Composition with sleep improving function as well as preparation method and application thereof

Abstract

The invention discloses a composition with a sleep improving function as well as a preparation method and application thereof, and the composition is prepared from the following raw materials in parts by weight: 50-100 parts of acanthopanax root, 30-50 parts of lotus seed, 50-100 parts of spina date seed, 30 parts of lily, 30 parts of longan, 30-50 parts of poria cocos, 30 parts of radix ophiopogonis, 10-30 parts of rehmannia, 10-30 parts of gastrodia elata, 2 parts of glutamic acid, 0.1 part of vitamin B, 0.1 part of vitamin B6 and 0.1 part of gamma-aminobutyric acid. The traditional single target spot limitation is broken through, a synergistic effect system of tonifying the spleen and soothing the nerves-neurotransmitter regulation and control-intestinal brain axis regulation is formed, a buffer solution of pH simulation biological fluid is adopted as a non-organic extraction medium in the process, the ultrasonic cavitation effect and the plasma activation effect are combined, the temperature is controlled in the whole process, and the preparation method is simple and easy to implement. The problems of vortex, uneven extraction, dead volume, solvent residue, active ingredient damage and the like in traditional extraction are fundamentally solved, the composition capable of effectively improving the sleep quality is obtained, and animal model and crowd experiments prove that the composition can effectively improve the sleep quality and achieve a good sleep aiding effect.

Description

Technical Field

[0001] This invention relates to the field of composition technology for improving sleep, specifically to a composition for improving sleep, its preparation method, and its application. Background Technology

[0002] With the accelerating pace of modern life and the continuous increase in work pressure, sleep disorders have become a common health problem worldwide. Statistics show that the prevalence of sleep disorders among adults in my country is as high as 43.4%, with difficulty falling asleep, difficulty maintaining sleep, and decreased sleep quality being the main manifestations, seriously affecting an individual's cognitive function, immune system, and mental health.

[0003] Currently, sleep improvement products on the market are mainly divided into three categories: chemical sedative-hypnotic products, traditional combinations, and ordinary supplements. However, all of them have core problems that urgently need to be solved, making it difficult to meet people's needs for "safe, efficient, and comprehensive" sleep improvement. Chemical sedative-hypnotic products: significant safety concerns and dependence risks. Clinically commonly used chemicals such as benzodiazepines and zopiclone, while able to rapidly shorten sleep latency by directly inhibiting the central nervous system, have significant limitations with long-term use: First, they easily induce tolerance, requiring continuously increasing doses to maintain the original sleep-inducing effect, forming a "dose-dependent cycle"; second, they are highly addictive, and withdrawal reactions such as rebound insomnia, anxiety, and tremors are common after discontinuation, making them particularly unsuitable for long-term intervention in people with chronic insomnia; third, they have significant residual side effects, easily causing a "hangover effect" during the day (such as dizziness, inattention, and slowed reaction time), and some people may also experience neuropsychiatric adverse reactions such as memory loss and irritability, making them extremely unsuitable for people who need to maintain normal work and study during the day (such as office workers and students).

[0004] Traditional Combinations: Insufficient Targeted Formulation and Technological Defects Limit Effectiveness. Existing compositions based on classic formulas such as Gui Pi Tang and Jiao Tai Wan from *Shang Han Lun* and *Qian Jin Fang* generally suffer from two major problems: 1. Strong limitation of formulation and single syndrome coverage: Most formulas focus on a single insomnia syndrome. For example, compositions with jujube seed as the core are only suitable for "heart and liver yin and blood deficiency type" insomnia, and have limited regulatory effects on complex syndromes such as "liver stagnation and spleen deficiency type" (manifested as insomnia accompanied by abdominal distension and fatigue) and "yin deficiency and internal heat type" (manifested as insomnia accompanied by dry mouth and hot palms and soles). On the other hand, tonifying formulas with ginseng and astragalus as the core are too rich and greasy, which can easily hinder the spleen and stomach's digestive function, leading to secondary problems such as abdominal distension and loss of appetite in some people after taking them, and failing to meet the dual needs of "aiding sleep" and "protecting the spleen and stomach". 2. Outdated extraction technology and low utilization rate of active ingredients: Traditional water decoction method has a dissolution rate of less than 30% for fat-soluble active ingredients (such as jujube seed saponins, eleutherococcus senticosus saponins, and other core sleep-aiding ingredients), and the high temperature of 100℃ can easily destroy heat-sensitive ingredients (such as polysaccharides and vitamins); if the parameters of the ethanol precipitation method are not properly controlled (such as ethanol concentration and precipitation temperature), it is easy for active ingredients such as alkaloids and flavonoids to be lost along with impurities such as starch and protein, and the residual ethanol may cause gastrointestinal irritation; in addition, traditional processes generally have problems such as "uneven vortex extraction", "dead volume of equipment leading to component retention" and "oxidation and destruction of active ingredients", resulting in significant differences in the effects between batches of products and insufficient stability in clinical application.

[0005] Common supplements: Their mechanisms of action are singular, lacking multi-dimensional synergistic regulation. Most sleep-improving supplements on the market (such as GABA-based or melatonin-based products) focus on a single target: either alleviating nerve excitation by supplementing inhibitory neurotransmitters (such as GABA), or improving sleep onset rhythm by regulating circadian rhythms (such as melatonin), failing to link the overall balance of the central nervous system, gut microbiota, and metabolism. For example, while some products can shorten sleep onset time in the short term, they cannot improve sleep depth (such as the proportion of slow-wave sleep) or reduce the number of nighttime awakenings; some products can regulate neurotransmitters but ignore the indirect impact of gut microbiota imbalance on sleep—studies show that people with sleep disorders commonly have gut microbiota dysbiosis (such as excessive Lactobacillus abundance and insufficient Alistipes abundance), and disordered microbiota can release inflammatory factors through the "gut-brain axis," exacerbating central anxiety and further worsening insomnia. This results in the one-sided improvement effect of existing supplements, failing to address the root cause of sleep quality problems.

[0006] Safety assessments are insufficient, and systematic validation data is lacking. Whether traditional compositions or common supplements, most have not undergone standardized toxicological and human clinical trials: First, acute toxicity data are lacking, and safety is judged solely based on experience, failing to rule out potential effects on liver and kidney function at high doses; second, long-term safety has not been validated. While some products have short-term animal study data, there is a lack of human safety monitoring (such as changes in blood routine tests and liver and kidney function indicators) for continuous use for more than one month.

[0007] In summary, existing sleep improvement products have significant shortcomings in terms of "safety (non-addictive, no side effects)," "comprehensive efficacy (multiple certifications, multiple targets)," "advanced technology (high dissolution, no residue)," and "data integrity (toxicology and human validation)." There is an urgent need for a sleep improvement product based on natural raw materials, with synergistic effects of multiple mechanisms, advanced technology, and a proven safety profile, in order to meet the diverse needs of different groups. Summary of the Invention

[0008] The purpose of this invention is to provide a composition with sleep-improving function, its preparation method, and its application. This invention is achieved through the following technical solution: A composition for improving sleep is prepared from the following raw materials in the indicated weight ratios: 50-100 parts of Acanthopanax senticosus, 30-50 parts of lotus seeds, 50-100 parts of jujube seed, 30 parts of lily bulb, 30 parts of longan, 30-50 parts of Poria cocos, 30 parts of Ophiopogon japonicus, 10-30 parts of Rehmannia glutinosa, 10-30 parts of Gastrodia elata, 2 parts of glutamic acid, 0.1 parts of vitamin B1, 0.1 parts of vitamin B6, and 0.1 parts of γ-aminobutyric acid.

[0009] Preferably, it is prepared from the following raw materials in the indicated weight ratios: 50 parts Acanthopanax senticosus, 50 parts lotus seeds, 100 parts jujube seed, 30 parts lily bulb, 30 parts longan, 30 parts Poria cocos, 30 parts Ophiopogon japonicus, 30 parts Rehmannia glutinosa, 10 parts Gastrodia elata, 2 parts glutamic acid, 0.1 parts vitamin B1, 1 part vitamin B6, and 0.1 parts γ-aminobutyric acid.

[0010] The method for preparing the composition using the above-mentioned raw materials for improving sleep function includes the following steps: (1) Wash Acanthopanax senticosus, lotus seeds, jujube seeds, lily bulbs, longan, poria cocos, ophiopogon japonicus, rehmannia glutinosa, and gastrodia elata, dry them at a low temperature of 60℃, pulverize them with an ultra-micro pulverizer and pass them through a 60-mesh sieve to collect uniform raw material powder; (2) Prepare 0.05 mol / L phosphate buffer (pH=7.2), add the buffer solution at 10 times the mass of the raw material powder and mix well to prepare the "raw material-buffer solution system", and soak at room temperature (25±2℃) for 15~20 minutes; (3) Place distilled water in a beaker, immerse the plasma nozzle 0.5 cm below the water surface, and treat with plasma for 90 s to prepare plasma activated water (PAW). Mix the "raw material-buffer system" and PAW at a liquid-liquid ratio of 3:1 and then treat with ultrasound. Extraction temperature: 30~40℃, ultrasound parameters: power 300W, frequency 40kHz, plasma parameters: voltage 200V, current 0.5A, gas flow rate 40L / h, extraction times: 2 times, each time 30~45 minutes; (4) After extraction, the extract was quickly separated by a combination of 300-mesh nylon filter cloth and centrifugal filtration (3000r / min, 10 minutes), and the two extraction filtrates were combined. (5) Transfer the combined filtrate into a vacuum concentration tank for vacuum concentration. The vacuum concentration conditions are: vacuum degree -0.08~-0.10MPa, temperature 40±2℃; (6) Transfer the concentrate to a high-speed low-temperature centrifuge and centrifuge at 4°C and 8000r / min for 15 minutes to remove large molecular impurities such as protein and starch; the supernatant is then filtered through a 3000Da ultrafiltration membrane to further remove colloidal impurities. (7) Add the prescribed amount of glutamic acid, vitamin B1, vitamin B6 and γ-aminobutyric acid to the ultrafiltration permeate, and stir magnetically for 30 minutes at a temperature below 25°C (200 r / min) to ensure that the excipients and active ingredients are mixed evenly and to avoid the degradation of vitamin B complex caused by high temperature. (8) Transfer the mixture to a freeze-drying tray and freeze-dry it in a vacuum freeze dryer. The freeze-drying conditions are: vacuum degree -0.08~-0.09MPa, temperature -60~-40℃; (9) The freeze-dried powder is pulverized by a high-speed pulverizer, passed through an 80-mesh sieve, and sealed for storage.

[0011] The active components obtained from the above raw materials can be added to various conventional excipients, such as lubricants, binders, and fillers, and can be formulated into any desired dosage form, such as powder, granules, pills, tablets, capsules, tea, oral liquid, and ointment, using conventional composition methods.

[0012] Animal experiments were conducted using the composition prepared by the above method, including direct sleep experiments, subthreshold dose sodium pentobarbital hypnotic experiments, sodium pentobarbital sleep latency experiments, and sodium pentobarbital sleep duration prolongation experiments. The results showed that there was no significant direct sleep effect; it increased the number of mice that slept in the subthreshold dose sodium pentobarbital hypnotic experiment; it significantly shortened the sodium pentobarbital sleep latency and prolonged the sodium pentobarbital-induced sleep time in mice, showing a significant difference compared to the control group. The experiments demonstrate that this composition has a sleep-improving effect.

[0013] Compared with existing technologies, the outstanding feature of this invention is that, based on the traditional diagnostic theory of "insomnia due to deficiency of both heart and spleen," it combines modern neuroregulatory mechanisms and optimizes the composition through multiple rounds of efficacy screening experiments, thereby optimizing the intestinal microecology and promoting gut-brain axis linkage. The inventors use Acanthopanax senticosus, lotus seed, jujube seed, lily bulb, longan, Poria cocos, Ophiopogon japonicus, and Rehmannia glutinosa as the core ingredients, supplemented with Gastrodia elata, glutamic acid, vitamin B1, vitamin B6, and γ-aminobutyric acid (GABA). This breaks through the limitations of traditional single-target formulations, forming a synergistic system of "tonifying the spleen and calming the mind - neurotransmitter regulation - gut-brain axis regulation." Specifically, Acanthopanax senticosus tonifies the kidneys and calms the mind; lotus seed astringes and calms the heart; jujube seed nourishes blood and calms the mind; lily bulb calms the mind and improves intelligence; longan relieves depression and calms the mind; Poria cocos strengthens the spleen and calms the mind; Ophiopogon japonicus moistens the lungs and clears the heart; and Rehmannia glutinosa clears heat and cools the blood. Combined with Gastrodia elata inhibiting central nervous system excitation, glutamic acid participating in GABA synthesis, vitamin B1 and vitamin B6 regulating nerve metabolism, and GABA lowering blood pressure, improving sleep, and improving liver, kidney, and brain function, the invention provides a comprehensive approach. The inventors screened out suitable raw materials for the composition through numerous experiments, formulated them according to a specific formula, and proved that the product has the effect of improving sleep by shortening the sleep latency and increasing sleep time.

[0014] Sour jujube seed has a sweet and sour taste, is neutral in nature, and enters the heart, liver, and gallbladder meridians. It nourishes the heart and calms the mind. It is primarily used to treat insomnia, palpitations, and anxiety caused by deficiency of yin and blood in the heart and liver, and is especially suitable for symptoms of heart malnourishment and restlessness. Studies have shown that its main active components are jujube seed saponins, flavonoids, and polysaccharides. Research has confirmed that sour jujube seed extract can significantly reduce spontaneous activity in mice by inhibiting central nervous system function, reducing the release of norepinephrine and dopamine; it can also synergistically prolong sleep time with sodium pentobarbital and antagonize the central excitatory effects of amphetamine, with the intensity of the effect being positively correlated with the dose.

[0015] Acanthopanax senticosus has a pungent and slightly bitter taste, is warm in nature, and enters the liver and kidney meridians. It has the effects of tonifying qi and strengthening the spleen, benefiting the kidneys and calming the mind, and is mainly used to treat insomnia due to spleen and lung qi deficiency and kidney deficiency. Its active ingredients are Acanthopanax saponins and polysaccharides. Modern research shows that Acanthopanax senticosus extract can regulate hypothalamic function, inhibit the rise of cortisol levels, and simultaneously exert a sedative and calming effect by improving the levels of neurotransmitters such as serotonin and norepinephrine in the brain, thus prolonging the sodium pentobarbital sleep time in mice.

[0016] Lotus seeds tonify the spleen and stop diarrhea, stop leukorrhea, benefit the kidneys and astringe essence, and nourish the heart and calm the mind. The key is "nourishing the heart," which is effective for insomnia caused by deficiency of both the heart and spleen and disharmony between the heart and kidneys, manifested as shallow sleep, easy awakening, accompanied by fatigue and loss of appetite.

[0017] Lily nourishes yin and moistens the lungs, clears the heart and calms the mind. It is good at "clearing heart fire and nourishing lung yin", and is effective for insomnia caused by yin deficiency and internal heat, and insomnia caused by deficiency fire disturbing the mind, which manifests as irritability, insomnia, dreaminess, dry mouth and throat, and hot palms and soles.

[0018] Longan nourishes the heart and spleen, replenishes blood, and calms the mind. It is particularly beneficial for insomnia caused by insufficient qi and blood, and deficiency of both the heart and spleen, manifested as insomnia with excessive dreaming, palpitations, forgetfulness, pale complexion, and fatigue.

[0019] Poria cocos is sweet in taste and neutral in nature, entering the heart, lung, spleen, and kidney meridians. It strengthens the spleen and directly calms the mind and spirit, stabilizing the mind at its root by addressing spleen deficiency. Poria cocos acid can cross the blood-brain barrier and act on the central nervous system, inhibiting over-excitation and producing a sedative effect; it may also regulate the hypothalamus-pituitary-adrenal axis, reducing the impact of stress on sleep. Poria cocos polysaccharides can improve the body's immunity and metabolism, indirectly alleviating sleep disturbances caused by spleen deficiency.

[0020] Ophiopogon japonicus has a sweet and slightly bitter taste, and is slightly cold in nature. It enters the heart, lung, and stomach meridians. It can nourish the heart yin and clear away deficiency fire. By replenishing yin fluids and calming deficiency fire, it can soothe a disturbed mind. Ophiopogon japonicus saponins can inhibit central nervous system excitation and prolong sleep time. At the same time, it may improve the increased nerve excitability caused by "yin deficiency and internal heat" by anti-oxidation and reducing oxidative stress damage in the brain. The polysaccharide components can regulate endocrine function, making it suitable for insomnia caused by "yin deficiency and excessive fire".

[0021] Rehmannia root is sweet in taste and cold in nature, and it enters the heart, liver, and kidney meridians. It can clear blood heat and nourish yin fluids, making it suitable for insomnia caused by "heat evil" disturbing the mind. Catalpol has sedative and anti-anxiety effects, and can reduce the excitability of the central nervous system; at the same time, it can improve insomnia caused by "heat disturbing the mind" by inhibiting inflammatory responses.

[0022] Gastrodia elata has a sweet taste and neutral properties, and enters the liver meridian. Traditional theory believes that it can calm the liver and extinguish wind, unblock the meridians and relieve pain. Herbal texts throughout history have listed Gastrodia elata as a superior herb, praising its ability to "calm the mind and relieve fright." Gastrodia elata is the main active ingredient in Gastrodia elata. Studies have confirmed that Gastrodia elata can cross the blood-brain barrier and act directly on the central nervous system, inhibiting the ascending activating system of the brainstem reticular formation, reducing the number of spontaneous activities in mice, shortening the sleep latency induced by sodium barbital, and increasing the number of mice that experience sleep induced by subthreshold doses of sodium barbital.

[0023] Glutamate is a major excitatory amino acid in the central nervous system. As a precursor to GABA, it is converted into an inhibitory neurotransmitter under the catalysis of glutamate decarboxylase. Studies have shown that exogenous glutamate supplementation can promote GABA synthesis in the brain, reduce the firing frequency of cortical neurons, and prolong the seizure latency in a pentylenetetrazol-induced seizure model. Clinical studies have shown that the combined use of glutamate and benzodiazepines can enhance the sedative effect without increasing dependence.

[0024] Vitamin B1, as a coenzyme of α-keto acid oxidative decarboxylase, participates in neuronal energy metabolism. Its deficiency can lead to pyruvate accumulation, inhibit mitochondrial function, and induce demyelinating lesions in the central nervous system. Studies have confirmed that vitamin B1 supplementation can improve sleep fragmentation in mice and increase the duration of slow-wave sleep; its mechanism is related to maintaining myelin integrity and promoting acetylcholine synthesis. Clinically, vitamin B1 is often used to treat insomnia caused by neurasthenia.

[0025] Vitamin B6, as a coenzyme for amino acid decarboxylases, participates in the synthesis of neurotransmitters such as serotonin and gamma-aminobutyric acid (GABA). Experiments show that vitamin B6 can promote the conversion of tryptophan to serotonin, increasing serotonin levels in the hypothalamus, increasing GABA concentration in the brain, and inhibiting the excitability of the arousal center. Clinical studies have shown that vitamin B6 is effective for menopausal insomnia and anxiety; when used in combination with vitamin B1, it can shorten sleep latency and reduce the number of awakenings.

[0026] Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system. Its core function is to "balance nerve excitability"—when brain nerve cells are overactive (such as when anxious, tense, or overthinking), GABA can help the brain relax by inhibiting nerve signal transmission, thereby creating conditions for sleep initiation.

[0027] Beneficial effects: Compared with existing sleep improvement products, the core competitiveness of this composition lies in its advanced process that achieves high dissolution and no residue. Based on the principle of "no direct hypnotic activity", it achieves "safe, comprehensive and clinically appropriate" sleep improvement through a "synergistic effect" mechanism. This avoids the side effect risks of direct hypnotic products and solves the limitations of single-effect products. At the same time, it provides a new path of "reduced dosage and improved effect" through multiple syndromes and multiple targets, improving safety with no dependence and no side effects. It is especially suitable for people with mild insomnia who need assistance and synergistic effects and have high safety requirements (such as the elderly and people with sensitive constitutions). Attached Figure Description

[0028] Figure 1 Effect of the composition on mouse body weight; Figure 2 Effects of the composition on food and water intake in mice; Figure 3 Effects of the composition on sleep duration and sleep latency in mice; Figure 4 An example illustration of the composition inducing sleep behavior in mice using sodium pentobarbital; Figure 5 Example of mouse sleep and wakefulness comparison; Figure 6 Examples of mouse states after administration of the composition; Figure 7Effect of the composition on GABA content in mouse brain tissue; Figure 8 Effect of the composition on 5-HT content in mouse brain tissue; Figure 9 Effect of the composition on DA content in mouse brain tissue; Figure 10 Effect of the composition on NE content in mouse brain tissue; Figure 11 Effect of the composition on Glu content in mouse brain tissue; Figure 12 Bar chart of relative abundance of Lactobacillus at the genus level; Figure 13 Alistipes genus-level relative abundance bar chart; Figure 14 Lachnospiraceae_unclassified genus-level relative abundance bar chart; Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be further described below in conjunction with the embodiments. However, the described embodiments are some embodiments of the present invention, not all embodiments. Any modifications or changes to the technical solutions of the present invention without departing from the technical solutions of the present invention will be included within the scope of the claims of the present invention.

[0030] The experimental methods, production processes, and instruments and equipment involved in the embodiments of this invention are all conventional names in the art. Those skilled in the art can understand the process steps and apply the corresponding instruments and equipment based on these names, and implement them according to conventional conditions or conditions recommended by the manufacturer.

[0031] Unless otherwise specified, the experimental methods used in the examples are all conventional techniques; the instruments and equipment used are all commonly used laboratory equipment; and the experimental materials are all purchased through conventional biochemical reagent channels.

[0032] Example 1 A composition for improving sleep is prepared from the following raw materials in the indicated weight ratios: 50 parts of Acanthopanax senticosus, 50 parts of lotus seeds, 100 parts of jujube seed, 30 parts of lily bulb, 30 parts of longan, 30 parts of Poria cocos, 30 parts of Ophiopogon japonicus, 30 parts of Rehmannia glutinosa, 10 parts of Gastrodia elata, 2 parts of glutamic acid, 0.1 parts of vitamin B1, 0.1 parts of vitamin B6, and 0.1 parts of γ-aminobutyric acid.

[0033] The preparation method is as follows: (1) Wash Acanthopanax senticosus, lotus seeds, jujube seeds, lily bulbs, longan, poria cocos, ophiopogon japonicus, rehmannia glutinosa and gastrodia elata, dry them at a low temperature of 60℃, pulverize them with an ultra-micro pulverizer and pass them through a 60-mesh sieve to collect uniform raw material powder; (2) Prepare 0.05 mol / L phosphate buffer (pH=7.2) (simulate the human body fluid environment to enhance the dissolution selectivity of active ingredients such as alkaloids, saponins, and flavonoids). Add the buffer solution at 10 times the mass of the raw material powder and mix well to prepare the "raw material-buffer solution system". Soak at room temperature (25±2℃) for 15~20 minutes. (3) Place distilled water in a beaker, immerse the plasma nozzle 0.5 cm below the water surface, and treat with plasma for 90 s to prepare plasma activated water (PAW). Mix the "raw material-buffer system" and PAW at a liquid-liquid ratio of 3:1 and then treat with ultrasound. Extraction temperature: 30~40℃, ultrasound parameters: power 300W, frequency 40kHz, plasma parameters: voltage 200V, current 0.5A, gas flow rate 40L / h, extraction times: 2 times, each time 30~45 minutes; (4) After extraction, the extract was quickly separated by a combination of 300-mesh nylon filter cloth and centrifugal filtration (3000r / min, 10 minutes), and the two extraction filtrates were combined. (5) Transfer the combined filtrate into a low-temperature vacuum concentration tank for vacuum concentration; (6) Transfer the concentrate to a high-speed low-temperature centrifuge and centrifuge at 4°C and 8000r / min for 15 minutes to remove large molecular impurities such as protein and starch; the supernatant is then filtered through a 3000Da ultrafiltration membrane (operating temperature ≤25°C) to further remove colloidal impurities. (7) Add glutamic acid, vitamin B1, vitamin B6 and γ-aminobutyric acid to the ultrafiltration permeate, and stir magnetically for 30 minutes at a temperature below 25°C (200 r / min) to ensure that the excipients and active ingredients are mixed evenly and to avoid the degradation of vitamin B complex caused by high temperature. (8) Transfer the mixture to a freeze-drying tray and freeze-dry it in a vacuum freeze dryer; (9) The freeze-dried powder is pulverized by a high-speed pulverizer, passed through an 80-mesh sieve, and sealed for storage.

[0034] (10) Mix the powder evenly and dissolve it in physiological saline to prepare an oral solution.

[0035] Example 2 The difference between this embodiment and Embodiment 1 is that the weight ratio of lotus seeds and poria cocos is different.

[0036] Specifically, the ingredients are: 50 parts Acanthopanax senticosus, 30 parts lotus seeds, 100 parts Ziziphus jujuba var. spinosa, 30 parts lily bulbs, 30 parts longan, 50 parts Poria cocos, 30 parts Ophiopogon japonicus, 30 parts Rehmannia glutinosa, 10 parts Gastrodia elata, 2 parts glutamic acid, 0.1 parts vitamin B1, 0.1 parts vitamin B6, and 0.1 parts γ-aminobutyric acid.

[0037] The preparation method is the same as in Example 1.

[0038] Example 3 The difference between this embodiment and Embodiment 1 is that the weight ratio of Acanthopanax senticosus and Ziziphus jujuba seeds is different.

[0039] Specifically, the ingredients are: 100 parts Acanthopanax senticosus, 50 parts lotus seeds, 50 parts jujube seed, 30 parts lily bulb, 30 parts longan, 30 parts Poria cocos, 30 parts Ophiopogon japonicus, 30 parts Rehmannia glutinosa, 10 parts Gastrodia elata, 2 parts glutamic acid, 0.1 parts vitamin B1, 0.1 parts vitamin B6, and 0.1 parts γ-aminobutyric acid.

[0040] The preparation method is the same as in Example 1.

[0041] Example 4 The difference between this embodiment and Embodiment 1 is that the weight ratio of Rehmannia glutinosa and Gastrodia elata is different.

[0042] 50 parts of Acanthopanax senticosus, 50 parts of lotus seeds, 100 parts of jujube seed, 30 parts of lily bulb, 30 parts of longan, 30 parts of Poria cocos, 30 parts of Ophiopogon japonicus, 10 parts of Rehmannia glutinosa, 30 parts of Gastrodia elata, 2 parts of glutamic acid, 0.1 parts of vitamin B1, 0.1 parts of vitamin B6 and 0.1 parts of γ-aminobutyric acid.

[0043] Comparative Example 1 The total amount in this comparative example is the same as that in Example 1, which is 362.3 parts. The difference is that Acanthopanax senticosus is removed and the amount of Rehmannia glutinosa and Gastrodia elata is increased proportionally.

[0044] Specifically, the ingredients are: 50 parts lotus seeds, 100 parts jujube seeds, 30 parts lily bulbs, 30 parts longan, 30 parts poria cocos, 30 parts ophiopogon japonicus, 55 parts rehmannia glutinosa, 35 parts gastrodia elata, 2 parts glutamic acid, 0.1 parts vitamin B1, 0.1 parts vitamin B6, and 0.1 parts γ-aminobutyric acid.

[0045] The preparation method is the same as in Example 1.

[0046] Comparative Example 2 The total amount in this comparative example is the same as that in Example 1, which is 362.3 parts. The difference is that: the jujube seed is removed and the amount of Acanthopanax senticosus and Poria cocos is increased proportionally.

[0047] Specifically: 100 parts of Acanthopanax senticosus, 50 parts of lotus seeds, 30 parts of lily bulbs, 30 parts of longan, 80 parts of Poria cocos, 30 parts of Ophiopogon japonicus, 30 parts of Rehmannia glutinosa, 10 parts of Gastrodia elata, 2 parts of glutamic acid, 0.1 parts of vitamin B1, 0.1 parts of vitamin B6, and 0.1 parts of γ-aminobutyric acid.

[0048] The preparation method is the same as in Example 1.

[0049] Experiment Example 1: Efficacy Verification An oral liquid prepared from the above powder was used as a sample in a mouse experiment to improve sleep function. The experimental results are as follows: The oral liquid composition obtained in the above examples and comparative examples was used as an experimental subject in SPF-grade male KM mice to demonstrate that the composition of the present invention has the effect of improving sleep.

[0050] 1. Laboratory animals SPF-grade male KM mice, weighing 18-22g. Provided by Liaoning Changsheng Biotechnology Co., Ltd., Production License: NO.SCXK (Liaoning) 2020-0001.

[0051] 2. Test materials and reagents Diazepam tablets (Shanghai Xinyi Pharmaceutical Co., Ltd., batch number 14161201); normal saline (Chenxin Pharmaceutical Co., Ltd., batch number: 170829072); sodium pentobarbital (Sigma-Aldrich, USA, batch number P11011); sodium barbital (Sigma-Aldrich, USA, batch number B0500).

[0052] 3. Dosage design 320 mice were randomly divided into 8 groups of 40 mice each (10 mice per experiment): negative control group (saline), positive control group (diazepam 2 mg / kg), Example 1 group (0.065 g / kg), Example 2 group (0.065 g / kg), Example 3 group (0.065 g / kg), Example 4 group (0.065 g / kg), Comparative Example 1 group (0.065 g / kg), and Comparative Example 2 group (0.065 g / kg). Mice in each group were administered the drug by gavage once a day at a dose of 0.1 mL / 10 g for 30 consecutive days.

[0053] 4. Experimental Methods (1) Direct Sleep Experiment The test group was given the test sample, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug, with continuous administration for 30 days. On the 30th day, mice were administered the test sample by gavage for 30 minutes, and the presence of sleep was observed. Sleep was defined as the disappearance of the righting reflex. When a mouse was placed in a dorsal position, it should be able to right itself immediately. If it could not right itself within 30-60 seconds, the righting reflex was considered to have disappeared, and the mouse had entered sleep. The recovery of the righting reflex was considered awakening, and the period from the disappearance to the recovery of the righting reflex was considered sleep time. The number of animals falling asleep and the sleep time were recorded in the negative control group, positive control group, and test sample group.

[0054] (2) Experiment on prolonging sodium pentobarbital sleep time The test group was given the test sample, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug. Administration continued for 30 days. On day 30, 30 minutes after gavage, mice in each group were intraperitoneally injected with 50 mg / kg sodium pentobarbital solution (0.1 mL / 10 g). The sleep time of each mouse was calculated based on the disappearance of the righting reflex for 60 seconds, to observe whether the test sample could prolong the sleep time caused by sodium pentobarbital.

[0055] (3) Subthreshold dose hypnotic experiment with sodium pentobarbital The test group was given the test sample, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug. The administration was carried out continuously for 30 days. On the 30th day, 30 minutes after the mice were gavaged, each group of mice was intraperitoneally injected with 30 mg / kg sodium pentobarbital solution, with an injection volume of 0.1 mL / 10 g. The number of mice that fell asleep within 30 minutes was recorded as the indicator that the righting reflex disappeared for 60 seconds.

[0056] (4) Sodium barbiturate sleep latency test The test group was given the test drug, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug. The administration was repeated for 30 days. On day 30, 30 minutes after gavage, mice in each group were intraperitoneally injected with 300 mg / kg sodium barbital solution (0.1 mL / 10 g). The sleep latency of mice in the negative control group, positive control group, and test sample group was recorded, using the disappearance of the righting reflex for 60 seconds as an indicator, to observe the effect of the test sample on the sleep latency of sodium barbital.

[0057] 5. Statistical methods: SPSS 27.0 was used for statistical analysis. The sleep onset rate of mice undergoing direct sleep and the sleep onset rate of mice undergoing subthreshold doses of sodium pentobarbital were count data, and the chi-square test was used. Other indicators were measurement data, and experimental data were analyzed using... ±S represents the mean. One-way ANOVA was used for comparisons among multiple groups, and t-tests were used for comparisons between groups. A p-value < 0.05 was considered statistically significant.

[0058] 6. Experimental Results (1) Results of the direct sleep experiment The results showed that no mice in any group experienced sleep within 30 minutes, indicating that the test sample had no significant direct hypnotic effect on the mice. The experimental results are shown in Table 1.

[0059] Table 1. Results of the composition on direct sleep in mice ( ±S, n=10) (2) Results of the experiment on prolonging the sleep time of sodium pentobarbital The results showed that, compared with the negative control group, both the Example 1-4 groups and the positive control group prolonged the sleep time of the pentobarbital sodium mice. The sleep duration extension in the Example 1 group was significantly longer than that in the Example 2-4 groups, indicating that the compositions provided in Examples 1-4 of this invention can prolong sleep time, with Example 1 showing the best effect; the difference was statistically significant (P < 0.05). Compared with the negative control group, the sleep time of mice in the Comparative Example 1-2 groups showed no significant change (P > 0.05), indicating that the compositions provided in Comparative Example 1-2 did not have the effect of prolonging sleep time. The results are shown in Table 2.

[0060] Table 2. Results of prolonging sodium pentobarbital sleep time in mice ( ±S, n=10) Note: Compared with the negative control group * P<0.05, ** P<0.01.

[0061] (3) Results of subthreshold dose hypnotic experiments with sodium pentobarbital The results showed that, compared with the negative control group, both the Example 1-4 groups and the positive control group increased the number of animals falling asleep. The number of animals falling asleep in Example 1 group was significantly higher than that in Example 2-4 groups (P < 0.05). However, there was no significant change in the number of animals falling asleep in the Comparative Examples 1-2 groups compared with the negative control group (P > 0.05). The results are shown in Table 3.

[0062] Table 3. Results of subthreshold dose hypnotic experiments with sodium pentobarbital ( ±S, n=10) Note: Compared with the negative control group * P<0.05, ** P<0.01.

[0063] (4) Results of the sodium barbital sleep latency test The results showed that, compared with the negative control group, both the Examples 1-4 groups and the positive control group shortened the sleep latency of sodium barbital mice, and the differences were statistically significant (P < 0.05), indicating that the compositions provided in Examples 1-4 of this invention can shorten the sleep latency. However, the sleep latency of sodium barbital mice in Comparative Examples 1-2 groups did not show a significant change compared with the negative control group (P > 0.05), indicating that the compositions provided in Comparative Examples 1-2 groups did not have the effect of shortening the sleep latency. The results are shown in Table 4.

[0064] Table 4. Results of the sodium barbital sleep latency test ±S, n=10) Note: Compared with the negative control group * P<0.05, ** P<0.01 (5) Summary In Examples 1-4, all three experiments—the pentobarbital sodium sleep time prolongation experiment, the pentobarbital sodium subthreshold dose hypnotic experiment, and the barbital sodium sleep latency experiment—were positive, and there was no obvious direct sleep effect. Therefore, Examples 1-4 can be determined to have a sleep-improving effect. The experiments show that Comparative Examples 1-2, which removed the main components Acanthopanax senticosus or Ziziphus jujuba seed, did not have a sleep-improving effect, demonstrating the synergistic effect between the components of the composition provided by this invention.

[0065] Experimental Example 2: Study on Improving Sleep Function The composition obtained in Example 1 was used as an experimental subject in SPF-grade male KM mice to demonstrate that the composition of the present invention has the effect of improving sleep.

[0066] 1. Laboratory animals SPF-grade male KM mice, weighing 18-22g. Provided by Liaoning Changsheng Biotechnology Co., Ltd., Production License: NO.SCXK (Liaoning) 2020-0001. AH is the high-dose group of Example 1 of this invention, AL is the low-dose group of Example 1 of this invention, HH is the high-dose group of some components of Example 1 of this invention, and HL is the low-dose group of some components of Example 1 of this invention.

[0067] 2. Test materials and reagents Diazepam tablets (Shanghai Xinyi Pharmaceutical Co., Ltd., batch number 14161201); normal saline (Chenxin Pharmaceutical Co., Ltd., batch number: 170829072); sodium pentobarbital (Sigma-Aldrich, USA, batch number P11011); sodium barbital (Sigma-Aldrich, USA, batch number B0500).

[0068] 3. Experimental Methods (1) Direct Sleep Experiment The test groups were given different doses of the test sample, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug. Administration continued for 30 days. On day 30, mice were administered the drug via gavage for 30 minutes, and the presence of sleep was observed. Sleep was defined as the disappearance of the righting reflex. When a mouse was placed in a dorsal position, it should be able to right itself immediately. If it could not right itself within 30-60 seconds, the righting reflex was considered to have disappeared, and the mouse had entered sleep. The recovery of the righting reflex was considered awakening, and the period from the disappearance to the recovery of the righting reflex was considered sleep time. The number of animals falling asleep and the sleep time were recorded in the negative control group, positive control group, and test sample group.

[0069] (2) Experiment on prolonging sodium pentobarbital sleep time The test groups were given different doses of the test sample, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug. The administration was repeated for 30 days. On day 30, 30 minutes after gavage, each group of mice was intraperitoneally injected with 50 mg / kg sodium pentobarbital solution (0.1 mL / 10 g). The sleep time of each mouse was calculated based on the disappearance of the righting reflex for 60 seconds, to observe whether the test sample could prolong the sleep time caused by sodium pentobarbital.

[0070] (3) Subthreshold dose hypnotic experiment with sodium pentobarbital The test groups were given different doses of the test sample, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug. The administration was carried out continuously for 30 days. On the 30th day, 30 minutes after the mice were gavaged, each group of mice was intraperitoneally injected with 30 mg / kg sodium pentobarbital solution, with an injection volume of 0.1 mL / 10 g. The number of mice that fell asleep within 30 minutes was recorded as the indicator that the righting reflex disappeared for 60 seconds.

[0071] (4) Sodium barbiturate sleep latency test The test groups were given different doses of the test drug, the negative control group was given the same volume of physiological saline, and the positive control group was given the positive drug. The administration was repeated for 30 days. On day 30, 30 minutes after gavage, mice in each group were intraperitoneally injected with 300 mg / kg sodium barbital solution (0.1 mL / 10 g). The sleep latency of mice in the negative control group, positive control group, and test sample group was recorded, using the disappearance of the righting reflex for 60 seconds as an indicator, to observe the effect of the test sample on the sleep latency of sodium barbital.

[0072] 4. Statistical methods: SPSS 27.0 was used for statistical analysis. The sleep onset rate of mice undergoing direct sleep and the sleep onset rate of mice undergoing subthreshold doses of sodium pentobarbital were count data, and the chi-square test was used. Other indicators were measurement data, and experimental data were analyzed using... ±S represents the mean. One-way ANOVA was used for comparisons among multiple groups, and t-tests were used for comparisons between groups. A p-value < 0.05 was considered statistically significant.

[0073] 5. Measurement of neurotransmitter content in brain tissue Brain tissue was removed from a -80°C freezer and accurately weighed. The tissue was placed in a centrifuge tube, along with two steel balls and 1 mL of pre-cooled PBS. The tissue was then ground using a homogenizer (the steel balls in the homogenizer should be pre-cooled at -20°C; ensure the sample is balanced when placing it). The homogenizer was ground twice according to the preset parameters (60Hz frequency, 60s time, 5s pause). After grinding, the sample was allowed to stand at 4°C for 5 minutes, followed by centrifugation at 12000 rpm for 5 minutes. The supernatant was used for neurotransmitter detection. To avoid repeated freeze-thaw cycles, the samples were aliquoted and labeled. The neurotransmitter content in mouse brain tissue was determined using an ELISA kit.

[0074] 6. Effects of the composite composition on the diversity of the intestinal microbiota in mice Mice were sacrificed one hour after the final administration of the drug in the last experiment. Fresh fecal particles and feces from the distal colon near the anus were collected from each group of mice and stored at -80°C. The gut microbiota composition was analyzed using 16S rDNA high-throughput sequencing.

[0075] 7. Experimental Results (1) Effect of the composition on mouse body weight Mouse body weight can reflect their growth status to some extent. After weighing during the adaptation period, the mice are randomly divided into cages, with each cage containing mice of equal body weight. For example... Figure 1 As shown, the mice were in normal condition and good mental state during the administration period. There was no significant difference in body weight between the combination group and the control group.

[0076] (2) Effects of the composition on the food and water intake of mice The way mice eat and drink can reflect their health status to some extent, such as... Figure 2 As shown, the mice in the composition group provided by the present invention showed no significant difference in food and water intake compared to the control group during the experiment.

[0077] (3) Effect of the composition on sodium pentobarbital-induced sleep behavior The effects of the composition provided in this invention, in synergy with sodium pentobarbital, on sleep in mice were investigated using a pentobarbital sodium sleep behavior experiment. The results are as follows: Figure 3 As shown, compared with the negative control group, the low-dose group, the high-dose group, and the positive control group of the test sample all prolonged the sleep time and shortened the sleep latency of sodium pentobarbital mice, and the differences were statistically significant (P < 0.05). Figure 4-6 The figure shows an example of the effect of the composition of the present invention on the sleep behavior induced by sodium pentobarbital in mice and the state of the mice after administration. As shown in the figure, the mice were in good health after administration of the composition of the present invention, which can prove to a certain extent that the composition of the present invention is non-toxic and has an effective sleep-inducing effect.

[0078] (4) Effect of the composition on neurotransmitter content in mouse brain tissue The neurotransmitter content of brain tissue from mice in groups AH and AL, as provided in this invention, was detected. Figure 7 As shown, the composition upregulated the GABA concentration in mouse brain tissue, showing a significant difference compared to the control group. Figure 8 As shown, the composition upregulated the concentration of 5-HT in mouse brain tissue, showing a significant difference compared to the control group. Figure 9 As shown, the composition significantly downregulated the concentration of dopamine (DA) in mouse brain tissue compared to the control group. Figure 10 As shown, the composition significantly downregulated the concentration of norepinephrine (NE) in mouse brain tissue compared to the control group. Figure 11 As shown, the composition significantly reduced the concentration of Glu in mouse brain tissue compared to the control group. Studies have found that the 5-HT system promotes sleep; therefore, the composition provided in this invention improves sleep by increasing 5-HT levels in mouse brain tissue. Higher doses of the composition showed better effects on changes in GABA, DA, NE, and Glu levels in brain tissue. GABA is an inhibitory neurotransmitter in the brain, and the composition provided in this invention significantly increases its content in brain tissue. Glu, as a precursor to GABA, is an excitatory neurotransmitter, and the composition provided in this invention significantly reduces its content in brain tissue. NE is one of the main neurotransmitters promoting wakefulness and participates in the ascending reticular activating system; its level affects the effects of many products that promote wakefulness and sedation. The composition of this invention significantly reduces NE content in mouse brain tissue.

[0079] (5) Effects of the composite composition on the diversity of the mouse gut microbiota The relative abundance of genera associated with insomnia in mice was extracted and statistically analyzed. The results are as follows: Figure 12-14 As shown, compared with the CON group, the abundance of Lactobacillus was significantly reduced in the AH and AL groups (P<0.05). The abundance of Alistipes was significantly increased in the AH and AL groups (P<0.05), while the abundance of Lachnospiraceae_unclassified was significantly increased in the AH and AL groups (P<0.05). These findings suggest that sleep deprivation disrupts the gut microbiota, leading to dysbiosis. However, the compound composition of the present invention effectively improves the balance of the gut microbiota, with the AH group showing a particularly strong effect in improving these imbalances.

[0080] Experimental Example 3 Acute toxicity test in mice 1. Laboratory animals SPF-grade KM mice, half male and half female, weighing 18-22g. Provided by Liaoning Changsheng Biotechnology Co., Ltd., Production License: NO.SCXK (Liaoning) 2020-0001.

[0081] 2. Dosage design Forty SPF-grade KM mice, half male and half female, were selected. Ten male mice were randomly selected as the test sample group, and the remaining ten male mice served as the negative control group. Female mice were grouped in the same manner. The experimental group was given the oral solution prepared by the method in Example 1 of this invention. The maximum tolerated dose (MTD) method was used in the experiment. Mice were fasted for 12 hours before the experiment, but water intake was not restricted. The maximum concentration of the test sample was administered by gavage at a volume of 20 mL / kg, based on the maximum tolerated gavage dose for mice. The administration was carried out three times a day, with an interval of 6 hours between each administration, at a dose of 2.6 g / kg, for a total dose of 7.8 g / kg (equivalent to 600 times the recommended human dose). The mice were observed for 14 consecutive days, and their general condition, weight changes, signs of poisoning, and mortality were recorded to determine the maximum tolerated dose (MTD). After the experiment, the mice in each group were euthanized by cervical dislocation, and the appearance changes of the major organs were observed by dissection. Remove all major organs intact, rinse briefly with physiological saline, and pat dry. Immediately weigh them on a balance with a sensitivity of 1 / 100th of a gram. Divide the weight by the body weight to obtain the coefficient of each organ. The calculation formula is as follows: 3. Statistical methods: SPSS 27.0 was used for statistical analysis. Changes in mouse body weight and organ indices were used as quantitative data. Experimental data were analyzed using... ±S represents the mean ± standard deviation. One-way ANOVA was used to compare multiple groups. A p-value < 0.05 was considered statistically significant.

[0082] 4. Results of acute toxicity experiments in mice Mice of both sexes were administered the test sample three times via gavage, with a total gavage dose of 7.8 g / kg. During the 14-day observation period, all mice remained in normal condition, without any abnormalities such as convulsions, respiratory distress, or diarrhea. No mice died after administration, and no obvious signs of poisoning were observed. From the time of administration until the end of day 14, there was no statistically significant difference in body weight among the groups. After the experiment, the mice were euthanized and dissected. Macroscopic examination of major organs such as the kidneys, stomach, small intestine, large intestine, cecum, lungs, liver, pancreas, heart, spleen, thymus, and brain revealed no significant abnormalities in size, morphology, structure, or color. There were no statistically significant differences in organ indices among the groups. The maximum tolerated dose (MTD) via oral administration was >7.8 g / kg for both male and female mice (equivalent to 600 times the recommended human dose). According to the acute toxicity grading criteria, this test sample was classified as non-toxic. The results are shown in Tables 9-11.

[0083] Table 9. Results of body weight changes in mice during acute toxicity experiments ( ±S, n=10) Table 10. Results of poisoning symptoms and mortality in mice in the acute toxicity experiment ( ±S, n=10) Table 11. Results of organ indices in mice during acute toxicity experiments ( ±S, n=10) Experiment Example 4 The application effect of the composition provided by this invention in improving sleep quality (oral administration experiment in human population). The effectiveness and safety of the compositions provided by this invention in improving sleep quality in people with sleep disorders were observed.

[0084] 1. Test Methods The study employed a randomized, double-blind, placebo-controlled design with a 21-day observation period, including a 7-day baseline period before administration, a 7-day administration period, and a 7-day follow-up period after administration.

[0085] 2. Subject population Sixty male and sixty female volunteers, aged 25–60 years (mean age 40.86 ± 7.56 years), with a Pittsburgh Sleep Quality Index (PSQI) score > 7 and who had not taken sedative-hypnotic drugs in the past month, participated in the study. All volunteers signed informed consent forms before the start of the experiment.

[0086] 3. Exclusion criteria Patients with a history of severe cardiovascular or cerebrovascular disease, mental illness, drug dependence, or allergy to the test ingredient.

[0087] 4. Sample size A total of 120 patients were included and randomly divided into an experimental group (n=60) and a placebo control group (n=60). There were no statistically significant differences in gender, age, or baseline PSSQI score between the two groups (P>0.05).

[0088] 5. Dosage design The experimental group took the oral liquid prepared according to the method of Example 1 of this invention at a dosage that meets human recommendations, while the control group took a placebo that had the same appearance and taste and did not contain any traditional Chinese medicine ingredients. The medication was taken twice daily, 30 minutes after breakfast and dinner, for 7 consecutive days.

[0089] 6. Observation Indicators Objective indicators: Daily sleep latency, total sleep time, and number of nighttime awakenings were recorded using a portable sleep monitoring device; the average of the first 7 days of use was taken as the baseline, and the average of the last 7 days of use was taken as the result.

[0090] Subjective indicators: Sleep quality was assessed using the PSQI scale, with a total score of 21 points. The higher the score, the worse the sleep quality. The duration of sleep onset was recorded daily. Sleep satisfaction was also assessed, with a total score of 5 points. The higher the score, the more satisfied the sleep.

[0091] 7. Statistical Methods Statistical analysis was performed using SPSS 27.0, and quantitative data were analyzed using... ±S indicates that the formula t-test was used to compare the results before and after administration within the group, and the independent t-test was used to compare the results between the groups. P < 0.05 was considered statistically significant, and P < 0.01 was considered extremely significant.

[0092] 8. Results of the human trial In the experimental group, the sleep latency was significantly shortened compared to baseline (P < 0.01), the total sleep time was significantly prolonged (P < 0.01), and the number of awakenings was significantly reduced (P < 0.01) after administration; there was no significant difference in the placebo control group (P > 0.05). In the experimental group, the PSQI total score was significantly reduced (P < 0.01), the time to fall asleep was significantly shortened (P < 0.01), and sleep satisfaction was significantly improved (P < 0.01); there was no significant difference in the placebo control group (P > 0.05). No adverse reactions such as dizziness or nausea occurred in either group during the trial, and blood routine and liver and kidney function tests were normal. The composition provided by this invention, after continuous administration for 7 days, can significantly shorten sleep latency, prolong total sleep time, reduce the number of awakenings, and improve subjective sleep quality, with good safety. The results are shown in Tables 12-13.

[0093] Table 12. Changes in objective sleep indicators in the two groups of subjects ( ±S, n=60) Table 13. Changes in subjective sleep indicators in the two groups of subjects ( ±S, n=60)

Claims

1. A composition having sleep-improving function, characterized in that: It is prepared from the following raw materials in the following weight proportions: Material A contains 50-100 parts of Acanthopanax senticosus, 30-50 parts of lotus seeds, 50-100 parts of jujube seed, 30 parts of lily bulb, 30 parts of longan, 30-50 parts of Poria cocos, 30 parts of Ophiopogon japonicus, 10-30 parts of Rehmannia glutinosa, and 10-30 parts of Gastrodia elata; Material B contains 2 parts of glutamic acid, 0.1 parts of vitamin B1, 0.1 parts of vitamin B6, and 0.1 parts of γ-aminobutyric acid.

2. The composition with sleep-improving function according to claim 1, characterized in that: Acanthopanax senticosus 50 parts, lotus seeds 50 parts, jujube seed 100 parts, lily bulb 30 parts, longan 30 parts, poria cocos 30 parts, ophiopogon japonicus 30 parts, rehmannia glutinosa 30 parts, gastrodia elata 10 parts, glutamic acid 2 parts, vitamin B1 0.1 parts, vitamin B6 1 part, γ-aminobutyric acid 0.1 parts.

3. A method for preparing a composition with sleep-improving function according to claim 1 or 2, characterized in that, Includes the following steps: (1) Crush and sieve material A, and collect the powder; (2) Prepare 0.05 mol / L phosphate buffer (pH=7.2), add the buffer solution at 10 times the mass of the raw material powder and mix well to prepare the "raw material-buffer solution system", and soak at room temperature (25±2℃) for 15~20 minutes; (3) Place distilled water in a beaker, immerse the plasma nozzle 0.5 cm below the water surface, and treat with plasma for 90 s to prepare plasma activated water (PAW). Mix the "raw material-buffer system" and PAW at a liquid-liquid ratio of 3:1 and then treat with ultrasound. Extraction temperature: 30~40℃, ultrasound parameters: power 300W, frequency 40kHz, plasma parameters: voltage 200V, current 0.5A, gas flow rate 40L / h, extraction times: 2 times, each time 30~45 minutes; (4) Use a combination of filter cloth and centrifugation to quickly separate the extract; (5) Concentrate the filtrate under reduced pressure; (6) Centrifuge the concentrate to remove impurities; filter the supernatant using an ultrafiltration membrane; (7) Add material B to the ultrafiltration permeate and mix well; (8) Freeze-dry the mixture; (9) Grind the dry paste powder into powder, sieve it, and store it in a sealed container.

4. The use of the composition according to claim 1 or 2 in the preparation of compositions for improving sleep function, characterized in that... The composition contains a carrier acceptable for the composition of claim 1, wherein the dosage form of the composition is a powder, granule, pill, tablet, capsule, tea, oral liquid, or ointment.

5. The use of the composition according to claim 1 or 2 in the preparation of a composition for improving sleep function, characterized in that... It is used to prolong sleep time, shorten sleep latency, or increase sleep depth.

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