Compositions containing akk and gaba for improving mood and preventing and treating depression

Abstract

The application discloses a composition containing Akkermansia (AKK) and gamma-aminobutyric acid (GABA) for improving mood and preventing and treating depression. The composition contains AKK and GABA and can be used for preventing or treating depressive mood disorders and improving adverse moods such as anxiety and stress. The administration time of AKK and GABA is 1-28 days, and the composition can further comprise probiotics, prebiotics, minerals, vitamins, plant extracts and other ingredients, and is prepared into various forms such as beauty compositions, nutritional compositions, foods, dietary supplements, medical foods or drugs, and is administered through oral administration and other modes, thereby providing a new way for mood improvement and depression treatment.

Description

Technical Field

[0001] This invention belongs to the field of health products and relates to a composition containing Akkermansia (AKK) and γ-aminobutyric acid (GABA), which is used to improve mood and prevent and treat depression-related symptoms. Background Technology

[0002] Depression and mood disorders seriously affect people's quality of life. Current treatments have certain limitations, such as significant drug side effects and long onset times. Therefore, it is crucial to find safe and effective alternative or adjunctive treatments.

[0003] There is a close connection between the gut microbiota and the brain, known as the gut-brain axis. Studies have shown that imbalances in the gut microbiota are associated with the development and progression of various mental illnesses. Akkermansia (AKK), as an important beneficial gut bacterium, plays a crucial role in maintaining intestinal barrier function and regulating immunity. Existing research has shown that AKK has a positive impact on gut-related physiological functions; however, its application in improving mood and treating depression has not been fully explored.

[0004] Gamma-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid in the human body and an important inhibitory neurotransmitter in the central nervous system. It can regulate neuronal excitability and has effects such as anti-anxiety, improved sleep, and stress relief. However, when used alone, GABA's absorption and effects in the body are somewhat limited.

[0005] Currently, there are no reports of combining AKK and GABA for improving mood and treating depression. Developing a composition that contains both of these ingredients is expected to provide a new approach for the treatment and prevention of depression and mood disorders. Summary of the Invention

[0006] This invention creatively combines Akkermansia myxophilus with γ-aminobutyric acid (GABA) to achieve the prevention and treatment of mood disorders through a bidirectional regulatory mechanism of the gut-microbiota-brain axis. In particular, it was discovered that when live / inactivated Akkermansia myxophilus is used in combination with a specific dose of GABA, a synergistic effect exceeding that of a single component can be produced.

[0007] The present invention provides a composition comprising Akkermansia (AKK) and γ-aminobutyric acid (GABA) for the prevention or treatment of depressive mood disorders and for improving negative emotional states such as anxiety and stress.

[0008] In some embodiments, the Akemanella in the composition of the present invention includes one or more of A. muciniphila, A. massiliensis, and A. biwaensis, which may be in live cell form or in non-living cell form after treatment such as pasteurization.

[0009] In some embodiments, the Akkermansia bacteria in the composition of the present invention are administered at a dose of 10 mg / day. 6 Up to 10 12 10 cells / serving, preferably 10 per day 8 Up to 10 10 Cells / part.

[0010] In some embodiments, the composition of the present invention contains γ-aminobutyric acid (GABA), which directly affects cognitive functions such as attention, memory, and mood regulation by modulating neurotransmitter levels or neuronal activity. The GABA is either naturally derived or artificially synthesized.

[0011] In some embodiments, the composition of the present invention is administered at a dose of 10 mg to 500 mg of GABA daily. In some embodiments, oral supplementation with 100 to 300 mg of GABA daily can reduce stress cortisol levels and has an anti-anxiety effect. In some embodiments, oral supplementation with 250 mg of GABA before bedtime daily can shorten sleep onset time and has a sleep-aiding effect. Specifically, the composition of the present invention contains GABA at a concentration of 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 220, 240, 250, 260, 280, 300, 320, 340, 350, 360, 380, 400, 420, 440, 450, 460, 480, or 500 mg per serving.

[0012] In some embodiments, the composition of the present invention contains GABA derived from germinated brown rice, green tea extract, ginkgo leaf extract, fermented legumes and / or grains.

[0013] In some embodiments, the composition of the present invention further comprises one or more components selected from probiotics, bacteria, yeast, microorganisms, prebiotics, or combinations thereof.

[0014] The composition of the present invention contains probiotics that can improve cognition, soothe mood, reduce stress and anxiety, improve sleep and gastrointestinal discomfort.

[0015] In some embodiments, the probiotics in the composition of the present invention include one or more of the following: Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium animalis, Bifidobacterium adolescentis, Lactobacillus plantarum, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus bulgaricus, Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus casei, Streptococcus thermophilus, Clostridium butyricum, and Bacillus coagulans.

[0016] In some embodiments, the composition of the present invention contains ≥10 probiotics. 6 CFU / serving, specifically, the probiotic content is ≥1×10⁻⁶. 6 1×10 7 1×10 8 2×10 8 3×10 8 5×10 8 1×10 9 5×10 9 1×10 10 5×10 10 1×10 11 5×10 11 CFU / serving. Furthermore, the probiotic content is preferably 10... 6 Up to 10 12 CFU / serving, and more preferably, the probiotic content is 10. 8 Up to 10 10 CFU / serving

[0017] Examples of yeasts described in this invention include, but are not limited to, *Saccharomyces cerevisiae*, *Saccharomyces boulardii*, *Kluyveromyces martensii*, and any combination thereof. The yeast content is ≥10%. 5 CFU / serving, specifically, the yeast content is ≥1×10⁻⁶. 5 1×10 6 1×10 7 1×10 8 2×10 8 3×10 8 5×10 8 1×10 9 5×10 9 1×10 10 5×10 10 1×10 11 5×10 11 CFU / serving. Further, the yeast content is preferably 10. 6 Up to 10 12 CFU / serving

[0018] Examples of prebiotics described in this invention include, but are not limited to, polyphenols, inulin, and inulin-type fructans, fructooligosaccharides, β-glucan, xylose, arabinose, arabinoxylan, ribose, galactose, rhamnose, cellobiose, fructose, lactose, salicin, sucrose, glucose, aescin, trehalose, maltose, mannose, melibiose, raffinose, galactooligosaccharides, amino acids, alcohols, and fermentable carbohydrates and any combination thereof.

[0019] In some embodiments, the compositions of the present invention further comprise minerals or vitamins or combinations thereof.

[0020] In some embodiments, the minerals in the composition of the present invention further include one or more of magnesium and zinc.

[0021] Magnesium participates in various physiological processes in the human body and is crucial for the function of the nervous system. It regulates the release of neurotransmitters and affects the levels of neurotransmitters such as serotonin in the brain. Serotonin is closely related to mood regulation, and sufficient magnesium helps improve mood and alleviate anxiety and depressive symptoms. In some embodiments, the magnesium content is 10 to 300 mg, preferably 50 to 300 mg, specifically, such as 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 mg / serving.

[0022] Zinc plays a vital role in brain development and nerve function. It participates in the synthesis and metabolism of various enzymes and is essential for maintaining normal neurotransmission and cellular function. Studies have shown that zinc deficiency is associated with mood disorders such as depression and anxiety, and appropriate zinc supplementation can help regulate mood. The recommended zinc content is 10 to 100 mg, preferably 10 to 50 mg, specifically, at doses of 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 mg per serving.

[0023] In some embodiments, the composition of the present invention further comprises one or more vitamins, including vitamin B6 and vitamin D.

[0024] Vitamin B6 participates in the synthesis of neurotransmitters such as serotonin, dopamine, and gamma-aminobutyric acid (GABA). It promotes the conversion of tryptophan into serotonin, and increased serotonin levels help improve mood and reduce symptoms of depression and anxiety. The vitamin B6 content is 1 to 20 mg, preferably 1 to 10 mg, specifically, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mg per serving.

[0025] Vitamin D is not only important for bone health but also plays a vital role in the nervous system. It regulates the synthesis and metabolism of neurotransmitters, influencing brain development and function. Studies have found that vitamin D deficiency is associated with an increased risk of depression, and vitamin D supplementation can help improve mood. The recommended vitamin D content is 200 to 1000 International Units (IU), specifically 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, and 2000 IU per serving.

[0026] In some embodiments, the compositions of the present invention further comprise plant extracts. The plant extracts include one or more of the following: French coastal pine bark extract, chamomile extract, saffron extract, pomegranate extract, rice germ extract, jujube seed extract, ashwagandha extract, spearmint extract, black pepper extract, pistachio extract, walnut peptide powder, hops extract, lemon verbena extract, valerian extract, Ghana seed extract, St. John's wort extract, and Rhodiola rosea extract.

[0027] In some embodiments, the main active ingredient of the French coastal pine bark extract in the composition of the present invention is pycnogenol, which can reduce oxidative damage to brain nerve cells by resisting oxidative stress response, maintaining the normal function of nerve cells, and thus helping to stabilize mood. Simultaneously, its anti-inflammatory properties can improve the brain microenvironment and regulate the metabolism and transmission of neurotransmitters, such as promoting the synthesis and release of neurotransmitters like serotonin. Serotonin, as a neurotransmitter closely related to mood, helps alleviate negative emotions such as anxiety and depression by increasing its level, making people feel more cheerful. It plays an important synergistic role in the composition of the present invention for improving mood. The content of the French coastal pine bark extract is 50 to 150 mg / serving, specifically, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, and 150 mg / serving.

[0028] In some embodiments, the chamomile extract active ingredients, flavonoids and terpenes, in the composition of the present invention have a certain sedative and calming effect, thereby relieving tension and anxiety and helping people restore a calm state of mind. The chamomile extract content is 400 to 1000 mg / serving, specifically, such as 400, 500, 600, 700, 800, 900, or 1000 mg / serving.

[0029] In some embodiments, the composition of the present invention contains saffron extract with crocin and saffron aldehyde, which can relieve stress and regulate mood. The saffron extract content is 20 to 30 mg / serving, specifically, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 mg / serving.

[0030] In some embodiments, the composition of the present invention contains pomegranate extract with pungentin, ellagic acid, and anthocyanins as active ingredients, which have antioxidant and mood-improving effects. The pomegranate extract content is 100 to 250 mg / serving, specifically, such as 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, and 250 mg / serving.

[0031] In some embodiments, the composition of the present invention contains rice germ extract containing GABA and polyamine active ingredients, which have sleep-aiding and mood-improving effects. The rice germ extract content is 50 to 100 mg / serving, specifically, such as 50, 60, 70, 80, 90, or 100 mg / serving.

[0032] In some embodiments, the composition of the present invention contains jujube seed extract containing jujube seed saponins, flavonoids, and polysaccharide active ingredients, which have sleep-aiding and anxiety-relieving effects. The content of jujube seed extract is 250 to 500 mg / serving, specifically, such as 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 570, 480, 490, and 500 mg / serving.

[0033] In some embodiments, the composition of the present invention contains Ashwagandha extract which has sleep-aiding, stress-relieving, and immunity-boosting effects. The Ashwagandha extract content is 200 to 300 mg / serving, specifically, such as 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 mg / serving.

[0034] In some embodiments, the composition of the present invention contains spearmint extract containing rosmarinic acid, salvianolic acid, shikonin, and caffeic acid, which can enhance overall memory and improve sleep. The spearmint extract content is 500 to 1200 mg / serving, specifically, such as 500, 600, 700, 800, 900, 1000, 1100, or 1200 mg / serving.

[0035] In some embodiments, the composition of the present invention contains pistachio extract that can improve sleep. The pistachio extract content is 10 to 100 mg / serving, specifically, such as 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 mg / serving.

[0036] In some embodiments, the composition of the present invention, wherein the walnut peptide powder has the effects of soothing nerves and improving sleep. The walnut peptide powder content is 200 to 500 mg / serving, specifically, such as 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, and 500 mg / serving.

[0037] In some embodiments, the composition of the present invention contains flavonoids in the hop extract, which have sleep-promoting and stress-relieving effects. The hop extract content is 200 to 500 mg / serving, specifically, such as 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, and 500 mg / serving.

[0038] In some embodiments, the composition of the present invention contains volatile components such as geraniol and nerol, as well as phenolic compounds such as caffeic acid and rosmarinic acid, which play an important role in regulating mood. The volatile components such as geraniol and nerol in the lemon verbena extract can act on the limbic system and hypothalamus, the brain's mood regulation centers, through the olfactory system. When people inhale these volatile substances, they stimulate olfactory nerve endings, transmitting signals to areas of the brain related to mood control and promoting the release of neurotransmitters such as gamma-aminobutyric acid (GABA). GABA, as an inhibitory neurotransmitter, can reduce neuronal excitability, producing a feeling of relaxation and calm, thereby effectively relieving anxiety. The lemon verbena extract content is 300 to 500 mg / serving, specifically, such as 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, and 500 mg / serving.

[0039] In some embodiments, the composition of the present invention contains valerin and other components in the valerian extract that can regulate the GABA system, increase the release of GABA or prolong its duration of action, reduce the excitability of the nervous system, thereby relieving anxiety and depression. It can also act on the central nervous system, producing a sedative and calming effect. The valerian extract content is 300 to 600 mg / serving, specifically, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, 500, 520, 540, 560, 580, and 600 mg / serving.

[0040] In some embodiments, the composition of the present invention contains Ghana seed extract rich in 5-hydroxytryptophan (5-HTP), a precursor to serotonin (5-hydroxytryptamine), which can cross the blood-brain barrier to enter the brain, be converted into serotonin in the body, increase serotonin levels in the brain, and improve mood. It helps regulate the function of the hypothalamus-pituitary-adrenal (HPA) axis, restore balance to the neuroendocrine system under stress, and reduce depression-related physiological responses. The Ghana seed extract content is 50 to 300 mg / serving, specifically, such as 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, and 300 mg / serving.

[0041] In some embodiments, the composition of the present invention, wherein the main component of the St. John's wort extract, hypericin, etc., can inhibit the reuptake of serotonin, dopamine, and norepinephrine by nerve cells, thereby increasing the concentration of these neurotransmitters in the synaptic cleft, enhancing nerve signal transmission, and improving depressive symptoms. The content of the St. John's wort extract is 900 to 1800 mg / serving, specifically, such as 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, or 1800 mg / serving.

[0042] In some embodiments, the composition of the present invention contains rhodiola rosea extract and other components, which can improve the body's adaptability to stress states such as hypoxia and fatigue, reduce physical fatigue, regulate the HPA axis, restore the normal secretion of stress hormones such as cortisol, and improve depressive mood caused by neuroendocrine disorders. The content of rhodiola rosea extract is 300 to 600 mg / serving, specifically, such as 300, 350, 400, 450, 500, 550, and 600 mg / serving.

[0043] In some embodiments, the compositions described in this invention are cosmetic compositions, nutritional compositions, foods, dietary supplements, medical foods, or pharmaceuticals.

[0044] In some embodiments, the compositions of the present invention are in dosage forms including tablets, capsules, soft capsules, granules, oral liquids, crystals, chewable tablets, effervescent tablets, jellies, popping candies, and gummies.

[0045] In some embodiments, the compositions of the present invention are used for the prevention or treatment of early stages of depressive mood disorders, said early stages including stages that meet the diagnostic criteria for depression but have milder symptoms. For example, days 1, 2, 3, 4, 5, 6, and 7 after the onset of symptoms.

[0046] In some embodiments, the composition of the present invention is applied in sufficient quantities prior to a stressful event that may trigger depression or mood problems to prevent the development of related mood disorders.

[0047] The composition of the present invention involves the combined application of Akkermansia and γ-aminobutyric acid for 1 to 28 days, preferably 2 to 14 days, and more preferably 3 to 7 days. For example, it can be applied continuously for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 27, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, and 28 days.

[0048] In some embodiments, the composition of the present invention is applied once, twice, or three times a day. In some embodiments, the composition of the present invention is applied once, twice, three times, four times, five times, six times, or seven times a week.

[0049] Terminology Explanation

[0050] The genus *Akkermansia* refers to a group of obligate anaerobic, Gram-negative bacteria belonging to the phylum Verrucomicrobiota, which primarily colonize the mucus layer of the mammalian intestine. Representative species include *Akkermansia muciniphila*, *Akkermansia massiliensis*, and *Akkermansia biwaensis*, which play roles in maintaining intestinal microecological balance, regulating immunity, and influencing metabolism.

[0051] The term "pasteurization" refers to a mild sterilization method that kills or inactivates microorganisms by heating to a certain temperature (usually not exceeding 100°C) and maintaining it for a period of time, while minimizing damage to the product's components.

[0052] The term "Akk pasteurized bacteria" refers to Akkella myxophilus (Akk bacteria) that has undergone pasteurization and is no longer viable. Pasteurized Akkella myxophilus is a metabiotic; although it loses its ability to grow after inactivation, its cellular components (such as cell walls and cell membranes) and metabolites may still have beneficial effects on the host, such as improving gut health and enhancing immune function.

[0053] The term "probiotics" refers to a general term for live beneficial microorganisms that can improve the composition and microecological balance of a host's flora in a certain part of the body and exert beneficial effects by colonizing the human body (mainly the intestines and reproductive system).

[0054] The term "prebiotic" refers to a class of substances, such as substances that humans cannot digest, but which regulate the composition and / or activity of the gut microbiota through gut microbial metabolism, thereby producing beneficial physiological effects on the host.

[0055] The term "plant extract" refers to a substance extracted or processed from plants (whole or part of a plant) using appropriate solvents or methods.

[0056] The term "anxiety" refers to a state of unease experienced by the subject, such as worry, tension, or fear, which may be mild or moderate. Typical symptoms may include elevated blood pressure. In a preferred embodiment, anxiety includes intense fear and distress, often accompanied by insomnia and early awakening. Detailed Implementation

[0057] 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.

[0058] Example

[0059] Example 1

[0060] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 1 × 10⁻⁶. 8 100 mg of γ-aminobutyric acid (GABA) per cell / dose.

[0061] Example 2

[0062] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 1 × 10⁻⁶. 8 100 mg of γ-aminobutyric acid (GABA) per serving, derived from germinated brown rice. Also added: Bifidobacterium bifidum at a concentration of 1 × 10⁻⁶ cells / serving. 8 CFU / serving, inulin as needed.

[0063] Example 3

[0064] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 1 × 10⁻⁶. 8 100 mg of γ-aminobutyric acid (GABA) per serving, derived from germinated brown rice. Also added: Bifidobacterium bifidum at a concentration of 1 × 10⁻⁶ cells / serving. 8 CFU / serving, inulin as needed. Further add 50 mg / serving magnesium and 3 mg / serving vitamin B6.

[0065] Example 4

[0066] A composition for regulating mood, comprising Akkermansia myxophilus at a dose of 5 × 10⁻⁶. 9 1 cell / dose, γ-aminobutyric acid (GABA), dose 200 mg.

[0067] Example 5

[0068] A composition for regulating mood, comprising Akkermansia myxophilus at a dose of 5 × 10⁻⁶. 9 1 cell / serving, γ-aminobutyric acid (GABA), dosage 200 mg. The probiotics selected are Lactobacillus acidophilus and Bifidobacterium animalis, with a content of 3 × 10⁻⁶ cells / serving. 8 CFU / serving and 2×10 8 CFU / serving

[0069] Example 6

[0070] A composition for regulating mood, comprising Akkermansia myxophilus at a dose of 5 × 10⁻⁶. 9 1 cell / serving, γ-aminobutyric acid (GABA), dosage 200 mg. The probiotics selected are Lactobacillus acidophilus and Bifidobacterium animalis, with a content of 3 × 10⁻⁶ cells / serving. 8 CFU / serving and 2×10 8 CFU / serving. Vitamin D 400 IU / serving, and pistachio extract 80 mg / serving.

[0071] Example 7

[0072] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 8 × 10⁻⁶. 10 1 cell / dose, γ-aminobutyric acid (GABA), dose 250 mg.

[0073] Example 8

[0074] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 8 × 10⁻⁶. 10per cell / serving, γ-aminobutyric acid (GABA), GABA derived from fermented legumes, at a dose of 250 mg, combined with 350 mg / serving of jujube seed extract.

[0075] Example 9

[0076] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 8 × 10⁻⁶. 10 per cell / serving, γ-aminobutyric acid (GABA), GABA derived from fermented legumes, at a dose of 250 mg, combined with 250 mg / serving of Ashwagandha extract from South Africa.

[0077] Example 10

[0078] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 1 × 10⁻⁶. 11 1 cell / dose, γ-aminobutyric acid (GABA), dose 300 mg.

[0079] Example 11

[0080] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 1 × 10⁻⁶. 11 1 cell / serving, γ-aminobutyric acid (GABA), dosage 300 mg. The probiotics are a combination of Bifidobacterium longum, Bifidobacterium breve, and Bifidobacterium infantis, each at a concentration of 1×10⁻⁶ cells / serving. 8 CFU / serving

[0081] Example 12

[0082] A composition for regulating mood, comprising Akkermansia myxophilus, at a dose of 1 × 10⁻⁶. 11 300 mg of γ-aminobutyric acid (GABA) per serving, administered per cell. Combined with 300 mg of walnut peptide powder per serving.

[0083] Example 13: Gummies

[0084] formula:

[0085] Akkermansia myxophilus: 1×10 8 Cells / particles

[0086] GABA: 100 mg / capsule

[0087] Powdered sugar: as needed

[0088] Pectin: as needed

[0089] Purified water: appropriate amount

[0090] Preparation process: As described in Example 1, the freeze-dried powder of *Ackermania mucilage* and GABA powder were mixed evenly. An appropriate amount of purified water was added to a pot and heated to boiling. Then, powdered sugar and pectin were added and stirred until completely dissolved. The mixed bacterial powder and GABA were added to the syrup and stirred evenly. The mixture was poured into molds, cooled to room temperature, and then refrigerated until solidified. After demolding, it was packaged to obtain the finished soft candy.

[0091] Example 14: Popping Candy

[0092] formula:

[0093] Akkermansia myxophilus: 5 × 10 9 Cells / bag

[0094] GABA: 200 mg / bag

[0095] Disintegrant: Sodium bicarbonate: Citric acid = 3:2

[0096] Purified water: appropriate amount

[0097] Preparation process: As described in Example 4, the freeze-dried powder of Akkermansia melanophila was mixed evenly with GABA powder. Sodium bicarbonate and citric acid (3:2 ratio) were added as disintegrants and premixed in a vibrating screen (amplitude 2mm, frequency 25Hz). Granulation was carried out in a centrifugal spray drying tower (inlet air temperature 45℃, outlet air temperature 28℃). Packaging was performed under nitrogen protection using an aluminum-plastic composite film.

[0098] Example 15 Soft Capsules

[0099] formula:

[0100] Akkermansia myxophilus: 8 × 10 10 Cells / particles

[0101] GABA: 250 mg / capsule

[0102] Vegetable oil: 0.5 ml soybean oil per capsule

[0103] Purified water: appropriate amount

[0104] Preparation process: As described in Example 7, the freeze-dried powder of Akkermansia muciniphila was mixed evenly with GABA powder. The mixture was dissolved in an appropriate amount of soybean oil and stirred until homogeneous, thus preparing an oil solution for the soft capsule contents. The soft capsule contents were then quantitatively filled into soft capsule shells made of gelatin, glycerin, water, etc., and the soft capsules were pressed. The capsules were then washed, dried, and packaged.

[0105] Example 16 Jelly

[0106] formula:

[0107] Akkermansia myxophilus: 1×10 11Cells / strip

[0108] GABA: 300 mg / sachet

[0109] Jelly base: water, sugar, and carrageenan (appropriate amount)

[0110] Preparation process: As described in Example 10, the freeze-dried powder of Acetobacter melanophilus and GABA powder were mixed evenly, and an appropriate amount of purified water was added to form a solution. The jelly matrix, water, sugar and carrageenan were added and stirred evenly. After heating to boiling, the mixture was filled into sterile jelly strips, cooled and solidified, and then sealed to obtain the jelly.

[0111] Example 17 Powder Strip Packet

[0112] 300 mg of walnut peptide powder, 300 mg of GABA, and 1×10 11 Cellular AKK probiotics are mixed, and then excipients such as rice flour and maltodextrin are added to prepare powder strips. The preparation method includes mixing walnut peptide powder, GABA and other excipients, then mixing them evenly with AKK bacterial solution, and then making powder by spray drying, which is then filled into aseptic strips.

[0113] Example 18 Mouse Experiment

[0114] Six-week-old male C57BL / 6 mice were used to establish a chronic unpredictable mild stress (CUMS) depression model. Mice were exposed to stressors for four consecutive weeks. After modeling, the mice were randomly divided into four groups of three mice each: a control group, an AKK group (1×10⁻⁶ mice), and a control group. 8 (cells / part), GABA group (100mg), AKK+GABA (1×10) 8 The mice were administered GABA 100mg (100 cells / dose) via gavage daily for 7 consecutive days. Eight hours after the last administration, a tail suspension test was performed. The mice were secured approximately 1 cm from the tail end to a tail suspension frame, hanging upside down 20 cm above the table. A timer was started to record the immobility time and struggling time over 6 minutes. Immobility time was defined as the time the mouse ceased struggling and remained passively suspended; struggling time was the time the mouse continuously twisted its body and swung its limbs in an attempt to escape. The results are as follows:

[0115] Average time remaining stationary (minutes) Average number of struggles (times) Blank group 5 3 AKK Group 2 8 GABA group 1 6 AKK+GABA group 0 12

[0116] Experimental results show that the combined use of AKK bacteria and GABA has a synergistic effect, which can more significantly alleviate the depressive symptoms of mice and enhance their active coping ability.

[0117] 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.

[0118] 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 composition, characterized in that, Including Akkermansia (AKK) and gamma-aminobutyric acid (GABA), it is used to prevent or treat depressive mood disorders, as well as improve negative emotional states such as anxiety and stress.

2. The composition according to claim 1, characterized in that, The Akkermania species include one or more of A. muciniphila, A. massiliensis, and A. biwaensis, which can be in live cell form or in non-living cell form after pasteurization or other treatments.

3. The composition according to claim 2, characterized in that, The dosage of Akkermansia is 10 mg / day. 6 Up to 10 12 10 cells / serving, preferably 10 per day 8 Up to 10 10 Cells / part.

4. The composition according to claim 1, characterized in that, The γ-aminobutyric acid is either naturally extracted or artificially synthesized.

5. The composition according to claim 4, characterized in that, The dosage of the γ-aminobutyric acid is 10 mg to 500 mg per day.

6. The composition according to claim 4, characterized in that, The GABA is derived from germinated brown rice, green tea extract, ginkgo leaf extract, fermented beans and / or grains.

7. The composition according to claim 1, characterized in that, It also includes one or more ingredients selected from probiotics, bacteria, yeast, microorganisms, prebiotics, or combinations thereof.

8. The composition according to claim 7, wherein the probiotics comprise one or more of the following: Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium animalis, Bifidobacterium adolescentis, Lactobacillus plantarum, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus bulgaricus, Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus casei, Streptococcus thermophilus, Clostridium butyricum, and Bacillus coagulans.

9. The composition according to claim 1, characterized in that, It also includes minerals or vitamins or combinations thereof.

10. The composition according to claim 9, wherein the mineral further comprises one or more of magnesium and zinc.

11. The composition according to claim 10, wherein the magnesium content is 10 to 300 mg / part.

12. The composition according to claim 10, wherein the zinc content is 10 to 100 mg / part.

13. The composition according to claim 8, wherein the vitamin further comprises one or more of vitamin B6 and vitamin D.

14. The composition according to claim 13, wherein the vitamin B6 content is 1 to 20 mg / part.

15. The composition according to claim 13, wherein the vitamin D content is 200 to 1000 international units (IU) per serving.

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

17. The composition according to claim 16, wherein the plant extract comprises one or more of the following: French coastal pine bark extract, chamomile extract, saffron extract, pomegranate extract, rice germ extract, jujube seed extract, ashwagandha extract, spearmint extract, black pepper extract, pistachio extract, walnut peptide powder, hops extract, lemon verbena extract, valerian extract, Ghana seed extract, St. John's wort extract, and rhodiola rosea extract.

18. The composition according to claim 1, characterized in that, The composition is a cosmetic composition, a nutritional composition, a food, a dietary supplement, a medical food, or a drug.

19. The composition according to claim 1, characterized in that, The dosage forms of the composition include tablets, capsules, soft capsules, granules, oral liquids, crystals, chewable tablets, effervescent tablets, jelly, popping candy, and gummies.

20. The composition according to claim 1, characterized in that, The early stages used for the prevention or treatment of depressive mood disorders include stages that meet the diagnostic criteria for depression but have milder symptoms.

21. The composition according to claim 1, characterized in that, Apply a sufficient amount of the composition before a stressful event that may trigger depression or mood problems to prevent the development of related mood disorders.

22. The composition according to claim 1, characterized in that, The Akkermansia and γ-aminobutyric acid were administered in combination for 1 to 28 days, preferably 2 to 14 days, and more preferably 3 to 7 days.