Traditional Chinese medicine composition for improving sleep as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for improving sleep as well as a preparation method and application thereof, when traditional Chinese medicinal materials are used as starting raw materials, the traditional Chinese medicine composition is prepared from the following components in percentage by weight: 3.59-78.62% of spina date seeds, 0.61-14.97% of schisandra chinensis, 0.39-54.73% of polygala tenuifolia, 4.71-74.45% of poria cocos, 1.12-46.86% of cape jasmine and 0.16-7.38% of ginseng. When a traditional Chinese medicine extract is taken as an initial raw material, the traditional Chinese medicine composition is prepared from the following components in percentage by weight: 2.10 to 56.5 percent of a spina date seed extract, 1.34 to 38.93 percent of a schisandra chinensis extract, 2.92 to 61.43 percent of a polygala tenuifolia extract, 3.39 to 46.72 percent of a poria cocos extract, 1.46 to 51.20 percent of a gardenia extract and 0.56 to 21.60 percent of a ginseng extract. The traditional Chinese medicine composition can remarkably improve body sleep, consolidate the foundation, strengthen the brain, soothe the nerves and tonify qi.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine and health food, specifically relating to a traditional Chinese medicine composition for improving sleep, its preparation method and application. Background Technology

[0002] Sleep is an indispensable physiological need for humans. Healthy and sufficient sleep helps eliminate fatigue, restore energy, and improve immunity. Insomnia is a common sleep disorder in clinical practice, which can manifest as difficulty falling asleep, difficulty maintaining sleep, and symptoms such as daytime fatigue, decreased attention, irritability, and reduced cognitive function. Statistics show that about 30% of people worldwide experience one or more symptoms of insomnia. The "2022 China National Health White Paper" shows that 57% of adults suffer from varying degrees of sleep disorders. Improving sleep quality has become a key concern in the field of public health. Insomnia is a major factor affecting normal sleep, causing great discomfort and suffering in patients' daily lives. Long-term insomnia can induce various cardiovascular diseases and diabetes, increasing the burden on patients, and in severe cases, it can lead to death. According to relevant reports, about 15% of the population has suffered from pain or distress caused by insomnia.

[0003] In recent years, medications for treating various types of insomnia have been widely used. Currently, the drugs most commonly used in clinical practice for treating insomnia are chemical drugs, including benzodiazepines. Receptor agonists, melatonin and its receptor agonists, antidepressants, antipsychotics, and antihistamines are among the medications mentioned. These drugs have significant side effects, such as daytime sleepiness, cognitive impairment, and withdrawal symptoms. While their efficacy in treating acute insomnia has been well-proven, their effectiveness in treating chronic insomnia is poor, possibly due to tolerance. Furthermore, long-term use of these drugs has a profound impact on the physiological structure of sleep, potentially leading to pathophysiological changes in related tissues. For example, melatonin is an indole hormone secreted by the pineal gland that regulates the sleep-wake cycle. Clinically, exogenous melatonin supplementation commonly uses rameltetin and agomelatine, which can normalize disrupted circadian rhythms. However, long-term use of melatonin can inhibit pineal gland secretion, reducing endogenous melatonin levels and thus causing insomnia again. Simultaneously, excessive melatonin intake can also lead to lethargy and persistent drowsiness in insomnia patients.

[0004] Due to the various toxic side effects of chemical drugs, researchers are inclined to develop new therapeutic drugs with fewer side effects and stronger sleep-improving effects, leading to a growing interest in traditional Chinese medicine. Traditional Chinese medicine is a traditional and advantageous pharmaceutical industry in my country, employing a holistic approach and syndrome differentiation as its treatment principles, giving it unique advantages in treating insomnia. Developing safe and effective sleep-improving functional foods from medicinal and edible herbs has become an important development trend and direction for sleep improvement products. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition for improving sleep, its preparation method and application. This traditional Chinese medicine composition can significantly improve sleep, strengthen the body's foundation and brain, calm the mind and invigorate qi, and can prevent and treat long-term insomnia caused by sleep disorders.

[0006] To achieve the above objectives, the present invention provides a traditional Chinese medicine composition for improving sleep. When using traditional Chinese medicinal materials as starting materials, it is prepared from the following components in weight percentage: 3.59-78.62% Ziziphus jujuba seed, 0.61-14.97% Schisandra chinensis fruit, 1.50-54.73% Polygala tenuifolia fruit, 4.71-71.86% Poria cocos, 1.12-46.86% Gardenia jasminoides fruit, and 0.16-7.38% Ginseng. When using traditional Chinese medicine extracts as starting materials, it is prepared from the following components in weight percentage: 2.10-56.5% Ziziphus jujuba seed extract, 1.34-38.93% Schisandra chinensis fruit extract, 2.92-61.43% Polygala tenuifolia fruit extract, 3.39-46.72% Poria cocos extract, 1.46-51.20% Gardenia jasminoides fruit extract, and 0.56-21.60% Ginseng extract.

[0007] Preferably, when using Chinese medicinal herbs as starting materials, the extract is prepared from the following components in weight percentage: 3.59-9.35% Ziziphus jujuba seed, 1.44-14.97% Schisandra chinensis fruit, 1.50-4.61% Polygala tenuifolia fruit, 55.32-71.86% Poria cocos, 1.12-27.66% Gardenia jasminoides fruit, and 1.20-7.38% Ginseng. When using Chinese medicinal herb extracts as starting materials, the extract is prepared from the following components in weight percentage: 2.10-6.08% Ziziphus jujuba seed extract, 3.38-38.93% Schisandra chinensis fruit extract, 2.92-8.10% Polygala tenuifolia fruit extract, 32.41-46.72% Poria cocos extract, 1.46-32.41% Gardenia jasminoides fruit extract, and 3.89-21.60% Ginseng extract.

[0008] Preferably, the traditional Chinese medicine composition is prepared into oral liquid, tablets, capsules or granules by adding medicinal or edible excipients.

[0009] Preferably, the extract includes extracts obtained by water decoction and extracts obtained by ethanol extraction.

[0010] Preferably, the excipient is one or more of the following: microcrystalline silica gel, sodium carboxymethyl starch, dextrin, lactose, starch, sucrose, glucose, microcrystalline cellulose, mannose, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, steviol, sorbitol, talc, and magnesium stearate.

[0011] Preferably, the excipient is an auxiliary material composed of micronized silica gel, sorbitol, sodium carboxymethyl starch, microcrystalline cellulose, talc, and magnesium stearate.

[0012] To achieve the above-mentioned objective, the present invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition for improving sleep. When traditional Chinese medicinal materials are used as starting materials, the preparation method includes the following steps:

[0013] S1. Take jujube seed, schisandra fruit, polygala root, gardenia fruit and ginseng and extract them together. Extract them 2-3 times with 50-85% ethanol. Combine the decoctions and concentrate the filtrate under reduced pressure to a relative density of 1.20-1.30 at 65℃. Recover the ethanol to obtain concentrated solution I.

[0014] S2. Poria cocos is decocted twice with 6-10 times the amount of water. The decoctions are combined and concentrated to a relative density of 1.10-1.20 at 65°C. Ethanol is added and stirred to make the alcohol content reach 60-85% by volume percentage. The mixture is allowed to stand, filtered, and the filtrate is concentrated under reduced pressure to a relative density of 1.20-1.30 at 65°C. The ethanol is then recovered to obtain concentrated solution II.

[0015] S3. Combine concentrated liquid I and concentrated liquid II, add water and excipients to prepare oral liquid, or spray dry the concentrated liquid and add excipients to prepare capsules, tablets or granules;

[0016] When using extracts of traditional Chinese medicine as starting materials, the preparation method includes the following steps:

[0017] Extracts of jujube seed, schisandra fruit, polygala root, poria cocos, gardenia fruit, and ginseng are prepared into oral liquids, capsules, tablets, and granules with appropriate excipients.

[0018] To achieve the above-mentioned objectives, the present invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of drugs or functional foods for improving sleep.

[0019] The active ingredients extracted from the raw materials of this invention are scientifically formulated. This invention optimizes and screens traditional Chinese medicine compositions with sleep-improving effects in direct sleep experiments, pentobarbital sodium sleep time prolongation experiments, pentobarbital sodium sleep latency experiments, and p-chlorophenylalanine-induced insomnia models, and confirms their sleep-improving effects, providing a new treatment option for the clinical prevention or treatment of sleep disorders and chronic insomnia. Attached Figure Description

[0020] Figure 1 This is the effect of the traditional Chinese medicine composition in Example 6 on prolonging the sodium pentobarbital sleep time (ST) in normal mice;

[0021] Figure 2 This describes the effect of the herbal composition in Example 6 on the sleep latency (SL) of normal mice.

[0022] Figure 3This describes the effect of each test drug in Example 7 on prolonging sodium pentobarbital sleep time (ST) in p-chlorophenylalanine-induced insomnia mice;

[0023] Figure 4 This describes the effect of each test drug in Example 7 on the serotonin (5-HT) content in the hippocampus of insomniac mice;

[0024] Figure 5 This describes the effect of each test drug in Example 7 on the GABA content in the hippocampus of insomniac mice;

[0025] Figure 6 This is a schematic diagram showing the effects of each test drug on the hippocampal lesions of insomnia mice before and after the experiment in Example 7. In the diagram, A to E are, in order: blank group, model group, low-dose group, medium-dose group, and high-dose group.

[0026] In the above figure: compared with the blank group, # P<0.05, ## P<0.01, ### P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001. Detailed Implementation

[0027] The present invention will be further described in detail below with reference to specific embodiments.

[0028] 1. Research on extraction process

[0029] Formula 1: Ziziphus jujuba seed (71.6 mg / kg BW), Schisandra chinensis (28.7 mg / kg BW), Polygala tenuifolia (91.87 mg / kg BW), Poria cocos (1102.2 mg / kg BW), Gardenia jasminoides (551.1 mg / kg BW), and Panax ginseng (146.96 mg / kg BW); the corresponding Chinese herbal composition is prepared from the following ingredients in weight percentage: Ziziphus jujuba seed 3.59%, Schisandra chinensis 1.44%, Polygala tenuifolia 4.61%, Poria cocos 55.32%, Gardenia jasminoides 27.66%, and Panax ginseng 7.38%; Formula 1 is the formula described in Example 1 obtained through the following extraction process.

[0030] S1. Take jujube seed, schisandra fruit, polygala root, gardenia fruit and ginseng according to formula one and combine them. Extract with 50-85% ethanol 2-3 times. Combine the decoctions and concentrate the filtrate under reduced pressure to a relative density of 1.20-1.30 at 65℃. Recover the ethanol to obtain concentrated solution I.

[0031] S2. Take Poria cocos according to formula one and decoct it twice with 6-10 times the amount of water. Combine the decoctions and concentrate them to a relative density of 1.10-1.20 at 65℃. Add ethanol and stir to make the alcohol content reach 60-85% by volume percentage. Let it stand, filter, and concentrate the filtrate under reduced pressure to a relative density of 1.20-1.30 at 65℃. Recover the ethanol to obtain concentrated solution II.

[0032] S3. Combine concentrated solution I and concentrated solution II, both of which contain extracts of traditional Chinese medicinal materials.

[0033] Formula 2: Ziziphus jujuba seed (136.2 mg / kg BW), Schisandra chinensis (108.8 mg / kg BW), Polygala tenuifolia (696.27 mg / kg BW), Poria cocos (130.6 mg / kg BW), Gardenia jasminoides (130.6 mg / kg BW), and Panax ginseng (69.64 mg / kg BW); the corresponding Chinese herbal composition is prepared from the following ingredients in weight percentage: Ziziphus jujuba seed 10.71%, Schisandra chinensis 8.55%, Polygala tenuifolia 54.73%, Poria cocos 10.27%, Gardenia jasminoides 10.27%, and Panax ginseng 5.47%; the formula obtained by the extraction process of this invention is the same as the formula described in Example 2; the extraction process is the same as the extraction process described in Formula 1 above.

[0034] Formula 3: Ziziphus jujuba seed (206.8 mg / kg BW), Schisandra chinensis (330.95 mg / kg BW), Polygala tenuifolia (33.07 mg / kg BW), Poria cocos (1588.6 mg / kg BW), Gardenia jasminoides (24.80 mg / kg BW), and Panax ginseng (26.48 mg / kg BW); the corresponding Chinese herbal composition is prepared from the following ingredients in weight percentage: Ziziphus jujuba seed 9.35%, Schisandra chinensis 14.97%, Polygala tenuifolia 1.50%, Poria cocos 71.86%, Gardenia jasminoides 1.12%, and Panax ginseng 1.20%; the formula obtained by the extraction process of this invention is the same as the formula described in Example 3; the extraction process is the same as that described in Formula 1 above.

[0035] Formula 4: Ziziphus jujuba seed (453.4 mg / kg BW), Schisandra chinensis (11.35 mg / kg BW), Polygala tenuifolia (290.13 mg / kg BW), Poria cocos (217.60 mg / kg BW), Gardenia jasminoides (870.40 mg / kg BW), and Panax ginseng (14.52 mg / kg BW); the corresponding Chinese herbal composition is prepared from the following ingredients in weight percentage: Ziziphus jujuba seed 24.41%, Schisandra chinensis 0.61%, Polygala tenuifolia 15.62%, Poria cocos 11.72%, Gardenia jasminoides 46.86%, and Panax ginseng 0.78%; the formula obtained by the extraction process of this invention is the same as the formula described in Example 4; the extraction process is the same as the extraction process described in Formula 1 above.

[0036] Formula 5: Ziziphus jujuba seed (605 mg / kg BW), Schisandra chinensis (30.25 mg / kg BW), Polygala tenuifolia (12.07 mg / kg BW), Poria cocos (2323.3 mg / kg BW), Gardenia jasminoides (45.20 mg / kg BW), and Panax ginseng (4.84 mg / kg BW); the corresponding Chinese herbal composition is prepared from the following ingredients in weight percentage: Ziziphus jujuba seed 20.03%, Schisandra chinensis 1.00%, Polygala tenuifolia 0.40%, Poria cocos 76.91%, Gardenia jasminoides 1.50%, and Panax ginseng 0.16%; the formula obtained by the extraction process of this invention is the same as the formula described in the comparative example; the extraction process is the same as that described in Formula 1 above.

[0037] Formula Six: Ziziphus jujuba seed (1921 mg / kg BW), Schisandra chinensis fruit (192.10 mg / kg BW), Polygala tenuifolia fruit (153.67 mg / kg BW), Poria cocos (115.20 mg / kg BW), Gardenia jasminoides fruit (57.60 mg / kg BW), and Ginseng (3.84 mg / kg BW). The corresponding herbal composition is prepared from the following ingredients in weight percentage: Ziziphus jujuba seed 78.62%, Schisandra chinensis fruit 7.86%, Polygala tenuifolia fruit 6.29%, Poria cocos 4.71%, Gardenia jasminoides fruit 2.36%, and Ginseng 0.16%. Formula Six, obtained through the extraction process described in this invention, is the same as the formula described in Example Five; the extraction process is consistent with that described in Formula One above.

[0038] 2. Pharmacological studies on sleep improvement

[0039] Comparative Example

[0040] A traditional Chinese medicine composition for improving sleep is prepared from the following ingredients in weight percentages: 17.80% Ziziphus jujuba seed extract, 3.56% Schisandra chinensis extract, 1.06% Polygala tenuifolia extract, 68.33% Poria cocos extract, 8.54% Gardenia jasminoides extract and 0.71% Panax ginseng extract.

[0041] Example 1

[0042] A traditional Chinese medicine composition for improving sleep is prepared from the following ingredients in weight percentages: 2.10% Ziziphus jujuba seed extract, 3.38% Schisandra chinensis extract, 8.10% Polygala tenuifolia extract, 32.41% Poria cocos extract, 32.41% Gardenia jasminoides extract and 21.60% Ginseng extract.

[0043] Example 2

[0044] A traditional Chinese medicine composition for improving sleep is prepared from the following ingredients in weight percentages: 4.01% Ziziphus jujuba seed extract, 12.80% Schisandra chinensis extract, 61.43% Polygala tenuifolia extract, 3.84% Poria cocos extract, 7.68% Gardenia jasminoides extract and 10.24% Panax ginseng extract.

[0045] Example 3

[0046] A traditional Chinese medicine composition for improving sleep is prepared from the following ingredients in weight percentages: 6.08% Ziziphus jujuba seed extract, 38.93% Schisandra chinensis extract, 2.92% Polygala tenuifolia extract, 46.72% Poria cocos extract, 1.46% Gardenia jasminoides extract and 3.89% Panax ginseng extract.

[0047] Example 4

[0048] A traditional Chinese medicine composition for improving sleep is prepared from the following ingredients in weight percentages: 13.33% Ziziphus jujuba seed extract, 1.34% Schisandra chinensis extract, 25.60% Polygala tenuifolia extract, 6.40% Poria cocos extract, 51.20% Gardenia jasminoides extract and 2.13% Panax ginseng extract.

[0049] Example 5

[0050] A traditional Chinese medicine composition for improving sleep is prepared from the following ingredients in weight percentages: 56.5% Ziziphus jujuba seed extract, 22.6% Schisandra chinensis extract, 13.56% Polygala tenuifolia extract, 3.39% Poria cocos extract, 3.39% Gardenia jasminoides extract and 0.56% Ginseng extract.

[0051] Example 6: Experiment on the compatibility of traditional Chinese medicine formulas to optimize and improve sleep

[0052] 1. Effects of direct sleep on mice in the direct sleep experiment

[0053] The experimental animals were male Kunming mice, with 10 mice randomly assigned to each group. The mice were administered the drug by gavage once a day at a dose of 10 mL / kg BW for 21 consecutive days. The mice were observed to fall asleep immediately within 1 hour after the last administration.

[0054] Formula 1 (Example 1): Ziziphus jujuba seed extract (3.58 mg / kg BW), Schisandra chinensis extract (5.74 mg / kg BW), Polygala tenuifolia extract (13.78 mg / kg BW), Poria cocos extract (55.11 mg / kg BW), Gardenia jasminoides extract (55.11 mg / kg BW), Ginseng extract (36.74 mg / kg BW);

[0055] Formula 2 (Formula 2 of Example): Ziziphus jujuba seed extract (6.81 mg / kg BW), Schisandra chinensis extract (21.76 mg / kg BW), Polygala tenuifolia extract (104.44 mg / kg BW), Poria cocos extract (6.53 mg / kg BW), Gardenia jasminoides extract (13.06 mg / kg BW), Ginseng extract (17.41 mg / kg BW);

[0056] Formula 3 (Formula 3 of Example): Ziziphus jujuba seed extract (10.34 mg / kg BW), Schisandra chinensis extract (66.19 mg / kg BW), Polygala tenuifolia extract (4.96 mg / kg BW), Poria cocos extract (79.43 mg / kg BW), Gardenia jasminoides extract (2.48 mg / kg BW), Ginseng extract (6.62 mg / kg BW);

[0057] Formula 4 (Formula 4 of Example): Ziziphus jujuba seed extract (22.67 mg / kg BW), Schisandra chinensis extract (2.27 mg / kg BW), Polygala tenuifolia extract (43.52 mg / kg BW), Poria cocos extract (10.88 mg / kg BW), Gardenia jasminoides extract (87.04 mg / kg BW), Ginseng extract (3.63 mg / kg BW);

[0058] Formula 5 (comparative formulation): Ziziphus jujuba seed extract (30.25 mg / kg BW), Schisandra chinensis extract (6.05 mg / kg BW), Polygala tenuifolia extract (1.81 mg / kg BW), Poria cocos extract (116.16 mg / kg BW), Gardenia jasminoides extract (14.52 mg / kg BW), and Panax ginseng extract (1.21 mg / kg BW);

[0059] Formula 6 (Formula 5 of Example): Ziziphus jujuba seed extract (96.05 mg / kg BW), Schisandra chinensis extract (38.42 mg / kg BW), Polygala tenuifolia extract (23.05 mg / kg BW), Poria cocos extract (5.76 mg / kg BW), Gardenia jasminoides extract (5.76 mg / kg BW), Ginseng extract (0.96 mg / kg BW);

[0060] Blank control group: Administered 0.9% sodium chloride injection via gavage;

[0061] Table 1. Number of mice that fell asleep in the direct sleep experiment.

[0062]

[0063] Table 1 shows the effect of the above-mentioned traditional Chinese medicine composition on the direct sleep of mice (compared with the blank control group; n=10). As can be seen from Table 1, the above-mentioned traditional Chinese medicine composition has no significant effect on the direct sleep of mice.

[0064] 2. Effects of sodium pentobarbital on sleep time in mice during the experiment to prolong sleep time.

[0065] The experimental animals were male Kunming mice, with 10 mice randomly assigned to each group. The mice were administered the drug by gavage once a day at a dose of 10 mL / kg BW for 21 consecutive days. Thirty minutes after the last administration, each group of mice was injected intraperitoneally with sodium pentobarbital at a dose of 49 mg / kg BW. Mice fell asleep as defined by the disappearance of the righting reflex, i.e., the mice were placed in a supine position and could not right themselves within 1 minute. The time interval from the disappearance of the righting reflex to its reappearance was recorded as the mouse's sleep time (ST).

[0066] Formula 1 (Example 1): Ziziphus jujuba seed extract (3.58 mg / kg BW), Schisandra chinensis extract (5.74 mg / kg BW), Polygala tenuifolia extract (13.78 mg / kg BW), Poria cocos extract (55.11 mg / kg BW), Gardenia jasminoides extract (55.11 mg / kg BW), Ginseng extract (36.74 mg / kg BW);

[0067] Formula 2 (Formula 2 of Example): Ziziphus jujuba seed extract (6.81 mg / kg BW), Schisandra chinensis extract (21.76 mg / kg BW), Polygala tenuifolia extract (104.44 mg / kg BW), Poria cocos extract (6.53 mg / kg BW), Gardenia jasminoides extract (13.06 mg / kg BW), Ginseng extract (17.41 mg / kg BW);

[0068] Formula 3 (Formula 3 of Example): Ziziphus jujuba seed extract (10.34 mg / kg BW), Schisandra chinensis extract (66.19 mg / kg BW), Polygala tenuifolia extract (4.96 mg / kg BW), Poria cocos extract (79.43 mg / kg BW), Gardenia jasminoides extract (2.48 mg / kg BW), Ginseng extract (6.62 mg / kg BW);

[0069] Formula 4 (Formula 4 of Example): Ziziphus jujuba seed extract (22.67 mg / kg BW), Schisandra chinensis extract (2.27 mg / kg BW), Polygala tenuifolia extract (43.52 mg / kg BW), Poria cocos extract (10.88 mg / kg BW), Gardenia jasminoides extract (87.04 mg / kg BW), Ginseng extract (3.63 mg / kg BW);

[0070] Formula 5 (comparative formulation): Ziziphus jujuba seed extract (30.25 mg / kg BW), Schisandra chinensis extract (6.05 mg / kg BW), Polygala tenuifolia extract (1.81 mg / kg BW), Poria cocos extract (116.16 mg / kg BW), Gardenia jasminoides extract (14.52 mg / kg BW), and Panax ginseng extract (1.21 mg / kg BW);

[0071] Formula 6 (Formula 5 of Example): Ziziphus jujuba seed extract (96.05 mg / kg BW), Schisandra chinensis extract (38.42 mg / kg BW), Polygala tenuifolia extract (23.05 mg / kg BW), Poria cocos extract (5.76 mg / kg BW), Gardenia jasminoides extract (5.76 mg / kg BW), Ginseng extract (0.96 mg / kg BW);

[0072] Blank control group: Administered 0.9% sodium chloride injection via gavage;

[0073] Figure 1 The effect of the above-mentioned traditional Chinese medicine composition on prolonging the sleep time (ST) of sodium pentobarbital (compared with the blank control group); n = 7-10), from Figure 1 It was found that, compared with the blank control group, both Formula 1 and Formula 3 significantly prolonged the sodium pentobarbital sleep time in experimental mice (P<0.05); except for Formula 5, the sleep time of mice in the other experimental groups showed a trend of prolongation, but the differences were not statistically significant. These experimental results indicate that, with different proportions of the above traditional Chinese medicine compositions, there are two distinctly different effects: synergistic and antagonistic.

[0074] DPS statistical software was used to perform regression analysis on the response values ​​corresponding to the dosages of Ziziphus jujuba seed, Schisandra chinensis, Polygala tenuifolia, Poria cocos, Gardenia jasminoides, and ginseng. The regression equation for the sleep time Y1 of mice in the prolonged sodium pentobarbital sleep experiment was obtained as follows: Y1=2444.714139-0.015805232849X1*X1+0.15746538359X4*X4-0.9772291444X1*X4-1.5383737906X2*X5, where: Y1 represents the sleep time of mice in the prolonged sodium pentobarbital sleep experiment, X1 is the dosage of Ziziphus jujuba seed, X2 is the dosage of Schisandra chinensis, X4 is the dosage of Poria cocos, and X5 is the dosage of Gardenia jasminoides. The regression equations show that Polygala tenuifolia and ginseng had little or no effect on prolonging sleep time in mice tested for sodium pentobarbital sleep. The dosages of Ziziphus jujuba var. spinosa, Schisandra chinensis, and Gardenia jasminoides were negatively correlated with sleep time in the experimental animals, while the dosage of Poria cocos was positively correlated with sleep time. This indicates a synergistic or antagonistic relationship between the drugs, rather than a simple additive effect. The animal experimental results corroborate the conclusions of the DPS statistical analysis.

[0075] The results of the weight statistics of mice in each of the above test groups at the same time point are shown in Table 2 below. As can be seen from Table 2, there was no statistically significant difference in weight among the test groups at the same time point compared with the control group, indicating that the test substance had no effect on the weight of the experimental animals.

[0076] Table 2. Changes in mouse body weight (x±s, n=10, unit: g)

[0077]

[0078] Formulas 1 through 6 in Tables 1 and 2 were obtained from Formulas 1 through 6 in the above extraction process study.

[0079] 3. Effects of sodium pentobarbital on sleep latency in mice during the sleep latency experiment.

[0080] Kunming male mice were randomly assigned to each group (n=10 per group). They were administered the drug by gavage once daily at a dose of 10 mL / kg body weight (BW) for 21 consecutive days. Thirty minutes after the last administration, each group of mice was injected intraperitoneally with sodium pentobarbital at a dose of 30 mg / kg BW. Mice fell asleep as determined by the disappearance of the righting reflex, i.e., the time it took for a mouse to fall asleep in a supine position and not be able to right itself within one minute was recorded as the sleep latency (SL).

[0081] Formula 1 (Example 1): Ziziphus jujuba seed extract (3.58 mg / kg BW), Schisandra chinensis extract (5.74 mg / kg BW), Polygala tenuifolia extract (13.78 mg / kg BW), Poria cocos extract (55.11 mg / kg BW), Gardenia jasminoides extract (55.11 mg / kg BW), Ginseng extract (36.74 mg / kg BW);

[0082] Formula 2 (Formula 2 of Example): Ziziphus jujuba seed extract (6.81 mg / kg BW), Schisandra chinensis extract (21.76 mg / kg BW), Polygala tenuifolia extract (104.44 mg / kg BW), Poria cocos extract (6.53 mg / kg BW), Gardenia jasminoides extract (13.06 mg / kg BW), Ginseng extract (17.41 mg / kg BW);

[0083] Formula 3 (Formula 3 of Example): Ziziphus jujuba seed extract (10.34 mg / kg BW), Schisandra chinensis extract (66.19 mg / kg BW), Polygala tenuifolia extract (4.96 mg / kg BW), Poria cocos extract (79.43 mg / kg BW), Gardenia jasminoides extract (2.48 mg / kg BW), Ginseng extract (6.62 mg / kg BW);

[0084] Formula 4 (Formula 4 of Example): Ziziphus jujuba seed extract (22.67 mg / kg BW), Schisandra chinensis extract (2.27 mg / kg BW), Polygala tenuifolia extract (43.52 mg / kg BW), Poria cocos extract (10.88 mg / kg BW), Gardenia jasminoides extract (87.04 mg / kg BW), Ginseng extract (3.63 mg / kg BW);

[0085] Formula 5 (comparative formulation): Ziziphus jujuba seed extract (30.25 mg / kg BW), Schisandra chinensis extract (6.05 mg / kg BW), Polygala tenuifolia extract (1.81 mg / kg BW), Poria cocos extract (116.16 mg / kg BW), Gardenia jasminoides extract (14.52 mg / kg BW), and Panax ginseng extract (1.21 mg / kg BW);

[0086] Formula 6 (Formula 5 of Example): Ziziphus jujuba seed extract (96.05 mg / kg BW), Schisandra chinensis extract (38.42 mg / kg BW), Polygala tenuifolia extract (23.05 mg / kg BW), Poria cocos extract (5.76 mg / kg BW), Gardenia jasminoides extract (5.76 mg / kg BW), Ginseng extract (0.96 mg / kg BW);

[0087] Blank control group: Administered 0.9% sodium chloride injection via gavage;

[0088] Figure 2 The effect of the above-mentioned traditional Chinese medicine composition on the sleep latency (SL) of sodium pentobarbital (compared with the blank control group; x±s, n=8-10) was determined by... Figure 2 It can be seen that, compared with the blank control group, the sleep latency of mice in Formula 3 was significantly shortened. The sleep latency of mice in other experimental groups all showed a shortening trend to varying degrees, but the differences were not statistically significant.

[0089] Example 7: In order to further verify whether different drug compositions have a regulatory effect on the pathology of sleep disorders, a confirmatory experiment on improving sleep disorders - the effect of pentobarbital sodium on the sleep time of chlorophenylalanine (PCPA) insomnia mice in the experiment of prolonging the sleep time of chlorophenylalanine (PCPA) will be carried out. This example is based on Example 6 to further verify the reliability of the above invention, and is not a limitation on the inventiveness of the present invention, nor does it affect the scope of the inventiveness of the invention.

[0090] The experimental animals were male Kunming mice, randomly divided into a blank control group, a model group, a low-dose group of Formula 3 (85 mg / kg BW), a medium-dose group of Formula 3 (170 mg / kg BW), and a high-dose group of Formula 3 (850 mg / kg BW). Mice were first intraperitoneally injected with PCPA at a dose of 400 mg / kg BW for 3 days to establish an insomnia mouse model. Then, the mice were administered the corresponding dosages to each experimental group via gavage at a volume of 10 mL / kg BW, once daily for 21 consecutive days. Thirty minutes before the last administration, each group of mice was intraperitoneally injected with sodium pentobarbital at a dose of 49 mg / kg BW. Mice fell asleep as determined by the disappearance of the righting reflex; that is, the mouse was placed in a supine position and could not right itself within 1 minute. The time interval from the disappearance of the righting reflex to its reappearance was recorded as the mouse's sleep time (ST).

[0091] Blank control group: 0.9% sodium chloride injection was administered by gavage; no PCPA intervention was performed.

[0092] Model group: administered 0.9% sodium chloride injection via gavage;

[0093] Formula 3 low-dose group: Ziziphus jujuba seed extract (5.17 mg / kg BW), Schisandra chinensis extract (33.10 mg / kg BW), Polygala tenuifolia extract (2.48 mg / kg BW), Poria cocos extract (39.72 mg / kg BW), Gardenia jasminoides extract (1.24 mg / kg BW), Ginseng extract (3.31 mg / kg BW);

[0094] Formula 3, medium dose group: Ziziphus jujuba seed extract (10.34 mg / kg BW), Schisandra chinensis extract (66.19 mg / kg BW), Polygala tenuifolia extract (4.96 mg / kg BW), Poria cocos extract (79.43 mg / kg BW), Gardenia jasminoides extract (2.48 mg / kg BW), Ginseng extract (6.62 mg / kg BW);

[0095] Formula 3 (high-dose group): Ziziphus jujuba seed extract (20.69 mg / kg BW), Schisandra chinensis extract (132.39 mg / kg BW), Polygala tenuifolia extract (9.93 mg / kg BW), Poria cocos extract (158.86 mg / kg BW), Gardenia jasminoides extract (4.96 mg / kg BW), and Ginseng extract (13.24 mg / kg BW);

[0096] The results of prolonging mouse sleep time are as follows Figure 3 (Compared with the model group;) As shown in n=7-9): Compared with the blank control group, the sleep time of mice in the model group was significantly shortened, indicating that PCPA induced insomnia in the mice, and the model was successfully established. Compared with the model group, the sleep time of mice in each experimental treatment group was significantly prolonged (P<0.05, P<0.01, P<0.001), indicating that Formula 3 has an ameliorative effect on PCPA-induced insomnia in mice.

[0097] The levels of 5-HT and GABA in the hippocampus of insomniac mice were measured using an ELISA kit during an experiment to prolong sodium pentobarbital sleep time.

[0098] 5-HT measurement results are as follows Figure 4 As shown (compared with the model group); (n=8): Compared with the blank control group, the 5-HT content in the hippocampus of experimental mice in the model group was significantly reduced; compared with the model group, the 5-HT content in the hippocampus of each experimental treatment group was significantly increased (P<0.001). The above experimental results indicate that the improvement of sleep ability in experimental mice by formula 3 is related to the increase of 5-HT concentration in brain tissue.

[0099] GABA determination results are as follows: Figure 5 As shown (compared to the blank group); (n=7) Compared with the control group, the GABA content in the hippocampus of mice in each experimental group was reduced, but there was no statistically significant difference. Compared with the model group, there was no statistically significant difference in the changes of GABA content in the brain of each experimental treatment group.

[0100] Mice were rapidly dissected and perfused. Brain tissue was collected and placed in 4% paraformaldehyde, then transferred to 10% formaldehyde for fixation for 24 hours. The tissue was then transferred to 10% decalcification solution and decalcified at room temperature for 3 weeks. Afterward, it was dehydrated and cleared with ethanol and xylene, embedded in paraffin, and sectioned into 5μm thick sections. Hematoxylin and eosin (H&E) staining was performed, and the histopathological changes in the colon tissue were observed and photographed using an optical microscope. The histopathological observation results are as follows: Figure 6 As shown, the results indicated that, except for the control group, all other groups showed varying degrees of damage and inflammatory infiltration in the hippocampus after PCPA intervention. After drug intervention, the damaged tissues in each group showed varying degrees of repair. Under a light microscope, the hippocampal pyramidal cells in the normal control group were neatly arranged, densely packed, evenly distributed, plump in shape, and had clear nucleoli. In the model control group, the hippocampal pyramidal cells were slightly disordered and loosely arranged, with some neurons showing unclear structure, reduced number, and loss of normal morphology. After drug intervention, the above changes in hippocampal pyramidal cells were partially restored, with a more neat arrangement and a slightly increased cell number.

Claims

1. A traditional Chinese medicine composition for improving sleep, characterized in that, When using Chinese medicinal herbs as starting materials, the extract is prepared from the following components by weight percentage: Ziziphus jujuba seed 3.59-78.62%, Schisandra chinensis fruit 0.61-14.97%, Polygala tenuifolia fruit 1.50-54.73%, Poria cocos 4.71-71.86%, Gardenia jasminoides fruit 1.12-46.86%, and Panax ginseng 0.16-7.38%. When using Chinese medicinal herb extracts as starting materials, the extract is prepared from the following components by weight percentage: Ziziphus jujuba seed extract 2.10-56.5%, Schisandra chinensis fruit extract 1.34-38.93%, Polygala tenuifolia fruit extract 2.92-61.43%, Poria cocos extract 3.39-46.72%, Gardenia jasminoides fruit extract 1.46-51.20%, and Panax ginseng extract 0.56-21.60%.

2. The traditional Chinese medicine composition for improving sleep according to claim 1, characterized in that, When using Chinese medicinal herbs as starting materials, the extract is prepared from the following components by weight percentage: Ziziphus jujuba seed 3.59-9.35%, Schisandra chinensis 1.44-14.97%, Polygala tenuifolia 1.50-4.61%, Poria cocos 55.32-71.86%, Gardenia jasminoides 1.12-27.66%, and Panax ginseng 1.20-7.38%. When using Chinese medicinal herb extracts as starting materials, the extract is prepared from the following components by weight percentage: Ziziphus jujuba seed extract 2.10-6.08%, Schisandra chinensis extract 3.38-38.93%, Polygala tenuifolia extract 2.92-8.10%, Poria cocos extract 32.41-46.72%, Gardenia jasminoides extract 1.46-32.41%, and Panax ginseng extract 3.89-21.60%.

3. A traditional Chinese medicine composition for improving sleep according to claim 1 or 2, characterized in that, The traditional Chinese medicine composition is processed into oral liquid, tablets, capsules or granules by adding medicinal or edible excipients.

4. A traditional Chinese medicine composition for improving sleep according to claim 1 or 2, characterized in that, Extracts include extracts obtained by water decoction and extracts obtained by ethanol extraction.

5. The traditional Chinese medicine composition for improving sleep according to claim 3, characterized in that, The excipient is one or more of the following: microcrystalline silica gel, sodium carboxymethyl starch, dextrin, lactose, starch, sucrose, glucose, microcrystalline cellulose, mannose, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, steviol, sorbitol, talc, and magnesium stearate.

6. The traditional Chinese medicine composition for improving sleep according to claim 5, characterized in that, The excipient is an auxiliary material composed of micronized silica gel, sorbitol, sodium carboxymethyl starch, microcrystalline cellulose, talc, and magnesium stearate.

7. A method for preparing a traditional Chinese medicine composition for improving sleep as described in claim 1 or 2, characterized in that, When using Chinese medicinal herbs as the starting material, the preparation method includes the following steps: S1. Take jujube seed, schisandra fruit, polygala root, gardenia fruit and ginseng and extract them together. Extract them 2-3 times with 50-85% ethanol. Combine the decoctions and concentrate the filtrate under reduced pressure to a relative density of 1.20-1.30 at 65℃. Recover the ethanol to obtain concentrated solution I. S2. Poria cocos is decocted twice with 6-10 times the amount of water. The decoctions are combined and concentrated to a relative density of 1.10-1.20 at 65°C. Ethanol is added and stirred to make the alcohol content reach 60-85% by volume percentage. The mixture is allowed to stand, filtered, and the filtrate is concentrated under reduced pressure to a relative density of 1.20-1.30 at 65°C. The ethanol is then recovered to obtain concentrated solution II. S3. Combine concentrated liquid I and concentrated liquid II, add water and excipients to prepare oral liquid, or spray dry the concentrated liquid and add excipients to prepare capsules, tablets or granules; When using extracts of traditional Chinese medicine as starting materials, the preparation method includes the following steps: Extracts of jujube seed, schisandra fruit, polygala root, poria cocos, gardenia fruit, and ginseng are prepared into oral liquids, capsules, tablets, and granules with appropriate excipients.

8. The use of the traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of drugs or functional foods for improving sleep.

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