean, 2-10 parts of light bamboo leaf, 5-20 parts of stir-fried jujube seed, 2-10 parts of Buddha's hand, 2-10 parts of citron, 3-17 parts of longan pulp, and 3-17 parts of poria cocos.

[0007] In the traditional Chinese medicine composition provided by this invention, Gardenia jasminoides effectively clears heat from the three jiaos (upper, middle, and lower burners) and relieves irritability and fever. Fermented soybean (Dancho sibiricum) effectively clears irritability and fever in the chest. Lophatherum gracile (Lophatherum gracile) is light and ascending, and can purge irritability and fever from the upper jiao. Ziziphus jujuba (Ziziphus jujuba seed) effectively nourishes the blood of the heart and liver and is a commonly used medicine for treating insomnia. Citrus medica (Buddha's hand) has a fragrant aroma and a mild nature, and is effective in soothing the liver, regulating qi, resolving phlegm, and relieving chest congestion. Citron (Citrus medica) regulates the qi of the upper jiao and strengthens the spleen in the middle jiao. Longan pulp benefits the spleen, nourishes the heart, and replenishes blood, and can calm the mind and promote restful sleep. Poria cocos promotes diuresis, eliminates dampness, strengthens the spleen, and calms the mind.

[0008] The rationale behind the herbal composition of this invention is as follows: The heart is the source of insomnia, and in the above-mentioned herbal composition of this invention, gardenia and fermented soybean are primarily used to purge the heart. Gardenia, a bitter herb, can clear heat and detoxify, relieve irritability and purge fire, and is effective in treating heat-related irritability; fermented soybean, a sour herb, can also relieve exterior symptoms, disperse heat, and relieve irritability. The two are used together as the principal herbs, one purging and the other astringing, specifically clearing heat stagnation in the chest and diaphragm, calming the mind and relieving irritability. Lophatherum gracile is good at clearing fire in the upper burner of the heart and lungs, assisting gardenia and fermented soybean in clearing the heart and relieving irritability; "Those who are overworked and overthinking will inevitably suffer from blood depletion and loss of spirit, thus causing insomnia." Ziziphus jujuba seed can replenish the blood of the heart and liver, giving the mind something to rely on and the liver spirit something to attach to; Citrus medica has a fragrant aroma and is good at soothing the liver and regulating qi. The two are used together to replenish without causing stagnation. The three are used together as assistant herbs to assist the principal herbs, nourishing the mind and calming the spirit. Prolonged illness inevitably leads to deficiency; therefore, it is essential to first strengthen the areas unaffected by pathogenic factors. This formula uses citron, longan pulp, and poria as adjuvant herbs, which not only invigorate qi and strengthen the spleen, nourish blood and calm the mind, but also embody the principle of "treating liver disease by first strengthening the spleen." The entire formula works synergistically to relieve depression and irritability, nourish the heart and calm the mind. It is effectively used to treat insomnia caused by liver stagnation transforming into fire, demonstrating good efficacy, safe use, and outstanding therapeutic results, which have been fully proven through clinical trials.

[0009] Preferably, the traditional Chinese medicine composition comprises or is prepared from the following raw materials in parts by weight: 3-9 parts of stir-fried gardenia, 3-9 parts of fermented soybean, 3-9 parts of light bamboo leaf, 6-18 parts of stir-fried jujube seed, 3-9 parts of Buddha's hand, 3-9 parts of citron, 5-15 parts of longan pulp, and 5-15 parts of poria cocos.

[0010] Preferably, the mass ratio of stir-fried gardenia to fermented soybean in the raw materials is 1:0.8~1.2. More preferably, it is 1:1. Controlling the mass ratio of stir-fried gardenia to fermented soybean within this range is more conducive to the synergistic effect of the two.

[0011] Preferably, in the raw materials, the total mass ratio of stir-fried gardenia and fermented soybean to the total mass ratio of bamboo leaf, stir-fried jujube seed, and Buddha's hand is 1:1.8~2.2. More preferably, it is 1:2. Controlling the mass ratio of the principal drug and the assistant drug within this range is more conducive to the assistant drug assisting the principal drug in exerting its effect.

[0012] As a preferred embodiment of the present invention, the traditional Chinese medicine composition comprises or is prepared from the following raw materials in parts by weight: 3 parts of stir-fried gardenia, 3 parts of fermented soybean, 3 parts of light bamboo leaf, 6 parts of stir-fried jujube seed, 3 parts of Buddha's hand, 3 parts of citron, 5 parts of longan pulp, and 5 parts of poria cocos.

[0013] The traditional Chinese medicine composition or its raw materials described in this invention may consist only of the above-mentioned raw materials, or may be further compounded with other raw materials that do not substantially change the compatibility relationship of this invention.

[0014] All of the above-mentioned active pharmaceutical ingredients can be obtained through commercial channels, and this invention does not impose any special restrictions on the source of the active pharmaceutical ingredients.

[0015] As a specific embodiment of the present invention, the traditional Chinese medicine composition may be composed of or made from the above-mentioned raw materials.

[0016] As a specific embodiment of the present invention, the traditional Chinese medicine composition is an extract (preferably an aqueous extract) obtained by extracting the above-mentioned raw materials.

[0017] The traditional Chinese medicine composition of the present invention has a significant effect on improving insomnia, effectively relieving symptoms such as difficulty falling asleep, frequent awakenings, short sleep duration, and fatigue, shortening sleep latency, increasing sleep duration, and alleviating weight problems caused by insomnia.

[0018] Secondly, the present invention provides a traditional Chinese medicine preparation comprising the traditional Chinese medicine composition described in the first aspect above or prepared from raw materials comprising the traditional Chinese medicine composition described in the first aspect above.

[0019] Preferably, the traditional Chinese medicine preparation is made solely from the above-mentioned traditional Chinese medicine composition, or from the above-mentioned traditional Chinese medicine composition and a pharmaceutically usable carrier or excipient.

[0020] The carrier or excipients include fillers, disintegrants, binders, lubricants / flow aids, flavoring agents / fragrances, wetting agents / solvents, etc.

[0021] Furthermore, the traditional Chinese medicine preparations include granules, tablets, pills, capsules, powders, mixtures, or oral liquids.

[0022] When the traditional Chinese medicine composition of the present invention is prepared into different dosage forms, one or more carriers / excipients permitted in the pharmaceutical field can be selected and combined according to actual needs. The amount of each excipient can be routinely adjusted according to the formulation process, dosage form characteristics, and clinical needs, all of which fall within the protection scope of the present invention. For example, when preparing granules, excipients such as fillers, binders, flavoring agents, and wetting agents can be selected; when preparing oral liquids, excipients such as solvents, flavoring agents, and preservatives can be selected; when preparing capsules, excipients such as fillers and lubricants can be selected.

[0023] Thirdly, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition or the traditional Chinese medicine preparation, the method comprising: extracting the raw material drug using an extractant.

[0024] Preferably, the extractant is water.

[0025] More preferably, the method includes: mixing all the raw materials and then extracting them with water by heating; or further concentrating; or further drying.

[0026] The heating extraction is preferably performed by decoction. After heating extraction, the extract can be concentrated, and after concentration, it can be dried to prepare a medicinal powder.

[0027] In some embodiments of the present invention, the method includes: the heating extraction includes: mixing all raw materials and then mixing with 6 to 12 times the amount of water, soaking for 20 to 80 minutes, first boiling over high heat and then simmering over low heat for 25 to 45 minutes, filtering to obtain the first decoction; mixing the residue with 4 to 10 times the amount of water, simmering over low heat for 15 to 35 minutes, filtering to obtain the second decoction; combining the two decoctions, filtering and concentrating.

[0028] Fourthly, the present invention provides the use of the above-described traditional Chinese medicine composition or the traditional Chinese medicine preparation in the preparation of a medicament for treating or preventing insomnia or insomnia accompanied by fatigue.

[0029] Preferably, the insomnia or insomnia with fatigue is characterized by difficulty falling asleep, frequent awakenings, short sleep duration, or one or more of the following symptoms: fatigue.

[0030] Fifthly, the present invention provides a method for improving or treating insomnia, the method comprising: administering the above-described traditional Chinese medicine composition or preparation to a test subject.

[0031] The preferred method of administration is oral administration.

[0032] The beneficial effects of the present invention include at least the following: The traditional Chinese medicine composition provided by the present invention combines stir-fried gardenia, fermented soybean, bamboo leaves, stir-fried jujube seed, citron, citron, longan pulp and poria, which can effectively relieve insomnia-induced difficulty falling asleep, easy awakening, short sleep duration, and accompanying fatigue symptoms. It can be used to treat insomnia, significantly shorten sleep latency, prolong sleep duration, and reduce fatigue symptoms, and has good application prospects in improving and treating insomnia. Attached Figure Description

[0033] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0034] Figure 1 In the experimental example of this invention, the effect of the traditional Chinese medicine composition on the percentage of hours in the 24-hour sleep-wake cycle (WAKE (A)) and sleep (B) of mice was investigated.

[0035] Figure 2In the experimental example of this invention, the effect of the traditional Chinese medicine composition on the time occupied by WAKE (A), NREM (B) and REM (C) in the 24-hour sleep-wake cycle of mice was investigated.

[0036] Figure 3 The effects of the traditional Chinese medicine composition on sleep-wake cycles in mice, as described in the experimental examples of this invention, include the characteristics of electroencephalography (EEG) and electromyography (EMG) (A), as well as typical examples of EEG spectra, EMG and corresponding hypnotic graphs (B).

[0037] Figure 4 This is an experimental example of the present invention, showing the effect of the traditional Chinese medicine composition on the body weight of mice.

[0038] Figure 5 In the experimental example of this invention, the effects of the traditional Chinese medicine composition on the total distance (A), average speed (B), total distance of the surrounding area (C), and number of times the mouse enters the central area (D) in an open field are shown.

[0039] Figure 6 This is an experimental example of the present invention, showing the effect of the traditional Chinese medicine composition on the proportion of time mice spent moving at different speeds in an open field.

[0040] Figure 7 In the experimental example of this invention, the effect of the traditional Chinese medicine composition on the number of electric shocks received by mice in the treadmill test was shown.

[0041] Figure 8 In the experimental example of this invention, the effects of the traditional Chinese medicine composition on sleep latency (A) and sleep duration (B) in the sodium pentobarbital righting test of mice are shown. Detailed Implementation

[0042] The English abbreviations involved in this invention are shown in Table 1.

[0043] Table 1: English Abbreviations

[0044] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0045] Unless otherwise specified, the techniques or conditions described in the following examples shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0046] Example 1 This embodiment provides a traditional Chinese medicine composition, which is composed of the following raw materials: 3g of stir-fried gardenia, 3g of fermented soybean, 3g of bamboo leaves, 6g of stir-fried jujube seed, 3g of Buddha's hand, 3g of citron, 5g of longan pulp, and 5g of poria cocos.

[0047] This embodiment also provides a traditional Chinese medicine, made from the traditional Chinese medicine composition of this embodiment, and the preparation method is as follows: (1) Weigh each raw material according to the above proportions; (2) Mix the raw materials weighed in step (1), add 8 times the amount of water (about 250 mL) and soak for 30 min. After boiling over high heat, simmer over low heat for 30 min. Filter to obtain the first decoction. Add 6 times the amount of water (about 200 mL) to the dregs and simmer over low heat for 20 min. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate to 400 mL to obtain the final product.

[0048] Example 2 This embodiment provides a traditional Chinese medicine composition, which is composed of the following raw materials: 9g of stir-fried gardenia, 9g of fermented soybean, 9g of bamboo leaves, 18g of stir-fried jujube seed, 9g of Buddha's hand, 9g of citron, 15g of longan pulp, and 15g of poria cocos.

[0049] This embodiment also provides a traditional Chinese medicine, made from the traditional Chinese medicine composition of this embodiment, and the preparation method is as follows: (1) Weigh each raw material according to the above proportions; (2) Mix the raw materials weighed in step (1), add 10 times the amount of water (about 300 mL) and soak for 60 min. After boiling over high heat, simmer over low heat for 40 min. Filter to obtain the first decoction. Add 8 times the amount of water (about 250 mL) to the dregs and simmer over low heat for 30 min. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate to 400 mL to obtain the final product.

[0050] Comparative Example 1 This comparative example provides a traditional Chinese medicine composition, which is composed of the following raw materials: 3g of stir-fried gardenia, 3g of fermented soybean, 3g of bamboo leaf, 3g of citron, 12g of longan pulp, and 5g of poria.

[0051] This comparative example also provides a traditional Chinese medicine, which is made from the traditional Chinese medicine composition of this comparative example, and the preparation method is the same as in Example 1.

[0052] Comparative Example 2 This comparative example provides a traditional Chinese medicine composition, which is composed of the following raw materials: 6g of stir-fried gardenia, 3g of light bamboo leaves, 6g of stir-fried jujube seed, 3g of Buddha's hand, 3g of citron, 5g of longan pulp, and 5g of poria cocos.

[0053] This comparative example also provides a traditional Chinese medicine, which is made from the traditional Chinese medicine composition of this comparative example, and the preparation method is the same as in Example 1.

[0054] Comparative Example 3 This comparative example provides a traditional Chinese medicine composition, which is composed of the following raw materials: 6g of fermented soybean, 3g of bamboo leaves, 6g of stir-fried jujube seed, 3g of Buddha's hand, 3g of citron, 5g of longan pulp, and 5g of Poria cocos.

[0055] This comparative example also provides a traditional Chinese medicine, which is made from the traditional Chinese medicine composition of this comparative example, and the preparation method is the same as in Example 1.

[0056] Animal experiments on the treatment of insomnia with traditional Chinese medicine compositions. 1. Materials 1.1 Medicines and Reagents Test drug: Traditional Chinese medicine (i.e., concentrated extract after decoction) prepared in each example and comparative example.

[0057] Positive control drug: Eszopiclone.

[0058] 1.2 Animals Twenty-four SPF-grade, 7-8 week old male C57BL / 6N mice (weighing 20-25g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were selected for the experiment. All mice were housed under identical conditions: caged, with 12 hours of light and 12 hours of darkness daily (7:00-19:00), an ambient temperature of 22±2℃, and a relative humidity of 50-60%. Mice were fed standard feed and clean drinking water, and had free access to food and water. A 7-day acclimatization period was provided before the experiment to allow the mice to fully adapt to the conditions. All animal experiments complied with and strictly adhered to the relevant guidelines of the China Animal Protection Association.

[0059] 2. Experimental Methods 2.1 Modeling, grouping, and drug administration Except for the pentobarbital sodium righting test, C57BL / 6N mice were randomly divided into a blank control group (Control group), a model group (Model group), the herbal medicine group of Example 1 (Herb group), and a positive control group (Eszopiclone group) according to the Excel random number table method.

[0060] Mice in the Model, Herb, and Eszopiclone groups were intraperitoneally injected with para-chlorophenylalanine (PCPA, 350 mg / kg) once daily for 3 days. The blank control group received the same dose of the solvent for 3 consecutive days. When the animals exhibited loss of circadian rhythm, excessive daytime activity, weight loss, irritability, and increased aggression, showing significant differences from the control group, it indicated that the model was successfully established.

[0061] The dosages for the Herb and Eszopiclone groups were calculated based on human-to-mouse equivalent doses. Using the dosage for a 60kg adult, and based on the equivalent body surface area conversion in *Methodology of Traditional Chinese Medicine Pharmacology Research*, the equivalent dose coefficient for mice compared to humans was 9.1, resulting in a dosage of 4.7g crude drug / kg, administered via gavage at a volume of 10 ml / kg, with a concentration of 0.47 g / mL. The positive control dose for clinical patients was 1 mg / day (based on a 60kg body weight). Based on the human-to-mouse body surface area conversion coefficient of 9.1, the equivalent dose for mice was set at 0.15mg / kg, administered via gavage at a volume of 10 ml / kg, with a concentration of 0.015 g / L. The blank control group and model group received an equal volume of 0.9% saline. All mice in the above groups were administered the drug via gavage, starting after model establishment, once daily for 7 consecutive days.

[0062] 2.2 Electroencephalogram (EEG) detection in mice 2.2.1 Electrode implantation surgery After isoflurane gas anesthesia, the mouse's hind legs were clamped with forceps to check for the knee-jerk reflex. Once the reflex completely disappeared, electrode implantation surgery was performed. First, the mouse was fixed on the experimental table, and hair was trimmed 2 mm to the left and right of the sagittal suture to expose the skin, which was then disinfected with 75% alcohol. After disinfection, an incision was made along the sagittal suture 1.5 cm anterior and posterior to the Bregma origin with a scalpel to expose the skull. The scalp on both sides of the sagittal suture was grasped with a leather clip to expose the visual field. The periosteum in the exposed area was removed with hydrogen peroxide to prevent electrode dislodgement due to periosteal necrosis. Holes were drilled in the skull using a 0.8 mm diameter drill bit, 3 mm posterior to the Bregma origin and 3 mm to the left and right of the sagittal suture, as the implantation points for the positive and negative electrodes. Holes were drilled 3 mm anterior to the Bregma origin and 3 mm to the left or right of the Bregma origin as reference electrode implantation points. The prepared electrodes were inserted into both sides of the neck and fixed with 502 glue. After fixing for 1 minute to allow the glue to solidify, apply dental cement evenly to completely cover the wound and electrodes. After the surgery, move the mouse to a heated blanket to regain consciousness, then transfer it to a cage and place it in a light:dark (12h:12h) environment for 7-14 days to allow it to acclimatize before testing.

[0063] 2.2.2 Electroencephalogram (EEG) detection The male and female terminals of the electrodes implanted in the mouse's head were connected, with the female wire connected to the lower end of a 6-wire universal wheel. The upper end of the universal wheel was connected to a Labchart signal amplifier and a Labchart signal acquisition unit. The mice were allowed free movement, eating, and drinking, and the electrical signals of their cerebral cortex cell populations were recorded. The signals were processed by the Labchart system software and analyzed using Lunion software. The mice were always kept in a light:dark (12h:12h) environment.

[0064] 2.3 Behavioral testing of mice 2.3.1 Open Field Experiment Behavioral analysis software was used to analyze the total distance traveled, the distance to the central grid, and the number of modifications made by mice in each group within 5 minutes. Mice were kept quiet during the testing period, and the open field chamber was cleaned promptly. The open field consisted of square chambers (50×50cm), with the central square area (25×25cm) defined as the central zone. Before each test, the mice were placed in an environment with dim red light for at least 30 minutes to acclimatize. During the test, each mouse was placed in the center of the open field and allowed to move freely for 10 minutes; their activity was recorded by a video tracking system on top. The time spent in the central zone and the total distance traveled were analyzed. After each experiment, the instrument was cleaned with 75% ethanol to remove the mice's odor and excrement.

[0065] 2.3.2 Treadmill Experiment Mice were placed on a track with a speed of 12, and the number of electric shocks received by each mouse within 3 minutes was recorded. After the test, the track was wiped with 75% alcohol, and the next mouse treadmill test was conducted only after the odor dissipated. The entire experimental process was conducted in a quiet environment.

[0066] 2.3.3 Mouse pentobarbital-induced suprathreshold sleep synergistic experiment On day 7, after EEG testing, each mouse was intraperitoneally injected with 45 mg / kg sodium pentobarbital. Then, the mice were placed on a mat with their tails lifted. Sleep latency and duration were recorded. The disappearance of the righting reflex was defined as sleep, and its recovery as wakefulness. If recovery of the righting reflex was uncertain, the mice were immediately repositioned back to their supine position after the first righting. If they automatically rolled over within 1 minute, the previous time was considered the recovery time; otherwise, the second rollover time was used. Sleep patterns were observed, with sleep defined as more than 1 minute after the righting reflex disappeared. Sleep latency and duration were recorded for each group.

[0067] 3. Results 3.1 Effects of Traditional Chinese Medicine Composition on Sleep in PCPA-Induced Insomnia Mice 3.1.1 Effects of Traditional Chinese Medicine Composition on Cumulative Sleep Amount in PCPA-Induced Insomnia Mice at Different Time Phases The effects of the traditional Chinese medicine composition on the percentage of hours in the 24-hour sleep-wake cycle of mice are shown in the following results. Figure 1 Where n=5, At baseline, there was no statistically significant difference in the percentage of sleep-wake cycles among the four groups. p>0.05. Ten days later, a comparison of the percentages of WAKE and SLEEP within 24 hours between the Model group and the Control group showed that both showed... p <0.05; Both the Model group and the Herb group showed... p <0.01; Both the Model group and the Eszopiclone group showed... p <0.05.

[0068] The effects of the traditional Chinese medicine composition on the time spent in WAKE, NREM, and REM sleep cycles in mice are shown in the figure. Figure 2 Where L represents light; D represents darkness; n=5, Comparing the time spent on WAKE between the Model and Control groups within 24 hours. p <0.05; Comparison between the Model group and the Herb group, p <0.01; Compared with the Eszopiclone group, the Model group, p <0.05. Comparison of the time spent in the dark period (WAKE) between the Model and Control groups within 24 hours. p <0.05; Comparison between the Model group and the Herb group, p <0.01; Compared with the Eszopiclone group, the Model group, p <0.05. Comparison of REM time during the dark period in the Model group and the Herb group within 24 hours. p <0.05; Compared with the Eszopiclone group, Herb group, p <0.01.

[0069] Mice were acclimatized for 7 days before electrode implantation and allowed 7 days of recovery. On day 14, mice were randomly divided into Control, Model, Herb, and Eszopiclone groups. The Control group received an equal dose of saline for 3 consecutive days, while the other three groups received intraperitoneal injections of PCPA 350 mg / kg once daily for 3 consecutive days. Treatment began on day 17 and lasted for one week. Mice received saline, the positive control drug, or the drug from Example 1 at 7:00 AM. Electroencephalography (EEG) and electromyography (EMG) were performed before modeling, 3 days after modeling, and 7 days after drug administration. Mice were allowed 1 day to acclimatize to the recording cable before each test.

[0070] The effects of the traditional Chinese medicine composition on sleep-wake cycles in mice are shown in the following results. Figure 3The characteristics of EEG and EMG in different sleep states are as follows: during wakefulness, EEG is high-frequency and low-amplitude, while EMG shows strong discharge; during NREM sleep, EEG is low-frequency and high-amplitude, while EMG is relatively quiet; during REM sleep, EEG is similar to that during wakefulness, both being high-frequency and low-amplitude, but EMG remains very quiet, consistent with NREM sleep. Figure 3 (A in the middle). Figure 3 Figure B shows typical examples of electroencephalograms, electromyograms, and corresponding hypnotic graphs of mice in the Control, Model, Herb, and Eszopiclone groups 7 days after treatment.

[0071] By statistically analyzing the duration of wakefulness (WAKE), non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, the baseline status of mice in each group before modeling was calculated, and the cumulative amount of each sleep phase after 7 days of drug administration was obtained, thus yielding experimental results. Figure 1 , Figure 2 ).

[0072] Seven days after treatment, analysis of cumulative WAKE levels in mice showed that, compared with the Control group, the 24-hour cumulative WAKE levels in the Model group were significantly higher. p <0.05); compared with the Model group, the Herb group mice at 24 hours ( p <0.01) and the Dark Ages ( p <0.001) WAKE accumulation was significantly reduced in mice in the Eszopiclone group after 24 hours ( p <0.05) and the Dark Ages ( p <0.01) WAKE accumulation significantly decreased ( Figure 2 (A in the middle).

[0073] Seven days after treatment, analysis of NREM sleep accumulation in mice showed that, compared with the control group, the NREM sleep accumulation during the dark period was significantly reduced in the model group mice. p <0.05; Compared with the Model group, the Eszopiclone group mice had significantly increased NREM sleep accumulation over 24 hours, during both dark and light periods ( p <0.05; Compared with the Model group, the Herb group increased the cumulative NREM sleep volume of mice during 24 hours, in both dark and light periods, but the difference was not statistically significant. p >0.05)( Figure 2 (B in the middle).

[0074] Seven days after treatment, analysis of cumulative REM sleep in mice showed that, compared with the Model group, mice in the Herb group had significantly lower REM sleep volume over 24 hours. p <0.05), photoperiod ( p<0.05) and the Dark Ages ( p <0.05) REM sleep accumulation was significantly increased; compared with the control group, the Herb group mice had significantly increased REM sleep accumulation during the dark period ( p <0.05; Compared with the Eszopiclone group, the Herb group mice had a significantly higher cumulative REM sleep during the dark period ( p <0.01)( Figure 2 (C in the middle).

[0075] The above results show that after 7 days of administration, the traditional Chinese medicine composition in Example 1 can effectively reduce the increase of WAKE accumulation in PCPA-induced insomnia mice during the 24-hour and dark periods, and increase REM accumulation during the dark period. Its effect on treating insomnia alone is comparable to that of the positive control drug Eszopiclone.

[0076] 3.2 Effects of Traditional Chinese Medicine Composition on Behavioral Characteristics of PCPA-Induced Insomnia in Mice 3.2.1 Effects of Traditional Chinese Medicine Composition on Body Weight in PCPA-Induced Insomnia Mice The effect of traditional Chinese medicine composition on mouse body weight is shown in the figure. Figure 4 Where n=6, A PCPA-induced insomnia mouse model was established. After modeling, mice in the control group had smooth fur, good mental state, normal appetite, and normal diurnal rhythm. After PCPA administration, mice developed dull yellow fur, increased diurnal activity, abnormal restlessness upon exposure to sound or light stimuli, and decreased appetite. Body weight changes in the four groups were recorded continuously for 10 days starting from day 1 of modeling. On day 1 of modeling, there were no statistically significant differences in body weight among the four groups. p >0.05); After modeling was completed, on the first day of drug administration, the body weight of mice in the three groups modeled with PCPA was significantly lighter than that of the control group ( p <0.05); On day 7 after drug administration, the Herb group mice were significantly lighter than the Control group mice ( p <0.05); On days 1 and 5 after administration, mice in the Herb group had a lighter body weight than mice in the Eszopiclone group (# p <0.05); On days 3, 4, and 5 after administration, the Herb group mice weighed less than the Model group mice (※ p <0.05). Monitoring mouse weight over 10 days suggests that this traditional Chinese medicine composition may reduce diurnal activity and feeding frequency in mice by enhancing sedation and tranquilization, thereby affecting the weight recovery process. No obvious toxic reactions were observed.

[0077] 3.2.2 Open Field Experiment The effects of the traditional Chinese medicine composition on the total distance (A), average speed (B), total distance in the peripheral zone (C), and number of times the mouse entered the central zone (D) in an open field are shown in the figure. Figure 5 The effect on the proportion of time mice spent moving at different speeds in an open field is shown in [reference needed]. Figure 6 Where n=6, the total distance traveled by the four groups of mice within 5 minutes in the open field experiment ( p >0.05), average speed ( p >0.05), surrounding area movement distance ( p >0.05), Number of times entering the central area ( p >0.05) and the percentage of time spent moving at different speeds ( p >0.05) No statistically significant difference was observed. The above results indicate that the traditional Chinese medicine compound had no significant side effects on the spontaneous movement ability and emotional state of mice during the 1-week treatment period.

[0078] 3.2.3 Treadmill Test The effect of the traditional Chinese medicine composition on the number of electric shocks received by mice on the treadmill is shown in the figure. Figure 7 Where n=6, The Herb group mice received significantly fewer electric shocks than the Control group mice. p <0.05); the Model group mice received significantly more electric shocks than the Herb group mice ( p <0.05) and Eszopiclone group mice ( p <0.05). Treadmill test results showed that the PCPA modeling agent reduced the exercise endurance of mice, while the traditional Chinese medicine composition and Eszopiclone both improved the exercise endurance of mice after modeling, with the traditional Chinese medicine composition showing a more significant improvement.

[0079] 3.2.4 Sodium pentobarbital righting test Experimental mice were randomly divided into 8 groups: blank control group (Control group), model group (Model group), positive control group (Eszopiclone group), Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group, with 6 mice in each group. A PCPA-induced insomnia mouse model was established. After the last gavage administration, mice in each group were intraperitoneally injected with a suprathreshold dose of sodium pentobarbital. Sleep latency and sleep duration were recorded. The results are shown below. Figure 8 And Table 2.

[0080] Table 2 Results of the pentobarbital-induced suprathreshold sleep synergistic experiment in each group of mice ( )

[0081] Note: # P <0.05, ##P <0.01, ### P <0.001, compared with the Control group; Compare with the Model group; ※※ P <0.01, ※※※ P <0.001, compared with Example 1 group; ▲▲ P <0.01, compared with Example 2 group.

[0082] Sleep latency results as follows Figure 8 As shown in A and Table 2. Compared with the Control group, the sleep latency of mice in the Model group was significantly prolonged ( ## P <0.01 indicates successful replication of the PCPA insomnia model. Compared with the Model group, the sleep latency of mice in the Eszopiclone group, Example 1 group, and Example 2 group was significantly shortened ( or The shortening was particularly significant in groups 1 and 2 of the example; while the sleep latency of mice in comparative groups 1, 2, and 3 showed a certain decreasing trend compared to the model group, the difference was not statistically significant. P >0.05).

[0083] Sleep duration results as follows Figure 8 As shown in B and Table 2. Compared with the Control group, the sleep duration of mice in the Model group was significantly shortened ( ### P <0.001). Compared with the Model group, the sleep duration of mice in the Eszopiclone group, Example 1 group, and Example 2 group was significantly prolonged ( Although the sleep duration of mice in Comparative Group 1, Comparative Group 2, and Comparative Group 3 was slightly longer than that in the Model group, the difference was not statistically significant. P >0.05). Further inter-group comparisons showed that the sleep duration of mice in Comparative Example 1, Comparative Example 2, and Comparative Example 3 was significantly lower than that in Example 1 ( ※※ P <0.01, ※※※ P <0.001), and the sleep duration of mice in Comparative Example 1 was also significantly lower than that in Example 2 ( ▲▲ P <0.01).

[0084] The above results indicate that the traditional Chinese medicine composition of the present invention (Examples 1 and 2) can significantly reverse the prolonged sleep latency and shortened sleep duration induced by PCPA in a mouse insomnia model, and its effect is significantly better than that of the comparative groups. Although the comparative groups contain some of the same medicinal ingredients, they failed to produce a synergistic effect comparable to that of the example groups, suggesting that the specific formulation and ratio of the present invention have significant compatibility advantages in improving sleep disorders and enhancing the synergistic hypnotic effect of sodium pentobarbital.

[0085] 4. Conclusion The traditional Chinese medicine composition provided by this invention (composed of stir-fried gardenia, fermented soybean, bamboo leaves, stir-fried jujube seed, citron, citron, longan pulp, and poria cocos in a specific weight ratio) has a significant ameliorative effect on PCPA-induced insomnia mouse model, and exhibits clear advantages in formulation compatibility and good safety.

[0086] Regarding the improvement of sleep structure, this traditional Chinese medicine composition effectively reduced the cumulative amount of wakefulness (WAKE) in insomnia mice over 24 hours and during the dark period, and significantly increased the cumulative amount of rapid eye movement (REM) sleep during the dark period. In the sodium pentobarbital suprathreshold sleep synergistic experiment, it significantly shortened sleep latency and prolonged sleep duration. These results suggest that this composition can improve sleep disorders through multiple targets and pathways by regulating the sleep-wake cycle and enhancing the synergistic effect of central sedative-hypnotic drugs.

[0087] Regarding the formulation and inventiveness, compared with the comparative groups lacking roasted jujube seed and fermented soybean or with altered proportions of the principal and assistant herbs, the specific formulation and proportions of the present invention (Examples 1 and 2) exhibit a significant synergistic effect in reversing PCPA-induced prolongation of sleep latency and shortening of sleep duration. None of the comparative groups produced pharmacological effects comparable to those of the Example groups. These results suggest that roasted jujube seed, fermented soybean, and other herbs, along with their specific proportions with gardenia and fermented soybean, are indispensable in this formula, collectively constituting the core technical solution for treating insomnia. This demonstrates the rigorous and unpredictable nature of the formulation of the present invention.

[0088] Regarding behavioral characteristics and safety evaluation, the traditional Chinese medicine composition did not significantly affect the spontaneous movement ability, exploratory behavior, or emotional state of mice in the open field experiment, indicating that its sedative-hypnotic effect is not accompanied by excessive central inhibition or motor dysfunction. In the treadmill experiment, it significantly improved the exercise endurance of insomniac mice, and the effect was superior to the positive control drug eszopiclone, suggesting that the composition can alleviate the accompanying physical fatigue symptoms while improving sleep, which is consistent with the treatment positioning of "insomnia with fatigue". In addition, the effect of the composition on the weight recovery process of insomniac mice may be related to enhancing the sedative and calming effect, reducing abnormal activity and feeding frequency, and no obvious toxic reactions were observed.

[0089] In summary, the traditional Chinese medicine composition and its preparations of the present invention can be effectively used to treat or prevent insomnia, especially suitable for insomnia patients with fatigue and decreased exercise tolerance. Its formulation is concise, its compatibility is rigorous, its efficacy is definite, and its safety is good, showing significant clinical application prospects and development value in improving sleep disorders and accompanying physical symptoms.

[0090] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, The traditional Chinese medicine composition comprises or is prepared from the following raw materials in parts by weight: 2-10 parts of stir-fried gardenia, 2-10 parts of fermented soybean, 2-10 parts of light bamboo leaf, 5-20 parts of stir-fried jujube seed, 2-10 parts of Buddha's hand, 2-10 parts of citron, 3-17 parts of longan pulp, and 3-17 parts of poria cocos.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition comprises or is prepared from the following raw materials in parts by weight: 3-9 parts of stir-fried gardenia, 3-9 parts of fermented soybean, 3-9 parts of light bamboo leaf, 6-18 parts of stir-fried jujube seed, 3-9 parts of Buddha's hand, 3-9 parts of citron, 5-15 parts of longan pulp, and 5-15 parts of poria cocos.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The traditional Chinese medicine composition comprises or is prepared from the following raw materials in parts by weight: 3 parts of stir-fried gardenia, 3 parts of fermented soybean, 3 parts of light bamboo leaf, 6 parts of stir-fried jujube seed, 3 parts of Buddha's hand, 3 parts of citron, 5 parts of longan pulp, and 5 parts of poria cocos.

4. The traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The traditional Chinese medicine composition is an extract obtained by extracting the raw material; Preferably, the extract is an aqueous extract.

5. A traditional Chinese medicine preparation, characterized in that, The traditional Chinese medicine preparation comprises the traditional Chinese medicine composition according to any one of claims 1 to 4 or is prepared from raw materials comprising the traditional Chinese medicine composition according to any one of claims 1 to 4.

6. The traditional Chinese medicine preparation according to claim 5, characterized in that, The traditional Chinese medicine preparations include granules, tablets, pills, capsules, powders, mixtures, or oral liquids.

7. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 4 or the traditional Chinese medicine preparation according to claim 5 or 6, characterized in that, The method includes: extracting the active pharmaceutical ingredient using an extractant.

8. The preparation method according to claim 7, characterized in that, The extractant is water.

9. The preparation method according to claim 7 or 8, characterized in that, The method includes: mixing all raw materials and then extracting them with water by heating; or further concentrating; or further drying. Preferably, the method includes: mixing all the raw materials and then mixing them with 6 to 12 times the amount of water, soaking for 20 to 80 minutes, bringing to a boil over high heat and then simmering over low heat for 25 to 45 minutes, filtering to obtain the first decoction; mixing the dregs with 4 to 10 times the amount of water, simmering over low heat for 15 to 35 minutes, filtering to obtain the second decoction; combining the two decoctions, filtering, and concentrating.

10. The use of the traditional Chinese medicine composition according to any one of claims 1 to 4 or the traditional Chinese medicine preparation according to claim 5 or 6 in the preparation of a medicament for treating or preventing insomnia or insomnia accompanied by fatigue.

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