A composition, pharmaceutical preparation and use for improving sleep, anti-anxiety and depression

Abstract

The application provides a composition, a pharmaceutical preparation and an application for improving sleep, resisting anxiety and depression, and relates to the technical field of traditional Chinese medicines.The composition comprises the following components: poria cocos, jujube seed, lily, mulberry, bergamot, wheat, jujube, ganoderma lucidum, gastrodia elata blume powder, licorice, and donkey-hide gelatin.The composition prepared by the application has better effects of improving sleep and resisting anxiety and depression, the raw materials are simple and easy to obtain, safe and non-toxic, and the preparation method is simple and suitable for industrial promotion.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and specifically relates to a composition for improving sleep, resisting anxiety and depression, a pharmaceutical preparation and an application thereof. Background Art

[0002] Insomnia generally refers to a subjective experience in which a patient is dissatisfied with sleep time and / or sleep quality, and the condition affects daytime social functions. Insomnia is manifested as difficulty in falling asleep (sleep onset time exceeding 30 minutes), sleep maintenance disorder (number of awakenings throughout the night ≥ 2 times), early awakening, decreased sleep quality and reduced total sleep time (usually less than 6 hours), accompanied by daytime functional impairment. According to the course of the disease, insomnia is classified as: acute insomnia (course of disease ≥ 1 month); subacute insomnia (course of disease ≥ 1 month and < 6 months); and chronic insomnia (course of disease ≥ 6 months). With the change of people's lifestyles and the acceleration of population aging, the incidence of neurological diseases, especially insomnia caused by stress and anxiety, has increased significantly. The age range of people with sleep disorders is also gradually expanding, usually accompanied by depression, anxiety and other complications. Studies show that 40% of insomnia patients are associated with one or more mental disorders, among which anxiety disorders account for as high as 24%.

[0003] At present, the main treatment methods for people with anxiety-type insomnia include psychological counseling and adjuvant chemical drug therapy. However, chemical drug therapy often brings a series of side effects, for example, symptoms such as dizziness, headache, nausea, loss of appetite, and stomach pain may occur in the initial stage of administration, and long-term use may lead to stomach discomfort, decreased appetite, and even drug resistance and drug dependence.

[0004] In contrast, traditional Chinese medicine prescriptions have fewer side effects, and are less likely to cause drug resistance and drug dependence. According to traditional Chinese medicine theory, insomnia falls into the categories of "insomnia", "sleepless eyes", "inability to lie down" and the like. The heart houses the spirit, and restlessness of the spirit leads to difficulty in falling asleep; the liver houses the ethereal soul, and unrest of the liver's ethereal soul leads to easy awakening and difficulty in sleeping. Deficiency of both heart and liver blood results in malnutrition of the spirit and ethereal soul, leading to inability to sleep at night. In treatment, the methods of nourishing the heart to calm the spirit and soothing the liver to relieve depression should be adopted, aiming at regulating and calming the mind so as to achieve stable sleep.

[0005] Chinese patent CN 117562958 A discloses a sophora japonica and tangerine peel composition for improving sleep and relieving anxiety, and its preparation method. The composition contains tangerine peel extract, sophora japonica extract, banana powder, daylily powder, jujube seed powder, perilla powder, white hyacinth bean seed coat extract, modified Lactobacillus reuteri, and modified Bifidobacterium animalis. Most of the raw materials are food and medicine homologous, and the composition is safe with no toxic side effects. The specially processed components combine to synergistically promote sleep, improve anxiety, and combat depression. Experiments have shown that the efficacy is rapid and significant, can shorten the treatment course, and has no side effects or dependence, making it particularly suitable for patients with mild to moderate anxiety, insomnia, and depression. However, the preparation method of this composition is complex; the tangerine peel extract, sophora japonica extract, and white hyacinth bean seed coat extract all require enzymatic hydrolysis, making it unsuitable for large-scale promotion.

[0006] Chinese Patent CN 115645462 A discloses a traditional Chinese medicine composition for improving sleep and relieving depression, its preparation method, and its uses. The composition is made from the following raw materials in parts by weight: Atractylodes lancea 4-6 parts, Poria cocos 4-9 parts, Ligusticum chuanxiong 3-6 parts, Angelica sinensis 3-9 parts, Bupleurum chinense 2-6 parts, Glycyrrhiza uralensis 2-6 parts, Uncaria rhynchophylla 3-9 parts, and Ziziphus jujuba 2-4 parts. It has the effects of improving sleep, relieving anxiety, treating post-traumatic stress disorder, and relieving depression. However, its effects are not ideal and still need improvement.

[0007] Therefore, developing a traditional Chinese medicine composition that can effectively improve people's sleep quality and relieve anxiety and depression is of great significance for improving people's quality of life and reducing the burden of medical care. Summary of the Invention

[0008] To address the aforementioned problems, this invention provides a composition, pharmaceutical preparation, and application for improving sleep and relieving anxiety and depression. The composition of this invention comprises Poria cocos, Ziziphus jujuba seed, lily bulb, mulberry, citron, wheat, jujube, Ganoderma lucidum, Gastrodia elata powder, licorice, and donkey-hide gelatin. By optimizing the component ratio, the obtained traditional Chinese medicine composition is safe and non-toxic, has low side effects, and has good effects on improving sleep and relieving anxiety and depression.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] On the one hand, the present invention provides a composition for improving sleep and relieving anxiety and depression, comprising the following components: Poria cocos, Ziziphus jujuba seed, lily bulb, mulberry, citron, wheat, jujube, Ganoderma lucidum, Gastrodia elata powder, licorice, and donkey-hide gelatin.

[0011] This invention provides a composition for improving sleep and combating anxiety and depression. Poria cocos is the principal ingredient, invigorating the spleen and calming the mind, promoting diuresis and eliminating dampness, and soothing the nerves. It has a good effect on insomnia, excessive dreaming, and palpitations caused by deficiency of both the heart and spleen and internal retention of dampness. Ziziphus jujuba seed, combined with Poria cocos, nourishes the heart and liver, calms the mind and relieves irritability, and promotes body fluid production and soothes the nerves. It strengthens the calming effect of the principal ingredient for symptoms of insomnia, palpitations, and excessive dreaming, thus calming the mind. Lily bulb and mulberry are listed as assistant ingredients. Lily bulb clears the heart and lungs, nourishes yin and calms the mind, effectively relieving anxiety and depression caused by yin deficiency and excessive fire, and emotional distress. Mulberry nourishes yin and blood, promotes body fluid production and moistens dryness. The combination of the two nourishes the yin of the heart and liver and soothes a restless mind. Buddha's Hand citron and wheat, both serving as assistant herbs, are used to soothe the liver, relieve depression, regulate qi, and harmonize the middle jiao, specifically designed for anxiety and depression caused by liver qi stagnation. Wheat, sweet and cool in nature, nourishes the heart, relieves irritability, and benefits the kidneys, making it especially suitable for those with excessive heart fire and restlessness. Jujube, Ganoderma lucidum, and Gastrodia elata powder are used as adjuvant herbs. Jujube tonifies the middle jiao, replenishes qi, nourishes blood, and calms the mind, complementing Ganoderma lucidum to not only enhance immunity but also deepen the calming and depression-relieving effects. Ganoderma lucidum tonifies qi, calms the mind, stops coughs, and relieves asthma, significantly benefiting those with chronic insomnia and neurasthenia. Gastrodia elata powder calms wind, stops spasms, and suppresses liver yang, effectively relieving dizziness, headaches, irritability, and anger caused by liver yang hyperactivity, assisting the principal and assistant herbs in overcoming anxiety and depression. Licorice, as the guiding herb, tonifies qi, detoxifies, and harmonizes the other herbs, reducing their harshness and promoting synergistic effects, making the entire formula mild and easily absorbed by the body. While donkey-hide gelatin doesn't directly affect sleep and mood, its properties of nourishing blood and yin, moistening dryness, and stopping bleeding indirectly improve restlessness caused by blood and yin deficiency, adding a finishing touch to the overall nourishing effect of the herbal paste. The above-mentioned herbal paste, through the careful combination of herbs such as Poria cocos and jujube seed, achieves a comprehensive effect of improving sleep and combating anxiety and depression, making it suitable for people suffering from long-term insomnia, anxiety, and depression.

[0012] Preferably, the composition comprises, by weight parts, the following components: 8-32 parts of Poria cocos, 4-16 parts of Ziziphus jujuba var. spinosa, 4-18 parts of lily bulb, 1-15 parts of mulberry fruit, 18-40 parts of Citrus medica var. sarcodactylis, 10-28 parts of wheat, 2-12 parts of jujube, 5-22 parts of Ganoderma lucidum, 2-12 parts of Gastrodia elata powder, 4-16 parts of licorice root, and 4-16 parts of donkey-hide gelatin.

[0013] More preferably, the composition comprises, by weight parts, the following components: 10-30 parts Poria cocos, 5-15 parts Ziziphus jujuba var. spinosa, 4-15 parts Lilium brownii, 1-10 parts Morus alba, 20-40 parts Citrus medica var. sarcodactylis, 10-25 parts wheat, 2-10 parts jujube, 5-20 parts Ganoderma lucidum, 2-10 parts Gastrodia elata powder, 5-15 parts Glycyrrhiza uralensis, and 5-15 parts donkey-hide gelatin.

[0014] More preferably, the composition comprises, by weight parts, the following components: 15-25 parts Poria cocos, 5-8 parts Ziziphus jujuba var. spinosa, 5-8 parts Lilium brownii, 2-5 parts Morus alba, 25-35 parts Citrus medica var. sarcodactylis, 15-25 parts wheat, 3-8 parts Ziziphus jujuba, 10-20 parts Ganoderma lucidum, 3-5 parts Gastrodia elata powder, 5-12 parts Glycyrrhiza uralensis, and 5-15 parts Colla corii asini.

[0015] Most preferably, the composition comprises, by weight parts, the following components: 20 parts Poria cocos, 8 parts Ziziphus jujuba var. spinosa, 8 parts Lilium brownii, 2 parts Morus alba, 30 parts Citrus medica var. sarcodactylis, 20 parts wheat, 5 parts jujube, 15 parts Ganoderma lucidum, 3 parts Gastrodia elata powder, 10 parts Glycyrrhiza uralensis, and 10 parts Colla corii asini.

[0016] On the other hand, the present invention provides a method for preparing the above-described composition, comprising the following steps:

[0017] S1: Take Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum and licorice, add solvent to extract, concentrate 1-3 times to obtain concentrated solution;

[0018] S2: Melt the donkey-hide gelatin and crush the jujube seed. Add the melted donkey-hide gelatin, gastrodia elata powder, and jujube seed powder to the concentrated liquid obtained in S1, mix, and let stand at 0-5℃ for 10-15 hours. Separate and take the supernatant to obtain the extract.

[0019] Preferably, in S1, the solvent is water, and the mass of the water is 8-12 times the total mass of Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum and licorice; more preferably, in S1, the solvent is water, and the mass of the water is 8-12 times the total mass of Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum and licorice.

[0020] Preferably, the extraction described in S1 is a heating reflux extraction at a temperature of 95-100℃; more preferably, the temperature is 100℃.

[0021] Preferably, in step S2, the solvent is water, and the mass of the water is 8-12 times the total mass of Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum, and licorice. More preferably, in step S2, the solvent is water, and the mass of the water is 10 times the total mass of Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum, and licorice.

[0022] Preferably, the preparation method further includes the following steps: concentrating the extract into a thick paste, drying it, and pulverizing it to obtain the extract.

[0023] Preferably, the preparation method further includes the following steps: concentrating the extract under reduced pressure to a thick paste with a relative density of 1.28-1.31, drying under reduced pressure at 60-70°C, and pulverizing into powder to obtain the extract.

[0024] Preferably, in the above steps, auxiliary materials may also be added.

[0025] Preferably, the excipients include isomaltooligosaccharide and maltitol.

[0026] On the other hand, the present invention provides a pharmaceutical formulation comprising the composition described above.

[0027] Preferably, the dosage form of the pharmaceutical preparation includes ointment, pill, capsule, granule, oral liquid, powder, tablet, lozenge, and sugar lozenge.

[0028] More preferably, the dosage form of the pharmaceutical preparation is an ointment.

[0029] The drug carrier used can be solid, liquid, or gaseous. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate, and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0030] In preparing compositions for oral dosage forms, any convenient pharmaceutical medium can be used. For example, water, ethanol, oils, alcohols, flavoring agents, preservatives, coloring agents, etc., can be used to form oral liquid dosage forms, such as suspensions, solutions, and granules; while carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulators, emulsifiers, lubricants, binders, and disintegrants, can be used to form oral solid dosage forms, such as powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or non-aqueous techniques.

[0031] Tablets containing the compositions of the present invention can be prepared by compression or molding, optionally using one or more excipients or adjuvants. The active ingredient can be compressed in a free-flowing form (e.g., powder or granules) in a suitable machine, optionally mixed with a binder, lubricant, inert diluent, surfactant, or dispersant. Molded tablets can be formed in a suitable machine from a mixture of powdered compounds moistened with an inert liquid diluent.

[0032] In another aspect, the present invention provides the use of the above-mentioned composition or pharmaceutical preparation in improving sleep and relieving anxiety and depression.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] This invention provides a traditional Chinese medicine composition comprising 11 components, including Poria cocos, Ziziphus jujuba seed, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum, Gastrodia elata powder, licorice, and donkey-hide gelatin. By optimizing the components and their proportions, it was found that under specific components and proportions, the composition has better effects on improving sleep and relieving anxiety and depression. Furthermore, the raw materials are simple and readily available, safe and non-toxic, and have no side effects. The preparation method is simple and suitable for industrial promotion. Detailed Implementation

[0035] To make the technical means, creative features, achieved objectives, and effects of this invention readily understandable, the invention is further illustrated below with specific embodiments. However, these embodiments are merely preferred embodiments and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described herein without creative effort are all within the scope of protection of this invention. It is worth noting that the raw materials used in this invention are all common commercially available products, and their sources are not specifically limited. The technical and scientific terms used in the embodiments have the meanings commonly understood by those skilled in the art to which this invention pertains.

[0036] Example 1

[0037] A composition that improves sleep and combats anxiety and depression:

[0038] By weight, it contains the following components: 20 parts Poria cocos, 8 parts Ziziphus jujuba var. spinosa, 8 parts Lilium brownii, 2 parts Morus alba, 30 parts Citrus medica var. sarcodactylis, 20 parts Wheat, 5 parts Jujube, 15 parts Ganoderma lucidum, 3 parts Gastrodia elata powder, 10 parts Glycyrrhiza uralensis, and 10 parts Colla corii asini.

[0039] Preparation method: Take Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum and licorice, add 10 parts water and heat under reflux at 100℃ to extract, concentrate 1-3 times to obtain concentrated solution; take donkey-hide gelatin and dissolve it in water, add the dissolved donkey-hide gelatin, Gastrodia elata powder and jujube seed to the above concentrated solution, stir for 30 minutes, let stand at 4℃ for 12 hours, separate the supernatant, concentrate to a thick paste with a relative density of 1.28-1.31, dry under reduced pressure at 60-70℃, and pulverize into powder.

[0040] Example 2

[0041] A composition that improves sleep and combats anxiety and depression:

[0042] By weight, it contains the following components: 30 parts Poria cocos, 15 parts Ziziphus jujuba var. spinosa, 15 parts Lilium brownii, 10 parts Morus alba, 40 parts Citrus medica var. sarcodactylis, 10 parts wheat, 10 parts jujube, 5 parts Ganoderma lucidum, 10 parts Gastrodia elata powder, 5 parts Glycyrrhiza uralensis, and 5 parts donkey-hide gelatin.

[0043] Preparation method: Same as in Example 1.

[0044] Example 3

[0045] A composition that improves sleep and combats anxiety and depression:

[0046] By weight, it contains the following components: 10 parts Poria cocos, 5 parts Ziziphus jujuba var. spinosa, 4 parts Lilium brownii, 1 part Morus alba, 20 parts Citrus medica var. sarcodactylis, 25 parts Wheat, 2 parts Jujube, 20 parts Ganoderma lucidum, 2 parts Gastrodia elata powder, 15 parts Glycyrrhiza uralensis, and 15 parts Colla corii asini.

[0047] Preparation method: Same as in Example 1.

[0048] Comparative Example 1

[0049] A composition that improves sleep and combats anxiety and depression:

[0050] By weight, it contains the following components: 32 parts Poria cocos, 20 parts Ziziphus jujuba var. spinosa, 20 parts Lilium brownii, 0.5 parts Morus alba, 15 parts Citrus medica var. sarcodactylis, 8 parts wheat, 12 parts Jujube, 21.5 parts Ganoderma lucidum, 1 part Gastrodia elata powder, 3 parts Glycyrrhiza uralensis, and 4 parts Colla corii asini.

[0051] Preparation method: Same as in Example 1.

[0052] Comparative Example 2

[0053] A composition that improves sleep and combats anxiety and depression:

[0054] By weight, it contains the following components: 6 parts Poria cocos, 2 parts Ziziphus jujuba var. spinosa, 2 parts Lilium brownii, 12 parts Morus alba, 42 parts Citrus medica var. sarcodactylis, 26 parts wheat, 1 part Jujube, 4 parts Ganoderma lucidum, 12 parts Gastrodia elata powder, 18 parts Glycyrrhiza uralensis, and 18 parts Colla corii asini.

[0055] Preparation method: Same as in Example 1.

[0056] Comparative Example 3

[0057] A composition that improves sleep and combats anxiety and depression:

[0058] By weight, it contains the following components: 8 parts of jujube seed, 10 parts of licorice root, and 20 parts of poria cocos.

[0059] Preparation method: Licorice and Poria cocos are extracted with solvent and concentrated 1-3 times to obtain concentrated solution; Ziziphus jujuba seeds are added to concentrated solution, mixed, and allowed to stand at 0-5℃ for 10-15h. The supernatant is separated, concentrated, and the extract is dried and pulverized.

[0060] Comparative Example 4

[0061] A composition that improves sleep and combats anxiety and depression:

[0062] By weight, it contains the following components: 10 parts licorice, 20 parts wheat, and 5 parts jujube.

[0063] Preparation method: Licorice, wheat and jujube are extracted with solvent, concentrated 1-3 times to obtain concentrated solution, further concentrated to obtain extract, dried and pulverized.

[0064] Comparative Example 5

[0065] A composition that improves sleep and combats anxiety and depression:

[0066] By weight, it contains the following components: 3 parts Gastrodia elata and 15 parts Ganoderma lucidum.

[0067] Preparation method: Ganoderma lucidum is extracted with solvent and concentrated 1-3 times to obtain concentrated liquid. Gastrodia elata is added to the concentrated liquid, mixed, and allowed to stand at 0-5℃ for 10-15 hours. The supernatant is separated, concentrated, and the extract is dried and pulverized.

[0068] The compositions prepared in Examples 1-3 and Comparative Examples 1-5 were subjected to tests for improving sleep and alleviating anxiety and depression.

[0069] Test Example 1: Sleep Improvement Detection

[0070] a) Laboratory animals:

[0071] Three hundred and thirty SPF-grade healthy male ICR mice (6-8 weeks old, weighing 18-22g, purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., license number: SCXK(Su)2023-0009) were acclimatized for one week under conditions of room temperature 25℃, humidity 60%, and 12h light-dark cycle. They were then randomly divided into 11 groups of 30 mice each. All animals were given the same amount of ordinary feed and drinking water.

[0072] The experiment was divided into three batches, with 10 mice in each batch. Batch A conducted direct sleep experiments and experiments to prolong sodium pentobarbital sleep time; batch B conducted subthreshold dose sodium pentobarbital hypnotic experiments; and batch C conducted sodium barbital sleep latency experiments.

[0073] b) The groups were set as follows: model control group, Bailuomian capsule group (positive control group), low-dose group of Example 1, high-dose group of Example 1, group of Example 2, group of Example 3, comparative example 1, comparative example 2, comparative example 3, comparative example 4, and comparative example 5.

[0074] c) Drug preparation and daily dosage:

[0075] Model control group: physiological saline;

[0076] Bailuomian Capsule Group (Positive Control): Bailuomian capsules, purchased from Yangtze River Pharmaceutical Group Co., Ltd., approval number: National Drug Approval Number Z20020131; drug specification: 0.27g*56 capsules / box; dosage: 0.27g·kg -1 ·d -1Dissolved in physiological saline.

[0077] Example 1 Low-dose group: The composition prepared in Example 1 was administered at a dose of 0.9 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0078] Example 1 High-dose group: The composition prepared in Example 1 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0079] Example 2 group: The composition prepared in Example 2 was administered at a dosage of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0080] Example 3 group: The composition prepared in Example 3 was administered at a dosage of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0081] Comparative Example 1: The composition prepared in Comparative Example 1 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0082] Comparative Example 2: The composition prepared in Comparative Example 2 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0083] Comparative Example 3: The composition prepared in Comparative Example 3 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0084] Comparative Example 4: The composition prepared in Comparative Example 4 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0085] Comparative Example 5: The composition prepared in Comparative Example 5 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline.

[0086] All animals were given the same amount of normal feed and drinking water. Mice in each group were administered medication by gavage once daily in the morning for 30 consecutive days, at a volume of 10 mL / kg. -1 ·d -1 .

[0087] d) Test items:

[0088] 1) Direct Sleep Experiment

[0089] After the mice were given saline and different test samples for the last time, the presence of sleep phenomena was observed in the model control group and each test sample group. Sleep was defined as the disappearance of the righting reflex; when a mouse was placed in a dorsal position, it should be able to immediately right itself. 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 number of animals that fell asleep in each group was recorded, and the sleep rate was calculated.

[0090] Sleep rate % = (Number of mice that successfully fell asleep / Total number of mice) × 100%.

[0091] 2) Experiment on prolonging sodium pentobarbital sleep time

[0092] Before commencing formal experiments, a preliminary experiment was conducted to determine the optimal sodium pentobarbital dose (45 mg / kg) that would induce complete sleep in mice without prolonging their sleep duration. This dose was then used in subsequent experiments. Fifteen minutes before the peak effect of the last administration of saline and different test samples, mice in each group were intraperitoneally injected with sodium pentobarbital (freshly prepared before use) at a dose of 0.2 mL / 20 g. The disappearance of the righting reflex was used as the criterion to observe whether the test samples could prolong the sleep time caused by sodium pentobarbital.

[0093] 3) Subthreshold dose hypnotic experiment with sodium pentobarbital

[0094] Before conducting the formal experiments, a preliminary experiment was performed to determine the maximum subthreshold dose of sodium pentobarbital (determined to be 25 mg / kg) that would prevent the righting reflex from disappearing in 80-90% of mice. This dose was then used in subsequent experiments. Fifteen minutes before the peak effect of the last administration of saline and different test samples, mice in each group were intraperitoneally injected with the maximum subthreshold hypnotic dose of sodium pentobarbital (freshly prepared before use), at a dose of 0.2 mL / 20 g. The number of animals falling asleep within 30 minutes (when the righting reflex disappeared for more than 60 seconds) was recorded, and the sleep rate was calculated.

[0095] Sleep rate % = (Number of mice that successfully fell asleep / Total number of mice) × 100%.

[0096] 4) Sodium barbital sleep latency test

[0097] Before commencing the formal experiments, a preliminary experiment was conducted to determine the optimal sodium barbital dose (250 mg / kg) that would induce complete sleep in mice without causing excessively long sleep duration. This dose was then used in subsequent experiments. Fifteen minutes after the mice received their last dose of saline and different test samples, each group of mice was intraperitoneally injected with sodium barbital (freshly prepared before use) at a dose of 0.2 mL / 20 g. The effect of the test samples on the sodium barbital sleep latency (the time from injection of sodium pentobarbital to initiation of sleep) was observed, using the disappearance of the righting reflex as an indicator.

[0098] e) Test Results

[0099] 1) Effects on mouse body weight

[0100] Based on the data shown in Table 1, the body weight of mice in the direct sleep experiment after 30 days of drug administration was recorded and analyzed using ANOVA. The results showed that there was no significant difference in body weight between the mice in each test sample group and the model control group (P>0.05).

[0101] Table 1. Effects on body weight of mice in the direct sleep experiment ( n=10)

[0102] 1 Model control group 40.2±0.5 2 Bailumian Capsule Group 40.7±0.6 3 Example 1 Low-dose group 40.3±1.9 4 Example 1 High-dose group 41±1.3 5 Example 2 group 40.8±0.7 6 Example 3 Group 40.6±1.1 7 Comparative Example 1 40.1±1.8 8 Comparative Example 2 40.5±0.8 9 Comparative Example 3 Groups 41.3±1.2 10 Comparative Example 4 Groups 40.6±1.1 11 Comparative Example 5 Groups 40.9±0.3

[0103] 2) Effects on the number of mice falling asleep and the sleep rate in the direct sleep experiment

[0104] As shown in Table 2, compared with the model control group, the number of babies falling asleep and the time to fall asleep were all 0 in the Bai Le Mian capsule group, the low-dose group of Example 1, the high-dose group of Example 1, the groups of Examples 2-3, and the comparative examples 1-5, with no statistically significant difference (P>0.05). This proves that the solvent physiological saline, Bai Le Mian capsule, and the compositions prepared in Examples 1-3 and the comparative examples 1-5 have no direct hypnotic effect.

[0105] Table 2. Effects of drug administration on direct sleep in mice in each group ( n=10)

[0106] 1 Model control group 0 0 2 Bailumian Capsule Group 0 0 3 Example 1 Low-dose group 0 0 4 Example 1 High-dose group 0 0 5 Example 2 group 0 0 6 Example 3 Group 0 0 7 Comparative Example 1 0 0 8 Comparative Example 2 0 0 9 Comparative Example 3 Groups 0 0 10 Comparative Example 4 Groups 0 0 11 Comparative Example 5 Groups 0 0

[0107] 3) Effect on prolonging sodium pentobarbital sleep duration in mice

[0108] As can be seen from Table 3, after administration, compared with the model control group, the low-dose group of Example 1 and the comparative groups 3-5 showed a trend of prolonging the sleep time of mice, but the effect was not significant.

[0109] Compared with the model control group, the other groups showed the following prolongations: Bai Le Mian capsule group (54.30%, P<0.001), high-dose group of Example 1 (57.81%, P<0.001), group of Example 2 (55.47%, P<0.001), group of Example 3 (49.22%, P<0.001), comparative example 1 (17.19%, P<0.05), and comparative example 2 (21.09%, P<0.05).

[0110] Compared with the low-dose group of Example 1, the high-dose group of Example 1 showed significantly higher efficacy (P < 0.01). Compared with the high-dose group of Example 1, there were no significant differences in groups 2-3, while significant differences were observed in groups 3-5 (P < 0.01, P < 0.001), demonstrating that the composition of the present invention is most effective under specific formulations and ratios. These results indicate that the high-dose group of Example 1 and groups 2-3 can significantly prolong the sleep duration of sodium pentobarbital and improve sleep.

[0111] Table 3. Effects of pentobarbital sodium administration on sleep onset time in mice of different groups ( n=10)

[0112]

[0113]

[0114] Note: Compared with the model control group, * P < 0.05 ** P < 0.01, *** P < 0.001;

[0115] Compared with the low-dose group in Example 1, ◆ P < 0.05 ◆◆ P < 0.01, ◆◆◆ P < 0.001;

[0116] Compared with the high-dose group in Example 1, # P < 0.05 ## P < 0.01, ### P < 0.001.

[0117] 4) Effects of subthreshold doses of sodium pentobarbital on hypnosis in mice

[0118] As shown in Table 4, compared to the model control group mice which only showed a 10% sleep onset rate after injection of subthreshold doses of sodium pentobarbital, the sleep onset rates of mice in each test sample group increased after treatment with the same dose, showing different synergistic effects. Specifically, although the low-dose group of Example 1 and the comparative groups 3-5 had some promoting effect, the increase in sleep onset rate was the most moderate, all increasing by 10% compared to the model control group. In contrast, the performance of the comparative groups 1-2 was more obvious, with an increase in sleep onset rate of 20%-30%. It is particularly noteworthy that the Bai Le Mian capsule group, the high-dose group of Example 1, and the groups of Examples 2-3 showed more obvious sleep-aiding effects, with an increase in sleep onset rate far exceeding 40%, highlighting the better efficacy of these samples in promoting sleep, and suggesting that the combination effect of the compositions of the present invention is optimal, and the ratio should be within a certain range.

[0119] Table 4. Effects of each group of mice on the sleep rate after administration of subthreshold doses of sodium pentobarbital (Table 4.) n=10)

[0120]

[0121]

[0122] 5) Effects on sodium barbital sleep latency in mice

[0123] As shown in Table 5, after administration, compared with the model control group, the low-dose group of Example 1 and the comparative groups 3-5 showed a trend of shortening the sleep latency, but the difference was not statistically significant. Compared with the model control group, the other groups showed the following reductions: Bai Le Mian capsule group (66.60%, P < 0.001), high-dose group of Example 1 (64.58%, P < 0.001), group 2 (60.41%, P < 0.001), group 3 (63.87%, P < 0.001), comparative group 1 (16.53%, P < 0.05), and comparative group 2 (15.82%, P < 0.05). Compared with the low-dose group of Example 1, the high-dose group of Example 1 showed significantly higher efficacy (P < 0.01). Compared with the high-dose group of Example 1, there was no significant difference in the groups of Examples 2-3, while there was a significant difference in the groups of Comparative Examples 1-5 (P<0.05, P<0.01), which proves that the specific components and proportions of the composition of the present invention have a significant effect on improving sleep. The above results show that the high-dose group of Example 1 and the groups of Examples 2-3 can significantly shorten the sleep latency and improve sleep.

[0124] Table 5. Effects of each group of mice on the sleep latency of sodium barbital after administration ( n=10)

[0125]

[0126]

[0127] Note: Compared with the model control group, * P < 0.05 ** P < 0.01, *** P < 0.001;

[0128] Compared with the low-dose group in Example 1, ◆ P < 0.05 ◆◆ P < 0.01, ◆◆◆ P < 0.001;

[0129] Compared with the high-dose group in Example 1, # P < 0.05 ## P < 0.01, ### P < 0.001.

[0130] Test Example 2: Anti-anxiety and Anti-depression Test

[0131] a) Laboratory animals:

[0132] Three hundred and thirty SPF-grade healthy male ICR mice (6-8 weeks old, weighing 18-22g) were randomly divided into three large groups, 110 mice per large group. The first large group consisted of 11 subgroups, 10 mice per subgroup. The groups were: model control group, Shugan Jieyu capsule group (positive control), low-dose group of Example 1, high-dose group of Example 1, group of Example 2, group of Example 3, comparative group 1, comparative group 2, comparative group 3, comparative group 4, and comparative group 5. Forced swimming test was performed on each group one month after drug administration. The second large group of mice underwent tail suspension test one month after drug administration, with the same grouping as the first large group. The third large group underwent light and dark box test one month after drug administration, with the same grouping as the first large group. All experimental animals were tested only once. (The experimental animals were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., license number: SCXK(Su)2023-0009). They were acclimatized for at least one week under the conditions of room temperature 25℃, humidity 60%, and 12h light-dark cycle. All animals were given equal amounts of ordinary feed and drinking water.

[0133] b) Drug preparation and daily dosage:

[0134] Model control group: physiological saline;

[0135] Liver-Soothing and Depression-Relieving Capsule Group (Positive Control): Liver-Soothing and Depression-Relieving Capsules were purchased from Chengdu Kanghong Pharmaceutical Group Co., Ltd., Approval Number: National Drug Approval Number Z20080580; Drug Specification: 0.36g*28 capsules / box; Dosage: 0.22g·kg -1 ·d -1 Dissolved in physiological saline.

[0136] Example 1 Low-dose group: The composition prepared in Example 1 was administered at a dose of 0.9 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0137] Example 1 High-dose group: The composition prepared in Example 1 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0138] Example 2 group: The composition prepared in Example 2 was administered at a dosage of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0139] Example 3 group: The composition prepared in Example 3 was administered at a dosage of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0140] Comparative Example 1: The composition prepared in Comparative Example 1 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0141] Comparative Example 2: The composition prepared in Comparative Example 2 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0142] Comparative Example 3: The composition prepared in Comparative Example 3 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0143] Comparative Example 4: The composition prepared in Comparative Example 4 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline;

[0144] Comparative Example 5: The composition prepared in Comparative Example 5 was administered at a dose of 1.8 g / kg. -1 ·d -1 Dissolved in physiological saline.

[0145] All animals were given the same amount of normal feed and drinking water. Mice in each group were administered medication by gavage once daily in the morning for 30 consecutive days, at a volume of 10 mL / kg. -1 ·d -1 .

[0146] c) Test items:

[0147] 1) Forced swimming experiment:

[0148] Experimental preparation: Prepare a transparent pool with water depth sufficient to prevent mice from standing or lying flat without touching the surface. Typically, the forced swimming pool for mice is 10 cm in diameter and 25 cm high. Configure a backlighting system to minimize the impact of water droplets on the experiment, and use a thermostat to maintain the water temperature at 23-25℃ to ensure consistent experimental conditions.

[0149] Experimental procedure: Gently place the mice into the pool and record their swimming behavior. The experimental animals swam in the pool for 6 minutes, and the time the animals remained still in the water for 4 minutes afterward was recorded.

[0150] 2) Tail Suspension Test

[0151] Experimental preparation: suspension device (including transparent tape), video recording equipment, cages, and data recording and analysis software, etc. The suspension device should be stable, and the height should be such that the mouse's tail is at least 25 cm off the ground to ensure that the mouse cannot reach any support.

[0152] Experimental procedure: Gently grasp the mouse and suspend it on the suspension device with tape, approximately 1-2 cm from the tip of the tail. Hang the experimental animal upside down in the tail-suspended box and record the time the animal remains still for the last 4 minutes of the 5-minute period.

[0153] 3) Dark and Light Box Experiment

[0154] Experimental preparation: darkroom, partition door, and data recording and analysis software. Before each experiment, ensure the darkroom is clean and odorless.

[0155] Experimental Procedure: Gently place the animal into the dark area of ​​the light-dark chamber, facing the passageway, and close the passageway. Allow the animal to acclimatize to the dark environment for approximately 5 minutes. Open the small door connecting the light and dark areas, start the timer, and allow the animal to move freely within the light-dark chamber for 5 minutes. Use a camera to record the animal's behavior during the experiment and the duration of time the animal spends in the light chamber.

[0156] d) Test Results

[0157] 1) Effects on the forced swimming test in mice

[0158] The immobility time of mice within 4 minutes after swimming for 6 minutes was recorded, and the data were statistically analyzed. The experimental results are shown in Table 6. After 30 days of continuous administration, compared with the model control group, the immobility time of mice was shortened by 6.99% in the low-dose group of Example 1, 8.61% in the comparative group 1, 6.65% in the comparative group 2, 7.41% in the comparative group 3, 9.30% in the comparative group 4, and 5.57% in the comparative group 5, but none of these results were statistically significant. Compared with the model control group, the immobility time of mice in other groups was shortened by 27.74% (P < 0.01) in the Shugan Jieyu Capsule group, 23.57% (P < 0.01) in the high-dose group of Example 1, 25.27% (P < 0.01) in the group of Example 2, and 21.47% (P < 0.01) in the group of Example 3, all of which were statistically significant. Compared with the immobility time of the low-dose group in Example 1, the high-dose group in Example 1 showed significantly higher efficacy (P < 0.05). Compared with the high-dose group in Example 1, there was no significant difference in groups 2-3, while significant differences were observed in groups 1-5 (P < 0.05, P < 0.01), demonstrating that the composition of the present invention is more effective under specific components and ratios. These results indicate that the high-dose group in Example 1 and groups 2-3 can significantly reduce immobility time and improve depressive symptoms in mice.

[0159] Table 6. Effects on the forced swimming test in mice ( n=10)

[0160]

[0161]

[0162] Note: Compared with the model control group, * P < 0.05 ** P < 0.01, *** P < 0.001;

[0163] Compared with the low-dose group in Example 1, ◆ P < 0.05 ◆◆ P < 0.01, ◆◆◆ P < 0.001;

[0164] Compared with the high-dose group in Example 1, # P < 0.05 ## P < 0.01, ### P < 0.001.

[0165] 2) Effects on the mouse tail suspension test

[0166] The immobility time of mice within 5 minutes after tail suspension and 4 minutes thereafter was recorded, and the data were statistically analyzed. The experimental results are shown in Table 7. After 30 days of continuous administration, compared with the model control group, the immobility time of mice was shortened by 9.37% in the low-dose group of Example 1, 13.32% in Comparative Example 1, 16.89% in Comparative Example 2, 19.31% in Comparative Example 3, 9.49% in Comparative Example 4, and 8.80% in Comparative Example 5, but none of these results were statistically significant. Compared with the model control group, the immobility time of mice in other groups was shortened by 92.22% (P < 0.001) in the Shugan Jieyu Capsule group, 91.87% (P < 0.001) in the high-dose group of Example 1, 63.21% (P < 0.01) in the group of Example 2, and 78.97% (P < 0.01) in the group of Example 3, all of which were statistically significant. Compared with the high-dose group of Example 1, there was no significant difference in the groups of Examples 2-3, while there was a significant difference in the groups of Comparative Examples 1-5 (P<0.01, P<0.001), which proves that the composition of the present invention is more effective under specific components and ratios. The above results indicate that the high-dose group of Example 1 and the groups of Examples 2-3 can significantly shorten the immobility time of mice with tail-reduced suspension and alleviate the depressive symptoms of mice.

[0167] Table 7. Effects on mouse tail suspension test ( n=10)

[0168]

[0169]

[0170] Note: Compared with the model control group, * P < 0.05 ** P < 0.01, *** P < 0.001;

[0171] Compared with the low-dose group in Example 1, ◆ P < 0.05 ◆◆ P < 0.01, ◆◆◆ P < 0.001;

[0172] Compared with the high-dose group in Example 1, # P < 0.05 ## P < 0.01, ### P < 0.001.

[0173] 3) Effects on the light-dark chamber experiment in mice

[0174] As shown in Table 8, compared with the model control group, the time to enter the bright field was prolonged by 8.24% in the low-dose group of Example 1, 12.33% in Comparative Example 1, 9.55% in Comparative Example 2, 7.32% in Comparative Example 3, 6.16% in Comparative Example 4, and 9.01% in Comparative Example 5, but none of these results were statistically significant. Compared with the model control group, the other groups showed a 37.67% prolongation in the Shugan Jieyu Capsule group (P < 0.001), a 38.75% prolongation in the high-dose group of Example 1 (P < 0.001), and a 34.44% prolongation in the group of Example 2 (P < 0.001). Compared with the low-dose group of Example 1, the high-dose group of Example 1 showed significantly higher efficacy (P < 0.001). Compared with the high-dose group of Example 1, there was no significant difference in the groups of Examples 2-3, while there was a significant difference in the groups of Comparative Examples 1-5 (P<0.01, P<0.001), which proves that the composition of the present invention is more effective under specific components and ratios. The above results indicate that the high-dose group of Example 1 and the groups of Examples 2-3 can significantly increase the time mice spend in the bright field and reduce the anxiety symptoms of mice.

[0175] Table 8. Effects on the light-dark chamber test in mice ( n=10)

[0176]

[0177]

[0178] Note: Compared with the model control group, * P < 0.05 ** P < 0.01, *** P < 0.001;

[0179] Compared with the low-dose group in Example 1, ◆ P < 0.05 ◆◆ P < 0.01, ◆◆◆ P < 0.001;

[0180] Compared with the high-dose group in Example 1, # P < 0.05 ## P < 0.01, ### P < 0.001.

[0181] In the results of this invention, prior to modeling, a direct sleep experiment demonstrated that the 30-day administration had no significant effect on mouse body weight and did not directly induce sleep in mice. The pentobarbital sodium sleep duration prolongation experiment showed that the high-dose group of Example 1 significantly prolonged mouse sleep time compared to the low-dose group of Example 1 and Comparative Examples 1-5 (P<0.01, P<0.001), with no significant difference compared to the Bai Le Mian capsule group and Example 2-3 groups. The pentobarbital sodium subthreshold dose hypnotic experiment showed that the sleep onset rate of mice in the high-dose group of Example 1 was better than that in the low-dose group and Comparative Examples 1-5, and similar to that in the Bai Le Mian capsule group and Example 2-3 groups. The pentobarbital sodium sleep latency experiment showed that the sleep latency of mice in the high-dose group of Example 1 was significantly shorter than that in the low-dose group of Example 1 and Comparative Examples 1-5 (P<0.05, P<0.01), with no significant difference compared to the Bai Le Mian capsule group and Example 2-3 groups. The above results all indicate that this formula has the effect of improving sleep, suggesting that this combination of formulas has the best effect, and the combination ratio should be within a certain range.

[0182] Further investigation was conducted using three mouse behavioral experiments to explore the effects of each drug administration group on depression and anxiety, two mental disorders in mice. The forced swimming and tail suspension tests showed that the immobility time of mice in the high-dose group of Example 1 was significantly shorter than that of the low-dose group of Example 1 and Comparative Examples 1-5 (P<0.05, P<0.01, P<0.001), but there was no significant difference compared to the Shugan Jieyu Capsule group and Examples 2-3, indicating that this formulation has a certain antidepressant effect. The light-dark box test showed that the duration of immobility in the high-dose group of Example 1 in the light field was significantly longer than that of the low-dose group of Example 1 and Comparative Examples 1-5 (P<0.01, P<0.001), but there was no significant difference compared to the Shugan Jieyu Capsule group and Examples 2-3, indicating that this formulation has a certain anti-anxiety effect. All these results indicate that this formulation has antidepressant and anti-anxiety effects, and suggest that the combination of these formulations is optimal, and the combination ratio should be within a certain range.

[0183] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for improving sleep and relieving anxiety and depression, characterized in that, The composition, by weight, is made from the following raw materials: 10-30 parts of Poria cocos, 5-15 parts of Ziziphus jujuba var. spinosa, 4-15 parts of lily bulb, 1-10 parts of mulberry fruit, 20-40 parts of Citrus medica var. sarcodactylis, 10-25 parts of wheat, 2-10 parts of jujube, 5-20 parts of Ganoderma lucidum, 2-10 parts of Gastrodia elata powder, 5-15 parts of licorice root, and 5-15 parts of donkey-hide gelatin.

2. The method for preparing the composition according to claim 1, characterized in that, Includes the following steps: S1: Take Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum and licorice, add solvent to extract, concentrate 1-3 times to obtain concentrated solution; S2: Melt the donkey-hide gelatin and crush the jujube seed. Add the melted donkey-hide gelatin, gastrodia elata powder, and jujube seed powder to the concentrated liquid obtained in S1, mix, and let stand at 0-5℃ for 10-15 hours. Separate and take the supernatant to obtain the extract.

3. The preparation method according to claim 2, characterized in that, In S1, the solvent is water, and the mass of water is 8-12 times the total mass of Poria cocos, lily bulb, mulberry, Buddha's hand, wheat, jujube, Ganoderma lucidum and licorice.

4. The preparation method according to claim 3, characterized in that, In S1, the extraction is performed by heating and reflux extraction at a temperature of 95-100℃.

5. The preparation method according to claim 2, characterized in that, The preparation method further includes the following steps: concentrating the extract into a thick paste, drying it, pulverizing it, and obtaining the extract.

6. The preparation method according to claim 5, characterized in that, The preparation method further includes the following steps: concentrating the extract under reduced pressure to a thick paste with a relative density of 1.28-1.31, drying under reduced pressure at 60-70°C, and pulverizing into powder to obtain the extract.

7. A pharmaceutical preparation, characterized in that, It is made from the composition for improving sleep and relieving anxiety and depression as described in claim 1.

8. Use of the composition of claim 1 or the pharmaceutical preparation of claim 7 in the preparation of a medicament for improving sleep and relieving anxiety and depression.

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