Ergothioneine sleep-aiding nutrition capsule and application thereof

Abstract

The invention relates to the technical field of sleep-aiding capsules, and particularly discloses ergothioneine sleep-aiding nutritional capsules and a process thereof. The capsule is prepared from the following components in parts by mass: 80 to 120 mg of gamma-aminobutyric acid (GABA), 130 to 170 mg of a magnesium citrate compound, 20 to 28 mg of magnesium, 25 to 35 mg of nano ergothioneine, 180 to 220 mg of a South African drunken solanum extract, 15 to 25 mg of pyrroloquinoline quinone (PQQ), 8 to 12 mg of spermidine, 45 to 55 mg of jujuboside A and 1.8 to 2.2 mg of melatonin sustained-release microspheres. The prepared capsule can be used for adjusting nerve excitability and enhancing the function of a GABA receptor; the traditional Chinese medicine composition has the effects of resisting oxidation and inflammation, improving brain microenvironment, providing energy support for sleep and adjusting sleep rhythm, is more comprehensive and remarkable in effect, high in safety and small in side effect compared with a single-component product, and has a remarkable effect compared with a chemically synthesized hypnotic. The traditional Chinese medicine composition has no drug dependence and tolerance, reduces the burden on the body, and is suitable for long-term administration.

Description

Technical Field

[0001] The invention belongs to the technical field of sleep-aiding capsules, and particularly relates to ergothioneine sleep-aiding nutritious capsules and applications thereof. Background Art

[0002] With the accelerated pace of life and increasing work pressure in modern society, sleep disorders have become a common health problem that plagues hundreds of millions of people around the world. Long-term lack of sleep not only leads to short-term symptoms such as fatigue, lack of concentration, and decreased immunity, but may also increase the risk of chronic diseases such as cardiovascular disease and mental illness, seriously affecting people's quality of life and physical health.

[0003] At present, the common sleep aid products on the market mainly include chemical synthetic sleeping pills and natural sleep aid health products. Chemical synthetic sleeping pills, such as benzodiazepines Benzodiazepines and non-benzodiazepines Although these drugs have the characteristics of rapid onset of action, long-term use can easily lead to drug dependence and tolerance, and may also cause side effects such as dizziness, drowsiness, memory loss, and even serious risks such as respiratory depression. Traditional natural sleep aids are mostly based on a single ingredient or simple formula. For example, melatonin products are relatively safe, but they only work on regulating circadian rhythms. They have limited effect on improving sleep problems caused by complex mechanisms such as neurotransmitter imbalance and mitochondrial dysfunction, and are difficult to meet diverse market needs.

[0004] At the same time, ergothioneine is a natural antioxidant. Recent studies have found that it can cross the blood-brain barrier and exert antioxidant and anti-inflammatory effects in the brain. It has potential value in improving sleep, but the oral bioavailability of ordinary ergothioneine is low.

[0005] In summary, the present invention provides an ergothioneine sleep-aiding nutritional capsule and a process thereof. Summary of the invention

[0006] The object of the present invention is to provide a kind of ergothioneine sleep-aiding nutritious capsule and application thereof, so as to solve the problems raised in the above-mentioned background technology.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] A sleep-aiding ergothioneine nutritional capsule comprises the following steps:

[0009] The capsule comprises the following components in parts by mass: 80-120 mg of γ-aminobutyric acid (GABA), 130-170 mg of magnesium citrate complex containing 20-28 mg of elemental magnesium, 25-35 mg of nanoergothioneine, 180-220 mg of Withania somnifera extract, 15-25 mg of pyrroloquinoline quinone (PQQ), 8-12 mg of spermidine, 45-55 mg of jujuboside A, and 1.8-2.2 mg of melatonin sustained-release microspheres.

[0010] Preferably, the γ-aminobutyric acid (GABA) is in the form of pH-sensitive enteric-coated sustained-release microcapsules, and the magnesium citrate complex contains 20-28 mg of elemental magnesium and is chelated by citric acid and malic acid in a molar ratio of 1:0.3-0.7.

[0011] A preparation process of an ergothioneine sleep-aid nutritional capsule comprises the following steps:

[0012] S1. GABA inclusion

[0013] Put 10 kg of GABA and β-cyclodextrin (molar ratio 1:2) into a 2000 L reaction kettle, add pH 6.0 phosphate buffer solution (material-liquid ratio 1:10), stir at 60 °C for 4 hours (rotation speed 120 rpm),

[0014] Centrifugally separate (8000 rpm, 30 min), collect the wet inclusion product, and vacuum dry at 60 °C until the water content ≤ 3%;

[0015] Liposome encapsulation: Dissolve soybean phospholipid and cholesterol (4:1, total weight 5 kg) in ethanol, rotate and evaporate at 55 °C to form a film, add the aqueous solution of GABA inclusion product (50 kg), and perform high-pressure homogenization (100 MPa, 3 cycles) to obtain a liposome suspension;

[0016] Use a fluidized bed coater (inlet air temperature 40 °C) to coat with Eudragit L100-55 (solid content 15%) and control the film thickness to 20 μm;

[0017] S2. Preparation of magnesium citrate complex

[0018] Dissolve 15 kg of magnesium citrate and malic acid (molar ratio 1:0.5) in 500 L of purified water, react at 50 °C for 2 hours, and perform spray drying (Büchi B-290, inlet air temperature 180 °C, outlet air temperature 80 °C) to obtain nano composite particles;

[0019] S3. Nanoergothioneine liposome

[0020] Dissolve ergothioneine (3 kg) and lactoferrin (0.9 kg) in 200 L of purified water, perform high-pressure homogenization at 150 MPa for 3 cycles, and control the temperature in an ice bath ≤ 10 °C,

[0021] EDC / NHS (molar ratio 1:1.2) was added, and the reaction was carried out at pH 5.5 for 6 hours. After centrifugal purification (10,000 rpm, 20 min), brain-targeted nanoparticles were obtained;

[0022] S4, Withania somnifera extract immediate-release granules

[0023] Withania somnifera raw materials (200 kg) were put into the extraction kettle, and CO was used for dynamic extraction at 35 MPa and 45 °C for 4 hours (entrainer: 70% ethanol) to obtain an extract containing 6% withanolide; after the extract was spray-dried, it was treated by ultrasonic cell disruption (20 kHz, power 800 W, 30 min) to prepare porous microspheres; 2

[0024] S5, PQQ-spermidine complex

[0025] PQQ (2 kg) and hydroxypropyl-β-cyclodextrin (6 kg) were dissolved in 200 L of ethanol / water (1:4), stirred at 50 °C for 3 hours, spermidine (1 kg) was added, and high-speed shear emulsification was carried out (10,000 rpm, 15 min), and then spray-dried to obtain composite particles (particle size ≤100 μm, moisture content ≤2%);

[0026] S6, Melatonin biphasic controlled-release microspheres

[0027] Immediate-release layer: Melatonin (0.5 kg) and mannitol (2.5 kg) were mixed, and fluidized bed spray granulation was carried out (binder: 5% PVP ethanol solution) to obtain immediate-release granules;

[0028] Sustained-release layer: Melatonin (1.5 kg) and HPMC K100M (3 kg) were mixed, and fluidized bed layer-by-layer coating was carried out (inlet air temperature 50 °C) to form 12-hour sustained-release pellets;

[0029] S7, Gradient mixing and granulation

[0030] GABA microcapsules (10 kg), magnesium citrate complex (15 kg), nanoergothioneine (3 kg), and Withania somnifera granules (20 kg) were put into a mixer and mixed at 25 rpm for 30 minutes.

[0031] Binder spraying: PQQ-spermidine complex (3 kg) was added, and 15% HPMC ethanol solution was sprayed in (spray rate 20 L / h) to obtain spherical particles with a size of 0.8 - 1.2 mm;

[0032] Fluidized bed drying: Inlet air temperature 60 °C, bed temperature ≤45 °C, moisture content ≤3%;

[0033] S8, Capsule filling

[0034] Stratified filling was carried out using a filling machine.

[0035] Preferably, the layering filled in the S8 is specifically as follows: bottom layer: wild jujube seed targeted nanoemulsion particles, middle layer: mixed active particles, top layer: melatonin biphasic microspheres.

[0036] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0037] Through scientific formulation design, the capsules prepared by the present invention can regulate nerve excitability and enhance the function of GABA receptors; have antioxidant and anti-inflammatory effects, improve the brain microenvironment, provide energy support for sleep, and regulate the sleep rhythm. Each component cooperates with each other to achieve multi-path and multi-target synergistic improvement of sleep. Compared with single-component products, the effect is more comprehensive and significant. At the same time, it has high safety and small side effects. Compared with chemically synthesized sleeping pills, it does not have drug dependence and tolerance, avoids side effects such as dizziness and drowsiness, has higher safety, reduces the burden on the body, is suitable for long-term use, and provides a safer sleep aid option for people with sleep disorders.

[0038] At the same time, the present invention improves the stability and release controllability of the components, greatly improves the absorption efficiency and effect of each component in the body, and ensures the effectiveness of the product. Ensure that the product quality is stable and uniform, meets the relevant quality standards, and provides reliable products for consumers. Specific embodiments

[0039] The following will combine the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.

[0040] Example 1:

[0041] A l-ergothioneine sleep aid nutritional capsule,

[0042] Specific components: γ-aminobutyric acid (GABA) 100 mg, magnesium citrate complex 150 mg, nano-l-ergothioneine 30 mg, Withania somnifera extract 200 mg, pyrroloquinoline quinone (PQQ) 20 mg, spermidine 10 mg, jujuboside A 50 mg, melatonin sustained-release microspheres 2 mg.

[0043] A preparation process of a l-ergothioneine sleep aid nutritional capsule:

[0044] (1) GABA inclusion

[0045] Preparation of inclusion complex: 10 kg of GABA and β-cyclodextrin (molar ratio 1:2) were added into a 2000 L reactor, and pH 6.0 phosphate buffer solution (material-liquid ratio 1:10) was added. Stir at a speed of 120 rpm at 60 °C for 4 hours to fully encapsulate GABA with β-cyclodextrin. After the reaction, the wet inclusion complex was collected by centrifugation (8000 rpm, 30 min), and then placed in a vacuum drying oven at 60 °C to dry until the moisture content ≤ 3%.

[0046] Liposome encapsulation: Weigh soy lecithin and cholesterol (mass ratio 4:1, total weight 5 kg), dissolve them in ethanol, and form a thin film at 55 °C using a rotary evaporator. Then add 50 kg of aqueous solution of GABA inclusion complex, and perform 3 cycles of treatment at a pressure of 100 MPa using a high-pressure homogenizer to obtain a GABA liposome suspension.

[0047] Enteric coating: Using a fluidized bed coater, Eudragit L100-55 was formulated into a coating solution with a solid content of 15%, and the GABA liposomes were coated at an inlet air temperature of 40 °C, controlling the film thickness to reach 20 μm (weight gain 15%) to obtain pH-sensitive enteric-coated GABA sustained-release microcapsules.

[0048] (II) Preparation of magnesium citrate complex

[0049] Dissolve 15 kg of magnesium citrate and malic acid (molar ratio 1:0.5) in 500 L of purified water, and react at 50 °C for 2 hours to fully chelate magnesium citrate and malic acid. After the reaction, spray drying was carried out using a Büchi B-290 spray dryer, setting the inlet air temperature at 180 °C and the outlet air temperature at 80 °C to obtain magnesium citrate nanocomposite particles with high absorption rate.

[0050] (III) Nano-ergothioneine liposome

[0051] Dissolve 3 kg of ergothioneine and 0.9 kg of lactoferrin in 200 L of purified water, and perform 3 cycles of treatment at a pressure of 150 MPa using a high-pressure homogenizer. During the process, control the temperature ≤ 10 °C through an ice bath to ensure the full combination of ergothioneine and lactoferrin. Then add EDC / NHS (molar ratio 1:1.2), react at pH 5.5 for 6 hours, and after the reaction, centrifuge and purify (10000 rpm, 20 min) to obtain nano-ergothioneine liposome particles with brain targeting characteristics.

[0052] (IV) Immediate-release granules of Withania somnifera extract

[0053] Put 200 kg of Withania somnifera raw materials into the extraction kettle, and carry out CO at a pressure of 35 MPa and a temperature of 45 °C 2Dynamic extraction was carried out for 4 hours (with 70% ethanol as the entrainer), and an extract containing 6% withanolide was obtained. After spray-drying the extract, it was subjected to cell wall breaking treatment for 30 minutes by ultrasonic wave at a frequency of 20 kHz and a power of 800 W, and finally, Withania somnifera immediate-release microspheres with a porous structure were prepared.

[0054] (V) PQQ-spermidine complex

[0055] 2 kg of PQQ and 6 kg of hydroxypropyl-β-cyclodextrin were dissolved in 200 L of ethanol / water (volume ratio 1:4) mixed solution, and stirred at 50 °C for 3 hours to fully include PQQ with hydroxypropyl-β-cyclodextrin. Subsequently, 1 kg of spermidine was added, emulsified at a speed of 10000 rpm for 15 minutes by a high-speed shear emulsifier, and finally spray-dried to obtain PQQ-spermidine composite particles with a particle size ≤100 μm and a moisture content ≤2%.

[0056] (VI) Melatonin biphasic controlled-release microspheres

[0057] Preparation of the immediate-release layer: 0.5 kg of melatonin and 2.5 kg of mannitol were mixed evenly, and spray granulation was carried out using a fluidized bed spray granulator with 5% PVP ethanol solution as the binder to obtain melatonin immediate-release granules.

[0058] Preparation of the sustained-release layer: 1.5 kg of melatonin and 3 kg of HPMC K100M were mixed, and coating treatment was carried out through a fluidized bed lamination coater at an inlet air temperature of 50 °C to form melatonin pellets with a 12-hour sustained-release effect. The immediate-release granules were mixed with the sustained-release pellets to obtain melatonin biphasic controlled-release microspheres.

[0059] (VII) Gradient mixing and granulation

[0060] Preliminary mixing: The prepared GABA microcapsules (10 kg), magnesium citrate complex (15 kg), nanoergothioneine (3 kg), and Withania somnifera granules (20 kg) were put into a mixer and mixed at a speed of 25 rpm for 30 minutes to preliminarily and evenly disperse each component.

[0061] Granulation: 3 kg of PQQ-spermidine complex was added, and at the same time, 15% HPMC ethanol solution was sprayed in as a binder at a spraying rate of 20 L / h, and spherical particles with a particle size of 0.8 - 1.2 mm were obtained through granulation equipment.

[0062] Drying: The obtained wet granules were transferred to a fluidized bed dryer, the inlet air temperature was set at 60 °C, and the bed layer temperature was controlled ≤45 °C for drying until the moisture content of the granules ≤3%.

[0063] (VIII) Capsule filling

[0064] Stratified filling is carried out using a dedicated filling machine. The bottom layer is filled with targeted nanoemulsion particles of wild jujube seeds, the middle layer is filled with mixed active particles (i.e., the particles obtained from the gradient mixing and granulation steps), and the top layer is filled with melatonin biphasic microspheres to ensure the reasonable distribution of each component in the capsule and play a synergistic role. After filling, the capsules are sealed to obtain the finished product of ergothioneine sleep-aid nutritional capsules.

[0065] After the preparation is completed, the products of the present invention are tested.

[0066] Appearance inspection: The capsules should be of uniform size, with a smooth surface, consistent color, and no phenomena such as damage, deformation, or powder leakage.

[0067] Content uniformity: Randomly select 20 capsules and accurately weigh the content of each capsule separately. The content uniformity limit should be within ±10%.

[0068] Disintegration time limit: Test according to the relevant regulations of the Chinese Pharmacopoeia. Enteric-coated capsules should not disintegrate within 2 hours in artificial gastric juice and should completely disintegrate within 1 hour in artificial intestinal juice.

[0069] Content determination: Use suitable analytical methods such as high-performance liquid chromatography (HPLC) to determine the contents of main components such as γ-aminobutyric acid, nanoergothioneine, and jujuboside A in the capsules to ensure that the contents of each component meet the formula requirements.

[0070] The specific equipment models used in the present invention include a high-pressure homogenizer (APV-1000 type), a fluidized bed coater (Glatt GPCG-30), a centrifuge (BECKMAN Avanti J-26XP), a high-pressure homogenizer (Niro Soavi NS1001L), a coupling reaction kettle (1000L), supercritical CO 2 extractor (Waters MV-10), an ultrasonic cell disruptor (Hielscher UP2000HT), a high-speed shear emulsifier (Silverson L5M-A), a vacuum drying oven, a fluidized bed granulator (Freund-Vector FLM-15), a high-efficiency coater, a three-dimensional motion mixer (SYH-3000), and a fluidized bed dryer (FL-120). All of them can be purchased on the market.

[0071] Example 2

[0072] A l-ergothioneine sleep-aiding nutritional capsule, the capsule comprising the following parts by mass: 80 mg of γ-aminobutyric acid (GABA) (microencapsulated and sustained-release), 130 mg of magnesium citrate complex (containing 20 mg of elemental magnesium); 25 mg of nano-ergothioneine in the plant energy synergistic group, 180 mg of Withania somnifera extract (6% withanolide); 15 mg of pyrroloquinoline quinone (PQQ) (cyclodextrin inclusion) and 8 mg of spermidine in the mitochondrial energizing group; 45 mg of jujuboside A and 1.8 mg of melatonin sustained-release microspheres (0.4 mg of immediate release + 1.4 mg of sustained release) in the new ingredient group. At the same time, excipients such as microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate are prepared.

[0073] Among them, the magnesium citrate complex is chelated by citric acid and malic acid in a molar ratio of 1:0.3, and GABA is in the form of pH-sensitive enteric-coated sustained-release microcapsules.

[0074] II. Pretreatment of each component

[0075] (I) Treatment of GABA microcapsules

[0076] Mix GABA with an enteric coating material (Eudragit L100-55) in a ratio of 1:0.25, add an appropriate amount of isopropanol solution as a solvent, and stir evenly at a stirring speed of 150 rpm. Subsequently, microencapsulation is carried out by spray drying, with an inlet air temperature of 65 °C and an outlet air temperature of 42 °C, to obtain GABA microcapsules with intestinal-targeted release.

[0077] (II) Treatment of magnesium citrate complex

[0078] Mix magnesium citrate with compound citric acid and malic acid in a ratio of 1:0.4:0.3, add an appropriate amount of deionized water, and stir and dissolve at 52 °C to form a uniform solution. Dry it using a spray drying device, with an inlet air temperature of 85 °C and an outlet air temperature of 52 °C, to obtain magnesium citrate complex particles with high absorption rate.

[0079] (III) Treatment of nano-ergothioneine

[0080] According to the ratio of phospholipid, cholesterol and nano-ergothioneine of 2:1:0.8, dissolve it in dichloromethane, and evaporate dichloromethane under reduced pressure on a rotary evaporator to form a lipid film. Then add Tris-HCl buffer solution (pH 7.2) containing lactoferrin, and ultrasonically treat it at 48 °C for 25 minutes to hydrate the lipid film to form liposomes, obtaining nano-ergothioneine liposome particles with increased brain concentration.

[0081] (IV) Treatment of Withania somnifera extract

[0082] Carry out CO on the Withania somnifera extract 2Supercritical extraction was carried out under the extraction conditions of a pressure of 32 MPa, a temperature of 42 °C, and an extraction time of 3.5 hours. The entrainer used was 65% ethanol. The extract after extraction was then subjected to ultrasonic cell wall breaking treatment (frequency 22 kHz, power 700 W, treatment time 25 min). After that, an appropriate amount of ethanol solution was added and stirred to dissolve at 32 °C to form a solution with a high concentration of active substances.

[0083] (V) Treatment with PQQ and spermidine

[0084] PQQ (cyclodextrin inclusion) and spermidine were mixed at a ratio of 1.8:1, and an appropriate amount of deionized water was added and stirred evenly at 42 °C to form an electron transfer chain synergistic system solution.

[0085] (VI) Treatment with jujuboside A

[0086] Jujuboside A was added to an appropriate amount of methanol solution and stirred to dissolve for standby.

[0087] (VII) Treatment with melatonin sustained-release microspheres

[0088] Immediate-release part: 0.4 mg of melatonin and the immediate-release material polyvinylpyrrolidone were mixed at a ratio of 1:1.8, added to an ethanol solution to dissolve, and immediate-release microspheres were obtained by spray drying. Sustained-release part: 1.4 mg of melatonin and the sustained-release material ethyl cellulose were mixed at a ratio of 1:2.8, added to an acetone solution to dissolve, and sustained-release microspheres were prepared by centrifugal granulation method. Subsequently, the immediate-release microspheres and the sustained-release microspheres were mixed evenly.

[0089] III. Mixing and granulation

[0090] The pretreated GABA microcapsules, magnesium citrate complex particles, nanoergothioneine liposome particles, Withania somnifera extract solution, PQQ and spermidine synergistic system solution, jujuboside A solution, melatonin sustained-release microspheres, as well as the excipients microcrystalline cellulose and sodium carboxymethyl starch were added into the mixing tank together for wet mixing, and the mixing time was 22 minutes. Then an appropriate amount of ethanol-water mixed solution (volume ratio 1:1) was added as a binder for granulation, and the wet granules were obtained by passing through a 20-mesh sieve.

[0091] IV. Drying

[0092] The wet granules were transferred to a fluidized bed dryer, the drying temperature was set at 52 °C, and the drying time was 32 minutes to control the water content of the granules within 3.2% - 4.8%.

[0093] V. Screening and total mixing

[0094] The dried granules were screened through a 20-mesh sieve for screening to remove lumps and oversized particles. Then the screened granules and magnesium stearate were added to the total mixer at a ratio of 100:0.8 and mixed for 16 minutes to ensure the uniformity of the materials.

[0095] VI. Capsule Filling

[0096] Use a capsule filling machine to select capsule shells of appropriate specifications for filling, and strictly control the filling amount to ensure that the content of each component in each capsule meets the formula requirements.

[0097] Innovatively, the present invention scientifically formulates components such as γ-aminobutyric acid (GABA), magnesium citrate complex, nanoergothioneine, Withania somnifera extract, pyrroloquinoline quinone (PQQ), spermidine, jujuboside A, and melatonin sustained-release microspheres. Among them, GABA, as an inhibitory neurotransmitter, synergizes with the magnesium citrate complex to regulate nerve excitability and enhance the function of GABA receptors; under the action of liposomes and lactoferrin carriers, the brain concentration of nanoergothioneine is significantly increased, exerting antioxidant and anti-inflammatory effects and improving the brain microenvironment; Withania somnifera extract and jujuboside A regulate the sleep mechanism from multiple targets; PQQ and spermidine form an electron transfer chain synergy system to optimize mitochondrial function and provide energy support for sleep; the melatonin sustained-release microspheres precisely regulate the sleep rhythm through a double-layer controlled release technology. Each component cooperates with each other to achieve multi-path and multi-target synergistic improvement of sleep, and compared with single-component products, the effect is more comprehensive and significant.

[0098] Advanced processes improve bioavailability: Adopt advanced formulation technologies such as pH-sensitive enteric coating, liposome encapsulation, nanonization, and ultrasonic cell wall breaking. GABA is in the form of a pH-sensitive enteric-coated sustained-release microcapsule, which can avoid degradation in the stomach, achieve intestinal targeted release, and improve bioavailability; the magnesium citrate complex is chelated by citric acid and malic acid in a specific molar ratio, and the absorption rate is increased to 3 times that of the traditional form; the liposome encapsulation of nanoergothioneine combined with lactoferrin carrier technology increases its brain concentration by 52%; the Withania somnifera extract is treated by 2 supercritical extraction and ultrasonic cell wall breaking, and the yield of active substances is increased to 98%; the cyclodextrin inclusion technology of PQQ and the double-layer controlled release technology of melatonin effectively improve the stability and release controllability of the components. The application of these process technologies greatly improves the absorption efficiency and action effect of each component in the body, ensuring the effectiveness of the product.

[0099] High safety and few side effects: The main components of the product of the present invention are all derived from natural extracts or substances existing in the human body itself. Compared with chemically synthesized sleeping pills, it does not have drug dependence and tolerance, avoids side effects such as dizziness and drowsiness, and has higher safety. At the same time, through scientific formula design and process optimization, it is ensured that each component can play a gentle and continuous role in the body, reducing the burden on the body, being suitable for long-term use, and providing a safer sleep aid option for people with sleep disorders.

[0100] Precise Release and Long-lasting Effect: The melatonin sustained-release microspheres adopt a double-layer controlled-release technology. The rapid-release part can take effect quickly, helping users fall asleep quickly, and the sustained-release part continuously releases to maintain the blood drug concentration for 8 hours, ensuring the sleep quality throughout the night; The pH-sensitive enteric coating of GABA enables targeted release in the intestine, allowing the components to exert their effects at the appropriate site; Through corresponding formulation technologies, other components also achieve precise release and long-lasting effect, ensuring the effectiveness and stability of the product during the sleep regulation process.

[0101] Controlled Quality and Strong Stability: During the preparation process, strict process parameters and quality control standards are formulated for each link, including the pretreatment, mixing granulation, drying, filling, etc. of each component. From the screening of raw materials, the determination of component content, to the detection of the appearance, filling quantity difference, disintegration time limit, etc. of the finished product, it is ensured that the product quality is stable and uniform, meeting the relevant quality standards, and providing reliable products for consumers.

[0102] It should be understood that in the development process of any actual implementation, such as in any engineering or design project, a large number of specific implementation decisions can be made. Such development efforts may be complex and time-consuming, but for those ordinary technical personnel who benefit from this disclosure, without excessive experimentation, the development efforts will be a routine task of design, manufacturing, and production.

[0103] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not restrictive. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the claims of the present invention.

Claims

1. A thioneine sleep-aiding nutritional capsule, characterized in that, The capsule comprises the following ingredients in parts by mass: 80-120 mg of gamma-aminobutyric acid (GABA), 130-170 mg of magnesium citrate complex, 20-28 mg of elemental magnesium, 25-35 mg of nano-ergothioneine, 180-220 mg of ashwagandha extract, 15-25 mg of pyrroloquinoline quinone (PQQ), 8-12 mg of spermidine, 45-55 mg of jujuboside A, and 1.8-2.2 mg of melatonin sustained-release microspheres.

2. A kind of ergothioneine sleep-aiding nutritional capsule according to claim 1, characterized in that: The gamma-aminobutyric acid (GABA) is in the form of a pH-sensitive enteric-coated sustained-release microcapsule, and the magnesium citrate complex contains 20-28 mg of elemental magnesium and is formed by chelating citric acid and malic acid at a molar ratio of 1:0.3-0.

7.

3. according to the preparation technology of a kind of ergothioneine sleep-aiding nutritious capsule described in any one of claim 1-2, it is characterized in that: The following steps are involved: S1, GABA inclusion 10 kg of GABA and β-cyclodextrin (molar ratio 1:2) were placed in a 2000 L reactor, and pH 6.0 phosphate buffer (solid-liquid ratio 1:10) was added, and stirred at 60°C for 4 hours (rotation speed 120 rpm). Centrifuge (8000 rpm, 30 min), collect the wet inclusion complex, and vacuum dry at 60°C until the moisture content is ≤3%; For liposome encapsulation, soybean lecithin and cholesterol (4:1, total weight 5 kg) were dissolved in ethanol, and a thin film was formed by rotary evaporation at 55 °C, and an aqueous solution of GABA inclusion complex (50 kg) was added, and high pressure homogenization (100 MPa, 3 cycles) was performed to obtain a liposome suspension; Use a fluidized bed coater (inlet air temperature 40°C) to coat with Eudragit L100-55 (solid content 15%), and control the film thickness to 20 μm; S2. Preparation of magnesium citrate complex 15 kg of magnesium citrate and malic acid (molar ratio 1:0.5) were dissolved in 500 L of purified water, reacted at 50° C. for 2 hours, and spray dried (Büchi B-290, inlet air temperature 180° C., outlet air temperature 80° C.) to obtain nanocomposite particles; S3, Nano-ergothioneine Liposome Ergothioneine (3 kg) and lactoferrin (0.9 kg) were dissolved in 200 L of purified water, and homogenized at 150 MPa for 3 cycles, with the temperature controlled at ≤ 10 °C in an ice bath. EDC / NHS (molar ratio 1:1.2) was added, reacted at pH 5.5 for 6 hours, and purified by centrifugation (10000 rpm, 20 min) to obtain brain-targeted nanoparticles; S4, Ashwagandha Extract Rapid Release Granules The raw material of South African somnifera (200 kg) was put into an extraction kettle, and dynamically extracted with CO2 at 35 MPa and 45°C for 4 hours (entrainer: 70% ethanol) to obtain an extract containing 6% withanolide; after the extract was spray-dried, ultrasonic wall breaking treatment (20 kHz, power 800 W, 30 min) was performed to obtain porous microspheres; S5, PQQ-spermidine complex PQQ (2 kg) and hydroxypropyl-β-cyclodextrin (6 kg) were dissolved in 200 L ethanol / water (1:4), stirred at 50°C for 3 hours, spermidine (1 kg) was added, high-speed shear emulsification (10000 rpm, 15 min), and spray-dried to obtain composite particles (particle size ≤ 100 μm, moisture ≤ 2%); S6, melatonin biphasic controlled release microspheres Immediate-release layer: Melatonin (0.5 kg) and mannitol (2.5 kg) were mixed and granulated by fluidized bed spray (binder: 5% PVP ethanol solution) to prepare immediate-release granules; Sustained-release layer: Melatonin (1.5 kg) and HPMC K100M (3 kg) were mixed and coated by fluidized bed layering (inlet air temperature 50 °C) to form 12-hour sustained-release pellets; S7, gradient mixing and granulation GABA microcapsules (10 kg), magnesium citrate complex (15 kg), nano-ergothioneine (3 kg), and ashwagandha granules (20 kg) were put into a mixer and mixed at 25 rpm for 30 minutes; Binder spraying: Add PQQ-spermidine complex (3 kg) and spray 15% HPMC ethanol solution (spray rate 20 L / h) to obtain 0.8-1.2 mm spherical particles; Fluidized bed drying: inlet air temperature 60°C, bed temperature ≤45°C, moisture ≤3%; S8, capsule filling Use filling machine to carry out layered filling.

4. The preparation process of a kind of ergothioneine sleep-aiding nutritional capsule according to claim 3, characterized in that: The filling layers in S8 are specifically as follows: bottom layer: spiny jujube seed targeted nanoemulsion particles, middle layer: mixed active particles, and top layer: melatonin biphasic microspheres.