Melatonin-containing probiotic composition and application of melatonin-containing probiotic composition in sleep

Abstract

The invention provides a composition containing melatonin and probiotics and application of the composition in the aspect of improving sleep. The composition can effectively improve sleep, reduce sleep latency, increase non-rapid eye movement sleep (NREM) time, improve immunity, protect gastrointestinal functions, improve intestinal health, relieve pressure and improve mood problems, inattention, cognitive dysfunction, memory deterioration and the like caused by sleep disorders.

Description

[0001] This application claims priority to Chinese Application No. 202411640807.1, filed on November 18, 2024, entitled “A probiotic composition containing melatonin and its use in sleep”, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention belongs to the field of health products and relates to a composition comprising melatonin and probiotics and its use in improving sleep. This composition can effectively improve sleep, reduce sleep latency, increase non-rapid eye movement (NREM) sleep time, and also enhance immunity, protect gastrointestinal function, improve gut health, relieve stress, and improve mood problems, poor concentration, cognitive impairment, and memory decline caused by sleep disorders. Background Technology

[0003] Sleep disorders refer to symptoms or pathophysiological physical or mental disorders related to sleep, including diseases that induce and maintain sleep (insomnia), excessive sleepiness, circadian rhythm disorders, and sleep-related functional disorders. The main clinical symptoms of insomnia are difficulty falling asleep, long sleep latency, easy awakening, early awakening, decreased sleep quality, and reduced total sleep time, accompanied by daytime functional disorders such as fatigue, low mood, physical discomfort, decreased attention, and slow reaction (Chinese Society of Neurology, Chinese Society of Neurology Sleep Disorders Group. Guidelines for the Diagnosis and Treatment of Insomnia in Chinese Adults (2017 Edition) [J]. Chinese Journal of Neurology, 2018, 51(5): 324-335.).

[0004] Chronic insomnia can induce a series of metabolic syndromes, depression, and cardiovascular diseases, while anxiety and depression can conversely worsen insomnia, seriously affecting people's daily lives and work. Sleep disorders can activate the hypothalamic-pituitary-adrenal axis (HPA), leading to an increase in reactive oxygen species in the gut, an imbalance in the gut microbiota, and consequently, damage to the gastric mucosa and disruption of intestinal cell structure.

[0005] Melatonin (MT) is a neurohormonal substance secreted by the pineal gland in the human brain. It is a powerful antioxidant that can effectively eliminate reactive oxygen species and improve sleep disorders caused by circadian rhythm disruption by regulating the biological clock.

[0006] Studies have found that gut microbiota can regulate sleep through pathways such as the gut-brain axis, neuroendocrine system, and vagus nerve. On the one hand, probiotics can alter neurotransmitter levels, thereby relieving stress and improving anxiety. On the other hand, the gut is an important site for the synthesis and storage of melatonin; supplementing with gut probiotics can improve gut health, promote melatonin synthesis in the body, and thus improve sleep quality. Simultaneously, gut probiotics play an important role in maintaining the balance of the mucosal microecology and protecting the mucosal barrier, and can repair gastric mucosal damage caused by sleep disorders while improving sleep.

[0007] Combining probiotics and melatonin can effectively improve sleep, reduce sleep latency, increase the quality and quantity of non-rapid eye movement (NREM) sleep, and also enhance immunity, protect gastrointestinal function, improve gut health, relieve stress, and improve mood problems, poor concentration, cognitive impairment, and memory decline caused by sleep disorders. Summary of the Invention

[0008] The purpose of this invention is to provide a composition comprising melatonin and probiotics and its use in improving sleep. This composition can effectively improve sleep, reduce sleep latency, increase non-rapid eye movement (NREM) sleep time, and also enhance immunity, protect gastrointestinal function, improve gut health, relieve stress, and improve mood problems, poor concentration, cognitive impairment, and memory decline caused by sleep disorders.

[0009] The melatonin-containing probiotic composition provided by this invention has the following advantages: (1) It can effectively improve sleep, reduce sleep latency, and increase non-rapid eye movement (NREM) sleep time; (2) It can effectively improve intestinal health, regulate and balance intestinal flora, colonize beneficial bacteria, eliminate harmful bacteria, and protect gastrointestinal function; (3) It can relieve stress and improve emotional problems, poor concentration, cognitive impairment, and memory decline caused by sleep disorders.

[0010] The present invention provides a probiotic composition containing melatonin, wherein the composition comprises probiotics and melatonin.

[0011] In one embodiment, the probiotic composition of the present invention contains melatonin at a concentration of ≥0.5 mg / serving, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 15 mg / serving.

[0012] In a preferred embodiment, the probiotic composition of the present invention contains melatonin at a content of 0.5-10 mg / serving.

[0013] In a more preferred embodiment, the probiotic composition of the present invention contains melatonin at a content of 0.5-5 mg / serving.

[0014] In a more preferred embodiment, the probiotic composition of the present invention contains melatonin at a content of 1-5 mg / serving.

[0015] In a particularly preferred embodiment, the probiotic composition of the present invention contains 2-5 mg of melatonin per serving.

[0016] In one embodiment, the probiotic composition of the present invention comprises one or more of the following genera: Lactobacillus, Akkermansia, Lactobacillus, Bifidobacterium, Enterococcus, Bacillus, Lactobacillus mucinus, Lactobacillus, Streptococcus, Lactococcus, Pediococcus, Clostridium, and Vibrio.

[0017] In one embodiment, the probiotic composition of the present invention comprises *Lactobacillus paracasei*, *Lactobacillus rhamnosus*, *Lactobacillus casei*, *Ackermania mucilage*, *Lactobacillus plantarum*, *Bifidobacterium adolescentis*, *Bifidobacterium animalis* subsp. *animal*, *Bifidobacterium animalis* subsp. *lactospirum*, *Bifidobacterium bifidum*, *Bifidobacterium longum* subsp. *infant*, *Bifidobacterium longum* subsp. *infant*, *Bifidobacterium pseudosporidis*, *Enterococcus faecalis*, *Bacillus subtilis*, *Mucobacterium reuteri*, and *Mucobacterium fermentum*. The bacteria include one or more of the following: *Streptococcus thermophilus*, *Lactobacillus acidophilus*, *Lactobacillus helveticus*, *Lactobacillus brevis*, *Lactobacillus delbrueckii* subsp. bulgaricus, *Lactobacillus delbrueckii* subsp. lactis, *Lactococcus curvularis*, lactic acid bacteria, *Lactococcus lactis*, *Lactobacillus gasseri*, *Lactobacillus johnsonii*, *Lactobacillus maltii* subsp. *maltii*, *Pediococcus pentosus*, *Pediococcus lactis*, *Streptococcus thermophilus*, *Streptococcus faecalis*, *Bacillus coagulans*, *Bacillus licheniformis*, *Bacillus natto*, *Clostridium butyricum*, *Vibrio butyricum*, and lactic acid bacteria.

[0018] In one embodiment, the probiotic composition of the present invention has a probiotic cell count of not less than 1 × 10⁻⁶. 5 CFU / part composition.

[0019] In a preferred embodiment, the probiotic composition of the present invention has a probiotic cell count greater than or equal to 1 × 10⁻⁶. 7 CFU / part composition.

[0020] In one embodiment, the probiotic composition of the present invention further includes plant extracts.

[0021] In one embodiment, the probiotic composition of the present invention contains plant extracts at a concentration of ≥0.5 mg / serving, such as 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, or 100 mg / serving.

[0022] In one embodiment, the probiotic composition of the present invention contains a plant extract at a content of 2 mg or more per serving.

[0023] In a preferred embodiment, the probiotic composition of the present invention contains a plant extract content of 5 mg or more per serving.

[0024] In one embodiment, the probiotic composition of the present invention comprises the following plant extracts: Gastrodia elata extract, Milk thistle extract, Ziziphus jujuba seed extract, Aristolochia debilis extract, Schisandra chinensis extract, Ganoderma lucidum extract, Gardenia jasminoides extract, Poria cocos extract, Acanthopanax senticosus extract, Apocynum venetum extract, Polygala tenuifolia extract, Platycladus orientalis seed extract, Lilium brownii extract, Pueraria lobata extract, Polygonum multiflorum vine extract, Bambusa textilis extract, Citrus reticulata peel extract, Bupleurum chinense extract, Poria cocos extract, Paeonia lactiflora extract, Albizia julibrissin bark extract, Pistachio nut extract, Mushroom extract, Ashwagandha extract, Scutellaria baicalensis extract, Portulaca oleracea extract, Spearmint extract, Hops extract, Walnut peptide powder, Valerian extract, Cyperus rotundus extract. One or more of the following extracts: Atractylodes macrocephala, mulberry, cucumber, banana, passionflower, lotus seed, black summer solstice grass, green tea, black tea, oolong tea, chestnut, tomato, spinach, broccoli, cabbage, cauliflower, Brussels sprouts, sweet potato, pumpkin, Polygonum multiflorum, lychee, longan, jujube, tomato, onion, cherry, almond, black walnut, hawthorn, chamomile, lavender, ginkgo, red ginseng, sour cherry juice, and lemon balm.

[0025] In one embodiment, the probiotic composition of the present invention contains one or more of the following plant extracts: organic acids, volatile oils, polysaccharides, terpenoids, flavonoids, phenolic compounds, alkaloids, glycosides, sterols, and minerals.

[0026] In one embodiment, the probiotic composition of the present invention comprises one or more of jujube saponins, ginsenosides, saponins, cardiac glycosides, baicalin, betulinic acid, oleanolic acid, pomodoroic acid, betulinic acid, geniposide, lupeol, gastrodin, guanosine, adenosine, and cytidine.

[0027] In one embodiment, the probiotic composition of the present invention comprises one or more of heliotropin, jujube alkaloid, magnoflorine, lotus leaf alkaloid, ephedrine, hyoscyamine, berberine, synephrine, and N-methyltyramine.

[0028] In one embodiment, the probiotic composition of the present invention comprises phenolic compounds including tea polyphenols, tocopherols, tocotrienols, magnolol, tert-butylhydroquinone, anthocyanins, astaxanthin, quercetin, ellagic acid, catechins, proanthocyanidins, rosmarinic acid, curcumin, resveratrol, lignans, luteolin, cat's tail isoflavones, eugenol, oleuropein, oleuropein, kaempferol, apigenin, isorhamnetin, gallic acid, vanillic acid, eugenol, p-coumaric acid, ferulic acid, phytocannabinoids, and epicatechin. Epicatechin-3-gallate, caffeic acid, chlorogenic acid, cinnamic acid, cinnamaldehyde, cinnamyl alcohol, eugenol, vanillin, coumarin, kaempferol, hesperidin, naringenin, sennaol, delphinidin, cyanidin, silymarin, puerarin, schisandrin, apple polyphenols, crocin, saffron aldehyde, ellagic acid, mulberry leaf polyphenols, hydroxytyrosol, rosmarinic acid, salvianolic acid, lithospermic acid, fulvic acid, sarsaparilla acid, chestnut peel polyphenols, tannins, baicalin, sennain A, emodin, anthocyanins, litchi polyphenols, or one or more of these.

[0029] In one embodiment, the probiotic composition of the present invention comprises one or more of sarcosine, creatine, naringin, rosmarinic acid, clove oil, thiotaurine, boswellic acid, oleic acid, linoleic acid, myristic acid, lauric acid, palmitic acid, stearic acid, arachidic acid, arachienoic acid, linolenic acid, succinic acid, chlorogenic acid, citric acid, and malic acid.

[0030] In one embodiment, the probiotic composition of the present invention comprises one or more of the following polysaccharides: Gastrodia elata polysaccharide, Gardenia jasminoides polysaccharide, L-arabinose, Dendrobium nobile polysaccharide, Auricularia auricula-judae polysaccharide, D-mannose, D-galactose, Astragalus membranaceus polysaccharide, Lycium barbarum polysaccharide, Lentinus edodes polysaccharide, Ginseng polysaccharide, Glycyrrhiza uralensis polysaccharide, Tremella fuciformis polysaccharide, Pueraria lobata polysaccharide, Mulberry polysaccharide, Oat polysaccharide, Ophiopogon japonicus polysaccharide, Aloe vera polysaccharide, Sophora japonica polysaccharide, β-glucan, α-glucan, β-galactoglucan, L-fucose, D-xylose, D-glucose, glucuronic acid, and Ganoderma lucidum polysaccharide.

[0031] In one embodiment, the probiotic composition of the present invention comprises one or more of the following flavonoids: apigenin, epigallocatechin, luteolin-3′,7-di-O-glucose, quercetin, hyperoside, flavonoids, flavanones, hesperidin, norihesperidin, neohesperidin, naringin, rutin, polymethoxyflavonoids, flavonols, dihydroflavonoids, dihydroflavonols, isoflavones, dihydroisoflavones, chalcones, dihydrochalcones, hesperidin, anthocyanins, rutin, daidzein, anthocyanins, flavanols, and proanthocyanidins.

[0032] In one embodiment, the probiotic composition of the present invention comprises one or more of the following steroidal compounds: β-sitosterol, campesterol, lanosterol, stigmasterol, stigmasterol, lupeol, n-trigecanol, β-amyrin, patchouli alcohol, inositol, 3β,5α,6β-trihydroxystigmasterane, daucosterol, diosgenin, stigmasterane-3,5-diene, campesterol, γ-sitosterol, cholesterol, ergosterol, cholesterol, lanosterol, lanolin alcohol, lanolinic acid, phytosterols, and rice bran fatty alkyl alcohols.

[0033] In one embodiment, the probiotic composition of the present invention comprises one or more of the following terpenoid compounds: betulinol, betulinic acid, pachymic acid, ebric acid, pachytriterpenes, ginkgolide, ginsenosides, linalool, citronellol, geraniol, eugenol, carotene, lycopene, zeaxanthin, betulinol, tea saponins, fucoxanthin, styraxol, sapindus muscaria, limonene, pinene, caryophyllene, humulene, and boswellic acid.

[0034] In one embodiment, the probiotic composition of the present invention comprises one or more of α-guaiacene, α-buniene, β-caryophyllene, α-patchoulene, pinene, α-thujone, α-pinene, β-pinene, β-myrcene, octanal, limonene, terpineol, citronellol, carvacrol, octanol, eugenol, hexanoic acid, p-methoxyphenyldione, and saikosamol.

[0035] In one embodiment, the probiotic composition of the present invention comprises one or more of magnesium, calcium, zinc, iron, and potassium.

[0036] In a preferred embodiment, the probiotic composition of the present invention comprises at least one or more of the following plant extracts: tart cherry juice, lemon balm extract, passionflower extract, valerian extract, and milk thistle extract.

[0037] In a more preferred embodiment, the probiotic composition of the present invention contains at least milk thistle extract.

[0038] In one embodiment, the probiotic composition of the present invention contains milk thistle extract at a concentration of ≥0.2 mg / serving, such as 0.2, 0.5, 1, 1.5, 2, 3, 4, 5, or 10 mg / serving.

[0039] In a preferred embodiment, the probiotic composition of the present invention contains a milk thistle extract at a content of 1 mg or more per serving.

[0040] In a preferred embodiment, the probiotic composition of the present invention comprises one or more of the active ingredients of the milk thistle extract, including silybin A, silybin B, isosilybin A, isosilybin B, silybinine, isosilybinine, silybinin, taxanein, and apigenin.

[0041] In a more preferred embodiment, the probiotic composition of the present invention comprises at least one or more of apigenin and silybin as active ingredients of the milk thistle extract.

[0042] In a particularly preferred embodiment, the probiotic composition of the present invention contains at least apigenin as an active ingredient of the milk thistle extract.

[0043] In one embodiment, the probiotic composition of the present invention contains ≥20% silybin in the milk thistle extract.

[0044] In a preferred embodiment, the probiotic composition of the present invention contains ≥30% silybin in the milk thistle extract.

[0045] In a preferred embodiment, the probiotic composition of the present invention contains ≥40% silybin in the milk thistle extract.

[0046] In a preferred embodiment, the probiotic composition of the present invention contains ≥50% silybin in the milk thistle extract.

[0047] In a preferred embodiment, the probiotic composition of the present invention contains ≥60% silybin in the milk thistle extract.

[0048] In a preferred embodiment, the probiotic composition of the present invention contains ≥70% silybin in the milk thistle extract.

[0049] In a preferred embodiment, the probiotic composition of the present invention contains ≥80% silybin in the milk thistle extract.

[0050] In a preferred embodiment, the probiotic composition of the present invention contains ≥85% silybin in the milk thistle extract.

[0051] In a preferred embodiment, the probiotic composition of the present invention contains ≥90% silybin in the milk thistle extract.

[0052] In a preferred embodiment, the probiotic composition of the present invention contains ≥95% silybin in the milk thistle extract.

[0053] In a preferred embodiment, the probiotic composition of the present invention contains ≥20% apigenin in the milk thistle extract.

[0054] In one embodiment, the method for preparing the plant extract is selected from enzymatic hydrolysis, water extraction, alcohol extraction, ultrasonic extraction, and supercritical fluid extraction.

[0055] In one embodiment, the method for preparing the plant extract specifically includes: (1) selecting and processing plant raw materials, such as washing, cutting or crushing; (2) Active ingredients are extracted using enzymatic hydrolysis, water extraction, alcohol extraction, ultrasonic extraction, and supercritical fluid extraction. (3) The extract was separated and purified by methods such as filtration, centrifugation, chromatography, membrane separation and crystallization; (4) Concentrate and dry the extract using techniques such as evaporation, freeze drying or spray drying.

[0056] In one embodiment, the probiotic composition of the present invention further includes amino acids.

[0057] In a preferred embodiment, the probiotic composition of the present invention includes, but is not limited to, γ-aminobutyric acid, L-theanine, tryptophan, L-glycine, and theanine.

[0058] In a more preferred embodiment, the probiotic composition of the present invention includes at least γ-aminobutyric acid (GABA).

[0059] In a particularly preferred embodiment, the probiotic composition of the present invention contains γ-aminobutyric acid (GABA).

[0060] In one embodiment, the probiotic composition of the present invention contains amino acids at a content greater than or equal to 1 mg / serving, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 mg / serving.

[0061] In one embodiment, the probiotic composition of the present invention further includes vitamins.

[0062] In a preferred embodiment, the probiotic composition of the present invention includes, but is not limited to, vitamins C, D, B, E, K, A, niacin, folic acid, pantothenic acid, choline, and biotin.

[0063] In a preferred embodiment, the probiotic composition of the present invention includes one or more of vitamin B3 and vitamin B6.

[0064] In a more preferred embodiment, the probiotic composition of the present invention includes one or more of vitamin B, vitamin E, niacin, and folic acid.

[0065] In one embodiment, the probiotic composition of the present invention contains vitamins at a concentration of 3 mg or more per serving, such as 3, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100 mg per serving.

[0066] In one embodiment, the probiotic composition of the present invention further includes minerals.

[0067] In a preferred embodiment, the probiotic composition of the present invention includes, but is not limited to, magnesium, calcium, iron, zinc, potassium, manganese, and copper.

[0068] In one embodiment, the probiotic composition of the present invention has a magnesium content of 5 mg or more per serving.

[0069] This invention provides a probiotic composition containing melatonin, wherein the composition is prepared into a formulation easily accepted by the human body by adding excipients, including but not limited to tablets, capsules, powders, oral liquids, sprays, and solid beverages.

[0070] The present invention also provides the use of any of the melatonin-containing probiotic compositions in improving sleep, enhancing immunity, improving gut health, relieving stress, and improving mood problems, poor concentration, cognitive impairment, and memory decline caused by sleep disorders.

[0071] Furthermore, the present invention also provides the use of any of the melatonin-containing probiotic compositions in improving sleep.

[0072] Furthermore, the present invention provides the use of any of the melatonin-containing probiotic compositions in enhancing immunity, improving gut health, and relieving stress.

[0073] Furthermore, the present invention provides the use of any of the melatonin-containing probiotic compositions in improving mood problems, poor concentration, cognitive impairment, and memory decline caused by sleep disorders.

[0074] This invention provides a composition comprising melatonin and probiotics and its use in improving sleep. This composition can effectively improve sleep, reduce sleep latency, increase non-rapid eye movement (NREM) sleep time, and also enhance immunity, protect gastrointestinal function, improve gut health, relieve stress, and improve mood problems, poor concentration, cognitive impairment, and memory decline caused by sleep disorders. Terminology Explanation

[0075] The term "probiotics" refers to a general term for live beneficial microorganisms with definite health benefits that colonize the human body (mainly the intestines and reproductive system), improve the composition and microecological balance of the host's flora in a certain part, and exert beneficial effects. *Lactobacillus* genus includes, but is not limited to, *Lactobacillus casei*, *Lactobacillus paracasei*, and *Lactobacillus rhamnosus*. *Lactobacillus casei* can withstand the organism's defense mechanisms and can accumulate in large quantities in the intestines after entering the human body, playing a role in regulating the balance of intestinal flora and promoting human digestion and absorption. *Lactobacillus rhamnosus* is a probiotic that can regulate the microecological balance and enhance the host's intestinal resistance. *Lactobacillus paracasei* has the ability to withstand acid and bile salts and can maintain good activity in simulated digestive juices. It also has antibacterial ability and good cell adhesion characteristics, which can regulate intestinal flora, protect the intestinal epithelial barrier, reduce inflammatory factors in the intestine, and alleviate colitis. *Akkermania* genus includes, but is not limited to, *Akkermansia myxophilus*. Akkermansia myxophilus (Akk bacteria) is a beneficial intestinal bacterium that can alleviate enteritis symptoms, regulate immune responses in the spleen, intestines, and mesenteric lymph nodes, reduce intestinal inflammation levels, and prevent colorectal cancer caused by enteritis. Lactobacillus spp. includes, but is not limited to, *Lactobacillus plantarum*. *Lactobacillus plantarum* has strong acid and bile salt resistance, and also possesses probiotic properties such as enhancing immunity, improving intestinal flora structure and function, maintaining intestinal flora balance, and lowering cholesterol. After colonizing the intestines, *Lactobacillus plantarum* can produce antibacterial substances such as bacteriocins, organic acids, and diacetyl, thereby inhibiting the growth of harmful bacteria and maintaining intestinal flora balance. Bifidobacteria spp. have the effects of regulating intestinal flora and immune system. Bifidobacteria spp. includes, but is not limited to, *Bifidobacterium adolescentis*, *Bifidobacterium animalis* subspecies, *Bifidobacterium animalis* subspecies, *Bifidobacterium bifidum*, *Bifidobacterium longum* subspecies, *Bifidobacterium longum* subspecies, and *Bifidobacterium pseudosporidis*. Bifidobacterium lactis (now updated to Bifidobacterium animalis subspecies and Bifidobacterium animalis subspecies) is a probiotic for the gut. It can inhibit the growth of putrefactive bacteria in the intestines and participate in the synthesis of vitamins B1, B2, B6, and K. It can also promote the degradation and absorption of food and prevent iron-deficiency anemia or osteomalacia. In addition, Bifidobacterium lactis has a role in creating a biological barrier for human health, and has certain effects in enhancing immunity and anti-tumor activity. The large amount of short-chain fatty acids it secretes can acidify the intestines and control abnormal fermentation caused by harmful bacteria. Bifidobacterium adolescentis is a probiotic that can treat chronic diarrhea and constipation and has anti-aging effects. Bifidobacterium longum subspecies effectively inhibits pathogenic bacteria in the intestines. By producing organic acids such as lactic acid and acetic acid and secreting antibacterial compounds such as bacteriocins, it effectively lowers the pH of the environment, inhibits the growth and reproduction of acid-sensitive pathogens, and regulates intestinal flora imbalance.Bifidobacterium pseudosporidis is the most morphologically varied Bifidobacterium species, widely present in the intestines of children, adults, and healthy elderly individuals. It possesses beneficial functions such as regulating immunity, reducing inflammation, regulating the nervous system, and improving glucose and lipid metabolism in obese children. Bifidobacterium bifidum can scavenge DPPH (1,1-diphenyl-2-trinitrophenylhydrazine) and ABTS (2,2'-azido-bis-3-ethylbenzothiazoline-6-sulfonic acid) free radicals. Enterococci include, but are not limited to, Enterococcus faecalis. Enterococci are present in the upper respiratory tract, digestive tract, and reproductive tract of humans and animals, forming part of the normal intestinal flora. They produce bacteriocins and other antibacterial substances, inhibiting the growth of pathogens such as Escherichia coli and Salmonella, and improving the intestinal microenvironment. Bacillus includes, but is not limited to, Bacillus subtilis, Bacillus coagulans, Bacillus licheniformis, and Bacillus natto. During its growth, *Bacillus subtilis* produces active substances such as subtilisin, polymyxin, nystatin, and bacitracin, which significantly inhibit pathogenic bacteria or opportunistic pathogens causing endogenous infections. It rapidly consumes free oxygen in the intestines, creating intestinal hypoxia, promoting the growth of beneficial anaerobic bacteria, and indirectly inhibiting the growth of other pathogenic bacteria. *Bacillus subtilis* itself synthesizes enzymes such as α-amylase, protease, lipase, and cellulase, which work in conjunction with digestive enzymes in the digestive tract (in animals and humans). It can also synthesize various B vitamins, including B1, B2, B6, and niacin, and enhance the activity of interferon and macrophages in animals and humans. *Lactobacillus* genus includes, but is not limited to, *Lactobacillus fermentum* and *Lactobacillus reuteri*. *Lactobacillus fermentum* (formerly *Lactobacillus fermentum*) has antibacterial and anti-inflammatory capabilities, can maintain intestinal microecological balance, promote digestion and absorption, and improve immunity. *Lactobacillus reuteri* (formerly *Lactobacillus reuteri*) has a strong adhesion ability to the intestinal mucosa, which can improve the distribution of intestinal flora, antagonize the colonization of harmful bacteria, prevent intestinal diseases, improve human function, enhance immunity, and thus promote human health. *Streptococcus* spp. includes, but is not limited to, *Streptococcus thermophilus* subsp. *salivarius* and *Streptococcus faecalis*. *Streptococcus thermophilus* subsp. *salivarius* can produce extracellular polysaccharides, bacteriocins, and vitamins, and is a potentially beneficial bacterium. It can improve the intestinal microenvironment, lower intestinal pH, promote intestinal peristalsis, and prevent pathogen colonization. *Lactobacillus* spp. is a general term for various bacteria that can break down sugars such as glucose into lactic acid. They have a strong ability to metabolize carbohydrates and produce acid, can synthesize glucans and heteropolysaccharides, and can ferment sugars to produce lactic acid or other acidic substances. Lactobacilli that parasitize the intestines and vagina have a protective effect on the body; they have functions such as regulating intestinal flora, enhancing immunity, protecting the gastric mucosa, improving intestinal function, promoting digestion, anti-tumor, and antioxidant effects. Lactobacillus includes, but is not limited to, Lactobacillus acidophilus, Lactobacillus curvaturei, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus delbrueckii subsp. lactis, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus maltii subsp. maltii, Lactobacillus brevis, and lactic acid bacteria.*Lactobacillus acidophilus* can inhibit the growth of *Escherichia coli*, improve the intestinal environment, relieve stomach discomfort, and has anti-allergic effects. It can reduce the production of toxins in the body and alleviate the liver's detoxification burden. *Lactobacillus helveticus* has strong proteolytic activity, and its fermented dairy products have a high polypeptide content, thus possessing the potential to produce bioactive peptides. *Lactobacillus helveticus* hydrolyzes milk protein to produce angiotensin-converting enzyme inhibitory peptide (ACEIP), which is the most frequently reported lactic acid bacteria in blood pressure-lowering studies. It also has functions such as relieving hypertension, maintaining intestinal flora balance, promoting calcium absorption, and improving sleep. *Lactobacillus brevis* is resistant to acid and salt, allowing it to survive in harsh environments. It can reach the intestines alive, remain there, and produce large amounts of lactic acid to inhibit the growth of harmful bacteria and regulate the intestinal environment. *Lactobacillus de Germany* subsp. Bulgaria has important physiological functions such as regulating gastrointestinal health, promoting digestion and absorption, increasing immune function, and anti-cancer and anti-tumor effects. Lactic acid bacteria produce a large amount of organic acids, which can lower the pH of the environment, inhibit the reproduction of pathogenic bacteria, activate macrophages, improve the body's immune function, and enhance local anti-infection ability. They can also produce hydrogen peroxide, antimicrobial peptides, and bacteriocins, which have a significant inhibitory effect on pathogenic bacteria. *Lactobacillus johnsonii* has the effect of improving obese physique, reducing body fat and cholesterol, while stabilizing the intestinal flora, maintaining an intestinal ecology with more beneficial bacteria than harmful bacteria, thereby stimulating the mucosa to strengthen the immune system and having a cleansing and protective effect on the intestines. *Lactobacillus gasseri*, also known as *Lactobacillus gasseri*, has the ability to regulate the intestinal flora, which is beneficial to improving intestinal immunity and resistance. It can maintain the acid-base balance of the intestine, inhibit the growth of harmful bacteria, promote the reproduction of beneficial bacteria, and maintain the balance of the intestinal flora. In addition, *Lactobacillus gasseri* can also increase the function of the intestinal mucosal barrier, preventing the invasion and absorption of harmful substances and protecting intestinal health.

[0076] The term "plant extract" refers to substances extracted or processed from plants (whole or part of a plant) using appropriate solvents or methods. Gastrodia elata extract is a brownish-yellow fine powder extracted from the dried tuber of the orchid Gastrodia elata Blume. It possesses various pharmacological effects, including sedation, anticonvulsant, antioxidant, and antidepressant properties. It can balance neurotransmitter release, reduce inflammatory factor expression, regulate HPA axis function, regulate intestinal microbial abundance, and increase 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) levels, thus improving insomnia. Ziziphus jujuba seed extract has the effects of nourishing the heart and liver, calming the mind and soothing the nerves. It can improve insomnia caused by insufficient yin and blood in the heart and liver. Its main component, flavonoids, can achieve its anti-anxiety, sedative, and hypnotic effects by regulating 5-HT1A receptors. Star vine extract has the effects of regulating uric acid, anti-oxidation, assisting in lowering blood sugar, improving immunity, improving sleep, promoting metabolism, and preventing cardiovascular diseases. Schisandra chinensis extract, rich in lignans, volatile oils, and polysaccharides, has a good therapeutic effect on hepatitis, improving symptoms such as loss of appetite, fatigue, and insomnia. It also protects the liver, promotes hepatocyte regeneration, enhances liver detoxification, and strengthens adrenal cortex function. Ganoderma lucidum extract possesses antioxidant capabilities and exhibits anti-inflammatory, anti-fatigue, sleep-improving, insomnia-relieving, neuroprotective, liver-function-improving, and blood sugar-stabilizing effects. Gardenia jasminoides extract contains various active ingredients such as geniposide and quercetin, with gardenia yellow pigment having a sleep-improving effect. Poria cocos extract, primarily composed of pachymic acid, can increase the levels of GABA receptor α and β subunits and decrease the level of γ subunits, achieving a sedative-hypnotic effect. Acanthopanax senticosus extract has the effects of invigorating qi and spleen, tonifying the kidneys and calming the mind, and is often used for spleen and kidney yang deficiency, physical weakness, loss of appetite, lower back and knee pain, and insomnia with excessive dreaming. Apocynum venetum extract, derived from the leaves of the Apocynum venetum plant (Apocynum venetum, Apocynaceae family), has the effects of clearing heat and calming the liver, promoting diuresis and reducing swelling. It is mainly used to treat hypertension, dizziness, headache, palpitations, insomnia, and edema with scanty urine. Polygala tenuifolia extract has the effects of calming the mind and improving intelligence, expectorant, and reducing swelling. It is used for symptoms such as insomnia, dreaminess, forgetfulness, palpitations, mental confusion, cough with phlegm, sores and carbuncles, and breast swelling and pain caused by disharmony between the heart and kidneys. Platycladus orientalis seed extract is mainly used to nourish the heart and calm the mind, and moisten the intestines and promote bowel movements. It is used for symptoms such as insomnia due to deficiency and restlessness, palpitations, and constipation due to intestinal dryness. Lily extract is a chemical substance extracted from lily. It has the effects of nourishing yin and moistening the lungs, calming the mind and soothing the nerves, anti-inflammatory, antioxidant, antibacterial, hypoglycemic, and hypolipidemic effects. It is used for chronic cough due to yin deficiency, hemoptysis, restlessness and palpitations, insomnia, dreaminess, mental confusion, improving liver function, and reducing fatigue. Kudzu root extract is rich in up to 13 kinds of isoflavones, which have very good regulatory effects on the human body. Among them, active substances such as daidzein, daidzein, and puerarin can promote blood flow in the cardiovascular and retinal systems, relax smooth muscles and relieve spasms, resist cancer and induce cancer cell differentiation, lower blood sugar, lower blood pressure, resist oxidation, relieve fever and hangover, improve memory and enhance immunity.Polygonum multiflorum vine contains anthraquinone compounds, including emodin, chrysophanol, emodin methyl ether, and β-sitosterol, which have sedative and hypnotic effects, inhibit hyperlipidemia, prevent and treat arteriosclerosis, and promote immune function. Bamboo shavings extract is an active substance extracted from the grasses *Phyllostachys edulis* or *Phyllostachys pubescens*, containing alkaloids, tannins, saponins, amino acids, organic acids, reducing sugars, triterpenes, and various trace elements, possessing anti-fatigue, anti-hyperlipidemia, and anti-hypertensive physiological functions. Tangerine peel extract has hepatoprotective, choleretic, expectorant, antiasthmatic, anti-inflammatory, anti-allergic, antibacterial, antiviral, antioxidant, and hydroxyl free radical scavenging effects. Bupleurum chinense, mainly composed of saikosaponins, prolongs hypnosis time in mice and significantly reduces spontaneous acquired epilepsy, demonstrating good sedative and hypnotic effects. Poria cocos extract is the white part naturally containing pine roots (i.e., *Poria cocos* wood) in the center of the sclerotium of *Poria cocos*, a polypore fungus, and is mainly used to treat palpitations due to heart deficiency, forgetfulness, insomnia, epilepsy, and dysuria. Paeonia lactiflora extract, primarily composed of paeoniflorin, can increase the level of endogenous 5-HT in cerebrospinal fluid, thus exerting a sedative and hypnotic effect. Albizia julibrissin bark extract, a yellow-brown powder extracted from the dried bark of the legume Albizia julibrissin, contains albizia glycosides, saponins, tannins, and other components. It has the effects of relieving depression and calming the mind, promoting blood circulation and reducing swelling. It improves sleep and anxiety by inhibiting oxidative stress induced by glutamate and can reduce nerve damage in brain tissue. Polygonum multiflorum extract is neutral in nature and non-toxic, with a sweet and slightly bitter taste. It enters the heart and liver meridians and has the effects of calming the mind, nourishing blood, dispelling wind, and unblocking the meridians. It is mainly used to treat insomnia, fatigue, excessive sweating, blood deficiency and body pain, carbuncles, scrofula, and skin sores and scabies. Mushroom extract has anti-inflammatory, antioxidant, endocrine-regulating, and immunomodulatory effects, and shows some efficacy in the treatment of chronic ulcers and inflammation. It contains ergothioneine, which can improve memory and concentration, and slow the rate of cognitive decline in the elderly. Mushroom extract also has stress-relieving, mood-stabilizing, and antidepressant effects. Scutellaria baicalensis extract has anti-inflammatory, antimicrobial, antipyretic, hypotensive, choleretic, and sedative effects. Portulaca oleracea extract can enhance brainpower, cognitive health, and improve sleep. Spearmint extract contains more than 50 phenolic compounds, including rosmarinic acid, salvianolic acid, shikonin, and caffeic acid, and has antioxidant, anti-inflammatory, and sleep-improving effects, including enhancing overall working memory and spatial working memory accuracy. Pistachio extract's main component is melatonin, which improves sleep. Walnut peptide powder has nerve-soothing and sleep-improving effects. Hops extract contains flavonoids and other active ingredients, and has sleep-promoting, antibacterial, and sedative effects. Spinach extract contains abundant antioxidants such as vitamin E and selenium, which have anti-aging and cell-proliferation-promoting effects. It can activate brain function, enhance vitality, and help prevent brain aging and Alzheimer's disease. Broccoli extract is rich in sulforaphane, which has anti-cancer, lung-cleansing, and gout-preventing effects. It can also eliminate free radicals, prevent aging, and provide antioxidant benefits.Ashwagandha, also known as Indian ginseng, has significant antioxidant and immune-boosting properties and has been used to induce sleep. Valerian extract has antidepressant, sedative, hypnotic, anticonvulsant, antibacterial, antiviral, and antitumor effects. Cyperus rotundus extract exerts neuroprotective effects by reducing corticosterone-induced lactate dehydrogenase release levels and decreasing cell apoptosis. Atractylodes macrocephala extract's main components, atractylenolide II and atractylenolide III, regulate GABA levels in the body, resulting in sedative, hypnotic, and anti-anxiety effects. Furthermore, Atractylodes macrocephala can improve nervous system function by reducing apoptosis genes and proteins in hypoxic nerve cells and increasing the production of anti-apoptotic genes and proteins, thereby reducing nerve cell apoptosis. Mulberry extract has the effects of nourishing blood and yin, promoting body fluid production and moistening dryness, and is often used for dizziness, tinnitus, palpitations, insomnia, premature graying of hair, thirst due to fluid depletion, internal heat and thirst, and constipation due to blood deficiency. The cellulose in cucumbers helps promote the elimination of putrefactive substances in the intestines and lowers cholesterol, thus strengthening the body, improving brain and nervous system function, calming the mind, and assisting in the treatment of insomnia. Banana extract is rich in serotonin and tryptophan, which can improve sleep and relax the mind. Passionflower extract has sedative, antispasmodic, anti-anxiety, blood pressure-lowering, anti-inflammatory, and sleep-inducing effects, improving sleep quality and reducing anxiety. Lotus seed extract, extracted from mature lotus seeds, can be used for chronic diarrhea due to spleen deficiency, palpitations, and insomnia. Black summer solstice grass extract has antiemetic, antispasmodic, sedative, expectorant, astringent, hemostatic, diuretic, and uterine-contracting effects; it is used as an antiemetic to treat nausea and vomiting; it is also used for nausea caused by inner ear disorders; and it can also treat nervous indigestion, insomnia, tension, pruritus, and has antispasmodic effects.

[0077] Milk thistle (Silybum marianum (L) Gaertn), also known as water pheasant, is a plant containing fumaric acid and flavonoids. Its seeds are rich in silymarin (a collective term for silybin A, silybin B, silybinine, silybinin, etc.), which has effects such as stabilizing cell membranes, anti-inflammation, anti-cancer, and cardiovascular protection. It is commonly used for liver damage, hypochondriac pain, and jaundice. Silymarin also has anti-lipid peroxidation, free radical scavenging, antioxidant, and glutathione-enhancing effects. Milk thistle can improve hypothermia after melatonin use, increase liver metabolism, reduce the side effects of melatonin, and improve fatigue after waking up. Apigenin (4',5,7-trihydroxyflavone) in milk thistle has therapeutic and sleep-improving effects; therefore, adding milk thistle can improve sleep. Other studies have shown that silymarin has certain effects on various intestinal bacteria, and intestinal bacteria can use silymarin as the sole carbon source to maintain normal cell growth. Attached Figure Description

[0078] Figure 1 A typical illustration of zebrafish behavior; Figure 2Increase the activity level of zebrafish during awakening; Figure 3 This is the time for zebrafish to awaken and become active. Detailed Implementation

[0079] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments. The content mentioned in the embodiments is not intended to limit the present invention. Example Example 1

[0080] The composition was obtained by adding melatonin and Akkella myxophila. Example 2

[0081] The composition was obtained by adding melatonin, Lactobacillus paracasei, and milk thistle extract. Example 3

[0082] The composition was obtained by adding melatonin, Bifidobacterium adolescentis, milk thistle extract, and γ-aminobutyric acid. Example 4

[0083] The composition was obtained by adding melatonin, Bacillus subtilis, and valerian extract. Example 5

[0084] The composition was obtained by adding melatonin, fermented Lactobacillus mucilaginosus, milk thistle extract, and passion fruit extract. Example 6

[0085] The composition was obtained by adding melatonin, Lactobacillus acidophilus, milk thistle extract, tart cherry juice, and magnesium. Example 7

[0086] The composition was obtained by adding melatonin, Lactobacillus brevis, milk thistle extract, and L-theanine. Example 8

[0087] The composition was prepared by adding melatonin, lactic acid bacteria, lemon balm extract, and vitamin E. Example 9

[0088] The composition was obtained by adding melatonin, Lactococcus lactis, milk thistle extract, and tryptophan. Example 10

[0089] The composition was obtained by adding melatonin, Clostridium butyricum, Akkella myxophila (Akk bacteria), and milk thistle extract. Example 11

[0090] The composition was obtained by adding melatonin, Lactobacillus acidophilus, γ-aminobutyric acid, and magnesium. Example 12

[0091] The composition was prepared by adding melatonin, Lactobacillus brevis, tart cherry juice, valerian extract, L-theanine, and vitamin B6.

[0092] Example 13: Probiotic jelly containing melatonin Mix 2 mg of melatonin with 1×10 8 CFU of probiotics (such as Akk bacteria) is mixed and added to a jelly base (water, sugar, carrageenan, etc.) to produce a probiotic jelly containing melatonin. The preparation method includes mixing melatonin with Akk bacteria solution, adding the jelly base and stirring evenly, heating to boiling, filling into aseptic jelly strips, cooling and solidifying, and then sealing.

[0093] Example 14: Probiotic powder strips containing melatonin Mix 3 mg of melatonin with 1×10 8 A mixture of CFU probiotics (such as Lactobacillus paracasei) and 5 mg of milk thistle extract is added, along with excipients such as rice flour and maltodextrin, to produce a probiotic powder strip containing melatonin. The preparation method involves mixing melatonin, milk thistle extract, and other excipients, mixing thoroughly with the bacterial solution, spray-drying to form a powder, and then filling the powder into aseptic strips.

[0094] Example 15: Probiotic oral liquid containing melatonin Mix 2 mg of melatonin with 1×10 8 CFU of probiotics (such as Lactobacillus acidophilus) is mixed with 4 mg of γ-aminobutyric acid (GABA) and 5 mg of magnesium salts (such as magnesium glycine or magnesium citrate). Appropriate amounts of glycerol, potassium sorbate, and other stabilizers and preservatives are added to produce a melatonin-containing probiotic oral solution. The preparation method involves dissolving γ-aminobutyric acid and magnesium salts (such as magnesium glycine or magnesium citrate) in sterile water, mixing thoroughly with Lactobacillus acidophilus, adjusting the pH, filtering to remove bacteria, filling into sterile bottles, and sealing.

[0095] Example 16: Probiotic Gummies Containing Melatonin Mix 2 mg of melatonin with 1×10 8 A mixture of CFU probiotics (such as Lactobacillus brevis) is added, along with 4 mg L-theanine, 5 mg tart cherry juice, 5 mg valerian extract, and 3 mg vitamin B6. Appropriate amounts of syrup, gelatin, pectin, and other excipients are also added to produce melatonin-containing probiotic gummies. The preparation method involves thoroughly mixing melatonin, L-theanine, tart cherry juice, valerian extract, vitamin B6, and Lactobacillus acidophilus, adding excipients, cooking with sugar to obtain a thick syrup, cooling to a suitable temperature, and cutting to obtain melatonin-containing probiotic gummies.

[0096] Example 17: Probiotic tablets containing melatonin Mix 3 mg of melatonin with 1×108 CFU of probiotics (such as *Lactobacillus fermentum*) is mixed with 5 mg of milk thistle extract and 5 mg of passion fruit extract, along with appropriate amounts of calcium bicarbonate, pregelatinized starch, and other excipients, to produce probiotic tablets containing melatonin. The preparation method includes unpacking, cleaning, sterilizing, and sieving the excipients, mixing them with *Lactobacillus fermentum*, melatonin, milk thistle extract, and passion fruit extract, adding a lubricant, inspecting the tableting process, and drying to obtain probiotic tablets containing melatonin. Test case

[0097] Test Example 1: Zebrafish Sleep Experiment 1.1. Sample Information Sample: Prepared with DMSO, use immediately. Positive control: Melatonin, batch number 21090517, TMstandard, stored at -20 ℃. Prepared as a 50 mg / mL stock solution with DMSO, stored at -20 ℃.

[0098] Table 1 Group Dosage normal control group / Model control group / melatonin Melatonin 3mg 1 <![CDATA[Melatonin 3 mg + Lactobacillus paracasei 1×10 6 cfu]]> 2 <![CDATA[Melatonin 3 mg + Lactobacillus paracasei 1×10 8 cfu]]> 3 <![CDATA[Melatonin 3 mg + Lactobacillus paracasei 1×10 8 cfu + Silybum marianum 5 mg]]> 1.2. Laboratory Animals Zebrafish were all raised in aquarium water at 28 ℃ (water quality: 200 mg of readily soluble sea salt added per 1 L of reverse osmosis water; conductivity 450-550 μS / cm; pH 6.5-8.5; hardness 50-100 mg / L CaCO3), bred and provided by our company's aquarium. Wild-type AB strain zebrafish were bred through natural pair mating. Zebrafish aged 5 days post-fertilization (5 dpf) were used to evaluate the sleep-improving effects.

[0099] 1.3. Instruments, Consumables and Reagents Dissecting microscope (Mingmei, China); Precision electronic balance (XSR205, METTLER, USA); 6-well plate (BIOFILBiotech, China); 96-well plate (BIOFILBiotech, China); Behavior analyzer (V3.11, ViewPointLifeSciences, France).

[0100] Pentylenetetrazole (PTZ, batch number 54-95-5, Shanghai Yihe Biotechnology Co., Ltd., China); Dimethyl sulfoxide (DMSO, batch number BCCD8942, Sigma, USA).

[0101] 1.4. Evaluation of its sleep-improving effects Wild-type AB strain zebrafish with a 5-day pf growth rate were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). After incubation at 28 ℃ for 24 h, the zebrafish were transferred to 96-well plates, 180 μL / zebrafish, 1 fish / well. Except for the normal control group, each well of the other experimental groups was injected with 20 μL of 50 mM PTZ to establish a zebrafish insomnia model.

[0102] Under the monitoring of a behavior analyzer, the movement of zebrafish was categorized into low-speed movement (displayed as a black line, movement speed less than 4 mm / s, representing a stationary state); medium-speed movement (displayed as a green line, movement speed between 4-20 mm / s, representing a normal movement state); and high-speed movement (displayed as a red line, movement speed greater than 20 mm / s, representing an insomnia state). The activity level (wakefulness activity level) and activity duration (wakefulness activity time) of zebrafish in the insomnia state were measured using the behavior analyzer. The sleep-improving efficacy of the samples was evaluated based on the statistical analysis results of these indicators. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS 22.0 software, and p < 0.05 indicated a statistically significant difference.

[0103] The results are as follows Figure 1 , Figure 2 , Figure 3 As shown in the figure. Experimental results show that zebrafish given the composition of the present invention exhibited significantly reduced arousal activity and total arousal time, indicating that the composition of the present invention can effectively improve sleep and increase non-rapid eye movement (NREM) sleep time and quality.

[0104] It will be understood by those skilled in the art that, unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. It should also be understood that terms such as those defined in general dictionaries should be understood to have the same meaning as in the context of the prior art, and should not be interpreted in an idealized or overly formal sense unless specifically defined as herein.

[0105] It should be understood that the above detailed description of the technical solutions of the present invention with reference to preferred embodiments is illustrative and not restrictive. Those skilled in the art can modify the technical solutions described in the embodiments or make equivalent substitutions for some of the technical features based on reading this specification; however, these modifications or substitutions do not cause the essence of the corresponding technical solutions to depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A probiotic composition containing melatonin, wherein, Including probiotics and melatonin.

2. The composition according to claim 1, characterized in that, The probiotics are one or more of the following genera: Lactobacillus, Akkermansia, Lactobacillus, Bifidobacterium, Enterococcus, Bacillus, Lactobacillus mucosae, Lactobacillus, Streptococcus, and Lactococcus.

3. The composition according to claim 2, characterized in that, The probiotics mentioned are *Lactobacillus paracasei*, *Lactobacillus rhamnosus*, *Lactobacillus casei*, *Akermansia muciniphila*, *Lactobacillus plantarum*, *Bifidobacterium adolescentis*, *Bifidobacterium animalis* subsp. *animal*, *Bifidobacterium animalis* subsp. *lactobacter*, *Bifidobacterium bifidum*, *Bifidobacterium longum* subsp. *infant ... pseudosporidis*, *Enterococcus faecalis*, *Bacillus subtilis*, *Mucobacterium reuteri*, *Mucobacterium fermentum*, *Streptococcus salivarius* subsp. *thermophilus*, etc. Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus brevis, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus delbrueckii subsp. lactis, Lactobacillus curvatureii, Lactobacillus lactis, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus maltii subsp. maltii, Pediococcus pentosaceus, Pediococcus lactis, Streptococcus salivarius subsp. thermophilus, Enterococcus faecalis, Bacillus coagulans, Bacillus licheniformis, Bacillus natto, Clostridium butyricum, Vibrio butyricum, and one or more of the following lactobacilli.

4. The composition according to claim 2, characterized in that, The probiotic cell count is not less than 1×10⁻⁶. 5 CFU / part composition.

5. The composition according to claim 1, characterized in that, The composition also includes plant extracts.

6. The composition according to claim 5, characterized in that, The plant extracts include Gastrodia elata extract, Milk thistle extract, Ziziphus jujuba seed extract, Aristolochia debilis extract, Schisandra chinensis extract, Ganoderma lucidum extract, Gardenia jasminoides extract, Poria cocos extract, Acanthopanax senticosus extract, Apocynum venetum extract, Polygala tenuifolia extract, Platycladus orientalis seed extract, Lilium brownii extract, Pueraria lobata extract, Polygonum multiflorum vine extract, Bambusa textilis shavings extract, Citrus reticulata peel extract, Bupleurum chinense extract, Poria cocos extract, Paeonia lactiflora extract, Albizia julibrissin bark extract, Pistachio nut extract, Mushroom extract, Ashwagandha extract, Scutellaria baicalensis extract, Portulaca oleracea extract, Spearmint extract, Hops extract, Walnut peptide powder, Valerian extract, Cyperus rotundus extract, Atractylodes macrocephala extract, and Mulberry extract. The following are extracts: cucumber extract, banana extract, passion fruit extract, lotus seed extract, black summer solstice grass extract, green tea extract, black tea extract, oolong tea extract, chestnut extract, tomato extract, spinach extract, broccoli extract, cabbage extract, cauliflower extract, Brussels sprouts extract, sweet potato extract, pumpkin extract, Polygonum multiflorum extract, lychee extract, longan extract, jujube extract, tomato extract, onion extract, cherry extract, almond extract, black walnut extract, hawthorn extract, chamomile extract, lavender extract, ginkgo extract, red ginseng extract, sour cherry juice, and lemon balm extract.

7. The composition according to claim 5, characterized in that, The active ingredients of the plant extract are one or more of the following: organic acids, volatile oils, polysaccharides, terpenoids, flavonoids, phenolic compounds, alkaloids, glycosides, sterols, and minerals.

8. The composition according to claim 7, characterized in that, The glycosides are one or more of the following: jujube saponins, ginsenosides, saponins, cardiac glycosides, baicalin, betulinic acid, oleanolic acid, pomoformin, betulinic acid, geniposide, lupeol, gastrodin, guanosine, guanosine, adenosine, and cytidine.

9. The composition according to claim 7, characterized in that, The alkaloids are one or more of the following: heliotropin, jujube alkaloid, magnoflorine, lotus leaf alkaloid, ephedrine, hyoscyamine, berberine, synephrine, and N-methyltyramine.

10. The composition according to claim 7, characterized in that, The phenolic compounds mentioned are tea polyphenols, tocopherols, tocotrienols, magnolol, tert-butylhydroquinone, anthocyanins, astaxanthin, quercetin, ellagic acid, catechins, proanthocyanidins, rosmarinic acid, curcumin, resveratrol, lignans, luteolin, cattail isoflavones, eugenol, oleuropein, oleuropein, kaempferol, apigenin, isorhamnetin, gallic acid, vanillic acid, eugenol, p-coumaric acid, ferulic acid, cannabinoids, epicatechin, epicatechin-3-gallic acid. One or more of the following: esters, caffeic acid, chlorogenic acid, cinnamic acid, cinnamaldehyde, cinnamyl alcohol, eugenol, vanillin, coumarin, kaempferol, hesperidin, naringenin, sennaol, delphinidin, cyanidin, silymarin, puerarin, schisandrin, apple polyphenols, crocin, saffron aldehyde, ellagic acid, mulberry leaf polyphenols, hydroxytyrosol, rosmarinic acid, salvianolic acid, shikonin, fulvic acid, sarsaparilla acid, chestnut peel polyphenols, tannins, baicalin, sphaeropicrin A, emodin, anthocyanins, and litchi polyphenols.

11. The composition according to claim 7, characterized in that, The organic acid is one or more of the following: sarcosine, creatine, naringin, rosmarinic acid, clove oil, thiotaurine, boswellic acid, oleic acid, linoleic acid, myristic acid, lauric acid, palmitic acid, stearic acid, arachidic acid, arachienoic acid, linolenic acid, succinic acid, chlorogenic acid, citric acid, and malic acid.

12. The composition according to claim 7, characterized in that, The polysaccharides are one or more of the following: Gastrodia elata polysaccharide, Gardenia jasminoides polysaccharide, L-arabinose, Dendrobium nobile polysaccharide, Auricularia auricula-judae polysaccharide, D-mannose, D-galactose, Astragalus membranaceus polysaccharide, Lycium barbarum polysaccharide, Lentinus edodes polysaccharide, Ginseng polysaccharide, Glycyrrhiza uralensis polysaccharide, Tremella fuciformis polysaccharide, Pueraria lobata polysaccharide, Mulberry polysaccharide, Oat polysaccharide, Ophiopogon japonicus polysaccharide, Aloe vera polysaccharide, Sophora japonica polysaccharide, β-glucan, α-glucan, β-galactose-glucan, L-fucose, D-xylose, D-glucose, glucuronic acid, and Ganoderma lucidum polysaccharide.

13. The composition according to claim 7, characterized in that, The flavonoids mentioned are one or more of the following: apigenin, epigallocatechin, luteolin-3′,7-di-O-glucose, quercetin, hyperoside, flavonoids, flavanones, hesperidin, norihesperidin, neohesperidin, naringin, rutin, polymethoxyflavonoids, flavonols, dihydroflavonoids, dihydroflavonols, isoflavones, dihydroisoflavones, chalcones, dihydrochalcones, hesperidin, anthocyanins, rutin, daidzein, anthocyanins, flavanols, and proanthocyanidins.

14. The composition according to claim 7, characterized in that, The steroidal compounds are one or more of the following: β-sitosterol, campesterol, lanosterol, stigmasterol, stigmasterol, lupeol, n-trigecanol, β-amyrin, patchouli alcohol, inositol, 3β,5α,6β-trihydroxystigmasterane, daucosterol, diosgenin, stigmasterane-3,5-diene, campesterol, γ-sitosterol, cholesterol, ergosterol, cholesterol, lanosterol, lanolin alcohol, lanolin acid, phytosterols, and rice bran fatty alkyl alcohols.

15. The composition according to claim 7, characterized in that, The terpenoid compounds are one or more of the following: betulinol, betulinic acid, pachymic acid, ibric acid, pachytriterpenes, ginkgolide, ginsenosides, linalool, citronellol, geraniol, eugenol, carotene, lycopene, zeaxanthin, betulinol, tea saponins, fucoxanthin, styraxol, sapinene, limonene, pinene, caryophyllene, humulene, and boswellic acid.

16. The composition according to claim 7, characterized in that, The volatile oil is one or more of α-guaiacene, α-buniene, β-caryophyllene, α-patchoene, pinene, α-thujene, α-pinene, β-pinene, β-myrcene, octanal, limonene, terpineol, citronellol, carvacrol, octanol, eugenol, hexanoic acid, p-methoxyphenyldione, and saikosauceol.

17. The composition according to claim 7, characterized in that, The mineral is one or more of magnesium, calcium, zinc, iron, and potassium.

18. The composition according to claim 8, characterized in that, The plant extract contains at least one or more of the following: tart cherry juice, lemon balm extract, passionflower extract, valerian extract, and milk thistle extract.

19. The composition according to claim 18, characterized in that, The plant extract contains at least milk thistle extract.

20. The composition according to claim 18, characterized in that, The active ingredients in the milk thistle extract include at least one or more of apigenin and silybin.

21. The composition according to claim 20, characterized in that, The active ingredient in the milk thistle extract includes at least apigenin.

22. The composition according to claim 1, characterized in that, The composition also includes amino acids.

23. The composition according to claim 22, characterized in that, The amino acids include one or more of γ-aminobutyric acid, L-theanine, tryptophan, L-glycine, and theanine.

24. The composition according to claim 1, characterized in that, The composition also contains vitamins.

25. The composition according to claim 24, characterized in that, The vitamins include one or more of vitamin C, vitamin D, vitamin B, vitamin E, vitamin K, vitamin A, niacin, folic acid, pantothenic acid, choline, and biotin.

26. The composition according to claim 1, characterized in that, The composition also includes minerals.

27. The composition according to claim 26, characterized in that, The minerals include one or more of magnesium, calcium, iron, zinc, potassium, manganese, and copper.

28. The composition according to any one of claims 1-27, characterized in that, The composition, when combined with excipients, is prepared into one or more of the following: tablets, soft capsules, capsules, powders, oral liquids, sprays, solid beverages, gummies, and jellies.

29. The composition according to any one of claims 1-27, and its use in improving sleep, enhancing immunity, improving gut health, relieving stress, and improving mood problems, inattention, cognitive impairment, and memory loss caused by sleep disorders.

30. The use of the composition according to any one of claims 1-27 in improving sleep.

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