Combined use of cedarwood essential oil and cypress essential oil, and composition for improving sleep disorder or anxiety

Abstract

The invention provides application of combined use of cypress essential oil and cypress essential oil in a composition for improving sleep disorder or anxiety. The invention also provides a composition for improving sleep disorder or anxiety. The composition is suitable for prevention and treatment of diseases and daily health care, and is also suitable for sleep disorder and anxiety caused by special environments such as plateau, diving and aviation.

Description

Technical Field

[0001] The invention relates to the combined use of cedarwood essential oil and cypresswood essential oil, and a composition for improving sleep disorder or anxiety. Background Art

[0002] Sleep disorders refer to functional disorders that occur during the initiation and maintenance of the sleep-wake cycle, including insomnia, sleep apnea syndrome, parasomnias, circadian rhythm disorders, and other problems. Sleep is beneficial to physical and mental recovery, while sleep disorders can cause sensory dysfunction, reduced daytime work ability, and decreased immunity, leading to the occurrence and development of heart disease, Alzheimer's disease, anxiety, depression, and other diseases. With the accelerated pace of life, sleep disorders have become one of the common problems that affect people's daily work and life.

[0003] Special environments such as plateaus, diving and aviation can lead to instability in the human body's feedback control system, causing sleep disorders. Sleep disorders are the most common health problems for people living in high altitude areas, and plateau sleep disorders are also one of the most common discomfort reactions for people who first enter the plateau, usually manifested as difficulty falling asleep, difficulty maintaining sleep, sleep rhythm disorders, frequent dreams, easy awakening, etc.

[0004] Anxiety is a common emotional state, which is mainly manifested as excessive worry, tension, and uneasiness. Anxiety makes the brain highly active, making it difficult to relax and fall asleep; it causes physical tension, which prevents muscles from relaxing, affects sleep quality, and causes sleep disorders. Sleep disorders can make people feel exhausted, and physical and mental fatigue can further aggravate anxiety; it can also affect the balance of neurotransmitters in the brain, such as serotonin and dopamine. These neurotransmitters are closely related to emotional regulation, and imbalance can aggravate anxiety symptoms.

[0005] Benzodiazepines are currently commonly used in clinical practice to treat sedatives and hypnotics. Non-benzodiazepines Drugs such as melatonin receptor agonists and antidepressants for the treatment of sleep disorders; benzodiazepines Drugs such as analgesia and antidepressants can improve anxiety. However, these drugs are prone to tolerance, dependence and addiction, and may cause adverse reactions such as drowsiness, dizziness, fatigue, and memory loss. Sudden discontinuation of the drug may also cause withdrawal reactions.

[0006] External treatment of sleep disorders and anxiety by traditional Chinese medicine has significant advantages such as few side effects, overall regulation, and good comprehensive efficacy. External treatment of traditional Chinese medicine usually does not pass through the digestive system and liver metabolism, which reduces the stimulation of the gastrointestinal tract and the burden on the liver, and reduces the risk of adverse drug reactions; it can also avoid interactions with other drugs. It can also regulate multiple internal organs and meridian systems at the same time to achieve overall balance and coordination, improve immunity and self-regulation ability, and prevent the recurrence of diseases. Chinese aromatherapy is an important part of external treatment of traditional Chinese medicine. Chinese herbal essential oils usually have strong pharmacological activity, are aromatic, pungent, dispersing, warming, and their molecules are fine, highly volatile, and highly fat-soluble. They can easily pass through the biological membranes in the body, have high bioavailability, and can be quickly absorbed and effective through the gastrointestinal tract, nasal, oral mucosa, skin, etc. Chinese herbal essential oils can directly act on the brain's limbic system through the olfactory nerves to improve sleep disorders and anxiety; they can also enter the human body through the respiratory mucosa, alveoli, skin, etc., act on the internal organs and meridians, promote the circulation of qi and blood, balance the body's yin and yang, and regulate the body's functions as a whole. They can not only improve the symptoms of sleep disorders and anxiety, but also improve immunity and self-regulation ability to prevent recurrence. Chinese herbal essential oils act quickly, safely, effectively, and gently, and are not easy to produce drug resistance and dependence, making them suitable for long-term use.

[0007] Extracted from the plant Juniperus virginiana in the Cupressaceae family, cypress essential oil has a soft woody smell, similar to the scent of pencils, and a hint of a faint sandalwood scent. It is light yellow or light orange in color and has a viscous texture. The main chemical components of cypress essential oil include cedrene, sesquiterpenes, and cedrehol. It has a calming effect on the skin, relieves itching, and has an astringent effect, which is beneficial for acne, oily skin, and hair and dandruff. In addition, cypress essential oil helps treat chest and urinary tract infections, can be used as a general tonic, has a significant effect on mucous membranes, and has a calming and soothing effect on the nerves, which is very helpful for anxiety and nervous tension. Zhang Kai, Study on the anti-anxiety effect and mechanism of cypress essential oil, School of Agriculture and Biology, Shanghai Jiao Tong University, November 2019, disclosed that sesquiterpenoid compounds (such as cypress alcohol) in cypress essential oil have the function of regulating the activity of the autonomic nervous system, and the essential oil has an anti-anxiety effect under two intake routes: olfaction and intraperitoneal injection.

[0008] Cypress essential oil is a natural substance extracted from the bark and leaves of cypress (Chamaecyparis obtusa) by steam distillation, and has multiple functions and uses. Cypress essential oil is known for its calming and relaxing properties, and can help relieve stress and anxiety. It can be used for bathing or steam inhalation to completely relax the body and mind. CN202310933611.0, invention name: solidified particles containing cypress essential oil, preparation method and application of cypress essential oil, discloses a solidified particle containing cypress essential oil, the solidified particle is obtained by adsorbing and encapsulating plant essential oil containing cypress essential oil with mesoporous molecular sieve, and at the same time discloses the extraction method and practical application of cypress essential oil, which is applied to a sleep-aiding pillow to effectively improve the sleep-aiding effect of the human body; eliminate insomnia, headache, anxiety, help respiratory organs and lung function, improve blood circulation and heart vitality, reduce hypertension and prevent vascular sclerosis, and promote the activation of systemic cell metabolism.

[0009] Since the effect of a single essential oil is relatively simple, multiple essential oils are usually used in combination. Currently, there are no literature reports on the combined use of cypress essential oil and cypress essential oil, nor are there any reports on prescriptions containing cypress essential oil and cypress essential oil. Summary of the invention

[0010] The invention provides a cedarwood essential oil and a cypresswood essential oil for use in combination to improve sleep disorders or anxiety. The invention also provides a composition containing the cedarwood essential oil and the cypresswood essential oil.

[0011] The invention provides use of cedarwood essential oil and juniperwood essential oil in combination in a composition for improving sleep disorders or anxiety.

[0012] Among them, the weight ratio of the cedar essential oil to the cypress essential oil is: 1-2 parts of cedar essential oil, 1-2 parts of cypress essential oil; preferably, the weight ratio of the cedar essential oil to the cypress essential oil is: 1.5 parts of cedar essential oil, 1.5 parts of cypress essential oil; the composition is used to improve high altitude sleep disorders.

[0013] The present invention also provides a composition for improving sleep disorders or anxiety, which is prepared from raw materials containing the following weight ratios:

[0014] 1-2 parts of cypress essential oil, 1-2 parts of juniper essential oil.

[0015] Furthermore, the raw material also contains lavender essential oil, vetiver essential oil, agarwood essential oil, and dalbergia odorifera essential oil, and the weight ratio thereof is:

[0016] 1.0-3.0 parts of lavender essential oil, 1.0-3.0 parts of vetiver essential oil, 0.2-0.8 parts of agarwood essential oil, and 0.5-1.5 parts of dalbergia odorifera essential oil.

[0017] The composition of the present invention is prepared from the following raw materials in weight ratio:

[0018] 1.0-3.0 parts of lavender essential oil, 1.0-3.0 parts of vetiver essential oil, 0.2-0.8 parts of agarwood essential oil, 0.5-1.5 parts of dalbergia odorifera essential oil, 1-2 parts of cypress essential oil, 1-2 parts of cypress essential oil;

[0019] Preferably, it is prepared from the following raw materials in weight ratio:

[0020] 2.0 parts of lavender essential oil, 2.0 parts of vetiver essential oil, 0.5 parts of agarwood essential oil, 1.0 parts of dalbergia odorifera essential oil, 1.5 parts of cypress essential oil, and 1.5 parts of cypress essential oil.

[0021] The raw materials also contain 0.2 to 3 parts of geranium essential oil, chamomile essential oil, orange blossom essential oil, ylang-ylang essential oil, bergamot essential oil, lemon essential oil or sandalwood essential oil.

[0022] The composition of the present invention is prepared from the following raw materials in weight ratio:

[0023] 1.0-3.0 parts of lavender essential oil, 1.0-3.0 parts of vetiver essential oil, 0.2-0.8 parts of agarwood essential oil, 0.5-1.5 parts of dalbergia odorifera essential oil, 1-2 parts of cypress essential oil, 1-2 parts of juniper essential oil, 0.2-3 parts of geranium essential oil, chamomile essential oil, neroli essential oil, ylang-ylang essential oil, bergamot essential oil, lemon essential oil or sandalwood essential oil;

[0024] Preferably, the weight ratio of the raw materials is:

[0025] 2.0 parts of lavender essential oil, 2.0 parts of vetiver essential oil, 0.5 parts of agarwood essential oil, 1.0 parts of dalbergia odorifera essential oil, 1.5 parts of cypress essential oil, 1.5 parts of cypress essential oil, and 2.0 parts of geranium essential oil.

[0026] The composition of the present invention is prepared from raw materials in the following weight ratio: it is a preparation prepared by adding the raw materials as active ingredients to excipients or auxiliary ingredients acceptable in pharmacy or health products.

[0027] Among them, the preparations are inhalation preparations and external preparations; the inhalation preparations include aerosols, inhalation powder aerosols, nebulized inhalation preparations, inhalation liquid preparations, nasal sprays, and aromatherapy agents; the external preparations include aqueous solutions, emulsions, creams, ointments, oils, and liniments.

[0028] The present invention provides use of the composition in preparing medicines or health products for improving high-altitude sleep disorders.

[0029] The combined use of cypress essential oil and juniper essential oil can enhance the soothing and anti-anxiety effects, and the scent is richer. Both of them help to clear the respiratory tract and maintain respiratory health.

[0030] Lavender is a common medicinal plant used by the Uygur ethnic group in Xinjiang. It has the effects of drying and generating heat, removing abnormal mucus, clearing the brain, nourishing the meridians and calming the nerves. Lavender volatile oil is its main functional part. It can be used to treat neurasthenia, insomnia, and improve cognitive dysfunction. Lavender volatile oil can regulate the secretion level of neurotransmitters in brain tissue and play a role in helping sleep. Vetiver essential oil can deeply relax the nerves, improve insomnia and sleep disorders caused by stress, anxiety, etc., and is called "tranquility oil". The combination of lavender essential oil and vetiver essential oil can relieve tension and anxiety, help relax the body and mind, and enter deep sleep. They are both monarch drugs. Agarwood essential oil has the effects of promoting qi and relieving pain, calming the nerves and helping sleep. It can promote the circulation of qi and blood in the body and relieve insomnia symptoms; Dalbergia odorifera essential oil has the effects of removing blood stasis and stopping bleeding, regulating qi and relieving pain. It can relieve physical and psychological tension by regulating the circulation of qi and blood, thereby helping to improve sleep quality; the combination of agarwood essential oil and Dalbergia odorifera essential oil can further enhance the effects of lavender essential oil and vetiver essential oil in relieving tension and anxiety and calming the nerves and helping sleep, and they are both ministerial drugs. Cypress essential oil and cypress essential oil can soothe nerves, relax the body and mind, and thus help improve sleep, and are adjuvant drugs. Geranium essential oil, chamomile essential oil, ylang-ylang essential oil and other essential oils have sweet, delicate and elegant aromas, can be used to adjust the fragrance, and also have the effects of balancing the body and mind and relieving stress. They can help people relax the body and mind, relieve anxiety and tension, and thus improve sleep quality, and are adjuvant drugs. After the essential oils of the prescription are combined, the overall effect of relieving tension, calming the nerves and helping sleep can be played, which can improve sleep quality and increase deep sleep.

[0031] The invention provides an essential oil composition for improving sleep disorders and anxiety, which is suitable for the prevention and treatment of diseases and daily health care, and is also suitable for sleep disorders and anxiety caused by special environments such as plateaus, diving and aviation. DETAILED DESCRIPTION

[0032] Use steam distillation, molecular distillation, supercritical CO2 extraction, immersion, pressing and other extraction methods to extract single essential oils or purchase commercially available products.

[0033] The selection of the optimal ratio of essential oils is based on a comprehensive consideration of factors such as the therapeutic effect and the fragrance, properties, safety, and irritation of the essential oils after combination.

[0034] Example 1 Preparation of the composition of the present invention

[0035] 2.0g lavender essential oil, 2.0g vetiver essential oil, 1.0g agarwood essential oil, 1.0g dalbergia odorifera essential oil.

[0036] Example 2 Preparation of the composition of the present invention

[0037] 2.0g lavender essential oil, 1.0g vetiver essential oil, 0.2g agarwood essential oil, 1.5g dalbergia odorifera essential oil.

[0038] Example 3 Preparation of the composition of the present invention

[0039] Lavender essential oil 1.0g, Vetiver essential oil 2.0g, Agarwood essential oil 0.8g, Dalbergia odorifera essential oil 1.0g.

[0040] Example 4 Preparation of the composition of the present invention

[0041] Lavender essential oil 2.0g, vetiver essential oil 2.0g, agarwood essential oil 0.5g, dalbergia odorifera essential oil 1.0g, cypress essential oil 1.5g, cypress essential oil 1.5g.

[0042] Example 5 Preparation of the composition of the present invention

[0043] Lavender essential oil 2.0g, vetiver essential oil 2.0g, agarwood essential oil 0.5g, dalbergia odorifera essential oil 1.0g, cypress essential oil 1.0g, cypress essential oil 2.0g.

[0044] Example 6 Preparation of the composition of the present invention

[0045] Lavender essential oil 2.0g, vetiver essential oil 2.0g, agarwood essential oil 0.5g, dalbergia odorifera essential oil 1.0g, cypress essential oil 2.0g, cypress essential oil 1.0g.

[0046] Example 7 Preparation of the composition of the present invention

[0047] Lavender essential oil 2.0g, vetiver essential oil 2.0g, agarwood essential oil 0.5g, dalbergia odorifera essential oil 1.0g, cypress essential oil 1.5g, juniper essential oil 1.5g, geranium essential oil 2.0g.

[0048] Example 8 Preparation of the composition of the present invention

[0049] Lavender essential oil 2.0g, vetiver essential oil 2.0g, agarwood essential oil 0.5g, dalbergia odorifera essential oil 1.0g, cypress essential oil 1.5g, juniper essential oil 1.5g, geranium essential oil 1.0g.

[0050] Example 9 Preparation of the composition of the present invention

[0051] Lavender essential oil 2.0g, vetiver essential oil 2.0g, agarwood essential oil 0.5g, dalbergia odorifera essential oil 1.0g, cypress essential oil 1.5g, juniper essential oil 1.5g, ylang-ylang essential oil 0.2g.

[0052] Example 10 Preparation of the composition of the present invention

[0053] Lavender essential oil 2.0g, vetiver essential oil 2.0g, agarwood essential oil 0.5g, dalbergia odorifera essential oil 1.0g, cypress essential oil 1.5g, juniper essential oil 1.5g, ylang-ylang essential oil 0.5g.

[0054] The compositions in the above examples are obtained by directly mixing the essential oils.

[0055] When the components in the essential oil composition are matched, the selection of the dosage needs to comprehensively consider the efficacy after matching and the smell, properties, safety, irritation and other factors of the essential oil after matching. The efficacy pre-test screens the ratio of essential oil matching. In the light and dark box experiment, the essential oil composition can significantly increase the latency, number and residence time of mice entering the light box. In the open field experiment, the essential oil composition can significantly increase the total movement distance of mice, the movement distance of the central area and the residence time of the central area of ​​mice, and the essential oil composition has a significant anti-anxiety effect. The essential oil composition significantly shortens the sleep latency of mice induced by the above-threshold dose of sodium pentobarbital and prolongs the duration of sleep in mice. In the above embodiments, the essential oil of Example 4 has the best effect, followed by Example 9, Example 9 is better than Example 10, Example 10 is better than Example 7, Example 7 is better than Example 5 and Example 6, and Example 3 has the worst effect. Example 7 has the best odor acceptability.

[0056] The beneficial effects of the present invention are demonstrated by the following efficacy tests.

[0057] Test Example 1: Anxiolytic Effect

[0058] 1. Experimental grouping, modeling and drug administration methods

[0059] 140 SPF KM mice, weighing 20±2g, half ♀ and half ♂, were kept in the laboratory for 3 days. The mice were subjected to the light-dark box experiment, and the latency (the first time to completely enter the light box from the dark box), the number of times and the residence time of the mice entering the light box within 10 minutes were recorded. The time the mice stayed in the light box should be less than 40% of the total time. The mice that did not enter the dark box for 5 minutes and the mice that entered the light box less than or equal to 10 times were eliminated. A total of 125 mice met the requirements, including 61 ♀ and 64 ♂.

[0060] A total of 120 KM mice that met the requirements were randomly divided into blank group, model group, lavender essential oil group, vetiver essential oil group, agarwood essential oil group, dalbergia odorifera essential oil group, cypress essential oil group, cypress essential oil group, cypress-cypress essential oil group (cypress-cypress 1:1), compound essential oil group 1 (lavender-vetiver-agarwood-dalbergia odorifera 2:2:0.5:1), compound essential oil group 2 (lavender-vetiver-agarwood-dalbergia odorifera-cypress-cypress 2:2:0.5:1:1.5:1.5), and compound essential oil group 3 (lavender-vetiver-agarwood-dalbergia odorifera-cypress-cypress 2:2:0.5:1:1.5:1.5), with 10 mice in each group. There was no significant difference in the number of times mice in each group entered the light box and the time they stayed in the light box (P>0.05).

[0061] The mice in the blank group, model group, and essential oil group were subjected to nebulized aromatherapy for 15 minutes. The blank group and model group were given 25 ml of water, and the essential oil group was given 2 drops of essential oil in 25 ml of water, about 0.05 g. The volume of the animal aromatherapy room was about 50 L (52 cm × 38 cm × 25 cm). The dosage was 0.25 g / kg (calculated as essential oil dosage); the drug was administered continuously for 14 days.

[0062] On the 8th day of administration, except for the blank group, the mice in the other groups were subcutaneously injected with 8 mg / kg MCPP once a day for 3 times. The blank group was injected with an equal volume of normal saline.

[0063] 2. Light and dark box experiment

[0064] The light-dark box experiment was performed 1.0 h after the last inhalation of drug administration, and the latency (the first time the mouse completely entered the light box from the dark box), number of times and residence time of the mouse entering the light box within 10 min were recorded.

[0065] 2.1 Results of light-dark box experiment

[0066] Compared with the blank group, the latency of mice in the model group to enter the light box was significantly prolonged, and the number of mice entering the light box and the time they stayed there were significantly reduced (<0.05). Compared with the model group, the compound essential oil group could significantly shorten the latency of mice entering the light box, and the agarwood essential oil, cypress-juniper essential oil, and compound essential oil could increase the number of mice entering the light box and the time they stayed there (P<0.05), with compound essential oil 2 having the best effect; compared with the blank group, there was no significant difference in the compound essential oil group. The results are shown in Table 1.

[0067] Table 1 Results of light-dark box experiment

[0068]

[0069] Compared with the model group, * P<0.05, ** P<0.01; compared with the blank group,# P<0.05, ## P < 0.01;

[0070] 3. Open field experiment

[0071] After the light and dark box experiment, the mice were allowed to recover and adapt for 3 days, during which aromatherapy was continued. The open field experiment was conducted 1.0 h after the last inhalation administration. The mice were placed in the central area of ​​the open field test box, and a computer monitoring and analysis system was used to record the total distance traveled by the mice, the distance traveled in the central area, and the time they stayed in the central area within 10 min.

[0072] 3.1 Open field test results

[0073] Compared with the blank group, the total movement distance, central movement distance and central residence time of mice in the model group were significantly reduced. Compared with the model group, the single essential oil group, the cypress-juniper drug pair essential oil group, and the compound essential oil group could significantly increase the total movement distance and central movement distance of mice (P < 0.05); agarwood essential oil, cypress-juniper drug pair essential oil, and compound essential oil could significantly increase the central residence time of mice; compared with the normal group, the total movement distance, central movement distance and central residence time of mice in the single essential oil group were significantly reduced (P < 0.05), and there was no significant difference in the compound essential oil group. The results are shown in Table 2.

[0074] Table 2 Results of light-dark box experiment

[0075]

[0076] Compared with the model group, * P<0.05, ** P<0.01; compared with the blank group, # P<0.05, ## P < 0.01;

[0077] Test Example 2 Sedative and hypnotic effect (Effect of p-chlorophenylalanine (PCPA) on insomniac mice)

[0078] 1. Reproduction of insomnia mouse model

[0079] The mice were intraperitoneally injected with para-chlorophenylalanine (PCPA) suspension at a dose of 350 mg / kg, once a day for 3 consecutive days, to induce the insomnia mouse model. After the model was established, the behavior, morphology and excretion of the mice were observed. The model was considered successful if the mice had messy and dark hair, gray feces, increased urine and feces, increased activity, irritability, lack of circadian rhythm, and uninterrupted activity during the day and night.

[0080] 2. Experimental Grouping and Drug Administration

[0081] A total of 130 SPF KM mice, weighing 20±2g, with half ♀ and half ♂, were housed in the laboratory for 3 days and randomly divided into blank group, model group, lavender essential oil group, vetiver essential oil group, agarwood essential oil group, dalbergia odorifera essential oil group, cypress essential oil group, cypress essential oil group, cypress-cypress essential oil group, compound essential oil group 1 (lavender-vetiver-agarwood-dalbergia odorifera 2:2:0.5:1), compound essential oil group 2 (lavender-vetiver-agarwood-dalbergia odorifera-cypress-cypress 2:2:0.5:1:1.5:1.5), compound essential oil group 3 (lavender-vetiver-agarwood-dalbergia odorifera-cypress-cypress-cypress 2:2:0.5:1:1.5:1.5), and diazepam-positive group, with 10 mice in each group.

[0082] The mice in the blank group were not treated, and the mice in the model group and the experimental group were treated with the insomnia mouse model according to the method in 2.2.1. The mice in the blank group, the model group, and the essential oil group were subjected to atomized aromatherapy for 15 minutes. The blank group and the model group were treated with 25 ml of water, and the essential oil group was treated with 2 drops of essential oil in 25 ml of water, about 0.05 g. The volume of the animal aromatherapy room was about 50 L (52 cm × 38 cm × 25 cm), and the dosage was 0.25 g / kg. The diazepam-positive group was given oral administration at a dose of 1.5 mg / Kg; the administration lasted for 7 consecutive days.

[0083] 3. Effect of suprathreshold dose of sodium pentobarbital on sleep time of mice

[0084] 1.0h after the last administration, mice in each group were intraperitoneally injected with amobarbital at a dose of 45mg / kg, and the sleep latency (the time from administration to the disappearance of righting reflex for more than 30s) and sleep duration (the time from the disappearance of righting reflex to recovery) of mice were measured.

[0085] Compared with the blank group, the sleep latency of mice in the model group was significantly prolonged, and the sleep duration was significantly shortened (P<0.01). Compared with the model group, the single essential oil group, the cypress-juniper essential oil group, the compound essential oil group, and the positive drug group could significantly shorten the sleep latency and prolong the sleep duration (P<0.05). Compared with the blank group, there was no significant difference in the sleep latency between the agarwood essential oil group and the compound essential oil group (P>0.05), the sleep latency in the positive drug group was significantly shortened (P<0.05), and the sleep latency in the other groups was significantly prolonged (P<0.05); there was no significant difference in the sleep duration in the agarwood essential oil group (P>0.05), the sleep duration in the compound essential oil group and the positive drug group was significantly prolonged (P<0.05), and the sleep duration in the other groups was significantly shortened (P<0.05). Compared with the positive drug diazepam group, the compound essential oil group had no significant difference in sleep latency and sleep duration (P>0.05), except that the sleep duration of compound essential oil group 2 was significantly prolonged (P<0.05); the sleep latency of the single essential oil group was significantly prolonged, and the sleep duration was significantly shortened (P<0.05). The results are shown in Table 3.

[0086] Table 3 Effects of suprathreshold dose of sodium pentobarbital on sleep time in mice

[0087]

[0088] Compared with the model group, * P<0.05, ** P<0.01; compared with the blank group, # P<0.05, ## P<0.01; compared with the positive group, & P<0.05, && P < 0.01;

[0089] 4. Elisa method to determine the content of 5-HT and GABA in hippocampal tissue

[0090] After the mice woke up, they were killed by dislocation, and the hippocampal tissue of the mice was removed. The brain tissue was rinsed with pre-cooled phosphate buffered saline (PBS, pH 7.4) solution, and the excess liquid was absorbed with filter paper. 100 mg of brain tissue was accurately weighed, 1 ml of pre-cooled PBS (pH 7.4) was added, and the mixture was homogenized in an ice bath to prepare hippocampal tissue homogenate. The mixture was centrifuged at 4000 r / min at 4°C for 20 min, and the supernatant was taken. The contents of 5-HT and GABA were determined according to the steps in the Elisa kit manual.

[0091] Compared with the blank group, the contents of 5-HT and GABA in the hippocampus of mice in the model group were significantly reduced (P < 0.01). Compared with the model group, the single essential oil group, the cypress-juniper drug pair essential oil group, the compound essential oil group, and the positive drug group could significantly increase the contents of 5-HT and GABA in the hippocampus of mice (P < 0.05). Compared with the blank group, there was no significant difference in the contents of 5-HT and GABA in the hippocampus of the compound essential oil group (P > 0.05), the contents of 5-HT and GABA in the hippocampus of mice in the single essential oil group and the cypress-juniper drug pair essential oil group were significantly reduced (P < 0.05), and the contents of 5-HT and GABA in the hippocampus of mice in the positive drug group were significantly increased (P < 0.05). Compared with the positive drug diazepam group, the contents of 5-HT and GABA in the hippocampus of mice in each essential oil group were significantly reduced (P < 0.05). The results are shown in Table 4.

[0092] Table 4 Effects of 5-HT and GABA content in hippocampal tissue

[0093]

[0094]

[0095] Compared with the model group, * P<0.05,** P<0.01; compared with the blank group, # P<0.05, ## P<0.01; compared with the positive group, & P<0.05, && P < 0.01;

[0096] Single essential oil, cypress-juniper essential oil and compound essential oil can improve the sleep of mice with insomnia caused by chlorophenylalanine (PCPA). The effect of cypress-juniper drug pair is better than single cypress essential oil and single cypress essential oil, and is equivalent to single vetiver essential oil. The effect of compound essential oil is better than each single essential oil and cypress-juniper essential oil. There is no significant difference in the content of 5-HT and GABA in the brain tissue of mice in the compound essential oil group and the normal group. The content of 5-HT and GABA in the brain tissue of mice in the positive drug group is significantly higher than that in the normal group. The abnormal increase of 5-HT and GABA content will induce adverse reactions such as nausea, vomiting, drowsiness, ataxia and tolerance.

[0097] Clinical efficacy of test example 3

[0098] The compound essential oil 3-chain triglyceride (MCT) or grape seed oil or peony seed oil or safflower seed oil or olive oil or rice oil is used as a diluent to prepare essential oil bursting beads with an essential oil concentration of 10% to 50%, and the essential oil bursting beads are placed in the cavity of the oxygen generating valve of the oxygen cylinder. When used, the bursting beads are squeezed and oxygen is inhaled as a fluid aromatherapy to evaluate the effect of improving sleep disorders.

[0099] The compound essential oil 3 was diluted with multi-chain triglycerides (MCT) to an essential oil concentration of 25% and prepared into burst beads.

[0100] 1. Recruit 100 healthy adult volunteers who are visiting Tibet for the first time, including 60 males and 40 females, aged (32.55±9.49) years, height (162.37±9.15) cm, weight (58.33±11.29) kg, who have not experienced one or more abnormal sleep symptoms such as difficulty falling asleep, waking up easily, waking up early, etc. in the past two weeks, and have not taken sleep aids or received non-drug treatment in the past month. After clinical medical examination, they have no acute or chronic diseases such as circulatory, respiratory, and gastrointestinal diseases.

[0101] 2. Inclusion criteria

[0102] After three days in the Tibetan area, they experienced one or more abnormal sleep symptoms such as difficulty falling asleep, waking up easily, and waking up early on two days. Among them, there were 32 males and 22 females. The sleep quality index of five dimensions, including subjective sleep quality, sleep time, sleep efficiency, sleep disorders, and daytime dysfunction, was self-assessed. Each dimension was scored on a scale of 0-3 points, with "0" indicating no difficulty and "3" indicating very difficult. The scores of each dimension were added together to form the total score of the sleep index, which ranged from 0 to 15. The higher the score, the worse the sleep quality. "0" means no difficulty, and "15" means very difficult in all dimensions. The self-assessment form of the sleep quality index is shown in Appendix 1.

[0103] 3. A randomized single-blind experiment was conducted to divide volunteers who experienced symptoms of sleep disorders into two groups: a control group that only inhaled oxygen, and an experimental group that inhaled essential oil oxygen. There were 27 people in each group, including 16 males and 11 females. There was no significant difference in general information such as gender, age, weight, and sleep quality index between the two groups (P>0.05), so the two groups were comparable.

[0104] 4. The volunteers in both groups inhaled oxygen or essential oil oxygen for 15 minutes 30 minutes before going to bed every day for 3 consecutive days. The main complaints were asked and the number of people whose sleep disorder symptoms were significantly alleviated or disappeared was recorded. The sleep quality index was self-assessed.

[0105] The therapeutic efficacy was determined based on the treatment score: cured: efficacy index ≥ 75%; markedly effective: efficacy index 50% ≤ efficacy index < 75%; effective: 25% ≤ efficacy index < 50%; ineffective: efficacy index < 25%.

[0106] Therapeutic index = (score before oxygen inhalation - score after treatment) / score before treatment × 100%.

[0107] 5. Clinical efficacy analysis

[0108] Compared with the control group, the number of volunteers in the experimental group who felt that their sleep disorder symptoms were significantly reduced or disappeared was significantly higher than that of the control group, and the sleep quality index was significantly reduced. The cure rate, significant efficacy and effective rate of sleep disorders were all higher than those of the control group. The experimental results are shown in Table 5.

[0109] Table 5 Effects on sleep disorder symptoms

[0110]

[0111] Compared with before oxygen inhalation, * P<0.05, ** P<0.01; compared with the control group, ▲ P<0.05, ▲▲ P<0.01

[0112] In summary, the essential oil composition for improving sleep disorders and anxiety provided by the present invention has a scientific compatibility and significant therapeutic effect, can be used for daily health care and disease prevention and treatment, and can also be used in special environments such as plateaus, diving and aviation.

[0113] Annex 1

[0114] Sleep quality index self-assessment form and statistical method

[0115] The sleep quality index self-assessment form consists of five dimensions: subjective sleep quality, sleep onset time, sleep efficiency, sleep disorders, and daytime functional disorders. Each dimension is scored on a 0-3 scale, with "0" indicating no difficulty and "3" indicating very difficult. The scores of each dimension are added together to form the total score of the sleep index, which ranges from 0 to 15. The higher the score, the worse the sleep quality. "0" means no difficulty, and "15" means very difficult in all dimensions.

[0116] Sleep quality index self-assessment form

[0117]

[0118] Total score of sleep index = sleep quality score + sleep time score + sleep efficiency score + sleep disorder score + daytime dysfunction score

Claims

1. Use of cedarwood essential oil and cypresswood essential oil in combination in a composition for improving sleep disorders or anxiety.

2. The use according to claim 1, characterized in that: The weight ratio of the cedar essential oil to the cypress essential oil is: 1-2 parts of cedar essential oil and 1-2 parts of cypress essential oil; preferably, the weight ratio of the cedar essential oil to the cypress essential oil is: 1.5 parts of cedar essential oil and 1.5 parts of cypress essential oil; the composition is used to improve high altitude sleep disorders.

3. A composition for improving sleep disorders or anxiety, characterized in that: It is prepared from raw materials containing the following weight ratios: 1-2 parts of cypress essential oil, 1-2 parts of juniper essential oil.

4. The composition for improving sleep disorders or anxiety according to claim 3, characterized in that: The raw materials also contain lavender essential oil, vetiver essential oil, agarwood essential oil, and dalbergia odorifera essential oil, and the weight ratio thereof is: 1.0-3.0 parts of lavender essential oil, 1.0-3.0 parts of vetiver essential oil, 0.2-0.8 parts of agarwood essential oil, and 0.5-1.5 parts of dalbergia odorifera essential oil.

5. The composition for improving sleep disorders or anxiety according to claim 4, characterized in that: It is prepared from the following raw materials in weight ratio: 1.0-3.0 parts of lavender essential oil, 1.0-3.0 parts of vetiver essential oil, 0.2-0.8 parts of agarwood essential oil, 0.5-1.5 parts of dalbergia odorifera essential oil, 1-2 parts of cypress essential oil, 1-2 parts of cypress essential oil; Preferably, it is prepared from the following raw materials in weight ratio: 2.0 parts of lavender essential oil, 2.0 parts of vetiver essential oil, 0.5 parts of agarwood essential oil, 1.0 parts of dalbergia odorifera essential oil, 1.5 parts of cypress essential oil, and 1.5 parts of cypress essential oil.

6. The composition for improving sleep disorders or anxiety according to claim 4, characterized in that: The raw materials also contain 0.2-3 parts of geranium essential oil, chamomile essential oil, orange blossom essential oil, ylang-ylang essential oil, bergamot essential oil, lemon essential oil or sandalwood essential oil.

7. The composition for improving sleep disorders or anxiety according to claim 6, characterized in that: It is prepared from the following raw materials in weight ratio: 1.0-3.0 parts of lavender essential oil, 1.0-3.0 parts of vetiver essential oil, 0.2-0.8 parts of agarwood essential oil, 0.5-1.5 parts of dalbergia odorifera essential oil, 1-2 parts of cypress essential oil, 1-2 parts of juniper essential oil, 0.2-3 parts of geranium essential oil, chamomile essential oil, neroli essential oil, ylang-ylang essential oil, bergamot essential oil, lemon essential oil or sandalwood essential oil; Preferably, the weight ratio of the raw materials is: 2.0 parts of lavender essential oil, 2.0 parts of vetiver essential oil, 0.5 parts of agarwood essential oil, 1.0 parts of dalbergia odorifera essential oil, 1.5 parts of cypress essential oil, 1.5 parts of cypress essential oil, and 2.0 parts of geranium essential oil.

8. The composition for improving sleep disorders or anxiety according to any one of claims 3 to 7, characterized in that: The preparation is prepared from raw materials in the following weight ratio: the raw materials are used as active ingredients, and adjuvants or auxiliary ingredients acceptable in pharmacy or health products are added to prepare the preparation.

9. The composition for improving sleep disorders or anxiety according to claim 8, characterized in that: The preparations are inhalation preparations and external preparations; the inhalation preparations include aerosols, inhalation powder sprays, nebulized inhalation preparations, inhalation liquid preparations, nasal sprays, aromatherapy agents, and bursting beads; the external preparations include aqueous solutions, emulsions, creams, ointments, oils, and liniments.

10. Use of the composition according to any one of claims 3 to 9 in the preparation of a medicine or health product for improving high altitude sleep disorders.

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