Compound essential oil microcapsule sustained-release preparation for improving sleep quality

Abstract

This invention relates to the field of traditional Chinese medicine preparations, specifically to a compound essential oil microcapsule sustained-release preparation for improving sleep quality. It comprises the following raw materials in the indicated weight percentages: dry extract powder, osmanthus extract, acorus calamus essential oil, sandalwood essential oil, natural borneol, sustained-release microcapsule encapsulating agent, transdermal penetration enhancer, and herbal plants, with the remainder being a solvent. In this invention, the synergistic effect of natural borneol and the transdermal penetration enhancer breaks through the skin barrier, achieving highly efficient and rapid delivery of active ingredients. Furthermore, the sustained-release microcapsule technology precisely encapsulates the essence of traditional Chinese medicine formulas and compound essential oils, forming a dual-phase release characteristic that combines rapid and long-lasting effects. The entire process avoids the first-pass effect in the liver and gastrointestinal degradation, perfectly integrating the systemic conditioning advantages of traditional Chinese medicine formulas with the rapid neuromodulation effect of aromatic molecules. This significantly improves bioavailability and onset speed, achieving multi-target, non-drug-dependent natural regulation of the sleep physiological process.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, and more specifically, to a compound essential oil microcapsule sustained-release preparation for improving sleep quality. Background Technology

[0002] The "Calming the Mind and Saving Sleep Formula" (from *Shengji Zonglu*) is composed of ginseng, poria cocos, and polygala tenuifolia, among other ingredients. It has the effects of calming the mind, stabilizing the spirit, invigorating qi, and relieving anxiety, and is suitable for symptoms such as insomnia, excessive dreaming, and easy awakening. This formula uses ginseng, poria cocos, and polygala tenuifolia as the principal herbs, supplemented with dragon's teeth, acorus tatarinowii, and other medicinal materials. It improves sleep quality by harmonizing qi and blood and facilitating communication between the heart and kidneys.

[0003] However, in current clinical applications of the Zhenxin Shengshui formula, due to the traditional oral administration method, the active ingredients such as ginseng, poria cocos, and polygala tenuifolia are easily degraded by digestive enzymes and affected by the first-pass effect in the gastrointestinal tract, resulting in a significant decrease in their bioavailability and a prolonged onset time of more than 14 days. Furthermore, the inherent bitter taste of the herbs and the requirement for long-term use further reduce patient compliance, making it difficult for the formula to fully exert its calming, stabilizing, and tranquilizing effects, and especially failing to meet the urgent need of modern people for rapid sleep aids.

[0004] On the other hand, existing single-ingredient essential oil sleep aids, such as osmanthus extract and calamus essential oil, while possessing certain sedative or mind-clearing effects, lack synergy with the multi-component formulations found in traditional medicine due to their singular target. Furthermore, most commercially available sleep aids rely on chemically synthesized ingredients or oral dosage forms, with transdermal absorption products being scarce, making it impossible to achieve both rapid and long-lasting effects through skin administration. Summary of the Invention

[0005] The purpose of this invention is to solve the problems that existing sleep aids generally suffer from, such as slow onset of action, low bioavailability, and difficulty in achieving both rapid and long-lasting effects.

[0006] The purpose of this invention is to provide a compound essential oil microcapsule sustained-release formulation for improving sleep quality. This microcapsule sustained-release formulation takes effect rapidly through a multi-target synergistic mechanism, improves bioavailability, and thus effectively improves sleep.

[0007] To achieve the above objectives, the present invention aims to provide a compound essential oil microcapsule sustained-release formulation for improving sleep quality, comprising the following raw materials in the indicated weight percentages: The ingredients include: 1-4% dry powder, 0.001-0.250% osmanthus extract, 0.01-0.30% acorus calamus essential oil, 0.001-0.300% sandalwood essential oil, 0.05-0.15% natural borneol, 5-10% sustained-release microcapsule encapsulation agent, 3-6% transdermal penetration enhancer, 0.1-1.5% herbal plants, and the remainder being solvent.

[0008] As a further improvement to this technical solution, the dry ointment powder is obtained by mixing Polygala tenuifolia, Alpinia oxyphylla and Acorus calamus, followed by water decoction, concentration, alcohol precipitation and spray drying.

[0009] As a further improvement to this technical solution, the mass ratio of Polygala tenuifolia, Alpinia oxyphylla and Acorus tatarinowii in the dry ointment powder is 6:1:1.

[0010] As a further improvement to this technical solution, the herbaceous plant comprises the following raw materials in the following weight percentages: The ingredients are: 12% jujube seed, 8% acorus calamus, 15% osmanthus, 20% lavender, 18% cypress seed, 15% Roman chamomile, 7% sandalwood, and 5% bergamot.

[0011] As a further improvement to this technical solution, the cypress seed kernel is a processed cypress seed kernel, and the Roman chamomile is Roman chamomile essential oil, wherein the content of bisabolol is not less than 3.0%.

[0012] As a further improvement to this technical solution, the sustained-release microcapsule encapsulating agent is one of chitosan, sodium alginate, or cyclodextrin.

[0013] As a further improvement to this technical solution, the transdermal penetration enhancer is either oleic acid or menthol.

[0014] As a further improvement to this technical solution, the natural borneol is extracted from the branches and leaves of camphor tree by steam distillation.

[0015] As a further improvement to this technical solution, the solvent is either water or ethanol.

[0016] In this invention, the synergistic effect of natural borneol and transdermal penetration enhancers breaks through the skin barrier to achieve efficient and rapid delivery of active ingredients. Furthermore, sustained-release microcapsule technology is used to precisely encapsulate the essence of traditional prescriptions and compound essential oils, forming a dual-phase release characteristic that combines rapid and long-lasting effects.

[0017] The entire process avoids the first-pass effect of the liver and the degradation of the gastrointestinal tract, while perfectly integrating the systemic conditioning advantages of traditional Chinese medicine prescriptions with the rapid neuromodulation effect of aromatic molecules. Thus, it achieves multi-target, non-drug-dependent natural regulation of the sleep physiological process while significantly improving bioavailability and onset speed.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: This compound essential oil microcapsule sustained-release formulation for improving sleep quality uses natural borneol and a complex transdermal penetration enhancer to form a rapid-acting penetration engine. Natural borneol, with its small molecular structure and high lipid solubility, disturbs the lipid bilayer arrangement of the stratum corneum of the skin, opening up transdermal channels for subsequent active ingredients. At the same time, osmanthus extract, acorus calamus essential oil, and sandalwood essential oil reach the central limbic system through the olfactory pathway, instantly regulating the release of GABAergic neurotransmitters to achieve a rapid initial calming and soothing effect. The above-mentioned active ingredients and sustained-release microcapsule encapsulation agents are used to construct a nanoscale microcapsule primary emulsion, which forms a reservoir on the skin surface. This not only protects the volatile components from premature loss, but also controls the release rate through a pH response mechanism. Furthermore, the water-soluble active ingredients in the dry powder, together with components such as jujube seed saponins and cypress seed oil extracted from herbal plants, work synergistically to continuously act on the 5-HT system and the meridian pathways connecting the heart and kidneys, thus consolidating the calming effect. This formulation utilizes three major mechanisms—transdermal-olfactory dual-pathway delivery, microencapsulated sustained release, and multi-target synergy—to overcome the first-pass effect bottleneck of traditional oral formulations, successfully achieving both rapid and long-lasting effects, thereby improving bioavailability and completely resolving the technical dilemma of existing sleep aids being slow to take effect and having short-lived effects. Attached Figure Description

[0019] Figure 1 A schematic diagram showing the scavenging rate of DPPH free radicals by osmanthus extract at different test concentrations; Figure 2 A schematic diagram illustrating the inhibitory effect of osmanthus extract on non-enzymatic glycosylation. Figure 3 This is a schematic diagram illustrating the inhibitory effect of osmanthus extract on MMP-1 activity. Detailed Implementation

[0020] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] The purpose of this invention is to provide a compound essential oil microcapsule sustained-release formulation for improving sleep quality, comprising the following raw materials in the indicated weight percentages: The ingredients include: 1-4% dry powder, 0.001-0.250% osmanthus extract, 0.01-0.30% acorus calamus essential oil, 0.001-0.300% sandalwood essential oil, 0.05-0.15% natural borneol, 5-10% sustained-release microcapsule encapsulation agent, 3-6% transdermal penetration enhancer, 0.1-1.5% herbal plants, and the remainder being solvent.

[0022] In this invention's sustained-release formulation, natural borneol serves as a "guide" ingredient, leveraging its superior transdermal absorption capabilities to rapidly open absorption channels. Synergistically, it combines the sedative effects of osmanthus extract, the stimulating effects of calamus oil, and the calming effects of sandalwood oil, targeting the central nervous system through both olfactory and transdermal pathways for rapid onset of action. Sustained-release microcapsules encapsulate the volatile essential oils and water-soluble components of the dry powder, forming a drug reservoir on the skin surface. This allows for the continuous and gentle release of active ingredients, extending the duration of action to 6-8 hours and effectively preventing nighttime awakenings.

[0023] In addition, this composition combines traditional Chinese medicine formulas (dry ointment powder) with modern aromatherapy (compound essential oils), and acts on multiple aspects such as the GABAergic system, 5-HT system, and regulation of Qi and blood, and communication between the heart and kidneys, to achieve comprehensive sleep conditioning without drug dependence, fundamentally solving the problem of single-component single-target and limited efficacy.

[0024] The aforementioned dry powder is obtained by mixing Polygala tenuifolia, Alpinia oxyphylla (the fruit of Alpinia oxyphylla, a plant in the ginger family), and Acorus calamus, followed by decoction, concentration, alcohol precipitation, and spray drying.

[0025] The mass ratio of Polygala tenuifolia, Alpinia oxyphylla, and Acorus tatarinowii in the dry extract powder is 6:1:1.

[0026] This dry extract powder formula is derived from a classic calming prescription, with the three ingredients in a 6:1:1 ratio, creating a well-structured composition that works synergistically to calm the mind, stabilize the spirit, and harmonize the heart and kidneys. Furthermore, it employs a modern extraction process of "water decoction → concentration → alcohol precipitation → spray drying," which efficiently enriches the active ingredients such as polygala saponins, alpinia oxyphylla volatile oil, and acorus tatarinowii volatile oil, while removing most macromolecular impurities such as starch and protein. The resulting dry extract powder has higher purity and better solubility, making it more suitable for transdermal formulations, and significantly improving bioavailability compared to traditional decoctions.

[0027] In addition, the herbal plants include the following raw materials in the following weight percentages: The ingredients are: 12% jujube seed, 8% acorus calamus, 15% osmanthus, 20% lavender, 18% arborvitae seed, 15% Roman chamomile, 7% sandalwood, and 5% bergamot. The arborvitae seed is processed arborvitae seed, and the Roman chamomile is Roman chamomile essential oil, in which the content of bisabolol is not less than 3.0%.

[0028] The herbal formula creates a synergistic calming aroma matrix. Jujube seed and cypress seed enhance the heart-nourishing and calming effects; lavender and Roman chamomile provide powerful sedative and anti-anxiety support; osmanthus and bergamot offer soothing aromas and regulate mood; and the combination of calamus and sandalwood strengthens the effects of opening the mind and calming the nerves.

[0029] Among them, the processing of cypress seed can reduce its laxative side effects, making its medicinal properties more focused on "nourishing the heart and calming the mind", thus improving the safety of the preparation and focusing on its core efficacy; the use of Roman chamomile essential oil with a content of no less than 3.0% of the core soothing ingredient bisabolol ensures that the raw material has stable and strong anti-inflammatory and sedative biological activity, which is the key guarantee for the preparation to exert a reliable and immediate soothing effect.

[0030] The sustained-release microcapsule encapsulating agent is one of chitosan, sodium alginate, or cyclodextrin.

[0031] Chitosan, sodium alginate, and cyclodextrin are all natural, biocompatible polymers. Chitosan / sodium alginate can form stable composite microcapsules through electrostatic interactions, achieving high encapsulation efficiency and intelligent release in response to the skin's pH level. Their unique cavity structure effectively encapsulates essential oil molecules, significantly reducing their evaporation rate and improving water solubility. These materials together construct a reliable sustained-release system, effectively overcoming the volatility and instability of essential oils, ensuring product stability throughout its shelf life and long-lasting effectiveness.

[0032] The transdermal penetration enhancer is either oleic acid or menthol.

[0033] Oleic acid, as an unsaturated fatty acid, can disrupt the skin's lipid bilayer, increasing its fluidity. Menthol not only effectively promotes penetration but also has a cooling sensation and mild local analgesic effect, enhancing comfort during use. Together with natural borneol, these two components form a multi-layered, highly efficient transdermal absorption enhancement system, a core technology for achieving rapid results.

[0034] Natural borneol is extracted from the fresh branches and leaves of camphor tree through steam distillation. The main component of natural borneol obtained in this way is dextrorotatory borneol, which has better transdermal penetration and orifice-opening effects than synthetic borneol (racemic) or other plant-derived borneol. This ensures the high activity and high purity of this key "guiding" component, thereby guaranteeing the stability of the overall rapid effect of the preparation.

[0035] The solvent is either water or ethanol. Ethanol has good dissolving power and can dissolve multiple components in essential oils and dry powders simultaneously to form a homogeneous system. It also has a slight penetration-enhancing effect and can provide a rapid skin feel. Water, as the base solvent, is used to adjust the viscosity and irritation of the formulation.

[0036] The above-mentioned herbal plants were extracted by steam distillation to obtain the distillate as the aqueous phase, which was then mixed with osmanthus extract, calamus essential oil, sandalwood essential oil, natural borneol and sustained-release microcapsule encapsulation agent. The mixture was homogenized under high pressure (12000 rpm, 15 min) to prepare a microencapsulated primary emulsion. The dry ointment powder was then dispersed in the primary emulsion, and a transdermal penetration enhancer and solvent were added. After a second homogenization and emulsification, the mixture was filled into the container to obtain the compound essential oil microcapsule sustained-release preparation.

[0037] In the compound essential oil microcapsule sustained-release formulation prepared in this invention, osmanthus extract and acorus tatarinowii essential oil serve as core aromatic medicinal materials, exerting a sleep-aiding effect through a multi-target synergistic mechanism. In the osmanthus extract, linalool enhances the GABAergic effect by activating the parasympathetic nervous system in synergy with lavender; γ-decanolide stimulates the piriform cortex via the olfactory pathway to induce theta waves; ionone inhibits CRH expression in the amygdala, blocking stress responses; and phenylethanol regulates prefrontal dopamine to alleviate rumination. Acorus tatarinowii, with β-asarone as its core, prolongs slow-wave sleep by regulating NMDA receptors, enhances GABAA receptor sensitivity by α-asarone, and reduces cortisol levels by inhibiting the HPA axis; at the neurotransmitter level, it increases GABA concentration and inhibits glutamate release; at the limbic system level, it inhibits the amygdala anxiety reflex and synchronizes hippocampal theta waves; and at the circadian rhythm level, it promotes melatonin secretion and regulates core body temperature.

[0038] Its synergistic mechanism is manifested in the following ways: β-asarone and jujube seed saponins regulate the HPA axis through dual channels; linalool and linalyl acetate amplify the GABAA receptor effect; and ionone and calendula ketone jointly block the anxiety-insomnia cycle. This ultimately forms a rapid-acting and long-lasting synergistic system—the essential oil components take effect transdermally within 5 minutes, while the formula extract continuously regulates sleep structure, increasing transdermal absorption rate to 82.5%, deep sleep duration by 40%, and extending the duration of action to 6.8 hours through a microcapsule co-crystal structure.

[0039] The following specific embodiments will further illustrate the compound essential oil microcapsule sustained-release formulation for improving sleep quality provided by the present invention. Example

[0040] This embodiment provides a compound essential oil microcapsule sustained-release formulation for improving sleep quality, comprising the following raw materials in the indicated weight percentages: The ingredients are: 1% dry powder, 0.250% osmanthus extract, 0.01% acorus calamus essential oil, 0.300% sandalwood essential oil, 0.05% natural borneol, 10% sustained-release microcapsule encapsulation agent, 3% transdermal penetration enhancer, 1.5% herbal plants, and the remainder is solvent.

[0041] The dry extract powder is obtained by mixing Polygala tenuifolia, Alpinia oxyphylla and Acorus calamus in a mass ratio of 6:1:1, followed by decoction with water, concentration, alcohol precipitation and spray drying.

[0042] In addition, the herbal plants include the following raw materials in the following weight percentages: The ingredients are: 12% jujube seed, 8% acorus calamus, 15% osmanthus, 20% lavender, 18% arborvitae seed, 15% Roman chamomile, 7% sandalwood, and 5% bergamot. The arborvitae seed is processed arborvitae seed, and the Roman chamomile is Roman chamomile essential oil, in which the content of bisabolol is not less than 3.0%.

[0043] The sustained-release microcapsule encapsulating agent is chitosan; the transdermal penetration enhancer is menthol; and the natural borneol is extracted from the branches and leaves of the camphor tree via steam distillation. The solvent is ethanol.

[0044] The above-mentioned herbal plants were extracted by steam distillation to obtain the distillate as the aqueous phase, which was then mixed with osmanthus extract, calamus essential oil, sandalwood essential oil, natural borneol and sustained-release microcapsule encapsulation agent. The mixture was homogenized under high pressure (12000 rpm, 15 min) to prepare a microencapsulated primary emulsion. The dry ointment powder was then dispersed in the primary emulsion, and a transdermal penetration enhancer and solvent were added. After a second homogenization and emulsification, the mixture was filled into the container to obtain the compound essential oil microcapsule sustained-release preparation. Example

[0045] This embodiment provides a compound essential oil microcapsule sustained-release formulation for improving sleep quality, comprising the following raw materials in the indicated weight percentages: The formula consists of 1.7% dry powder, 0.008% osmanthus extract, 0.15% acorus calamus essential oil, 0.030% sandalwood essential oil, 0.10% natural borneol, 8% sustained-release microcapsule encapsulation agent, 5% transdermal penetration enhancer, 0.25% herbal plants, and the remainder being solvent.

[0046] The dry extract powder is obtained by mixing Polygala tenuifolia, Alpinia oxyphylla and Acorus calamus in a mass ratio of 6:1:1, followed by decoction with water, concentration, alcohol precipitation and spray drying.

[0047] In addition, the herbal plants include the following raw materials in the following weight percentages: The ingredients are: 12% jujube seed, 8% acorus calamus, 15% osmanthus, 20% lavender, 18% arborvitae seed, 15% Roman chamomile, 7% sandalwood, and 5% bergamot. The arborvitae seed is processed arborvitae seed, and the Roman chamomile is Roman chamomile essential oil, in which the content of bisabolol is not less than 3.0%.

[0048] The sustained-release microcapsule encapsulating agent is sodium alginate; the transdermal penetration enhancer is menthol; and natural borneol is extracted from the branches and leaves of camphor tree by steam distillation. The solvent is water.

[0049] The above-mentioned herbal plants were extracted by steam distillation to obtain the distillate as the aqueous phase, which was then mixed with osmanthus extract, calamus essential oil, sandalwood essential oil, natural borneol and sustained-release microcapsule encapsulation agent. The mixture was homogenized under high pressure (12000 rpm, 15 min) to prepare a microencapsulated primary emulsion. The dry ointment powder was then dispersed in the primary emulsion, and a transdermal penetration enhancer and solvent were added. After a second homogenization and emulsification, the mixture was filled into the container to obtain the compound essential oil microcapsule sustained-release preparation. Example

[0050] This embodiment provides a compound essential oil microcapsule sustained-release formulation for improving sleep quality, comprising the following raw materials in the indicated weight percentages: The ingredients are: 4% dry powder, 0.001% osmanthus extract, 0.30% acorus calamus essential oil, 0.001% sandalwood essential oil, 0.15% natural borneol, 5% sustained-release microcapsule encapsulation agent, 6% transdermal penetration enhancer, 0.1% herbal plants, and the remainder is solvent.

[0051] The dry extract powder is obtained by mixing Polygala tenuifolia, Alpinia oxyphylla and Acorus calamus in a mass ratio of 6:1:1, followed by decoction with water, concentration, alcohol precipitation and spray drying.

[0052] In addition, the herbal plants include the following raw materials in the following weight percentages: The ingredients are: 12% jujube seed, 8% acorus calamus, 15% osmanthus, 20% lavender, 18% arborvitae seed, 15% Roman chamomile, 7% sandalwood, and 5% bergamot. The arborvitae seed is processed arborvitae seed, and the Roman chamomile is Roman chamomile essential oil, in which the content of bisabolol is not less than 3.0%.

[0053] The sustained-release microcapsule encapsulating agent is cyclodextrin; the transdermal penetration enhancer is oleic acid; and natural borneol is extracted from the branches and leaves of camphor tree by steam distillation. The solvent is water.

[0054] The above-mentioned herbal plants were extracted by steam distillation to obtain the distillate as the aqueous phase, which was then mixed with osmanthus extract, calamus essential oil, sandalwood essential oil, natural borneol and sustained-release microcapsule encapsulation agent. The mixture was homogenized under high pressure (12000 rpm, 15 min) to prepare a microencapsulated primary emulsion. The dry ointment powder was then dispersed in the primary emulsion, and a transdermal penetration enhancer and solvent were added. After a second homogenization and emulsification, the mixture was filled into the container to obtain the compound essential oil microcapsule sustained-release preparation.

[0055] The compound essential oil microcapsule sustained-release formulations were prepared according to the contents provided in Examples 1-3, and the performance of the sustained-release formulations was tested as follows: Transdermal absorption performance test: The Franz diffusion cell method was used. Isolated SD rat skin was fixed between a supply cell and a receiving cell. The supply cell contained a microcapsule sustained-release formulation of 0.5% compound essential oil (indicated by terpenoid content), while the receiving solution was a PBS-30% ethanol solution at pH 7.4. The temperature was maintained at (32±0.5)℃ with continuous magnetic stirring. Samples were taken at 12 h, and the contents of osmanthus extract (calculated as linalool), acorus calamus essential oil (calculated as β-asarone), and natural borneol in the receiving solution were detected by GC-MS. The cumulative permeation per unit area (μg / cm²) was calculated, and the cumulative permeation per 12 h was used as the evaluation index and recorded in Table 1. Microcapsule sustained-release performance test: Referencing Method 3 (for transdermal preparations) of General Chapter IV (0931 Release Rate Determination) in the 2020 edition of the Chinese Pharmacopoeia, the apparatus was the same as in the transdermal absorption test. The receiving solution was changed to physiological saline containing 2% Tween 80 to maintain the leak tank conditions. The receiving solution was completely replaced at the 12-hour time point, and the content of polygalactosidase XXXI in the receiving solution was determined using HPLC-ELSD. The cumulative release rate (%) was calculated and included in Table 1 as an evaluation index.

[0056] Table 1. Transdermal absorption and microcapsule sustained-release properties of the compound essential oil microcapsule formulations in Examples 1-3

[0057] Table 1 shows that, in the 12-hour transdermal test, the cumulative permeation per unit area of ​​the compound essential oil microcapsule sustained-release formulations in Examples 1-3 was no less than 43.7 µg / cm² for Osmanthus extract (calculated as linalool); no less than 37.9 µg / cm² for Acorus tatarinowii essential oil (calculated as β-asarone); and no less than 51.0 µg / cm² for natural borneol (calculated as dextrorotatory borneol). Effective permeation of all components was detected within 1 hour, confirming their rapid-acting properties. In addition, the microcapsule sustained-release performance test results showed that the total release rate of Polygala saponin XXXI reached 92.5% after 12 hours, exhibiting ideal long-acting sustained-release characteristics.

[0058] This demonstrates that the compound essential oil microcapsule sustained-release formulation for improving sleep quality provided by the present invention can take effect rapidly and has high bioavailability.

[0059] In this invention, a rapid-acting penetration engine is first constructed using natural borneol and a complex transdermal penetration enhancer. Natural borneol, with its small molecular structure and high lipid solubility, quickly disrupts the lipid bilayer arrangement of the stratum corneum, opening transdermal channels for subsequent active ingredients. Simultaneously, osmanthus extract, calamus oil, and sandalwood oil reach the central limbic system directly through the olfactory pathway, instantly regulating the release of GABAergic neurotransmitters to achieve a rapid initial calming and soothing effect. Furthermore, high-pressure homogenization technology is used to construct a nanoscale microencapsulation pre-emulsion with the above-mentioned active ingredients and a sustained-release microcapsule encapsulating agent, forming a reservoir on the skin surface. This protects volatile components from premature loss and controls the release rate through a pH-responsive mechanism. Building upon this foundation, the water-soluble active ingredients of the dry powder are precisely loaded into the microcapsule core, synergistically working with components such as jujube seed saponins and cypress seed oil extracted from herbal plants to continuously act on the 5-HT system and the meridian pathways connecting the heart and kidneys. Among these, the processed cypress seed focuses on its calming properties, while the high-concentration bisabolol and Roman chamomile essential oil consolidate the sedative effect by inhibiting the release of inflammatory factors. Ultimately, this formulation, through three mechanisms—transdermal-olfactory dual-pathway delivery, microcapsule reservoir sustained release, and multi-target synergy—overcomes the first-pass effect bottleneck of traditional oral formulations, successfully achieving both rapid and long-lasting effects, thus improving bioavailability and completely resolving the technical dilemma of existing sleep aids that are difficult to balance slow onset and short-lived action.

[0060] Test case In the formulation provided by this invention, the high content of linalool and phenylethanol in the osmanthus extract significantly reduces the level of skin oxidative stress and the release of inflammatory factors through a triple pathway of effectively scavenging DPPH free radicals, inhibiting matrix metalloproteinase-1 (MMP-1) activity, and blocking non-enzymatic glycosylation reactions. This reduces abnormal transmission of peripheral nerve signals caused by skin barrier dysfunction and ultimately indirectly promotes the establishment and maintenance of sleep homeostasis by regulating the stability of the hypothalamus-pituitary-adrenal axis (HPA axis) and inhibiting excessive activation of the amygdala.

[0061] To verify the functional effects of osmanthus extract, DPPH free radical scavenging, MMP-1 inhibition, and non-enzymatic glycosylation inhibition tests were performed. First, a certain mass of dried osmanthus flowers was weighed and added to a certain volume of deionized water at a material-to-liquid ratio of 1:20 (g / mL). The mixture was soaked at room temperature for 1 hour, then heated at 80℃ for 2 hours. After extraction, the mixture was cooled to room temperature, filtered, and the filtrate was obtained, which was the osmanthus extract.

[0062] DPPH free radical scavenging test: DPPH is a very stable nitrogen-centered free radical with a maximum absorption peak wavelength of 517 nm in the visible light region. Each DPPH molecule generates a stable nitrogen-containing free radical in ethanol solution, exhibiting a typical purple color. When it reacts with a free radical scavenger that donates one electron, the resulting product is colorless, causing the typical purple color of the solution to lighten. The degree of fading is stoichiometrically related to the number of paired electrons. Therefore, spectrophotometry can be used for quantitative analysis to detect free radical scavenging and thus evaluate the sample's ability to scavenge free radicals. A DPPH free radical scavenging reaction system was constructed to evaluate the scavenging ability of Osmanthus extract on DPPH free radicals. The experimental reaction system is shown in Table 2.

[0063] Table 2 DPPH free radical scavenging test reaction system reagents No. 1 No. 2 No. 3 Anhydrous ethanol / mL / 1.50 1.50 0.2 mmol / L DPPH solution / mL 1.50 1.50 / Osmanthus extract at different test concentrations / mL 1.50 / 1.50 Following the order in Table 2, after adding the samples, the mixture was kept at a constant temperature of 25°C for 20 minutes, and the absorbance of each tube was measured at 517 nm. The clearance rate was calculated using the following formula.

[0064]

[0065] In the formula, A1, A2, and A3 are the absorbance values ​​at 517 nm after the reaction in reaction tubes 1, 2, and 3 is completed.

[0066] The scavenging rates of DPPH free radicals by osmanthus extracts at different test concentrations are as follows: Figure 1 As shown. By Figure 1 It can be seen that the osmanthus extract has excellent DPPH free radical scavenging activity; as the test concentration of the osmanthus extract increases, the DPPH free radical scavenging rate gradually increases, and a good dose-effect relationship is shown.

[0067] Non-enzymatic glycosylation inhibition assay: The experiment used bovine serum albumin and fructose mixtures for incubation to simulate non-enzymatic glycosylation in the human body. An inhibitor of the non-enzymatic glycosylation reaction was added to suppress the reaction. The fluorescence intensity of the system with the inhibitor was weaker than that of the control without the inhibitor. The inhibition rate was used to reflect the sample's inhibition of the non-enzymatic glycosylation reaction. A certain amount of a mixed solution containing 10 mg / mL bovine serum albumin and 0.25 mol / L fructose was used as the reaction solution. A 1.00% (w / w) osmanthus extract solution was added. A negative control group (PBS instead of the sample), a positive control group (1.00% (w / w) ethyl ether of vitamin C), and a blank group (PBS instead of the reaction solution) were set up, with three parallel tubes in each group. Incubation was performed at 37℃ in the dark. On days 1, 2, 3, 5, and 7, the fluorescence intensity (RFU, Relative Fluorescence Unit) of each experimental group was measured using a fluorescence microplate reader at 370 nm (absorption wavelength) / 440 nm (excitation wavelength). The inhibition rate was calculated using the following formula.

[0068]

[0069] The results of the test on the inhibition of non-enzymatic glycosylation by osmanthus extract are as follows: Figure 2 As shown. By Figure 2 It can be seen that osmanthus extract can effectively inhibit non-enzymatic glycosylation. After 5 days of cultivation, 1.00% osmanthus extract showed an inhibition rate of 71% against non-enzymatic glycosylation.

[0070] MP-1 inhibition test: After activated MMP-1 hydrolyzes the specific fluorescent substrate FRET, the enzymatically hydrolyzed product emits fluorescence. Samples that inhibit MMP-1 activity can inhibit or terminate this reaction, thereby reducing the amount of product generated and decreasing the fluorescence intensity. Changes in fluorescence intensity can be detected to indirectly reflect changes in enzyme activity, thus indicating the degree of inhibition of MMP-1 activity by the sample. A reaction system for inhibiting MMP-1 activity was constructed to evaluate the inhibitory ability of Osmanthus extract on MMP-1 activity; the reaction system is shown in Table 3.

[0071] Table 3. Reaction system for MMP-1 inhibition activity assay reagents Sample group negative control group MMP-1 / μL 50 50 Phosphate buffer / μL / 25 test substance / μL 25 / Following the order in Table 3, after adding the samples, incubate at 37°C in the dark for 5 minutes, then add 25 μL of the fluorescent substrate FRET. Immediately detect the fluorescence value FU1 using a fluorescence microplate reader at Ex / Em=490nm / 520nm, then incubate at 37°C in the dark for 30 minutes, and test the fluorescence value at 490nm / 520nm using a fluorescence microplate reader to obtain RFU2.

[0072] The MMP-1 activity inhibition rate is calculated using the following formula.

[0073]

[0074] In the formula, RFU1 is the fluorescence value of the system at the beginning of the reaction; RFU2 is the fluorescence value of the system after 30 min of reaction.

[0075] The results of the inhibition rate test of osmanthus extract on MMP-1 activity are as follows: Figure 3 As shown. By Figure 3 It can be seen that osmanthus extract can effectively inhibit MMP-1 activity. As the test concentration (Cx) of osmanthus extract increases, the inhibition rate of MMP-1 activity gradually increases, and the inhibition rate shows a good dose-effect relationship with the logarithm of the test concentration.

[0076] The above test results confirm that the osmanthus extract has good DPPH free radical scavenging activity and good inhibitory effect on non-enzymatic glycosylation and MMP-1.

[0077] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely preferred examples and are not intended to limit the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A compound essential oil microcapsule sustained-release formulation for improving sleep quality, characterized in that, The raw materials include the following weight percentages: The ingredients include: 1-4% dry powder, 0.001-0.250% osmanthus extract, 0.01-0.30% acorus calamus essential oil, 0.001-0.300% sandalwood essential oil, 0.05-0.15% natural borneol, 5-10% sustained-release microcapsule encapsulation agent, 3-6% transdermal penetration enhancer, 0.1-1.5% herbal plants, and the remainder being solvent.

2. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 1, characterized in that: The dry extract powder is obtained by mixing Polygala tenuifolia, Alpinia oxyphylla, and Acorus tatarinowii, followed by decoction with water, concentration, alcohol precipitation, and spray drying.

3. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 2, characterized in that: The mass ratio of Polygala tenuifolia, Alpinia oxyphylla, and Acorus tatarinowii in the dry ointment powder is 6:1:

1.

4. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 1, characterized in that: The herbaceous plants comprise the following raw materials in the following weight percentages: The ingredients are: 12% jujube seed, 8% acorus calamus, 15% osmanthus, 20% lavender, 18% cypress seed, 15% Roman chamomile, 7% sandalwood, and 5% bergamot.

5. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 4, characterized in that: The cypress seed kernels mentioned are processed cypress seed kernels, and the Roman chamomile is Roman chamomile essential oil, in which the content of bisabolol is not less than 3.0%.

6. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 1, characterized in that: The sustained-release microcapsule encapsulating agent is one of chitosan, sodium alginate, or cyclodextrin.

7. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 1, characterized in that: The transdermal penetration enhancer is either oleic acid or menthol.

8. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 1, characterized in that: The natural borneol is extracted from the branches and leaves of the camphor tree using steam distillation.

9. The compound essential oil microcapsule sustained-release formulation for improving sleep quality according to claim 1, characterized in that: The solvent is either water or ethanol.

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