A refreshing compound essential oil composition and application thereof
By using a compound essential oil composition such as bergamot essential oil to regulate neurotransmitter balance and the sympathetic nervous system, the problem of the single mechanism of action of existing energizing products is solved, and a multi-level regulation of central fatigue and an energizing effect are achieved.
Patent Information
- Application Number
- CN202611457430.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-09-18
- Publication Date
- 2026-11-06
AI Technical Summary
Existing energizing products have a single mechanism of action, cannot effectively relieve central fatigue, and have problems such as incomplete treatment and recurrence of symptoms.
This product uses a compound composition of bergamot essential oil, white lemon essential oil, forsythia essential oil, sweet orange essential oil, cinnamon essential oil, anethole essential oil, borneol essential oil, and peppermint essential oil. It regulates neurotransmitter balance through olfactory and transdermal pathways, activates the sympathetic nervous system, regulates the hypothalamic-pituitary-adrenal axis rhythm, and improves chronic fatigue.
It achieves multi-level and multi-target regulation of central fatigue, significantly improves attention and alertness, improves emotional fatigue, restores abnormal biological rhythms, and provides multi-level refreshing and invigorating effects.
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Figure CN123038185A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of essential oil technology and relates to an invigorating compound essential oil composition and its application. Background Technology
[0002] Fatigue is defined as "the body's physiological processes failing to maintain their functions at a specific level, or an organ failing to maintain its predetermined exercise intensity." Fatigue is an important feedback mechanism in the human body, naturally occurring after prolonged or high-intensity physiological activity. Its main function and purpose is to signal to the exerciser or body that the current exercise intensity or workload has exceeded the body's normal adaptive capacity, thus prompting people to realize the need to reduce activity intensity, adjust exercise plans, or take sufficient rest. Fatigue not only causes physiological damage, impairing various bodily functions and exacerbating physical and mental exhaustion, but it also triggers psychological problems, adversely affecting thinking and reaction abilities, manifesting as slowed reaction time, decreased situational awareness, confused thinking, and blurred consciousness. Furthermore, patients with chronic fatigue syndrome often experience persistent fatigue, joint pain, headaches, sleep disorders, poor concentration, and short-term memory loss.
[0003] Fatigue is a disease caused by multiple factors, and its pathogenesis is diverse and complex. Therefore, modern medical research has not fully elucidated the main pathogenic mechanisms at different stages of fatigue, leading to incomplete treatment and recurring symptoms. The development of fatigue involves multiple mechanisms, broadly categorized into peripheral fatigue and central fatigue. Peripheral fatigue mainly includes energy depletion, accumulation of metabolic products, oxidative stress, and muscle damage; central fatigue mainly includes abnormal inflammatory factors, neurotransmitter imbalance, and autonomic nervous system dysfunction.
[0004] Neurotransmitter balance is crucial in the mechanisms of central nervous system fatigue, involving the interactions between various neurotransmitters such as serotonin, dopamine, glutamate, and gamma-aminobutyric acid (GABA). Under normal circumstances, these neurotransmitters maintain a certain ratio to preserve the stability of the central nervous system. For example, a decrease in dopamine levels is often accompanied by an increase in serotonin (5-HT), which can exacerbate fatigue. Studies have found that supplementing with specific nutrients can alter the degree of fatigue by affecting neurotransmitter synthesis or release, indicating that maintaining neurotransmitter balance is important for alleviating central nervous system fatigue and providing a key perspective for a deeper understanding of its mechanisms.
[0005] Autonomic dysfunction (such as hypothalamic-pituitary-adrenal (HPA) axis disorder) is closely related to fatigue, specifically manifested as abnormal cortisol circadian rhythms. Fatigued individuals exhibit a more gradual decline in cortisol levels, particularly in the evening, where cortisol levels are significantly higher than in non-fatigued individuals. This flattening of the rhythm indicates impaired HPA axis regulation. This change cannot be explained by emotions, treatment, or other factors, suggesting that the dysregulation of cortisol secretion rhythm (rather than changes in the average level) is itself a key physiological mechanism leading to persistent fatigue. HPA axis regulation is a complex negative feedback loop process. Its basic working principle is as follows: when the brain senses physiological or psychological stress, the hypothalamus releases corticotropin-releasing hormone (CRH); CRH then stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH); ACTH reaches the adrenal cortex via the bloodstream, stimulating the synthesis and release of glucocorticoids such as cortisol. Ultimately, elevated cortisol levels in the blood exert negative feedback inhibition on the hypothalamus and pituitary gland, reducing further secretion of CRH and ACTH, thus restoring cortisol levels to homeostasis and completing one regulatory cycle.
[0006] Clinical evidence shows that patients with chronic fatigue syndrome (CFS) have significantly elevated levels of peripheral blood pro-inflammatory factors such as interleukin-6, tumor necrosis factor, and interleukin-1β. The persistent presence of these pro-inflammatory factors can trigger chronic inflammation and exacerbate hypothalamic-pituitary-adrenal axis dysfunction, ultimately leading to neuroendocrine-immune system disorders and triggering physical and central nervous system symptoms such as muscle soreness, headache, decreased attention, and depression. Therefore, CFS may be a chronic inflammatory state, and the persistent presence of pro-inflammatory factors IL-6, TNF-x, and IL-1β may be key to determining the prognosis of CFS. Furthermore, current treatments for mental illnesses such as depression often improve symptoms by reducing the levels of pro-inflammatory factors, suggesting that reducing pro-inflammatory factor levels may also help improve the physical and mental symptoms of CFS patients.
[0007] According to Armstrong et al., patients with chronic fatigue syndrome exhibit significant glycolysis inhibition, leading to insufficient supply of acetyl-CoA in the tricarboxylic acid cycle. This forces the body to accelerate amino acid breakdown to maintain energy supply. Simultaneously, elevated creatinine levels indicate that muscles rely on anaerobic metabolism to produce ATP, which is inefficient and prone to fatigue. The core reason for fatigue caused by energy metabolism imbalance lies in its disruption of the entire system of cellular energy generation, utilization, and antioxidant defense. This metabolic disorder is closely related to oxidative stress. Decreased uric acid and elevated allantoin suggest the accumulation of reactive oxygen species (ROS), which further impairs mitochondrial function (Christopher WA, Neil RM, Donald PL, Henry LB, Paul RG, et al. Metabolic Profiling Reveals Anomalous Energy Metabolism and Oxidative Stress Pathwaysin Chronic Fatigue Syndrome Patients[J], Metabolomics : Official journal of the Metabolomic Society, 2015, 11(6): 1626-1639.). Mensah et al.'s research further revealed that the abnormally elevated expression of CD24 on B cells is associated with the activation of the AMPK signaling pathway, which disrupts normal glucose metabolism and lactate production, exacerbating the energy crisis from an immunometabolic perspective (Fane FKM, Christopher WA, Venkat R, Amolak SB, Saul B, Maria JL, Geraldine C, et al. CD24 Expression and B Cell Maturation Shows a Novel Link with Energy Metabolism: Potential Implications for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome[J], Frontiers in immunology, 2018, 9).In addition, Agudelo et al. found that insufficient function of PGC-1α1 in skeletal muscle impairs kynurenine metabolism, affects malate-aspartate shuttle efficiency, thereby reducing the bioenergy efficiency of glucose oxidation and making muscles more prone to fatigue (Xi X, Yijian D, Yunxia Y, Yan G, Qi S, Junhao L, Xiao Y, Junsong W, Jianfa Z, et al. β-Glucan Salecan Improves Exercise Performance and Displays Anti-Fatigue Effects Through Regulating Energy Metabolism and Oxidative Stress in Mice[J], Nutrients, 2018, 10(7)). Finally, Xu et al.'s research shows that energy metabolism imbalance is often accompanied by a weakening of the antioxidant defense system, and oxidative stress can directly damage cell structure and accelerate fatigue (Emer EH, Hugo C, Seonadh MO, Laura EG, Natalia M, Sarah C, Anna W, DanielG WJ, Michelle AW, Alicia S, Mireille O, Kathryn JM, Ed CL, Sinead CC, Stephen VG, Joseph K, Frederick JS, et al. Mycobacterium Tuberculosis Limits Host Glycolysis and IL-1β by Restriction of PFK-M Via MicroRNA-21.[J], Cellular reprogramming, 2020, 30(1): 124-136.e4.). Therefore, energy metabolism imbalance leads to fatigue by directly inhibiting ATP synthesis, inducing oxidative stress, and disrupting metabolic signaling networks.
[0008] During high-intensity or prolonged exercise, the rapid increase in energy metabolism leads to a rate of metabolic waste production far exceeding its clearance rate, resulting in excessive accumulation of these waste products in muscles and blood. These accumulated metabolic products are not inert substances; they interfere with normal physiological and biochemical processes through multiple pathways. For example, the hydrogen ions released from lactate significantly lower intracellular pH, directly inhibiting the activity of key enzymes such as phosphofructokinase, hindering glycolysis and ATP resynthesis, reducing the affinity of troponin for calcium ions, decreasing the number and effectiveness of cross-bridges, ultimately leading to decreased muscle contractility and output power. Simultaneously, the decrease in blood pH also affects brain cell function, promoting central protective inhibition. Furthermore, the accumulation of ammonia consumes α-ketoglutarate, an important intermediate in the tricarboxylic acid cycle, disrupting the integrity of energy metabolism and potentially crossing the blood-brain barrier to exert toxicity on the central nervous system, interfering with neurotransmitter balance. Therefore, the accumulation of metabolic products, through multiple effects such as disrupting homeostasis, inhibiting energy metabolism, and weakening muscle contraction function, constitutes a key link in inducing and exacerbating exercise-induced fatigue.
[0009] Western medicine currently treats fatigue through various methods, including: polysaccharides, which regulate energy metabolism and provide antioxidant effects; polyphenols and flavonoids, which rely on their strong antioxidant activity; anthocyanins, which integrate metabolic regulation and gene expression control; and others such as the ketogenic diet, ketamine, and trace element chelates, which exert their effects through unique pathways such as optimizing energy supply, antagonizing NMDA receptors, and enhancing bioavailability. While these various Western medical treatments for fatigue each have their own mechanisms of action, they all possess certain limitations or potential risks.
[0010] Natural plant essential oils, due to their high safety, ease of use, and ability to exert effects through olfaction and transdermal pathways, have gradually become a research hotspot for fatigue relief products. For example, patent CN109432318B discloses a compound essential oil with fatigue-relieving and mind-refreshing effects, along with its applications and products. Its core formula, by volume, includes 1-10 parts geranium oil, 1-5 parts cedarwood oil, 1-3 parts jasmine oil, 1-3 parts lemon oil, and 1-3 parts bergamot oil, and may optionally include one or more of rosemary oil, clary sage oil, frankincense oil, grapefruit oil, sweet orange oil, citrus oil, magnolia oil, and lemongrass oil. This patent uses pure natural plant essential oil concentrates as raw materials, and through reasonable formulation and scientific proportioning, achieves synergistic effects, resulting in a compound essential oil with good fatigue-relieving effects. However, its efficacy verification is primarily peripheral, lacking verification of central mechanisms, and its mechanism of action is relatively simple.
[0011] Therefore, effectively alleviating and treating fatigue progression is of great significance in today's clinical practice and represents a significant challenge. Summary of the Invention
[0012] The purpose of this invention is to overcome the single mechanism of action of existing energizing products and to provide an energizing compound essential oil composition and its application.
[0013] The objective of this invention can be achieved through the following technical solutions: The first aspect of this invention provides a refreshing compound essential oil composition, which is composed of the following components in parts by weight: 25-50 parts of bergamot essential oil, 9-25 parts of white lemon essential oil, 2-7 parts of forsythia essential oil, 4-10 parts of sweet orange essential oil, 1-5 parts of cinnamon essential oil, 2-10 parts of anethole essential oil, 1-6 parts of borneol essential oil, 2-8 parts of peppermint essential oil, and 5-20 parts of lemon essential oil.
[0014] Furthermore, the invigorating compound essential oil composition is composed of the following components in parts by weight: 30-40 parts bergamot essential oil, 10-20 parts white lemon essential oil, 3-6 parts forsythia essential oil, 5-8 parts sweet orange essential oil, 2-4 parts cinnamon essential oil, 4-8 parts anethole essential oil, 2-5 parts borneol essential oil, 3-7 parts peppermint essential oil, and 8-12 parts lemon essential oil.
[0015] Furthermore, the invigorating compound essential oil composition is composed of the following components in parts by weight: 32-38 parts bergamot essential oil, 12-18 parts white lemon essential oil, 4-6 parts forsythia essential oil, 6-8 parts sweet orange essential oil, 2-3 parts cinnamon essential oil, 5-7 parts anethole essential oil, 3-5 parts borneol essential oil, 4-6 parts peppermint essential oil, and 9-11 parts lemon essential oil.
[0016] Furthermore, the invigorating compound essential oil composition is composed of the following components in parts by weight: 32 parts bergamot essential oil, 18 parts white lemon essential oil, 6 parts forsythia essential oil, 6 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 5 parts peppermint essential oil, and 10 parts lemon essential oil.
[0017] Furthermore, the invigorating compound essential oil composition is composed of the following components in parts by weight: 38 parts bergamot essential oil, 12 parts white lemon essential oil, 4 parts forsythia essential oil, 8 parts sweet orange essential oil, 2 parts cinnamon essential oil, 7 parts anethole essential oil, 3 parts borneol essential oil, 6 parts peppermint essential oil, and 9 parts lemon essential oil.
[0018] In some preferred embodiments of the present invention, the invigorating compound essential oil composition is composed of the following components in parts by weight: 35 parts bergamot essential oil, 15 parts white lemon essential oil, 5 parts forsythia essential oil, 7 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 5 parts peppermint essential oil, and 10 parts lemon essential oil.
[0019] The second aspect of the present invention provides a method for preparing a refreshing compound essential oil composition, comprising the following steps: weighing each component essential oil raw material according to the weight parts, stirring and mixing to obtain the refreshing compound essential oil composition.
[0020] In some embodiments of the present invention, the essential oil raw materials of each component are commercially available or extracted by distillation.
[0021] In some preferred embodiments of the present invention, the stirring and mixing are carried out under light-protected conditions.
[0022] A third aspect of the present invention provides a stimulating compound essential oil product, comprising an active ingredient and a product carrier, wherein the active ingredient is the stimulating compound essential oil composition as described in any one of claims 1-6, and the product carrier is at least one of a loading material, a matrix, an excipient, or a structural component.
[0023] In some embodiments of the present invention, the product is a product used by smelling, applying or diffusering, and is selected from at least one of essential oil rollerballs, essential oil inhalers, essential oil aromatherapy sprays, essential oil massage oils, essential oil aromatherapy candles, essential oil diffusers, essential oil patches, essential oil sachets, essential oil ointments or essential oil lotions.
[0024] Specific product formats can be listed below: A refreshing and invigorating blend of essential oils roll-on, comprising a roll-on bottle and contents, the contents containing a refreshing blend of essential oils, or a mixture of the blend with a plant-based oil. For use, apply to the temples, forehead, philtrum, wrists, back of the neck, or behind the ears for a refreshing and invigorating effect through application and inhalation.
[0025] A stimulating and invigorating compound essential oil inhaler includes an inhalation tube and an adsorption core loaded with the aforementioned stimulating and invigorating compound essential oil composition. It is used by inhalation through the nasal cavity to relieve fatigue through smelling.
[0026] This is a refreshing and invigorating blend of essential oils aromatherapy spray, comprising a spray bottle and contents. The contents consist of the aforementioned refreshing blend of essential oils, ethanol, and water. When used, it is sprayed into the air, inside a car, indoors, or onto fabrics to refresh and invigorate the mind through aromatherapy or inhalation.
[0027] This invigorating and stimulating blend of essential oils for massage comprises the aforementioned invigorating blend of essential oils and a plant-based base oil. When using, apply to the temples, neck, shoulders, hands, feet, or back and massage. Its effects are achieved through application, massage, and inhalation.
[0028] This is a scented candle containing a blend of invigorating and refreshing essential oils, comprising a wax base, a wick, and the aforementioned blend of invigorating essential oils. When lit, it releases fragrance through diffuser application, serving to invigorate the mind and relieve fatigue.
[0029] A fragrance diffuser containing a stimulating and invigorating compound essential oil, comprising a porous diffuser carrier on which the stimulating and invigorating compound essential oil composition is loaded. The diffuser carrier may be a diffuser stone, diffuser wood, diffuser ceramic, or diffuser sheet, and is inhaled through natural evaporation.
[0030] A refreshing and invigorating compound essential oil patch, comprising a backing layer and a gel layer, the gel layer containing the aforementioned refreshing compound essential oil composition. Applied to the temples, forehead, neck, or clothing, it exerts its effects through inhalation or transdermal application.
[0031] A sachet containing a refreshing and invigorating compound essential oil comprises a breathable bag and an absorbent carrier, the absorbent carrier loading the aforementioned refreshing compound essential oil composition. It can be hung in a car, indoors, inside a bag, or worn on the person to refresh and invigorate through inhalation.
[0032] A stimulating and invigorating compound essential oil ointment or lotion, comprising the aforementioned stimulating compound essential oil composition and an ointment or lotion base. Apply to the temples, philtrum, wrists, or back of the neck to relieve fatigue through application and inhalation.
[0033] Compared with the prior art, the present invention has the following advantages: (1) The bergamot essential oil in the composition of the present invention contains a high concentration of limonene and linalyl acetate, which can quickly activate the prefrontal cortex through the olfactory pathway and enhance attention and alertness; the furanocoumarins in the white lemon essential oil can synergistically regulate the release of monoamine neurotransmitters and enhance central excitability; the forsythoside and forsythoside ester in the forsythia essential oil can maintain the effective concentration of dopamine and norepinephrine in the synaptic cleft by inhibiting monoamine oxidase activity; the d-limonene contained in the sweet orange essential oil can significantly reduce cortisol levels, and its pleasant aroma can quickly improve emotional fatigue; the cinnamaldehyde in the cinnamon essential oil activates the sympathetic nervous system through transient receptor potential channels. The system promotes the release of catecholamines, directly increasing the basal metabolic rate; anise borneol essential oil, as a partial agonist of GABA receptors, produces a mild excitatory effect at low concentrations and can enhance the transdermal absorption of other essential oils; borneol essential oil can quickly cross the blood-brain barrier and enhance wakefulness by activating the locus coeruleus-norepinephrine system; menthol in peppermint essential oil produces a cold stimulus through the TRPM8 channel, directly activating the reticular activating system and producing a significant refreshing response within 30 seconds; β-pinene and γ-terpinene in lemon essential oil work synergistically to improve circadian rhythm disorders caused by chronic fatigue by regulating the hypothalamic-pituitary-adrenal axis rhythm.
[0034] (2) This invention combines the anti-fatigue theories of traditional Chinese and Western medicine with modern aromatherapy. The resulting invigorating compound essential oil composition can exert the synergistic effect of multiple essential oil components through a simple essential oil diffusion method, effectively relieving fatigue symptoms and having a good invigorating effect. Based on the concept of aromatherapy in traditional Chinese medicine, this composition utilizes the stimulating effect of aromatherapy on the body to promote the restoration of abnormal biological rhythms to normal, regulate the operation of various tissue systems in the body, and enable them to perform at their best.
[0035] (2) The refreshing compound essential oil composition prepared by the present invention uses a variety of natural plant ingredients and has the synergistic pharmacological characteristics of multiple components, multiple targets and multiple mechanisms. It can make up for the shortcomings of traditional single Western medicine and improve the relief effect on fatigue symptoms. In addition, when using compound essential oils, essential oils with similar functions can be blended together to enhance the efficacy; essential oils with large differences in function can be blended together to expand the therapeutic effect.
[0036] (4) The invigorating compound essential oil composition prepared by this invention has advantages such as high permeability and fast metabolism. Due to its high lipid solubility, the essential oil can easily cross the blood-brain barrier and exert a better effect, achieving the therapeutic purpose of refreshing the mind and opening the orifices. At the same time, the essential oil can make up for the defect of traditional volatile aromatic Chinese medicines in terms of the loss of aroma during decoction, which affects the efficacy. In addition, the essential oil is convenient to carry and easy to use. Attached Figure Description
[0037] Figure 1 This is a network pharmacology analysis diagram of the present invention.
[0038] Figure 2 This shows the changes in mouse body weight during the behavioral experiments of this invention.
[0039] Figure 3 This is a comparative diagram showing the open-arm movement of mice in the elevated cross maze test of this invention.
[0040] Figure 4 This is a comparison diagram of autonomous activity in the open field test of this invention.
[0041] Figure 5 This is a comparison chart of the 5-HT content in mouse serum as part of the physiological index testing of this invention.
[0042] Figure 6 This is a comparison chart of DA content in mouse serum for physiological index testing according to the present invention.
[0043] Figure 7 This is a comparison chart of GABA content in mouse serum for physiological index testing according to the present invention.
[0044] Figure 8 This is a comparison chart of ACTH levels in mouse serum as part of the physiological index testing of this invention.
[0045] Figure 9This is a comparison chart of CORT levels in mouse serum for physiological index testing according to the present invention.
[0046] Figure 10 This is a comparison chart of CRH levels in mouse serum used in the physiological index testing of this invention.
[0047] Figure 11 This is a comparison chart of MDA content in mouse serum for physiological index testing according to the present invention. Detailed Implementation
[0048] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. These embodiments are based on the technical solution of the present invention and provide detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is not limited to the following embodiments.
[0049] Unless otherwise specified, the reagents, methods, instruments, and equipment used in this invention are conventional in the art. Unless otherwise specified, the reagents and materials used in the following examples are all commercially available.
[0050] The essential oils used in this invention were purchased commercially from Shanxi Hongyi Traditional Chinese Medicine Technology Co., Ltd.
[0051] Bergamot essential oil, white lemon essential oil, and lemon essential oil are prepared from the peels of different citrus plants. Their botanical origins are different, their volatile components are significantly different, and their efficacy characteristics are significantly different. They do not belong to the same type of essential oil. This plan limits the types to be mutually exclusive to avoid confusion.
[0052] Example 1: A stimulating compound essential oil composition is prepared by weighing the individual essential oils according to the following weight proportions, placing them in a clean brown glass bottle, and stirring and mixing them in the dark to obtain the stimulating compound essential oil composition: 32 parts bergamot essential oil, 18 parts white lemon essential oil, 6 parts forsythia essential oil, 6 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 5 parts peppermint essential oil, and 10 parts lemon essential oil.
[0053] Example 2: A stimulating compound essential oil composition is prepared by weighing each single essential oil in the following proportions, placing them in a clean brown glass bottle, and stirring and mixing them in the dark to obtain the stimulating compound essential oil composition: 38 parts bergamot essential oil, 12 parts white lemon essential oil, 4 parts forsythia essential oil, 8 parts sweet orange essential oil, 2 parts cinnamon essential oil, 7 parts anethole essential oil, 3 parts borneol essential oil, 6 parts peppermint essential oil, and 9 parts lemon essential oil.
[0054] Example 3: A stimulating compound essential oil composition is prepared by weighing each single essential oil in the following proportions, placing them in a clean brown glass bottle, and stirring and mixing them in the dark to obtain the stimulating compound essential oil composition: 35 parts bergamot essential oil, 15 parts white lemon essential oil, 5 parts forsythia essential oil, 7 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 5 parts peppermint essential oil, and 10 parts lemon essential oil.
[0055] Comparative Example 1 (lacking lemon essential oil) A stimulating compound essential oil composition is prepared by weighing each essential oil in the following proportions, placing them in a clean brown glass bottle, and stirring and mixing them in the dark to obtain the stimulating compound essential oil composition: 35 parts bergamot essential oil, 15 parts white lemon essential oil, 5 parts forsythia essential oil, 7 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, and 15 parts peppermint essential oil.
[0056] Comparative Example 2 (lacking Forsythia essential oil) A stimulating compound essential oil composition is prepared by weighing each single essential oil in the following proportions, placing them in a clean brown glass bottle, and stirring and mixing them in the dark to obtain the stimulating compound essential oil composition: 35 parts bergamot essential oil, 20 parts white lemon essential oil, 7 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 10 parts peppermint essential oil, and 10 parts lemon essential oil.
[0057] Comparative Example 3 (lacking sweet orange and cinnamon essential oils) A refreshing compound essential oil composition is prepared by weighing each single essential oil in the following proportions, placing them in a clean brown glass bottle, and stirring and mixing them in the dark to obtain the refreshing compound essential oil composition: 35 parts bergamot essential oil, 15 parts white lemon essential oil, 15 parts forsythia essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 5 parts peppermint essential oil, and 10 parts lemon essential oil.
[0058] Comparative Example 4 (lacking anethole and borneol essential oils) A refreshing compound essential oil composition is prepared by weighing each single essential oil in the following proportions, placing them in a clean brown glass bottle, and stirring and mixing them in the dark to obtain the refreshing compound essential oil composition: 35 parts bergamot essential oil, 15 parts white lemon essential oil, 5 parts forsythia essential oil, 7 parts sweet orange essential oil, 3 parts cinnamon essential oil, 5 parts peppermint essential oil, and 20 parts lemon essential oil.
[0059] Test case I. Network Pharmacological Analysis 1. Experimental Methods (1) Screening of potential pharmacologically active ingredient targets in energizing essential oils First, the active ingredients of the energizing essential oil were entered into PubChem (https: / / PubChem.ncbi.nlm.nih.gov / ), the world's largest free chemical information database, to obtain corresponding chemical structure data. Then, the potential targets of the energizing essential oil were predicted using the SwissTargetPrediction (http: / / www.swisstargetprediction.ch / ) database, and a relevant target library was constructed.
[0060] (2) Acquisition of fatigue-related targets Using "fatigue" as the keyword, this study explored fatigue-related target information using the therapeutic target database TTD (https: / / db.idrblab.net / ttd / ), the human gene database GeneCards (http: / / www.genecards.org / ), and the human Mendelian genetics database OMIM (https: / / www.omim.org / ). After integrating the target data from these multiple sources and removing duplicate entries, a target intersection analysis was conducted using the Bioinformatics platform (http: / / www.bioinformatics.com.cn / ) to identify the overlap between the active ingredient targets of the energizing essential oil and fatigue-related targets.
[0061] (3) Construction and visualization of protein-protein interaction (PPI) networks Import the relevant target data into the STRING database (https: / / cn.string-db.org / ) to draw a protein-protein interaction network diagram. Then, import the obtained network file into Cytoscape 3.10.0 software for visualization analysis. The core targets were selected based on the criteria of having median centrality, proximity centrality, and degree values higher than the average value. The selection criteria were: degree > median, be-weenness > median, and closeness > median.
[0062] (4) Pathway enrichment analysis Common drug-disease targets were uploaded to the Metascape database (https: / / metascape.org / ), and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analyses were performed to obtain relevant functional information such as molecular function, biological process, cellular components, and KEGG pathways corresponding to the targets. GO and KEGG maps were generated using a bioinformatics platform (http: / / www.bioinformatics.com.cn / ), and related visualization analyses were completed using Cytoscape 3.10.0 software.
[0063] 2. Results and Discussion (1) Construction of disease targets for fatigue and prediction of target targets for each component of energizing essential oil Based on GC-MS component data, bioinformatics methods were used to search and deduplicate data in the PubChem and Swiss TargetPrediction databases, identifying 137 predicted sites of action for energizing essential oils. Furthermore, a mapping analysis was performed between these sites and 10,051 fatigue-related pathological targets. Figure 1 As shown in (A), the analysis results indicate that there are 132 common targets between the active ingredients of the energizing essential oil and fatigue. These 132 key targets constitute the molecular basis for the anti-fatigue effect of the energizing essential oil. Future research will focus on functional enrichment analysis of these targets to clarify the specific central and metabolic pathways they regulate.
[0064] (2) Protein-protein interactions Protein-protein interaction (PPI) information for the 132 intersecting target sites was obtained from the STRING database and converted to TSV format for network construction in Cytoscape 3.10.0 software. The network was then subjected to topological evaluation and visualization modifications using the CentiScaPe 2.2 plugin. Figure 1 -(B) From this, 40 key targets of energizing essential oils, represented by CYP3A4, PIK3R1, CYP19A1, PIK3CD, and MAOA, were extracted from the complex network. These key targets mainly involve critical physiological processes such as monoamine neurotransmitter metabolism, signal transduction, and energy metabolism. This suggests that energizing essential oils may achieve their effects of energizing and relieving fatigue by synergistically regulating central nervous system excitability and metabolic balance.
[0065] (3) Pathway enrichment analysis Enrichment calculations for GO function and KEGG pathway of the aforementioned comorbidity targets were performed using the Metascape database. In the GO enrichment analysis, the top 10 significant items from biological processes (BP), cellular composition (CC), and molecular function (MF) were extracted according to the p-value from smallest to largest and plotted as follows: Figure 1 -(C). The results showed that MF mainly involves steroid hydroxylase activity, steroid binding, and kinase binding; BP covers steroid metabolism, olefin metabolism, and exogenous substance metabolism; while CC focuses on the mitochondrial membrane. For the KEGG pathway, enrichment analysis was performed with a P<0.01 screening threshold, and significantly enriched pathways were visualized, such as... Figure 1-(D). The analysis shows that the potential pathways for the refreshing effect of the refreshing compound essential oil include steroid hormone biosynthesis, drug metabolism - cytochrome P450, and chemical carcinogenesis - receptor activation.
[0066] II. Animal behavior test The present invention conducts the following animal behavior tests on the refreshing compound essential oil composition prepared in the above examples and the single essential oils of the comparative examples: 1) Animal selection and breeding: Healthy SPF-grade ICR mice, male, 6-8 weeks old, with a body mass of 27-33 g, were selected and purchased from Shanghai Jiesijie Laboratory Animal Co., Ltd., with the animal certificate number SCXK(Shanghai) 2023-0004. The animals were raised in an SPF environment under conventional feeding conditions, at a temperature of 22-25°C, a humidity of 40%-70%, and a 12-hour light-dark cycle.
[0067] 2) Establishment of the mouse weight-loaded exhaustive swimming model (WST model) and drug administration: The animals were acclimatized to the environment for 7 days, weighed, and randomly divided into 9 groups, with 5 mice in each group. The groups were respectively a blank group (Control), a model group (Model), and essential oil groups (including 7 groups from Comparative Examples 1 to 4 and Examples 1 to 3). Mice in the blank group were not given any stimulation. Except for the blank control group, mice in all other groups underwent daily weight-loaded forced swimming experiments until exhaustion to establish a fatigue model. The water temperature was maintained at about 25°C, and the load was 5% of the mouse's body weight. This modeling process lasted for 17 days. During the modeling period, a 17-day continuous administration regimen was implemented simultaneously. Mice in the essential oil groups inhaled 0.1% of the corresponding essential oil vapor prepared in the examples or comparative examples for 15 minutes every day, while mice in the blank control group and the model group inhaled distilled water vapor. The body weight of the mice was continuously weighed and recorded during the experiment. The behavioral test started on the first day after the last administration.
[0068] 3) Behavioral test: ① Elevated plus maze test Before the test, each mouse was placed in the test site to acclimatize to the environment for 5 minutes. After allowing the mouse to explore freely for 5 minutes, it was quickly placed in the central area of the elevated plus maze with its head facing the open arm. After release, four indicators were measured: the number of entries into the open arm (OE), the time spent in the open arm (OT), the number of entries into the closed arm (CE), and the time spent in the closed arm (CT). The proportion of the number of entries into the open arm (OE%) and the proportion of the time spent in the open arm (OT%) were calculated based on OE, OT, CE, and CT. Each measurement lasted for 5 minutes. After each test, 75% alcohol was used to clean residual impurities such as feces and urine on the elevated plus maze and remove odors, followed by drying with a dry cloth.
[0069] ③ Open field test Before the experiment, mice were placed in the central square of a 40cm×40cm×40cm black open box for 3 minutes to acclimatize. During the experiment, the mice's activities in the open field were recorded on video for 5 minutes, and the total distance traveled and the distance traveled in the central area were analyzed. The experimental environment was kept quiet, and after each mouse was tested, the open field test box was wiped with 75% alcohol and excrement was removed before testing another mouse.
[0070] ④ ELISA method for determining the expression of fatigue-related indicators After the behavioral tests, blood was collected from the orbital cavity of anesthetized mice. After standing for 2 hours, the blood was centrifuged twice, and the supernatant was collected after 20 minutes. The levels of various physicochemical indicators in mouse serum were measured according to the steps listed on the respective ELISA kits for mice.
[0071] Mice were euthanized, and their brains were quickly dissected, rinsed with physiological saline, and rapidly frozen at -80°C. A specific amount of tissue was weighed from each group using a precision balance to prepare a homogenate. The supernatant was collected, and the levels of various physicochemical parameters in the mouse brain tissue were determined according to the steps listed on the mouse ELISA kit.
[0072] Data are expressed as mean ± standard deviation. SPSS 13.0 software was used for statistical analysis, and one-way ANOVA was employed to determine statistical significance. p < 0.05 was considered statistically significant. Origin 2023 was used for graphing.
[0073] The results of the above behavioral tests are as follows: (1) Behavioral experiments on mice Table 1. Changes in mouse body weight before and after modeling
[0074] The changes in mouse body weight during the experiment are shown in Table 1 and Figure 2 As shown, the weight of mice in the control group steadily increased. Compared with the control group, the weight of mice in the model group and each essential oil group decreased significantly in the early stage of modeling, indicating that the fatigue model was successfully established. After 17 days of essential oil intervention (the control group and the model group were given distilled water), the weight loss trend of mice in each essential oil treatment group was effectively alleviated and showed a recovery growth, suggesting that essential oil inhalation can alleviate fatigue in mice and promote the recovery of food intake and physiological indicators.
[0075] Further comparison of the intervention effects of different formulation groups revealed a synergistic effect and gradient differences in the improvement of mouse body weight by compound essential oils: the optimal formulation with all components (Example 3) showed the most significant relief of fatigue in mice, with the highest degree of weight recovery after intervention; followed by Examples 1 and 2, whose weight recovery effects were also superior to the comparative examples; Comparative examples 1 and 3, lacking a single component, showed the next best recovery effects; while comparative examples 2 and 4, lacking two components, showed relatively weaker recovery effects. These results fully demonstrate that the whole-component formulation has a synergistic effect, and the absence of key components weakens its anti-fatigue and recovery-promoting efficacy.
[0076] Table 2. Behavioral results of mice in the elevated cross maze model.
[0077] The behavioral effects of mice in the elevated cross maze model are shown in Table 2 and Figure 3 As shown in the figure, compared with the control group, the proportion of mice entering the open arm and the proportion of time spent in the open arm were significantly reduced in the model group (p<0.01), indicating that the mice in the model group had reduced interest in exploring novel environments and increased anxiety / fear, thus successfully establishing the fatigue model. Compared with the model group, the proportion of mice entering the open arm and the proportion of time spent in the open arm were increased to varying degrees in each essential oil intervention group, indicating that inhaling essential oils can effectively improve the anxiety state of fatigued mice and restore their exploratory behavior.
[0078] Further comparison revealed that the anti-fatigue and anti-anxiety effects of the compound essential oils exhibited synergistic effects and gradient differences: the optimal formulation with all components (Example 3) showed the most significant improvement in the elevated cross maze indicators in mice, with the highest proportion of entries into the open arm and the highest dwell time, closest to the control group; Examples 1 and 2 showed the next best effects, but were still superior to their respective comparative examples; Comparative examples 1 and 3, lacking a single component, showed the next best improvement; while comparative examples 2 and 4, lacking two components, showed the smallest improvement. These results demonstrate that the whole-component combination has a synergistic effect, and the synergistic effect of each component is superior to the formulation lacking any component, which can more effectively restore the exploratory interest of fatigued mice and improve fatigue-like anxiety behavior.
[0079] Table 3. Behavioral results of mice in the open field test.
[0080] The behavioral results of mice in the open field test are shown in Table 3 and Figure 4As shown in the figure, compared with the control group, the total distance traveled and the central distance traveled in the open field test of the model group mice were significantly reduced (p<0.05), indicating that the spontaneous activity ability and spatial exploration initiative of the model group mice were reduced, and the fatigue model was successfully established. Compared with the model group, the movement and exploration behavior of mice in each essential oil intervention group were restored to varying degrees in the open field, indicating that inhaling essential oils can effectively improve the spontaneous activity and anxiety state of fatigued mice.
[0081] Further comparison revealed that the optimal formulation with all components (Example 3) showed the most significant improvement, with both total distance and central distance reaching the highest levels. Examples 1 and 2 were the next most effective, but both were superior to their respective comparative examples. Comparative examples 1 and 3, lacking a single component, showed the next least improvement. Comparative examples 2 and 4, lacking two components, showed the smallest improvement. These results demonstrate that the formulation with all components has a synergistic effect, and the absence of key components weakens its efficacy in relieving mental fatigue and restoring spontaneous activity.
[0082] (2) Expression of physiological indicators in mice The compound essential oil group of Example 3, which showed better relief of fatigue symptoms in mice in animal behavior studies, was selected for testing of the expression of various physiological indicators in mice.
[0083] Table 4. Results of neurotransmitter content in mouse brain tissue
[0084] As shown in Table 4 and Figure 5 , 6 As shown in Figure 7, based on research on the function of the central monoamine neurotransmitter system and the mechanism of fatigue, decreased levels of monoamine neurotransmitters (5-HT and DA) and imbalance of amino acid neurotransmitter (GABA) homeostasis are key factors leading to central fatigue. Among them, dopamine (DA) mainly participates in motivation and arousal regulation, serotonin (5-HT) is closely related to central nervous system emotions and the sleep-wake cycle, while γ-aminobutyric acid (GABA) is closely related to central inhibition and post-fatigue repair processes. Maintaining these three substances at reasonable levels is of great significance for improving fatigue and enhancing physical vitality.
[0085] Compared with the control group, the levels of 5-HT, DA, and GABA in the brain tissue of mice in the model group were significantly reduced (p<0.05), suggesting that under fatigue model conditions, excessive consumption of neurotransmitters maintaining wakefulness and motivation led to an imbalance in the central nervous system's excitation and inhibition regulation system, consistent with fatigue behavioral manifestations. Compared with the model group, after intervention with the compound essential oil in Example 3, the levels of 5-HT and DA in the mouse brain showed a significant recovery, and GABA levels also recovered significantly, with all indicators superior to the model group and approaching the levels of the control group. These results indicate that the compound essential oil can significantly enhance the excitability and stability of the nervous system by promoting the release and homeostasis of central monoamine neurotransmitters, regulating amino acid neurotransmitter metabolism, and thus exerting a significant effect of refreshing and anti-fatigue.
[0086] Table 5 Results of hormone levels in the HPA axis of mice
[0087] Based on research on the neuroendocrine and central fatigue mechanisms, overactivation of the HPA axis is closely related to the occurrence of chronic fatigue. (See Table 5 and...) Figure 8 , 9 As shown in Figure 10, stress or chronic fatigue can lead to hyperactivity of the HPA axis, increased secretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), and consequently, a sustained increase in terminal glucocorticoid levels. Excessive CORT not only inhibits immune and metabolic balance but also affects the excitability and energy homeostasis of the central nervous system, further exacerbating fatigue and cognitive decline. Compared with the control group, the serum levels of CRH, ACTH, and CORT in the model group mice were significantly increased (P<0.05), indicating that the fatigue model successfully induced HPA axis hyperactivity and neuroendocrine homeostasis imbalance. Compared with the model group, after intervention in Example 3, all three indicators showed varying degrees of regression, with a particularly significant decrease in CORT levels. This indicates that the intervention can effectively inhibit excessive activation of the HPA axis, reduce stress-induced increases in glucocorticoids, and help restore neuroendocrine balance, thereby improving fatigue-related physiological and behavioral performance and providing neuroendocrine-level mechanistic support for its invigorating and anti-fatigue effects.
[0088] Table 6 Results of serum oxidative stress markers in mice
[0089] Studies have shown that oxidative stress is closely related to the occurrence and development of fatigue. (See Table 6 and...) Figure 11As shown, under chronic fatigue, the body generates more free radicals and its antioxidant capacity decreases, leading to elevated levels of lipid peroxidation products such as malondialdehyde (MDA). MDA is the end product of membrane lipid peroxidation, and its content directly reflects the degree of oxidative damage, thereby affecting cellular energy metabolism and neuromuscular function, resulting in increased fatigue and delayed physical recovery. Compared with the control group, the serum MDA content in the model group mice was significantly increased (P<0.05), indicating that the fatigue model successfully induced oxidative stress in the body, exacerbating lipid peroxidation damage. Compared with the model group, the MDA level after the intervention in Example 3 was significantly reduced, recovering to levels close to those in the control group, suggesting that this intervention can effectively reduce oxidative stress damage and inhibit lipid peroxidation. This helps protect the integrity of cell structure and maintain stable energy metabolism, thus providing important antioxidant mechanisms to alleviate fatigue, enhance physical endurance, and promote recovery.
[0090] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.
Claims
1. A stimulating compound essential oil composition, characterized in that, It is composed of the following ingredients in parts by weight: 25-50 parts bergamot essential oil, 9-25 parts white lemon essential oil, 2-7 parts forsythia essential oil, 4-10 parts sweet orange essential oil, 1-5 parts cinnamon essential oil, 2-10 parts anethole essential oil, 1-6 parts borneol essential oil, 2-8 parts peppermint essential oil, and 5-20 parts lemon essential oil.
2. The invigorating compound essential oil composition according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 30-40 parts bergamot essential oil, 10-20 parts white lemon essential oil, 3-6 parts forsythia essential oil, 5-8 parts sweet orange essential oil, 2-4 parts cinnamon essential oil, 4-8 parts anethole essential oil, 2-5 parts borneol essential oil, 3-7 parts peppermint essential oil, and 8-12 parts lemon essential oil.
3. The invigorating compound essential oil composition according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 32-38 parts bergamot essential oil, 12-18 parts white lemon essential oil, 4-6 parts forsythia essential oil, 6-8 parts sweet orange essential oil, 2-3 parts cinnamon essential oil, 5-7 parts anethole essential oil, 3-5 parts borneol essential oil, 4-6 parts peppermint essential oil, and 9-11 parts lemon essential oil.
4. The invigorating compound essential oil composition according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 32 parts bergamot essential oil, 18 parts white lemon essential oil, 6 parts forsythia essential oil, 6 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 5 parts peppermint essential oil, and 10 parts lemon essential oil.
5. The invigorating compound essential oil composition according to claim 1, characterized in that, The following components are composed of the following parts by weight: 38 parts bergamot essential oil, 12 parts white lemon essential oil, 4 parts forsythia essential oil, 8 parts sweet orange essential oil, 2 parts cinnamon essential oil, 7 parts anethole essential oil, 3 parts borneol essential oil, 6 parts peppermint essential oil, and 9 parts lemon essential oil.
6. The invigorating compound essential oil composition according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 35 parts bergamot essential oil, 15 parts white lemon essential oil, 5 parts forsythia essential oil, 7 parts sweet orange essential oil, 3 parts cinnamon essential oil, 6 parts anethole essential oil, 4 parts borneol essential oil, 5 parts peppermint essential oil, and 10 parts lemon essential oil.
7. A method for preparing a stimulating compound essential oil composition as described in any one of claims 1-6, characterized in that, Includes the following steps: Weigh out each component essential oil raw material according to the weight proportions, stir and mix well to obtain the invigorating compound essential oil composition.
8. The method for preparing a stimulating compound essential oil composition according to claim 7, characterized in that, The mixing and blending are carried out under light-protected conditions.
9. A compound essential oil product for refreshing and invigorating the mind, characterized in that, It includes an active ingredient and a product carrier, wherein the active ingredient is a stimulating compound essential oil composition as described in any one of claims 1-6, and the product carrier is at least one of a loading material, a matrix, an excipient, or a structural component.
10. A stimulating and invigorating compound essential oil product according to claim 9, characterized in that, The product is a product used by smelling, applying or absorbing aromatherapy, and is selected from at least one of essential oil rollerballs, essential oil inhalers, essential oil aromatherapy sprays, essential oil massage oils, essential oil aromatherapy candles, essential oil diffusers, essential oil patches, essential oil sachets, essential oil ointments or essential oil lotions.
Citation Information
Patent Citations
Compound essential oils, their applications, and compound essential oil products
CN109432318B
