Composition for improving sleep and resisting anxiety and depression, pharmaceutical preparation and application

Abstract

The invention provides a composition for improving sleep and resisting anxiety and depression, a pharmaceutical preparation and application, and relates to the technical field of traditional Chinese medicines. The composition comprises the following components: poria cocos, spina date seeds, lily bulbs, mulberries, fingered citron, wheat, Chinese dates, lucid ganoderma, gastrodia elata powder, licorice roots and donkey-hide gelatin. Under the specific components and proportions, the prepared composition has better effects of improving sleep and resisting anxiety and depression; the raw materials are simple, easy to obtain, safe, toxic and free of side effects; the preparation method is simple and suitable for industrial popularization.

Description

Technical Field

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

[0002] Insomnia usually refers to a subjective experience in which patients are dissatisfied with sleep time and / or quality and their daytime social functions are affected. Insomnia is manifested as difficulty falling asleep (sleep time exceeds 30 minutes), sleep maintenance disorder (awakening ≥2 times throughout the night), early awakening, decreased sleep quality and reduced total sleep time (usually less than 6 hours), accompanied by daytime functional disorders. Insomnia is divided into acute insomnia (course ≥1 month); subacute insomnia (course ≥1 month, <6 months) and chronic insomnia (course ≥6 months) according to the course of the disease. With the changes in 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 has also gradually expanded, usually accompanied by depression, anxiety and other complications. Studies have shown that 40% of insomnia patients have one or more mental disorders, of which anxiety disorders account for as high as 24%.

[0003] Currently, the main treatments for anxiety-related insomnia include psychological counseling and auxiliary chemotherapy. However, chemotherapy often brings a series of side effects, such as dizziness, headache, nausea, loss of appetite, stomach pain and other symptoms in the early stage of taking it. Long-term use may cause stomach discomfort, loss of appetite, and even drug resistance and drug dependence.

[0004] In contrast, Chinese medicine formulas have fewer side effects and are less likely to cause drug resistance and drug dependence. According to TCM theory, insomnia belongs to the categories of "insomnia", "eyes cannot close", "cannot lie down", etc. The heart stores the spirit, and it is difficult to fall asleep if the mind is restless; the liver stores the soul, and it is easy to wake up and have difficulty sleeping if the liver and soul are restless. If the heart and liver are deficient in blood, the spirit and soul will not be nourished, and you will not be able to sleep at night. During treatment, the method should be to nourish the heart and calm the mind, and to soothe the liver and relieve depression, aiming to harmonize the mind and make sleep stable.

[0005] Chinese patent CN 117562958 A discloses a composition of Sophora japonica and tangerine peel for improving sleep and relieving anxiety and its preparation method, the composition contains tangerine peel extract, Sophora japonica extract, banana powder, day lily powder, Ziziphus jujuba powder, Perilla powder, white lentil seed coat extract, modified Lactobacillus reuteri and modified animal Bifidobacterium; mostly raw materials of medicinal and edible homology, safe composition, no risk of toxic and side effects. The components treated specially are combined, with the effects of synergistically promoting sleep, improving anxiety and anti-depression, and the experimental results show that the curative effect is fast and obvious, can shorten the course of treatment, has no side effects and dependence, and is particularly suitable for patients with moderate and mild anxiety, insomnia and depression. However, the preparation method of the composition is complicated, and tangerine peel extract, Sophora japonica extract and white lentil seed coat extract all need enzymolysis, which is not suitable for large-scale promotion.

[0006] Chinese patent CN 115645462 A provides a Chinese medicine composition for improving sleep and resisting depression, a preparation method and use thereof, wherein the Chinese medicine composition is made of the following raw materials in parts by weight: 4-6 parts of Atractylodes, 4-9 parts of Poria, 3-6 parts of Chuanxiong, 3-9 parts of Angelica, 2-6 parts of Bupleurum, 2-6 parts of Licorice, 3-9 parts of Uncaria, and 2-4 parts of Red Dates, and has the effects of improving sleep, relieving anxiety, treating post-traumatic stress disorder and resisting depression. However, its effect is not ideal and still needs to be improved.

[0007] Based on this, developing a Chinese medicine composition that can effectively improve people's sleep quality and relieve anxiety and depression is of great significance to improving people's quality of life and reducing medical burden. Summary of the invention

[0008] In view of the above problems, the present invention provides a composition for improving sleep and relieving anxiety and depression, a pharmaceutical preparation and application. The composition of the present invention comprises Poria cocos, Ziziphus jujuba seeds, lily, mulberry, bergamot, wheat, jujube, Ganoderma lucidum, Gastrodia elata powder, licorice and donkey-hide gelatin. By optimizing the composition ratio, the obtained traditional Chinese medicine composition has safe and non-toxic ingredients, low side effects and good effects of improving sleep and relieving anxiety and depression.

[0009] To achieve the above purpose, 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, spiny jujube seeds, lily, mulberry, bergamot, wheat, jujube, Ganoderma lucidum, Gastrodia elata powder, licorice, and donkey-hide gelatin.

[0011] The present invention provides a composition for improving sleep and resisting anxiety and depression. Among them, Poria cocos is the first of the main drugs, which can strengthen the spleen and calm the mind, promote diuresis and eliminate dampness, calm the mind and stabilize the spirit, and has a good therapeutic effect on insomnia, dreaminess, palpitations and anxiety caused by deficiency of both heart and spleen and retention of dampness. Ziziphus jujuba seeds and Poria cocos are combined to nourish the heart and liver, calm the mind and eliminate vexation, promote the production of body fluid and calm the mind, and strengthen the calming effect of the main drug for the symptoms of insomnia, palpitations and dreaminess due to deficiency and vexation. It can calm the mind. Lily and mulberry are listed as minister drugs. Lily can clear the heart and moisten the lungs, nourish yin and calm the mind, and effectively relieve anxiety and depression caused by yin deficiency, fire and emotional depression; mulberry can nourish yin and blood, promote the production of body fluid and moisten dryness. The combination of the two can not only nourish the yin of the heart and liver, but also calm the restless mind. Buddha's hand and wheat are both in the camp of ministerial drugs. Buddha's hand can relieve liver qi and depression, regulate qi and harmonize the middle, and is specially designed for anxiety and depression caused by liver qi stagnation; wheat is sweet and cool to nourish the heart, relieve restlessness and benefit the kidney, and is especially suitable for those with strong heart fire and restlessness. Jujube, Ganoderma lucidum, and Gastrodia elata powder are used as adjuvant drugs. Jujube can replenish qi, nourish blood and calm the mind, and complement Ganoderma lucidum. It not only enhances immunity, but also deepens the effect of calming the mind and relieving depression; Ganoderma lucidum can replenish qi and calm the mind, relieve cough and asthma, and has significant benefits for those with long-term insomnia and neurasthenia; Gastrodia elata powder can calm wind and stop spasms, calm liver yang, and effectively relieve dizziness, headache, irritability and anger caused by hyperactivity of liver yang, and assist the monarch and ministerial drugs to overcome anxiety and depression. Licorice, as a messenger drug, replenishes qi and detoxifies, and harmonizes various drugs. It not only reduces the harshness of the drug properties, but also promotes the synergistic effect between the drugs, making the entire paste mild in nature and easy for the human body to absorb. Although donkey-hide gelatin does not directly affect sleep and mood, its properties of nourishing blood and yin, moistening dryness and stopping bleeding can indirectly improve the restlessness caused by blood deficiency and yin deficiency, adding the finishing touch to the overall tonic effect of the paste. The above paste achieves the comprehensive effect of improving sleep and resisting anxiety and depression through the careful combination of medicinal materials such as Poria cocos and Ziziphus jujuba seeds, and is suitable for people who suffer from insomnia, anxiety and depression for a long time.

[0012] Preferably, the composition comprises the following components by mass: 8-32 parts of Poria cocos, 4-16 parts of Ziziphus jujuba seeds, 4-18 parts of lilies, 1-15 parts of mulberries, 18-40 parts of bergamots, 10-28 parts of wheat, 2-12 parts of jujubes, 5-22 parts of Ganoderma lucidum, 2-12 parts of Gastrodia elata powder, 4-16 parts of licorice, and 4-16 parts of donkey-hide gelatin.

[0013] Further preferably, the composition comprises the following components by mass: 10-30 parts of Poria cocos, 5-15 parts of Ziziphus jujuba seeds, 4-15 parts of lilies, 1-10 parts of mulberries, 20-40 parts of bergamots, 10-25 parts of wheat, 2-10 parts of jujubes, 5-20 parts of Ganoderma lucidum, 2-10 parts of Gastrodia elata powder, 5-15 parts of licorice, and 5-15 parts of donkey-hide gelatin.

[0014] More preferably, the composition comprises the following components by weight: 15-25 parts of Poria cocos, 5-8 parts of Ziziphus jujuba seeds, 5-8 parts of lilies, 2-5 parts of mulberries, 25-35 parts of bergamots, 15-25 parts of wheat, 3-8 parts of jujubes, 10-20 parts of Ganoderma lucidum, 3-5 parts of Gastrodia elata powder, 5-12 parts of licorice, and 5-15 parts of donkey-hide gelatin.

[0015] Most preferably, the composition comprises the following components by mass: 20 parts of Poria cocos, 8 parts of Ziziphus jujuba seeds, 8 parts of lilies, 2 parts of mulberries, 30 parts of bergamot, 20 parts of wheat, 5 parts of jujube, 15 parts of Ganoderma lucidum, 3 parts of Gastrodia elata powder, 10 parts of licorice, and 10 parts of donkey-hide gelatin.

[0016] In another aspect, the present invention provides a method for preparing the above-mentioned composition, comprising the following steps:

[0017] S1: Take Poria cocos, lily, mulberry, bergamot, wheat, jujube, ganoderma lucidum and licorice, add solvent to extract, concentrate 1-3 times, and obtain a concentrated solution;

[0018] S2: Melt donkey-hide gelatin and crush spinach kernel, add melted donkey-hide gelatin, gastrodia powder and spinach kernel powder to the concentrated solution obtained in S1, mix, let stand at 0-5℃ for 10-15h, 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, mulberry, bergamot, wheat, jujube, Ganoderma lucidum and licorice; further preferably, in S1, the solvent is water, and the mass of the water is 8-12 times the total mass of Poria cocos, lily, mulberry, bergamot, wheat, jujube, Ganoderma lucidum and licorice.

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

[0021] Preferably, in S2, the solvent is water, and the mass of the water is 8-12 times the total mass of Poria cocos, lily, mulberry, bergamot, wheat, jujube, ganoderma lucidum and licorice. Further preferably, in S2, the solvent is water, and the mass of the water is 10 times the total mass of Poria cocos, lily, mulberry, bergamot, wheat, jujube, ganoderma lucidum and licorice.

[0022] Preferably, the preparation method further comprises the following steps: concentrating the extract into a thick paste, drying, and crushing to obtain an extract.

[0023] Preferably, the preparation method further comprises 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 crushing into powder to obtain an extract.

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

[0025] Preferably, the auxiliary materials include isomaltooligosaccharide and maltitol.

[0026] In another aspect, the present invention provides a pharmaceutical preparation comprising the above-mentioned composition.

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

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

[0029] The pharmaceutical carrier used can be solid, liquid or gas. 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] When preparing the composition for oral dosage form, any convenient pharmaceutical medium can be used. For example, water, ethanol, oil, alcohol, flavoring agent, preservative, coloring agent, etc. can be used to form oral liquid preparations, such as suspensions, elixirs and solutions; while carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulating agents, emulsifiers, lubricants, binders, disintegrants can be used to form oral solid preparations, 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 composition of the invention may be prepared by tabletting or molding, optionally with the use of one or more auxiliary ingredients or adjuvants. Compressed tablets may be prepared by tabletting the active ingredient in a free-flowing form (such as powder or granules) in a suitable machine, optionally mixed with a binder, lubricant, inert diluent, surface active substance or dispersant. Molded tablets may be molded in a suitable machine, i.e. a mixture of powdered compounds moistened with an inert liquid diluent.

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

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

[0034] The invention provides a traditional Chinese medicine composition, comprising 11 components, namely, Poria cocos, spiny jujube seeds, lily, mulberry, citron, wheat, jujube, ganoderma lucidum, gastrodia elata powder, liquorice, donkey-hide gelatin, etc. By optimizing the components and proportions, it is found that under specific components and proportions, the composition has better effects of improving sleep and relieving anxiety and depression; and the raw materials are simple and easy to obtain, safe, non-toxic, and have no side effects; the preparation method is simple, and is suitable for industrial promotion. DETAILED DESCRIPTION

[0035] In order to make the technical means, creative features, purpose and effect of the present invention easy to understand, the present invention is further explained below in conjunction with specific embodiments, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without making creative work all belong to the protection scope of the present invention. It is worth noting that the raw materials used in the present invention are all common commercial products, and their sources are not specifically limited. The technology and scientific terms used in the embodiments have the meanings commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0036] Example 1

[0037] A composition for improving sleep and resisting anxiety and depression:

[0038] The composition comprises the following components by weight: 20 parts of Poria cocos, 8 parts of Semen Ziziphi Spinosae, 8 parts of Lilium, 2 parts of Mulberry, 30 parts of Citron, 20 parts of Wheat, 5 parts of Jujube, 15 parts of Ganoderma Lucidum, 3 parts of Gastrodia elata powder, 10 parts of Licorice, and 10 parts of Donkey-hide Gelatin;

[0039] Preparation method: Take Poria cocos, lily, mulberry, bergamot, wheat, jujube, Ganoderma lucidum and licorice, add 10 parts of water, heat and reflux at 100°C for extraction, and concentrate 1-3 times to obtain a concentrated solution; take donkey-hide gelatin and add water to melt it, add the melted donkey-hide gelatin, gastrodia powder and spiny jujube kernel to the above concentrated solution, stir for 30 minutes, let stand at 4°C for 12 hours, separate the supernatant, concentrate it to a thick paste with a relative density of 1.28-1.31, dry it under reduced pressure at 60-70°C, and grind it into powder.

[0040] Example 2

[0041] A composition for improving sleep and resisting anxiety and depression:

[0042] The composition comprises the following components by weight: 30 parts of Poria cocos, 15 parts of Semen Ziziphi Spinosae, 15 parts of Lilium Bulbs, 10 parts of Mulberries, 40 parts of Citron, 10 parts of Wheat, 10 parts of Jujube, 5 parts of Ganoderma Lucidum, 10 parts of Gastrodia elata Powder, 5 parts of Licorice, and 5 parts of Donkey-hide Gelatin;

[0043] Preparation method: Same as Example 1.

[0044] Example 3

[0045] A composition for improving sleep and resisting anxiety and depression:

[0046] The composition comprises the following components by weight: 10 parts of Poria cocos, 5 parts of Semen Ziziphi Spinosae, 4 parts of Lilium, 1 part of Mulberry, 20 parts of Citron, 25 parts of Wheat, 2 parts of Jujube, 20 parts of Ganoderma Lucidum, 2 parts of Gastrodia elata Powder, 15 parts of Licorice, and 15 parts of Donkey-hide Gelatin;

[0047] Preparation method: Same as Example 1.

[0048] Comparative Example 1

[0049] A composition for improving sleep and resisting anxiety and depression:

[0050] The composition comprises the following components by weight: 32 parts of Poria cocos, 20 parts of Ziziphus jujuba seeds, 20 parts of Lilium, 0.5 parts of Mulberry, 15 parts of Citron, 8 parts of Wheat, 12 parts of Jujube, 21.5 parts of Ganoderma lucidum, 1 part of Gastrodia elata powder, 3 parts of Licorice, and 4 parts of Donkey-hide gelatin;

[0051] Preparation method: Same as Example 1.

[0052] Comparative Example 2

[0053] A composition for improving sleep and resisting anxiety and depression:

[0054] The composition comprises the following components by weight: 6 parts of Poria cocos, 2 parts of Ziziphus jujuba seeds, 2 parts of Lilium bulbs, 12 parts of Mulberries, 42 parts of Citron, 26 parts of Wheat, 1 part of Jujube, 4 parts of Ganoderma lucidum, 12 parts of Gastrodia elata powder, 18 parts of Licorice, and 18 parts of Donkey-hide gelatin;

[0055] Preparation method: Same as Example 1.

[0056] Comparative Example 3

[0057] A composition for improving sleep and resisting anxiety and depression:

[0058] The composition comprises the following components by weight: 8 parts of Semen Ziziphi Spinosae, 10 parts of Licorice, and 20 parts of Poria;

[0059] Preparation method: extract licorice and poria with solvent, concentrate 1-3 times to obtain a concentrated solution; add spiny jujube seeds to the concentrated solution, mix, stand at 0-5°C for 10-15h, separate the supernatant, concentrate to obtain an extract solution, dry and crush.

[0060] Comparative Example 4

[0061] A composition for improving sleep and resisting anxiety and depression:

[0062] The composition comprises the following components by weight: 10 parts of licorice, 20 parts of wheat, and 5 parts of jujube;

[0063] Preparation method: extract liquorice, wheat and jujube with solvent, concentrate 1-3 times to obtain concentrated solution, further concentrate to obtain extract solution, dry and crush.

[0064] Comparative Example 5

[0065] A composition for improving sleep and resisting anxiety and depression:

[0066] The composition comprises the following components by weight: 3 parts of Gastrodia elata and 15 parts of Ganoderma lucidum;

[0067] Preparation method: Ganoderma lucidum is extracted with solvent, concentrated 1-3 times to obtain a concentrated solution, Gastrodia elata is added to the concentrated solution, mixed, allowed to stand at 0-5°C for 10-15h, the supernatant is separated, concentrated to obtain an extract solution, dried, and crushed.

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

[0069] Test Example 1: Improving sleep detection

[0070] a) Experimental animals:

[0071] 330 SPF healthy male ICR mice (6-8 weeks old, body weight 18-22 g, purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., license number: SCXK (Su) 2023-0009) were adaptively raised for 1 week at room temperature 25°C, humidity 60%, and 12h light and dark cycle. They were randomly divided into 11 groups, with 30 mice in each group. All animals were given an equal amount of ordinary feed + drinking water.

[0072] The experiment was divided into three groups, with 10 mice in each group. Group A conducted direct sleep experiments and experiments on prolonged sleep time with sodium pentobarbital; Group B conducted subthreshold hypnosis experiments with sodium pentobarbital; and Group C conducted sodium pentobarbital sleep latency experiments.

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

[0074] c) Drug configuration and daily dosage:

[0075] Model control group: normal saline;

[0076] Bailemian capsule group (positive control): Bailemian capsule, purchased from Yangtze River Pharmaceutical Group Co., Ltd., approval number: National Medicine Standard Z20020131; drug specification: 0.27g*56 capsules / box; dosage: 0.27g·kg -1 ·d -1, dissolved in saline.

[0077] Example 1 Low-dose group: The composition prepared in Example 1, the dosage was 0.9 g·kg -1 ·d -1 , dissolved in saline;

[0078] Example 1 High-dose group: The composition prepared in Example 1, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0079] Example 2 group: the composition prepared in Example 2, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0080] Example 3 group: the composition prepared in Example 3, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0081] Comparative Example 1: The composition prepared in Comparative Example 1, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0082] Comparative Example 2: The composition prepared in Comparative Example 2, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0083] Comparative Example 3: The composition prepared in Comparative Example 3, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0084] Comparative Example 4: The composition prepared in Comparative Example 4, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0085] Comparative Example 5: The composition prepared in Comparative Example 5, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline.

[0086] All animals were given an equal amount of ordinary feed + drinking water. According to the above daily dosage, mice in each group were gavaged once every morning for 30 consecutive days, with a gavage volume of 10 mL·kg -1 ·d -1 .

[0087] d) Test items:

[0088] 1) Direct sleep experiment

[0089] After the mice were given physiological saline and different test samples for the last time, the model control group and each test sample group were checked for sleep. The loss of righting reflex was used as an indicator of sleep. When the mouse was placed in a dorsal position, it could turn right immediately. If it could not turn right for more than 30-60 seconds, it was considered that the righting reflex disappeared and the mouse fell asleep. The number of sleeping animals in each group was recorded, and the sleeping rate was calculated.

[0090] Sleeping rate % = number of mice that successfully fell asleep / total number of mice × 100%.

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

[0092] Before the formal experiment, a preliminary experiment was conducted to find the dose of sodium pentobarbital (determined to be 45 mg / kg) that would make the mice fall asleep completely but not for too long, and the subsequent experiments were carried out at this dose. After the mice were given normal saline and different test samples for the last time, 15 minutes before the peak effect appeared, each group of mice was intraperitoneally injected with sodium pentobarbital (freshly prepared before use), with an injection volume of 0.2 mL / 20 g, and the disappearance of the righting reflex was used as the standard to see whether the test sample could prolong the sleep time of sodium pentobarbital.

[0093] 3) Subthreshold dose hypnosis experiment of sodium pentobarbital

[0094] Before the formal experiment, a preliminary experiment was conducted to find the maximum subthreshold dose of sodium pentobarbital (determined to be 25 mg / kg) that prevented the righting reflex of 80-90% of mice from disappearing, and the subsequent experiments were carried out at this dose. After the mice were last given normal saline and different test samples, 15 minutes before the peak effect appeared, each group of mice was intraperitoneally injected with the maximum subthreshold hypnotic dose of sodium pentobarbital (freshly prepared before use), with an injection volume of 0.2 mL / 20 g, and the number of animals that fell asleep within 30 minutes (the righting reflex disappeared for more than 60 seconds) was recorded, and the sleeping rate was calculated.

[0095] Sleeping rate % = number of mice that successfully fell asleep / total number of mice × 100%.

[0096] 4) Sodium barbital sleep latency experiment

[0097] Before the formal experiment, a preliminary experiment was conducted to find the dose of sodium barbital (determined to be 250 mg / kg) that would make the mice fall asleep completely but not for too long, and the subsequent experiments were carried out at this dose. 15 minutes after the mice were last given normal saline and different test samples, each group of mice was intraperitoneally injected with sodium barbital (freshly prepared before use), with an injection volume of 0.2 mL / 20 g. Using the disappearance of the righting reflex as an indicator, the effect of the test sample on the sodium barbital sleep latency (the time from the injection of sodium pentobarbital to the onset of sleep) was observed.

[0098] e) Test results

[0099] 1) Effect on the body weight of mice

[0100] According to the data shown in Table 1, the body weight of the mice in the direct sleep experiment after 30 days of drug administration was recorded and variance analysis was performed. The results showed that the body weight of the mice in each test sample group was not significantly different from that of the model control group (P>0.05).

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

[0102] Serial number Group Weight (g) 1 Model control group 40.2±0.5 2 BELAMINE CAPSULE SET 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 41.3±1.2 10 Comparative Example 4 40.6±1.1 11 Comparative Example 5 40.9±0.3

[0103] 2) Effect on the number of sleeping mice and sleep rate in direct sleep experiment

[0104] As can be seen from Table 2, compared with the model control group, the number of sleep onset and the sleep onset time of the Bailemian capsule group, the low-dose group of Example 1, the high-dose group of Example 1, the Example 2-3 group and the comparative example 1-5 group were all 0, and the difference was not statistically significant (P>0.05), which proves that the solvent physiological saline, Bailemian capsules, Examples 1-3 and the compositions prepared by Comparative Examples 1-5 have no direct hypnotic effect.

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

[0106] Serial number Group Number of sleeping animals Sleeping rate (%) 1 Model control group 0 0 2 BELAMINE CAPSULE SET 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 0 0 10 Comparative Example 4 0 0 11 Comparative Example 5 0 0

[0107] 3) Effects of sodium pentobarbital on the prolonged sleep duration of mice

[0108] It can be seen from Table 3 that after administration, compared with the model control group, the low-dose group of Example 1 and the comparative example groups 3-5 had a tendency to prolong the sleeping time of mice, but it was not significant.

[0109] Compared with the model control group, the other groups were: the Bailemian capsule group was extended by 54.30% (P < 0.001), the high-dose group of Example 1 was extended by 57.81% (P < 0.001), the Example 2 group was extended by 55.47% (P < 0.001), the Example 3 group was extended by 49.22% (P < 0.001), the comparative example 1 group was extended by 17.19% (P < 0.05), and the comparative example 2 group was extended by 21.09% (P < 0.05).

[0110] Compared with the low-dose group of Example 1, the high-dose group of Example 1 has a much higher therapeutic effect than the former and is significant (P < 0.01). Compared with the high-dose group of Example 1, there is no significant difference in the Example 2-3 group, and there is a significant difference in the comparative example 3-5 group (P < 0.01, P < 0.001), which proves that the composition of the present invention has the best effect under a specific formula and ratio. The above results show that the high-dose group of Example 1 and the Example 2-3 group can significantly prolong the sleep time of sodium pentobarbital and improve sleep.

[0111] Table 3. Effects of sodium pentobarbital on sleep time in mice of each group after administration ( 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 with the model control group mice, which only showed a 10% sleep rate after injection of a subthreshold dose of sodium pentobarbital, the mice in each test sample group achieved an increase in sleep rate after the same dose treatment, showing different synergistic effects. Specifically, although the low-dose group of Example 1 and the comparative example 3-5 groups had a certain promoting effect, the increase in the sleep rate was the most moderate, both of which were 10% higher than the model control group. In contrast, the performance of the comparative example 1-2 group was more obvious, with an increase in the sleep rate of 20%-30%. It is particularly noteworthy that the Bailemian capsule group, the high-dose group of Example 1, and the Example 2-3 group showed a more obvious sleep-aiding effect, and the increase in their sleep rates was far more than 40%, highlighting that these samples have better efficacy in promoting sleep, and suggesting that the combination effect of the composition of the present invention is the best, and the ratio should be within a certain range.

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

[0120]

[0121]

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

[0123] As can be seen from Table 5, after administration, compared with the model control group, the low-dose group of Example 1 and the comparative examples 3-5 groups had a tendency to shorten the sleep latency, but there was no significance. Compared with the model control group, the other groups, the Bailemian capsule group, shortened by 66.60% (P < 0.001), the high-dose group of Example 1 shortened by 64.58% (P < 0.001), the Example 2 group shortened by 60.41% (P < 0.001), the Example 3 group shortened by 63.87% (P < 0.001), the comparative example 1 group shortened by 16.53% (P < 0.05), and the comparative example 2 group shortened by 15.82% (P < 0.05). Compared with the low-dose group of Example 1, the high-dose group of Example 1 had a much higher efficacy than the former and was significant (P < 0.01). Compared with the high-dose group of Example 1, there was no significant difference in Example 2-3 groups, and there was a significant difference in Comparative Example 1-5 groups (P < 0.05, P < 0.01), which proved 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 latency to fall asleep and improve sleep.

[0124] Table 5. Effects of sodium barbiturate on sleep latency of mice in each group 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 depression test

[0131] a) Experimental animals:

[0132] 330 SPF healthy male ICR mice (6-8 weeks old, body weight 18-22g) were randomly divided into three large groups, 110 / large group; the first large group of experimental animals was divided into 11 groups, 10 / group. The groups were set as: model control group, Shugan Jieyu capsule group (positive control), low-dose group of Example 1, high-dose group of Example 1, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, Comparative Example 5 group, and forced swimming test was performed 1 month after administration. The second large group of experimental animals were respectively subjected to tail suspension test for 1 month, and the grouping was the same as the first large group; the third large group was respectively subjected to light and dark box experiment for 1 month, and the grouping was the same as the first large group; all experimental animals were used only once. (The experimental animals were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., license number: SCXK(Su)2023-0009) and were adaptively raised under the conditions of room temperature of 25 °C, humidity of 60%, and 12 h light-dark cycle for at least 1 week, and all animals were given an equal amount of ordinary feed + drinking water.

[0133] b) Drug configuration and daily dosage:

[0134] Model control group: normal saline;

[0135] Shugan Jieyu Capsule Group (positive control): Shugan Jieyu Capsule, purchased from Chengdu Kanghong Pharmaceutical Group Co., Ltd., approval number: National Medicine Standard Z20080580; drug specification: 0.36g*28 capsules / box; dosage: 0.22g·kg -1 ·d -1 , dissolved in saline.

[0136] Example 1 Low-dose group: The composition prepared in Example 1, the dosage was 0.9 g·kg -1 ·d -1 , dissolved in saline;

[0137] Example 1 High-dose group: The composition prepared in Example 1, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0138] Example 2 group: the composition prepared in Example 2, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0139] Example 3 group: the composition prepared in Example 3, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0140] Comparative Example 1: The composition prepared in Comparative Example 1, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0141] Comparative Example 2: The composition prepared in Comparative Example 2, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0142] Comparative Example 3: The composition prepared in Comparative Example 3, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0143] Comparative Example 4: The composition prepared in Comparative Example 4, the dosage was 1.8 g·kg -1 ·d -1 , dissolved in saline;

[0144] Comparative Example 5: The composition prepared in Comparative Example 5, the dosage is 1.8 g·kg -1 ·d -1 , dissolved in saline.

[0145] All animals were given an equal amount of ordinary feed + drinking water. According to the above daily dosage, mice in each group were gavaged once every morning for 30 consecutive days, with a gavage volume of 10 mL·kg -1 ·d -1 .

[0146] c) Test items:

[0147] 1) Forced swimming test:

[0148] Experimental preparation: Prepare a transparent pool. The depth of the water should be such that the mice cannot stand or lie flat without touching the water surface. Usually, the diameter of the bucket in which the mice are forced to swim is 10 cm and the height is 25 cm. Configure a backlight system to reduce the impact of water droplets in the transparent bucket on the experiment, and use a constant temperature device to maintain the water temperature at 23-25℃ to ensure the consistency of experimental conditions.

[0149] Experimental steps: The mice were gently placed in the pool and their swimming behavior was recorded. The experimental animals swam in the swimming tank for 6 minutes, and the immobility time of the experimental animals in the water was tested 4 minutes later.

[0150] 2) Tail suspension test

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

[0152] Experimental steps: Gently catch the mouse and hang it on the hanging device with tape at the tail about 1-2 cm from the tip of the tail. Hang the experimental animal upside down in the tail hanging box and record the immobility time of the experimental animal in the last 4 minutes of the 5 minutes.

[0153] 3) Light and dark box experiment

[0154] Experimental preparation: light and dark box, partition door, and data recording and analysis software. Before each experiment, make sure the light and dark box is clean and odor-free.

[0155] Experimental steps: Gently place the animal in the dark area of ​​the light-dark box, facing the passage, and close the passage to allow the animal to adapt to the dark environment for about 5 minutes. Open the small door connecting the light and dark areas, start the timer, and allow the animal to move freely in the light-dark box for 5 minutes. Use a camera to record the animal's behavior during the experiment and record the length of time the experimental animal is in the light box.

[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 continuous administration for 30 days, compared with the immobility time of the model control group, the low-dose group of Example 1 was shortened by 6.99%, the immobility time of the comparative example 1 group was shortened by 8.61%, the immobility time of the comparative example 2 group was shortened by 6.65%, the immobility time of the comparative example 3 group was shortened by 7.41%, the immobility time of the comparative example 4 group was shortened by 9.30%, and the immobility time of the comparative example 5 group was shortened by 5.57%, but none of them showed significance. Compared with the immobility time of the model control group, the other groups were 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 Example 2 group, and 21.47% (P < 0.01) in the Example 3 group, all of which were significant. Compared with the immobility time of the low-dose group of Example 1, the therapeutic effect of the high-dose group of Example 1 is much higher than the former and is significant (P < 0.05). Compared with the high-dose group of Example 1, there is no significant difference in the groups of Examples 2-3, and there is a significant difference in the groups of Comparative Examples 1-5 (P < 0.05, P < 0.01), which proves that the composition of the present invention has better effects under specific components and ratios. The above results show that the high-dose group of Example 1 and the groups of Examples 2-3 can significantly reduce the immobility time and improve the depression symptoms of 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 4 minutes after the tail suspension was recorded within 5 minutes, and the data were statistically analyzed. The experimental results are shown in Table 7. After continuous administration for 30 days, compared with the immobility time of the model control group, the low-dose group of Example 1 was shortened by 9.37%, the comparative example 1 group was shortened by 13.32%, the comparative example 2 group was shortened by 16.89%, the comparative example 3 group was shortened by 19.31%, the comparative example 4 group was shortened by 9.49%, and the comparative example 5 group was shortened by 8.80%, but none of them showed significance. Compared with the immobility time of the model control group, the other groups were 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 Example 2 group, and 78.97% (P < 0.01) in the Example 3 group, all of which were significant. Compared with the high-dose group of Example 1, there was no significant difference in Example 2-3 groups, and there was a significant difference in Comparative Example 1-5 groups (P < 0.01, P < 0.001), which proved that the composition of the present invention has better effects under specific components and ratios. The above results show that the high-dose group of Example 1 and the groups of Examples 2-3 can significantly shorten the immobility time of tail-suspended mice and alleviate the depressive symptoms of mice.

[0167] Table 7. Effects on the 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 box experiment of mice

[0174] As shown in Table 8, compared with the time of the model control group entering the bright field, the low-dose group of Example 1 was extended by 8.24%, the comparative example 1 group was extended by 12.33%, the comparative example 2 group was extended by 9.55%, the comparative example 3 group was extended by 7.32%, the comparative example 4 group was extended by 6.16%, and the comparative example 5 group was extended by 9.01%, but none of them showed significance. Compared with the model control group, the other groups were extended by 37.67% (P < 0.001) in the Shugan Jieyu Capsule group, 38.75% (P < 0.001) in the high-dose group of Example 1, and 34.44% (P < 0.001) in the Example 2 group. Compared with the time of the low-dose group of Example 1 entering the bright field, the therapeutic effect of the high-dose group of Example 1 was much higher than the former and was significant (P < 0.001). Compared with the high-dose group of Example 1, there was no significant difference in Example 2-3 groups, and there was a significant difference in Comparative Example 1-5 groups (P < 0.01, P < 0.001), which proved that the composition of the present invention has better effects under specific components and ratios. The above results show that the high-dose group of Example 1 and Example 2-3 groups can significantly increase the time of mice in the bright field and reduce the anxiety symptoms of mice.

[0175] Table 8. Effects on the light-dark box test of 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 research results of the present invention, before modeling, through direct sleep experiments, it was proved that administration for 30 days had no significant effect on the weight of mice, and had no direct sleep effect on mice. The experiment of extending the sleep time of sodium pentobarbital showed that the high-dose group of Example 1 extended the sleep time of mice significantly better than the low-dose group of Example 1 and the comparative example 1-5 groups (P<0.01, P<0.001), and there was no significant difference between the Bailemian capsule group and the Example 2-3 groups. The subthreshold dose hypnosis experiment of sodium pentobarbital showed that the sleep rate of mice in the high-dose group of Example 1 was better than the low-dose group and the comparative example 1-5 groups, and was similar to the sleep rate between the Bailemian capsule group and the Example 2-3 groups. The sodium pentobarbital sleep latency experiment showed that the sleep latency of mice in the high-dose group of Example 1 was significantly less than that in the low-dose group of Example 1 and the comparative example 1-5 groups (P<0.05, P<0.01), and there was no significant difference between the Bailemian capsule group and the Example 2-3 groups. The above results all indicate that this prescription has the effect of improving sleep, suggesting that this prescription combination has the best effect and the combination ratio must be within a certain range.

[0182] Further through three kinds of mouse behavioral experiments, the effects of each administration group on depression and anxiety, two kinds of mouse mental disorders, were explored in depth. The results of the forced swimming test and tail suspension test of mice 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 the comparative example 1-5 groups (P<0.05, P<0.01, P<0.001), and there was no significant difference between the Shugan Jieyu Capsule group and the Example 2-3 groups, indicating that this prescription has a certain antidepressant effect. The light and dark box experiment of mice showed that the duration of the high-dose group of Example 1 in the bright field was significantly higher than that of the low-dose group of Example 1 and the comparative example 1-5 groups (P<0.01, P<0.001), and there was no significant difference between the Shugan Jieyu Capsule group and the Example 2-3 groups, indicating that this prescription has a certain anti-anxiety effect. The above results all show that this prescription has the effects of anti-depression and anti-anxiety, and at the same time, it is suggested that the combination effect of this prescription is the best, 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, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate 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: Contains the following ingredients: Poria cocos, spiny jujube seeds, lily, mulberry, bergamot, wheat, jujube, Ganoderma lucidum, Gastrodia elata powder, licorice, and donkey-hide gelatin.

2. The composition according to claim 1, characterized in that The composition comprises the following components by weight: 8-32 parts of Poria cocos, 4-16 parts of Ziziphus jujuba seeds, 4-18 parts of lilies, 1-15 parts of mulberries, 18-40 parts of bergamots, 10-28 parts of wheat, 2-12 parts of jujubes, 5-22 parts of Ganoderma lucidum, 2-12 parts of Gastrodia elata powder, 4-16 parts of licorice, and 4-16 parts of donkey-hide gelatin.

3. The composition according to claim 2, characterized in that The composition comprises the following components by weight: 10-30 parts of Poria cocos, 5-15 parts of Ziziphus jujuba seeds, 4-15 parts of lilies, 1-10 parts of mulberries, 20-40 parts of bergamots, 10-25 parts of wheat, 2-10 parts of jujubes, 5-20 parts of Ganoderma lucidum, 2-10 parts of Gastrodia elata powder, 5-15 parts of licorice, and 5-15 parts of donkey-hide gelatin.

4. A method for preparing the composition according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1: Take Poria cocos, lily, mulberry, bergamot, wheat, jujube, ganoderma lucidum and licorice, add solvent to extract, concentrate 1-3 times, and obtain a concentrated solution; S2: Melt donkey-hide gelatin and crush spinach kernel, add melted donkey-hide gelatin, gastrodia powder and spinach kernel powder to the concentrated solution obtained in S1, mix, let stand at 0-5℃ for 10-15h, separate and take the supernatant to obtain the extract.

5. The preparation method according to claim 4, characterized in that: In S1, the solvent is water, and the mass of the water is 8-12 times the total mass of Poria cocos, lily, mulberry, bergamot, wheat, jujube, Ganoderma lucidum and licorice; in S2, the solvent is water, and the mass of the water is 8-12 times the total mass of Poria cocos, lily, mulberry, bergamot, wheat, jujube, Ganoderma lucidum and licorice.

6. The preparation method according to claim 4, characterized in that: In S1, the extraction is a heating reflux extraction at a temperature of 95-100°C.

7. The preparation method according to claim 4, characterized in that: The preparation method further comprises the following steps: concentrating the extract into a thick paste, drying, and crushing to obtain an extract.

8. The preparation method according to claim 7, characterized in that: The preparation method further comprises 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 crushing into powder to obtain an extract.

9. A pharmaceutical preparation, characterized in that A composition for improving sleep and relieving anxiety and depression comprising any one of claims 1 to 3.

10. Use of the composition according to any one of claims 1 to 3 or the pharmaceutical preparation according to claim 9 in improving sleep and combating anxiety and depression.

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