A process for the preparation of a sleep-aiding spray

Abstract

The present application relates to the technical field of pharmaceutical preparation, in particular to a preparation process of sleep-aiding spray, which specifically comprises the steps of preparing Zanthoxylum bungeanum extract, preparing mixed solvent, preparing composite transdermal accelerant, dissolving melatonin, filtering and defoaming, and filling and packaging; the filtering equipment in S5 comprises a rack fixed on the top of a cabinet, a circular table arranged above the rack, and a lifting rack arranged above the circular table, a three-stage filtering array group is arranged above the circular table, and the three-stage filtering array group comprises a coarse filter membrane, a fine filter membrane and a sterilization filter membrane. The filtering equipment provided by the present application adopts three cylindrical seats with gradually changing diameters which are coaxially sleeved and arranged in a ring array to install the through openings, the coarse filter membrane, the fine filter membrane and the sterilization filter membrane are integrated, the lifting rack, the filtering flow supply mechanism and the cleaning flow supply mechanism are matched with the circular table and the driving mechanism to form a compact layout, the equipment volume is greatly reduced, the space occupation of the traditional multi-stage filtering equipment is significantly reduced, and the production line miniaturization is facilitated.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, specifically to a preparation process for a sleep aid spray. Background Technology

[0002] Sleep disorders have become a global health problem. Melatonin, as a commonly used substance for regulating sleep, suffers from the first-pass effect in the liver when administered orally, resulting in low bioavailability and large fluctuations in blood drug concentration. Although transdermal administration can avoid the first-pass effect, the skin stratum corneum barrier limits the transdermal efficiency of melatonin.

[0003] Existing transdermal drug delivery technologies have several shortcomings: on the one hand, transdermal formulations struggle to balance high penetration and low irritation; on the other hand, the delivery methods are limited, lacking precise and controllable application strategies; furthermore, specialized preparation equipment and processes for transdermal sprays are not yet perfected, making it difficult to guarantee the uniformity of formulation quality. Therefore, there is an urgent need to develop an innovative melatonin transdermal drug delivery system and its supporting preparation technology.

[0004] In the actual preparation process of sleep aid sprays, a multi-stage filtration system is usually used, that is, at least three-stage filtration equipment is used to filter the medicine. Traditional three-stage filtration equipment, whether vertical or horizontal, has the problem of excessive space occupation, which seriously restricts the development of production line miniaturization. Moreover, in the actual filtration process, the filter membrane is prone to clogging in traditional filtration methods, requiring frequent shutdowns for maintenance or replacement of the filter membrane. The long downtime leads to low production continuity, which affects production efficiency and increases operating costs. Summary of the Invention

[0005] The purpose of this invention is to provide a preparation process for a sleep aid spray to solve the technical problems mentioned in the background section.

[0006] To achieve the above objectives, the present invention provides the following technical solution.

[0007] A preparation process for a sleep aid spray, wherein the sleep aid spray formulation comprises, by weight, 1-3 parts melatonin, 1-3 parts 4-aminobutyric acid, 3-7 parts compound transdermal penetration enhancer, 10-20 parts ethanol, and 75-85 parts water. The compound transdermal penetration enhancer formulation, by mass percentage, includes 10-30 parts of Sichuan pepper extract, 20-40 parts of Tween, 10-30 parts of NMP, 10-30 parts of azone, and 10-30 parts of JFC. The preparation process specifically includes the following steps: S1. Preparation of Sichuan pepper extract: Take dried Sichuan pepper, pulverize it and pass it through a 60-100 mesh sieve. Add ethanol at a material-to-liquid ratio of 1:5-1:10. Reflux at 50-70℃ for 2-3 times, 1-2 hours each time. Combine the extracts and concentrate under reduced pressure to a relative density of 1.1-1.3 to obtain Sichuan pepper extract for later use. S2. Preparation of mixed solvent: Add the prescribed amount of water and ethanol to the mixing tank and stir at 200-300 rpm for 10-15 minutes. S3. Preparation of composite transdermal penetration enhancer: Add the prescribed amounts of Tween, NMP, azone, and JFC to the mixed solvent in sequence and emulsify and stir at 3000 rpm for 20-30 minutes. Add the Sichuan pepper extract and stir for 10-20 minutes. S4. Dissolve melatonin: Add the prescribed amount of melatonin, 4-aminobutyric acid, and compound transdermal penetration enhancer to the mixed solvent, and stir at 300-500 rpm at 30-50℃ until completely dissolved. S5. Filtration and degassing: After coarse filtration, fine filtration and sterile filtration of the solution in sequence, degas under vacuum at -0.08 to -0.1 MPa for 5-10 minutes; S6. Filling and sealing: Fill the filtered and degassed solution into the spray bottle, install the sterile spray pump head and seal it.

[0008] Preferably, in S5, a filtration device is used for filtration. The filtration device includes a frame fixed to the top of the cabinet, a truncated cone above the frame, and a lifting platform above the truncated cone. A three-stage filtration array is installed above the truncated cone, comprising a coarse filter membrane, a fine filter membrane, and a sterilizing filter membrane. Three cylindrical seats with gradually changing diameters are installed above the truncated cone, arranged coaxially in sequence. Each cylindrical seat has several mounting ports arranged in a ring around the axial direction. The innermost mounting ports each contain a coarse filter membrane, the middle mounting ports each contain a fine filter membrane, and the outermost mounting ports each contain a... It has a sterilizing filter membrane. A filtration supply mechanism and a cleaning supply mechanism are arranged in a circular array below the lifting platform, and the two are arranged alternately. There is a gap between two adjacent cylindrical seats for the filtration supply mechanism and the cleaning supply mechanism to enter. The filtration supply mechanism can form a filtration channel with three installation ports located at the same radial position on the three cylindrical seats, which passes through the coarse filter membrane, fine filter membrane and sterilizing filter membrane in sequence. The cleaning supply mechanism can form a cleaning channel with three installation ports located at the same radial position on the three cylindrical seats, which passes through the sterilizing filter membrane, fine filter membrane and coarse filter membrane in sequence. A drive mechanism is provided below the platform to drive the truncated cone to rotate.

[0009] Preferably, the cross-section of each installation port has a gradually expanding arc shape in the horizontal direction, with the outermost installation port having a larger size towards the periphery. The outermost installation port has a larger size in the lateral direction than the adjacent inner installation port. The shape and size of the coarse filter membrane, fine filter membrane, and sterilization filter membrane are respectively matched with the corresponding installation ports.

[0010] Preferably, the filtration supply mechanism includes a liquid collection hood, a liquid inlet hood, a liquid guide hood A, and a liquid guide hood B. A suspension plate A is installed in a circular array on the lower surface of the lifting frame. The liquid inlet hood, liquid guide hood B, liquid guide hood A, and liquid collection hood are sequentially installed below the suspension plate A from the inner perimeter to the outer perimeter via connecting rods. The openings of the liquid collection hood and the liquid inlet hood are opposite. The liquid inlet hood is used to fit against the inner edge wall of the inner cylindrical seat and cover the installation port. The liquid collection hood is used to fit against the outer edge wall of the outer cylindrical seat and cover the corresponding installation port. The liquid guide cover A and liquid guide cover B are both open at both ends. Liquid guide cover A is used to connect the outer and middle installation ports, and liquid guide cover B is used to connect the inner and middle installation ports. The liquid inlet cover is connected to a positive pressure liquid supply pipe, and the end of the positive pressure liquid supply pipe is connected to a positive pressure flow supply device. The liquid collection cover is connected to a negative pressure liquid suction pipe, and the end of the negative pressure liquid suction pipe is connected to a negative pressure flow diversion device. The liquid inlet cover, liquid guide cover B, liquid guide cover A and liquid collection cover and the corresponding installation ports form a filtration channel.

[0011] Preferably, the clean air supply mechanism includes an air inlet hood, an air collection hood, an air guide hood A, and an air guide hood B. Suspension plates B are respectively installed on the lower surface of the lifting platform between two adjacent suspension plates A. The air collection hood, air guide hood B, air guide hood A, and air inlet hood are sequentially installed below the suspension plates B from the inner perimeter to the outer perimeter via connecting rods. The openings of the air inlet hood and the air collection hood are opposite. The air collection hood is used to fit against the inner edge wall of the inner cylindrical seat and cover the installation opening. The air inlet hood is used to fit against the outer edge wall of the outer cylindrical seat and cover the... The corresponding installation ports are provided. Both air guide hoods A and B are open at both ends. Air guide hood A is used to connect the outer and middle installation ports, and air guide hood B is used to connect the inner and middle installation ports. A positive pressure air supply pipe is connected to the air inlet hood, and the end of the positive pressure air supply pipe is connected to the positive pressure air supply equipment. A negative pressure air suction pipe is connected to the air collection hood, and the end of the negative pressure air suction pipe is connected to the negative pressure suction equipment. The air inlet hood, air guide hood A, air guide hood B and air collection hood form a cleaning channel with the corresponding installation ports.

[0012] Preferably, each port of the liquid collection hood, liquid inlet hood, liquid guide hood A and liquid guide hood B, as well as the air inlet hood, air collection hood, air guide hood A and air guide hood B, is fixed with a rectangular sealing airbag. Each rectangular sealing airbag is connected to the air filling and emptying system through an air filling and emptying pipe. The cross-section at the bottom of each cylindrical seat is V-shaped. Temporary storage areas are formed on both sides of the corresponding filter membrane at the bottom of each cylindrical seat, and the temporary storage areas are deeper as they are closer to the filter membrane.

[0013] Preferably, three annular mounting seats are fixed on the upper surface of the cylindrical platform and arranged coaxially from the inside to the outside. Each annular mounting seat is provided with several slots. The bottom end of the three cylindrical seats is provided with a plug at the position corresponding to each slot, and each plug has a locking screw hole. Each annular mounting seat is provided with a mounting hole corresponding to the slot. Each mounting hole is fitted with a fastening screw, which can be threaded into the corresponding locking screw hole.

[0014] Preferably, the drive mechanism includes a mounting bracket fixed below the frame, a drive motor and a reducer mounted on the mounting bracket, and a shaft vertically and rotatably mounted on the frame. The shaft extends through to the top of the frame and is fixed to the lower surface of the truncated cone. The input end of the reducer is fixed to the output shaft of the drive motor, and the output end is fixed to the bottom end of the shaft.

[0015] Preferably, a number of support seats are fixed in an array around the shaft on the support platform. Each support seat has a spherical cavity on its top, and a rolling ball is rolled and embedded in each spherical cavity. The rolling ball corresponds to and abuts against the lower surface of the frustum.

[0016] Preferably, a lifting mechanism is provided above the platform for driving the lifting platform to adjust its height. The lifting mechanism includes a cylinder, and the platform has an upper frame. The top of the upper frame is fixed to a mounting plate by a suspension weld. The cylinder is vertically fixed to the mounting plate, and its telescopic end is fixed to the upper surface of the lifting platform.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0018] This invention significantly enhances the transdermal efficiency of melatonin and 4-aminobutyric acid through the synergistic effect of a composite transdermal penetration enhancer. Combined with the application method of the wound dressing, precise drug delivery is achieved by limiting the spray dosage and application time, avoiding drug waste and the risk of overdose, effectively improving the sleep quality of people with sleep deprivation. Using ethanol and water as the main solvents, experiments have verified that it has minimal skin irritation. The waterproof wound dressing creates a closed drug delivery environment, further reducing external irritation and ensuring high safety.

[0019] The system uses three cylindrical seats with gradually changing diameters to coaxially mount and arrange the installation ports in a ring array, integrating the three-stage filtration membranes of coarse filtration membrane, fine filtration membrane, and sterilization filtration membrane. The lifting platform, filtration supply mechanism, cleaning supply mechanism, and the circular platform and drive mechanism work together to form a compact layout, which greatly reduces the size of the equipment and significantly reduces the space occupied by traditional multi-stage filtration equipment, which is conducive to the miniaturization of the production line.

[0020] The filter supply mechanism and the cleaning supply mechanism are arranged in an alternating ring array, which works in conjunction with the drive mechanism to drive the truncated cone to rotate, so that the filter station switches between the filter channel and the cleaning channel. The filter membrane is backflushed and cleaned by the positive pressure air supply pipe and the negative pressure air suction pipe of the cleaning supply mechanism. The V-shaped cross section at the bottom of the cylindrical seat and the temporary storage area reduce residues, realize online cleaning, avoid frequent downtime maintenance, and significantly improve production efficiency.

[0021] The installation port adopts a gradually expanding arc-shaped design with the outer dimension being larger than the inner dimension, so that the filtration area of ​​the coarse filter membrane, fine filter membrane, and sterilization filter membrane increases in a gradient, effectively balancing the filtration resistance caused by the reduction of the filter pore diameter. Combined with the positive pressure supply pipe for positive pressure flow and the negative pressure suction pipe for negative pressure drainage, the filtration rate and uniformity of the reagent are improved. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the preparation process in this invention; Figure 2 This is a schematic diagram of the overall structure of the filtration equipment used in this process; Figure 3 for Figure 2 The structural diagram of the cabinet is omitted in the diagram shown. Figure 4 This is one of the schematic diagrams of a partial structure above the platform in this invention; Figure 5 for Figure 4 A cross-sectional schematic diagram of the structure shown; Figure 6 This is a schematic diagram of the three-stage filter array group structure in this invention; Figure 7 for Figure 6 The diagram shows a cross-sectional view of the structure. Figure 8 for Figure 7 Enlarged schematic diagram of the structure at point A in the middle; Figure 9 for Figure 7 Enlarged schematic diagram of the structure at point B; Figure 10 This is a schematic diagram of the filter supply mechanism in this invention; Figure 11 This is a schematic diagram of the clean flow supply mechanism in this invention; Figure 12 This is the second schematic diagram of a partial structure above the platform in this invention; Figure 13 This is a schematic diagram of the drive mechanism structure in this invention; Figure 14 A schematic diagram showing the interaction between the filter supply mechanism and the three-stage filter array structure. Figure 15 This is a schematic diagram showing the interaction between the clean water supply mechanism and the three-stage filter array.

[0023] In the diagram: 01. Connecting rod; 02. Rectangular sealing airbag; 021. Inflation / depression pipe; 03. Filter channel; 04. Cleaning channel; 1. Stand; 11. Cabinet; 12. Upper rack; 2. Frustum; 21. Support base; 22. Spherical cavity; 23. Rolling ball; 3. Drive mechanism; 31. Mounting bracket; 32. Drive motor; 33. Reducer; 34. Shaft; 4. Three-stage filter array; 41. Cylindrical base; 411. Annular mounting base; 412. Slot; 413. Insert; 414. Mounting hole; 415. Fastening screw; 416. Locking screw hole; 42. Mounting port ; 421. Temporary storage area; 43. Coarse filter membrane; 44. Fine filter membrane; 45. Sterilizing filter membrane; 5. Lifting platform; 6. Filtration supply mechanism; 61. Suspension plate A; 62. Liquid collection hood; 621. Negative pressure suction pipe; 63. Liquid inlet hood; 631. Positive pressure supply pipe; 64. Liquid guide hood A; 65. Liquid guide hood B; 7. Cleaning supply mechanism; 71. Suspension plate B; 72. Air inlet hood; 721. Positive pressure air supply pipe; 73. Air collection hood; 731. Negative pressure suction pipe; 74. Air guide hood A; 75. Air guide hood B; 8. Lifting mechanism; 81. Suspension; 82. Mounting plate; 83. Cylinder. Detailed Implementation

[0024] The embodiments of the present invention will now be described with reference to the accompanying drawings.

[0025] In the description of the embodiments of the present invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "connection" and "installation" should be interpreted broadly. For example, "connection" can be a detachable connection or a non-detachable connection; it can be a direct connection or an indirect connection through an intermediate medium. Furthermore, "connection" can be a direct connection or an indirect connection through an intermediate medium. "Fixed" means that the devices are connected to each other and their relative positional relationship remains unchanged after the connection. The directional terms mentioned in the embodiments of the present invention, such as "inner," "outer," "top," and "bottom," are only for reference to the directions in the accompanying drawings. Therefore, the directional terms used are for better and clearer explanation and understanding of the embodiments of the present invention, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the embodiments of the present invention.

[0026] In this embodiment of the invention, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined with "first" and "second" may explicitly or implicitly include one or more of that feature.

[0027] In this embodiment of the invention, "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent three cases: A existing alone, A and B existing simultaneously, and B existing alone. Additionally, the character " / " in this document generally indicates that the preceding and following related objects have an "or" relationship.

[0028] References to "one embodiment" or "some embodiments" as used in this specification mean that a particular feature, structure, or characteristic described in connection with that embodiment is included in one or more embodiments of the invention. Therefore, the phrases "in one embodiment," "in some embodiments," "in other embodiments," "in still other embodiments," etc., appearing in different parts of this specification do not necessarily refer to the same embodiment, but rather mean "one or more, but not all, embodiments," unless otherwise specifically emphasized. The terms "comprising," "including," "having," and variations thereof mean "including, but not limited to," unless otherwise specifically emphasized. Example 1

[0029] Please see Figure 1 This invention provides a preparation process for a sleep aid spray. The sleep aid spray formula, by weight, includes 2 parts melatonin, 2 parts 4-aminobutyric acid, 5 parts compound transdermal penetration enhancer, 15 parts ethanol, and 80 parts water. The compound transdermal penetration enhancer formulation, by mass percentage, includes 20 parts of Sichuan pepper extract, 30 parts of Tween, 20 parts of NMP (N-methylpyrrolidone), 20 parts of azone, and 20 parts of JFC (fatty alcohol polyoxyethylene ether compound). The preparation process specifically includes the following steps: S1. Preparation of Sichuan pepper extract: Take dried Sichuan pepper, pulverize it and pass it through an 80-mesh sieve. Add ethanol at a material-to-liquid ratio of 1:8, and reflux at 60°C twice for 1.5 hours each time. Combine the extracts and concentrate under reduced pressure to a relative density of 1.2 to obtain Sichuan pepper extract for later use. S2. Preparation of mixed solvent: Add the prescribed amount of water and ethanol to the mixing tank and stir at 250 rpm for 10 minutes; S3. Preparation of composite transdermal penetration enhancer: Add the prescribed amounts of Tween, NMP, azone, and JFC to the mixed solvent in sequence and emulsify and stir at 3000 rpm for 25 minutes. Add the Sichuan pepper extract and stir for 15 minutes. S4. Dissolve melatonin: Add the prescribed amount of melatonin, 4-aminobutyric acid, and composite transdermal penetration enhancer to the mixed solvent and stir at 400 rpm at 40°C until completely dissolved. S5. Filtration and degassing: After coarse filtration, fine filtration and sterile filtration of the solution in sequence, degas under vacuum of -0.09MPa for 10 minutes; S6. Filling and sealing: Fill the filtered and degassed solution into the spray bottle, install the sterile spray pump head and seal it.

[0030] Experimental testing Melatonin transdermal spray transdermal penetration rate test protocol I. Materials 1. Example 1 of this application describes the preparation of a sleep aid spray; the existing sleep aid spray contains (2g melatonin, 10ml azone, 10ml ethanol, 3ml glycerin, 0.5ml phenoxyethanol, appropriate amount of citrate-sodium citrate buffer (adjusted to pH 5.5), and purified water added to 100ml. Preparation: First, dissolve melatonin in ethanol, add azone and glycerin and mix well, adjust the pH with buffer, add purified water, and finally add phenoxyethanol, stir well, and fill into spray bottles).

[0031] 2. Excised skin: Pig skin is commonly used (hair removed and processed for later use). It is necessary to ensure the integrity and freshness of the skin, and the uniform thickness (generally, the stratum corneum is intact and the thickness is controlled within an appropriate range, such as 0.5-1mm).

[0032] 3. Receiving solution: Phosphate-buffered saline (PBS, pH 7.4, to ensure that melatonin is stable and well soluble in the receiving solution).

[0033] 4. Standard: Melatonin reference standard (purity ≥98%), used to prepare standard curve.

[0034] 5. Reagents: Chromatographic grade reagents such as methanol and acetonitrile (for high performance liquid chromatography detection); analytical grade reagents such as ethanol and purified water.

[0035] II. Instruments 1. Franz diffusion cell (vertical, including supply and receiving cells, volume 3-10ml).

[0036] 2. Constant temperature water bath (the temperature of the diffusion cell is controlled at 32℃±0.5℃ to simulate the temperature of human skin).

[0037] 3. Magnetic stirrer (placed below the receiving tank to ensure uniform receiving liquid and stable stirring speed, such as 300-500 r / min).

[0038] 4. High-performance liquid chromatography (HPLC, equipped with a UV detector or fluorescence detector; since melatonin has UV absorption, UV detection is commonly used, with a detection wavelength of 220-230 nm).

[0039] 5. Analytical balance (accuracy 0.0001g, used for weighing standards, reagents, etc.).

[0040] 6. Pipettes (with a volume range of 10 μl to 1 ml, for accurate liquid transfer).

[0041] 7. Centrifuge, microporous filter membrane (0.45μm, organic or aqueous phase filter membrane, used for filtering samples).

[0042] III. Preparations before the experiment 1. Skin pretreatment: Take fresh pig skin, remove subcutaneous fat tissue, rinse thoroughly with physiological saline, and cut into appropriate sizes (matching the effective contact area of ​​the diffusion pool, 2.5cm in diameter, circular) for later use. The treated skin can be refrigerated (4℃, not exceeding 24 hours) and brought to room temperature before use.

[0043] 2. Preparation of Standard Curve: Accurately weigh an appropriate amount of melatonin standard, dissolve and dilute it with methanol or receiving buffer to prepare a series of standard solutions with concentration gradients (e.g., 0.1, 0.5, 1, 5, 10 μg / ml). Inject each solution into HPLC and record the peak area. Perform linear regression of peak area (Y) against concentration (X) to obtain the standard curve equation (Y = aX + b), where a is the slope and b is the intercept.

[0044] 3. Preparation of diffusion cell: Install the Franz diffusion cell in a constant temperature water bath, add an appropriate amount of receiving liquid to the receiving cell (so that the liquid surface just covers the skin after contact, generally 3-5 ml), turn on magnetic stirring, preheat to 32℃±0.5℃, and stabilize for 30 min.

[0045] IV. Transdermal Test Procedure 1. Sample loading and contact: The pretreated skin is fixed between the supply pool and the receiving pool, with the stratum corneum facing the supply pool. Melatonin transdermal spray (Example 1, prior art) is added to the supply pool to evenly cover the skin surface (the application area is consistent with the effective contact area of ​​the diffusion pool), and the start time is recorded.

[0046] 2. Sample Collection: At predetermined time points (e.g., 0.5, 1, 2, 4, 6, 8, 12 hours), use a pipette to aspirate all the receiving liquid from the receiving cell, and simultaneously replenish with an equal volume of fresh receiving liquid at the same temperature to ensure stable volume and concentration in the receiving cell. The collected samples are filtered through a 0.45 μm microporous membrane and then transferred to a sample vial for HPLC analysis.

[0047] 3. Continuation and Termination of the Experiment: Continue the experiment until the transdermal rate stabilizes or the preset time (e.g., 24 hours) is reached. After the experiment, remove the skin, rinse it thoroughly with physiological saline, and determine the amount of drug remaining in the skin for material balance calculation.

[0048] V. HPLC Detection 1. Chromatographic conditions: Select a C18 column (e.g., 4.6 mm × 150 mm, 5 μm); use a methanol-water (60:40) system as the mobile phase; flow rate 1.0 ml / min; detection wavelength approximately 222 nm; column temperature 30 ℃.

[0049] The results showed that the transdermal absorption of melatonin in Example 1 within 12 hours was 1.3 times that of the prior art.

[0050] Sleep duration test Ten volunteers who slept less than 6 hours were randomly divided into two groups: a sleep aid spray (administration method) as described in Example 1 and a control group that received oral melatonin. Both groups used the spray for 7 consecutive days.

[0051] The method of administration is as follows: Before going to bed, spray the melatonin transdermal absorption spray evenly onto the surface of the waterproof bandage, and then apply the bandage tightly to the skin area such as the arm. The next morning, remove the bandage and thoroughly wash the skin at the application site with clean water.

[0052] The results showed that volunteers who used the sleep aid spray of the present invention had an average sleep time that increased by 1.5-2 hours, a significant improvement in sleep quality scores, and no obvious adverse reactions. Example 2

[0053] Please see Figures 2-15 This embodiment provides the specific structure and working principle of the filtration device. The filtration device is applied to the filtration step in Embodiment 1. Specifically, it includes a frame 1 fixed on the top of the cabinet 11, a truncated cone 2 above the frame 1, and a lifting frame 5 above the truncated cone 2. A three-stage filter array group 4 is provided above the truncated cone 2. A filter supply mechanism 6 and a cleaning supply mechanism 7 are arranged in a circular array below the lifting frame 5, and the two are arranged alternately. A drive mechanism 3 is provided below the frame 1. The drive mechanism 3 drives the truncated cone 2 to rotate, which in turn drives the three-stage filter array group 4 to rotate, realizing the rotational switching of the filtration station. A lifting mechanism 8 is provided above the frame 1 to drive the lifting frame 5 to adjust its height.

[0054] The three-stage filtration array group 4 includes a coarse filter membrane 43, a fine filter membrane 44, and a sterilizing filter membrane 45. Three cylindrical seats 41 with gradually changing diameters are installed above the frustum 2. The three cylindrical seats 41 are coaxially arranged sequentially. Each cylindrical seat 41 has several mounting ports 42 arranged in a ring around the axial direction. The innermost mounting ports 42 each contain a coarse filter membrane 43, the middle mounting ports 42 each contain a fine filter membrane 44, and the outermost mounting ports 42 each contain a sterilizing filter membrane 45. The coarse filter membrane 43... The filter pore size is 10μm for coarse filtration, the fine filter membrane 44 has a filter pore size of 0.45μm for fine filtration, and the sterilization filter membrane 45 has a filter pore size of 0.22μm for final sterilization filtration. The coarse filter membrane 43, the fine filter membrane 44, and the sterilization filter membrane 45 are arranged sequentially from the inside to the outside to form a three-level gradient filtration station. The filtration station is arranged in a ring array around the axis of the cylindrical seat 41. In addition, there is a gap between two adjacent cylindrical seats 41 for the filtration supply mechanism 6 and the cleaning supply mechanism 7 to enter.

[0055] In addition, the filter supply mechanism 6 and the cleaning supply mechanism 7 are arranged in an alternating ring array below the lifting platform 5. The spacing between adjacent filter supply mechanisms 6 and cleaning supply mechanisms 7 is consistent with the spacing between two adjacent filtration stations, so that the filter supply mechanism 6 and the cleaning supply mechanism 7 can correspond one-to-one with the position of the filtration station.

[0056] The filtration supply mechanism 6 can form a filtration channel 03 with the three mounting ports 42 located at the same radial position on the three cylindrical seats 41, through which the coarse filter membrane 43, fine filter membrane 44 and sterilization filter membrane 45 pass in sequence. The cleaning supply mechanism 7 can form a cleaning channel 04 with the three mounting ports 42 located at the same radial position on the three cylindrical seats 41, through which the sterilization filter membrane 45, fine filter membrane 44 and coarse filter membrane 43 pass in sequence.

[0057] When filtering the agent, the lifting platform 5 is first driven down by the lifting mechanism 8, so that the corresponding parts of the filter supply mechanism 6 and the cleaning supply mechanism 7 enter the gap between the two cylindrical seats 41. Then, the driving mechanism 3 drives the truncated cone 2 and the three-stage filter array group 4 to rotate, so that each filter supply mechanism 6 corresponds to several filter stations, completing the preparatory work for filtration. At this time, each cleaning supply mechanism 7 corresponds to the remaining filter stations. Next, the agent is supplied into the filter supply mechanism 6 through the positive pressure supply device and flows in the filter channel 03. Finally, the agent is drawn out by the negative pressure drainage device. When the agent is in the filter channel 03, it passes through the coarse filter membrane 43, the fine filter membrane 44 and the sterilization filter membrane 45 in sequence, thus completing the coarse filtration, fine filtration and sterilization filtration process. After a period of filtration, the drive mechanism 3 drives the frustum 2 and the three-stage filter array group 4 to rotate, so that the cleaning supply mechanism 7 is aligned with the used filtration station. At this time, the filtration supply mechanism 6 synchronously switches to the new filtration station to realize the alternating operation of filtration and cleaning.

[0058] The previous batch of filtration stations rotates to correspond one-to-one with each cleaning supply mechanism 7. High-pressure gas is supplied into the cleaning supply mechanism 7 through the positive pressure gas supply equipment and flows in the cleaning channel 04. Then, the gas in the cleaning channel 04 is sucked from the other side by the negative pressure suction equipment, forming a backflush airflow from the sterilization filter membrane 45 to the coarse filter membrane 43 in the cleaning channel 04. This backflush removes the solid impurities accumulated in the filter pores of the sterilization filter membrane 45, the fine filter membrane 44, and the coarse filter membrane 43. At the same time, the impurities are finally extracted and collected by the negative pressure suction equipment, thereby achieving backflush cleaning of each filter membrane.

[0059] In the specific filtration process, the reagent is supplied with positive pressure upstream of the filtration channel 03 and the filtered reagent is drawn out with negative pressure downstream of the filtration channel 03. The pressure difference formed by the positive and negative pressure enhances the driving force for the reagent to penetrate the filter membrane, so that the reagent passes through each layer of filter membrane evenly and efficiently. This can not only improve the filtration rate and ensure filtration accuracy, but also reduce the accumulation of impurities on the filter membrane surface and reduce the risk of clogging through negative pressure suction. At the same time, the positive pressure supply can ensure the continuous and stable flow of the reagent, while the negative pressure drawout facilitates the smooth collection of the filtered reagent, thereby achieving high efficiency, continuity and stability of the filtration process.

[0060] This application integrates three filter membranes evenly on three cylindrical seats 41 with gradually changing diameters and arranged coaxially in sequence to form multiple filtration stations in a ring array, thereby making the three-stage filtration system highly integrated, effectively reducing the size of the filtration equipment, and facilitating the miniaturization of the production line layout.

[0061] By arranging the filtration supply mechanism 6 and the cleaning supply mechanism 7 in an alternating circular array and corresponding them one-to-one with each filtration station, when the filtration supply mechanism 6 works with the filtration station to perform chemical filtration, the remaining filtration stations correspond one-to-one with the cleaning supply mechanism 7. The filtration supply mechanism 6 can be used to clean the non-working filtration stations. In conjunction with the drive mechanism 3, the three-stage filtration array group 4 is driven to rotate and adjust, so that the filtration stations alternate between filtration mode and cleaning mode. This eliminates the need for frequent shutdowns to maintain and replace the filter membrane, ensuring stronger operational continuity and effectively improving processing efficiency. Example 3

[0062] Please see Figure 4 and Figure 10 The difference between this embodiment and Embodiment 2 is that: The filtration supply mechanism 6 includes a liquid collection hood 62, a liquid inlet hood 63, a liquid guide hood A64, and a liquid guide hood B65. A suspension plate A61 is installed in a circular array on the lower surface of the lifting platform 5. The liquid inlet hood 63, liquid guide hood B65, liquid guide hood A64, and liquid collection hood 62 are sequentially installed below the suspension plate A61 from the inner perimeter to the outer perimeter via connecting rods 01. The openings of the liquid collection hood 62 and the liquid inlet hood 63 are opposite, while the liquid guide hoods A64 and B65 are both open at both ends. Figure 14 As shown, the liquid inlet cover 63 is attached to the inner edge wall of the inner cylindrical seat 41 and covers the corresponding mounting port 42. The liquid guide cover B65 is attached between the inner cylindrical seat 41 and the middle cylindrical seat 41 and covers the corresponding two mounting ports 42. The liquid guide cover A64 is attached between the middle cylindrical seat 41 and the outer cylindrical seat 41 and covers the corresponding two mounting ports 42. The liquid collection cover 62 is attached to the outer edge wall of the outer cylindrical seat 41 and covers the corresponding mounting port 42, thus forming the filter channel 03.

[0063] A positive pressure supply pipe 631 is connected to the liquid inlet hood 63, and the end of the positive pressure supply pipe 631 is connected to the positive pressure flow device. A negative pressure suction pipe 621 is connected to the liquid collection hood 62, and the end of the negative pressure suction pipe 621 is connected to the negative pressure drainage device. The positive pressure flow device introduces the agent into the liquid inlet hood 63 from the positive pressure supply pipe 631, and the negative pressure drainage device draws the filtered agent out from the negative pressure suction pipe 621 under negative pressure. The agent passes through the filtration channel 03 and passes through the coarse filter membrane 43, the fine filter membrane 44 and the sterilization filter membrane 45 in sequence to achieve step-by-step filtration.

[0064] Specifically, each installation port 42 has a gradually expanding arc shape in the horizontal direction, with the outermost installation port 42 having a larger size towards the outer edge. The outermost installation port 42 has a larger size in the horizontal direction than the adjacent inner installation port 42. The shape and size of the coarse filter membrane 43, fine filter membrane 44, and sterilization filter membrane 45 are matched with the corresponding installation ports 42. In addition, the sides of each installation port 42 on the three cylindrical seats 41 are on the same plane. This design ensures that the filtration area of ​​the filter membrane changes in a gradient that increases towards the outer edge.

[0065] Since the smaller the pore diameter, the greater the filtration resistance, the filtration area of ​​the filter membrane gradually increases towards the periphery, effectively balancing the increase in filtration resistance caused by the reduction in pore diameter. This allows the reagent to penetrate each layer of the filter membrane evenly and smoothly during the filtration process, thereby improving the filtration rate, ensuring filtration accuracy, and enhancing the continuity and stability of the filtration process. Example 4

[0066] Please see Figure 4 and Figure 11 The difference between this embodiment and embodiment 3 is that: The clean air supply mechanism 7 includes an air inlet hood 72, an air collection hood 73, an air guide hood A74, and an air guide hood B75. The lower surface of the lifting platform 5 is equipped with a suspension plate B71 between two adjacent suspension plates A61. The air collection hood 73, the air guide hood B75, the air guide hood A74, and the air inlet hood 72 are installed sequentially below the suspension plate B71 from the inner perimeter to the outer perimeter via a connecting rod 01. The openings of the air inlet hood 72 and the air collection hood 73 are opposite, and the air guide hood A74 and the air guide hood B75 are both through at both ends.

[0067] like Figure 15 As shown, the air collection hood 73 is attached to the inner edge wall of the inner cylindrical seat 41 and covers the corresponding installation port 42. The air guide hood B75 is attached between the inner cylindrical seat 41 and the middle cylindrical seat 41 and covers the corresponding two installation ports 42. The air guide hood A74 is attached between the middle cylindrical seat 41 and the outer cylindrical seat 41 and covers the corresponding two installation ports 42. The air intake hood 72 is attached to the outer edge wall of the outer cylindrical seat 41 and covers the corresponding installation port 42, thus forming the cleaning channel 04.

[0068] A positive pressure air supply pipe 721 is connected to the air intake hood 72, and the end of the positive pressure air supply pipe 721 is connected to the positive pressure air supply equipment. A negative pressure air suction pipe 731 is connected to the air collection hood 73, and the end of the negative pressure air suction pipe 731 is connected to the negative pressure suction equipment. The positive pressure air supply equipment supplies gas into the cleaning channel 04 through the positive pressure air supply pipe 721. The negative pressure suction equipment works to draw the gas out of the cleaning channel 04 under negative pressure from the negative pressure air suction pipe 731. During this process, under the action of positive and negative pressure, the impurities accumulated on the sterilization filter membrane 45, the fine filter membrane 44 and the coarse filter membrane 43 can be backflushed and cleaned in sequence, and then discharged by negative pressure airflow.

[0069] In addition, such as Figure 10 and Figure 11 As shown, each port of the liquid collection hood 62, liquid inlet hood 63, liquid guide hood A64 and liquid guide hood B65, as well as the air inlet hood 72, air collection hood 73, air guide hood A74 and air guide hood B75, is fixed with a rectangular sealing airbag 02. Each rectangular sealing airbag 02 is connected to the inflation / deflation system through an inflation / deflation pipe 021. By inflating each rectangular sealing airbag 02 through the inflation / deflation system, the liquid collection hood 62, liquid inlet hood 63, liquid guide hood A64, liquid guide hood B65, air inlet hood 72, air collection hood 73, air guide hood A74 and air guide hood B75 can fit more tightly with each cylindrical seat 41, resulting in a better sealing effect. When each rectangular sealing airbag 02 deflates, the gap between it and the cylindrical seat 41 increases, which facilitates the relative movement adjustment between the filter supply mechanism 6 and the cleaning supply mechanism 7 and the cylindrical seat 41.

[0070] like Figure 8As shown, the bottom cross-section of each cylindrical seat 41 is V-shaped. Temporary storage areas 421 are formed on both sides of the corresponding filter membrane at the bottom of each cylindrical seat 41. The temporary storage areas 421 are deeper as they are closer to the filter membrane. After filtration, the residual agent on each filter membrane will flow downward along the filter membrane and finally be collected and temporarily stored through the temporary storage areas 421, which can prevent a small amount of residual agent from flowing randomly and causing pollution.

[0071] like Figure 7 and Figure 9 As shown, three annular mounting seats 411 are fixed on the upper surface of the truncated cone 2, arranged coaxially from the inside to the outside. Each annular mounting seat 411 is provided with several slots 412. The bottom end of the three cylindrical seats 41 is provided with a plug 413 corresponding to the position of each slot 412, and each plug 413 has a locking screw hole 416. Each annular mounting seat 411 is provided with a mounting hole 414 corresponding to and communicating with the slot 412. Each mounting hole 414 is fitted with a fastening screw 415, which can be threaded into the corresponding locking screw hole 416.

[0072] By inserting the insert 413 into the slot 412 and locking the insert 413 in the slot 412 with the fastening screw 415, the cylindrical seat 41 can be detachably installed on the annular mounting base 411, thereby facilitating the disassembly of each cylindrical seat 41 for replacement or maintenance. Example 5

[0073] The difference between this embodiment and embodiment 4 is that: like Figure 13 As shown, the drive mechanism 3 includes a mounting bracket 31 fixed below the frame 1, a drive motor 32 and a reducer 33 mounted on the mounting bracket 31, and a shaft 34 vertically rotatably mounted on the frame 1. The shaft 34 extends through to the top of the frame 1 and is fixed to the lower surface of the frustum 2. The input end of the reducer 33 is fixed to the output shaft of the drive motor 32, and the output end is fixed to the bottom end of the shaft 34. Through the operation of the drive motor 32, the shaft 34 and the frustum 2 are driven to rotate under the transmission action of the reducer 33, thereby realizing the rotation adjustment of the three-stage filter array group 4 and providing a stable drive for the switching of the filter station.

[0074] like Figure 5 As shown, several support seats 21 are fixed in an array around the shaft 34 on the frame 1. Each support seat 21 has a spherical cavity 22 on its top. Each spherical cavity 22 has a rolling ball 23 that is rolled and embedded in it. The rolling ball 23 is in contact with the lower surface of the frustum 2. The support seats 21 and the rolling ball 23 form a support mechanism and are arranged in a ring array around the rolling ball 23. This ensures stable support for the frustum 2 and also minimizes friction between the support seats and the frustum 2.

[0075] like Figure 12As shown, the lifting mechanism 8 includes a cylinder 83. The platform 1 has an upper frame 12. The top of the upper frame 12 is welded and fixed to the mounting plate 82 via a suspension 81. The cylinder 83 is vertically fixed on the mounting plate 82, and its telescopic end is fixed to the upper surface of the lifting platform 5. The telescopic operation of the cylinder 83 can drive the lifting platform 5 and each filter supply mechanism 6 and cleaning supply mechanism 7 to rise and fall synchronously. When the lifting platform 5 rises, it makes room for maintenance or replacement of each cylindrical seat 41. When the lifting platform 5 falls, it adjusts the filter supply mechanism 6 and the cleaning supply mechanism 7 to the filtration position.

[0076] The control method of the present invention is automatic control through a controller. The control circuit of the controller can be implemented by simple programming by those skilled in the art. The power supply is also common knowledge in the art. Therefore, the present invention will not explain the control method and circuit connection in detail.

[0077] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the present invention.

Claims

1. A filtration device for the preparation process of a sleep aid spray, characterized in that: The filtration equipment includes a frame fixed to the top of the cabinet, a truncated cone above the frame, and a lifting frame above the truncated cone. A three-stage filtration array is provided above the truncated cone, and the three-stage filtration array includes a coarse filtration membrane, a fine filtration membrane, and a sterilization filtration membrane. Three cylindrical seats with gradually changing diameters are installed above the truncated cone. The three cylindrical seats are arranged coaxially in sequence. Each cylindrical seat has several installation ports arranged in a ring array around the axial direction. The innermost installation port is equipped with a coarse filter membrane, the middle installation port is equipped with a fine filter membrane, and the outermost installation port is equipped with a sterilization filter membrane. The lifting platform is arranged in a circular array below it, with a filtration supply mechanism and a cleaning supply mechanism arranged alternately. There is a gap between two adjacent cylindrical seats for the filtration supply mechanism and the cleaning supply mechanism to enter. The filtration supply mechanism can form a filtration channel with three mounting ports located at the same radial position on the three cylindrical seats, through which the coarse filter membrane, fine filter membrane and sterilization filter membrane pass in sequence. A drive mechanism is provided below the frame to drive the frustum to rotate; Suspension plates A are installed in a circular array on the lower surface of the lifting platform; The clean air supply mechanism includes an air inlet hood, an air collection hood, an air guide hood A, and an air guide hood B; The lower surface of the lifting platform is equipped with suspension plates B between two adjacent suspension plates A. The air collection hood, air guide hood B, air guide hood A and air inlet hood are installed sequentially from the inner circle to the outer circle below the suspension plate B via connecting rods. The air intake hood and the air collection hood have opposite openings. The air collection hood is used to fit against the inner edge wall of the inner cylindrical seat and cover the mounting port. The air intake hood is used to fit against the outer edge wall of the outer cylindrical seat and cover the corresponding mounting port. Both the air guide hood A and the air guide hood B are open at both ends. The air guide hood A is used to connect the outer side and the middle installation port, and the air guide hood B is used to connect the inner side and the middle installation port. The air intake hood is connected to a positive pressure air supply pipe, and the end of the positive pressure air supply pipe is connected to a positive pressure air supply device. The gas collection hood is connected to a negative pressure suction pipe, and the end of the negative pressure suction pipe is connected to a negative pressure suction device. The air intake hood, air guide hood A, air guide hood B, and air collection hood form a cleaning channel with the corresponding installation ports.

2. The filtration device according to claim 1, characterized in that: Each of the aforementioned mounting openings has a gradually expanding arc shape in the horizontal direction, with the size increasing towards the outer edge, and the outer mounting opening has a larger dimension in the lateral direction than the adjacent inner mounting opening. The shape and size of the coarse filter membrane, the fine filter membrane, and the sterilization filter membrane are respectively matched with the corresponding installation ports.

3. The filtration device according to claim 1, characterized in that: The filtration and supply mechanism includes a liquid collection hood, a liquid inlet hood, a liquid guide hood A, and a liquid guide hood B; The liquid inlet cover, liquid guide cover B, liquid guide cover A and liquid collection cover are installed sequentially from the inner perimeter to the outer perimeter below the suspension plate A via connecting rods; The liquid collection hood and the liquid inlet hood have opposite openings. The liquid inlet hood is used to fit against the inner edge wall of the inner cylindrical seat and cover the mounting port. The liquid collection hood is used to fit against the outer edge wall of the outer cylindrical seat and cover the corresponding mounting port. Both liquid guide cover A and liquid guide cover B are open at both ends. Liquid guide cover A is used to connect the outer side and the middle installation port, and liquid guide cover B is used to connect the inner side and the middle installation port. The liquid inlet hood is connected to a positive pressure liquid supply pipe, and the end of the positive pressure liquid supply pipe is connected to a positive pressure flow supply device. The liquid collection hood is connected to a negative pressure suction pipe, and the end of the negative pressure suction pipe is connected to a negative pressure drainage device. The liquid inlet hood, liquid guide hood B, liquid guide hood A, and liquid collection hood, together with their respective mounting ports, form the filtration channel.

4. The filtration device according to claim 3, characterized in that: Each port of the liquid collection hood, liquid inlet hood, liquid guide hood A and liquid guide hood B, as well as the air inlet hood, air collection hood, air guide hood A and air guide hood B, is fixed with a rectangular sealing airbag. Each of the rectangular sealing airbags is connected to the inflation / deflation system via an inflation / deflation tube; The cross-section at the bottom of each cylindrical seat is V-shaped; At the bottom of each cylindrical seat, temporary storage areas are formed on both sides of the corresponding filter membrane, and the temporary storage areas are deeper as they are closer to the filter membrane.

5. The filtration device according to claim 1, characterized in that: The upper surface of the circular platform is fixed with three annular mounting seats arranged coaxially from the inside to the outside, and each annular mounting seat is provided with several slots. Each of the three cylindrical bases has a plug at its bottom end corresponding to the position of each slot, and each plug has a locking screw hole. Each of the annular mounting bases is provided with mounting holes that correspond to and communicate with the slots. Each mounting hole is fitted with a fastening screw, which can be threaded into the corresponding locking screw hole.

6. The filtration device according to claim 1, characterized in that: The drive mechanism includes a mounting bracket fixed below the frame, a drive motor and a reducer mounted on the mounting bracket, and a shaft vertically and rotatably mounted on the frame. The shaft extends through to the top of the frame and is fixed to the lower surface of the frustum; The input end of the reducer is fixed to the output shaft of the drive motor, and the output end is fixed to the bottom end of the shaft.

7. The filtration device according to claim 6, characterized in that: Several support seats are fixed in an array around the shaft on the frame platform. Each support seat has a spherical cavity at its top, and a rolling ball is rolled and embedded in each spherical cavity. The rolling ball abuts against the lower surface of the frustum.

8. The filtration device according to claim 5, characterized in that: A lifting mechanism is provided above the platform for driving the lifting platform to adjust its height. The lifting mechanism includes a cylinder; The platform has an upper frame, and the top of the upper frame is fixed with a mounting plate by a suspension welding. The cylinder is vertically fixed on the mounting plate, and its telescopic end is fixed to the upper surface of the lifting frame.

9. A preparation process for a sleep aid spray, characterized in that: The sleep aid spray formula, by weight, includes 1-3 parts melatonin, 1-3 parts 4-aminobutyric acid, 3-7 parts compound transdermal penetration enhancer, 10-20 parts ethanol, and 75-85 parts water. The compound transdermal penetration enhancer formulation, by mass percentage, includes 10-30 parts of Sichuan pepper extract, 20-40 parts of Tween, 10-30 parts of NMP, 10-30 parts of azone, and 10-30 parts of JFC. The preparation process specifically includes the following steps: S1. Preparation of Sichuan pepper extract: Take dried Sichuan pepper, pulverize it and pass it through a 60-100 mesh sieve. Add ethanol at a material-to-liquid ratio of 1:5-1:

10. Reflux at 50-70℃ for 2-3 times, 1-2 hours each time. Combine the extracts and concentrate under reduced pressure to a relative density of 1.1-1.3 to obtain Sichuan pepper extract for later use. S2. Preparation of mixed solvent: Add the prescribed amount of water and ethanol to the mixing tank and stir at 200-300 rpm for 10-15 minutes. S3. Preparation of composite transdermal penetration enhancer: Add the prescribed amounts of Tween, NMP, azone, and JFC to the mixed solvent in sequence and emulsify and stir at 3000 rpm for 20-30 minutes. Add the Sichuan pepper extract and stir for 10-20 minutes. S4. Dissolve melatonin: Add the prescribed amount of melatonin, 4-aminobutyric acid, and compound transdermal penetration enhancer to the mixed solvent, and stir at 300-500 rpm at 30-50℃ until completely dissolved. S5. Filtration and degassing: After coarse filtration, fine filtration and sterile filtration of the solution in sequence, degas under vacuum at -0.08 to -0.1 MPa for 5-10 minutes; S6. Filling and sealing: Fill the filtered and degassed solution into the spray bottle, install the sterile spray pump head and seal it; S5 uses the filtration device as described in any one of claims 1 to 8 for filtration.

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