Spina date seed and poria cocos composition, oral preparation and application thereof

Abstract

The invention provides a semen ziziphi spinosae and poria cocos composition. The composition comprises semen ziziphi spinosae extract, poria cocos extract and gamma-aminobutyric acid, wherein the semen ziziphi spinosae extract is formed by combining semen ziziphi spinosae whole powder, semen ziziphi spinosae aqueous extract and semen ziziphi spinosae, and the poria cocos extract is formed by poria cocos powder and poria cocos aqueous extract. The invention also provides a preparation comprising the composition, and a food product comprising the composition or the preparation. The invention further provides application of the composition or the preparation in preparation of health care products or medicines. The composition provided by the invention is prepared by compatibility of pure natural components according to the theory of traditional Chinese medicine, can effectively prolong the sleep time of pentobarbital sodium and remarkably shorten the sleep latency of mice under the condition of not influencing direct sleep of the mice, and has a certain improvement effect on the sleep of the mice. The composition and the preparation provided by the invention have a remarkable improvement effect on sleep-related symptoms, and have important market value and development prospect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine and food technology, specifically relating to a composition of jujube seed and poria cocos and its oral preparation, as well as the application of the composition and preparation in the preparation of food, health food and medicine. Technical Background Sleep is a fundamental biological process for maintaining physiological homeostasis and cognitive function in humans. World Health Organization data shows that approximately 30% of adults worldwide experience varying degrees of sleep disorders, with the prevalence of insomnia, especially among those over 18 years of age, showing a rising trend and affecting increasingly younger individuals. Insomnia not only leads to decreased attention and memory, and reduced work and study efficiency, but is also significantly associated with the risk of anxiety, depression, hypertension, type II diabetes, coronary heart disease, immune dysfunction, and neurodegenerative diseases such as Alzheimer's disease. Therefore, safe, effective, and long-term interventions have become an urgent need in the field of public health.

[0002] Currently, first-line clinical treatment still primarily relies on benzodiazepines and non-benzodiazepines as sedative-hypnotics. However, long-term use can lead to hangover effects, dizziness, ataxia, cognitive decline, drug tolerance, and dependence; abrupt discontinuation may also induce rebound insomnia and withdrawal syndrome. Furthermore, elderly patients have a significantly increased risk of falls, fractures, and respiratory depression after taking these medications, limiting their widespread use. While melatonin receptor agonists and orexin receptor antagonists offer improved safety compared to traditional drugs, they are expensive, have limited efficacy for some patients, and still require prescription management.

[0003] Given the inherent limitations of chemically synthesized drugs, researchers and industries both domestically and internationally are actively seeking natural sleep-aiding ingredients derived from food, medicinal and edible resources, or probiotic metabolites. However, current market products derived from traditional Chinese medicine suffer from severe homogenization, unclear efficacy, or limited functionality, hindering their industrialization process. Summary of the Invention

[0004] In order to overcome the shortcomings of the prior art, the present invention provides a jujube seed and poria cocos composition to achieve the effects of helping to improve sleep, and further relieving anxiety and preventing depression.

[0005] In a first aspect, the present invention provides a jujube seed and poria cocos composition, the composition comprising the following components in parts by weight: 45-55 parts of jujube seed extract, 25-35 parts of poria cocos extract, and 0.1-1 parts of γ-aminobutyric acid. The composition is formed by directly mixing the above components.

[0006] The composition provided by the present invention combines the traditional Chinese medicine theory of the nature, flavor, and meridian tropism with the research results of Western pharmacology. Specifically: In the composition provided by the present invention, Semen Ziziphi Spinosae nourishes blood, soothes the heart, and calms the mind as the monarch drug, Poria cocos clears the heart, soothes the mind, and nourishes blood as the minister drug, and γ-aminobutyric acid regulates the heart and nourishes the brain as the assistant and guiding drug. On this basis, the dosages of each component are further optimized so that they work together to achieve synergistic effects and balance of restraint.

[0007] The raw material Semen Ziziphi Spinosae used in the present invention is the dried ripe seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou of the family Rhamnaceae. According to the "Chinese Pharmacopoeia (2025)", Semen Ziziphi Spinosae is sweet, sour, and flat in nature and flavor; it belongs to the liver, gallbladder, and heart meridians; it has the functions of nourishing the heart, tonifying the liver, calming the mind, arresting sweating, and promoting the production of body fluid; it is mainly used for restlessness and insomnia, palpitations and dreaminess, excessive sweating due to physical weakness, and thirst due to fluid impairment Ziziphus jujuba Mill.var. spinosa (Bunge)Hu ex H. F. Chou. According to the "Chinese Pharmacopoeia (2025)", Semen Ziziphi Spinosae is sweet, sour, and flat in nature and flavor; it belongs to the liver, gallbladder, and heart meridians; it has the functions of nourishing the heart, tonifying the liver, calming the mind, arresting sweating, and promoting the production of body fluid; it is mainly used for restlessness and insomnia, palpitations and dreaminess, excessive sweating due to physical weakness, and thirst due to fluid impairment.

[0008] When formulating the prescription, the extract of Semen Ziziphi Spinosae as the monarch drug is a mixture of Semen Ziziphi Spinosae powder, aqueous extract of Semen Ziziphi Spinosae, and Semen Ziziphi Spinosae oil in a mass ratio of (4 - 6):(7 - 10):(3 - 5). Through a large number of practices, the present invention has found that when the three extraction components of Semen Ziziphi Spinosae obtained by different principles and different processes are mixed in the above specific ratio and added to the composition, the overall effect of the composition can be optimized, which is significantly better than the scheme of only using a single Semen Ziziphi Spinosae powder, aqueous extract of Semen Ziziphi Spinosae, or Semen Ziziphi Spinosae oil.

[0009] The Semen Ziziphi Spinosae powder described in the present invention is prepared by drying and pulverizing the traditional Chinese medicine Semen Ziziphi Spinosae.

[0010] The aqueous extract of Semen Ziziphi Spinosae described in the present invention is prepared by using water equivalent to 10 - 20 times the weight of the raw material, through heat extraction, filtration, and drying with the traditional Chinese medicine Semen Ziziphi Spinosae as the raw material.

[0011] The Semen Ziziphi Spinosae oil described in the present invention is the fruit oil of Semen Ziziphi Spinosae obtained by using the supercritical carbon dioxide extraction method with the traditional Chinese medicine Semen Ziziphi Spinosae as the raw material. In order to make the composition more uniform and stable, the present invention preferably uses the fruit oil of Semen Ziziphi Spinosae as the core material, β-cyclodextrin and soy protein isolate as the wall materials, and prepares the Semen Ziziphi Spinosae oil microcapsules by spray drying method.

[0012] The raw material Poria cocos used in the present invention is the dried sclerotium of Poria cocos (Schw.) Wolf of the family Polyporaceae. According to the "Chinese Pharmacopoeia (2025)", Poria cocos is sweet, light, and flat in nature and flavor; it belongs to the heart, lung, spleen, and kidney meridians; it has the functions of promoting diuresis and excreting dampness, strengthening the spleen, and calming the mind; it is mainly used for edema with scanty urine, dizziness and palpitation due to phlegm retention, poor appetite due to spleen deficiency, loose stools, restlessness of mind, and palpitations and insomnia. Poria cocos (Schw.)Wolf. According to the "Chinese Pharmacopoeia (2025)", Poria cocos is sweet, light, and flat in nature and flavor; it belongs to the heart, lung, spleen, and kidney meridians; it has the functions of promoting diuresis and excreting dampness, strengthening the spleen, and calming the mind; it is mainly used for edema with scanty urine, dizziness and palpitation due to phlegm retention, poor appetite due to spleen deficiency, loose stools, restlessness of mind, and palpitations and insomnia.

[0013] In formulating the composition, the Poria cocos extract, as an adjuvant ingredient, is a mixture of Poria cocos powder and Poria cocos aqueous extract in a mass ratio of (1~2):(1~2). Similar to the main ingredient, Ziziphus jujuba seed extract, this invention has found through extensive practice that when two Poria cocos extracts obtained using different principles and processes are mixed in the above-mentioned specific ratio and added to the composition, the overall effect of the composition can be optimized, significantly better than the scheme using only Poria cocos powder or Poria cocos aqueous extract.

[0014] The Poria powder described in this invention is made from the traditional Chinese medicine Poria cocos through drying and pulverizing.

[0015] The Poria cocos water extract of the present invention is made by using the traditional Chinese medicine Poria cocos as raw material and water equivalent to 10 to 20 times the weight of the raw material, through hot extraction, filtration and drying.

[0016] The raw material used in this invention, γ-aminobutyric acid (GABA), is an active amino acid that plays an important role in the energy metabolism of the human brain. It has a variety of physiological functions, such as activating glucose metabolism in the brain, promoting acetylcholine synthesis, lowering blood ammonia, anticonvulsant, lowering blood pressure, improving brain function, stabilizing the mind, and promoting growth hormone secretion.

[0017] As a preferred embodiment of the present invention, the composition may further include water extracts of lily bulb, lotus seed, and longan pulp. These components, along with the Poria cocos extract, act as adjuvants, synergistically achieving the functions of calming the mind, soothing the nerves, and nourishing the blood, thereby enhancing the overall efficacy of the composition. Specifically, the composition also includes the following components in parts by weight: 5-10 parts of lily bulb water extract, 5-10 parts of lotus seed water extract, and 5-10 parts of longan pulp water extract.

[0018] The lily used in this invention is *Lilium tigrinum*, a plant belonging to the Liliaceae family. Lilium lancifolium Thunb., Lily Lilium brownii FE Brown var. viridulum Baker or Narrow-leaved Lily Lilium pumilum The dried fleshy scales of DC. According to the Chinese Pharmacopoeia (2025), lily is sweet and cold in nature; it enters the heart and lung meridians; it has the functions of nourishing yin and moistening the lungs, clearing the heart and calming the mind; it is mainly used for dry cough due to yin deficiency, cough with blood due to overwork, restlessness and palpitations, insomnia and dreaminess, and mental confusion.

[0019] The lotus seeds used in this invention are from the lotus plant (Nelumbo nucifera), a member of the Nymphaeaceae family. Nelumbo nucifera The dried, mature seeds of Gaertn. According to the Chinese Pharmacopoeia (2025), lotus seeds are sweet, astringent, and neutral in nature; they enter the spleen, kidney, and heart meridians; they have the functions of tonifying the spleen and stopping diarrhea, stopping leukorrhea, benefiting the kidneys and astringing essence, nourishing the heart and calming the mind; they are mainly used for spleen deficiency diarrhea, leukorrhea, seminal emission, palpitations, and insomnia.

[0020] The raw material used in this invention is longan pulp, a plant belonging to the Sapindaceae family. Dimocarpus longan The aril of Lour. According to the Chinese Pharmacopoeia (2025), longan pulp is sweet and warm in nature; it enters the heart and spleen meridians; it has the functions of tonifying the heart and spleen, nourishing blood and calming the mind; it is mainly used for qi and blood deficiency, palpitations, forgetfulness and insomnia, and blood deficiency and chlorosis.

[0021] The water extracts of the above-mentioned components are all made from the corresponding Chinese medicinal herbs, using water equivalent to 10 to 20 times the weight of the raw materials, through hot extraction, filtration, and drying.

[0022] As a preferred embodiment of the present invention, the composition may further include mulberry water extract and L-theanine. These components, along with γ-aminobutyric acid (GABA), act as adjuvants, synergistically achieving the effects of regulating the mind and nourishing the brain, thereby enhancing the overall efficacy of the composition. Specifically, the composition further includes 5-10 parts of mulberry water extract, and the ratio of L-theanine to GABA is (1-2):2, with the sum of their amounts being 0.1-1 parts.

[0023] The mulberry used in this invention is the fruit of a plant belonging to the genus *Morus* of the family Moraceae. It is a health-promoting food native to my country with a cultivation history of over a thousand years. According to the *Compendium of Materia Medica*, "Mulberry juice, when pounded and drunk, can relieve alcohol poisoning, promote urination, reduce swelling, nourish yin and replenish blood, and is used for liver and kidney deficiency, deficiency of essence and blood, dizziness, blurred vision, tinnitus, insomnia, and premature graying of hair." The mulberry water extract is made from dried mulberries using 10-20 times their weight in water, through hot extraction, filtration, and drying.

[0024] The raw material used in this invention, L-theanine, is a natural amino acid mainly found in tea. As a novel food ingredient, it offers various health benefits, including improving mental health, reducing stress, and promoting sleep.

[0025] As a specific embodiment of the present invention, the composition comprises the following components in parts by weight: 50-52 parts of jujube seed extract composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of (4-5):(8-9):(3-4); 30-32 parts of poria cocos extract composed of poria cocos powder and poria cocos water extract in a mass ratio of (1-1.5):(1.5-2); 7-8 parts of lily water extract; 7-8 parts of lotus seed water extract; 6-7 parts of longan pulp water extract; 6-7 parts of mulberry water extract; 0.5-0.6 parts of γ-aminobutyric acid; and 0.3-0.4 parts of L-theanine.

[0026] In a second aspect, the present invention provides an oral preparation of jujube seed and poria cocos, wherein the jujube seed and poria cocos composition described in the first aspect, and an appropriate amount of excipients acceptable in the fields of food, health food or pharmaceuticals.

[0027] In one specific embodiment of the present invention, the oral preparation is a tablet, preferably a regular tablet, lozenge, chewable tablet, dispersible tablet or effervescent tablet.

[0028] In one specific embodiment of the present invention, the oral preparation is a capsule, preferably a hard capsule or a soft capsule.

[0029] In one specific embodiment of the present invention, the oral preparation is a granule, preferably a soluble granule, a suspension granule, or an effervescent granule.

[0030] In one specific embodiment of the present invention, the oral preparation is a powder.

[0031] In one specific embodiment of the present invention, the oral preparation is a paste.

[0032] In one specific embodiment of the present invention, the oral preparation is a candy, preferably selected from hard candies, hard-filled candies, cream candies, gel candies, gum-based candies, aerated candies, or compressed candies. When the oral preparation is a compressed candy, xylitol is preferably used as the sweetener.

[0033] In one specific embodiment of the present invention, the oral preparation is a liquid preparation, preferably a syrup, oral liquid or beverage.

[0034] Thirdly, the present invention provides a food product comprising the jujube seed and poria cocos composition described in the first aspect or the jujube seed and poria cocos oral preparation described in the second aspect.

[0035] In the composition provided by this invention, all the raw materials for the extracts are derived from substances that are "both food and traditional Chinese medicine" as published by health administrative departments or from foods consumed in daily life. Furthermore, according to toxicological test results, the addition of appropriate amounts of γ-aminobutyric acid (GABA) to food is considered safe, and its application scope includes beverages, cocoa products, chocolate and its beverages, candies, baked goods, and puffed foods, etc.

[0036] Fourthly, the present invention provides the use of the Ziziphus jujuba seed and Poria cocos composition described in the first aspect or the Ziziphus jujuba seed and Poria cocos oral preparation described in the second aspect in the preparation of health foods that help improve sleep.

[0037] The composition provided by this invention can effectively prolong the sleep time of sodium pentobarbital and significantly shorten the sleep latency of mice without affecting their direct sleep, thus improving their sleep to a certain extent.

[0038] In a preferred embodiment of the present invention, the composition improves sleep by increasing the level of serotonin in brain tissue. Specifically, serotonin is an important neurotransmitter closely related to insomnia and a precursor to melatonin, which is converted into melatonin in a dark environment, promoting sleep. Therefore, the composition provided by the present invention can improve sleep by increasing serotonin levels.

[0039] In a preferred embodiment of the present invention, the composition improves sleep by increasing the content of γ-aminobutyric acid (GABA) in brain tissue. Specifically, GABA is a naturally occurring neurotransmitter in the human body that plays an important regulatory role in the central nervous system and helps promote sleep. Therefore, the composition provided by the present invention can improve sleep by increasing GABA levels.

[0040] In a preferred embodiment of the present invention, the composition improves sleep by reducing dopamine levels in brain tissue. Specifically, dopamine plays an important role in sleep regulation. Studies have shown that dopamine can indirectly affect sleep by inhibiting melatonin secretion, and excessively high levels may inhibit sleep onset. Therefore, the composition provided by the present invention can improve sleep by controlling dopamine levels.

[0041] Fifthly, the present invention provides the use of the Ziziphus jujuba seed and Poria cocos composition described in the first aspect or the oral preparation of Ziziphus jujuba seed and Poria cocos described in the second aspect in the preparation of medicines that help improve sleep, help relieve anxiety and / or prevent depression.

[0042] Low levels of neurotransmitters such as serotonin and gamma-aminobutyric acid (GABA) are closely related to anxiety and depression. Therefore, the composition provided by this invention, in addition to improving sleep, may also alleviate anxiety and prevent depression by increasing the levels of neurotransmitters such as serotonin and GABA in the brain.

[0043] Compared with existing technologies, the composition provided by this invention combines traditional Chinese medicine compatibility theory with modern pharmacological research results, and uses extracts obtained from different principles and processes in a balanced ratio, so that the components complement and enhance each other in terms of their mechanism of action. This results in an overall efficacy of the composition that is far greater than the simple sum of the individual effects of the components. Most of the raw materials selected in this invention are nationally approved medicinal and edible substances or food ingredients, ensuring high safety, low toxicity and side effects. Furthermore, the raw materials are widely available, possessing significant market value and development prospects. Detailed Implementation

[0044] The present invention provides the following embodiments to further illustrate various aspects of the invention. These embodiments are non-limiting and should not be construed as limiting any aspect of the invention. The scope of protection of the present invention is limited only by the claims. Various modifications and improvements can be made to various aspects of the present invention by those skilled in the art without departing from the scope of the claims, and these modifications and improvements also fall within the scope of protection of the present invention.

[0045] Additionally, it should be noted that, unless otherwise specified, all materials and reagents used in the following embodiments are commonly used in the art and can be obtained through conventional commercial means; all methods used are conventional methods known to those skilled in the art.

[0046] Example The following are ingredients used in the composition of the experimental examples: The jujube seed powder is prepared by the following method: take jujube seeds purchased from Tongrentang, dry them, and then grind them to 60 mesh.

[0047] The water extract of jujube seed is prepared by the following method: take jujube seed purchased from Tongrentang, dry and crush it, add water and boil it three times for 3 hours each time. The total amount of water used for extraction is equivalent to 20 times the weight of the Chinese medicine. Collect the extract, centrifuge and filter it, collect the filtrate, and spray dry it to obtain the extract.

[0048] The jujube seed oil is prepared by the following method: 1) Preparation of jujube seed oil: Jujube seeds purchased from Tongrentang are pre-dried and pulverized to 60 mesh. Extraction is then performed using a supercritical carbon dioxide extractor for 3 hours. The extraction pressure is 30 MPa, the temperature is 45 ℃, and the CO2 flow rate is 20 L / h. -1 2) Preparation of jujube seed oil microcapsules: β-cyclodextrin (β-CD) and soy protein isolate (SPI) were mixed at a mass ratio of 1:1, with a total wall material concentration of 3% (w / w, based on the total mass of the final emulsion); deionized water at 60 ℃ was added, and the mixture was sheared at 2000 r / min for 10 min to allow it to fully swell before cooling to 40 ℃; jujube seed oil was slowly added to the wall material solution to make the oil:wall ratio 1:4 (w / w); the mixture was subjected to high shearing at 60 ℃ and 10000 r / min for 5 min to form a crude emulsion; the mixture was homogenized twice at 40 MPa to obtain a stable O / W emulsion, which was immediately transferred to a 4 ℃ ice-water bath to inhibit oxidation; and spray-dried to obtain jujube seed oil microcapsules.

[0049] Poria powder is prepared by the following method: take raw sour Poria purchased from Tongrentang, dry it and then pulverize it to 60 mesh.

[0050] The water extract of Poria cocos was prepared by the following method: Poria cocos purchased from Tongrentang was dried, pulverized, and then boiled with water for 3 times, each time for 3 hours. The total amount of water used for extraction was equivalent to 20 times the weight of the Chinese medicine. The extract was collected, centrifuged and filtered, the filtrate was collected, and spray-dried to obtain the final product.

[0051] The water extract of lily is prepared by the following method: raw lily purchased from Tongrentang is dried and pulverized, then water is added and boiled for extraction 3 times, each time for 3 hours. The total amount of water used for extraction is equivalent to 20 times the weight of the Chinese medicine. The extract is collected, centrifuged and filtered, the filtrate is collected, and spray-dried to obtain the extract.

[0052] The lotus seed water extract is prepared by the following method: raw lotus seeds purchased from Tongrentang are dried, pulverized, and then boiled in water for 3 times, each time for 3 hours. The total amount of water used for extraction is equivalent to 20 times the weight of the Chinese medicine. The extract is collected, centrifuged and filtered, the filtrate is collected, and spray-dried to obtain the extract.

[0053] The water extract of longan pulp is prepared by the following method: Longan pulp purchased from Tongrentang is dried, pulverized, and then boiled with water for 3 times, each time for 3 hours. The total amount of water used for extraction is equivalent to 20 times the weight of the Chinese medicine. The extract is collected, centrifuged and filtered, the filtrate is collected, and spray-dried to obtain the final product.

[0054] The water extract of mulberry is prepared by the following method: take mulberry, dry and pulverize it, add water and boil it three times for 3 hours each time. The total amount of water used for extraction is equivalent to 20 times the weight of the Chinese medicine. Collect the extract, centrifuge and filter it, collect the filtrate, and spray dry it to obtain the extract.

[0055] Example 1 This embodiment provides a jujube seed and poria cocos composition, which is composed of the following components: 50 g of jujube seed extract composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of 4:8:3; 30 g of poria cocos extract composed of poria cocos powder and poria cocos water extract in a mass ratio of 2:3; and 0.5 g of γ-aminobutyric acid.

[0056] Example 2 This embodiment provides a jujube seed and poria cocos composition, which is composed of the following components: 52 g of jujube seed extract composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of 5:9:4; 32 g of poria cocos extract composed of poria cocos powder and poria cocos water extract in a mass ratio of 3:4; and 0.6 g of γ-aminobutyric acid.

[0057] Example 3 This embodiment provides a jujube seed and poria cocos composition, which is composed of the following components: 45 g of jujube seed extract composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of 4:7:3; 25 g of poria cocos extract composed of poria cocos powder and poria cocos water extract in a mass ratio of 1:2; and 0.1 g of γ-aminobutyric acid.

[0058] Example 4 This embodiment provides a jujube seed and poria cocos composition, which is composed of the following components: 55 g of jujube seed extract composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of 6:10:5; 35 g of poria cocos extract composed of poria cocos powder and poria cocos water extract in a mass ratio of 2:1; and 0.5 g of γ-aminobutyric acid.

[0059] Example 5 This embodiment provides a jujube seed and poria cocos composition, which is composed of the following components: 50 g of jujube seed extract, which is composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of 4:8:3; 30 g of poria cocos extract, which is composed of poria cocos powder and poria cocos water extract in a mass ratio of 2:3; 7 g of lily water extract; 7 g of lotus seed water extract; and 6 g of longan pulp water extract.

[0060] Example 6 This embodiment provides a jujube seed and poria cocos composition, which is composed of the following components: 52 g of jujube seed extract, which is composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of 5:9:4; 32 g of poria cocos extract, which is composed of poria cocos powder and poria cocos water extract in a mass ratio of 3:4; 8 g of lily water extract; 8 g of lotus seed water extract; and 7 g of longan pulp water extract.

[0061] Example 7 This embodiment provides a jujube seed and poria cocos composition, which differs from Example 5 only in that the composition also contains 6 g of mulberry water extract, 0.5 g of γ-aminobutyric acid, and 0.3 g of L-theanine.

[0062] Example 8 This embodiment provides a jujube seed and poria cocos composition, which differs from Example 6 only in that the composition also contains 7 g of mulberry water extract, 0.6 g of γ-aminobutyric acid, and 0.4 g of L-theanine.

[0063] Example 9 This embodiment provides a jujube seed and poria cocos compressed candy, prepared by a method including the following steps: 50 g of xylitol and 15 g of maltodextrin are passed through a 100-mesh sieve to obtain powder A; 5 g of the composition provided in Example 1 and 10 g of microcrystalline cellulose are passed through an 80-mesh sieve to obtain powder B; 0.8 g of magnesium stearate and 0.5 g of silicon dioxide are passed through a 60-mesh sieve to obtain powder C. Powder A and powder B are added to a three-dimensional mixer and mixed at 15 r / min for 10 min. After stopping the mixer, powder C is added and mixing continues for 5 min to obtain a homogeneous mixed powder; a high-speed shear granulator (paddle 300 r / min, cutter 1500 r / min) is turned on, and 50% ethanol is sprayed evenly, completing the process within 3 min, with an output particle size of 40 mesh; the product is dried in a fluidized bed at 55 ℃ to a moisture content of 3.0%, and then granulated through an 18-mesh vibrating sieve to obtain uniformly sized granules; finally, the product is compressed into tablets.

[0064] In the compressed candy provided in this embodiment, replacing the composition provided in Example 1 with the composition provided in Examples 2 to 8 will yield the corresponding compressed candy.

[0065] Example 10 This embodiment provides a jujube seed and poria cocos solid beverage (granules), which is prepared by a method including the following steps: 30 g of the composition provided in Example 1, 12 g of xylitol and 18 g of maltodextrin are mixed and granulated by dry granulation to obtain the product.

[0066] In the solid beverage provided in this embodiment, replacing the composition provided in Example 1 with the compositions provided in Examples 2 to 8 can yield the corresponding granules.

[0067] Comparative Example 1 This comparative example provides a composition that differs from Example 1 of the present invention only in that 50 g of jujube seed powder, a single component, is used instead of jujube seed extract, which consists of three components.

[0068] Comparative Example 2 This comparative example provides a composition that differs from Example 1 of the present invention only in that 50 g of a single-component jujube seed water extract is used instead of a jujube seed extract composed of three components.

[0069] Comparative Example 3 This comparative example provides a composition that differs from Example 1 of the present invention only in that 50 g of jujube seed oil, a single component, is used instead of jujube seed extract, which consists of three components.

[0070] Comparative Example 4 This comparative example provides a composition that differs from Example 1 of the present invention only in that the mass ratio of jujube seed powder, jujube seed water extract and jujube seed oil is 1:1:1.

[0071] Comparative Example 5 This comparative example provides a composition that differs from Example 1 of the present invention only in that 30 g of Poria cocos powder, a single component, is used instead of Poria cocos extract, which consists of two components.

[0072] Comparative Example 6 This comparative example provides a composition that differs from Example 1 of the present invention only in that 30 g of a single-component Poria cocos aqueous extract is used instead of a Poria cocos extract composed of two components.

[0073] Experimental Example 1. Direct Sleep Experiment Fifty mice were randomly divided into five groups of ten each. The test drug was administered via gavage at a dose of 10 mL / kg body weight (BW). The concentration of the test drug was further calculated from the recommended daily adult dose (2 g / d of the composition) to determine the optimal gavage dose for mice. One group served as a blank control (administered distilled water via gavage), while the other four experimental groups received the compositions provided in Examples 1, 3, 5, and 7, respectively. The mice were administered the test drug for 30 consecutive days. Sleep was observed 30 minutes after the last administration. The disappearance of the righting reflex was used as an indicator of sleep duration; the time from the disappearance of the righting reflex to its recovery was defined as the mouse's sleep time.

[0074] The results showed that after 30 days of continuous gavage, the mice all grew well, and there was no significant difference in body weight between the four experimental groups and the blank control group. Furthermore, no sleep phenomena were observed in the mice of any of the experimental groups or the blank control group (no righting reflex was lost), indicating that the compositions provided in each example have no direct sleep effect on mice and can be further evaluated in subsequent experiments.

[0075] 2. Experiment on prolonging sodium pentobarbital sleep time One hundred and ten mice were randomly divided into ten groups of ten each. The test drug was administered via gavage at a dose of 10 mL / kg body weight (BW). The concentration of the test drug was further calculated from the recommended daily adult dose (2 g / d of the composition) for mice. Eleven groups included a control group (gavage with distilled water) and ten experimental groups administered the compositions provided in Examples 1, 3, 5, 7, and Comparative Examples 1-6, respectively. The test drugs were administered continuously for 30 days. Thirty minutes after the last gavage, each group of mice was intraperitoneally injected with sodium pentobarbital at 45 mg / kg BW. The loss of the righting reflex was used as an indicator of sleepiness, and the average sleep time of each group was recorded. The results are shown in Table 1.

[0076] Table 1: Effect of sodium pentobarbital on sleep duration induced in mice (n=10)

[0077] As shown in Table 1, the compositions provided in each embodiment of the present invention can significantly prolong the sleep time induced by sodium pentobarbital in mice, and the effect is significantly better than that of each comparative example.

[0078] 3. Sodium barbital sleep latency test The number of animals, grouping, method of administration of the test sample, and dosage were all the same as in the experiment on "prolonging sodium pentobarbital sleep time". Twenty minutes after the last gavage administration of the test substance, mice in each group were intraperitoneally injected with sodium barbital at a dose of 250 mg / kg BW, with an injection volume of 0.2 mL / 20g BW. The absence of the righting reflex was used as the criterion to observe whether the experimental groups could shorten the sodium barbital sleep latency. The results are shown in Table 2.

[0079] Table 2: Effects of sodium barbital on sleep latency (n=10)

[0080] As shown in Table 2, the compositions provided in each embodiment of the present invention can significantly shorten the sleep latency of sodium barbital, and the effect is significantly better than that of each comparative example.

[0081] 4. Detection of 5-HT, GABA and DA levels in brain tissue The number of animals, grouping, method of administering test samples, and dosage were all the same as in the experiment on "prolonging sodium pentobarbital sleep time". Mice in each group were administered the medication by gavage for 30 consecutive days, then fasted for 12 hours, euthanized, and their brain tissue was removed. The brain tissue was rinsed with physiological saline and weighed. A 10% homogenate of the brain tissue was prepared using a homogenizer, centrifuged at 8000 r / min for 10 minutes at 4°C, and the supernatant was collected. The levels of serotonin (5-HT), γ-aminobutyric acid (GABA), and dopamine (DA) in the brain tissue of each group of mice were determined using ELISA according to the kit instructions (all ELISA kits used were purchased from Nanjing Jiancheng Biotechnology Research Institute Co., Ltd.). Data transformation and statistical analysis were performed using SPSS 21.0 software. The results are shown in Table 3.

[0082] Table 3: Results of Active Substance Detection

[0083] The results are shown in Table 3. The results show that the compositions provided in each embodiment of the present invention can significantly increase the content of serotonin and γ-aminobutyric acid in brain tissue and reduce the content of dopamine, thereby improving sleep; among them, the overall effect of Example 7 is the best.

[0084] Based on the above animal experimental results, the composition provided by this invention can effectively prolong the sodium pentobarbital sleep time and significantly shorten the sleep latency of mice without affecting their direct sleep, thus improving their sleep to a certain extent. Furthermore, the composition provided by this invention can effectively increase the content of 5-HT and GABA in tissues while decreasing the content of DA, suggesting that the composition may improve sleep by regulating the levels of neurotransmitters 5-HT, GABA, and DA in the brain. In addition, neurotransmitters such as 5-HT, GABA, and DA are associated with anxiety and depression, suggesting that the composition provided by this invention may also have a certain preventive or ameliorative effect on these symptoms.

[0085] Unless otherwise stated, the technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. This invention may also be practiced using any methods and materials similar to or equivalent to those described herein. While specific embodiments and preferred methods and materials are described herein, they do not impose any limitation on the invention.

Claims

1. A composition of jujube seed and poria cocos, characterized in that, It contains the following ingredients in parts by weight: 45-55 parts of Ziziphus jujuba seed extract, 25-35 parts of Poria cocos extract, and 0.1-1 parts of γ-aminobutyric acid; The jujube seed extract is made by mixing jujube seed powder, jujube seed aqueous extract, and jujube seed oil in a mass ratio of (4~6):(7~10):(3~5); the jujube seed powder is made from jujube seed, a traditional Chinese medicine, through drying and pulverizing; the jujube seed aqueous extract is made from jujube seed, a traditional Chinese medicine, through hot extraction, filtration, and drying using water equivalent to 10~20 times the weight of the raw material; the jujube seed oil is jujube seed fruit oil obtained by supercritical carbon dioxide extraction from jujube seed, a traditional Chinese medicine. The Poria cocos extract is made by mixing Poria cocos powder and Poria cocos water extract in a mass ratio of (1~2):(1~2); the Poria cocos powder is made by drying and pulverizing the Chinese herbal medicine Poria cocos; the Poria cocos water extract is made by using the Chinese herbal medicine Poria cocos as raw material, and then using water equivalent to 10~20 times the weight of the raw material, through hot extraction, filtration and drying.

2. The composition according to claim 1, characterized in that, The jujube seed oil is a microcapsule made by spray drying, using jujube seed oil as the core material and β-cyclodextrin and soy protein isolate as the wall material.

3. The composition according to claim 1, characterized in that, The composition also contains the following components in parts by weight: 5-10 parts of lily water extract, 5-10 parts of lotus seed water extract, and 5-10 parts of longan pulp water extract.

4. The composition according to claim 1, characterized in that, The composition further comprises 5-10 parts of mulberry water extract and L-theanine; in the composition, the sum of the amounts of γ-aminobutyric acid and L-theanine is 0.1-1 parts, and the ratio of the amounts is 2:(1-2).

5. The composition according to any one of claims 1 to 4, characterized in that, It contains the following components in parts by weight: 50-52 parts of jujube seed extract composed of jujube seed powder, jujube seed water extract and jujube seed oil in a mass ratio of (4-5):(8-9):(3-4); 30-32 parts of poria cocos extract composed of poria cocos powder and poria cocos water extract in a mass ratio of (1-1.5):(1.5-2); 7-8 parts of lily water extract; 7-8 parts of lotus seed water extract; 6-7 parts of longan pulp water extract; 6-7 parts of mulberry water extract; 0.5-0.6 parts of γ-aminobutyric acid; and 0.3-0.4 parts of L-theanine.

6. An oral preparation of Ziziphus jujuba seed and Poria cocos, characterized in that, The composition comprising the jujube seed and poria cocos according to any one of claims 1 to 5, and excipients; Preferably, the oral preparation is a tablet, preferably selected from ordinary tablets, lozenges, chewable tablets, dispersible tablets, or effervescent tablets; or, The oral preparation is a capsule, preferably a hard capsule or a soft capsule; or... The oral formulation is a granule, preferably a soluble granule, suspension granule, or effervescent granule; or... The oral preparation is a powder; or, The oral preparation is a paste; or, The oral preparation is a candy, preferably selected from hard candies, hard-filled candies, cream candies, gel candies, gum-based candies, aerated candies, or compressed candies; or, The oral preparation is a liquid preparation, preferably a syrup, oral liquid, or beverage.

7. The oral formulation according to claim 6, characterized in that, It is a compressed candy, and the sweetener used is xylitol.

8. A food product, characterized in that, The composition comprising any one of claims 1 to 5 or the oral preparation of jujube seed and poria cocos as described in claim 6 or 7.

9. The use of the Ziziphus jujuba seed and Poria cocos composition according to any one of claims 1 to 5 or the Ziziphus jujuba seed and Poria cocos oral preparation according to claim 6 or 7 in the preparation of health food that helps improve sleep.

10. The use of the Ziziphus jujuba seed and Poria cocos composition according to any one of claims 1 to 5 or the Ziziphus jujuba seed and Poria cocos oral preparation according to claim 6 or 7 in the preparation of a medicine that helps improve sleep, relieve anxiety and / or prevent depression.

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