A compound composition for synergistically improving sleep and a preparation method thereof

Abstract

This invention discloses a compound composition for synergistically improving sleep and its preparation method, relating to the fields of health food and functional technology. By weight, the raw materials include: 30-60 parts of broken-cell wall Ganoderma lucidum spore powder, 20-40 parts of roasted jujube seed extract, 5-20 parts of γ-aminobutyric acid (GABA), and 5-15 parts of lily extract, with an optimal ratio of 9:6:3:2. The composition strictly follows the traditional Chinese medicine principle of "principal, assistant, adjuvant, and guide" in its formulation, combined with modern nutritional research findings. The four ingredients synergistically enhance each other's effects, simultaneously shortening sleep latency, prolonging deep sleep duration, improving sleep maintenance disorders, and alleviating anxiety associated with insomnia. This solves the technical problems of existing sleep aids, such as single effects, lack of synergy, and significant side effects. Furthermore, all raw materials in the composition are nationally approved medicinal and edible materials and new food ingredients, ensuring safety and non-addictive properties. The preparation process is simple and easily industrialized, making it widely applicable in the preparation of various health foods and functional foods for improving sleep.

Description

Technical Field

[0001] This invention relates to the fields of health food and functional technology, specifically to a compound composition for synergistically improving sleep and its preparation method. Background Technology

[0002] With the accelerated pace of modern life and increasing work and life pressures, sleep disorders have become a prevalent public health and sub-health issue globally. According to the "2025 China Sleep Health White Paper," over 320 million people in my country suffer from varying degrees of sleep disorders, with an adult insomnia incidence rate as high as 39.2%, showing a trend of increasing year by year and affecting younger people. Long-term insomnia not only leads to poor concentration, memory decline, and weakened immunity, but also induces mental illnesses such as anxiety and depression, significantly increasing the risk of hypertension, diabetes, and cardiovascular disease, seriously impacting the physical and mental health and quality of life of the population.

[0003] Currently, clinical interventions for moderate to severe insomnia primarily rely on Western sedative-hypnotic drugs, mainly including benzodiazepines. Benzene dinitrates and non-benzodiazepines Receptor agonists, etc. Although these drugs can take effect quickly, they have significant technical drawbacks: they are prone to drug dependence and addiction, and withdrawal symptoms are likely to occur after discontinuation; they can easily cause adverse reactions such as hangover, dizziness, drowsiness, and memory loss; they can only relieve symptoms and cannot fundamentally repair damaged neuroregulatory function, making them unsuitable for long-term use and unable to meet the daily conditioning needs of people with mild to moderate insomnia.

[0004] Sleep aid products made from traditional Chinese medicine and food-grade ingredients have become a hot topic in industry research and development and a mainstream market trend due to their high safety, few side effects, and long-term suitability.

[0005] In existing technologies, jujube seed, Ganoderma lucidum, lily bulb, and γ-aminobutyric acid (hereinafter referred to as GABA) are all recognized sleep aid ingredients, and related products are emerging in large numbers. However, they generally have the following core technical defects: First, the compatibility lacks a scientific and rigorous logic. Most products are simply a combination of ingredients and do not follow the compatibility principle of "principal, assistant, adjuvant and guide" in traditional Chinese medicine. They cannot achieve synergistic effects between ingredients, and the sleep aid effect is singular. They can only solve the problem of difficulty falling asleep or shallow sleep, and cannot cover all the core symptoms of insomnia at the same time. They are difficult to improve sleep quality from the root. Second, the raw material ratios lack clear pharmacodynamic, toxicological, and compliance bases. Most ratios have not undergone systematic experimental verification, failing to maximize efficacy and even posing a risk of exceeding national food safety standards. The products lack stability, effectiveness, and compliance, failing to support the inventiveness requirements of invention patents. Third, existing compound formulas mostly consist of two or three raw materials, failing to fully combine the dual advantages of traditional Chinese medicine's calming and regulating effects with modern nutritional sedation and sleep aid. They cannot simultaneously address the immediate need for "quick sleep onset" and the fundamental need for "long-term improvement of sleep structure," resulting in significant limitations in clinical application and a narrow target population.

[0006] Therefore, developing a compound composition with a rigorous scientific formulation, significant synergistic effect, safety and non-addictive properties, and the ability to comprehensively improve multidimensional symptoms of insomnia solves many shortcomings of existing technologies, has important market value and social significance, and is in line with the research and development and regulatory guidelines of the health food industry. To this end, we propose a compound composition for synergistically improving sleep and its preparation method. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides a compound composition for synergistically improving sleep and its preparation method, thus solving the problems mentioned in the background art.

[0008] To achieve the above objectives, the present invention provides the following technical solution: a compound composition for synergistically improving sleep, wherein, by weight, the raw materials of the compound composition for synergistically improving sleep include: 30-60 parts of broken-cell wall Ganoderma lucidum spore powder, 20-40 parts of roasted jujube seed extract, 5-20 parts of γ-aminobutyric acid, and 5-15 parts of lily extract. The principal ingredient is broken-cell wall Ganoderma lucidum spore powder, which is sweet in taste and neutral in nature, and enters the heart, lung, liver, and kidney meridians. The Chinese Pharmacopoeia clearly records its core effects of "tonifying qi and calming the mind, relieving cough and asthma," and it is mainly used to treat restlessness, insomnia, and palpitations. Its core active ingredients are Ganoderma lucidum triterpenes and Ganoderma lucidum polysaccharides. Modern pharmacological studies have confirmed that it can achieve the effects of calming the mind and stabilizing the spirit by regulating the secretion of central neurotransmitters, inhibiting excessive sympathetic nerve excitation, and improving the body's microcirculation. This fundamentally improves sleep quality, reduces fatigue and weakness after waking, and simultaneously strengthens the body's resistance, improving the decline in immunity caused by long-term insomnia. It combines sleep aid with overall body conditioning, making it the principal ingredient in the formula.

[0009] The assistant ingredient is stir-fried jujube seed extract, which is sweet and sour in taste, neutral in nature, and enters the liver, gallbladder, and heart meridians. It is recognized by traditional Chinese medicine as the "primary medicine for nourishing the heart and calming the mind." The Chinese Pharmacopoeia records that it has the effects of "nourishing the heart and liver, calming the mind and soothing the nerves, and astringing sweat and promoting body fluids." It is mainly used to treat insomnia due to deficiency and restlessness, palpitations, and excessive dreaming. Its core active ingredients are jujube seed saponins and flavonoids. Modern pharmacological studies have confirmed that it can significantly prolong the duration of slow-wave sleep (deep sleep) and optimize sleep structure by activating the 5-hydroxytryptamine system in the brain and inhibiting the release of excitatory neurotransmitters such as glutamate. When combined with the principal ingredient, Ganoderma lucidum spore powder, it can synergistically enhance the calming and sleep-aiding effects, taking into account both sleep duration and sleep depth. It is the assistant ingredient in the formula.

[0010] Adjuvant: Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the human central nervous system. Modern nutritional studies have confirmed that it can rapidly inhibit neuronal over-excitation, reduce brain activity, and significantly shorten the sleep latency by specifically binding to GABA receptors in the brain, thus solving the core problem of "difficulty falling asleep." At the same time, it can effectively relieve negative emotions such as anxiety and tension. As an adjuvant in this composition, it can make up for the slow onset of action of traditional Chinese medicine components, achieving an organic combination of "rapid sleep aid" and "long-term conditioning." It also helps to enhance the calming effect of the principal and assistant herbs, thus serving as an adjuvant in the formula.

[0011] The guiding herb is lily extract, which is sweet in taste and slightly cold in nature. It enters the heart and lung meridians. According to the Chinese Pharmacopoeia, it has the effects of "nourishing yin and moistening the lungs, clearing the heart and calming the mind," and is mainly used to treat restlessness, palpitations, insomnia, and mental confusion. Its core active ingredients are lily polysaccharides and alkaloids, which can clear the heart and relieve restlessness, effectively improving anxiety and irritability associated with insomnia. At the same time, it can moderate the drying properties of roasted jujube seeds, harmonize the other herbs, and enhance the overall applicability of the formula. It is especially suitable for people with yin deficiency and excessive fire type insomnia, and is the guiding herb in the formula.

[0012] Preferably, the cell wall breakage rate of the broken Ganoderma lucidum spore powder is ≥98%, the content of Ganoderma lucidum triterpenes is ≥2%, the content of Ganoderma lucidum polysaccharides is ≥3%, and the moisture content is ≤8%. The preparation method of the broken-cell wall Ganoderma lucidum spore powder includes the following steps: S1: Collect mature spores of Ganoderma lucidum (red / purple); S2: Use air separation and a 120-150 mesh sieve to remove impurities, such as mud, sand, broken mushroom caps, and other impurities. S3: Dry at a low temperature of 40–60℃, control the moisture content to ≤8%, and prevent the degradation of active ingredients; S4: -60~-80℃ ultra-low temperature embrittlement for 2~3h, to improve the brittleness of the spore wall and facilitate cell wall breaking; S5: Employs a supersonic airflow pulverizer / vibration mill for low-temperature physical cell wall disruption, with temperature controlled at ≤40℃ throughout the process to ensure a cell wall disruption rate of ≥98%; S6: Remove coarse residue by passing through an 80–100 mesh sieve, then sterilize by irradiation.

[0013] Preferably, the content of jujuboside A in the roasted jujube seed extract is ≥0.5%; The preparation method of the stir-fried jujube seed extract includes the following steps: S1: Remove impurities from jujube seeds, wash them, and dry them at 40–50℃ with a moisture content of ≤8%; S2: Stir-fry at 130–160℃ for 3–10 minutes, until slightly yellow and caramelized, then let cool and set aside. S3: Crush using a pulverizer and pass through a 20–40 mesh sieve; S4: Add 10–15 times the amount of purified water, extract twice at 85–95℃, each time for 1.5–2 hours, combine the extracts, centrifuge and filter to remove the residue; S5: Concentrate under reduced pressure using a vacuum concentrator (temperature 60–70℃, vacuum -0.06 to -0.08MPa) to a clear paste with a relative density of 1.10–1.20; S6: Add 95% ethanol to a concentration of 60%–70%, let stand for 12–24 hours, and take the supernatant to recover the ethanol; S7: Vacuum drying yields a brownish-yellow powder; S8: The test result for jujube seed saponin A is ≥0.5%, and the moisture, ash, and microbial content are qualified.

[0014] Preferably, the lily extract contains ≥10% lily polysaccharides; its preparation method includes the following steps: S1: Remove impurities and wash dried lily scales, dry them at below 60℃, and pulverize them through a 20-40 mesh sieve; S2: Add 10–15 times the amount of purified water, extract twice at 85–95℃, 1.5–2 hours each time, and combine the extracts; S3: Obtain a clear extract by centrifugation and filtration; S4: Concentrate under reduced pressure at 60–70℃ to a clear extract with a relative density of 1.15–1.25; S5: Add 95% ethanol to a concentration of 70%, let stand for 12–24 hours, discard the precipitate and take the supernatant, and recover the ethanol; S6: Vacuum drying was performed using a vacuum dryer to obtain a pale yellow powder; S7: The powder is tested, and the lily polysaccharide content is ≥10%, while the moisture, ash content, and microbial content are qualified.

[0015] Preferably, the γ-aminobutyric acid is a food-grade raw material that meets national food safety standards and has a purity of ≥99%.

[0016] A method for preparing a compound composition that synergistically improves sleep includes the following steps: Step 1: Pass the broken-cell wall Ganoderma lucidum spore powder, stir-fried jujube seed extract, γ-aminobutyric acid, and lily extract through an 80-100 mesh sieve, and set them aside after passing the quality inspection according to the quality standards. Step 2: Weigh each pretreated raw material according to the weight ratio, and control the weighing error within ±0.5%; Step 3: Put all the weighed raw materials into the three-dimensional motion mixer and mix for 20 to 30 minutes until the material mixing uniformity RSD is ≤5%. This can ensure the material mixing uniformity to the greatest extent, avoid raw material stratification, and ensure the uniformity of the effective ingredient content of each unit of preparation.

[0017] Step 4: Mix the materials thoroughly and then process them into the desired finished dosage form using conventional formulation processes.

[0018] Preferably, in step three, the rotation speed of the three-dimensional motion mixer is 15-20 r / min, and the mixing time is 25 minutes.

[0019] Preferably, the dosage form of the composition is any one of hard capsules, tablets, granules, powders, and oral liquids, with hard capsules being the preferred dosage form. This dosage form allows for precise control of the dosage, is convenient to take, has good product stability, and can effectively isolate air and moisture, preventing the oxidation and degradation of the active ingredients.

[0020] Application of a compound composition that synergistically improves sleep in the preparation of products that improve sleep.

[0021] Preferably, the product is any one of health food, functional food, or special dietary food, and the product is used for at least one of the following purposes: shortening sleep latency, prolonging deep sleep duration, improving sleep maintenance disorders, and relieving anxiety associated with insomnia.

[0022] This invention provides a compound composition for synergistically improving sleep and its preparation method, which has the following beneficial effects: This compound composition for synergistically improving sleep and its preparation method, through the combination of broken-cell wall Ganoderma lucidum spore powder, roasted jujube seed extract, γ-aminobutyric acid (GABA), and lily extract, strictly follows the traditional Chinese medicine principle of "principal, assistant, adjuvant, and guide" in its formulation, combined with modern nutritional research findings. The four ingredients work synergistically to achieve multi-target synergistic effects, comprehensively improving insomnia symptoms. The compound composition targets four core areas: "central neurotransmitter regulation, sleep structure optimization, anxiety relief, and body conditioning." It can simultaneously address five core insomnia symptoms: difficulty falling asleep, shallow sleep, frequent awakenings at night, fatigue after waking, and insomnia accompanied by anxiety. This overcomes the technical limitations of existing sleep aids with only single-effect properties. GABA can... This product rapidly shortens the sleep latency period, addressing the immediate need for sleeplessness among insomniacs. The combination of roasted jujube seeds, Ganoderma lucidum spore powder, and lily bulbs provides long-term conditioning, optimizing sleep structure and repairing damaged nerve regulation functions, thus improving insomnia at its root. It achieves a combination of rapid onset of action and long-term cure, overcoming the shortcomings of existing products that only provide symptomatic relief. Furthermore, all raw materials are nationally approved medicinal and edible ingredients or new food ingredients, without the addictive properties or hangover effects of Western sedative-hypnotic drugs, and have no adverse reactions. It can be taken long-term and is suitable not only for those with primary insomnia but also for those with secondary insomnia such as those experiencing stress, menopause, sub-health conditions, or yin deficiency with excessive fire. Its applicability is far greater than existing products. Attached Figure Description

[0023] Figure 1 This is a schematic diagram showing the results of the subthreshold dose of sodium pentobarbital hypnosis experiment in mice of this invention. Figure 2 This is a schematic diagram of the results of the suprathreshold dose sleep experiment of sodium pentobarbital in mice in various groups according to the present invention. Detailed Implementation

[0024] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0025] Example 1 The present invention provides a technical solution: a compound composition for synergistically improving sleep, which is composed of the following raw materials in parts by weight: 45 parts of broken-cell wall Ganoderma lucidum spore powder, 30 parts of stir-fried jujube seed extract, 15 parts of γ-aminobutyric acid, and 10 parts of lily extract.

[0026] The preparation method includes the following steps: First, pass the broken-cell wall Ganoderma lucidum spore powder, stir-fried jujube seed extract, γ-aminobutyric acid, and lily extract through an 80-100 mesh sieve to remove lumps and impurities. Then, conduct a full inspection according to the above quality standards. Once qualified, they can be used for future use. According to the above weight ratio, use an electronic scale with an accuracy of not less than one-thousandth to weigh each pre-treated raw material, and control the weighing error within ±0.5%. All weighed raw materials were simultaneously put into the three-dimensional motion mixer. The speed was set to 15-20 r / min and the mixture was mixed for 20-30 minutes. After the mixing was completed, a sample was taken for testing. The material mixing uniformity RSD was 3.2%, which met the requirements. The well-mixed materials are filled into No. 0 gelatin hard capsules according to the conventional hard capsule formulation process, with each capsule containing 0.5g. After passing all inspections, the capsules are packaged and stored.

[0027] Example 2 Based on Example 1, the difference from Example 1 is that a compound composition for synergistically improving sleep is composed of the following raw materials in parts by weight: 40 parts of broken-cell wall Ganoderma lucidum spore powder, 35 parts of stir-fried jujube seed extract, 10 parts of γ-aminobutyric acid, and 15 parts of lily extract.

[0028] Example 3 Based on Example 1, the difference from Example 1 is that a compound composition for synergistically improving sleep is composed of the following raw materials in parts by weight: 50 parts of broken-cell wall Ganoderma lucidum spore powder, 25 parts of stir-fried jujube seed extract, 20 parts of γ-aminobutyric acid, and 5 parts of lily extract.

[0029] Example 4 Based on Example 1, the difference from Example 1 is that a compound composition for synergistically improving sleep is composed of the following raw materials in parts by weight: 30 parts of broken-cell wall Ganoderma lucidum spore powder, 40 parts of stir-fried jujube seed extract, 15 parts of γ-aminobutyric acid, and 15 parts of lily extract.

[0030] Example 5 Based on Example 1, the difference from Example 1 is that a compound composition for synergistically improving sleep is composed of the following raw materials in parts by weight: 60 parts of broken-cell wall Ganoderma lucidum spore powder, 20 parts of stir-fried jujube seed extract, 10 parts of γ-aminobutyric acid, and 10 parts of lily extract.

[0031] Experimental Example 1 Orthogonal experimental verification: To verify the scientific validity and optimality of the formulation of this invention, L9(3) was used. 4 An orthogonal experiment was conducted, using mouse sleep duration as the core evaluation index, to optimize and verify the ratio of the four ingredients. The experimental design and results are as follows: The experimental factors and levels were set as follows: broken-cell wall Ganoderma lucidum spore powder (A), stir-fried jujube seed extract (B), γ-aminobutyric acid (C), and lily extract (D). Each factor was set with 3 levels. The factor level table is shown in Table 1.

[0032] Table 1. Factor Level Table for Orthogonal Experiment Table 1

[0033] Experimental methods and results are as follows: L9(3)4 Nine groups of experiments were designed using an orthogonal array. For each group of experiments, a corresponding compound composition was prepared. The sleep duration of mice in each group was detected using the suprathreshold dose of sodium pentobarbital. The experimental method was the same as in Experiment 2. The experimental results and range analysis are shown in Table 2.

[0034] Table 2: Results of Orthogonal Experiments and Range Analysis Table 2

[0035] The range analysis results showed that the order of influence of the four ingredients on the compound sleep-aiding effect was: broken-cell wall Ganoderma lucidum spore powder > stir-fried jujube seed extract > γ-aminobutyric acid > lily extract. The optimal combination verified by the orthogonal experiment was A2B2C2D2, that is, 45 parts of broken-cell wall Ganoderma lucidum spore powder, 30 parts of stir-fried jujube seed extract, 15 parts of γ-aminobutyric acid, and 10 parts of lily extract, which is completely consistent with the optimal ratio of the present invention, proving that the ratio of the present invention has scientific and rigorous experimental support and is not a conventional choice for those skilled in the art.

[0036] Experiment Example 2: Pharmacodynamic Verification Experiment To verify the synergistic sleep-aiding effect of the compound composition of this invention, a mouse pentobarbital sodium-induced sleep experiment was conducted using the sleep improvement function test method specified in the national "Standardized Procedures and Test Methods for Functional Evaluation of Health Foods". The experimental design and results are as follows: 1. Experimental Materials 1.1 Experimental animals: SPF-grade Kunming mice, half male and half female, weighing 18-22g, provided by a unit with an experimental animal production license, acclimatized for 3 days, with free access to food and water, ambient temperature of 22±2℃, and 12h light-dark alternation. 1.2 Test Samples: Compound compositions prepared in Examples 1-3; Comparative Example 1 (single broken-cell wall Ganoderma lucidum spore powder), Comparative Example 2 (single roasted jujube seed extract), Comparative Example 3 (single γ-aminobutyric acid), Comparative Example 4 (GABA-deficient composition: 45 parts broken-cell wall Ganoderma lucidum spore powder, 30 parts roasted jujube seed extract, 10 parts lily extract), Comparative Example 5 (Ganoderma lucidum spore powder-deficient composition: 30 parts roasted jujube seed extract, 15 parts γ-aminobutyric acid, 10 parts lily extract), Comparative Example 6 (conventional formula in the prior art: 20 parts broken-cell wall Ganoderma lucidum spore powder, 40 parts roasted jujube seed extract, 30 parts γ-aminobutyric acid, 10 parts lily extract); 1.3. Reagents and instruments: sodium pentobarbital, physiological saline, electronic balance, gavage syringe, stopwatch, constant temperature incubator.

[0037] 2. Experimental Methods Mice were randomly divided into 12 groups of 10 each: blank control group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, Comparative Example 5 group, Comparative Example 6 group, and positive control group.

[0038] Administration methods for each group: Except for the blank control group which was given an equal volume of physiological saline and the positive control group which was given 2 mg / kg bw of hypnotic drug, the other groups were administered the corresponding test sample by gavage at a dose of 0.2 g / kg bw once a day for 7 consecutive days. The following experiment was conducted 1 hour after the last administration.

[0039] 2.1 Subthreshold dose of sodium pentobarbital for hypnosis: After the last administration, mice in each group were injected intraperitoneally with a subthreshold dose of sodium pentobarbital of 30 mg / kg. The disappearance of the righting reflex for ≥1 minute was used as the criterion for falling asleep. The number of mice falling asleep in each group within 30 minutes was recorded, the sleep rate was calculated, and the differences between the groups were compared.

[0040] 2.2 Suprathreshold dose sleep experiment of sodium pentobarbital: After the last administration, mice in each group were intraperitoneally injected with a suprathreshold dose of sodium pentobarbital of 45 mg / kg. Sleep began when the righting reflex disappeared and ended when the righting reflex returned. The sleep latency (time from the injection of sodium pentobarbital to the disappearance of the righting reflex) and sleep duration of each mouse were recorded, and the differences between the groups were compared.

[0041] Experimental results: Experimental data are expressed as mean ± standard deviation. Statistical analysis was performed using SPSS software. P < 0.05 was considered statistically significant. The experimental results are shown in Tables 3 and 4. Figure 1 and Figure 2 , Table 3 Results of the subthreshold dose of sodium pentobarbital for hypnosis in each group of mice Table 3

[0042] Table 4 Results of the suprathreshold dose sodium pentobarbital sleep experiment in each group of mice Table 4

[0043] Experimental conclusions (1) The results of the subthreshold dose hypnosis experiment showed that the sleep rate of mice in the 1-3 groups of the present invention was significantly higher than that of the blank control group, the single raw material comparison group, the tasteless comparison group and the prior art comparison group (P<0.05). Among them, the sleep rate of the optimal ratio group in Example 1 was as high as 90%, which was comparable to that of the positive control group and much higher than that of the single raw material group (30%~50%), proving that the compound composition of the present invention has a significant synergistic hypnotic effect.

[0044] (2) The results of the suprathreshold dose sleep experiment showed that the sleep latency and sleep duration of the mice in Examples 1-3 of this invention were significantly shortened. The differences were statistically significant compared with the blank control group, the single ingredient comparison group, the flavorless comparison group, and the prior art comparison group (P<0.05). Among them, the sleep latency of Example 1 group was shortened by 52.7% and the sleep duration was extended by 199.2% compared with the blank control group. The effect was significantly better than all comparison groups, which proved that the combination of the four ingredients achieved a synergistic sleep-aiding effect of 1+1>2.

[0045] (3) Comparison of the flavor-deficient control group and the first example group shows that the sleep-aiding effect of the compound is significantly reduced after removing any one ingredient, proving that the four ingredients of the present invention are indispensable, the ratio is scientific and rigorous, and it is irreplaceable.

[0046] (4) Comparing the existing technology comparative examples and Example 1, it can be seen that the sleep-aiding effect of the optimal ratio of the present invention is significantly better than that of the conventional ratio of the existing technology, which proves that the present invention has outstanding substantive features and significant progress, and meets the inventiveness requirements of the invention patent.

[0047] Experiment Example 3: Safety Verification Experiment To verify the food safety of the compound composition of this invention, an acute oral toxicity test in mice was conducted as specified in the "Procedures and Methods for Food Safety Toxicology Evaluation". The experimental methods and results are as follows: Experimental materials: 20 SPF-grade Kunming mice, half male and half female, weighing 18-22g; the compound composition prepared in Example 1.

[0048] Experimental methods: The maximum tolerated dose method was used. Mice were fasted for 16 hours before the experiment, but had free access to water. The compound composition was prepared into a suspension with physiological saline at the maximum dose of 20 g / kg body weight and administered to the mice by gavage once. The mice were observed for 14 consecutive days after gavage. The general condition, diet, activity, weight changes, poisoning symptoms and mortality of the mice were recorded. After the observation period, the mice were grossly dissected to examine the lesions of the major organs.

[0049] Results: During the 14-day observation period, all mice showed good growth, normal diet and activity, steady weight gain, no signs of poisoning, and no deaths. Dissection of the mice after the experiment revealed no visible abnormalities in major organs such as the heart, liver, spleen, lungs, and kidneys.

[0050] Experimental conclusion: The maximum tolerated acute oral dose of the compound composition of this invention in mice is greater than 20 g / kg·bw. According to the acute toxicity classification standard, it belongs to the practically non-toxic category, has high food safety, and meets the safety requirements of health food and functional food.

[0051] The compound composition for synergistically improving sleep provided by this invention has widely available and controllable raw materials, a scientifically rigorous formulation, significant synergistic effects, and is safe with no side effects. It can comprehensively improve the multidimensional symptoms of insomnia. At the same time, the preparation method provided by this invention is simple, the parameters are controllable, no special equipment is required, the product has good stability, is suitable for large-scale industrial production, and can be widely used in the preparation of various health foods and functional foods for improving sleep. It has good industrial applicability and market application prospects.

[0052] In summary, the compound composition for synergistically improving sleep and its preparation method involve first passing the broken-cell wall Ganoderma lucidum spore powder, stir-fried jujube seed extract, γ-aminobutyric acid, and lily extract through an 80-100 mesh sieve, and then using them after passing the quality standard inspection. Then, according to the weight ratio, weigh each pre-treated raw material, namely 45 parts of broken-cell wall Ganoderma lucidum spore powder, 30 parts of roasted jujube seed extract, 15 parts of γ-aminobutyric acid, and 10 parts of lily extract. The mass ratio of the raw materials is 9:6:3:2, and the weighing error is controlled within ±0.5%. Then, put all the weighed raw materials into the three-dimensional motion mixer and mix for 20-30 minutes until the material mixing uniformity RSD ≤ 5%; Finally, the well-mixed materials are processed into the required finished dosage form according to conventional formulation processes.

[0053] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A compound composition for synergistically improving sleep, characterized in that: The ingredients of the compound composition for synergistically improving sleep, by weight, include: 30-60 parts of broken-cell wall Ganoderma lucidum spore powder, 20-40 parts of stir-fried jujube seed extract, 5-20 parts of γ-aminobutyric acid, and 5-15 parts of lily extract.

2. The compound composition for synergistically improving sleep according to claim 1, characterized in that: The cell wall breakage rate of the broken Ganoderma lucidum spore powder is ≥98%, the content of Ganoderma lucidum triterpenes is ≥2%, the content of Ganoderma lucidum polysaccharides is ≥3%, and the moisture content is ≤8%. The preparation method of the broken-cell wall Ganoderma lucidum spore powder includes the following steps: S1: Collect mature spores of Ganoderma lucidum (red / purple); S2: Use air separation and a 120-150 mesh sieve to remove impurities, such as mud, sand, broken mushroom caps, and other impurities. S3: Dry at a low temperature of 40~60℃, control the moisture content to ≤8%, and prevent the degradation of active ingredients; S4: -60~-80℃ ultra-low temperature embrittlement for 2~3h, to improve the brittleness of the spore wall and facilitate cell wall breaking; S5: Employs supersonic airflow pulverization / vibration milling at low temperature for cell wall disruption, with temperature controlled at ≤40℃ throughout the process to ensure a cell wall disruption rate of ≥98%; S6: Remove coarse residue by passing through an 80–100 mesh sieve, then sterilize by irradiation.

3. The compound composition for synergistically improving sleep according to claim 1, characterized in that: The content of jujube seed saponin A in the roasted jujube seed extract is ≥0.5%; The preparation method of the stir-fried jujube seed extract includes the following steps: S1: Remove impurities from jujube seeds, wash them, and then dry them at 40-50℃ with a moisture content of ≤8%; S2: Stir-fry at 130-160℃ for 3-10 minutes until slightly yellow and fragrant, then let cool and set aside. S3: Crush using a pulverizer and pass through a 20–40 mesh sieve; S4: Add 10-15 times the amount of purified water, extract twice at 85-95℃, 1.5-2 hours each time, combine the extracts, centrifuge and filter to remove residue; S5: Concentrate under reduced pressure using a vacuum concentrator (temperature 60–70℃, vacuum -0.06 to -0.08 MPa) to a clear paste with a relative density of 1.10 to 1.20; S6: Add 95% ethanol to a concentration of 60%–70%, let stand for 12–24 hours, and take the supernatant to recover the ethanol; S7: Vacuum drying yields a brownish-yellow powder; S8: The content of jujube seed saponin A is ≥0.5%, and the moisture, ash and microbial content are qualified.

4. The compound composition for synergistically improving sleep according to claim 1, characterized in that: The lily extract contains ≥10% lily polysaccharides; its preparation method includes the following steps: S1: Remove impurities from lily scales and wash them, dry them below 60℃, pulverize them and pass them through a 20-40 mesh sieve; S2: Add 10–15 times the amount of purified water, extract twice at 85–95℃, 1.5–2 hours each time, and combine the extracts; S3: Obtain a clear extract by centrifugation and filtration; S4: Concentrate under reduced pressure at 60–70°C to a clear extract with a relative density of 1.15–1.25; S5: Add 95% ethanol to a concentration of 70%, let stand for 12–24 hours, discard the precipitate and take the supernatant, and recover the ethanol; S6: Vacuum drying was performed using a vacuum dryer to obtain a pale yellow powder; S7: The powder is tested, and the lily polysaccharide content is ≥10%, while the moisture, ash content, and microbial content are qualified.

5. The compound composition for synergistically improving sleep according to claim 1, characterized in that: The γ-aminobutyric acid is a food-grade raw material that meets national food safety standards, with a purity of ≥99%.

6. A method for preparing a compound composition for synergistically improving sleep according to any one of claims 1-5, characterized in that: Includes the following steps: Step 1: Pass the broken-cell wall Ganoderma lucidum spore powder, stir-fried jujube seed extract, γ-aminobutyric acid, and lily extract through an 80-100 mesh sieve, and set them aside after passing the quality inspection according to the quality standards. Step 2: Weigh each pretreated raw material according to the weight ratio, and control the weighing error within ±0.5%; Step 3: Add all weighed raw materials into the three-dimensional motion mixer and mix for 20-30 minutes until the material mixing uniformity RSD ≤ 5%; Step 4: Mix the materials thoroughly and then process them into the desired finished dosage form using conventional formulation processes.

7. The method for preparing a compound composition for synergistically improving sleep according to claim 6, characterized in that: In step three, the rotation speed of the three-dimensional motion mixer is 15-20 r / min, and the mixing time is 25 minutes.

8. The compound composition for synergistically improving sleep and its preparation method according to claim 6, characterized in that: The dosage form of the composition is any one of hard capsules, tablets, granules, powders, or oral liquids.

9. The use of the compound composition for synergistically improving sleep according to claim 1 in the preparation of products for improving sleep.

10. The application of the compound composition for synergistically improving sleep according to claim 9 in the preparation of products for improving sleep, characterized in that, The product is any one of health food, functional food, or special dietary food, and is used for at least one of the following purposes: shortening sleep latency, prolonging deep sleep duration, improving sleep maintenance disorders, and relieving anxiety associated with insomnia.

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