Traditional Chinese medicine composition for treating anxiety, depression and insomnia and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly discloses a traditional Chinese medicine composition for treating anxiety, depression and insomnia and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 3 to 6 parts of radix gentianae, 9 to 12 parts of radix paeoniae rubra, 6 to 9 parts of radix angelicae sinensis, 9 to 12 parts of cortex phellodendri, 9 to 12 parts of fried fructus gardeniae, 9 to 12 parts of rhizoma alismatis, 12 to 15 parts of raw semen coicis, 9 to 12 parts of radix rehmanniae, 6 to 9 parts of radix bupleuri, 12 parts of radix astragali seu hedysari, 1 to 3 parts of cortex cinnamomi, 9 to 12 parts of radix salviae miltiorrhizae, 9 to 13 parts of rhizoma chuanxiong and 12 to 15 parts of herba taraxaci. Compared with the prior art, the traditional Chinese medicine composition disclosed by the invention is cheap and easily available in medicinal materials, low in cost and high in safety, and achieves a treatment effect by soothing liver-qi stagnation, regulating qi and tonifying qi and relieving anxiety.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly to a traditional Chinese medicine composition for treating anxiety, depression and insomnia and its application. Background Art

[0002] Sleep disorder is a common and frequently-occurring disease in clinical practice, seriously affecting the quality of life of patients. At present, Western medicine mainly uses non-benzodiazepine drugs such as zolpidem, zopiclone, and eszopiclone for treatment. These drugs have significant short-term effects in treating insomnia, but generally easily cause nervous system side effects such as daytime sleepiness, dizziness, and decreased attention. Long-term use also poses risks of addiction and tolerance. Compared with Western medicine, traditional Chinese medicine has the advantages of syndrome differentiation and treatment, overall regulation, treating both the symptoms and the root cause, and small adverse reactions, showing good prospects in the treatment of insomnia. Traditional Chinese medicine classifies insomnia into the category of "insomnia", believing that its etiology is closely related to impaired liver function and emotional disorders. Therefore, liver qi stagnation is a common syndrome type in clinical practice. As recorded in "Plain Questions: Generation of the Five Viscera", "When a person lies down, the blood returns to the liver", indicating that sleep is closely related to the liver. The liver is in charge of dredging and dispersing. When liver qi is stagnated, the normal rise and fall, entry and exit of qi mechanism are disordered, qi and blood reverse upward, the brain spirit is disturbed, and the heart spirit is restless, thus leading to insomnia. At present, traditional Chinese medicine compounds for treating insomnia due to liver qi stagnation often use expensive medicinal flavors such as Ganoderma lucidum, Oyster, Dragon Bone, and Ziziphus jujuba var. spinosa, resulting in a relatively high treatment cost; some traditional Chinese medicine compounds often use medicinal flavors such as Hypericum perforatum and Caulis Polygoni Multiflori with certain liver and kidney toxicity and are not suitable for long-term use; some traditional Chinese medicine compounds contain heavy metal medicinal materials such as Calcined Magnetitum, and long-term use is likely to cause accumulation and is also not suitable for long-term use; some traditional Chinese medicine compounds are insufficient in targeting the concurrent syndromes (such as phlegm-heat, blood stasis, and spleen deficiency) of insomnia patients, often resulting in poor curative effects.

[0003] Therefore, it is of great significance to develop a traditional Chinese medicine compound with low medicinal flavor cost, high safety, strong pertinence to insomnia syndromes, definite curative effect, and treating both the symptoms and the root cause. Summary of the Invention

[0004] In order to solve the above technical problems, the present invention provides a traditional Chinese medicine composition for treating anxiety, depression and insomnia and its application.

[0005] To achieve the above object, the present invention is implemented according to the following technical scheme:

[0006] The first technical scheme provided by the present invention is a traditional Chinese medicine composition for treating anxiety, depression and insomnia, which is composed of the following raw materials in parts by weight: 3-6 parts of Gentiana scabra, 9-12 parts of Radix Paeoniae Rubra, 6-9 parts of Angelica sinensis, 9-12 parts of Phellodendron amurense, 9-12 parts of Fructus Gardeniae, 9-12 parts of Alisma orientale, 12-15 parts of Coix lacryma-jobi var. ma-yuen, 9-12 parts of Rehmannia glutinosa, 6-9 parts of Bupleurum chinense, 12 parts of Astragalus membranaceus, 1-3 parts of Cinnamomum cassia, 9-12 parts of Salvia miltiorrhiza, 9-13 parts of Ligusticum chuanxiong, 12-15 parts of Taraxacum mongolicum.

[0007] Preferably, the traditional Chinese medicine composition for treating anxiety, depression and insomnia of the present invention is composed of the following raw materials in parts by weight: 6 parts of gentian, 12 parts of red peony root, 6 parts of angelica, 12 parts of phellodendron bark, 10 parts of stir-fried gardenia, 10 parts of alisma orientale, 15 parts of coix seed, 10 parts of rehmannia root, 9 parts of bupleurum root, 12 parts of astragalus membranaceus, 3 parts of cinnamon, 12 parts of salvia miltiorrhiza, 10 parts of ligusticum wallichii, 15 parts of dandelion.

[0008] The second technical solution provided by the present invention is the application of a traditional Chinese medicine composition for treating anxiety, depression and insomnia in the preparation of a traditional Chinese medicine preparation for treating anxiety, depression and insomnia.

[0009] The third technical solution provided by the present invention is a traditional Chinese medicine preparation for treating anxiety, depression and insomnia, which contains the extract of the above-mentioned traditional Chinese medicine composition for treating anxiety, depression and insomnia.

[0010] Furthermore, the traditional Chinese medicine preparation for treating anxiety, depression and insomnia may further contain pharmaceutically acceptable carriers or excipients.

[0011] Furthermore, the dosage form of the traditional Chinese medicine preparation is one of granules, tablets, pills, capsules, powders, mixtures, oral liquids.

[0012] Furthermore, the preparation method of the extract of the traditional Chinese medicine composition for treating anxiety, depression and insomnia is as follows:

[0013] Take each raw material according to the ratio, decoct with water 30-60 times the total weight of the raw materials for 2 hours, filter and collect the filtrate, continue to concentrate the filtrate to 3-7 times the total weight of the raw materials to obtain the extract; or further concentrate or dry the extract to make a medicinal powder.

[0014] The present invention aims at insomnia caused by stagnation of liver qi. Following the traditional Chinese medicine compatibility theory of "the monarch drug treats the main disease, the minister drug assists in treatment, and the assistant and envoy drugs harmonize", with clearing liver heat, dispersing liver depression, nourishing heart blood, and regulating yin and yang as the core, through the combined use of cold and warm herbs, the simultaneous application of purging and tonifying, and the regulation of qi and blood, the treatment goal of "reducing fire, smoothing qi, calming blood, and tranquilizing the mind" is achieved. Gentiana scabra is used as the monarch drug, directly entering the liver and gallbladder meridians, specifically clearing the excess fire in the liver and gallbladder and purging the damp-heat in the lower jiao; Paeonia lactiflora is used as the minister drug, promoting blood circulation to remove blood stasis, cooling blood and relieving pain, not only assisting the monarch drug in clearing the blood heat in the liver meridian but also relieving the unsmooth blood circulation caused by qi stagnation, reflecting the compatibility logic of "when qi moves, blood moves; when blood is smooth, qi is comfortable"; Bupleurum chinense is an important herb for dispersing liver qi stagnation, synergizing with the monarch drug Gentiana scabra and the minister drug Paeonia lactiflora to disperse liver qi stagnation. Bupleurum chinense disperses the stagnated liver qi, and Paeonia lactiflora cools the liver and softens the liver. One disperses and one softens, enabling the liver qi to flow smoothly without being excessive; Phellodendron amurense, stir-fried Gardenia jasminoides, Alisma orientale, and Taraxacum mongolicum clear the damp-heat in the triple jiao. Phellodendron amurense clears the damp-heat in the lower jiao, stir-fried Gardenia jasminoides purges the heart fire, Alisma orientale promotes diuresis to eliminate dampness, and Taraxacum mongolicum disperses heat nodules to prevent the mutual binding of dampness and heat from aggravating the pathogenic fire; Rehmannia glutinosa and Angelica sinensis nourish the liver blood, prevent the injury of yin by fire heat, and since "the liver stores yin and governs yang", nourishing yin can assist the smooth flow of liver qi; Astragalus membranaceus invigorates the spleen and benefits qi, tonifying the acquired foundation to support the generation of qi and blood, preventing the consumption of qi and blood caused by long-term insomnia; A small amount of Cinnamomum cassia warms the kidney and aids yang, guiding the floating fire back to its origin and balancing the cold and bitter nature of the whole formula, reflecting "for those who are good at treating fire, guiding yang from yin and yin from yang"; Salvia miltiorrhiza and Ligusticum chuanxiong promote blood circulation and regulate qi, improving the chest and rib distension caused by qi stagnation and blood stasis and the restlessness of the mind due to the loss of nourishment, resulting in insomnia; Coix lacryma-jobi is used as the envoy drug, harmonizing all the herbs, strengthening the spleen and promoting diuresis to eliminate dampness, not only assisting Alisma orientale and Phellodendron amurense in clearing and promoting damp-heat but also preventing the cold and bitter herbs from injuring the spleen, which is an important guarantee for the whole formula to "clear heat without disturbing the stomach and dispel pathogenic factors without damaging healthy qi". The whole formula takes "Gentiana scabra - Paeonia lactiflora" as the core, through the multi-dimensional compatibility of "clearing liver fire, dispersing liver qi stagnation, communicating the heart and kidney, and nourishing blood and calming the mind", precisely targeting the five major pathogenesis of "fire, stasis, stasis, deficiency, and disharmony" of insomnia due to stagnation of liver qi. It can not only quickly relieve the insomnia symptoms of "fire disturbing the mind" but also through overall dispersing liver qi stagnation, smoothing qi stagnation, and balancing yin and yang and qi and blood, having the remarkable advantages of "combining quick effect and long effect, and treating both the symptoms and the root cause". The ingenious proportion of cold and warm herbs and the organic combination of purging and tonifying herbs in the formula reflect the compatibility wisdom of traditional Chinese medicine compound prescriptions of "strictly following the pathogenesis and treating according to the syndrome", and have been fully proved by clinical trials, and can be effectively used for insomnia due to stagnation of liver qi.

[0015] Compared with the prior art, the traditional Chinese medicine composition of the present invention has cheap and easily available medicinal materials, low cost, and high safety, and achieves the therapeutic effect by dispersing liver qi stagnation, regulating qi and tonifying qi, and relieving anxiety. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 Effect of LSJY on the body weight of CUMS - PCPA - induced insomnia mice;

[0017] Figure 2 Effect of LSJY on the total distance of spontaneous activity of CUMS - PCPA - induced insomnia mice within 5 minutes;

[0018] Figure 3Effect of LSJY on the average speed of spontaneous activity of CUMS-PCPA-induced insomnia mice within 5 min;

[0019] Figure 4 Effect of LSJY on the activity distance of CUMS-PCPA-induced insomnia mice in the central area within 5 min;

[0020] Figure 5 Effect of LSJY on the activity time of CUMS-PCPA-induced insomnia mice in the central area within 5 min;

[0021] Figure 6 Effect of LSJY on the spontaneous activity trajectory of CUMS-PCPA-induced insomnia mice within 5 min;

[0022] Figure 7 Effect of LSJY on the sleep latency of CUMS-PCPA-induced insomnia mice;

[0023] Figure 8 Effect of LSJY on the sleep duration of CUMS-PCPA-induced insomnia mice;

[0024] Figure 9 Effect of LSJY on the platform exploration time of CUMS-PCPA-induced insomnia mice;

[0025] Figure 10 Effect of LSJY on the total distance of platform exploration of CUMS-PCPA-induced insomnia mice;

[0026] Figure 11 Effect of LSJY on the number of times of finding the original platform of CUMS-PCPA-induced insomnia mice;

[0027] Figure 12 Effect of LSJY on the residence time of CUMS-PCPA-induced insomnia mice in the target quadrant;

[0028] Figure 13 Effect of LSJY on the swimming trajectory of CUMS-PCPA-induced insomnia mice in the water maze experiment;

[0029] Figure 14 Effect of LSJY on the content of 5-HT in the serum of CUMS-PCPA-induced insomnia mice;

[0030] Figure 15 Effect of LSJY on the content of DA in the serum of CUMS-PCPA-induced insomnia mice;

[0031] Figure 16 Effect of LSJY on the content of NE in the serum of CUMS-PCPA-induced insomnia mice. Detailed implementation mode

[0032] To make the objectives, technical solutions, and advantages of the present invention clearer and more understandable, the following further details the present invention in conjunction with embodiments. The specific embodiments described herein are only for explaining the present invention and are not used to limit the invention.

[0033] Example 1: Preparation of a Traditional Chinese Medicine Preparation for Treating Anxiety, Depression, and Insomnia

[0034] This example exemplarily provides a traditional Chinese medicine composition. Take the following raw medicinal materials: Gentiana scabra 6g, Paeonia lactiflora 12g, Angelica sinensis 6g, Phellodendron amurense 12g, stir-fried Gardenia jasminoides 10g, Alisma orientale 10g, Coix lacryma-jobi var. ma-yuen 15g, Rehmannia glutinosa 10g, Bupleurum chinense 9g, Astragalus membranaceus 12g, Cinnamomum cassia 3g, Salvia miltiorrhiza 12g, Ligusticum chuanxiong 10g, Taraxacum mongolicum 15g. Decoct with water for 2 hours, filter and collect the filtrate, and continue to concentrate the filtrate to 3 - 7 times the total weight of the raw medicinal materials to obtain a traditional Chinese medicine preparation for treating anxiety, depression, and insomnia, denoted as LSJY in the following examples.

[0035] Example 2: Animal Pharmacological Experiment

[0036] Materials Used:

[0037] Test Drug: The traditional Chinese medicine (LSJY) for treating anxiety, depression, and insomnia in Example 1.

[0038] Positive Control Drug: Eszopiclone Tablets (ESZ).

[0039] Test Animals:

[0040] Sixty 6-week-old male C57BL / 6N mice of SPF grade (weighing 18 - 22g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were selected as experimental mice. All mice were kept under the same conditions: cage breeding, exposed to 12 hours of light and 12 hours of darkness every day, with a light cycle of 7:00 - 19:00, an environmental temperature of 22 ± 2°C, and a relative humidity of 50 - 60%. The mice were fed with standard feed and clean drinking water, and they could freely eat and drink. All animal experiments complied with and strictly adhered to the relevant guidelines of the China Animal Protection Association.

[0041] It should be noted that the data in the following examples are expressed as mean ± standard deviation, and SPSS 27.0 and Graphpad prism 9.0 software were used for statistical analysis and plotting of the data. For data conforming to the normal distribution, one-way analysis of variance (One-way ANOVA) was used for inter-group comparison. For data not conforming to the normal distribution, non-parametric tests were used. P < 0.05 was considered statistically significant.

[0042] Experimental Method:

[0043] 1) Modeling, Grouping, and Drug Administration

[0044] C57BL / 6N mice were randomly divided into a normal group (Normal), a model group (Model), an LSJY group at a dose of 15 g crude drug / kg, an LSJY group at a dose of 30 g crude drug / kg, and an ESZ group at a dose of 0.46 mg / kg according to the Excel random number table method, with 12 mice in each group. The dosing doses of the LSJY group at 15 g crude drug / kg, the LSJY group at 30 g crude drug / kg, and the ESZ group at 0.46 mg / kg were obtained by converting the effective human dose. Except for the Normal group, all mice were exposed to two weeks of chronic unpredictable mild stress (CUMS), and each mouse randomly received one stress stimulus per day, including tail suspension (1 min), cold water swimming (in 4°C water, 5 min), food deprivation (24 h), water deprivation (24 h), circadian rhythm reversal (24 h), wet bedding (24 h), cage tilting at 45° (24 h), and limb restraint (24 h). The same stress stimulus was not used for any two consecutive days. Starting from the 15th day, except for the Normal group, mice in each group were intraperitoneally injected with p-chlorophenylalanine PCPA (300 mg / kg) at a dose of 10 mL / kg once a day for 2 consecutive days, and mice in the Normal group were injected with an equal volume of normal saline. When the animals showed disappearance of circadian rhythm, continuous activity during the day, weight loss, irritability, and enhanced aggression, it indicated that the modeling was successful. Starting from the end of modeling (the 17th day), mice in each group were gavaged with LSJY at a dose of 10 mL / kg once a day for 14 consecutive days.

[0045] 2) Measurement of mouse body weight

[0046] The body weights of the mice were weighed before modeling, at the end of modeling, and 2 weeks after drug administration. The effects of LSJY on the body weights of CUMS-PCPA-induced insomnia mice are shown in Figure 1 and Table 1.

[0047] Table 1

[0048]

[0049] Note: Compared with the Normal group: ## P < 0.01; compared with the Model group: ** P < 0.01; compared with the LSJY group at 15 g crude drug / kg: △△ P < 0.01.

[0050] By Figure 1As shown in Table 1, before modeling, there were no significant differences in the body weights of the mice in each group (P > 0.05). After modeling, compared with the Normal group, the body weights of the Model group, ESZ 0.46 mg / kg group, LSJY 15 g crude drug / kg group, and LSJY 30 g crude drug / kg group were all significantly decreased (all P < 0.01). Two weeks after administration, compared with the Normal group, the body weights of the Model group, ESZ 0.46 mg / kg group, LSJY 15 g crude drug / kg group, and LSJY 30 g crude drug / kg group were all significantly decreased (all P < 0.01); compared with the Model group, the body weights of the ESZ 0.46 mg / kg group, LSJY 15 g crude drug / kg group, and LSJY 30 g crude drug / kg group were all significantly increased (all P < 0.01); compared with the LSJY 15 g crude drug / kg group, the body weight of the LSJY 30 g crude drug / kg group was significantly increased (P < 0.01). The above results indicate that the body weight of insomnia mice induced by CUMS-PCPA is significantly decreased, and LSJY can significantly increase the body weight of mice, and its effect shows an obvious dose relationship.

[0051] The specific behavioral tests of the mice included:

[0052] 1. Open field test

[0053] On the 7th day after administration, all experimental animals were subjected to behavioral tests using the open field test: the open field reaction chamber was 50 cm high and the bottom side length was 50 cm. There was a video acquisition device directly above. After placing the mice in the center of the reaction chamber, the movement trajectory behavior analysis system of the mice was used to collect the activity of the mice within 5 minutes. The experiment should be carried out in a quiet and stable light environment. After each mouse was tested, the inner wall and bottom surface of the square box were wiped with 75% alcohol to prevent the remaining smell and excrement from affecting the subsequent behavioral tests of the mice. The test indicators included: the total distance of the mice in the open field movement, the average speed, the activity distance in the central area, and the activity time in the central area.

[0054] The effects of LSJY on the spontaneous activities of CUMS-PCPA-induced insomnia mice within 5 minutes are shown in Table 2. The effects of LSJY on the total activity distance of CUMS-PCPA-induced insomnia mice within 5 minutes are as Figure 2 shown. The effects of LSJY on the average speed of CUMS-PCPA-induced insomnia mice within 5 minutes are as Figure 3 shown. The effects of LSJY on the activity distance of CUMS-PCPA-induced insomnia mice within 5 minutes in the central area are as Figure 4 shown. The effects of LSJY on the activity time of CUMS-PCPA-induced insomnia mice within 5 minutes in the central area are as Figure 5 shown. The effects of LSJY on the activity trajectory of CUMS-PCPA-induced insomnia mice within 5 minutes are as Figure 6as shown

[0055] Table 2

[0056]

[0057] Note: Compared with the Normal group: ## P < 0.01; compared with the Model group: * P < 0.05, ** P < 0.01; compared with the ESZ 0.46 mg / kg group: ☆ P < 0.05, ☆☆ P < 0.01; compared with the LSJY 15 g crude drug / kg group: △ P < 0.05, △△ P < 0.01.

[0058] From Table 2 and Figures 2 - 6 it can be seen that, compared with the Normal group, the total moving distance, average speed, moving distance in the central area, and moving time in the central area of the Model group were all significantly decreased within 5 min (all P < 0.01); compared with the Model group, the total moving distance, average speed, and moving distance in the central area of the ESZ 0.46 mg / kg group, LSJY 15 g crude drug / kg group, and LSJY 30 g crude drug / kg group were all significantly increased within 5 min (all P < 0.05 or P < 0.01), and the moving time in the central area of the ESZ 0.46 mg / kg group and LSJY 30 g crude drug / kg group were both significantly increased within 5 min (all P < 0.01); compared with the ESZ 0.46 mg / kg group, the total moving distance, average speed, moving distance in the central area, and moving time in the central area of the LSJY 30 g crude drug / kg group were all significantly increased within 5 min (all P < 0.05 or P < 0.01); compared with the LSJY 15 g crude drug / kg group, the total moving distance, average speed, moving distance in the central area, and moving time in the central area of the LSJY 30 g crude drug / kg group were all significantly increased within 5 min (all P < 0.05 or P < 0.01). The above results indicate that the anxiety and tension levels of the insomnia mice induced by CUMS-PCPA are relatively high, and LSJY can significantly relieve the anxiety symptoms, and its effect is better than that of ESZ and shows an obvious dose relationship.

[0059] 2. Righting experiment

[0060] On the 8th day after administration, all mice were intraperitoneally injected with pentobarbital sodium solution at a concentration of 45 mg / kg. The animals were turned to the supine position. If the mice could maintain the supine position for more than 60 s, it was considered that their righting reflex disappeared and they entered the sleep state. Record the time from the injection of pentobarbital sodium to the disappearance of the righting reflex (i.e., the sleep latency) and the time from the disappearance of the righting reflex to the recovery of the righting reflex (i.e., the sleep duration).

[0061] The effects of LSJY on the sleep latency and sleep duration of CUMS-PCPA-induced insomnia mice are shown in Table 3. The effect of LSJY on the sleep latency of CUMS-PCPA-induced insomnia mice is as Figure 7 shown, and the effect of LSJY on the sleep duration of CUMS-PCPA-induced insomnia mice is as Figure 8 shown.

[0062] Table 3

[0063]

[0064] Note: Compared with the Normal group: ## P < 0.01; compared with the Model group: ** P < 0.01; compared with the ESZ 0.46 mg / kg group: ☆ P < 0.05; compared with the LSJY 15 g crude drug / kg group: △ P < 0.05.

[0065] As can be seen from Table 3 and Figures 7 - 8 it can be known that compared with the Normal group, the sleep latency of the Model group was significantly increased and the sleep duration was significantly decreased (both P < 0.01); compared with the Model group, the sleep latency of the ESZ 0.46 mg / kg group, LSJY 15 g crude drug / kg group, and LSJY 30 g crude drug / kg group was significantly decreased and the sleep duration was significantly increased (both P < 0.01); there was no significant difference in the sleep latency and sleep duration between the LSJY 30 g crude drug / kg group and the ESZ 0.46 mg / kg group (P > 0.05); compared with the LSJY 15 g crude drug / kg group, the sleep duration of the LSJY 30 g crude drug / kg group was significantly increased (P < 0.05). The above results indicate that the sleep latency of CUMS-PCPA-induced insomnia mice was significantly increased and the sleep duration was significantly decreased. LSJY can significantly relieve insomnia symptoms, significantly reduce its sleep latency and prolong its sleep duration. Its effect intensity is equivalent to that of ESZ, and there is an obvious dose relationship.

[0066] 3. Morris water maze experiment

[0067] On the 9th day after administration, the Morris water maze experiment was conducted. The Morris water maze system includes a white barrel, a white circular platform, a light-shielding curtain, and a video acquisition system. Tap water at 21°C and 45 cm in height was injected into the barrel, and the light around the barrel was blocked with a light-shielding curtain to prevent light refraction in the test environment. Titanium dioxide was added to the water and mixed evenly to make the water in the barrel the same color as the platform, forming a milky white solution to prevent the mice from developing color memory. First, memory training was carried out on the mice: the water surface of the pool was divided into 4 quadrants, and a circular platform with a diameter of 8 cm was placed 1 cm below the water surface in the fourth quadrant (the target quadrant). The mice were respectively placed into the water from the middle of the four quadrants with their backs against the barrel wall, each time for 60 s. If the mice could not find the platform within 60 s, they were guided to the platform and stayed for 10 s. Each mouse was trained 1 time in each of the four quadrants every day for 5 consecutive days, and the activity trajectory map of each mouse was recorded. After the training ended and the platform was removed, the mice were placed into the water from the second quadrant, and the video software tracking system automatically recorded the activity trajectory of the mice within 60 s, recording the platform exploration time, the total distance of platform exploration, the number of times the original platform was found, and the residence time in the target quadrant. If the mice found the quadrant where the original platform was located within 60 s, the time from when the mice entered the water to when they found the quadrant where the original platform was located was the platform exploration time. If the quadrant where the original platform was located was not found within 60 s, the platform exploration time was recorded as 60 s.

[0068] The effects of LSJY on the cognitive function of CUMS-PCPA-induced insomnia mice are shown in Table 4. The effects of LSJY on the platform exploration time of CUMS-PCPA-induced insomnia mice are as Figure 9 shown. The effects of LSJY on the total distance of platform exploration of CUMS-PCPA-induced insomnia mice are as Figure 10 shown. The effects of LSJY on the number of times the original platform was found in CUMS-PCPA-induced insomnia mice are as Figure 11 shown. The effects of LSJY on the residence time in the target quadrant of CUMS-PCPA-induced insomnia mice are as Figure 12 shown. The effects of LSJY on the swimming trajectory of CUMS-PCPA-induced insomnia mice in the water maze experiment are as Figure 13 shown.

[0069] Table 4

[0070]

[0071] Note: Compared with the Normal group: ## P < 0.01; compared with the Model group: * P < 0.05, ** P < 0.01; compared with the ESZ 0.46 mg / kg group: ☆ P < 0.05; compared with the LSJY 15 g crude drug / kg group: △P < 0.01.

[0072] As shown in Table 4 and Figures 9 - 13 it can be seen that compared with the Normal group, the platform exploration time and total platform exploration distance in the Model group were significantly increased (both P < 0.01), and the number of times of finding the original platform and the residence time in the target quadrant were significantly decreased (both P < 0.01); compared with the Model group, the platform exploration time and total platform exploration distance in the ESZ 0.46 mg / kg group, LSJY 15 g crude drug / kg group, and LSJY 30 g crude drug / kg group were significantly decreased (both P < 0.05 or P < 0.01), and the number of times of finding the original platform and the residence time in the target quadrant were significantly increased (both P < 0.05 or P < 0.01); there were no significant differences in the platform exploration time, total platform exploration distance, and the number of times of finding the original platform between the LSJY 15 g crude drug / kg group, LSJY 30 g crude drug / kg group and the ESZ 0.46 mg / kg group (all P > 0.05); the residence time in the target quadrant in the LSJY 30 g crude drug / kg group was significantly higher than that in the LSJY 15 g crude drug / kg group and the ESZ 0.46 mg / kg group (both P < 0.05). The above results indicate that the learning and memory ability of insomnia mice induced by CUMS-PCPA is significantly decreased, and LSJY can significantly improve the memory ability of insomnia mice, and its effect intensity is equivalent to that of ESZ.

[0073] 4. Determination of the contents of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in mouse serum

[0074] After the water maze experiment, all mice were fasted for 12 h, anesthetized with isoflurane, and blood was collected from the eyeballs after the mice were anesthetized. After the blood was left standing at room temperature for 0.5 - 1 h, it was centrifuged at 3500 rpm for 15 min. The serum was aspirated into a 1.5 mL tube, mixed well and then aliquoted, and stored at -80 °C. The contents of 5-HT, DA, and NE in the serum were detected according to the instructions of the ELISA kit.

[0075] The effects of LSJY on the contents of 5-HT, DA, and NE in the serum of insomnia mice induced by CUMS-PCPA are shown in Table 5. The effect of LSJY on the content of 5-HT in the serum of insomnia mice induced by CUMS-PCPA is as Figure 14 shown, the effect of LSJY on the content of DA in the serum of insomnia mice induced by CUMS-PCPA is as Figure 15 shown, and the effect of LSJY on the content of NE in the serum of insomnia mice induced by CUMS-PCPA is as Figure 16 shown.

[0076] Table 5

[0077]

[0078] Note: Compared with Normal: ## P < 0.01; compared with Model: ** P < 0.01.

[0079] As shown in Table 5 and Figures 14 - 16 it can be seen that compared with the Normal group, the content of 5-HT in the serum of the Model group was significantly decreased, while the contents of DA and NE were both significantly increased (both P < 0.01); compared with the Model group, the contents of 5-HT in the serum of the ESZ 0.46 mg / kg group, LSJY 15 g crude drug / kg group, and LSJY 30 g crude drug / kg group were all significantly increased, while the contents of DA and NE were both significantly decreased (both P < 0.01); there were no significant differences in the contents of 5-HT, DA, and NE in the serum between the LSJY 15 g crude drug / kg group and the LSJY 30 g crude drug / kg group and the ESZ 0.46 mg / kg group (both P > 0.05). The above results indicate that the content of 5-HT in the serum of insomnia mice induced by CUMS-PCPA was significantly decreased, while the contents of DA and NE were significantly increased; LSJY can significantly increase the content of 5-HT in the serum of insomnia mice and decrease the contents of serum DA and NE, and its effect intensity is equivalent to that of ESZ.

[0080] The traditional Chinese medicine composition of the present invention is aimed at insomnia caused by stagnation of liver qi. Following the traditional Chinese medicine compatibility theory of "the monarch drug treats the main disease, the minister drug assists in treatment, and the assistant and courier drugs harmonize the formula", it takes clearing liver heat, dispersing liver depression, nourishing heart blood, and regulating yin and yang as the core. By using cold and warm drugs together, attacking and tonifying simultaneously, and regulating qi and blood in unison, it achieves the treatment goal of "descending fire, smoothing qi, calming blood, and tranquilizing the mind". Gentiana scabra is used as the monarch drug, directly entering the liver and gallbladder meridians, specifically clearing the excessive fire in the liver and gallbladder and purging the damp-heat in the lower jiao; Red peony root is used as the minister drug, promoting blood circulation to remove stasis, cooling blood to relieve pain. It not only helps the monarch drug clear the blood heat in the liver meridian but also relieves the unsmooth blood circulation caused by qi stagnation, embodying the compatibility logic of "when qi moves, blood moves; when blood is smooth, qi is relaxed"; Bupleurum is an important drug for dispersing liver depression. It synergizes with the monarch drug Gentiana scabra and the minister drug Red peony root to disperse liver depression. Bupleurum scatters and ascends liver depression, while Red peony root cools the liver and softens the liver. One scatters and one softens, enabling the liver qi to flow smoothly without being rebellious; Phellodendron amurense, stir-fried Gardenia jasminoides, Alisma orientale, and Taraxacum mongolicum clear the damp-heat in the triple jiao. Phellodendron amurense clears the damp-heat in the lower jiao, stir-fried Gardenia jasminoides purges the heart fire, Alisma orientale promotes diuresis to eliminate dampness, and Taraxacum mongolicum disperses heat nodules, preventing the mutual binding of dampness and heat from aggravating the pathogenic fire; Rehmannia glutinosa and Angelica sinensis nourish the liver blood, prevent the damage of yin by fire heat, and since "the liver stores yin and governs yang", nourishing yin can help the liver qi flow smoothly; Astragalus membranaceus invigorates the spleen and replenishes qi, tonifying the acquired foundation to promote the generation of qi and blood, preventing the consumption of qi and blood caused by long-term insomnia; A small amount of Cinnamon twig warms the kidney and aids yang, guiding the floating fire back to its origin and balancing the cold and bitter nature of the whole formula, embodying "for those who are good at treating fire, guiding yang from yin and yin from yang"; Salvia miltiorrhiza and Ligusticum wallichii promote blood circulation and regulate qi, improving the chest and rib distension caused by qi stagnation and blood stasis and the restlessness of the mind at night due to the loss of nourishment; Coix seed is used as the courier drug, harmonizing all the drugs, strengthening the spleen and promoting diuresis to remove dampness. It not only helps Alisma orientale and Phellodendron amurense clear and remove damp-heat but also prevents the spleen from being damaged by the cold and bitter drugs, which is an important guarantee for the whole formula to "clear heat without disturbing the stomach and dispel pathogenic factors without harming the healthy qi". The whole formula takes "Gentiana scabra - Red peony root" as the core, through the multi-dimensional compatibility of "clearing liver and purging fire, dispersing liver depression, connecting the heart and kidney, nourishing blood and calming the mind", precisely targeting the five major pathogenesis of "fire, depression, stasis, deficiency, and disharmony" in insomnia of the liver qi stagnation type. It can not only quickly relieve the insomnia symptoms of "fire disturbing the mind" but also through overall dispersing liver depression, smoothing qi stagnation, and balancing yin and yang qi and blood, having the remarkable advantages of "combining quick effect with long effect and taking both symptomatic and root cause treatment into account". The ingenious proportion of cold and warm drugs and the organic combination of attacking and tonifying drugs in the formula embody the compatibility wisdom of traditional Chinese medicine compound prescriptions of "strictly following the pathogenesis and treating according to the syndrome", and have been fully proven by clinical trials, and can be effectively used for insomnia of the liver qi stagnation type.

[0081] In summary, the medicinal materials of the traditional Chinese medicine composition of the present invention are cheap and easily available, with low cost and high safety, and achieve the therapeutic effect by dispersing liver depression, regulating qi and replenishing qi, and relieving anxiety. Therefore, it can be used to prepare traditional Chinese medicine preparations for treating anxiety, depression, and insomnia. In some embodiments, the traditional Chinese medicine preparation of the present invention may further contain pharmaceutically acceptable carriers or excipients, and the dosage form of the traditional Chinese medicine preparation can be made into granules, tablets, pills, capsules, powders, mixtures, oral liquids, etc.

[0082] The technical solution of the present invention is not limited to the limitations of the above specific embodiments. Any technical deformation made according to the technical solution of the present invention falls within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating anxiety, depression and insomnia, characterized in that, It is composed of the following raw materials in parts by weight: 3 - 6 parts of gentiana, 9 - 12 parts of red peony root, 6 - 9 parts of angelica, 9 - 12 parts of phellodendron bark, 9 - 12 parts of stir-fried gardenia fruit, 9 - 12 parts of alisma orientale, 12 - 15 parts of coix seed, 9 - 12 parts of rehmannia root, 6 - 9 parts of bupleurum root, 12 parts of astragalus membranaceus, 1 - 3 parts of cinnamon, 9 - 12 parts of salvia miltiorrhiza, 9 - 13 parts of ligusticum wallichii, 12 - 15 parts of dandelion.

2. The traditional Chinese medicine composition for treating anxiety, depression and insomnia according to claim 1, wherein It is composed of the following raw materials in parts by weight: 6 parts of gentiana, 12 parts of red peony root, 6 parts of angelica, 12 parts of phellodendron bark, 10 parts of stir-fried gardenia fruit, 10 parts of alisma orientale, 15 parts of coix seed, 10 parts of rehmannia root, 9 parts of bupleurum root, 12 parts of astragalus membranaceus, 3 parts of cinnamon, 12 parts of salvia miltiorrhiza, 10 parts of ligusticum wallichii, 15 parts of dandelion.

3. Use of a traditional Chinese medicine composition for treating anxiety, depression and insomnia as claimed in claim 1 or 2 in the preparation of a traditional Chinese medicine preparation for treating anxiety, depression and insomnia.

4. A traditional Chinese medicine preparation for treating anxiety, depression and insomnia, characterized in that, An extract containing the traditional Chinese medicine composition for treating anxiety, depression and insomnia as claimed in claim 1 or 2.

5. The traditional Chinese medicine preparation for treating anxiety, depression and insomnia according to claim 4, characterized in that, It further contains a pharmaceutically acceptable carrier or excipient.

6. The traditional Chinese medicine preparation for treating anxiety, depression and insomnia according to claim 5, characterized in that The dosage form of the traditional Chinese medicine preparation is one of granule, tablet, pill, capsule, powder, mixture, oral liquid.

7. The traditional Chinese medicine preparation for treating anxiety, depression and insomnia according to claim 4, characterized in that, The preparation method of the extract of the traditional Chinese medicine composition for treating anxiety, depression and insomnia is as follows: Take each raw material according to the ratio, decoct with water 30 - 60 times the total weight of the raw materials for 2 hours, filter and collect the filtrate, continue to concentrate the filtrate to 3 - 7 times the total weight of the raw materials to obtain the extract; or further concentrate or dry the extract to make a medicinal powder.

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