Composition for treating depression and application thereof

Abstract

The invention provides a composition for preventing and / or treating major depression. The composition comprises ginsenoside Rg3, coenzyme Q10, polygala tenuifolia and semen ziziphi spinosae. The medicine prepared from the composition has the advantages of obvious anti-depression effect, low toxic and side effects and difficulty in drug resistance when being used for treating major depression. According to the composition disclosed by the invention, the depression-like behavior of a mouse with depression can be obviously relieved through combined application of all the components, and the treatment effect of a patient with severe depression can be greatly improved through combined action of multiple medicines.

Description

Technical Field

[0001] The present invention belongs to the field of medicine, and specifically relates to a composition for treating depression, especially major depression, and its application. Background Art

[0002] The main symptoms of major depressive disorder (MDD) include depression, anhedonia, behavioral despair, social avoidance, cognitive impairment, etc., and severe cases may have suicidal behavior. The latest survey results published by the World Health Organization (WHO) show that about 251 million to 310 million people are affected by depression worldwide, and depression has become one of the main causes of global disease burden. However, traditional antidepressants, such as tricyclic antidepressants, tetracyclic antidepressants, selective 5-HT reuptake inhibitors, norepinephrine reuptake inhibitors, neurotrophic factors, etc., have the disadvantages of slow onset, low cure rate, easy relapse, many adverse reactions, and easy drug resistance. Therefore, it is urgent to provide a new antidepressant composition. Summary of the invention

[0003] In view of the problems existing in the prior art, the present disclosure provides a composition for preventing and / or treating major depression. The pharmaceutical composition disclosed in the present disclosure has the advantages of obvious antidepressant effect, low toxicity and side effects, and low resistance to drugs for treating major depression. The combined use of ginsenoside Rg3, coenzyme Q10, polygala tenuifolia, and spiny date seed in the composition disclosed in the present disclosure can significantly alleviate the depressive-like behavior of depression mice, and the combined action of multiple drugs can greatly improve the therapeutic effect of patients with major depression.

[0004] According to one aspect of the present disclosure, a composition is provided, comprising ginsenoside Rg3, coenzyme Q10, Polygala tenuifolia and Semen Ziziphi Spinosae.

[0005] In some embodiments, the mass ratio of the ginsenoside Rg3 to the coenzyme Q10 is (0.5-3):1, for example, 0.5:1, 0.6:1, 0.7:1, 1:1, 1.2:1, 1.5:1, 1.8:1, 2.0:1, 2.2:1, 2.5:1, 2.8:1, 2.9:1, 3:1 or any value therebetween. In some preferred embodiments, the mass ratio of the ginsenoside Rg3 to the coenzyme Q10 is (1-2):1.

[0006] In some embodiments, the mass ratio of the wild jujube seeds to the polygala is (0.5-8):1, for example, 0.5:1, 1:1, 1.2:1, 1.5:1, 1.8:1, 2:1, 2.5:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 or any value therebetween. In some preferred embodiments, the mass ratio of the wild jujube seeds to the polygala is (1-2):1.

[0007] According to another aspect of the present disclosure, a pharmaceutical composition for preventing and / or treating depression is provided, the pharmaceutical composition comprising ginsenoside Rg3, coenzyme Q10, polygala root extract and spiny jujube seed extract.

[0008] In some embodiments, the pharmaceutical composition is made from the composition described in the present disclosure.

[0009] In some embodiments, in the pharmaceutical composition, the mass ratio of ginsenoside Rg3, coenzyme Q10, polygala root extract and spiny jujube seed extract is (0.1-15): (0.1-10): 1: (1-10), preferably (0.5-5): (0.2-4): 1: (1-6), and more preferably (1-2): 1: 1: (1-2). In some specific embodiments, in the pharmaceutical composition, the mass ratio of ginsenoside Rg3, coenzyme Q10, polygala root extract and spiny jujube seed extract is 1.5: 1: 1: 1.5.

[0010] In some embodiments, based on the mass content of the pharmaceutical composition, the content of ginsenoside Rg3 is 5%-60%, for example, 5%, 6%, 9%, 12%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 58%, 59%, 60% or any value therebetween. In some preferred embodiments, based on the mass content of the pharmaceutical composition, the content of ginsenoside Rg3 is 5%-50%, preferably 20%-40%.

[0011] In some embodiments, based on the mass content of the pharmaceutical composition, the mass content of the coenzyme Q10 is 5%-30%, for example, 5%, 6%, 7%, 9%, 12%, 15%, 18%, 20%, 25%, 28%, 29%, 30% or any value therebetween. In some preferred embodiments, based on the mass content of the pharmaceutical composition, the mass content of the coenzyme Q10 is 5%-25%, preferably 15%-25%.

[0012] In some embodiments, based on the mass content of the pharmaceutical composition, the mass content of the Polygala extract is 10%-70%, for example, 10%, 11%, 13%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 68%, 69%, 70% or any value therebetween. In some preferred embodiments, based on the mass content of the pharmaceutical composition, the mass content of the Polygala extract is 5%-40%, preferably 15%-25%.

[0013] In some embodiments, based on the mass content of the pharmaceutical composition, the mass content of the Chinese date seed extract is 10%-60%, for example, 10%, 11%, 12%, 13%, 19%, 22%, 28%, 38%, 39%, 40%, 48%, 50%, 53%, 54%, 55%, 58%, 59%, 60% or any value therebetween. In some preferred embodiments, based on the mass content of the pharmaceutical composition, the mass content of the Chinese date seed extract is 20%-50%, preferably 20%-40%.

[0014] In some embodiments, based on the mass content of the pharmaceutical composition, the content of ginsenoside Rg3 is 25-35%, the content of coenzyme Q10 is 15%-25%, the content of Polygala tenuifolia extract is 15%-25%, and the content of Ziziphus jujuba seed extract is 25-35%.

[0015] In some embodiments, based on the mass content of the pharmaceutical composition, the content of ginsenoside Rg3 is 28-32%, the content of coenzyme Q10 is 18-22%, the content of Polygala tenuifolia extract is 18-22%, and the content of Ziziphus jujuba seed extract is 28-32%.

[0016] In some embodiments, the Polygala root extract comprises a water extract of Polygala root.

[0017] In some embodiments, the spinach seed extract includes a water extract of stir-fried spinach seeds.

[0018] In some embodiments, Polygala tenuifolia and stir-fried Semen Ziziphi Spinosae are crushed and then mixed or decocted and filtered separately, and the filtrate is collected to obtain the Polygala tenuifolia extract and the Semen Ziziphi Spinosae extract.

[0019] In some embodiments, the Polygala extract is obtained by a method comprising the following steps: soaking Polygala in 1.5-3 times the mass of water for more than 2 hours, heating and simmering for 2-4 hours until the liquid volume is concentrated to 1 / 5-1 / 3 of the original, filtering, and the obtained filtrate is the Polygala extract.

[0020] In some embodiments, the Chinese jujube seed extract is obtained by a method comprising the following steps: crushing the fried Chinese jujube seeds, soaking them in 1.5-3 times the mass of water for more than 2 hours, heating and simmering them over low heat for 2-4 hours until the liquid volume is concentrated to 1 / 5-1 / 3 of the original amount, filtering, and the obtained filtrate is the Chinese jujube seed extract.

[0021] In some embodiments, the stir-frying comprises placing the sour jujube seeds in a stir-frying container and heating over a low heat until the seeds swell up, make crackling sounds, and become slightly darker in color, then taking the seeds out and letting them cool.

[0022] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0023] In some embodiments, the dosage form of the pharmaceutical composition includes any one of an emulsion, a solution, a suspension or a granule.

[0024] According to another aspect of the present disclosure, provided is a use of the composition of the present disclosure in the preparation of a medicament for preventing and / or treating depression.

[0025] In some embodiments, the depression comprises major depressive disorder.

[0026] In some embodiments, the pharmaceutical composition reduces the total score of the Montgomery-Asberg Depression Rating Scale (MADRS) by at least 4 points in a subject suffering from major depression.

[0027] In some embodiments, the total movement pattern of mice in an open field test of chronic unpredictable mild stress in mice is increased.

[0028] In some embodiments, the immobility time in water of mice in a chronic unpredictable mild stress mouse forced swim test is reduced.

[0029] In some embodiments, the immobility time of mice in the air in the chronic unpredictable mild stress mouse tail suspension test is reduced.

[0030] In some embodiments, the preference for sugar water in mice in a sugar water preference experiment of mice subjected to chronic unpredictable mild stress is increased.

[0031] The pharmaceutical composition of the present invention adopts active ingredients such as ginsenoside Rg3, coenzyme Q10, polygala tenuifolia, and spiny jujube seeds, and has the characteristics of obvious antidepressant effect, low toxic and side effects, and low resistance to drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Results of MADRS score reduction values ​​are shown. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical scheme and advantages of the present disclosure clearer, the present disclosure is further described in detail below in conjunction with the embodiments. The specific embodiments described herein are only used to explain the present disclosure and are not intended to constitute any limitation to the present disclosure. In addition, in the following description, the description of the well-known structures and technologies is omitted to avoid unnecessary confusion of the concepts of the present disclosure. Such structures and technologies are also described in many publications.

[0034] Examples are provided below to help understand the present disclosure. However, it should be understood that these examples are only used to illustrate the present disclosure and do not constitute any limitation. The actual protection scope of the present disclosure is set forth in the claims. It should be understood that any modifications and changes can be made without departing from the spirit of the present disclosure.

[0035] Example 1

[0036] 1. Pharmaceutical raw materials

[0037] The Chinese jujube seed extract is a water extract of fried Chinese jujube seeds, which is obtained by the following method: take clean jujube seeds, place them in a frying container and heat them over low heat until they swell, there is a popping sound, and the color becomes slightly darker, take them out, cool them, and then crush them, soak them in twice the mass of deionized water for 2 hours, heat them over low heat and boil them for 3 hours until the liquid volume is concentrated to 1 / 4 of the original, filter them, and obtain the filtrate for later use.

[0038] The polygala extract is a water extract of polygala, which is obtained by the following method: soak the polygala in deionized water twice its mass for more than 2 hours, heat and simmer for more than 3 hours until the liquid volume is concentrated to 1 / 4 of the original, filter, and obtain the filtrate for later use.

[0039] Ginsenoside Rg3 was purchased from APExBIO, CAS No.: 14197-60-5

[0040] Coenzyme Q10 was purchased from APExBIO, CAS No.: 303-98-0

[0041] 2. Drug Preparation

[0042] Ginsenoside Rg3, coenzyme Q10, and the prepared Ziziphus jujuba seed extract and Polygala tenuifolia extract are mixed to obtain the pharmaceutical composition of the present disclosure.

[0043] Example 2

[0044] 1. Experimental Animals

[0045] SPF male C57BL / 6J 12-week-old mice weighing 19g-21g were purchased from Hangzhou Ziyuan Experimental Animal Technology Co., Ltd., animal license number: SCXK (Zhe) 2019-0004, and were kept in the Experimental Animal Center of Bengbu Medical University. Ethical approval was obtained from the Experimental Animal Center of Bengbu Medical University, and the ethics approval number was Lundongkepizi

[2024] No. 571. This experiment minimized the use of experimental animals while ensuring sufficient experimental data.

[0046] 2. Animal Modeling

[0047] The chronic unpredictable mild stress model (CUMS) was established to simulate the disease state of patients with depression. The specific operations are as follows:

[0048] Four-week-old C57BL / 6J male mice were randomly divided into a normal control group and a modeling group after one week of adaptive culture. There were 8 mice in the normal group and 88 mice in the modeling group. The normal control group was not given any stimulation, and the modeling group was subjected to irregular stimulation for 4 weeks. Chronic stress stimuli included: ① 45-degree tilted cage for 7 hours; ② fasting for 24 hours; ③ water deprivation for 24 hours; ④ reversal of light day and night for 12 hours; ⑤ wet bedding for 24 hours; ⑥ swimming in ice water for 5 minutes; ⑦ foot electric shock for 1 minute (50V, 0.3s). The above stimulation was repeated 5 times, with a random order, but the same stressor should not be applied continuously, so that the mice could not predict the stimulus given.

[0049] 3. Grouping and Dosing

[0050] Four weeks after modeling, the mice in the modeling group were randomly divided into a model group and a drug administration group, with 8 mice in each group.

[0051] The administration components are as follows, and the pharmaceutical composition is prepared according to the method of Example 1:

[0052] Administration group 1: 42% ginsenoside Rg3, 28% coenzyme Q10, 10% polygala root extract, 20% jujube seed extract.

[0053] Administration group 2: 15% ginsenoside Rg3, 10% coenzyme Q10, 25% Polygala tenuifolia extract, 50% Ziziphus jujuba seed extract.

[0054] Administration group 3: 25% ginsenoside Rg3, 25% coenzyme Q10, 20% Polygala tenuifolia extract, 30% Ziziphus jujuba seed extract.

[0055] Administration group 4: 30% ginsenoside Rg3, 20% coenzyme Q10, 20% polygala root extract, 30% jujube seed extract.

[0056] Administration group 5: 20% ginsenoside Rg3, 10% coenzyme Q10, 10% polygala root extract, 60% jujube seed extract.

[0057] Administration group 6: 60% ginsenoside Rg3, 30% coenzyme Q10, 5% polygala root extract, 5% jujube seed extract.

[0058] Administration group 7: 5% ginsenoside Rg3, 5% coenzyme Q10, 40% Polygala tenuifolia extract, 50% Ziziphus jujuba seed extract.

[0059] Administration group 8: 50% ginsenoside Rg3, 20% polygala root extract, 30% jujube seed extract.

[0060] Administration group 9: 50% coenzyme Q10, 20% Polygala tenuifolia extract, 30% Ziziphus jujuba seed extract.

[0061] Administration group 10: 30% ginsenoside Rg3, 20% coenzyme Q10, 50% Polygala tenuifolia extract.

[0062] Administration group 11: 30% ginsenoside Rg3, 20% coenzyme Q10, 50% jujube seed extract.

[0063] The mice in the drug group were gavaged with an equal volume of normal saline, and the mice in the model group and the normal control group were gavaged with an equal volume of normal saline once a day, 200 μl each time, for 2 consecutive weeks. During the drug administration period, the model group and the drug group continued to be subjected to irregular stress stimulation in the same manner as in the aforementioned step 2.

[0064] 4. Mouse behavioral experiments

[0065] 4.1 Sucrose Preference Test (SPT)

[0066] Before the start of CUMS stimulation in animal modeling in step 2 above, all experimental mice were trained to adapt to sugar water for about 4 days. After placing two bottles of sugar water on the cage for 24 hours, one of the bottles of sugar water was replaced with pure water and left there for another 24 hours. They were then deprived of food and water for another 24 hours. Finally, each mouse was placed in a single cage, with a 100 ml bottle of pure water and a 100 ml bottle of 2% sucrose water (the bottles were swapped once during the test) placed on each cage for the mice to drink freely within 8 hours. The test was conducted once a week.

[0067] Evaluation index: Sugar water preference = 2% sucrose water consumption / (water consumption + 2% sucrose water consumption) × 100%

[0068] 4.2 Tail Suspension Test (TST)

[0069] On the 15th day after administration, the tail suspension test was performed, and the mice were transferred to a quiet test room 1 hour in advance. The mice were fixed and suspended by their tails with their heads down to simulate a helpless state. In this state, the mice will try to struggle to escape, but will eventually enter a state of immobility, which is considered a manifestation of "behavioral despair" and is similar to human depression symptoms.

[0070] Evaluation indicators: The experiment lasted for 6 minutes, of which the first 2 minutes were used for adaptation, and the cumulative immobility time of tail suspension in the last 4 minutes was recorded to evaluate the degree of depression of the mice.

[0071] 4.3 Forced Swimming Test (FST)

[0072] The forced swimming test was performed on the 15th day after administration, and the mice were transferred to a quiet test room 1 hour in advance. Before the experiment, the mice were placed in a transparent beaker (30 cm high, 20 cm in diameter) and injected with about 4L of distilled water at a temperature of 23°C-25°C. While the mice were swimming in the water, the immobility time of the mice was observed and recorded. The mice were considered immobile if they stopped swimming, floated in the water and remained motionless, or only made some slight movements necessary to maintain balance.

[0073] Evaluation indicators: The experiment lasted for 6 minutes, of which the first 2 minutes were used for adaptation, and the cumulative immobility time in the last 4 minutes was recorded to assess the degree of depression in mice.

[0074] 4.4 Open Field Test (OFT)

[0075] An open field test was performed on the 16th day after administration, and the mice were transferred to a quiet test room 1 hour in advance. The open field test apparatus is a box with a square bottom and a box size of (50cm×50cm×35cm); a camera is installed in a suitable position directly above the box to record the movement route and residence time of the mice in the box for subsequent analysis. Each mouse was gently placed in the central area of ​​the box. The test lasted for 6 minutes, and the data for the last 4 minutes was analyzed. After each test, 75% alcohol was used to remove the urine and feces of the mice in the box, and each corner was carefully wiped to eliminate odor interference. The mice recorded by the camera were analyzed using ANY-maze software, and the total movement route of the mice was used as the analysis indicator.

[0076] 5. Data analysis: All values ​​are expressed as mean ± standard deviation (SD).

[0077] The results of the open field test, forced swimming test and tail suspension test are shown in Table 1 , and the results of the sugar water preference test are shown in Table 2 .

[0078] Table 1

[0079]

[0080]

[0081] Table 2

[0082]

[0083]

[0084] As shown in Tables 1 and 2 above, the total open field route, forced swimming immobility time, tail suspension immobility time and sugar water preference percentage of the model group mice were significantly different from those of the normal control group (P<0.01), indicating that the animal model of the present invention was successfully established.

[0085] It can be further seen from the experimental data of each medication group in Table 1 and Table 2 that the pharmaceutical composition for treating major depression disclosed in the present invention can effectively alleviate the depressive-like behavior of mice.

[0086] In addition, according to the comparison of the medication groups in Table 1 and Table 2, it can be seen that the medication group 4 has a better effect in treating major depression, indicating that when the mass ratio of ginsenoside Rg3 to coenzyme Q10 in the pharmaceutical composition is 1.5:1, and the mass ratio of the jujube seed extract to the polygala extract is 1.5:1, the composition of the present invention has a better effect in treating major depression.

[0087] Example 3

[0088] This example provides an experiment on the application of the pharmaceutical composition of the present disclosure in treating major depression, the main purpose of which is to test the hypothesis that the pharmaceutical composition provided by the present disclosure can treat major depression.

[0089] 1. Evaluation indicators: measured by the change in the total score of the Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to 8 weeks. MADRS is a tool commonly used to assess the severity of depressive symptoms. It contains 10 items (observed depression, self-reported depression, inner tension, reduced sleep, decreased appetite, difficulty concentrating, fatigue, inability to feel, negative pessimism, suicidal ideation), each item is scored from 0 to 6, and the total score ranges from 0 to 60. The higher the MADRS score, the more severe the depressive symptoms. Generally, a change of 4 points or more in the MADRS score is considered a clinically significant improvement.

[0090] 2. Research subjects: A total of 30 patients with major depression who were outpatients and inpatients of the First Affiliated Hospital of Bengbu Medical College from May 2022 to August 2024 were collected.

[0091] 2.1 Inclusion criteria: ① The total score of the 17-item Hamilton Depression Rating Scale (HAMD-17) is ≥ 22; ② 18-65 years old, male or female; ③ No unstable serious illness; ④ The investigator is judged to be reliable and has sufficient understanding ability to carry out all tests or examinations required by the trial protocol; ⑤ The patient signs the informed consent form; ⑥ Meet the diagnostic criteria of single-episode or recurrent unipolar depressive disorder without psychotic symptoms as evaluated by DSM-IV-TR clinical assessment.

[0092] 2.2 Exclusion criteria: ① According to the DSM-IV-TR criteria, patients who have been diagnosed with any of the following diseases currently or in their lifetime: schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, mental disorder not otherwise specified, bipolar disorder type I or II, any type of delirium, any type of dementia, any mental disorder caused by systemic physical disease (unless there is clear evidence that the patient has been misdiagnosed); ② Pregnant or lactating women; ③ Received monoamine oxidase inhibitor (MAIO) treatment one month before or after participating in the study; ④ The researcher judged that there were strong or active suicidal ideas; ⑤ The researcher or patient believed that they should withdraw from the study.

[0093] 2.3 Treatment methods

[0094] 10 people in the administration group, 10 people in the fluoxetine group, and 10 people in the placebo group. The dosage and drug content ratio for the present embodiment are determined according to the administration components of the administration group 4 in Example 2, oral, 100 ml once, 3 times a day. The administration method of the placebo group (normal saline) is the same as that of the administration group, and the fluoxetine group is administered according to the instructions. The three groups were continuously administered for 8 weeks, during which visits were made once a week, wherein visit 1 was the 0th day of administration, and visits 2-9 were the 7th, 14th, 21st, 28th, 35th, 42nd, 49th, and 56th days of visits.

[0095] 2.4 Evaluation results:

[0096] The primary outcome measure of this trial was the mean reduction in the total score of the Montgomery Depression Rating Scale (MADRS) after 8 weeks of medication compared with the baseline.

[0097] The results are as follows Figure 1 As shown. The results showed that there was no significant difference in MADRS baseline between the groups (p>0.05). After 8 weeks of treatment, compared with the placebo group, taking the combination drug disclosed herein can significantly reduce the patient's MADRS score (p<0.05); compared with the fluoxetine group, taking the combination drug disclosed herein has no significant difference.

[0098] The results of this example show that the composition of the present invention has a good therapeutic effect in the clinical treatment of major depression.

[0099] The technical solution of the present disclosure is not limited to the above-mentioned specific embodiments, and all technical variations made according to the technical solution of the present disclosure fall within the protection scope of the present disclosure.

Claims

1. A composition comprising ginsenoside Rg3, coenzyme Q10, polygala root and spiny jujube seed.

2. The composition according to claim 1, characterized in that The mass ratio of the ginsenoside Rg3 to the coenzyme Q10 is (0.5-3):1, preferably (1-2):1; and / or The mass ratio of the Chinese jujube seeds to the polygala tenuifolia is (0.5-8):1, preferably (1-2):

1.

3. A pharmaceutical composition for preventing and / or treating depression, comprising ginsenoside Rg3, coenzyme Q10, polygala root extract and spiny jujube seed extract.

4. The pharmaceutical composition according to claim 3, characterized in that The pharmaceutical composition is made from the composition according to claim 1 or 2; Preferably, in the pharmaceutical composition, the mass ratio of ginsenoside Rg3, coenzyme Q10, Polygala tenuifolia extract and Ziziphus jujuba seed extract is (0.1-15):(0.1-10):1:(1-10), preferably (0.5-5):(0.2-4):1:(1-6), and more preferably (1-2):1:1:(1-2).

5. The pharmaceutical composition according to claim 4, characterized in that Based on the mass content of the pharmaceutical composition, the content of ginsenoside Rg3 is 5%-60%, preferably 5%-50%, more preferably 20%-40%; and / or The mass content of the coenzyme Q10 is 5%-30%, preferably 5%-25%, more preferably 15%-25%; and / or The mass content of the polygala root extract is 10%-70%, preferably 5%-40%, more preferably 15%-25%; and / or The mass content of the spinosa jujube seed extract is 5%-60%, preferably 20%-50%, more preferably 20%-40%; Preferably, based on the mass content of the pharmaceutical composition, the content of ginsenoside Rg3 is 25-35%, preferably 28-32%; the content of coenzyme Q10 is 15%-25%, preferably 18-22%; the content of Polygala tenuifolia extract is 15%-25%, preferably 18-22%; the content of Ziziphus jujuba seed extract is 25-35%, preferably 28-32%.

6. The pharmaceutical composition according to any one of claims 3 to 5, characterized in that The polygala root extract comprises a water extract of polygala root; and / or The Chinese jujube seed extract includes a water extract of fried Chinese jujube seeds; Preferably, the Polygala root and the stir-fried Semen Ziziphi Spinosae are crushed and then mixed or decocted and filtered separately, and the filtrate is collected to obtain the Polygala root extract and the Semen Ziziphi Spinosae extract; More preferably, the polygala extract is obtained by a method comprising the following steps: soaking the polygala in water with a mass of 1.5-3 times the mass for more than 2 hours, heating and decocting for 2-4 hours until the liquid volume is concentrated to 1 / 5-1 / 3 of the original, filtering, and obtaining the filtrate as the polygala extract; More preferably, the Chinese jujube seed extract is obtained by a method comprising the following steps: crushing the fried Chinese jujube seeds, soaking them in 1.5-3 times the mass of water for more than 2 hours, heating and simmering for 2-4 hours until the liquid volume is concentrated to 1 / 5-1 / 3 of the original, filtering, and the obtained filtrate is the Chinese jujube seed extract; more preferably, the frying includes placing the Chinese jujube seeds in a frying container and heating them over a low heat until they swell, there is a popping sound, and the color becomes slightly darker, and then taking them out to cool.

7. The pharmaceutical composition according to any one of claims 3 to 6, characterized in that The pharmaceutical composition further comprises a pharmaceutically acceptable excipient; The dosage form of the pharmaceutical composition includes any one of emulsion, solution, suspension or granule.

8. Use of the composition according to claim 1 or 2 or the pharmaceutical composition according to any one of claims 3 to 7 in the preparation of a medicament for preventing and / or treating depression.

9. The use according to claim 8, characterized in that The depression includes major depressive disorder.

10. The use according to claim 8 or 9, characterized in that The pharmaceutical composition has at least one of the following uses: (1) Increase the total movement route of mice in the open field test of chronic unpredictable mild stress mice; (2) reduce the immobility time of mice in the forced swimming test of chronic unpredictable mild stress mice; (3) reduce the immobility time of mice in the tail suspension test of chronic unpredictable mild stress mice; (4) Increase the amount of sugar water preferred by mice in the sugar water preference experiment of mice with chronic unpredictable mild stress; (5) Reduce the total score of the Montgomery-Asberg Depression Rating Scale (MADRS) by at least 4 points in subjects with major depression.

Images