Sleep-aiding and nerve-soothing oral liquid and preparation process thereof

Abstract

The invention belongs to the technical field of sleep-aiding oral liquids, and discloses a sleep-aiding nerve-calming oral liquid and a preparation process thereof, the oral liquid is composed of the following components: a plant fermentation broth, fructo-oligosaccharide, gamma-aminobutyric acid, casein hydrolysis peptide, a saussurea involucrata culture, and pyrroloquinoline quinone disodium salt; wherein the plant fermentation liquor is prepared from spina date seeds, poria cocos, lilies, Chinese dates, lotus seeds, lophatherum gracile, seville orange flowers, red roses with double petals, roselle, wheat, licorice roots, peach kernels, sweet-scented osmanthus and plant lactobacillus BXM2. The core component spina date seed saponin A is combined with gamma-aminobutyric acid to directly regulate the GABAergic nervous system, shorten the sleep latency and effectively help sleep and tranquilize the nerves; casein hydrolysis peptide promotes secretion of melatonin, and cooperates with the saussurea involucrata culture to resist oxidative stress, improve the sleep structure and restore circadian rhythm; small molecular active peptides and flavonoid glycosides are generated through fermentation, and anxiety mood, fatigue state and qi and blood circulation are improved; nano embedding and targeted delivery technologies are adopted in the whole process, the bioavailability is high, and the risk of drug dependence is avoided.

Description

Technical Field

[0001] The invention belongs to the technical field of sleep-aiding oral liquids, and particularly relates to a sleep-aiding and tranquilizing oral liquid and a preparation process thereof. Background Art

[0002] Light is the most important regulator of our biological clock. When light fades, the body secretes melatonin to encourage sleepiness. When daylight returns, the body begins to secrete serotonin, suppressing melatonin and dispelling sleepiness. Thus, we drift off to sleep and wake up again. Modern life is fast-paced and stressful, and many people compensate by staying up late, becoming habitual sleepers. This leads to difficulty falling asleep, sleepless nights, and poor or insufficient sleep, leaving them exhausted upon waking.

[0003] Insomnia poses serious health risks, manifesting in the following ways: Health-wise: It can cause immune and endocrine disorders, impact children's growth and development, and accelerate aging; it can also induce or aggravate cardiovascular diseases such as colds, diabetes, obesity, stroke, hypertension, and coronary heart disease. Behavioral-wise: It can cause fatigue, drowsiness, decreased alertness and concentration, leading to accidents; it can also impair judgment and memory, and reduce learning and work abilities. Psychologically: It can cause mood changes, irritability, and anger, and can even lead to mental and psychological disorders such as depression, anxiety, chronic pain, alcohol and drug dependence, and cognitive decline.

[0004] The most common Western medicine treatments, such as sleeping pills, have serious toxic side effects and can cause dependence if used for a long time. Summary of the Invention

[0005] In order to overcome the above technical problems, the present invention provides a sleep-aiding and tranquilizing oral liquid and a preparation process thereof.

[0006] The present invention adopts the following technical solutions: A sleep-inducing and tranquilizing oral liquid, comprising the following ingredients: Plant fermentation liquid 70-75ml, fructooligosaccharides (FOS) 8-10g, gamma-aminobutyric acid (GABA) 150-200mg, casein hydrolyzed peptide 300-400mg, snow lotus culture 50-80mg, pyrroloquinoline quinone disodium salt 0.5-1.0mg; Among them, the raw material ratio of plant fermentation liquid (dry matter basis): Ziziphus jujuba seed 12%, Poria 10%, Lily 8%, Jujube 8%, Lotus seed 8%, Bamboo leaves 6%, Daidaihua 5%, Double red rose 5%, Roselle 5%, Wheat 5%, Licorice 5%, Peach kernel 3%, Osmanthus 3%, Lactobacillus plantarum BXM2 3%.

[0007] A preparation process of a sleep-aiding and tranquilizing oral liquid comprises the following steps: Step 1: Preparation of plant fermentation liquid Raw material pretreatment Cleaning and sterilization: After the raw materials are cleaned with ozone water, they are dried with hot air at 60℃ until the moisture content is less than 8%; Wall breaking treatment: Ultra-fine grinding to below 300 mesh to increase the dissolution rate of active ingredients; Directed enzymatic hydrolysis Compound enzymatic hydrolysis: add purified water at a material-liquid ratio of 1:15, add cellulase (0.3%) and pectinase (0.2%); Gradient temperature control: 45℃ for 2h followed by 55℃ for 1h, pH 5.0-5.5; Probiotic fermentation Inoculation and fermentation: inoculation with Lactobacillus plantarum BXM2 (inoculation amount 5%); Temperature-controlled fermentation: Anaerobic fermentation at 37°C for 48 hours, pH value detected every 6 hours, end point pH ≤ 3.8; Termination of fermentation: inactivation at 80℃ for 15min, centrifugation at 8000rpm for 20min, and supernatant Step 2: Compounding of functional components Premix system construction Fructooligosaccharide and casein hydrolyzed peptide were dry-mixed by equal amount stepwise addition method; Nano-encapsulation technology was used to encapsulate GABA and snow lotus culture using β-cyclodextrin; Gradient Blending (1) 40°C, plant fermentation broth + oligofructose peptide, 300 rpm, 15 min; (2) Add GABA inclusion complex at 35°C and stir under vacuum (-0.08 MPa); (3) Add PPQ sodium salt at 25°C and stir magnetically; Step 3: Refining Membrane filtration Ceramic membrane pretreatment: 50nm pore size to remove macromolecular impurities; Ultrafiltration concentration: 10kDa molecular weight cut-off, concentrated to solids ≥ 25%; Sterilization The product is bottled using UHT instant sterilization combined with aseptic cold filling technology.

[0008] Preferably, the fermentation endpoint is: jujuboside A ≥ 0.8 mg / ml, γ-aminobutyric acid ≥ 1.5 mg / ml.

[0009] Compared with the prior art, the present invention has the following beneficial effects: Deep sleep promotion: The core ingredient, Jujuboside A, combined with γ-aminobutyric acid, directly regulates the GABAergic nervous system, shortens sleep latency, and effectively promotes sleep and calms the mind; Circadian rhythm regulation: Casein hydrolyzed peptides promote melatonin secretion, synergize with snow lotus culture to resist oxidative stress, improve sleep structure, and restore circadian rhythm; Synchronous repair of body and mind: 13 herbs in the plant fermentation liquid are fermented by probiotics in both directions to produce small molecule active peptides and flavonoid glycosides, which can simultaneously improve anxiety, fatigue and blood circulation; Nano-encapsulation and targeted delivery technology is used throughout the process, with high bioavailability and no risk of drug dependence. DETAILED DESCRIPTION

[0010] The following embodiments of the present invention are described in detail. Unless otherwise specified, the raw materials and equipment used are commercially available or commonly used in the art. The methods in the embodiments, unless otherwise specified, are conventional methods in the art. The following embodiments are exemplary and are intended only to explain the present invention and are not to be construed as limiting the present invention.

[0011] Sleep-aiding and tranquilizing oral solution, composed of the following ingredients: Plant fermentation liquid 70-75ml, fructooligosaccharides (FOS) 8-10g, gamma-aminobutyric acid (GABA) 150-200mg, casein hydrolyzed peptide 300-400mg, snow lotus culture 50-80mg, pyrroloquinoline quinone disodium salt 0.5-1.0mg; Among them, the raw material ratio of plant fermentation liquid (dry matter basis): Ziziphus jujuba seed 12%, Poria 10%, Lily 8%, Jujube 8%, Lotus seed 8%, Bamboo leaves 6%, Daidaihua 5%, Double red rose 5%, Roselle 5%, Wheat 5%, Licorice 5%, Peach kernel 3%, Osmanthus 3%, Lactobacillus plantarum BXM2 3%.

[0012] Preparation process of sleep-aiding and tranquilizing oral liquid Step 1: Preparation of plant fermentation liquid Cleaning and sterilization: The raw materials were ultrasonically cleaned for 15 min in three-stage ozone water tanks (ozone concentration 10 ppm); After draining, put it into a hot air circulation oven (60℃±2℃) and dry it until the moisture content is ≤8% (time 2-4h).

[0013] Wall breaking treatment: Use air flow ultrafine pulverizer (nitrogen protection), pulverization fineness ≤ 300 mesh (D90 ≥ 95%); Screening rate control: 100 mesh screen pass rate ≥99.5%.

[0014] Directed enzymatic hydrolysis Compound enzymatic hydrolysis: Enzyme activation: Cellulase and pectinase were pre-activated with 40°C warm water (solid-liquid ratio 1:50) for 10 min; Operation of enzymatic hydrolysis tank: the order of feeding is purified water → crushed raw materials → activated enzyme solution, and the material-liquid ratio is strictly 1:15 (w / v).

[0015] Gradient temperature control: Stage 1: Enzymatic hydrolysis at 45°C ± 1°C for 2 h, stirring speed 120 rpm; The second stage: enzymatic hydrolysis at 55°C ± 1°C for 1 h, stirring at 80 rpm; pH control: Automatically add food-grade citric acid solution to maintain pH 5.0-5.5 (online pH meter monitoring); Enzymatic hydrolysis endpoint: viscosity decrease ≥ 40% (detected by Brookfield viscometer); Probiotic fermentation Bacteria activation: Lactobacillus plantarum BXM2 was activated in MRS medium at 37°C to the logarithmic growth phase (OD600 ≥ 1.8); Temperature controlled fermentation: Inoculation amount: 5.0%±0.2% (volume fraction); Fermentation tank parameters: 37℃±0.5℃, anaerobic environment (nitrogen filling to maintain dissolved oxygen ≤0.5ppm); Process monitoring: Samples were taken every 6 hours to test pH, total acidity, and viable bacteria count (end point viable bacteria count ≥ 1×10 9 CFU / ml).

[0016] Stop fermentation: Double verification of fermentation endpoint: HPLC detection of jujuboside A (C58H94O26) ≥ 0.8 mg / ml; Amino acid analyzer detected γ-aminobutyric acid ≥1.5mg / ml; To ensure stability, 0.02% natural vitamin E can be added during the plant fermentation liquid stage.

[0017] Inactivation: 80℃±2℃ water bath for 15min (temperature uniformity ±1℃); Centrifuge: 8000 rpm in a tubular centrifuge (centrifugation factor ≥ 10000 × g), collect the supernatant; Step 2: Compounding of functional components Premix system construction Dry mixing operation: Fructooligosaccharide and casein hydrolyzed peptide were mixed in equal amounts three times at a volume ratio of 1:1; Mixing equipment: three-dimensional motion mixer (speed 12 rpm, mixing time 30 min); Nano-encapsulation: β-cyclodextrin solution (15%, w / v) was mixed with GABA and saussurea involucrata culture at a mass ratio of 1:5; Inclusion conditions: magnetic stirring at 40°C for 2 h → standing at 4°C for 12 h → freeze drying; Gradient mixing process 1. Place the plant fermentation liquid in a 40℃ constant temperature stirring tank, then slowly sprinkle in the oligofructose peptide mixture, and stir at 300rpm for 15min until it is completely dissolved without lumps. 2. At 35°C, switch to vacuum stirring (-0.08 MPa) and slowly add GABA inclusion compound freeze-dried powder until the foam height is ≤10% of the liquid level; 3. Protect the environment with nitrogen at 25℃, pre-dissolve PPQ sodium salt in water for injection and then add dropwise, operate in the dark, dissolution time ≤ 5min, and use magnetic stirring during the low-cost process.

[0018] Step 3: Refining process Membrane filtration system Ceramic membrane pretreatment: Operating pressure 0.3MPa, cross-flow filtration, membrane surface flow rate 3m / s; 660nm wavelength detection, filtrate transmittance ≥95%; Ultrafiltration concentration: Using 10kDa spiral membrane package, transmembrane pressure difference is 0.4MPa; End point determination: Refractometer detection of solid content ≥ 25% (20℃); Sterilization and filling UHT sterilization: 135℃±1℃ / 5s (plate heat exchanger, heating rate 20℃ / s); Cool to 30℃±2℃ and put into sterile buffer tank; Aseptic cold filling: Filling environment: Class A clean area (dynamic sedimentation bacteria ≤ 1 CFU / 4h); Filling accuracy: 10ml / tube ±0.15ml; Nitrogen filling protection: nitrogen filling immediately after filling (headspace oxygen ≤ 0.5%); Light-proof packaging: packaged in amber glass bottles.

[0019] Terminal filtration: 0.22μm polyethersulfone filter element for secondary filtration.

[0020] Light inspection standard: No visible foreign matter under ≥2000Lux light.

[0021] Directions for use: Drink directly.

[0022] The medication status of 60 patients with sleep difficulties is shown in Table 1 (double-blind randomized controlled trial).

[0023] Table 1 Although the embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations may be made to the above embodiments without departing from the principles and purpose of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

Claims

1. A sleep-inducing and tranquilizing oral liquid, characterized in that: It is composed of the following ingredients: Plant fermentation liquid 70-75ml, fructooligosaccharides (FOS) 8-10g, gamma-aminobutyric acid (GABA) 150-200mg, casein hydrolyzed peptide 300-400mg, snow lotus culture 50-80mg, pyrroloquinoline quinone disodium salt 0.5-1.0mg; Among them, the raw material ratio of plant fermentation liquid (dry matter basis): Ziziphus jujuba seed 12%, Poria 10%, Lily 8%, Jujube 8%, Lotus seed 8%, Bamboo leaves 6%, Daidaihua 5%, Double red rose 5%, Roselle 5%, Wheat 5%, Licorice 5%, Peach kernel 3%, Osmanthus 3%, Lactobacillus plantarum BXM2 3%.

2. A preparation process for a sleep-aiding and tranquilizing oral liquid, characterized in that: The following steps are involved: Step 1: Preparation of plant fermentation liquid Raw material pretreatment Cleaning and sterilization: After the raw materials are cleaned with ozone water, they are dried with hot air at 60℃ until the moisture content is less than 8%; Wall breaking treatment: Ultra-fine grinding to below 300 mesh to increase the dissolution rate of active ingredients; Directed enzymatic hydrolysis Compound enzymatic hydrolysis: add purified water at a material-liquid ratio of 1:15, add cellulase (0.3%) and pectinase (0.2%); Gradient temperature control: 45℃ for 2h followed by 55℃ for 1h, pH 5.0-5.5; Probiotic fermentation Inoculation and fermentation: inoculation with Lactobacillus plantarum BXM2 (inoculation amount 5%); Temperature-controlled fermentation: Anaerobic fermentation at 37°C for 48 hours, pH value detected every 6 hours, end point pH ≤ 3.8; Termination of fermentation: inactivation at 80℃ for 15min, centrifugation at 8000rpm for 20min, and supernatant Step 2: Compounding of functional components Premix system construction Fructooligosaccharide and casein hydrolyzed peptide were dry-mixed by equal amount stepwise addition method; Nano-encapsulation technology was used to encapsulate GABA and snow lotus culture using β-cyclodextrin; Gradient Blending (1) 40°C, plant fermentation broth + oligofructose peptide, 300 rpm, 15 min; (2) Add GABA inclusion complex at 35°C and stir under vacuum (-0.08 MPa); (3) Add PPQ sodium salt at 25°C and stir magnetically; Step 3: Refining Membrane filtration Ceramic membrane pretreatment: 50nm pore size to remove macromolecular impurities; Ultrafiltration concentration: 10kDa molecular weight cut-off, concentrated to solids ≥ 25%; Sterilization The product is bottled using UHT instant sterilization combined with aseptic cold filling technology.

3. A preparation process of a sleep-aiding and tranquilizing oral liquid according to claim 2, characterized in that: Fermentation endpoint: Jujuboside A ≥ 0.8 mg / ml, γ-aminobutyric acid ≥ 1.5 mg / ml.

Images