Application of combined use of radix bupleuri essential oil and rhizoma cyperi essential oil in preparation of non-oral administration medicine for treating liver depression and qi stagnation syndromes, and essential oil composition for treating liver depression and qi stagnation syndromes

Abstract

The invention provides application of combined use of radix bupleuri essential oil and rhizoma cyperi essential oil in preparation of a non-oral administration medicine for treating liver depression and qi stagnation syndromes. The weight ratio of the radix bupleuri essential oil to the rhizoma cyperi essential oil is as follows: 0.5-1.5 parts of the radix bupleuri essential oil and 0.5-1.0 part of the rhizoma cyperi essential oil. The invention also provides an essential oil composition for treating liver depression and qi stagnation syndromes through non-oral administration. When all the components in the essential oil composition are compatible, factors such as curative effect, character, fragrance, safety and irritation after all the components are compatible need to be comprehensively considered in dosage selection, all the medicines are combined to be used for treating the liver depression and qi stagnation syndrome, the synergistic effect can be achieved, the effect is better than that of single essential oil, and due to the adoption of a non-oral administration mode, the essential oil composition is safer to use and free of toxic and side effects. The medicine is easy to accept and suitable for clinical popularization.

Description

Technical Field

[0001] The invention relates to use of bupleurum essential oil and cyperus rotundus essential oil in combination in preparing a medicament for treating liver depression and qi stagnation syndrome by non-oral administration, and an essential oil composition for treating liver depression and qi stagnation syndrome by non-oral administration. Background Art

[0002] Liver depression and qi stagnation syndrome refers to a series of symptoms manifested by stagnant qi due to dysfunction of the liver's function of dispersing and discharging qi. It is often associated with emotional trauma, mental stimulation, improper diet, and excessive fatigue. It is one of the most common clinical syndromes in Traditional Chinese Medicine (TCM). With increasing stress and a faster pace of life, it affects an increasing number of people. Liver depression and qi stagnation syndrome involves a variety of diseases, and its symptoms are complex and varied, seriously impacting patients' lives, studies, and work.

[0003] "Suwen: The Great Treatise on the Correspondence of Yin and Yang" states, "Humans have five internal organs that transform five qi, giving rise to joy, anger, sorrow, worry, and fear." "The liver is associated with anger," and "anger harms the liver." "Suwen: The Treatise on Benbing" states, "When a person becomes angry, qi rises instead of descending, which injures the liver." The liver governs dispersal and drainage, its nature promoting upward flow and disliking depression. It regulates emotions, releases bile, aids the spleen and stomach in transporting and transforming qi, and promotes the circulation of blood and body fluids. Dysfunction of the liver's dispersal and drainage functions can lead to stagnation of liver qi, which in turn leads to qi stagnation and blood stasis. "Suwen: The Treatise on the Methods of Zangqi and the Seasons" states, "Pains in patients with liver disease may arise from pain below the ribs that extends to the lower abdomen, causing irritability." "Leizheng Zhicai" states, "The nature of wood rises and disperses. If not restrained and depressed, stagnation will cause qi reversal in the meridians." "Reading Medical Notes" states, "All diseases involving qi stagnation, blood coagulation, phlegm and fluid retention, and swelling...are caused by liver qi not flowing freely." If emotional distress causes the liver to lose its ability to flow freely and comfortably, and its function of dispersing and discharging is disrupted, liver qi stagnation and qi reversal and stagnation will initially occur. If liver qi stagnation invades the stomach, or if it rises upward and is accompanied by symptoms such as phlegm stagnation and food stagnation, this can lead to indigestion, vomiting, abdominal distension, abdominal pain, constipation, or diarrhea. If the liver loses its ability to flow freely, qi flow is sluggish, and qi obstruction and blood stasis can cause flank pain. If the liver fails to disperse and discharge, blood overflows from the vessels or blood flow is blocked, leading to qi stagnation and blood coagulation, which can cause menstrual disorders in women. Therefore, according to the theories that "the liver governs dispersing and dispersing, and pain results from obstruction" and "unblocking wood blocks the flow," treatment should focus on soothing the liver and regulating qi, promoting blood circulation and removing blood stasis, and relieving depression and calming the mind.

[0004] Currently, the main treatments for liver depression and qi stagnation syndrome include traditional Chinese medicine (TCM), acupuncture and massage, and psychological counseling. TCM regulates liver function by soothing the liver and regulating qi, relieving depression and calming the mind. While this can improve overall health, the bitter taste of TCM makes it difficult for some patients to tolerate, and the long duration of use results in poor patient compliance. Acupuncture and massage require specialized medical personnel and require high technical skills. Furthermore, patients need to visit medical institutions regularly for treatment, which can cause significant inconvenience in their daily lives and work. While psychological counseling can alleviate patients' emotional issues to a certain extent, it often fails to achieve the desired therapeutic effect for established liver depression and qi stagnation.

[0005] Aromatherapy in Traditional Chinese Medicine (TCM) is rooted in the profound theoretical foundations of Traditional Chinese Medicine. It utilizes the volatile components of aromatic herbs, acting on the human body through various means, such as inhalation and absorption through the skin, aiming to harmonize yin and yang, unclog the meridians, and balance the functions of internal organs. Essential oils, as the primary medium for aromatherapy, are natural plant extracts that have garnered widespread attention and application in the health field in recent years. Essential oils possess unique aromas and pharmacological activities. They are highly volatile and lipid-soluble, easily crossing biological membranes within the body and exhibiting high bioavailability. Essential oils contain a rich array of active ingredients that can rapidly act on the nervous and endocrine systems through gastrointestinal absorption, topical application to the skin, and through the nasal and oral mucosa routes, regulating the body's physiological functions. Summary of the Invention

[0006] The present invention provides use of bupleurum essential oil and cyperus rotundus essential oil in combination in preparing a medicament for treating liver depression and qi stagnation syndrome by non-oral administration, and an essential oil composition for treating liver depression and qi stagnation syndrome by non-oral administration.

[0007] The present invention provides a use of bupleurum essential oil and cyperus rotundus essential oil in combination for preparing a non-oral medicament for treating liver depression and qi stagnation syndrome. The weight ratio of the bupleurum essential oil and the cyperus rotundus essential oil is: 0.5-1.5 parts of bupleurum essential oil and 0.5-1.0 parts of cyperus rotundus essential oil.

[0008] The weight ratio of the bupleurum essential oil to the cyperus rotundus essential oil is: 1.0 part of bupleurum essential oil and 0.75 part of cyperus rotundus essential oil.

[0009] The present invention provides an essential oil composition for non-oral administration to treat liver depression and qi stagnation syndrome, which is prepared from the following raw materials in the following weight ratio:

[0010] 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil;

[0011] Preferably, the weight ratio is:

[0012] 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil.

[0013] Furthermore, it is prepared from the following raw materials in the following weight ratio:

[0014] 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil, and 0.5-1.0 parts of ligusticum chuanxiong essential oil;

[0015] Preferably, the weight ratio is:

[0016] 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, and 0.75 part of ligusticum chuanxiong essential oil.

[0017] Furthermore, it is prepared from the following raw materials in the following weight ratio:

[0018] 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil, 0.5-1.0 parts of ligusticum chuanxiong essential oil, 0.5-1.5 parts of tangerine peel essential oil, 0.5-1.0 parts of fructus aurantii essential oil, and 0.5-1.0 parts of clove essential oil;

[0019] Preferably, the weight ratio is:

[0020] 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of ligusticum chuanxiong essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, and 0.75 part of clove essential oil.

[0021] Furthermore, it is prepared from the following raw materials in the following weight ratio:

[0022] 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil, 0.5-1.0 parts of chuanxiong essential oil, 0.5-1.5 parts of angelica essential oil, 0.5-1.5 parts of tangerine peel essential oil, 0.5-1.5 parts of fructus aurantii essential oil, 0.5-1.0 parts of santalinum officinale, and 0.5-3 parts of one or more of rose essential oil, jasmine essential oil, neroli essential oil, or ylang-ylang essential oil;

[0023] Preferably, the weight ratio is: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 0.75 part of angelica essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, 0.75 part of sandalwood essential oil, 1.0 part of neroli essential oil, and 2.0 part of ylang-ylang essential oil.

[0024] The composition of the present invention is prepared from the raw material essential oil as an active ingredient, and pharmaceutically acceptable excipients or auxiliary ingredients are added to form a commonly used pharmaceutical preparation.

[0025] Among them, the preparations are inhalation preparations and external preparations; the inhalation preparations include aerosols, inhalation powders, nebulized inhalers, inhalation liquid preparations, nasal sprays, aromatherapy agents, and explosive beads; the external preparations include aqueous solutions, emulsions, creams, ointments, oils, liniments, films, gels, and patches.

[0026] In the essential oil formula of the present invention, Bupleurum chinense is the main ingredient, known for its light, clear, ascending, and dispersing properties. It excels at soothing the liver and relieving depression, and regulating the Qi mechanism. The Compendium of Materia Medica states that it "treats Yang Qi deficiency and calms the liver, gallbladder, triple burner, and pericardium fire." The auxiliary ingredient, Cyperus rotundus, is pungent and aromatic, dispersing, and uniquely enters the Jueyin meridian, relieving liver depression and regulating the Qi mechanism. It is particularly effective in regulating menstruation and relieving pain. The Bencao Qiuzhen states that it is "the general director of Qi diseases" and is used in conjunction with Bupleurum chinense to help the main ingredient promote the flow of liver Qi. Chuanxiong rhizome, which can both invigorate blood circulation and dissipate blood stasis and promote Qi and relieve pain, is considered a "Qi medicine in the blood." When used in combination with Bupleurum chinense and Cyperus rotundus, it balances Qi and blood, enhancing the effects of promoting Qi, activating blood circulation, and relieving pain. Angelica sinensis, with its blood-tonifying and active properties, regulates menstruation and relieves pain, and is the premier blood-tonifying herb. Its light and pungent Qi promotes blood circulation, tonifying while moving, and promoting while tonifying. When used in combination with Chuanxiong rhizome, it achieves dual Qi and blood regulation. Tangerine peel regulates qi and strengthens the spleen, while Citrus aurantium relieves distension and distension. Sandalwood warms the middle and promotes qi circulation and relieves pain, while clove warms the middle and reduces adverse reactions, collectively tonifying qi and regulating the middle. Orange blossom, jasmine, rose, and ylang-ylang, with their light and fragrant properties, not only correct odor but also soothe the liver and relieve depression, aligning with the principle that "the liver appreciates a smooth and unobstructed flow." The entire formula integrates liver-soothing, blood-regulating, and stomach-harmony, embodying the principle of "unblocking wood stagnation." Bupleurum chinense is the primary liver-soothing agent, complemented by aromatic qi-regulating herbs to promote qi flow, supplemented by blood-nourishing and harmonizing herbs to prevent pungent and dry properties from damaging yin, and finally, fragrant flowers to regulate emotions. These herbs work together to disperse liver qi, resolve blood stasis, and harmonize stomach qi.

[0027] When the components in the essential oil composition of the present invention are combined, the selection of their dosages needs to comprehensively consider factors such as the efficacy, properties, aroma, safety, and irritation of the combined components. The combined use of the components for treating liver depression and qi stagnation syndrome can exert a synergistic effect, and the effect is better than that of a single essential oil. Due to the non-oral administration method, the composition is safer to use, more acceptable, and suitable for clinical promotion. DETAILED DESCRIPTION

[0028] Extract individual essential oils using methods such as steam distillation, supercritical CO2 extraction, immersion, and pressing, or purchase commercially available products. Bupleurum essential oil is extracted using supercritical CO2 extraction; the remaining essential oils are extracted using steam distillation.

[0029] Preparation of essential oils

[0030] Example 1: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil

[0031] Example 2: 1.5 parts of bupleurum essential oil, 0.5 parts of cyperus rotundus essential oil

[0032] Example 3: 0.5 part of bupleurum essential oil, 1.0 part of cyperus rotundus essential oil

[0033] Example 4: 1.0 part of Bupleurum essential oil, 0.75 part of Cyperus rotundus essential oil, 0.75 part of Chuanxiong essential oil

[0034] Example 5: 1.0 part of Bupleurum essential oil, 0.75 part of Cyperus rotundus essential oil, 0.5 part of Chuanxiong essential oil

[0035] Example 6: 1.0 part of Bupleurum essential oil, 0.75 part of Cyperus rotundus essential oil, 1.0 part of Chuanxiong essential oil

[0036] Example 7: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, 0.75 part of clove essential oil

[0037] Example 8: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 1.0 part of tangerine peel essential oil, 1.0 part of fructus aurantii, 0.5 part of clove essential oil

[0038] Example 9: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 0.5 part of tangerine peel essential oil, 0.5 part of fructus aurantii, 1.0 part of clove essential oil

[0039] Example 10: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 0.75 part of angelica essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, 0.75 part of santalinum essential oil, 1.0 part of neroli essential oil, 2.0 parts of ylang-ylang essential oil

[0040] Example 11: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 1.0 part of angelica essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, 1.0 part of sandalwood essential oil, 0.5 part of neroli essential oil, 1.0 part of ylang-ylang essential oil

[0041] Example 12: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 0.5 part of angelica essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, 0.5 part of santalinum essential oil, 2.0 parts of neroli essential oil, 3.0 parts of ylang-ylang essential oil

[0042] Example 13: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 0.75 part of angelica essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, 1.0 part of santalinum essential oil, 1.0 part of neroli essential oil, 0.5 part of ylang-ylang essential oil

[0043] When combining the components of an essential oil composition, the dosage should be selected based on a comprehensive consideration of the therapeutic efficacy of the combination, as well as the aroma, properties, safety, and irritation of the combined essential oils. Preliminary efficacy testing screened the ratios of essential oil combinations. In a rat model of chronic stress with liver depression and qi stagnation syndrome, the combination of Bupleurum essential oil and Cyperus rotundus essential oil significantly shortened the rats' forced swimming immobility time compared to Bupleurum essential oil alone or Bupleurum essential oil alone. A 4:3 combination achieved the shortest forced swimming immobility time. Further formulation combinations were performed based on Example 1; Examples 4-13 all shortened the rats' forced swimming immobility time, with Examples 7-9 showing the greatest effect, followed by Examples 10-13. For functional dyspepsia, Examples 10-13 demonstrated the most significant effect in promoting stomach and small intestine function, followed by Examples 7-9. The rats showed improvements in activity, mental state, sleep quality, and appetite. The odors of Examples 7-13 were highly acceptable.

[0044] The beneficial effects of the present invention are demonstrated below through specific pharmacodynamic tests and clinical trials.

[0045] Experimental Example 1 Effect of the Composition of the Present Invention on Liver Depression and Qi Stagnation Syndrome in Chronic Stress Rats

[0046] 1 replicate rat model of chronic stress with liver depression and qi stagnation

[0047] Rats were subjected to chronic, unpredictable mild stress to replicate liver depression and qi stagnation. Stimuli included water deprivation (24 hours), food deprivation (24 hours), changes in housing (damp bedding, tilted cage for 24 hours), swimming in 4°C ice water (5 minutes), tail clamping (1 minute), 45°C heat stimulation (5 minutes), and horizontal oscillation at 60 vibrations / min for 10 minutes. Each type of stimulus was randomly administered daily, and the same stimulus could not be repeated within 2 days to prevent the rats from predicting the stimulus. Each stimulus was applied an average of four times over a period of 28 days.

[0048] 2 Experimental grouping, modeling and drug administration

[0049] 90 SPF-grade SD male rats, weighing 200±20 g, were housed in the laboratory for 5 days and randomly divided into a blank group, a model group, a Bupleurum essential oil group, a Cyperus rotundus essential oil group, a compound essential oil group 1 (Example 1), a compound essential oil group 2 (Example 4), a compound essential oil group 3 (Example 7), a compound essential oil group 4 (Example 10), and a positive drug fluoxetine hydrochloride group, with 10 rats in each group.

[0050] Except for the blank group, the other groups were treated with the chronic stress model of liver depression and qi stagnation syndrome in rats according to the method in 1.1, and medication was started on the first day of modeling.

[0051] Mice in the blank group, model group, and essential oil group were subjected to nebulized aromatherapy for 30 minutes. The blank group and model group were given 50 ml of water, and the essential oil group was given about 0.2 g of essential oil in 50 ml of water. The volume of the animal aromatherapy room was about 50 L (52 cm × 38 cm × 25 cm). The dosage was 0.1 g / kg. The fluoxetine group was given oral administration at a dose of 2.0 mg / kg, once a day, for 28 consecutive days.

[0052] 3 Behavioral evaluation of rats

[0053] 3.1 Sugar water preference experiment

[0054] Sugar water adaptation training was performed 3 days before the last administration. On the first day, two bottles of 1% sucrose solution were placed in each cage at the same time. On the second day, one bottle of 1% sucrose solution and one bottle of pure water were placed in each cage at the same time, and the positions of the two bottles were replaced 12 hours in the middle. On the third day, the rats were fasted and deprived of water for 12 hours.

[0055] After the adaptation training was completed, a sugar water preference test was conducted on the 4th day. One bottle of 1% sucrose aqueous solution and one bottle of pure water were placed in each cage at the same time. The experiment lasted for 24 hours, and the positions of the two bottles of solution were changed every 12 hours to prevent the rats from developing positional selectivity. The rats' intake of sugar water and pure water was calculated. Sugar water preference rate (%) =

[0056] (Sugar water intake) / (Sugar water intake + pure water intake) × 100%.

[0057] 3.2 Forced swimming test

[0058] Forced swimming tests were conducted in a transparent plexiglass tube 40 cm high and 34 cm in diameter, at a depth of 25 cm and a temperature of 20-25°C. One day before the experiment, rats underwent 15 minutes of forced swimming acclimatization training. Twenty-four hours after the actual experiment, the rats were placed in the water again and swam for 5 minutes. The immobility time was recorded as the time during which the rats stopped struggling, remained motionless in the water, or only slightly raised their heads.

[0059] 4 Determination of 5-HT, DA, and NE content in hippocampal tissue

[0060] After the experiment, the rats were sacrificed, the brain tissue was removed, and the hippocampus was quickly dissected. The cells were washed with 4°C cold saline, dried with filter paper, and weighed. PBS was added at a ratio of 1:10, and then a hippocampal tissue homogenate was prepared using a homogenizer. The tissue homogenate was shaken for 5 minutes, centrifuged at 3000 rpm for 10 minutes, and the supernatant was collected. ELISA was used to measure the levels of 5-HT, DA, and NE in the hippocampus according to the kit instructions.

[0061] 5 Data Processing

[0062] SPSS 19.0 software was used for data analysis, and t-test or rank-sum test was used; P < 0.05 indicated statistically significant differences.

[0063] 6 Experimental results

[0064] 6.1 Effects on rat behavior

[0065] Compared with the blank group, the model group rats' sugar water preference rate was significantly reduced, and the forced swimming immobility time was significantly increased, with statistically significant differences (P < 0.01). Compared with the model group, under the condition of the same essential oil dosage, the compound essential oil group and the positive group significantly increased the sugar water preference rate and reduced the forced swimming immobility time (P < 0.05). Compared with the positive group, the single essential oil group and the compound essential oil group 1 significantly reduced the sugar water preference rate, and the single essential oil group significantly increased the forced swimming immobility time (P < 0.05). There was no significant difference between the other compound essential oil groups and the positive group (P > 0.05). The results are shown in Table 1.

[0066] Table 1 Effects of sugar water preference rate and forced swimming immobility time on rats with liver depression and qi stagnation ( n=10) 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)

[0067] 6.2 Effects on 5-HT, DA, and NE Contents in Rat Hippocampus

[0068] Compared with the blank group, the levels of 5-HT, DA, and NE in the hippocampus of rats in the model group were significantly decreased (P < 0.01). Compared with the model group, under the condition of the same essential oil dosage, the levels of 5-HT, DA, and NE in the hippocampus of rats in the Bupleurum single essential oil group, the compound essential oil group, and the positive group were significantly increased (P < 0.05). Compared with the positive group, the levels of 5-HT in the hippocampus of rats in the compound essential oil group 1 and the compound essential oil group 2 were significantly decreased (P < 0.05). There was no significant difference in the levels of 5-HT in the hippocampus of rats in the other compound essential oil groups compared with the positive group. There was no significant difference in the levels of DA and NE in the hippocampus of rats in the compound essential oil group compared with the positive group (P > 0.05). The results are shown in Table 2.

[0069] Table 2 Effects on 5-HT, DA and NE contents in rat brain tissue

[0070]

[0071]

[0072] Compared with the model group, * P<0.05, ** P<0.01; compared with the blank group, # P<0.05, ## P < 0.01;

[0073] Compared with the positive group, ▲ P<0.05, ▲▲ P<0.01)

[0074] Experimental Example 2 Effect of the Composition of the Present Invention on Rats with Functional Dyspepsia

[0075] 1. Replicate functional dyspepsia model rats

[0076] A functional dyspepsia model was established in rats using a composite factor approach (tail clamping, excessive fatigue, and dietary irregularities). Tail clamping was performed twice daily for 30 minutes each time. One hour after the tail clamping, the rats were forced to swim until exhaustion. They were also fed irregularly, with no food (no water) on odd-numbered days and a normal diet on even-numbered days. After 21 days of modeling, the rats developed sparse, dull fur, decreased water and food intake, loose stools, lethargy, and significantly reduced reflexes, indicating successful model establishment.

[0077] 2 Experimental grouping, modeling and drug administration

[0078] 96 SPF-grade Sprague-Dawley rats, half ♀ and half ♂, weighing 200 ± 20 g, were housed in the laboratory for 5 days. Ten rats were randomly selected as the blank group and maintained normally. The remaining rats were induced into the functional dyspepsia model according to the method in 2.1. 81 rats were successfully modeled, including 40 ♀ and 41 ♂.

[0079] The 80 rats with successful modeling were randomly divided into a model group, a Bupleurum essential oil group, a Cyperus rotundus essential oil group, a compound essential oil group 1 (Example 1), a compound essential oil group 2 (Example 4), a compound essential oil group 3 (Example 7), a compound essential oil group 4 (Example 10), and a positive drug mosapride group, with 10 rats in each group.

[0080] The medication started on the second day after the modeling was completed. The mice in the blank group, model group, and essential oil group were subjected to atomized aromatherapy for 30 minutes. The blank group and model group were given 50 ml of water, and the essential oil group was given about 0.2 g of essential oil in 50 ml of water. The volume of the animal aromatherapy room was about 50 L (52 cm × 38 cm × 25 cm). The dosage was 0.1 g / kg, and the medication was given twice a day. The mosapride group was given an oral administration of 0.75 mg / kg, and the medication was given twice a day for 14 consecutive days.

[0081] 3. Effects on gastrointestinal motility

[0082] Determine the gastric emptying rate and small intestinal propulsion rate. After the last administration, the rats were fasted but not watered for 24 hours, and gavaged with 4 mL of semisolid nutrient paste containing charcoal powder (the mass was weighed in advance). 30 minutes later, the rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital. The rats were subjected to laparotomy, the pylorus and cardia were ligated, the whole stomach was taken out to weigh the total weight of the stomach, and the net weight of the stomach was weighed after the stomach contents were fully cleared, and the gastric emptying rate was calculated. Gastric emptying rate (%) = [1-(total weight of stomach - net weight of stomach) ÷ weight of semisolid nutrient paste containing charcoal powder] × 100%. The total length of the small intestine (pylorus to ileocecal part) and the propulsion length of the semisolid nutrient paste containing charcoal powder were measured to calculate the small intestinal propulsion rate. Small intestinal propulsion rate (%) = propulsion length of nutrient paste ÷ total length of small intestine × 100%

[0083] 4 Data Processing

[0084] SPSS 19.0 software was used for data analysis, and t-test or rank-sum test was used; P < 0.05 indicated statistically significant differences.

[0085] 5 Experimental results

[0086] Compared with the blank group, the model group rats' sugar water preference rate was significantly reduced, and the forced swimming immobility time was significantly increased, with statistically significant differences (P < 0.01). Compared with the model group, under the condition of the same essential oil dosage, the compound essential oil group and the positive group significantly increased the sugar water preference rate and reduced the forced swimming immobility time (P < 0.05). Compared with the positive group, the single essential oil group and the compound essential oil group 1 significantly reduced the sugar water preference rate, and the single essential oil group significantly increased the forced swimming immobility time (P < 0.05). There was no significant difference between the other compound essential oil groups and the positive group (P > 0.05). The results are shown in Table 3.

[0087] Table 3 Effects of gastric emptying rate and small intestinal propulsion rate on dyspepsia rats ( n=10)

[0088]

[0089] Compared with the model group, * P<0.05, ** P<0.01; compared with the blank group, # P<0.05, ## P < 0.01;

[0090] Compared with the positive group, ▲ P<0.05, ▲▲ P<0.01)

[0091] Test Example 3 Clinical efficacy of the composition of the present invention

[0092] 1. Impact of functional dyspepsia

[0093] Mix compound essential oil 4 with base oil to prepare a 10% massage oil. Apply 5 ml of the oil to the abdomen and massage the Xiawan, Zhongwan, and Tianshu acupoints for 15 minutes. Evaluate the efficacy of this massage oil on functional dyspepsia.

[0094] 1.1 General Information

[0095] A total of 96 patients with functional dyspepsia who were admitted to a tertiary hospital in Chengdu from January 2023 to June 2024 were selected, including 46 males and 50 females with an age range of 16 to 68 years. They were randomly divided into a control group and an observation group, with 48 cases in each group. There was no statistically significant difference in gender, age, course of disease, condition, and past medical history among the patients in each group (P>0.05), and the groups were comparable.

[0096] 1.2 Diagnostic criteria

[0097] Refer to the diagnostic criteria in the "Chinese Expert Consensus on Functional Dyspepsia." Traditional Chinese Medicine (TCM) defines liver depression and qi stagnation as a syndrome of liver depression and qi stagnation: primary symptoms include epigastric distension and pain, irritability, and belching; secondary symptoms include bitter taste in the mouth, a foreign body sensation in the throat, depression, acid reflux, and poor appetite; tongue and pulse characteristics include a pale or red tongue with a yellow coating and a rapid, stringy pulse. The syndrome is confirmed by combining two primary symptoms and one secondary symptom, or one primary symptom and two secondary symptoms, with the tongue and pulse.

[0098] 1.3 Inclusion criteria

[0099] (1) The above-mentioned diagnostic and dialectical criteria must be met;

[0100] (2) Being conscious and able to correctly describe one's own wishes;

[0101] (3) Voluntarily fill out the informed consent form and agree to participate in clinical trials;

[0102] (4) Good compliance and cooperation with relevant treatments.

[0103] 1.4 Exclusion criteria

[0104] (1) does not meet the above diagnostic and dialectical criteria;

[0105] (2) those with a recent history of abdominal surgery;

[0106] (3) Pregnant or breastfeeding women;

[0107] (4) Patients with mental illness and severe primary heart, liver, and kidney diseases;

[0108] (5) Those who are allergic or intolerant to essential oils;

[0109] 1.5 Treatment

[0110] The control group took mosapride citrate tablets orally, 5 mg / time, 3 times a day, half an hour before meals, for 2 consecutive weeks.

[0111] The observation group was given a 10% massage oil prepared by mixing Composition 4 with a base oil. 5 ml of the oil was applied to the abdomen, followed by massage of the Xiawan, Zhongwan, and Tianshu points for 15 minutes, twice daily, once in the morning on an empty stomach and once before bedtime, for 2 consecutive weeks.

[0112] 1.6 Evaluation Method

[0113] The efficacy of the treatment was observed before and after administration using a Traditional Chinese Medicine (TCM) syndrome scoring table. The TCM syndrome scoring table uses a semi-quantitative scoring system based on the diagnostic criteria for primary and secondary symptoms. Primary symptoms are scored as 0, 2, 4, and 6 points, respectively, based on severity, from none, mild, moderate, to severe. Secondary symptoms are scored as 0, 1, 2, and 3 points, respectively.

[0114] 1.7 Criteria for determining efficacy

[0115] Cured: symptoms and signs disappear or almost disappear, and the TCM syndrome reduction rate is ≥95%;

[0116] Markedly effective: symptoms and signs are significantly improved, with the TCM syndrome reduction rate being 70% to 95% (inclusive);

[0117] Effective: Symptoms and signs have improved, and the TCM syndrome reduction rate is 30% to 70% (inclusive);

[0118] Ineffective: There is no significant improvement in symptoms and signs, or they may even worsen, and the TCM syndrome reduction rate is less than 30%.

[0119] Total effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%

[0120] Score reduction rate = (score before treatment - score after treatment) / score before treatment × 100%.

[0121] 1.8 Data Processing

[0122] SPSS 19.0 software was used for data analysis, and X-ray diffraction analysis was used for count data. 2 The measurement data were analyzed using t-test or rank sum test; P < 0.05 indicated that the difference was statistically significant.

[0123] 1.9 Comparison of treatment effects between the two groups

[0124] Compared with the control group, the cure rate, marked efficacy rate, efficacy rate, and total efficacy rate in the observation group were all higher than those in the control group. The compound essential oil can effectively alleviate the discomfort symptoms of functional dyspepsia. The results are shown in Table 4.

[0125] Table 4 Comparison of clinical efficacy between the two groups of patients with functional dyspepsia

[0126]

[0127] 2. Impact of liver depression and qi stagnation type depression

[0128] 2.1 General Information

[0129] A total of 80 patients with liver depression and qi stagnation type depressive disorder who were admitted to a hospital in Chengdu from June 2023 to December 2024 were selected, including 36 males and 44 females, aged 15 to 62 years. They were randomly divided into a control group and an observation group, with 40 cases in each group. There was no statistically significant difference in gender, age, course of disease, and medical history between the two groups (P>0.05), and the two groups were comparable.

[0130] 2.2 Diagnostic criteria

[0131] Refer to the diagnostic criteria for depression in the International Classification of Diseases (ICD-10) and the diagnostic criteria for liver qi stagnation syndrome in the Guidelines for Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine Internal Medicine.

[0132] 2.3 Inclusion criteria

[0133] (1) Patients must meet both traditional Chinese and Western medical diagnoses of depression;

[0134] (2) Able to correctly describe their own wishes, voluntarily fill out the informed consent form, and agree to participate in clinical trials;

[0135] (3) not participating in other clinical studies;

[0136] (4) Good compliance and cooperation with relevant treatments.

[0137] (5) There are no contraindications for the use of fluvoxamine.

[0138] Only those who meet all five of the above conditions can be included.

[0139] 2.4 Exclusion criteria

[0140] (1) does not meet the diagnostic criteria;

[0141] (2) Pregnant, lactating women or women preparing to become pregnant;

[0142] (3) Those with severe depression or suicidal tendencies;

[0143] (4) Patients with mental illness or severe primary heart, liver, and kidney diseases;

[0144] (5) Those who have received other relevant treatments that may affect the effect indicators of this study;

[0145] If any of the appeal criteria occur, it will be excluded.

[0146] 2.5 Rejection criteria

[0147] (1) During the trial, it was found that the subject met the exclusion criteria or did not meet the inclusion criteria;

[0148] (2) Those who experienced serious adverse events during the study or voluntarily requested to withdraw;

[0149] (3) Those who are allergic or intolerant to essential oils and are unable to conduct the experiment;

[0150] 2.6 Treatment

[0151] The control group took fluvoxamine maleate tablets 100 mg / time, once / day, before bedtime for 6 consecutive weeks.

[0152] In addition to the control group, the observation group used the atomized aromatherapy of composition 3 30 minutes before going to bed every night, adding 2 to 4 drops each time, for 6 consecutive weeks.

[0153] 2.7 Evaluation Method

[0154] The Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD) and Traditional Chinese Medicine Syndrome Score Table were used to observe the efficacy of the patients before and after administration.

[0155] ①PSQI consists of seven parts: sleep quality, sleep onset time, sleep duration, sleep efficiency, sleep disorders, hypnotic medication, and daytime dysfunction. Each part is scored from 0 to 3 points. The sum of the scores of each component is the total PSQI score, which ranges from 0 to 21 points. The higher the score, the worse the sleep quality.

[0156] ②HAMD (24 items) includes a total score and a level of depression. A higher total score indicates more severe depression. Evaluation criteria: A total score of 8 or less indicates no depressive symptoms; a score of 20 or more indicates mild or moderate depression; and a score of 35 or more indicates severe depression.

[0157] The TCM syndrome scoring system includes primary symptoms (depression or irritability) and secondary symptoms (sleep quality, epigastric or flank pain, hiccups, sighing, foreign body sensation in the throat, bitter taste in the mouth, and poor appetite). The scoring method uses a semi-quantitative scoring system based on the primary and secondary symptoms. Primary symptoms are scored according to severity (none, mild, moderate, and severe) with scores of 0, 2, 4, and 6, respectively. Secondary symptoms are scored as 0, 1, 2, and 3, respectively.

[0158] 2.8 Criteria for determining efficacy

[0159] Cured: Depressive symptoms disappear, mood stabilizes, sleep returns to normal, and the PSQI score, HAMD score, and TCM syndrome score reduction rate are all ≥ 75%;

[0160] Markedly effective: Depressive symptoms are relieved, mood is basically stable, sleep is more than 4 hours at night, sleep is deep, and the PSQI score, HAMD score, and TCM syndrome score reduction rate are all 50% to 75% (inclusive);

[0161] Effective: Depressive symptoms are alleviated, mood is basically stable, sleep is more than 4 hours at night, and the PSQI score, HAMD score, and TCM syndrome score reduction rate are all 25% to 50% (including 25%);

[0162] Ineffective: Insomnia and depression symptoms were not relieved, mood was unstable, and the PSQI, HAMD and TCM syndrome score reduction rate was less than 25%.

[0163] Total effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%

[0164] Score reduction rate = (pre-treatment score / points - post-treatment score / points) / pre-treatment score / points × 100%.

[0165] 2.9 Data Processing

[0166] SPSS 19.0 software was used for data analysis, and X-ray diffraction analysis was used for count data. 2 The measurement data were analyzed using t-test or rank sum test; P < 0.05 indicated that the difference was statistically significant.

[0167] 2.10 Comparison of treatment effects between the two groups

[0168] Compared with the control group, the cure rate, marked efficacy rate, efficacy rate, and total efficacy rate of the observation group were all higher than those of the control group. The compound essential oil can improve the total efficacy rate of fluvoxamine in the treatment of depression. The results are shown in Table 5.

[0169] Table 5 Comparison of clinical efficacy between the two groups of patients with depressive disorders

[0170]

Claims

1. The use of bupleurum essential oil and cyperus rotundus essential oil in combination for preparing a non-oral medication for treating liver depression and qi stagnation syndrome, wherein the weight ratio of bupleurum essential oil and cyperus rotundus essential oil is: 0.5-1.5 parts of bupleurum essential oil and 0.5-1.0 parts of cyperus rotundus essential oil.

2. The use according to claim 1, characterized in that: The weight ratio of the bupleurum essential oil and the cyperus rotundus essential oil is: 1.0 part of bupleurum essential oil and 0.75 part of cyperus rotundus essential oil.

3. An essential oil composition for treating liver depression and qi stagnation syndrome by parenteral administration, characterized in that: It is prepared from the following raw materials in the following weight ratio: 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil; Preferably, the weight ratio is: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil.

4. The essential oil composition for treating liver depression and qi stagnation syndrome by parenteral administration according to claim 3, characterized in that: It is prepared from the following raw materials in the following weight ratio: 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil, and 0.5-1.0 parts of ligusticum chuanxiong essential oil; Preferably, the weight ratio is: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, and 0.75 part of ligusticum chuanxiong essential oil.

5. The essential oil composition for treating liver depression and qi stagnation syndrome by parenteral administration according to claim 4, characterized in that: It is prepared from the following raw materials in the following weight ratio: 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil, 0.5-1.0 parts of ligusticum chuanxiong essential oil, 0.5-1.5 parts of tangerine peel essential oil, 0.5-1.0 parts of fructus aurantii essential oil, and 0.5-1.0 parts of clove essential oil; Preferably, the weight ratio is: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of ligusticum chuanxiong essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, and 0.75 part of clove essential oil.

6. The essential oil composition for treating liver depression and qi stagnation syndrome by parenteral administration according to claim 5, characterized in that: It is prepared from the following raw materials in the following weight ratio: 0.5-1.5 parts of bupleurum essential oil, 0.5-1.0 parts of cyperus rotundus essential oil, 0.5-1.0 parts of chuanxiong essential oil, 0.5-1.5 parts of angelica essential oil, 0.5-1.5 parts of tangerine peel essential oil, 0.5-1.5 parts of fructus aurantii essential oil, 0.5-1.0 parts of santalinum officinale, and 0.5-3 parts of one or more of rose essential oil, jasmine essential oil, neroli essential oil, or ylang-ylang essential oil; Preferably, the weight ratio is: 1.0 part of bupleurum essential oil, 0.75 part of cyperus rotundus essential oil, 0.75 part of chuanxiong essential oil, 0.75 part of angelica essential oil, 0.75 part of tangerine peel essential oil, 0.75 part of fructus aurantii, 0.75 part of sandalwood essential oil, 1.0 part of neroli essential oil, and 2.0 part of ylang-ylang essential oil.

7. The essential oil composition for treating liver depression and qi stagnation according to any one of claims 3 to 6, characterized in that: The invention is prepared from the raw material essential oil as an active ingredient, and pharmaceutically acceptable auxiliary materials or auxiliary ingredients are added to prepare a commonly used pharmaceutical preparation.

8. The parenteral administration essential oil composition for treating liver depression and qi stagnation syndrome according to claim 7, characterized in that: The non-oral preparations are inhalation preparations and external preparations; the inhalation preparations include aerosols, inhalation powders, nebulized inhalers, inhalation liquid preparations, nasal sprays, aromatherapy agents, and explosive beads; the external preparations include aqueous solutions, emulsions, creams, ointments, oils, liniments, films, gels, and patches.

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