Lavender-containing sleep-aiding and nerve-calming essential oil slow-release nanofiber membrane and preparation method and application thereof

Abstract

The invention provides a lavender-containing sleep-aiding and nerve-calming essential oil slow-release nanofiber membrane as well as a preparation method and application thereof. The nanofiber membrane with a coaxial core-shell structure is prepared by adopting a coaxial electrostatic spinning technology, a shell layer of the nanofiber membrane is a polylactic acid, chitosan and polyvinyl alcohol ternary blending system, a core layer of the nanofiber membrane is a dispersion system formed by combining various essential oils, and the prepared nanofiber membrane has a narrow pore diameter of 50-120 nm, and has the advantages that the pore diameter of the nanofiber membrane is 50-120 nm; the oil carrying capacity and the entrapment efficiency of the fiber membrane are improved through a controllable microporous structure of the core-shell structure and a component adaptation mechanism, three-stage precise slow release is realized, the later release speed of the essential oil is remarkably reduced, and the slow release time is prolonged. Meanwhile, the problem that a single-layer ternary blending system is uncontrollable in compatibility and slow release is solved, by entrapping a specific essential oil combination, peak shifting and complementary effects are achieved, release according to a time sequence is achieved, the synergistic effect of various essential oils is promoted, the multi-layer sleep aiding effect is achieved, the overall sleep aiding effect is enhanced, and all stages of sleep can be better adjusted.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of nanomaterials and essential oil sustained-release control technology, and in particular to a lavender-containing sleep-aiding and tranquilizing essential oil sustained-release nanofiber membrane, a preparation method and application thereof. BACKGROUND

[0002] Essential oils, as a natural plant extract, are widely used in health care and daily life due to their mood-regulating, stress-relieving and sleep-aiding effects. Common methods of using essential oils include diffusion, drop and spray, which can achieve certain effects in a short time. However, these methods have the disadvantages of uncontrollable release rate, unstable effect and short action time. Traditional essential oil diffusion and drop methods have a fast evaporation rate, and the effect usually lasts for a short time. Moreover, the effect is unstable due to the influence of external environment (such as temperature and humidity), which affects the user experience.

[0003] Nanofiber membranes have rapidly developed in the field of plant essential oil encapsulation due to their high specific surface area, porous structure and controllable release performance, and are widely used in food preservation, medical dressings and antibacterial materials. Existing researches have used polylactic acid (PLA), chitosan (CS) and polyvinyl alcohol (PVA) to prepare essential oil sustained-release carriers through electrospinning technology. PLA provides mechanical support, CS enhances antibacterial properties, and PVA improves fiber formation. However, these technologies still have some obvious shortcomings. Direct blending of PLA (hydrophobic) and CS / PVA (hydrophilic) can lead to phase separation, and the fibers may be beaded or broken. Moreover, essential oils in the hydrophilic matrix (CS / PVA) can be released suddenly, and the hydrophobic PLA layer may hinder the release. Current researches have attempted to construct essential oil-loaded nanofiber membranes by blending or layering polylactic acid (PLA), chitosan (CS) and polyvinyl alcohol (PVA) to improve the release behavior and antibacterial properties of essential oils. For example, International Journal of Biological Macromolecules (2022) disclosed a PLA / CS / PVA three-component electrospinning lavender essential oil system, which constructed a double-layer structure through a step-by-step electrospinning process. The upper PLA layer was used to delay the evaporation of essential oils, and the lower CS / PVA layer was used as an oil loading layer to achieve a maximum of 72 hours of essential oil release effect, and exhibited an 85% antibacterial efficiency against Escherichia coli. However, this method has the problems of weak interfacial bonding force and easy delamination, and is mainly used for single essential oil, which is difficult to achieve the synergistic release of multiple components (due to the problems of release time sequence mismatch, poor compatibility and even interfacial instability).

[0004] In addition, a PLA / CS / PVA-eucalyptus oil fiber membrane system constructed by an emulsion electrospinning method is reported in Materials Science & Engineering C (2021), which emulsifies essential oil by Span 80 before spinning to improve its dispersibility, and is supplemented by UV crosslinking CS / PVA to improve fiber stability. The material exhibits pH-responsive release characteristics and can accelerate the release rate in an acidic environment, but this system relies on external condition stimulation to trigger release, making it difficult to achieve autonomous phased controlled release under normal temperature static conditions, and is limited to single-component eucalyptus oil release regulation.

[0005] The blending single-layer system based on PLA / CS / PVA is difficult to balance the hydrophobic / hydrophilic components and the compatibility between multiple oil molecules, and the pore size distribution will be widened and the migration channel will be uneven due to phase separation and beading, further amplifying the uncontrollability of multi-component release, and the release rate is faster in the later stage and the duration is shorter. And the following technical defects still exist in the layered preparation: (1) the combination between the structure layers is weak, the stability is poor, and the interlayer peeling is easy to occur; (2) lack of unified film forming system, unable to accurately control the pore size structure; (3) mainly used for single essential oil, lack of overall control of multi-component essential oil synergistic and staggered release; (4) unable to balance the comprehensive performance requirements of high loading rate, controllable slow release rate and synergistic efficacy enhancement. Therefore, it is urgent to develop a high-performance carrier system with stable structure, adjustable release rate, suitable for multi-component essential oil combination and synergistic slow release function, for packaging multi-component essential oil to realize multi-stage precise release and overall sleep aid efficiency improvement. SUMMARY

[0006] The technical problem to be solved by the present application is to solve the problems of poor compatibility, uncontrollable slow release and short duration of the existing PLA / CS / PVA fiber membrane blending single-layer system, and to provide a lavender-containing sleep aid and nerve calming essential oil slow-release nanofiber membrane, its preparation method and application.

[0007] The first object of the present application is to provide a core-shell coaxial nanofiber membrane.

[0008] The second object of the present application is to provide a preparation method of the coaxial nanofiber membrane.

[0009] The third object of the present application is to provide an application of the coaxial nanofiber membrane.

[0010] The fourth object of the present application is to provide a product.

[0011] The above objects of the present application are achieved by the following technical solutions: The application provides a kind of core-shell coaxial nanofiber membrane, the nanofiber membrane is coaxial core-shell structure, shell layer is composed of polylactic acid, chitosan and polyvinyl alcohol, core layer is essential oil combination dispersion system, which is prepared by coaxial electrospinning technology; The mass ratio of polylactic acid, chitosan and polyvinyl alcohol is (3-5):(3-4):(2-3). The essential oil combination dispersion system is obtained by dispersing essential oil combination in 3-8% PVA / ethanol solution and ultrasonic treatment. The essential oil combination contains lavender essential oil, chamomile essential oil, orange flower essential oil, rosemary essential oil and lemon grass essential oil, and the mass ratio is (4-6):(2-4):(1-3):(1-3):1. The pore size of the coaxial nanofiber membrane is 50-120 nm.

[0012] The application adopts coaxial electrospinning technology to prepare a nanofiber membrane with coaxial core-shell structure, the shell layer is a ternary blend system of polylactic acid (PLA), chitosan (CS) and polyvinyl alcohol (PVA), and the core layer is a dispersion system of multiple essential oil combinations. The prepared nanofiber membrane forms a narrow pore size distribution (PDI<0.2) microporous network with a peak value of 50-120 nm, so that the specific surface area of the carrier is >60 m 2 / g, and the porosity is >65%. The controlled microporous structure of the core-shell structure and the component matching mechanism improve the oil loading capacity and encapsulation efficiency of the fiber membrane, realize three-stage precise release, have more stable release, maintenance and tail release rates in the three stages, significantly reduce the late release speed of essential oils, and ensure that essential oil components are released at different rates at different time periods, have a long duration, and can effectively prolong the release effect. At the same time, the application overcomes the problems of the existing technology, such as the difficulty in balancing the hydrophobic / hydrophilic components and the compatibility between multiple oil molecules in the PLA / CS / PVA blend single-layer system, and the uncontrollable release, can realize the synergistic release of essential oil components at different stages, and finally achieve more durable and stable sleep aid effect. The application encapsulates specific essential oil combinations, has peak-shifting and complementary effects, realizes time-based release, and through specific core-shell structure design, essential oils are distributed in a gradient in the carrier, high-volatility components are preferentially enriched in the inner core, and low-volatility components form a "retarded release zone" in the outer shell, realize three-stage peak-shifting release, promote the synergistic effect of multiple essential oils, have multi-level sleep aid effect, enhance the overall sleep aid effect, and can better regulate each stage of sleep.

[0013] Preferably, the mass ratio of PLA, CS and PVA is 4:(3-4):(2-3).

[0014] Preferably, the mass ratio of lavender essential oil, chamomile essential oil, orange flower essential oil, rosemary essential oil and lemon grass essential oil in the essential oil combination is 5:(2-3):(2-3):(2-3):1.

[0015] More preferably, the mass ratio of lavender essential oil, chamomile essential oil, orange flower essential oil, rosemary essential oil and lemon grass essential oil in the essential oil combination is 5:3:2:2:1.

[0016] Preferably, the concentration of the essential oil combination dispersion system is 1-5 wt%.

[0017] The present application adopts specific lavender essential oil, chamomile essential oil, orange flower essential oil, rosemary essential oil and lemon grass essential oil, realizes the gradient distribution and phased release of multi-component essential oil in the fiber membrane carrier. Specifically, in the core part, the essential oil is dispersed well in the PVA / ethanol solution, in which the high volatile components (lavender essential oil and chamomile essential oil) are rapidly enriched in the core fiber layer during the spinning process, forming a higher concentration distribution; while the low volatile components (rosemary essential oil, lemon grass essential oil) are more distributed in the area close to the shell due to their diffusion speed. The shell part adopts a composite system of PLA, CS and PVA, which is dissolved in an organic solvent to prepare a mixed solvent, which can effectively regulate the volatilization behavior of the spinning solution, so that the shell layer of the fiber membrane forms a dense and uniform (50-120 nm) nanoporous network during the spinning solidification process. This dense structure can significantly limit the diffusion rate of low volatile essential oil components in the middle and late stages of essential oil release, achieving long-acting and stable sustained release effect.

[0018] Through this core-shell gradient structure design of loose core and dense shell, the fiber membrane can quickly release high volatile essential oil components such as lavender and chamomile in the early stage (0-6 hours) to quickly exert the calming effect; while in the middle stage (6-48 hours) and the late stage (48-72 hours), the low volatile components such as rosemary and lemon grass are slowly released and continuously act, playing a role in maintaining deep sleep and soothing nerves. The gradient structure and the difference in volatile rate of different essential oil components work together to ensure that each essential oil component is released at different peaks and exerts the best pharmacological synergistic effect.

[0019] In addition, PLA and PVA in the fiber membrane form hydrophobic-hydrophilic microphase separation, and CS forms weak hydrogen bond interaction with phenolic hydroxyl groups in the essential oil components through amino groups, effectively enhancing the entrapment efficiency of the fiber membrane to the essential oil (≥85%), and ensuring the compatibility between the essential oil components and the structural stability of the carrier system, realizing precise controlled release and optimizing the overall sleep-aiding and calming effect.

[0020] The synergistic mechanism of essential oils: By adjusting the combination ratio of essential oils, the chemical components of the five essential oils can synergize in different stages, complementing each other's pharmacological effects. Lavender essential oil: with its strong calming effect, it is released first in the opening stage, quickly relieving anxiety and helping sleep. Chamomile essential oil: in the maintenance stage, it plays a soothing and relaxing role, reducing nighttime awakenings, and maintaining the depth and quality of sleep. Orange flower essential oil: increases emotional regulation, alleviates sleep disturbances caused by stress, and enhances sleep stability. Rosemary essential oil: provides mild nervous system regulation, especially in the maintenance stage, playing an important role in maintaining deep sleep. Lemongrass essential oil: as a component of the tail release stage, it provides respiratory system support, prolonging the sleep aid effect. The volatility differences and complementary pharmacological effects of these essential oil components allow them to be released in different stages and synergistically enhance the sleep aid effect throughout the sleep process, ultimately achieving optimal sleep aid effect.

[0021] Nucleus-shell structure and three-stage release mechanism: The coaxial electrospinning forms a nucleus-shell structure, with the shell layer using PLA / CS / PVA, the outer layer rich in hydrophilic PVA / CS, and the inner layer rich in hydrophobic PLA. In the opening stage (0-6 h): the hydrophilic region rapidly absorbs water and swells, the micropores instantaneously increase, and the release rate is 1.0%-1.2% / h; in the maintenance stage (6-48 h): after swelling equilibrium, the designed pore size is restored, and the diffusion is synergistically regulated by hydrogen bonding and van der Waals force, with a rate of 0.6%-0.8% / h; in the tail release stage (48-72 h): the remaining essential oils are deeply embedded in the hydrophobic PLA microdomain, limited by dissolution kinetics and pore resistance, with a rate of 0.3%-0.5% / h. Combined with the micropore design of the nucleus-shell structure, essential oils are released in different stages according to their volatility, with high-volatility essential oils such as lavender and chamomile being released first in the opening stage, followed by low-volatility essential oils such as rosemary and lemongrass, ensuring the persistence of calming, soothing, and deep sleep effects during the sleep process. The mutual complementation of essential oil components and the coordinated pharmacological effects make the overall effect more balanced and stable.

[0022] The present application provides a preparation method of a nucleus-shell coaxial nanofiber membrane, comprising the following steps: S1, preparing the inner core spinning solution: mixing essential oil combinations in proportion and dispersing them in a 3-8% PVA / ethanol solution, then ultrasonicating to obtain the inner core spinning solution; S2, preparing the outer shell spinning solution: dissolving polylactic acid, chitosan, and polyvinyl alcohol in an organic solvent in a mass ratio, then stirring to obtain the outer shell spinning solution; S3, coaxial electrospinning: setting the inner core spinning solution flow rate to 0.3-1 mL / h and the outer shell spinning solution flow rate to 0.5-1 mL / h, under the action of an electric field with a voltage of 12-20 kV, a distance of 15-22 cm, and a humidity of 25%-50%, to prepare the nanofiber with a nucleus-shell structure, and then collecting the fiber into a membrane after deposition. S4, curing treatment: drying and curing the obtained fiber membrane to remove residual solvent, thereby obtaining a core-shell nano-fiber membrane.

[0023] Preferably, in S1, 3-5% PVA / ethanol solution is used for ultrasonic treatment for 8-10 min.

[0024] More preferably, 5% PVA / ethanol solution is used.

[0025] Preferably, in S2, the organic solvent is a mixed solution of halogenated hydrocarbon solvent and alcohol solvent, and the volume ratio of halogenated hydrocarbon solvent to alcohol solvent is (2-4):(1-2).

[0026] Further, the organic solvent used for the shell spinning solution is used to dissolve PLA (hydrophobic) and part of CS / PVA (hydrophilic) at the same time, to improve the compatibility of the multi-component system, and to form a microporous structure with a narrow pore size distribution in the electrospinning process by regulating the solvent evaporation behavior, thereby ensuring high encapsulation rate of essential oils and three-stage stable release performance. Based on the technical performance requirements and experimental feasibility optimization results of the previous research, it is shown that the use of a mixed solution of halogenated hydrocarbon solvent and alcohol solvent can effectively solve the compatibility problem of the PLA / CS / PVA blend system. Among them, the halogenated hydrocarbon solvent as the main solvent provides strong solubility and reduces the surface tension of the system; the alcohol solvent as a dissolving and evaporation behavior regulator is conducive to regulating the solution conductivity, jetting stability and drying film formation rate, so as to obtain a dense and uniform pore size distribution (50-120 nm) microporous network under the set humidity (30%-40%) and electrospinning parameters. Without departing from the concept of the present application, the halogenated hydrocarbon solvent is preferably chloroform, and other halogenated hydrocarbon solvents (such as dichloromethane) with similar solubility parameters and volatility characteristics can be used for equivalent replacement, and the alcohol solvent is preferably ethanol, and low molecular alcohols (such as methanol, isopropyl alcohol) can be used for equivalent replacement.

[0027] Preferably, the concentration of the inner core spinning solution is 1-5 wt%, and the concentration of the shell spinning solution is 3-8 wt%.

[0028] More preferably, the concentration of the inner core spinning solution is 4 wt%, and the concentration of the shell spinning solution is 5 wt%.

[0029] More preferably, in S2, chloroform / ethanol is used as the organic solvent, and the volume ratio is (2-4):(1-2).

[0030] Further preferably, chloroform / ethanol mixed solvent is used as the organic solvent, and the volume ratio is 3:2 (v / v).

[0031] Preferably, in S3, the voltage is 15-20 kV, the distance is 15-20 cm, and the humidity is 30%-40%.

[0032] The application provides application of the above-mentioned core-shell coaxial nanofiber membrane in sleep aiding and tranquilization, or in preparation of a product for improving insomnia and sleep aiding and tranquilization.

[0033] The application also provides a product containing the above-mentioned coaxial nanofiber membrane.

[0034] Preferably, the product is a sleep aiding pillow, a smart fragrance patch or a sleep aiding mask.

[0035] The application has the following beneficial effects: The application provides a lavender-containing sleep aiding and tranquilization essential oil sustained-release nanofiber membrane, which is prepared by coaxial electrospinning technology and has a coaxial core-shell structure, the shell layer is a PLA / chitosan / polyvinyl alcohol ternary blending system, and the core layer is a specific essential oil combination dispersion system. The prepared nanofiber membrane forms a narrow pore size distribution micropore network with a peak value of 50-120 nm, improves the specific surface area and porosity. The application improves the oil carrying capacity and encapsulation efficiency of the fiber membrane through the controllable micropore structure of the core-shell structure and the component matching mechanism, realizes three-stage precise release, has more stable three-stage release rates of opening, maintaining and tailing, significantly reduces the late release speed of the essential oil, and ensures that the essential oil components are released at different rates at different time periods, has a long duration, can effectively prolong the release effect. At the same time, the application overcomes the problems of difficulty in considering the compatibility of hydrophobic / hydrophilic components and multiple oil molecules and uncontrollable release of the existing PLA / CS / PVA blending single-layer system, can realize the synergistic release of essential oil components at different stages, and finally achieves more persistent and stable sleep aiding effect.

[0036] The application realizes time sequence release by encapsulating specific essential oil combinations and has peak-shifting and complementary effects. The specific core-shell structure design makes the essential oil present a gradient distribution inside the carrier, the high-volatility components are preferentially enriched in the inner core, and the low-volatility components form a “retarded release zone” in the outer shell, realize three-stage peak-shifting release, promote the synergistic effect of multiple essential oils, have multi-level sleep aiding effect, enhance the overall sleep aiding effect, and can better regulate each stage of sleep.

[0037] Therefore, the application not only realizes pharmacological synergy in component matching, but also realizes significant improvement of the essential oil combination release effect through specific pore size structure and core-shell gradient system at the structure design level. The application solves the compatibility problem of PLA / CS / PVA and multiple-component essential oils through nanofiber membrane structure design and phase boundary regulation mechanism, realizes precise controlled release of multiple essential oil combinations, reduces the late release speed, prolongs the release effect, and is verified by specific structure optimization and functional comparison, which strongly supports the innovativeness and industrial application value of the application, and provides more precise sustained-release essential oil products with tranquilization and sleep aiding effect. BRIEF DESCRIPTION OF DRAWINGS

[0038] Figure 1 Figure of expression results of GAD65 (a) and GABAARa1 (b) in mouse cerebral cortex, hippocampus and hypothalamus. DETAILED DESCRIPTION

[0039] The present application will be further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present application in any form. Unless otherwise specified, the reagents, methods and equipment used in the present application are conventional reagents, methods and equipment in the technical field.

[0040] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0041] Example 1 Selection of different essential oil combinations 1. Essential oil combination: Lavender essential oil, chamomile essential oil, orange flower essential oil, rosemary essential oil, and lemon grass essential oil were compounded in different proportions, and four different combinations were set, with the mass ratio of lavender: chamomile: orange flower: rosemary: lemon grass being A1 = 5:3:2:2:1, A2 = 4:3:3:2:1, A3 = 4:4:1:3:1, and A4 = 3:3:3:1:2.

[0042] Preparation of essential oil sustained-release film: essential oil combinations of the same concentration were prepared, and different essential oil combinations were dispersed in a 5% PVA / ethanol solution, ultrasonicated for 10 min to obtain a core spinning solution with a concentration of 4wt%; PLA, CS, and PVA were dissolved in chloroform / ethanol (volume ratio 3:2) at a mass ratio of 4:4:2, stirred for 10 h to obtain a shell spinning solution with a concentration of 5wt%; the core spinning solution and the shell spinning solution were respectively injected into the inner tube and the outer tube syringes of the coaxial electrospinning device, the core flow rate was set to 0.3 mL / h, and the shell flow rate was set to 0.5 mL / h; a voltage of 15 kV was used, the distance between the nozzle and the receiving plate was set to 18 cm, and the environmental humidity was controlled at 30%-40%. Under the action of the electric field, the double-liquid coaxial nozzle formed charged droplets, which were stretched by electrostatic traction to form nanofibers with a core-shell structure; the fibers were deposited on the receiving plate covered with aluminum foil and collected into a film; then the film was dried at room temperature and cured in a 50°C oven for 2 h to remove residual solvents, and a nanofiber film was obtained.

[0043] 2. Evaluation index: Encapsulation efficiency, segmented release rate (0-6 h, 6-48 h, 48-72 h), in vitro GC volatility curve, and mouse sleep model efficacy.

[0044] 3. Test method: ① Encapsulation efficiency determination method: Take a pre-weighed (10 mg) nanofiber membrane sample, place it in 10 mL of absolute ethanol, and ultrasonically extract for 30 minutes to ensure complete release of the essential oil into the solvent. The concentration of the representative component (such as linalool) in the solution is determined by gas chromatography (GC-FID, Agilent 7890A), and the total content is converted by combining the standard curve. The encapsulation efficiency calculation formula is as follows: Encapsulation efficiency = (measured essential oil content / theoretical added essential oil amount) x 100%.

[0045] ② Subsection release rate determination method: Place the same size membrane sample (1 cm x 1 cm) in a 25 mL closed bottle, and place it at 25°C and 50% relative humidity. Take gas phase samples at 0 h, 6 h, 48 h, and 72 h, and detect the target component concentration by GC-FID. The average release rate in each time period is calculated according to the following formula: R = [(C t -C t-1 ) / (t-t -1 )] x 100%.

[0046] ③ In vitro GC volatile curve test method: Refer to the release rate experiment, continuously monitor the concentration of linalyl acetate and 1,8-cineole in the sample at each time point, and draw the volatile rate-time curve. Each group has 3 parallel samples, and the average value is plotted. The results are used to judge the release rule and residual change trend.

[0047] ④ Mice sleep aid model efficacy test method: Test animals: ICR mice, half male and half female, body weight 18-22 g, adapt to the environment for 3 days, then randomly divided into groups, 10 mice per group.

[0048] Treatment: Cut the same amount of essential oil sustained-release film for each group and place it in the mouse cage for 30 minutes. Then intraperitoneally inject sodium pentobarbital at a dose of 0.045 g / kg.

[0049] Index recording: Sleep latency: The time from injection to the mouse's transition from activity to no voluntary activity.

[0050] Total sleep time: Timing from the start of loss of righting reflex to recovery of reflex.

[0051] Statistical method: Single factor analysis of variance (ANOVA) was performed using SPSS 23.0 software, with a significance level of p <0.05.

[0052] 4. Screening results The results are shown in Table 1 below. From the comparison results, it can be seen that by adjusting the ratio of the compound essential oil, the release effect and sleep aid effect are obviously different. Although the initial release rate of A2 group is slightly higher than that of A1, the release is unstable in the middle and late stages, and the overall sleep aid effect is inferior to that of A1. The package rate and performance of A3 and A4 ratios are significantly lower than those of A1 group. Therefore, A1 (5:3:2:2:1) is the optimal ratio with the best comprehensive performance, and its synergistic sleep aid effect and stable release are better than those of other ratios.

[0053] Table 1 Release and sleep aid effect of different essential oil combinations

[0054] Example 2 Preparation of core-shell nanofiber membrane S1, prepare the inner core spinning solution: disperse the essential oil combination (the combination of Example 1, the mass ratio is 5:3:2:2:1) in a 5% PVA / ethanol solution, ultrasonic for 10 min, to obtain the inner core spinning solution, the concentration is 4wt%; S2, prepare the shell spinning solution: dissolve PLA, CS, and PVA in chloroform / ethanol (volume ratio 3:2) at a mass ratio of 4:4:2, stir for 10 h, to obtain the shell spinning solution, the concentration is 5wt%; S3, coaxial electrospinning: the inner core spinning solution and the shell spinning solution are respectively filled into the inner tube and the outer tube syringe of the coaxial electrospinning device, the inner core flow rate is set to 0.3 mL / h, and the shell flow rate is set to 0.5 mL / h; use a voltage of 15 kV, the distance between the nozzle and the receiving plate is set to 18 cm, and the environmental humidity is controlled at 30%-40%. Under the action of the electric field, the double-liquid coaxial nozzle forms charged droplets, which are stretched by electrostatic traction to form nanofibers with core-shell structure; the fibers are deposited on the receiving plate covered with aluminum foil, and the membrane is collected; S4, post-processing: after room temperature quick drying, 50°C oven curing for 2 h, remove the residual solvent, to obtain the core-shell structure nanofiber membrane.

[0055] Example 3 Preparation of different essential oil nanofiber membranes Based on the previous pre-experimental research, the mixed solution of halogenated hydrocarbon solvents and alcohol solvents can effectively solve the compatibility problem of PLA / CS / PVA blending system, improve the compatibility of multi-component system, and at the same time, by regulating the evaporation behavior of the solvent, the micro-porous structure with narrow pore size distribution is formed in the electrospinning process, so as to ensure the package rate and release of essential oil.

[0056] Referring to the nanofiber membrane preparation method of Example 2, replace different essential oil components and the proportion of the shell spinning solution to prepare different nanofiber membranes, and then measure the pore size, loading efficiency, initial release rate, and maintenance stage parameters of the different nanofiber membranes. The method for measuring is as described in Example 1.

[0057] The measurement results are shown in Table 2. Example 2 forms a uniform microporous network with an average pore size of 100 ± 20 nm (PDI < 0.2) under the structure of PLA:CS:PVA = 4:4:2, with a loading efficiency of ≥85%, and a release rate of 1.1% / h in the initial stage (0-6 h), 0.7% / h in the middle stage (6-48 h), and 0.4% / h in the tail stage (48-72 h), which reflects good segmented release stability. The comparison groups 1-4 show different degrees of burst release or insufficient release in terms of pore size or release, indicating that the structure ratio has a significant impact on the release behavior.

[0058] Table 2 Measurement results of different comparison groups of nanofiber membranes

[0059] Although the loading efficiency and release rate of some essential oil ratios in comparison groups 3-5 in Table 2 remain at a good level within a certain range, this does not mean that the carrier has no selectivity or "can be replaced arbitrarily" for essential oil components. In fact, the core-shell structure of Example 2 combined with fine pore size control mechanism and specific essential oil combination can achieve differentiated spatial distribution and release path design under the conditions of different essential oil volatility and polarity. High-volatility essential oils such as lavender and chamomile gather towards the core and are stably loaded by hydrophilic PVA; low-volatility essential oils such as lemongrass and rosemary tend to be in the hydrophobic PLA region and are delayed in release due to limited diffusion channels in the shell.

[0060] This core-shell structure + component adaptation mechanism is different from traditional composite carriers. Traditional systems often cannot accurately match the diffusion resistance according to the differences in essential oil components due to single structure or interlayer separation problems, resulting in essential oil component burst release (high volatility), uneven component migration in the carrier (poor compatibility), and chaotic efficacy release timing (destroying drug efficacy synergy).

[0061] This example solves the above technical problems through the structural gradient design of PLA, CS, and PVA, and exhibits high stability and rhythm control in the release of multi-component essential oils. This is the specific advantage of this example.

[0062] Example 4 Preparation of nanofiber membrane S1, prepare the core spinning solution: disperse the essential oil combination A1 (5:3:2:2:1) of Example 1 in a 5% PVA / ethanol solution at a concentration of 4wt%; S2, preparation of shell spinning solution: PLA, CS, PVA were dissolved in chloroform / methanol (3:2) at a ratio of 4:4:2, and the concentration was 5wt%; S3, coaxial electrospinning: the inner core spinning solution and the shell spinning solution were respectively loaded into the inner tube and the outer tube injectors of the coaxial electrospinning device, the inner core flow rate was set to 0.3 mL / h, and the shell flow rate was set to 0.5 mL / h; the voltage used was 15 kV, the distance between the nozzle and the receiving plate was set to 18 cm, and the environmental humidity was controlled at 30%-40%. Under the action of the electric field, the double-liquid coaxial nozzle formed charged droplets, which were stretched by electrostatic traction to form nanofibers with a core-shell structure; the fibers were deposited on the receiving plate covered with aluminum foil and collected into a membrane; S4, curing treatment: the obtained fiber membrane was subjected to low-temperature drying or cross-linking curing treatment at 50°C to obtain a stable structure of the slow-release fiber membrane.

[0063] Example 5 Preparation of nanofiber membrane S1, preparation of inner core spinning solution: the essential oil combination A1 (5:3:2:2:1) of Example 1 was dispersed in a 5% PVA / ethanol solution, and the concentration was 4wt%; S2, preparation of shell spinning solution: PLA, CS, PVA were dissolved in dichloromethane / ethanol (3:2) at a ratio of 4:4:2, and the concentration was 5wt%; S3, coaxial electrospinning: the inner core spinning solution and the shell spinning solution were respectively loaded into the inner tube and the outer tube injectors of the coaxial electrospinning device, the inner core flow rate was set to 0.3 mL / h, and the shell flow rate was set to 0.5 mL / h; the voltage used was 15 kV, the distance between the nozzle and the receiving plate was set to 18 cm, and the environmental humidity was controlled at 30%-40%. Under the action of the electric field, the double-liquid coaxial nozzle formed charged droplets, which were stretched by electrostatic traction to form nanofibers with a core-shell structure; the fibers were deposited on the receiving plate covered with aluminum foil and collected into a membrane; S4, curing treatment: the obtained fiber membrane was subjected to low-temperature drying or cross-linking curing treatment at 50°C to obtain a stable structure of the slow-release fiber membrane.

[0064] Comparative Example 1 Essential oil group without encapsulation Directly use the essential oil combination A1 (5:3:2:2:1) of Example 1, directly smear on the surface of the ordinary pillow inner core, without using the electrospinning process for encapsulation.

[0065] Comparative Example 2 Essential oil group directly sprayed on the surface of the substrate Mix lavender essential oil (concentration of 5%) with non-woven fabric substrate, the ratio of essential oil to substrate is 1:1. Spray the mixture on the surface of the non-woven fabric to form an essential oil coating.

[0066] This comparative group is used to test the unencapsulated essential oil group and the volatile release rate of essential oil on the substrate surface, and to compare the slow-release effect of encapsulating essential oil using the electrospinning process in Example 2, to verify whether the electrospinning technology can effectively control the release rate of essential oil.

[0067] Test Example 1 Volatile Release Rate Test The essential oil release rate of different samples was analyzed using a gas chromatograph (GC), and the test steps were as follows: 1. Sample preparation: Comparative groups 1-4 in Example 1, Example 2, Comparative Example 1 and Comparative Example 2 were cut into 1 cm x 1 cm sample blocks, respectively, and placed in airtight 25 mL glass bottles, with 3 replicates for each group.

[0068] 2. Storage conditions: All samples were placed in a constant temperature incubator at 25°C and 50% relative humidity, avoiding direct sunlight and air flow disturbance.

[0069] 3. Determination time points: At 0 h, 6 h, 12 h, 24 h, 48 h, 72 h, 96 h and 120 h, respectively, samples were taken and the volatile component concentration in the bottle was analyzed using a gas chromatograph.

[0070] 4. Detection parameters: The main components in lavender essential oil, such as linalyl acetate and linalool, were selected as representative indicators for quantitative analysis by internal standard method.

[0071] 5. Results statistics: Calculate the relative volatile release rate (%) and residual rate of essential oil components, draw the volatile amount-time curve graph, and compare the slow-release performance and volatile stability of different samples. According to the experimental data, the durability of the slow-release effect of different essential oil combinations and the difference from the comparative group were evaluated. As a boundary reference, Comparative Example 1 (unencapsulated) and Comparative Example 2 (sprayed on the substrate surface) were used to evaluate the volatile baseline without electrospinning encapsulation, to verify the improvement of the controllability of the release rate by electrospinning technology.

[0072] The results of the determination are shown in Table 3, which shows that the volatile-time curve of Example 2 (core-shell fiber membrane) is relatively flat as a whole from 0 to 120 h, and still maintains a residual rate of >50% at 72 h, embodying good durability and stability; compared with the comparative groups with different structural parameters, it has better slow-release ability in the middle and later stages. In terms of structural factors, the comparative group 1 with too small pore size (50-80 nm) is limited in the initial release and has a low rate in the maintenance stage; and the comparative group 2 with too large pore size (150-200 nm) has more obvious burst release in the early stage, and the residual rate is about 40% at 72 h, which are all not conducive to long-acting and stable release. Compared with the above, the pore size window of 100±20 nm adopted in Example 2 balances the initial release and the maintenance in the middle and later stages. At the same time, the formula factors also have an influence: under the condition of keeping the core-shell structure and similar pore size, the shell system of PLA:CS:PVA=4:4:2 cooperates with the A1 essential oil ratio (5:3:2:2:1) to show higher encapsulation (≥85%) and more stable segmented rate, which is better than several comparative groups with adjusted ratios.

[0073] Table 3 Volatility results of different nanofiber membranes

[0074] Test Example 2 Verification of three-stage release effect In order to verify the relationship between the structural parameters and the release behavior of the nanofiber membrane of the application, in addition to the release rate test, the pore size distribution, specific surface area and porosity of the fiber membrane were tested, as follows: ①Pore size distribution and average pore size test: a full-automatic nitrogen adsorption-desorption instrument (Micromeritics ASAP2020) was used, the specific surface area of the sample was analyzed by BET method, and the pore size distribution was obtained by combining BJH model. The results show that the peak pore size of the nanofiber membrane prepared in Example 2 is 50-120 nm, and the PDI is <0.2.

[0075] ②Specific surface area test: BET (Brunauer-Emmett-Teller) method was used under liquid nitrogen condition, the adsorption gas was N2, and the test pressure range was 0.01-0.3 P / P0. The results show that the specific surface area of the nanofiber membrane prepared in Example 2 is >60 m 2 / g.

[0076] ③Porosity test: mercury intrusion porosimetry was used to determine the porosity. The results show that the porosity of the nanofiber membrane prepared in Example 2 is greater than 65%.

[0077] At the same time, a homogeneous comparative group without core-shell structure (non-coaxial "homogeneous comparative group without core-shell structure" fiber membrane prepared by single needle·single liquid electrospinning) was set. (1) Solution preparation: ① Solution A (hydrophobic phase) was prepared by dissolving PLA in chloroform / ethanol (3:2, v / v) with solid content of about 8%±0.5%, and stirring for 10 h until clear; ② Solution B (hydrophilic phase) was prepared by dissolving PVA in ethanol / water (70:30, v / v) to obtain a 5% (w / w) PVA solution, and adding CS (consistent with the mass fraction in Example 2) to the solution, and then dispersing the compound essential oil (same ratio as A1:5:3:2:2:1) in the solution B by ultrasonic for 10 min; ③ Phase combination and emulsification: under the shearing condition of 8000-12000 rpm, solution A was added to solution B dropwise for 5-10 min to form a stable emulsion type spinning solution; to improve the emulsion stability, a non-ionic emulsifier (such as Span 80) corresponding to 0.5-1.0 wt% of the mass of the essential oil can be optionally added.

[0078] (2) Electrospinning into a film: single needle-single liquid electrospinning (non-coaxial) was adopted, and the parameters were consistent with those in Example 2: high voltage 15 kV, push injection flow rate 0.8 mL / h, nozzle-collector plate distance 18 cm, and environmental humidity 30%-40%; after the collection into a film, post-treatment was performed.

[0079] (3) Post-treatment: room temperature quick drying, followed by oven curing at 50 ℃ for 2 h to remove residual solvent, to obtain the "non-core-shell homogeneous comparison group" fiber membrane.

[0080] The above parameters and the key conditions used are consistent with the disclosure of Example 2, only the coaxial structure is cancelled and replaced by the single liquid method, to ensure the fairness of "changing only the structure, not the formula": the solvent and stirring time are from S2 in Example 2 (chloroform / ethanol 3:2, stirring for 10 h), and the electrospinning and curing conditions are from S3 / S4 (15 kV, 18 cm, 30-40% RH, 50 ℃ curing for 2 h). Then, Example 2 (core-shell fiber membrane) and the homogeneous comparison group (without core-shell structure) are subjected to three-stage release verification, the determination method is the same as that in Example 1, and samples are taken at 0, 6, 24, 48, 72 h, the contents of linalyl acetate in lavender essential oil and 1,8-eucalyptol in rosemary essential oil are determined by gas chromatography (GC-FID), and the release rates at each stage are calculated.

[0081] The determination results are shown in Table 4, which shows that Example 2 exhibits obvious three-stage segmented release characteristics: the high-volatility components are rapidly released in the initial release stage, the rate decreases in the maintenance stage, and the low-volatility components are continuously released in the tail release stage; the homogeneous comparison sample has no segmented characteristics, and the rates at each stage are close, the release rate is stable, and although the preparation by adding additional emulsifiers balances the hydrophobic / hydrophilic components and the compatibility between multiple oil molecules in the PLA / CS / PVA blended monolayer system, the release is still uncontrollable, which further proves that the coaxial core-shell structure prepared by the present application plays a decisive role in achieving three-stage staggered release.

[0082] Table 4 Three-stage release data comparison

[0083] Test Example 3 Sleep-aiding effect test Fifty healthy mice (half male and half female) were selected, and the mice used were clean grade ICR strain (Kunming species), half male and half female, weighing 18-22 g, purchased from Guangzhou Experimental Animal Center (qualification certificate number: SCXK (Yue) 2023-0002). They were randomly divided into 6 groups to test the sleep-aiding effect of different essential oil formulations. Each group of mice was fasted for 1 hour before the experiment and treated as follows: 1. Control group: Put a cotton ball soaked in 0.5 g of normal saline into the mouse cage as a control.

[0084] 2. Positive drug group: Gavage with Yixinning Shen tablets 1.58 g powder / kg for drug comparison verification.

[0085] 3. High-dose essential oil group: Place a cotton ball that has absorbed 1 g of essential oil (containing Example 2 nanofiber membrane) into the mouse cage.

[0086] 4. Medium-dose essential oil group: Place a cotton ball that has absorbed 0.5 g of essential oil (containing Example 2 nanofiber membrane) into the mouse cage.

[0087] 5. Low-dose essential oil group: Place a cotton ball that has absorbed 0.1 g of essential oil (containing Example 2 nanofiber membrane) into the mouse cage.

[0088] 6. Control drug group: No essential oil is used, only ordinary cotton balls are used.

[0089] The test results are shown in Table 5, which shows that compared with the control group, using the sustained-release nanofiber membrane of Example 2 for essential oil exposure can significantly shorten the sleep latency and prolong the total sleep time, and show a dose-dependent trend: the effect of the high-dose group is close to that of the positive drug group, the medium-dose group also has a statistically significant improvement, and the low-dose group has a smaller improvement.

[0090] Table 5 Sleep-aiding results of different nanofiber membranes

[0091] Test Example 4 Safety test Thirty healthy college student volunteers (no history of allergies) were tested for skin irritation and potential allergic reactions for 7 consecutive days. The test steps are as follows: 1. Samples: Example 2, Example 3, Example 4, Comparative Example 1, Comparative Example 2 (containing the same concentration of essential oil).

[0092] 2. Skin test: Apply the test sample (2 cm 2), and observe the skin irritation, redness, and allergic reactions within 48 hours.

[0093] 3. Adverse reaction rate: record the adverse reactions and their frequency after using each sample, and evaluate the safety of each group of samples.

[0094] 4. Subjective satisfaction score: assess the volunteers' comfort and satisfaction after using the samples through a questionnaire (score range 1-5, 1 indicating dissatisfaction, 5 indicating very satisfied). Collect the volunteers' feedback to understand the comfort and user experience of the product.

[0095] 5. Result analysis: calculate the average satisfaction of each sample based on the questionnaire feedback, and evaluate its overall safety and user experience.

[0096] The test results are shown in Table 6, which shows that the unsealed / sprayed samples (Comparative Examples 1 and 2) have a higher adverse reaction rate and lower subjective satisfaction, while the samples of the embodiments have a low overall adverse reaction rate and high satisfaction, with Example 2 performing best in terms of improving comfort and reducing irritation.

[0097] Table 6 Adverse reaction rate and satisfaction of different nanofiber membranes

[0098] Test Example 5 Effect on GAD65 and GABAARα1 expression in cerebral cortex, hippocampus and hypothalamus of mice An insomnia model was established by intraperitoneal injection of 25 mg / kg p-chlorophenylalanine (PCPA) weak alkaline saline suspension; about 28-32 h after administration, the circadian rhythm disappeared and the day-night activity continued, indicating that the modeling was successful. The mice were randomly divided into four groups: blank control group, model group (PCPA), positive control group (diazepam, DZP), and Example 2 nanofiber membrane group. The model group was not intervened; the positive control group was given DZP; the nanofiber membrane group was given aromatherapy inhalation, 7 days continuously, 1 hour per day (the nanofiber membrane loaded with essential oil was diluted with distilled water, the working solution was 3×10 -3 g / mL, and the intervention time was fixed at 8:00 every day).

[0099] After the cerebral cortex, hippocampus and hypothalamus of different mice were separated, the paraffin sections were heat repaired with sodium citrate buffer, and the S-P immunohistochemical method was used; DAB / H2O2 coloration, hematoxylin restain. Set up positive control (known positive section) and negative control (PBS instead of primary antibody) according to the instructions. Use a microscopic imaging system to collect images, and use Image-Pro Plus5.1 to calculate the integrated optical density (IOD) of GAD65 and GABAARα1 positive cells in the three brain regions.

[0100] The results are as follows Figure 1 As shown, positive expression of both indicators was observed in all three brain regions, presenting as brownish-yellow DAB staining and blue-purple counterstaining of cell nuclei; positive signals were also observed in the hippocampal dentate gyrus and pyramidal cell layer, cortical lamellar structures, and corresponding hypothalamic nuclei. Compared with the control group, the model group (PCPA) showed significantly reduced GAD65 and GABAARα1 IOD values ​​in the cerebral cortex, hippocampus, and hypothalamus. P <0.01). Compared with the model group, the IOD values ​​of the two indicators in the three brain regions of the positive control group (DZP) were significantly increased ( P <0.01. The expression of GAD65 and GABAARα1 in the three brain regions of the nanofiber membrane was also significantly upregulated ( P <0.01), the image showed an increase in brownish-yellow positive granules and deeper staining; the overall improvement was comparable to or close to that of the positive control. Continuous aromatherapy intervention with nanofiber membranes for 7 days simultaneously upregulated the expression of GAD65 and GABAARα1 in the cerebral cortex, hippocampus, and hypothalamus of insomnia model mice, promoting GABA synthesis of GAD65 and enhancing GABAARα1 receptor efficacy, thereby correcting the PCPA-induced central excitation-inhibition imbalance and improving insomnia.

[0101] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention are permitted.

Claims

1. A core-shell coaxial nanofiber membrane, characterized by, The nanofiber membrane is a coaxial core-shell structure, the shell layer is composed of polylactic acid, chitosan and polyvinyl alcohol, and the core layer is an essential oil combined dispersion system, which is prepared by coaxial electrospinning technology; The mass ratio of the polylactic acid, chitosan and polyvinyl alcohol is (3-5):(3-4):(2-3). The essential oil combined dispersion system is obtained by dispersing the essential oil combination in a 3-8% PVA / ethanol solution and then ultrasonic treatment. The essential oil combination comprises lavender essential oil, chamomile essential oil, orange flower essential oil, rosemary essential oil and lemon grass essential oil, and the mass ratio is (4-6):(2-4):(1-3):(1-3):

1. The pore size of the coaxial nanofiber membrane is 50-120 nm.

2. The core-shell coaxial nanofiber membrane according to claim 1, wherein, The mass ratio of the polylactic acid, chitosan and polyvinyl alcohol is 4:(3-4):(2-3).

3. The core-shell coaxial nanofiber membrane according to claim 1, wherein, The mass ratio of the lavender essential oil, chamomile essential oil, orange flower essential oil, rosemary essential oil and lemon grass essential oil in the essential oil combination is 5:(2-3):(2-3):(2-3):

1.

4. The method of producing the core-shell coaxial nanofiber film according to any one of claims 1 to 3, characterized by, The steps include: S1, preparing the inner core spinning solution: mixing the essential oil combination in a proportion, dispersing in a 3-8% PVA / ethanol solution, and then ultrasonic treatment to obtain the inner core spinning solution; S2, preparing the outer shell spinning solution: dissolving the polylactic acid, chitosan and polyvinyl alcohol in an organic solvent in a mass ratio, and then stirring to obtain the outer shell spinning solution; S3, coaxial electrospinning: setting the flow rate of the inner core spinning solution to 0.3-1 mL / h, the flow rate of the outer shell spinning solution to 0.5-1 mL / h, and the voltage to 12-20 kV, the distance to 15-22 cm, and the humidity to 25%-50% in the electric field to prepare the nanofiber with a core-shell structure, and then collecting the fiber into a membrane after deposition; S4, curing treatment: drying and curing the obtained fiber membrane to remove residual solvents, and then obtaining the coaxial nanofiber membrane with a core-shell structure.

5. The preparation method according to claim 4, characterized in that, In S1, 3-5% PVA / ethanol solution is ultrasonic treated for 8-10 min.

6. The preparation method according to claim 4, characterized in that, In S2, the organic solvent is a mixed solution of halogenated hydrocarbon solvents and alcohol solvents, and the volume ratio of the halogenated hydrocarbon solvents to the alcohol solvents is (2-4):(1-2).

7. The preparation method according to claim 4, characterized in that, In S3, the voltage is 15-20 kV, the distance is 15-20 cm, and the humidity is 30%-40%.

8. Use of the core-shell coaxial nanofiber membrane according to any one of claims 1-3 for helping sleep and calming the nerves, or for preparing a product for improving insomnia and helping sleep and calming the nerves.

9. A product characterized by, The product contains the coaxial nanofiber membrane according to any one of claims 1-3.

10. The product of claim 9, wherein, The product is a sleep-aiding pillow, a smart fragrance patch or a sleep-aiding face mask.

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