Traditional Chinese medicine composition for treating depression and application

Abstract

The invention discloses a traditional Chinese medicine composition for treating depression, and relates to the field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following medicinal components in parts by weight: 10-15 parts of ginseng, 1-5 parts of cinnamon, 12-18 parts of spina date seed, 7-13 parts of Chinese yam, 8-14 parts of poria cocos, 7-12 parts of dogwood, 7-13 parts of medlar, 1-5 parts of saffron crocus, 6-12 parts of sea-buckthorn, 5-10 parts of gardenia, 5-10 parts of sophora flower, 5-10 parts of honeysuckle, 5-10 parts of pericarpium citri reticulatae, 5-10 parts of purple perilla, 5-10 parts of cassia twig, 3-7 parts of liquorice and 2-7 parts of momordica grosvenori. The traditional Chinese medicine composition is unique and reasonable in compatibility, simple in preparation method, remarkable in curative effect and low in adverse reaction.

Description

Technical Field

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

[0002] Depression is the most common type of mental illness, mainly characterized by continuous and long-term low mood. In severe cases, symptoms such as hallucinations, delusions, and thinking disorders may occur, and even suicidal thoughts may arise, directly threatening life safety. The cause of depression is not yet clear. Studies suggest that its onset may be related to biological, psychological, social environment and other factors. Biological factors are reflected in genetics, neuroendocrine and other aspects; psychological factors are reflected in the psychological characteristics of patients before illness; social environment factors are reflected in stress events in life; all of the above are triggering factors for depression. The clinical manifestations of depression are being in a state of low mood and depression pessimism for a long time, slow thinking speed and dull reaction, slow behavior, unwillingness to communicate with people around, obvious cognitive dysfunction, and usually accompanied by sleep disorders, loss of appetite, weight loss, pain in some parts of the body, etc.

[0003] With the continuous change of people's living habits and the increase of work pressure, the incidence of depression shows an increasing trend year by year, bringing a heavy burden to patients, families and society. Therefore, how to effectively treat depression and improve the prognosis of patients has become the focus of people's attention. In recent years, the main clinical treatments for this disease are antidepressant and sedative drugs, such as paroxetine hydrochloride tablets, fluoxetine hydrochloride capsules, escitalopram tablets, agomelatine tablets, and voseroline hydrobromide tablets. Although they can effectively relieve clinical symptoms, long-term use is extremely likely to produce drug dependence, resulting in a decline in efficacy, high recurrence risk, large side effects and poor long-term efficacy. Traditional Chinese medicine has accumulated certain experience in the treatment of depression. Traditional Chinese medicine believes that depression belongs to the category of depression syndrome. Traditional Chinese medicine believes that this disease is mostly caused by emotional injuries, seven emotions causing depression, damaging the liver, spleen, stomach, and heart, poor circulation of the triple energizer, stagnation of qi and blood, and stagnation of visceral qi. The main pathogenesis is the failure of the liver to disperse and dredge, and stagnation of qi mechanism. The treatment is mostly based on the principles of soothing the liver and relieving depression, reconciling the shaoyang, clearing heat and calming the mind.

[0004] Many traditional Chinese medicine compositions for treating depression have been disclosed in the prior art. For example, patent number "CN116370583A" discloses a traditional Chinese medicine composition for treating depression, its preparation method, and its application, comprising the following raw materials in parts by weight: Tribulus terrestris 5-20 parts, Aristolochia debilis 5-20 parts, Cuscuta chinensis 5-20 parts, Saffron 20-40 parts, Paeonia suffruticosa 20-40 parts, Zanthoxylum bungeanum 5-20 parts, Aucklandia lappa 5-20 parts, Pinellia ternata 5-20 parts, Coix lacryma-jobi 20-40 parts, Houttuynia cordata 20-40 parts, Bupleurum chinense 20-40 parts, Anemarrhena asphodeloides 10-20 parts, Polygala tenuifolia 10-30 parts, Paeonia lactiflora 20-40 parts, Chrysanthemum morifolium 5-20 parts, Phyllanthus urinaria 20-40 parts, Ligusticum chuanxiong 5-20 parts, and Musk 5-20 parts. However, this patent application lacks clinical trial data, the compatibility needs improvement, and the therapeutic effect is unclear. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of this invention is to develop a traditional Chinese medicine composition for treating depression and its preparation method. The traditional Chinese medicine composition has a unique and reasonable formulation, significant efficacy, and low adverse reactions.

[0006] The technical solution of this invention is: This invention provides a traditional Chinese medicine composition for treating depression. The active ingredients of the traditional Chinese medicine composition are formulated and proportioned in the following weight parts: ginseng 10-15 parts, cinnamon 1-5 parts, jujube seed 12-18 parts, yam 7-13 parts, poria cocos 8-14 parts, cornus officinalis 7-12 parts, wolfberry 7-13 parts, saffron 1-5 parts, sea buckthorn 6-12 parts, gardenia 5-10 parts, sophora japonica flower 5-10 parts, honeysuckle 5-10 parts, tangerine peel 5-10 parts, perilla 5-10 parts, cinnamon twig 5-10 parts, licorice 3-7 parts, and monk fruit 2-7 parts.

[0007] Preferred Option 1: The formula and proportions of the traditional Chinese medicine composition are as follows: 12 parts ginseng, 3 parts cinnamon, 15 parts jujube seed, 9 parts yam, 9 parts poria cocos, 9 parts cornus officinalis, 9 parts wolfberry, 2 parts saffron, 9 parts sea buckthorn, 6 parts gardenia, 6 parts sophora japonica, 6 parts honeysuckle, 6 parts dried tangerine peel, 6 parts perilla, 6 parts cinnamon twig, 4 parts licorice, and 4 parts monk fruit.

[0008] Preferred Option 2: The formula and proportions of the traditional Chinese medicine composition are as follows: 10 parts ginseng, 5 parts cinnamon, 12 parts jujube seed, 7 parts yam, 8 parts poria cocos, 7 parts cornus officinalis, 7 parts wolfberry, 1 part saffron, 6 parts sea buckthorn, 5 parts gardenia, 5 parts sophora japonica, 5 parts honeysuckle, 5 parts dried tangerine peel, 5 parts perilla, 5 parts cinnamon twig, 5 parts licorice, and 5 parts monk fruit.

[0009] Preferably, the preparation method of the traditional Chinese medicine composition of the present invention includes the following steps: ginseng, cinnamon, jujube seed, yam, poria, cornus officinalis, wolfberry, saffron, sea buckthorn, gardenia, sophora japonica, honeysuckle, tangerine peel, perilla, cinnamon twig, licorice, and monk fruit are crushed into fine powder according to the above proportions and passed through a 60-100 mesh sieve to obtain the traditional Chinese medicine composition of the present invention.

[0010] Preferably, the traditional Chinese medicine composition of the present invention is further formulated into one of the following: powder, tablet, granule, pill, capsule, and oral liquid.

[0011] The present invention also provides the application of the traditional Chinese medicine composition in the preparation of a medicament for treating depression.

[0012] The prescription of this invention is explained as follows: The core pathogenesis of depression targeted by this formula can be succinctly summarized as: deficiency of heart and spleen yang, liver stagnation and blood heat, and insufficient kidney fire. The treatment principle should focus on warming and tonifying the heart and spleen, nourishing water to nourish wood, soothing the liver and cooling the blood, and guiding fire back to its source. It is a complex and ingenious approach that combines "warming, tonifying, unblocking, clearing, and guiding".

[0013] The classification of the active ingredients of this invention into principal, assistant, adjuvant, and guide components: Chief herb: Warms and invigorates the primordial yang, calms and nourishes the mind. Ginseng: Greatly replenishes vital energy, restores pulse and consolidates the body. It is the core ingredient for boosting overall energy, targeting fundamental functional deficiencies. It greatly replenishes vital energy, strengthens the spleen and lungs, calms the mind and improves intelligence.

[0014] Cinnamon: It tonifies fire and assists yang, guides fire back to its source, dispels cold and relieves pain. This is the key to the formula. Cinnamon has a deep and penetrating effect, directly entering the kidney meridian, warming the fire of the mortal gate, and guiding the floating deficiency fire back to its proper place, fundamentally resolving the complex situation of "upper heat and lower cold".

[0015] Sour jujube seed: Nourishes the heart and liver, calms the mind and soothes the nerves. It specifically enters the heart and liver meridians, making it a core medicine for nourishing and calming the mind, directly targeting the core symptoms of depression: "restlessness, insomnia, and palpitations." While warming the yang, it is essential to nourish the yin and blood to calm the mind, thus achieving a balance between yin and yang.

[0016] The accompanying medicine: strengthens the spleen and kidneys, invigorates blood circulation and relieves depression. Yam: Nourishes the spleen and lungs, strengthens the kidneys and replenishes essence. It assists ginseng in strengthening the spleen and replenishing qi, nourishing the foundation of acquired constitution, and promoting the generation of qi and blood from the source.

[0017] Poria cocos: Strengthens the spleen and calms the mind, promotes diuresis and eliminates dampness. It assists yam in strengthening the spleen and guides the dampness and turbidity of the heart and spleen downward, so that the tonifying effect is not stagnation, and enhances the calming effect.

[0018] Yam and Poria: Strengthen the spleen and replenish qi, eliminate dampness and calm the mind. They assist ginseng in protecting the foundation of acquired constitution, ensuring a source for the generation of qi and blood.

[0019] Cornus officinalis: Nourishes the liver and kidneys, astringes and consolidates. The liver and kidneys share the same origin; it nourishes liver blood to replenish heart yin, and works synergistically with Ziziphus jujuba seed to nourish yin and blood, and consolidate essence.

[0020] Goji berries: Nourish the liver and kidneys, benefit essence and improve eyesight. While clearing heat, they work synergistically with Cornus officinalis to prevent heat-clearing drugs from damaging yin, embodying the idea of ​​"combining attack and tonification".

[0021] Cornus officinalis and Lycium barbarum: Nourish the liver and kidneys, replenish essence and marrow. When these two herbs are combined with cinnamon, they are used in accordance with the concept of "Kidney Qi Pill," which warms the yang while nourishing the yin, thus "seeking yang within yin" and replenishing kidney essence.

[0022] Saffron: It invigorates blood circulation, removes blood stasis, cools the blood, detoxifies, relieves depression, and calms the mind. Its potent effects effectively clear deep-seated stagnation of qi and blood, making it an important medicine for relieving depression. Its penetrating medicinal properties effectively unblock deep-seated stagnation of qi and blood, and it has a unique effect on improving low mood and slow thinking.

[0023] Sea buckthorn: It strengthens the spleen and aids digestion, promotes blood circulation and removes blood stasis. It is warm in nature and has a sour and sweet taste. It can assist yam and poria in strengthening the spleen and stomach, and it can also assist saffron in promoting blood circulation and removing blood stasis. In addition, it is rich in vitamin C and has a "nourishing" effect, making it a "warm and nourishing agent".

[0024] Adjuvant herbs: Clear heat and regulate qi, counteract warming and drying properties. Gardenia: Clears heat and relieves irritability, promotes diuresis and eliminates dampness. It clears away "stagnant fire" caused by qi stagnation, and is an essential medicine for clearing the mind and relieving irritability, targeting "heat symptoms" such as restlessness, anxiety, and insomnia.

[0025] Sophora japonica flowers: cool the blood and stop bleeding, clear liver heat and purge fire. When combined with gardenia, their clearing and detoxifying power penetrates from the Qi level to the blood level, specifically targeting irritability, bitter taste in the mouth, and possible blood heat-induced erratic behavior caused by liver stagnation transforming into fire and disturbing the blood level.

[0026] Honeysuckle: Clears heat and detoxifies, disperses wind-heat. It assists gardenia and sophora japonica in enhancing their ability to clear heat and toxins.

[0027] Gardenia, Sophora japonica, and honeysuckle: These herbs clear heat, relieve irritability, cool the blood, and detoxify. They form a powerful heat-clearing regimen, specifically targeting the heat in the Qi and blood levels caused by liver stagnation. With cinnamon guiding the fire back to its source, these cooling herbs can be used boldly to clear the superficial heat in the upper burner without harming Yang.

[0028] Dried tangerine peel: It regulates qi, strengthens the spleen, dries dampness, and harmonizes the stomach. Adding dried tangerine peel to a large number of tonic herbs can make the tonics less greasy and promote the smooth flow of qi in the middle jiao (middle burner).

[0029] Perilla: It promotes the flow of qi, relieves chest congestion, and alleviates depression. Its aromatic properties can soothe stagnant qi, assist saffron in relieving depression, and also have a stomach-soothing effect.

[0030] Dried tangerine peel and perilla leaves: regulate qi and strengthen the spleen, promote qi circulation and relieve chest congestion. Among a large group of tonifying and heat-clearing herbs, these two herbs can soothe the flow of qi, preventing tonifying herbs from becoming stagnant and heat-clearing herbs from becoming too cooling.

[0031] Cinnamon twig: Its function is to warm and invigorate the heart yang and reach the limbs, assisting cinnamon in warming yang, but its main effect is on the heart and limbs, used to resolve symptoms such as palpitations and cold hands and feet.

[0032] Used as a harmonizing agent to regulate the effects of other herbs, employing a sweet and mild approach. Licorice: Tonifies the spleen and replenishes qi, clears heat and detoxifies, and harmonizes various herbs. It once again plays its role as a "national elder," harmonizing herbs of different temperatures and temperatures to allow them to work together to fight the disease.

[0033] Monk fruit: Clears heat and moistens the lungs, lubricates the intestines and promotes bowel movements. In warming yang medicines, its sweet and moistening properties are used to prevent dryness and heat from damaging body fluids, and it helps to expel pathogenic heat from below by promoting bowel movements.

[0034] This formula uses ginseng to replenish qi, cinnamon to warm yang, and jujube seed to nourish blood. These three form a triangular support of "qi-yang-blood," directly addressing the root cause of depression—insufficient energy (yang deficiency and qi deficiency) and malnourishment of the mind and spirit. Dioscorea opposita, Poria cocos, Cornus officinalis, and Lycium barbarum are responsible for "replenishing," consolidating the foundation of both innate and acquired constitution. Saffron and Hippophae rhamnoides are responsible for "unblocking," clearing stagnation of qi and blood. Replenishing without causing stagnation, and unblocking without harming the body's vital energy. Gardenia jasminoides, Sophora japonica, and Lonicera japonica restrain the warming and drying properties of the principal and assistant herbs. Tangerine peel and Perilla frutescens ensure smooth qi flow. Cinnamon twig assists in warming and unblocking. Together, they ensure that while the entire formula is "strongly warming and replenishing," it does not produce new pathological products. Licorice harmonizes, and monk fruit moistens, both guiding the medicinal power and moderating its effects, making the treatment process more stable. This formula resolves the core contradictions of "floating deficient yang" and "liver stagnation transforming into fire" through the complementary use of "guiding fire back to its source" (cinnamon) and "clearing and purging stagnant heat" (gardenia and sophora flowers), further supplemented by comprehensive tonification and unblocking. It fully embodies the profound wisdom of traditional Chinese medicine's "holistic view" and "treatment based on syndrome differentiation."

[0035] Compared with the prior art, the beneficial effects of the present invention are: 1. Pharmacokinetic study data of the present invention prove that the composition of the present invention can increase the body weight of depressed rats to varying degrees, increase the sucrose preference percentage of depressed rats, increase the open field test score of depressed rats, decrease the Glu content of depressed rats, and increase the γ-GABA content of depressed rats, thus having a good therapeutic effect on depressed rats.

[0036] 2. Clinical efficacy of the present invention: Patients treated with the composition of the present invention have high clinical efficacy, can effectively reduce TCM syndrome scores, HAMD and PSQI scores, can effectively increase BDNF and 5-HT levels, and have no adverse reactions.

[0037] 3. Compared with the comparative formulation, the compositions of the present invention produce a synergistic effect, resulting in a more significant therapeutic effect. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. The detailed description of the embodiments of the present invention provided in the specification is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0039] The weight parts mentioned in the embodiments of the present invention refer to mass, and the units are generally g or kg.

[0040] Example 1 A traditional Chinese medicine composition for treating depression, the formula and proportions of which are as follows by weight: 12 parts ginseng, 3 parts cinnamon, 15 parts jujube seed, 9 parts yam, 9 parts poria cocos, 9 parts cornus officinalis, 9 parts wolfberry, 2 parts saffron, 9 parts sea buckthorn, 6 parts gardenia, 6 parts sophora japonica, 6 parts honeysuckle, 6 parts dried tangerine peel, 6 parts perilla, 6 parts cinnamon twig, 4 parts licorice, and 4 parts monk fruit.

[0041] Preparation method: Ginseng, cinnamon, jujube seed, yam, poria, cornus officinalis, wolfberry, saffron, sea buckthorn, gardenia, sophora japonica, honeysuckle, tangerine peel, perilla, cinnamon twig, licorice, and monk fruit are ground into fine powder according to the above ratio and passed through a 60-100 mesh sieve to obtain the composition.

[0042] Comparative Example 1 A traditional Chinese medicine composition, the formula and proportions of which are as follows by weight: 12 parts ginseng, 3 parts cinnamon, 9 parts yam, 9 parts poria cocos, 9 parts cornus officinalis, 6 parts dried tangerine peel, 6 parts cassia twig, and 4 parts monk fruit.

[0043] Preparation method: Ginseng, cinnamon, yam, poria, tangerine peel, cassia twig, and monk fruit are crushed into fine powder according to the above ratio and passed through a 60-100 mesh sieve to obtain the composition.

[0044] Comparative Example 2 A traditional Chinese medicine composition, the formula and proportions of which are as follows by weight: 12 parts ginseng, 3 parts cinnamon, 9 parts yam, 9 parts poria cocos, 9 parts cornus officinalis, 6 parts tangerine peel, 6 parts gardenia, 6 parts sophora japonica, 6 parts wolfberry, 6 parts cassia twig, and 4 parts monk fruit.

[0045] Preparation method: Ginseng, cinnamon, yam, poria, cornus officinalis, wolfberry, gardenia, sophora japonica, tangerine peel, cassia twig, and monk fruit are ground into fine powder according to the above ratio and passed through a 60-100 mesh sieve to obtain the composition.

[0046] Example 2: Effects of the composition of Example 1 and the comparative pharmaceutical composition on a rat model of depression. 1. Experimental objective: This experiment investigated the therapeutic effect of the composition of Example 1 on rats with depression by replicating a rat model of depression, providing a pharmacological basis for the clinical application of the composition of Example 1.

[0047] 2. Test materials: Test substance (test sample): The composition of Example 1, Comparative Example 1 and Comparative Example 2 (provided by Guyitang Health Technology Group Co., Ltd.), intended route of clinical use: oral administration, 10g once, twice a day, intended course of clinical treatment: 3 months, positive control group, name: fluoxetine hydrochloride capsules, specification: 0.5mg×14 capsules, manufacturer: Tianjin Huai Ren Pharmaceutical Co., Ltd.

[0048] Experimental animals: 78 male SPF-grade SD rats, weighing between 180-200g.

[0049] 3. Experimental methods: (1) Dosage setting: The clinically intended dose of the compositions of Example 1, Comparative Example 1 and Comparative Example 2 is 20 g / day, which is converted to the clinically equivalent dose for rats based on body surface area = adult dose × 0.018 × 5 = 1.8 g / kg. The dose of the positive control group is set at 1.8 mg / kg according to the literature.

[0050] (2) Establishment of a rat depression model: 78 SD rats were randomly divided into a blank control group, a model control group, Example 1, Comparative Example 1 and Comparative Example 2, and a positive control group, with 13 rats in each group. The blank control group was housed in a normal group and fed a normal diet; the other groups were modeled using the chronic unpredictable mild stress model (CUMS method). CUMS stimulation methods included empty bottle stimulation (deprivation of water for 24 hours, followed by empty bottle), fasting (24 hours), tail clamping (clamping the tail 1 cm from the base, timing from the first cry, 1 min / time, 2 times / day), cage tilting (45°, 24 hours), high temperature stimulation (50°C, 10 min), wet bedding (bedding with a water content of 200 mL / 100 g, 3 hours / time, 2 times / day), cage shaking (5 min / time, 2 times / day), water deprivation (total 24 hours), and ultrasonic noise stimulation (3 hours / time, 2 times / day). Starting from day 1 of modeling, one or more stimuli were randomly assigned daily for 28 consecutive days, ensuring that the same stimulus was not used repeatedly. Behavioral observations revealed that, compared to the blank control group, rats in each group showed decreased scores in the open field test, significantly prolonged immobility time in the forced swimming test, and exhibited depressive-like behavioral changes such as reduced pleasure, decreased curiosity, and hopelessness. Successful modeling was then confirmed. After successful modeling, each group was administered the appropriate treatment via gavage: the blank control group and the model control group received distilled water, while groups in Example 1, Comparative Example 1 and Comparative Example 2, and the positive control group received the corresponding dose of medication. This administration continued until the end of the experiment on day 49.

[0051] (3) Weight test: The weight of rats in each group was measured on days 1, 28 and 49 of the experiment.

[0052] (4) Sugar water preference experiment. Before modeling, rats were trained to adapt to a 1% (w / v) sucrose solution. After fasting and water restriction for 48 hours, only a 1% (w / v) sucrose solution was provided. After a 3-day adaptation period, a 1-hour baseline test was conducted under a 23-hour fasting and water restriction condition. Pre-weighed bottles of 1% (w / v) sucrose solution and tap water were provided, and rats could freely choose between the two bottles. The percentage of sucrose preference = [sucrose intake (g) / (sucrose intake (g) + tap water intake (g))] × 100%. The sucrose preference of each group of rats was measured on days 1, 28, and 49 of the experiment.

[0053] (5) Open Field Experiment for Rats. An opaque open box device measuring 40cm×40cm×45cm was used, and rat behavior was recorded using animal spontaneous activity monitoring software. During the experiment, the rats were placed in the center of the open box, and after acclimatization for 2 minutes, their spontaneous activity was recorded continuously for 10 minutes. Behavioral scoring criteria: In horizontal movement, 1 point was awarded when all three paws of the rat simultaneously entered the grid area; in vertical movement, 1 point was awarded when both front paws of the rat were raised or climbed the box wall. To eliminate the influence of odors and feces left by the tested rats on the test rats, the feces of each rat were cleaned after the test, and the box was thoroughly wiped with 75% ethanol. Unnecessary stimulation was avoided during the experiment. Tests were conducted on days 1, 28, and 49 of the experiment, with each rat being tested three times, and the average value was taken as the final result.

[0054] (6) Determination of glutamate (Glu) and γ-aminobutyric acid (γ-GABA) content in rat hippocampal tissue. Immediately after blood collection, the rat was decapitated and the brain removed. Bilateral hippocampal tissue was rapidly separated and rinsed with phosphate buffer (0.02 mol / L, pH 7.0–7.2) at 4°C to remove residual blood. After preparing a homogenate of the hippocampal tissue, the contents of Glu and γ-GABA in the hippocampal tissue were determined by high-performance liquid chromatography using the pre-column derivatization method with o-phthalaldehyde.

[0055] Results Calculation and Statistics SPSS 21.0 software was used for statistical analysis. Experimental data are expressed as mean ± standard deviation (x±S). For comparisons among multiple groups, normality and homogeneity of variance were first compared. If the variances were homogeneous and normality was observed, one-way ANOVA was used. If normality was not observed, the Nonparametric T-test was used. If normality was observed but variances were unequal, Tamhane's T² test was used. If normality was not observed, the Kruskal-Wallis test was used. Pairwise comparisons were performed using the Mann-Whitney test. P < 0.05 was considered statistically significant, and P < 0.01 was considered highly significant.

[0056] 4. Experimental Results Effects on body weight of rats at different time points As shown in Table 1, there was no statistically significant difference in body weight among the groups on day 1. Compared with the blank control group, the body weight of the model control group was significantly lower on days 28 and 49 after modeling (P<0.01). Compared with the model control group, the body weight of Comparative Example 1, Comparative Example 2, Example 1, and the positive control group was significantly higher on days 28 and 49 after drug administration (P<0.05 or P<0.01). The body weight of Example 1 was significantly higher on days 28 and 49 compared with Comparative Example 1 and Comparative Example 2 (P<0.05 or P<0.01). There was no statistically significant difference between Example 1 and the positive control group on days 28 and 49 (P>0.05). The body weight of Comparative Example 2 was significantly higher on day 49 compared with Comparative Example 1 (P<0.05), and the body weight of Comparative Example 2 was higher on day 28 compared with Comparative Example 1, but the difference was not statistically significant (P>0.05). The results are shown in Table 1. The experimental results suggest that the composition of Example 1 can significantly increase the body weight of depressed rats.

[0057] Table 1. Effects of the composition of Example 1 on the body weight of rats at different time points ( (n=13)

[0058] Note: Compared with the blank control group, "**" indicates P<0.01; compared with the model control group, "**" indicates P<0.01. " indicates P < 0.05, " " " indicates P < 0.01, compared with Comparative Example 1; "##" indicates P < 0.05, "##" indicates P < 0.01, compared with Comparative Example 2; "▲" indicates P < 0.05. Comparison of sucrose preference percentage in rats at different time points As shown in Table 2, there was no statistically significant difference in the percentage of sucrose preference among the groups on day 1. Compared with the blank control group, the percentage of sucrose preference in the model control group was significantly lower on days 28 and 49 after modeling (P<0.01). Compared with the model control group, the percentage of sucrose preference in Comparative Example 1, Comparative Example 2, Example 1, and the positive control group was significantly higher on days 28 and 49 after drug administration (P<0.05 or P<0.01). The percentage of sucrose preference in Example 1 was significantly higher than that in Comparative Example 1 and Comparative Example 2 on days 28 and 49 (P<0.05). There was no statistically significant difference between Example 1 and the positive control group on days 28 and 49 (P>0.05). The percentage of sucrose preference in Comparative Example 2 was higher than that in Comparative Example 1 on days 28 and 49, but the difference was not statistically significant (P>0.05). The results are shown in Table 2. The experimental results suggest that the composition of Example 1 can significantly increase the percentage of sucrose preference in depressed rats.

[0059] Table 2 Comparison of the percentage of sucrose preference in rats at different time points for the composition of Example 1 ( (n=13)

[0060] Note: Compared with the blank control group, "**" indicates P<0.01; compared with the model control group, "**" indicates P<0.01. " indicates P < 0.05, " "#" indicates P < 0.01, compared with Comparative Example 1; "#" indicates P < 0.05, compared with Comparative Example 2; "▲" indicates P < 0.05. Comparison of open field test scores at different times in rats As shown in Table 3, there was no statistically significant difference in the open field test scores among the groups on day 1. Compared with the blank control group, the open field test scores of the model control group were significantly lower on days 28 and 49 after modeling (P<0.01). Compared with the model control group, the open field test scores of Comparative Example 1, Comparative Example 2, Example 1, and Positive Control Group were significantly higher on days 28 and 49 after drug administration (P<0.05 or P<0.01). The open field test scores of Example 1 were significantly higher than those of Comparative Example 1 and Comparative Example 2 on days 28 and 49 (P<0.05). There was no statistically significant difference between Example 1 and the Positive Control Group on days 28 and 49 (P>0.05). The open field test scores of Comparative Example 2 were higher than those of Comparative Example 1 on days 28 and 49, but the difference was not statistically significant (P>0.05). The results are shown in Table 3. The experimental results suggest that the composition of Example 1 can significantly increase the open field test scores of depressed rats.

[0061] Table 3. Comparison of open field test scores of rats at different time points using the composition of Example 1 ( (n=13)

[0062] Note: Compared with the blank control group, "**" indicates P<0.01; compared with the model control group, "**" indicates P<0.01. " indicates P < 0.05, " "#" indicates P < 0.01, compared with Comparative Example 1; "#" indicates P < 0.05, compared with Comparative Example 2; "▲" indicates P < 0.05. Comparison of Glu and γ-GABA content in rat hippocampus As shown in Table 4, compared with the blank control group, the Glu content in the model control group was significantly increased (P<0.01), and the γ-GABA content was significantly decreased (P<0.01), indicating successful modeling. Compared with the model control group, Glu was significantly decreased (P<0.05 or P<0.01) and the γ-GABA content was significantly increased (P<0.05 or P<0.01) in Comparative Example 1 and Comparative Example 1. Glu was significantly decreased (P<0.05) and the γ-GABA content was significantly increased (P<0.01) in Comparative Example 1 and Comparative Example 2. Glu was significantly decreased (P<0.05) and the γ-GABA content was significantly increased (P<0.05) in Comparative Example 1 and Comparative Example 2. There was no statistically significant difference between Comparative Example 1 and the positive control group (P>0.05). The γ-GABA content was significantly increased (P<0.05) and Glu was decreased in Comparative Example 2 compared with Comparative Example 1, but the difference was not statistically significant (P>0.05). The results are shown in Table 4. The experimental results suggest that the composition of Example 1 can significantly reduce the Glu content in depressed rats and significantly increase the γ-GABA content in depressed rats.

[0063] Table 4 Comparison of Glu and γ-GABA content in rat hippocampus of the composition of Example 1 ( (n=13)

[0064] Note: Compared with the blank control group, "**" indicates P<0.01; compared with the model control group, "**" indicates P<0.01. " indicates P < 0.05, " " " indicates P < 0.01, compared with Comparative Example 1; "#" indicates P < 0.05; "##" indicates P < 0.01, compared with Comparative Example 2; "▲" indicates P < 0.05. Conclusion: Under the conditions of this experiment, the compositions of Comparative Example 1, Comparative Example 2, and Example 1 could increase the body weight, sucrose preference percentage, open field test score, Glu content, and γ-GABA content of depressed rats to varying degrees. Example 1 showed better efficacy than Comparative Example 1 and Comparative Example 2, with a significant synergistic effect. The composition of Example 1 has a good therapeutic effect on depressed rats.

[0065] Example 3: Clinical analysis data of the composition of Example 1 for depression General Information: 126 patients meeting the diagnostic criteria for depression were selected for observation and randomly divided into Example 1 and a control group. Example 1 included 33 male and 30 female patients, aged 21–58 years (mean age 35.46±7.62 years), with a disease duration of 4–28 months (mean 13.25±3.14 months). The control group included 32 male and 31 female patients, aged 20–56 years (mean age 36.07±8.17 years), with a disease duration of 5–26 months (mean 13.81±3.45 months). There were no statistically significant differences in general characteristics between the two groups (P>0.05), indicating comparability.

[0066] Diagnostic Criteria: Western Medicine: Referencing the diagnostic criteria for depression in the *CCMD-3 Chinese Classification and Diagnostic Criteria for Mental Disorders*. A diagnosis is made primarily based on depressed mood, with at least four of the following criteria: loss of interest / pleasure; decreased energy or fatigue; psychomotor retardation or agitation; low self-esteem, self-blame, or guilt; difficulty concentrating or perceived decline in thinking ability; recurrent thoughts of death or suicidal / self-harming behavior; sleep disturbances such as insomnia, early awakening, or excessive sleep; decreased appetite or significant weight loss; decreased libido. Traditional Chinese Medicine: Referring to the diagnostic criteria for depression in the *Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Internal Medicine: Section on Traditional Chinese Medicine Diseases*, the syndrome is identified as Liver Qi Stagnation Syndrome. Main symptoms: Depression, chest and rib distension, frequent sighing, irritability; Secondary symptoms: Muscle pain, dizziness, headache, insomnia, epigastric fullness, belching, poor appetite; Tongue and pulse: Pale tongue with a thin white coating, wiry pulse.

[0067] Inclusion criteria: meeting the above diagnostic criteria; receiving full treatment; and being between 18 and 60 years of age.

[0068] Exclusion criteria: coexisting with other serious diseases affecting vital organs, malignant tumors or other types of mental illness; taking other antidepressants within the past 3 months; breastfeeding or pregnant women; dependence on alcohol or drugs.

[0069] Treatment methods: The control group took paroxetine hydrochloride tablets (Beijing Wansheng Pharmaceutical Co., Ltd., National Drug Approval Number H20133084) after breakfast, 20mg each time, once a day; the Example 1 group took the product of Example 1 of this invention (Guyitang Health Technology Group Co., Ltd., 10g / bag) orally, 1 bag each time, twice a day. Both groups of patients were treated continuously for 3 months.

[0070] Observation indicators: (1) Clinical efficacy.

[0071] (2) TCM syndrome score. According to the scoring criteria for liver qi stagnation syndrome in the "Guidelines for Diagnosis and Treatment of Common Diseases in TCM Internal Medicine: TCM Syndromes", the main symptoms (emotional depression, chest and rib distension, frequent sighing, and irritability) were scored as 0, 2, 4, and 6 points respectively, and the secondary symptoms (insomnia, belching, epigastric fullness, poor appetite, headache and dizziness, and muscle pain) were scored as 0, 1, 2, and 3 points respectively. The TCM syndrome score was obtained by adding the scores of the main and secondary symptoms. The higher the score, the more severe the symptoms.

[0072] (3) Depression level. The Hamilton Depression Rating Scale (HAMD) was used to assess the patient’s depression level before and after treatment. The scale includes 24 items, each item is scored from 0 to 4; a total score of 0 to 8 is normal, 9 to 19 is possible depression, 20 to 34 is definitely depression, and ≥35 is severe depression.

[0073] (4) Sleep quality. The Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality of patients before and after treatment. The scale has 7 items, each scored from 0 to 3 points, for a total of 21 points. The higher the score, the worse the sleep quality.

[0074] (5) Brain-derived nerve growth factor (BDNF) and serotonin (5-HT) levels. Before and after treatment, 3 ml of fasting venous blood was collected from patients in the morning. The blood was centrifuged at 3000 r / min for 10 min with a centrifugation radius of 15 cm. The supernatant was stored at -80℃ for later testing. Serum BDNF and 5-HT levels were measured using enzyme-linked immunosorbent assay (ELISA).

[0075] (6) Observation of the incidence of adverse reactions in the two groups of patients after treatment.

[0076] Efficacy criteria: Based on the relevant standards in the "Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine Internal Medicine: TCM Syndromes Section," and combined with clinical practice, the following criteria were established: Cured: Clinical symptoms disappear, efficacy index ≥ 95%, HAMD score reduction rate ≥ 75%; Significantly Effective: Clinical symptoms significantly improve, 70% ≤ efficacy index < 95%, 50% ≤ HAMD score reduction rate < 75%; Effective: Clinical symptoms are somewhat relieved, 30% ≤ efficacy index < 70%, 25% ≤ HAMD score reduction rate < 50%; Ineffective: Clinical symptoms do not improve or worsen, efficacy index and HAMD reduction rate < 25%. The efficacy index was calculated using the nimodipine method: Efficacy Index = (TCM syndrome score before treatment - TCM syndrome score after treatment) / TCM syndrome score before treatment × 100%. HAMD score reduction rate = (HAMD score before treatment - HAMD score after treatment) / HAMD score before treatment × 100%.

[0077] Statistical methods: SPSS 16.0 statistical software was used for data processing and analysis in this study. The t-test was used to compare continuous data, and the chi-square test was used to compare categorical data. P < 0.05 was considered statistically significant.

[0078] Comparison of clinical efficacy between the two groups: As shown in Table 5, the total effective rate of the Example 1 group and the control group was comparable, and the difference was not statistically significant (P>0.05).

[0079] Table 5 Comparison of clinical efficacy between the two groups [n(%)]

[0080] Comparison of TCM syndrome scores between the two groups: As shown in Table 6, there was no statistically significant difference before treatment (P>0.05); after treatment, the TCM syndrome scores of both groups decreased compared with those before treatment (P<0.01), and the TCM syndrome score of Example 1 was lower than that of the control group (P<0.05).

[0081] Table 6 Comparison of TCM syndrome scores before and after treatment in the two groups ( ,point)

[0082] Note: Compared with the pre-treatment values ​​in this group, "**" indicates P<0.01; compared with the post-treatment values ​​in the control group, "#" indicates P<0.05. Comparison of HAMD and PSQI scores before and after treatment in the two groups: as shown in Table 7. Before treatment, there was no statistically significant difference in HAMD and PSQI scores between the two groups (P>0.05); after treatment, both HAMD and PSQI scores decreased compared with those before treatment (P<0.05 or P<0.01), and the HAMD and PSQI scores of Example 1 group were comparable to those of the control group, with no statistically significant difference (P>0.05).

[0083] Table 7 Comparison of HAMD and PSQI scores before and after treatment in the two groups ( ,point)

[0084] Note: Compared with the pre-treatment values ​​in this group, "*" indicates P<0.05, and "**" indicates P<0.01. Table 8 shows the comparison of serum BDNF and 5-HT levels before and after treatment in the two groups. Before treatment, there was no statistically significant difference in serum BDNF and 5-HT levels between the two groups (P>0.05). After treatment, the BDNF and 5-HT levels in both groups increased compared with those before treatment (P<0.05). Furthermore, the BDNF and 5-HT level scores of the Example 1 group and the control group were comparable, with no statistically significant difference (P>0.05).

[0085] Table 8 Comparison of BDNF and 5-HT levels before and after treatment in the two groups ( )

[0086] Note: Compared with the pre-treatment values ​​in this group, "*" indicates P<0.05, and "**" indicates P<0.01. The incidence of adverse reactions in the two groups of patients was compared and observed, as shown in Table 9. Compared with the control group, the group of Example 1 had no adverse reactions, and the difference was statistically significant (P < 0.05). Table 9 Comparison of adverse reaction rates between the two groups [cases (%)]

[0087] Note: Compared with the control group after treatment, *P<0.05.

[0088] As shown in Tables 5-9, the clinical efficacy of Example 1 group was high, which could effectively reduce the TCM syndrome score, HAMD and PSQI scores, effectively increase BDNF and 5-HT levels, and had no adverse reactions.

[0089] Example 4 A traditional Chinese medicine composition for treating depression, the formula and proportions of which are as follows by weight: 10 parts ginseng, 5 parts cinnamon, 12 parts jujube seed, 7 parts yam, 8 parts poria cocos, 7 parts cornus officinalis, 7 parts wolfberry, 1 part saffron, 6 parts sea buckthorn, 5 parts gardenia, 5 parts sophora japonica flower, 5 parts honeysuckle, 5 parts dried tangerine peel, 5 parts perilla, 5 parts cinnamon twig, 5 parts licorice, and 5 parts monk fruit.

[0090] Preparation method: Ginseng, cinnamon, jujube seed, yam, poria, cornus officinalis, wolfberry, saffron, sea buckthorn, gardenia, sophora japonica, honeysuckle, tangerine peel, perilla, cinnamon twig, licorice, and monk fruit are ground into fine powder according to the above ratio and passed through a 60-100 mesh sieve to obtain the composition.

[0091] The efficacy of the traditional Chinese medicine composition in Example 4 is similar to that in Example 1, and will not be repeated here.

Claims

1. A traditional Chinese medicine composition for treating depression, characterized in that: The medicinal components of the aforementioned traditional Chinese medicine composition are formulated and proportioned in the following weight parts: ginseng 10-15 parts, cinnamon 1-5 parts, jujube seed 12-18 parts, yam 7-13 parts, poria cocos 8-14 parts, cornus officinalis 7-12 parts, wolfberry 7-13 parts, saffron 1-5 parts, sea buckthorn 6-12 parts, gardenia 5-10 parts, sophora japonica flower 5-10 parts, honeysuckle 5-10 parts, tangerine peel 5-10 parts, perilla 5-10 parts, cinnamon twig 5-10 parts, licorice 3-7 parts, and monk fruit 2-7 parts.

2. The traditional Chinese medicine composition for treating depression according to claim 1, characterized in that, The medicinal components of the aforementioned Chinese herbal composition are formulated and proportioned in the following weight parts: ginseng 12 parts, cinnamon 3 parts, jujube seed 15 parts, yam 9 parts, poria cocos 9 parts, cornus officinalis 9 parts, wolfberry 9 parts, saffron 2 parts, sea buckthorn 9 parts, gardenia 6 parts, sophora japonica flower 6 parts, honeysuckle 6 parts, tangerine peel 6 parts, perilla 6 parts, cinnamon twig 6 parts, licorice 4 parts, and monk fruit 4 parts.

3. The traditional Chinese medicine composition for treating depression according to claim 1, characterized in that, The medicinal components of the aforementioned traditional Chinese medicine composition are formulated and proportioned in the following weight parts: ginseng 10 parts, cinnamon 5 parts, jujube seed 12 parts, yam 7 parts, poria cocos 8 parts, cornus officinalis 7 parts, wolfberry 7 parts, saffron 1 part, sea buckthorn 6 parts, gardenia 5 parts, sophora japonica flower 5 parts, honeysuckle 5 parts, tangerine peel 5 parts, perilla 5 parts, cinnamon twig 5 parts, licorice 5 parts, and monk fruit 5 parts.

4. A traditional Chinese medicine composition for treating depression according to any one of claims 1-3, characterized in that, The preparation method includes the following steps: Ginseng, cinnamon, jujube seed, yam, poria, cornus officinalis, wolfberry, saffron, sea buckthorn, gardenia, sophora japonica, honeysuckle, tangerine peel, perilla, cinnamon twig, licorice, and monk fruit are crushed into fine powder according to the above proportions and passed through a 60-100 mesh sieve to obtain the traditional Chinese medicine composition of the present invention.

5. A traditional Chinese medicine composition for treating depression according to claim 4, characterized in that, The traditional Chinese medicine composition may be further formulated into one of the following: powder, tablet, granule, pill, capsule, and oral liquid.

6. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for treating depression.

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