Application of composition as synergist of depression treatment medicine

Abstract

The invention discloses application of a composition as a synergist of a drug for treating depression, the composition is prepared from pyrola, loranthus parasiticus, pyrrosia lingua, oldenlandia diffusa and achyranthes bidentata, and the drug for treating depression is prepared from astragalus membranaceus, bighead atractylodes rhizome, poria cocos, codonopsis pilosula, radix aconiti lateralis preparata (black prepared common monkshood daughter root), dogwood, salvia miltiorrhiza and motherwort. A drug combination prepared from the composition and a depression treatment drug can significantly improve depression-like behaviors of depression mice, relieve interest deficiency symptoms and increase neurotransmitter content in brains of the depression mice. Further clinical tests find that the medicine combination has remarkable clinical effects on depression of various traditional Chinese medicine syndromes such as liver depression and qi stagnation, liver depression transforming into fire, liver depression and spleen deficiency, phlegm and qi stagnation, heart and spleen deficiency, kidney deficiency and liver depression and the like, shows a good anti-depression effect and has a wide application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to application of a composition as a synergist of a drug for treating depression. Background Art

[0002] Depression is a type of mental disorder characterized by persistent low mood, lack of pleasure, and despair, accompanied by anxiety, insomnia, slow reaction, and decreased learning and memory ability. In severe cases, it can lead to suicidal tendencies. In recent years, the incidence of depression has been increasing year by year and is becoming younger. Therefore, the development of antidepressant drugs is crucial, and researchers have also developed many animal models for depression. At present, the Chronic Unpredictable Mild Stress (CUMS) model is considered to be the most classic and most commonly used animal model of depression, which is highly consistent with human depression.

[0003] Currently, most drugs for the treatment of depression are Western medicines, mainly including 5-hydroxytryptamine reuptake inhibitors, monoamine oxidase inhibitors, phenylpiperazine derivatives, 5-hydroxytryptamine-norepinephrine reuptake inhibitors, aminoketones, tricyclics, tetracyclic piperazine azapines and other chemical antidepressants. However, most chemical antidepressants have defects such as narrow antidepressant spectrum, large toxic side effects, high drug prices and easy relapse.

[0004] With its mild effects and few side effects, Chinese medicine antidepressants have gradually received widespread attention at home and abroad. However, the syndrome differentiation of depression in traditional Chinese medicine is very complicated. The "Guidelines for the Diagnosis and Treatment of Depression with Integrated Chinese and Western Medicine" issued by the Chinese Society of Integrated Traditional Chinese and Western Medicine, the Chinese Association of Traditional Chinese Medicine, and the Chinese Medical Association recommends that the syndrome differentiation of depression in traditional Chinese medicine include: liver depression and qi stagnation, liver depression and spleen deficiency, liver depression and fire transformation, heart and spleen deficiency, kidney deficiency and liver depression, and phlegm and qi stagnation syndrome. The application scope of existing traditional Chinese medicine for the treatment of depression is also relatively limited. For example, Zishui Qingganyin can only be used to treat depression with kidney deficiency and liver depression, Guipi Decoction can only be used to treat depression with heart and spleen deficiency, and Xiaoyaosan combined with Banxia Houpu Decoction can only be used to treat depression with liver depression and spleen deficiency. On the one hand, the treatment scope is narrow. On the other hand, the classification of traditional Chinese medicine is highly professional and complex. Incorrect classification often occurs, and incorrect classification will lead to the wrong medicine for the disease, which is not only a waste of medicine, but also a great pain for patients.

[0005] Therefore, it is of great significance to develop a Chinese medicine composition with a wide range of applications for intervening in depression. Summary of the invention

[0006] In order to overcome the above defects and shortcomings in the prior art, the present invention provides a composition for use as a synergist of a drug for treating depression.

[0007] The first object of the present invention is to provide a composition for use as a synergist of a drug for treating depression.

[0008] The second object of the present invention is to provide a use of the composition in preparing antidepressant drugs.

[0009] Therefore, the present invention claims the following:

[0010] A composition is used as a synergist of a drug for treating depression. The composition comprises, by weight, 28 to 32 parts by weight of herba schizonepetae, 23 to 27 parts by weight of herba schizonepetae, 17 to 21 parts by weight of herba pyrrosiae, 40 to 44 parts by weight of herba schizonepetae and 14 to 18 parts by weight of herba schizonepetae.

[0011] Preferably, based on weight, the composition comprises 30 parts by weight of Herba Hedyotis diffusae, 25 parts by weight of Herba Viscipiens, 19 parts by weight of Herba Pyrrosiae, 42 parts by weight of Herba Hedyotis diffusae and 16 parts by weight of Herba Cynoglossi.

[0012] Preferably, by weight, the depression therapeutic drug comprises 48-52 parts by weight of Astragalus, 17-21 parts by weight of Atractylodes, 17-21 parts by weight of Poria, 17-21 parts by weight of Codonopsis, 6-10 parts by weight of processed Aconitum (Heishunpian), 13-17 parts by weight of Cornus officinalis, 26-30 parts by weight of Salvia miltiorrhiza and 49-53 parts by weight of Leonurus japonicus.

[0013] More preferably, by weight, the depression therapeutic drug comprises 50 parts by weight of Astragalus, 19 parts by weight of Atractylodes, 19 parts by weight of Poria, 19 parts by weight of Codonopsis, 8 parts by weight of processed Aconitum (Heishunpian), 15 parts by weight of Cornus officinalis, 28 parts by weight of Salvia miltiorrhiza, and 51 parts by weight of Leonurus japonicus.

[0014] The Heishun tablets are processed aconite root, which is obtained by processing mud aconite root through salting, water soaking, boiling, frying and other methods.

[0015] Preferably, the depression therapeutic drug is a drug that improves depressive-like behavior.

[0016] Preferably, the depression therapeutic drug is a drug that improves the symptoms of loss of interest.

[0017] Preferably, the depression therapeutic drug is a drug that increases the content of neurotransmitters in brain tissue.

[0018] More preferably, the neurotransmitters include norepinephrine, dopamine and / or serotonin.

[0019] A use of a composition in preparing an antidepressant drug, the composition comprising, by weight, 48-52 parts by weight of astragalus, 28-32 parts by weight of herba pyrrosiae, 17-21 parts by weight of atractylodes, 17-21 parts by weight of tuckahoe, 17-21 parts by weight of codonopsis, 6-10 parts by weight of processed aconite (black shun tablets), 13-17 parts by weight of cornus officinalis, 26-30 parts by weight of salvia miltiorrhiza, 49-53 parts by weight of motherwort, 23-27 parts by weight of parasitic plant, 17-21 parts by weight of pyrrosia, 40-44 parts by weight of oldenlandia diffusa and 14-18 parts by weight of achyranthes bidentata.

[0020] Preferably, by weight, the composition comprises 50 parts by weight of Astragalus, 30 parts by weight of Herba Lycopi, 19 parts by weight of Atractylodes, 19 parts by weight of Poria, 19 parts by weight of Codonopsis, 8 parts by weight of Processed Aconitum (Heishunpian), 15 parts by weight of Cornus officinalis, 28 parts by weight of Salvia miltiorrhiza, 51 parts by weight of Leonurus japonicus, 25 parts by weight of Viscum album, 19 parts by weight of Pyrrosia, 42 parts by weight of Hedyotis diffusa and 16 parts by weight of Achyranthes bidentata.

[0021] Preferably, the antidepressant drug is a drug that improves depressive-like behavior and / or improves anhedonia symptoms.

[0022] Preferably, the antidepressant drug is a drug that increases the content of neurotransmitters in brain tissue.

[0023] More preferably, the neurotransmitters include norepinephrine, dopamine and / or serotonin.

[0024] Preferably, the depression includes depression caused by liver depression and qi stagnation, liver depression transforming into fire, liver depression and spleen deficiency, phlegm and qi stagnation, heart and spleen deficiency and / or kidney deficiency and liver depression.

[0025] Preferably, the dosage form of the drug includes but is not limited to tablets, capsules, granules, pills, powders, and mixtures.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The invention discloses an application of a composition as a synergist of a depression treatment drug, wherein the composition is prepared from Herba Astragali, Herba Mori, Herba Pyrrosiae, Herba Hedyotis Diffusae and Herba Cynoglossi, and the depression treatment drug is prepared from Herba Astragali, Herba Atractylodes, Herba Poriae, Herba Codonopsis, Herba Aconiti Lateralis (Heishun Pian), Herba Corni, Herba Salviae Miltiorrhizae and Herba Leonuri. The drug combination prepared from the composition and the depression treatment drug can significantly improve the depressive-like behavior of depressed mice, relieve the symptoms of anhedonia and increase the content of neurotransmitters in the brain of depressed mice. Further clinical trials have found that the drug combination of the present invention has significant clinical efficacy for various TCM syndrome depressions such as liver depression and qi stagnation type, liver depression and fire type, liver depression and spleen deficiency type, phlegm and qi stagnation type, heart and spleen deficiency type, kidney deficiency and liver depression type, etc., showing a good antidepressant effect and having broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The effect of the whole Chinese medicine combination and its separated prescriptions on the tail suspension immobility time of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with the corresponding dose group of the whole prescription, ## P<0.01, # P<0.05.

[0029] Figure 2 The effect of the whole Chinese medicine combination and its separate prescriptions on the open field test scores of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with the corresponding dose group of the whole prescription, ## P<0.01, # P<0.05.

[0030] Figure 3 The effect of the whole Chinese medicine combination and its separated prescriptions on the sugar preference index of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with the corresponding dose group of the whole prescription, ## P<0.01, # P<0.05.

[0031] Figure 4 The effects of different proportions of Chinese medicine composition on the tail suspension immobility time of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with group 1, ## P<0.01, # P<0.05.

[0032] Figure 5 The effects of different ratios of Chinese medicine composition on the open field test scores of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with group 1, ## P<0.01, # P<0.05.

[0033] Figure 6 The effect of different proportions of Chinese medicine composition on the sugar preference index of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with group 1, ## P<0.01, # P<0.05.

[0034] Figure 7 The effects of different formulations of Chinese medicine composition on the tail suspension immobility time of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with the whole prescription group, ## P<0.01, # P<0.05.

[0035] Figure 8 The effects of different formulas of Chinese medicine composition on the open field test scores of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with the whole prescription group, ## P<0.01, # P<0.05.

[0036] Fig. 9 The effect of different formulas of Chinese medicine combination on sugar preference index of depression model mice; compared with the model group, ** P<0.01, * P<0.05; compared with the whole prescription group, ## P<0.01, # P<0.05. DETAILED DESCRIPTION

[0037] The present invention is further described below with reference to specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0038] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0039] Example 1 Effects of the whole Chinese medicine composition and its separate prescriptions on the behavior of depression model mice

[0040] 1. Experimental Methods

[0041] 1. Preparation method of the whole Chinese medicine composition and its disassembled prescriptions

[0042] Whole recipe: Take 50 parts of Astragalus, 30 parts of Herba Luciliariae, 19 parts of Atractylodes macrocephalae, 19 parts of Poria, 19 parts of Codonopsis pilosulae, 8 parts of Aconite root (Heishunpian), 15 parts of Cornus officinalis, 25 parts of Morus parasiticus, 28 parts of Salvia miltiorrhiza, 51 parts of Leonurus japonicus, 19 parts of Pyrrosia rapa, 42 parts of Hedyotis diffusa, and 16 parts of Achyranthes bidentata, soak the medicinal materials in water for 30 minutes, decoct three times, add 7 times, 5 times, and 5 times of water respectively, decoct for 30 minutes each time, and combine the three medicinal liquids for later use;

[0043] Prescription 1: Take 50 parts of Astragalus, 19 parts of Atractylodes, 19 parts of Poria, 19 parts of Codonopsis, 8 parts of Aconite (Heishun Pian), 15 parts of Cornus, 28 parts of Salvia miltiorrhiza, and 51 parts of Leonurus japonicus. Soak the herbs in water for 30 minutes, then boil three times with 7 times, 5 times, and 5 times the amount of water added respectively. Boil for 30 minutes each time, and combine the three medicinal solutions for later use.

[0044] Recipe 2: Take 30 parts of Herba Lycopodii, 25 parts of Herba Viscume, 19 parts of Pyrrosiae, 42 parts of Herba Hedyotis diffusae and 16 parts of Herba Cynoglossi. Soak the herbs in water for 30 minutes, then decoct them three times with 7 times, 5 times and 5 times the amount of water added respectively. Decoction for 30 minutes each time and combine the three medicinal liquids for later use.

[0045] 2. Animal grouping and modeling

[0046] SPF male C57BL / 6 mice, male, weight 22±2g, were purchased from Guangdong Experimental Animal Center. The mice were randomly divided into 12 groups, 8 mice in each group, namely normal group, model group, fluoxetine group, high-dose split prescription group 1, medium-dose split prescription group 1, low-dose split prescription group 1, high-dose split prescription group 2, medium-dose split prescription group 2, low-dose split prescription group 2, high-dose whole prescription group, medium-dose whole prescription group, and low-dose whole prescription group.

[0047] Except for the normal group, the other groups were modeled with chronic unpredictable mild stimulation (CUMS). The mice were subjected to chronic mild unpredictable stress at irregular intervals every day. The specific method was: 12 kinds of stimulation were randomly arranged during the modeling period, one every day.

[0048] The 12 stimulations included: swimming in 4℃ ice water for 5 min, light-dark reversal for 24 h, swimming in 45℃ hot water for 5 min, food deprivation for 24 h, water deprivation for 24 h, tail clamping for 1 min, wet bedding for 24 h, restraint for 2 h, horizontal shaking for 10 min, tilted cage for 24 h, empty cage for 24 h, and lighting all night for 24 h.

[0049] 3. Method of administration

[0050] 14 days after modeling, the mice in the drug group were given corresponding doses of drugs by gavage, and the dosages are shown in Table 1. The mice in the normal group and the model group were given pure water.

[0051] Table 1 Dosages for each group of mice

[0052]

[0053] 4. Evaluation Method

[0054] On the 21st day of continuous daily administration, open field test and tail suspension test were performed to evaluate the behavior of mice.

[0055] Open field test: The inner wall of the open experimental box (100cm×100cm×50cm) was painted black, and the bottom was evenly divided into 25 small squares of 20cm×20cm. The central 60cm×60cm square area in the box was divided into the central area, and the rest were the edge areas. The mouse was placed in the central square at the bottom, and the number of squares crossed by the mouse (squares stepped into by all four limbs can be counted as horizontal movement scores) and the number of hind limbs upright (two front paws in the air or clinging to the wall, as vertical movement scores) within 5 minutes were observed and recorded. 1 point was awarded for crossing 1 square, and 1 point was awarded for both forelimbs leaving the ground once. During the experiment, a quiet and softly lit experimental environment was maintained, and the next mouse was observed after cleaning the open field experimental box. The spontaneous exploratory movement state of the mouse was examined by the horizontal movement score and the vertical movement score.

[0056] Tail suspension test: The tail suspension box is 50cm×50cm×30cm in size, standing on its side, with black walls and bottom. The operator uses non-stick adhesive to suspend the tip of the mouse's tail in the tail suspension box at 1 / 3, so that its head is facing the camera and about 10cm from the bottom of the box. The camera records the duration of the animal's immobility within 6 minutes and then 4 minutes. The immobility state means that the animal gives up active struggle and the body is in a suspended state without twisting. Each mouse is tested only once, and the excrement and odor must be cleaned after each test to avoid affecting the results of the next test.

[0057] Data analysis: Statistical analysis was performed using Prism 10 software, and the results were analyzed by t-test for inter-group testing. Data are expressed as mean ± standard deviation, and P < 0.05 was considered significant.

[0058] 2. Experimental Results

[0059] The behavioral scores of mice in each group were as follows Figure 1 and Figure 2 As shown. Figure 1 It can be seen that compared with the model group, the tail suspension immobility time of mice in the fluoxetine group, the high-dose group and the medium-dose group of separated prescription 1, and the high-, medium- and low-dose groups of the whole prescription were significantly reduced (P < 0.01), and there was a dose-effect relationship in reducing the tail suspension immobility time of depressed mice with separated prescription 1 and the whole prescription; compared with the corresponding dose groups of the whole prescription, the tail suspension immobility time of mice in each dose group of separated prescription 1 and each dose group of separated prescription 2 was significantly increased (P < 0.01).

[0060] Depend on Figure 2 It can be seen that compared with the model group, the open field test scores of mice in the fluoxetine group, the high-dose group and the medium-dose group of the split prescription 1, and the high-, medium-, and low-dose groups of the whole prescription were significantly increased (P < 0.01), and the split prescription 1 and the whole prescription increased the open field test scores of depressed mice in a dose-response relationship. Compared with the corresponding dose groups of the whole prescription, the open field test scores of mice in the split prescription 1 dose groups and the split prescription 2 dose groups were significantly reduced (P < 0.01).

[0061] The above results show that the use of separate prescription 1 alone can effectively increase the activity, interest and ability to explore the outside world of depression model mice, while separate prescription 2 alone has no such effect. However, after the combination of separate prescriptions 1 and 2, the whole prescription can significantly improve the depressive-like behavior of depressed mice, and the therapeutic effect is significantly improved, which is significantly better than the effect of separate prescription 1.

[0062] Example 2 Effects of the whole Chinese medicine composition and its separate prescriptions on sugar water preference in depression model mice

[0063] 1. Experimental Methods

[0064] The preparation method of the whole Chinese medicine composition and its separate prescriptions, animal grouping and modeling, and administration method are the same as in Example 1.

[0065] On the 18th day of administration, each cage of mice (3 mice per cage) was given 2 bottles of 1% sucrose water (w / v); on the 19th day, 1 bottle of 1% sucrose water (w / v) and 1 bottle of pure water were given, and the position of the water bottles was changed every 3 hours; on the 20th day, the mice were fasted and deprived of water for 24 hours; on the 21st day, each cage of mice was given 1 bottle of 1% sucrose water (w / v) and 1 bottle of pure water, and the consumed volume of sucrose solution and pure water was calculated after 24 hours.

[0066] Sugar water preference index = sugar water consumption / (sugar water consumption + pure water consumption).

[0067] 2. Experimental Results

[0068] The results are as follows Figure 3 As shown. Figure 3 It can be seen that compared with the model group, the sugar preference index of mice in the fluoxetine group, the high-dose group and the medium-dose group of the split prescription 1, and the high-, medium-, and low-dose groups of the whole prescription increased significantly (P < 0.01), and the split prescription 1 and the whole prescription increased the sugar preference index of depressed mice in a dose-effect relationship. Compared with the corresponding dose groups of the whole prescription, the sugar preference index of mice in the split prescription 1 dose groups and the split prescription 2 dose groups was significantly reduced (P < 0.01).

[0069] The above results show that the use of separate prescription 1 alone can effectively increase the interest of depression model mice in sugar water, while separate prescription 2 alone has no such effect. However, after the combination of separate prescriptions 1 and 2, the whole prescription can significantly improve the symptoms of depression mice's lack of interest in sugar water, and the therapeutic effect is significantly improved, and is significantly better than the effect of separate prescription 1.

[0070] Example 3 Effects of the whole Chinese medicine composition and its separate prescriptions on neurotransmitters in the brain of depression model mice

[0071] 1. Experimental Methods

[0072] The preparation method of the whole Chinese medicine composition and its separate prescriptions, animal grouping and modeling, and administration method are the same as in Example 1.

[0073] On the 21st day after continuous daily administration, 1 hour after the last administration, the mice were quickly killed by isoflurane anesthesia, and then the brains were removed by decapitation. After the cerebellum was carefully removed, the remaining brain tissue was kept at -80°C for later use. The contents of neurotransmitters norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in brain tissue were detected using ELISA kits.

[0074] 2. Experimental Results

[0075] The neurotransmitter contents in the brain tissue of mice in each group are shown in Table 2. As shown in Table 2, compared with the model group, the contents of 5-HT, NE and DA in the brain of mice in the fluoxetine group, the high-dose group and the medium-dose group of the split prescription 1, and the high-, medium- and low-dose groups of the whole prescription were significantly increased (P < 0.01), and the split prescription 1 and the whole prescription increased the neurotransmitters in the brain of depressed mice in a dose-effect relationship. Compared with the corresponding dose groups of the whole prescription, the contents of 5-HT, NE and DA in the brain of mice in the split prescription 1 dose groups and the split prescription 2 dose groups were significantly reduced (P < 0.01).

[0076] The above results show that the use of separate prescription 1 alone can effectively increase the content of neurotransmitters in the brain of depression model mice, while separate prescription 2 alone has no such effect. However, after the combination of separate prescriptions 1 and 2, the obtained whole prescription can significantly increase the content of neurotransmitters in the brain of depression model mice, and is significantly better than the effect of separate prescription 1.

[0077] Table 2 Effects of the whole Chinese medicine composition and its separate prescriptions on the content of neurotransmitters in the brain of depression model mice (n=8)

[0078]

[0079]

[0080] Note: Compared with the model group, **P<0.01, *P<0.05; compared with the corresponding dose group of the whole prescription, ## P<0.01, # P<0.05.

[0081] Example 4 Effects of different ratios of Chinese medicine compositions on depression model mice

[0082] 1. Experimental Methods

[0083] 1. Different ratios of Chinese medicine compositions and their preparation methods

[0084] The specific proportions of various medicinal materials in different proportions of the Chinese medicine composition are shown in Table 3, specifically:

[0085] Recipe 1: Each medicinal ingredient is 2 parts less by weight than the whole recipe of Example 1;

[0086] Recipe 2: Each medicinal ingredient contains 2 more parts by weight than the whole recipe of Example 1;

[0087] Recipe 3: Compared with the whole recipe of Example 1, the weight of Herba Lustriatae is changed from 30 parts by weight to 25 parts by weight, the weight of Herba Mori is changed from 25 parts by weight to 21 parts by weight, the weight of Pyrrosiae is changed from 19 parts by weight to 25 parts by weight, the weight of Hedyotis diffusa is changed from 42 parts by weight to 48 parts by weight, the weight of Achyranthes bidentatae is changed from 16 parts by weight to 12 parts by weight, and the weight of the other medicinal ingredients remains unchanged;

[0088] Recipe 4: Compared with the whole recipe of Example 1, Astragalus membranaceus is changed from 50 weight parts to 45 weight parts, Atractylodes macrocephala is changed from 19 weight parts to 25 weight parts, Poria cocos is changed from 19 weight parts to 25 weight parts, Codonopsis pilosula is changed from 19 weight parts to 25 weight parts, Aconite root (Heishun tablets) is changed from 8 weight parts to 5 weight parts, Cornus officinalis is changed from 15 weight parts to 22 weight parts, Salvia miltiorrhiza is changed from 28 weight parts to 23 weight parts, Leonurus japonicus is changed from 51 weight parts to 45 weight parts, and the weight parts of other medicinal ingredients remain unchanged;

[0089] Recipe 5: Compared with the whole recipe of Example 1, the weight of Astragalus is changed from 50 parts by weight to 45 parts by weight, the weight of Herba Lycopithecis is changed from 30 parts by weight to 25 parts by weight, the weight of Atractylodes macrocephala is changed from 19 parts by weight to 25 parts by weight, the weight of Poria cocos is changed from 19 parts by weight to 25 parts by weight, the weight of Codonopsis pilosula is changed from 19 parts by weight to 25 parts by weight, the weight of Aconite prepared (Heishunpian) is changed from 8 parts by weight to 5 parts by weight, the weight of Cornus officinalis is changed from 15 parts by weight to 22 parts by weight, the weight of Viscum album is changed from 25 parts by weight to 21 parts by weight, the weight of Salvia miltiorrhiza is changed from 28 parts by weight to 23 parts by weight, the weight of Leonurus japonicus is changed from 51 parts by weight to 45 parts by weight, the weight of Pyrola is changed from 19 parts by weight to 25 parts by weight, the weight of Hedyotis diffusa is changed from 42 parts by weight to 48 parts by weight, and the weight of Achyranthes bidentata is changed from 16 parts by weight to 12 parts by weight.

[0090] As shown in Table 3, take the medicinal materials of Recipe 1, Recipe 2, Recipe 3, Recipe 4 and Recipe 5 respectively, soak the medicinal materials in water for 30 minutes, and then boil them three times with 7 times, 5 times and 5 times the amount of water added respectively. Boil for 30 minutes each time and combine the three medicinal liquids for later use.

[0091] Table 3 Specific dosage of various medicinal materials in different proportions of Chinese medicine composition (by weight)

[0092]

[0093] 2. Animal grouping and modeling

[0094] SPF male C57BL / 6 mice, male, weight 22±2g, were purchased from Guangdong Experimental Animal Center. The mice were randomly divided into 8 groups, 8 mice in each group, namely normal group, model group, fluoxetine group, prescription 1 group, prescription 2 group, prescription 3 group, prescription 4 group, and prescription 5 group.

[0095] The modeling method was carried out according to Example 1.

[0096] 3. Method of administration

[0097] 14 days after modeling, the mice in the drug group were given corresponding doses of drugs by gavage, and the dosages are shown in Table 4. The mice in the normal group and the model group were given pure water.

[0098] Table 4 Dosages for each group of mice

[0099]

[0100] 4. Evaluation Method

[0101] The method of Example 1 was used to detect the behavioral effect of the Chinese medicine composition of this example on depression model mice, the method of Example 2 was used to detect the effect of the Chinese medicine composition of this example on the sugar water preference of depression model mice, and the method of Example 3 was used to detect the effect of the Chinese medicine composition of this example on neurotransmitters in the brain of depression model mice.

[0102] 2. Experimental Results

[0103] The behavioral results of each group of mice are shown in Figure 4 and Figure 5 .Depend on Figure 4 It can be seen that compared with the model group, the immobility time of the tails in the fluoxetine group, the prescription 1 group, the prescription 2 group, the prescription 3 group, the prescription 4 group, and the prescription 5 group was significantly reduced (P < 0.01); compared with the prescription 1 group, the immobility time of the tails in the prescription 3 group, the prescription 4 group, and the prescription 5 group was significantly increased (P < 0.01). Figure 5 It can be seen that compared with the model group, the open field test scores of mice in fluoxetine group, formula group 1, formula group 2, formula group 3, formula group 4, and formula group 5 were significantly increased (P < 0.01); compared with formula group 1, the open field test scores of mice in formula group 3, formula group 4, and formula group 5 were significantly reduced (P < 0.01). The results show that formula 1, formula 2, formula 3, formula 4, and formula 5 can significantly increase the activity, interest in exploring external things, and ability to explore in depression model mice, but the effect of formula 3, formula 4, and formula 5 on improving the depressive-like behavior of depressed mice is weaker than that of formula 1.

[0104] The results of sugar water preference of each group of mice are as follows Figure 6 As shown. Figure 6 It can be seen that compared with the model group, the sugar water preference index of mice in fluoxetine group, prescription 1 group, prescription 2 group, prescription 3 group, prescription 4 group, and prescription 5 group increased significantly (P < 0.01); compared with prescription 1 group, the sugar water preference index of mice in prescription 3 group, prescription 4 group, and prescription 5 group decreased significantly (P < 0.01). The results show that prescription 1, prescription 2, prescription 3, prescription 4, and prescription 5 can significantly increase the interest of depression model mice in sugar water, but the effect of prescription 3, prescription 4, and prescription 5 on improving the preference of depression mice for sugar water is weaker than that of prescription 1.

[0105] The content of neurotransmitters in the brain of mice in each group is shown in Table 5. As shown in Table 5, compared with the model group, the content of 5-HT, NE, and DA in the brain of mice in groups 1, 2, 3, 4, and 5 increased significantly (P < 0.01); compared with group 1, the content of 5-HT, NE, and DA in the brain of mice in groups 3, 4, and 5 decreased significantly (P < 0.01). The results suggest that formula 1, 2, 3, 4, and 5 can significantly increase the content of neurotransmitters in the brain of depression model mice, but formula 1 has a stronger effect than formula 3, 4, and 5 in increasing the content of neurotransmitters in the brain of depression model mice.

[0106] In summary, when the proportions of the constituent medicinal materials are within the weight range required by the present invention, the Chinese medicine composition prescriptions with different ratios have the same antidepressant effect and have the optimal antidepressant effect; if the proportions of some or all of the medicinal materials are not within the weight range required by the patent, the antidepressant effect of the Chinese medicine composition prescription with this ratio is significantly reduced and does not have the optimal antidepressant effect.

[0107] Table 5 Effects of different ratios of Chinese medicine compositions on the content of neurotransmitters in the brain of mice (mean ± SD, n = 8)

[0108] Grouping NE (pg / mg) DA (pg / mg) 5-HT (pg / mg) Normal group <![CDATA[112.83±10.29 ** ]]> <![CDATA[267.13±22.46 ** ]]> <![CDATA[871.18±50.26 ** ]]> Model Group 27.85±4.57 49.38±8.90 192.12±20.73 Fluoxetine group 31.57±5.12 69.34±10.36 <![CDATA[549.20±30.55 ** ]]> Square 1 Group <![CDATA[89.24±6.30 ** ]]> <![CDATA[131.25±15.28 ** ]]> <![CDATA[501.81±30.34 ** ]]> Square 2 Group <![CDATA[91.24±10.82 ** ]]> <![CDATA[129.37±17.20 ** ]]> <![CDATA[505.48±29.16 ** ]]> Square 3 Group <![CDATA[74.13±2.05 **## ]]> <![CDATA[105.24±8.41 **## ]]> <![CDATA[421.19±17.49 **## ]]> Square 4 Group <![CDATA[56.10±3.38 **## ]]> <![CDATA[79.40±5.73 **## ]]> <![CDATA[341.17±18.28 **## ]]> Square 5 Group <![CDATA[43.45±3.51 **## ]]> <![CDATA[75.72±7.95 **## ]]> <![CDATA[277.60±24.54 **## ]]>

[0109] Note: Compared with the model group, **P<0.01, *P<0.05; compared with the prescription 1 group, ## P<0.01, # P<0.05.

[0110] Example 5 Clinical efficacy of Chinese medicine composition on depression of different TCM syndromes

[0111] 1. Experimental Methods

[0112] 1. Research subjects

[0113] Referring to the Western and Chinese medicine diagnostic standards of the "Guidelines for the Diagnosis and Treatment of Depression with Integrated Chinese and Western Medicine" formulated by the Chinese Society of Integrated Chinese and Western Medicine, the Chinese Association of Traditional Chinese Medicine, and the Chinese Medical Association, two senior Chinese medicine physicians conducted Chinese medicine dialectical classification based on the Chinese medicine syndrome standards for depression recorded in the "Guidelines for the Diagnosis and Treatment of Depression with Integrated Chinese and Western Medicine" and the patient's symptom characteristics. The syndrome classification includes: liver depression and qi stagnation, liver depression transforming into fire, liver depression and spleen deficiency, phlegm and qi stagnation, heart and spleen deficiency, and kidney deficiency and liver depression. A total of 120 patients with mild and moderate depression were included, with 20 cases of each syndrome type.

[0114] Inclusion criteria: ① Patients with mild or moderate depression who meet the Western medicine diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Depression with Integrated Chinese and Western Medicine". ② Symptoms of each TCM syndrome that meet the TCM diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Depression with Integrated Chinese and Western Medicine". ③ 8≤Hamilton Depression Rating Scale-17 (HAMD-17)<24 points. ④ Unlimited gender, age ≥18 years and ≤65 years. ⑤ All patients had primary conditions. ⑥ Those who were not taking any medication or psychotherapy at the time of inclusion in the study.

[0115] Exclusion criteria: ① Secondary depression caused by other diseases. ② Patients with recurrent or refractory depression. ③ Patients with other mental disorders or a history of mental illness. ④ Patients with a history of organic brain damage or severe brain trauma. ⑤ Patients with severe heart, liver, and kidney dysfunction, metabolic disorders, and other serious physical diseases. ⑥ Patients prone to infection and bleeding. ⑦ Pregnant or lactating women. ⑧ Patients with contraindications to therapeutic drugs. ⑨ Patients with severe suicidal tendencies.

[0116] 2. Method of administration

[0117] 120 patients with depression were randomly divided into the whole prescription group in Example 1 and the Morinda Officinalis Oligosaccharide Capsule group, with 60 people in each group. Each group was required to include patients with liver depression and qi stagnation syndrome, liver depression and fire transformation syndrome, liver depression and spleen deficiency syndrome, phlegm and qi stagnation syndrome, heart and spleen deficiency syndrome, and kidney deficiency and liver depression syndrome, with 10 people in each syndrome. Morinda Officinalis Oligosaccharide Capsule is a drug recommended for kidney deficiency and liver depression depression in the "Guidelines for the Diagnosis and Treatment of Depression with Integrated Traditional Chinese and Western Medicine".

[0118] The whole formula in Example 1 was added with auxiliary materials such as silicon dioxide, magnesium stearate and low-substituted hydroxypropyl cellulose to prepare film-coated tablets, each tablet being 0.38 g. Oral administration, 8 tablets each time, 3 times a day.

[0119] Morinda officinalis oligosaccharide capsules, specifications: 0.3g per capsule (containing 150mg of Morinda officinalis oligosaccharide), produced by Tong Ren Tang Pharmaceutical Factory of Beijing Tong Ren Tang Co., Ltd. Take 1 capsule of Morinda officinalis oligosaccharide capsule orally, 1 capsule in the morning and 1 capsule in the evening.

[0120] 3. Observation indicators

[0121] After 8 weeks of administration, the clinical efficacy of the two drugs was evaluated based on the HAMD score reduction rate:

[0122] Recovery: The patient's depressive symptoms and accompanying symptoms basically disappear or completely disappear, and the HAMD score reduction rate after treatment is ≥ 75%;

[0123] Marked effect: The patient's depressive symptoms and accompanying symptoms are significantly alleviated compared with before treatment, and the HAMD score reduction rate is between 50% and 74%, which is markedly effective;

[0124] Effective: The patient's depressive symptoms and accompanying symptoms are improved compared with before treatment, and the HAMD score reduction rate is between 25% and 49%, which is effective;

[0125] Ineffective: The patient's depressive symptoms and accompanying symptoms have no significant improvement compared to before treatment, and the HAMD score reduction rate is <25%, which is ineffective.

[0126] The total effective rate of treatment = cure rate + marked effective rate + effective rate.

[0127] Prism 10 software was used for statistical analysis. HAMD scores were analyzed using t-test and expressed as mean ± standard deviation. Clinical efficacy data were analyzed using χ 2 P < 0.05 was considered significant.

[0128] 2. Experimental Results

[0129] As shown in Table 6: there was no significant difference in HAMD-17 scores among the patients in each group before treatment (P>0.05); compared with before treatment, after treatment with the whole prescription of Example 1, the HAMD-17 scores of patients with liver depression and qi stagnation type, liver depression and fire transformation type, liver depression and spleen deficiency type, phlegm and qi stagnation type, heart and spleen deficiency type, and kidney deficiency and liver depression type all decreased significantly (P<0.05), but after treatment with Morinda officinalis oligosaccharide capsules, only the HAMD-17 scores of patients with kidney deficiency and liver depression type all decreased significantly (P<0.05), and the HAMD-17 scores of the other groups did not decrease significantly (P>0.05); compared with treatment with Morinda officinalis oligosaccharide capsules, the HAMD-17 scores of patients in the liver depression and qi stagnation group, liver depression and fire transformation group, liver depression and spleen deficiency group, phlegm and qi stagnation group, and heart and spleen deficiency group after treatment with the whole prescription of Example 1 all decreased significantly (P<0.05).

[0130] Table 6 Comparison of HAMD-17 scores in patients with different syndromes of depression before and after treatment (mean±SD)

[0131]

[0132] Note: Compared with the group before treatment, * P<0.05; compared with the same period after Morinda officinalis oligosaccharide treatment, # P<0.05.

[0133] As shown in Table 7: The total effective rate of Example 1 in treating depression of different TCM syndromes is 90%, which is significantly higher than that of Morinda Officinalis Oligosaccharide Capsules (P < 0.05). This is because the whole prescription of Example 1 has significant clinical efficacy on depression of liver depression and qi stagnation type, liver depression transforming into fire type, liver depression and spleen deficiency type, phlegm and qi stagnation type, heart and spleen deficiency type, and kidney deficiency and liver depression type, while Morinda Officinalis Oligosaccharide Capsules only have significant clinical efficacy on depression of kidney deficiency and liver depression type.

[0134] Table 7 Comparison of clinical efficacy of two test substances in depression (unit: case)

[0135]

[0136]

[0137] Comparative Example 1 Effects of different formulations of Chinese medicine composition on depression model mice

[0138] 1. Experimental Methods

[0139] 1. Different formulations of Chinese medicine compositions and their preparation methods

[0140] (1) Replace the herb Morus alba with Cortex Acanthopanacis and replace Achyranthes bidentata with Cyathula officinalis in the whole prescription of Example 1, and obtain Prescription 6:

[0141] In parts by weight, take 50 parts of Astragalus, 30 parts of Herba Luzi, 19 parts of Atractylodes, 19 parts of Poria, 19 parts of Codonopsis, 8 parts of Aconite (Heishunpian), 15 parts of Cornus, 25 parts of Acanthopanax, 28 parts of Salvia, 51 parts of Leonurus, 19 parts of Pyrrosia, 42 parts of Hedyotis diffusa, and 16 parts of Cyathula, soak the medicinal materials in water for 30 minutes, decoct them three times, add 7 times, 5 times, and 5 times of water respectively, decoct for 30 minutes each time, and combine the three medicinal liquids for standby use.

[0142] (2) In the whole recipe of Example 1, the Radix Astragali in Example 1 is replaced by Radix Ginseng, the Atractylodes Macrocephala is replaced by Dioscorea opposita, and the Salvia miltiorrhiza is replaced by Carthamus tinctorius, to obtain Recipe 7:

[0143] In parts by weight, 50 parts of ginseng, 30 parts of deer tongue grass, 19 parts of yam, 19 parts of Poria, 19 parts of Codonopsis, 8 parts of processed aconite (Heishunpian), 15 parts of Cornus, 25 parts of Taxilla thunbergii, 28 parts of safflower, 51 parts of Leonurus japonicus, 19 parts of Pyrrosia ovata, 42 parts of Hedyotis diffusa, and 16 parts of Achyranthes bidentata are taken, and the medicinal materials are soaked in water for 30 minutes, and then decocted three times with 7 times, 5 times, and 5 times of water respectively, and decocted for 30 minutes each time, and the three medicinal liquids are combined for standby use.

[0144] (3) In the whole prescription of Example 1, the Radix Astragali in Example 1 is replaced by Radix Ginseng, the Atractylodes Macrocephala is replaced by Dioscorea opposita, the Salvia miltiorrhiza is replaced by Carthamus tinctorius, the Morus alba is replaced by Cortex Acanthopanacis, and the Achyranthes bidentata is replaced by Cyathula capitata, to obtain Prescription 8:

[0145] In parts by weight, take 50 parts of ginseng, 30 parts of deer tongue grass, 19 parts of yam, 19 parts of Poria, 19 parts of Codonopsis, 8 parts of processed aconite (Heishunpian), 15 parts of Cornus, 25 parts of Acanthopanax, 28 parts of Carthamus, 51 parts of Leonurus, 19 parts of Pyrrosia, 42 parts of Hedyotis diffusa, and 16 parts of Cyathula, soak the medicinal materials in water for 30 minutes, decoct them three times, add 7 times, 5 times, and 5 times of water respectively, decoct for 30 minutes each time, and combine the three medicinal liquids for standby use.

[0146] 2. Animal grouping and modeling

[0147] SPF grade male C57BL / 6 mice, male, weight 22±2g, were purchased from Guangdong Experimental Animal Center. The mice were randomly divided into 8 groups, 8 mice in each group, namely normal group, model group, fluoxetine group, whole prescription group, prescription 6 group, prescription 7 group, and prescription 8 group.

[0148] The modeling method was carried out according to Example 1.

[0149] 3. Method of administration

[0150] 14 days after modeling, the mice in the drug group were given corresponding doses of drugs by gavage, and the dosages are shown in Table 8. The mice in the normal group and the model group were given pure water.

[0151] Table 8 Dosages for each group of mice

[0152]

[0153] 4. Evaluation Method

[0154] The method of Example 1 was used to detect the behavioral effect of the Chinese medicine composition of this comparative example on the depression model mice, the method of Example 2 was used to detect the effect of the Chinese medicine composition of this comparative example on the sugar water preference of the depression model mice, and the method of Example 3 was used to detect the effect of the Chinese medicine composition of this comparative example on the neurotransmitters in the brain of the depression model mice.

[0155] 2. Experimental Results

[0156] The behavioral results of each group of mice are shown in Figure 7 and Figure 8 .Depend on Figure 7 It can be seen that compared with the model group, the tail suspension immobility time of mice in fluoxetine group, whole prescription group, prescription 6 group, prescription 7 group and prescription 8 group was significantly reduced (P < 0.01); compared with the whole prescription group, the tail suspension immobility time of mice in prescription 6 group, prescription 7 group and prescription 8 group was significantly increased (P < 0.01).

[0157] Depend on Figure 8 It can be seen that compared with the model group, the open field test scores of mice in the fluoxetine group, the whole prescription group, prescription 6 group, prescription 7 group and prescription 8 group were significantly increased (P < 0.01); compared with the whole prescription group, the open field test scores of mice in the prescription 6 group, prescription 7 group and prescription 8 group were significantly decreased (P < 0.01).

[0158] The above results show that the whole prescription group, prescription 6 group, prescription 7 group and prescription 8 group can significantly increase the activity, interest in exploring external things and ability of depression model mice, but the effect of prescription 6 group, prescription 7 group and prescription 8 group on improving the depressive-like behavior of depressed mice is weaker than that of the whole prescription group.

[0159] The results of sugar water preference of each group of mice are shown in Fig. 9 .Depend on Fig. 9It can be seen that compared with the model group, the sugar water preference index of mice in the fluoxetine group, the whole prescription group, prescription 6 group, prescription 7 group and prescription 8 group was significantly increased (P < 0.01); compared with the whole prescription group, the sugar water preference index of mice in the prescription 6 group, prescription 7 group and prescription 8 group was significantly decreased (P < 0.01).

[0160] The above results showed that the whole prescription group, prescription group 6, prescription group 7 and prescription group 8 could significantly increase the interest of depression model mice for sugar water, but the effect of prescription group 6, prescription group 7 and prescription group 8 in improving the preference of depression mice for sugar water was weaker than that of the whole prescription group.

[0161] The neurotransmitter contents in the brains of mice in each group are shown in Table 9. As shown in Table 9, compared with the model group, the contents of 5-HT, NE and DA in the brains of mice in the whole prescription group, prescription group 6, prescription group 7 and prescription group 8 were significantly increased (P < 0.01); compared with the whole prescription group, the contents of 5-HT, NE and DA in the brains of mice in the prescription group 6, prescription group 7 and prescription group 8 were significantly decreased (P < 0.01).

[0162] The above results show that the whole prescription group, prescription group 6, prescription group 7 and prescription group 8 can all significantly increase the neurotransmitter content in the brain of depression model mice, but the effect of prescription group 6, prescription group 7 and prescription group 8 in increasing the neurotransmitter content in the brain of depression model mice is stronger than that of the whole prescription group.

[0163] Table 9 Neurotransmitter content in the brain of mice in each group (mean±SD, n=8)

[0164] Grouping NE (pg / mg) DA (pg / mg) 5-HT (pg / mg) Normal group <![CDATA[115.35±11.61 ** ]]> <![CDATA[271.29±25.18 ** ]]> <![CDATA[875.23±49.92 ** ]]> Model Group 30.37±3.09 51.69±9.36 197.35±21.47 Fluoxetine group 33.45±5.90 68.12±9.48 <![CDATA[555.71±32.35 ** ]]> All-round group <![CDATA[92.56±7.85 ** ]]> <![CDATA[136.10±13.11 ** ]]> <![CDATA[407.93±26.46 ** ]]> Square 7 Group <![CDATA[76.23±3.76 **## ]]> <![CDATA[110.48±8.94 **## ]]> <![CDATA[431.57±17.14 **## ]]> Square 8 Group <![CDATA[60.37±5.56 **## ]]> <![CDATA[85.71±5.50 **## ]]> <![CDATA[362.18±20.95 **## ]]> Square 9 Group <![CDATA[50.63±4.61 **## ]]> <![CDATA[80.38±7.46 **## ]]> <![CDATA[285.72±23.34 **## ]]>

[0165] Note: Compared with the model group, ** P<0.01, * P<0.05; compared with the whole prescription group, ## P<0.01, # P<0.05.

[0166] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. Use of a composition as a synergist of a drug for treating depression, characterized in that: Based on weight, the composition comprises 28-32 parts by weight of Herba Hedyotis diffusae, 23-27 parts by weight of Herba Viscipiens, 17-21 parts by weight of Pyrrosiae, 40-44 parts by weight of Herba Hedyotis diffusae and 14-18 parts by weight of Herba Cynoglossi.

2. The use according to claim 1, characterized in that: Based on weight, the composition comprises 30 parts by weight of Herba Hedyotis diffusae, 25 parts by weight of Herba Viscipiens, 19 parts by weight of Herba Pyrrosiae, 42 parts by weight of Herba Hedyotis diffusae and 16 parts by weight of Herba Cynoglossi.

3. The use according to claim 1, characterized in that: By weight, the depression treatment drug contains 48-52 parts by weight of Astragalus, 17-21 parts by weight of Atractylodes, 17-21 parts by weight of Poria, 17-21 parts by weight of Codonopsis, 6-10 parts by weight of Heishun Pian, 13-17 parts by weight of Cornus officinalis, 26-30 parts by weight of Salvia miltiorrhiza and 49-53 parts by weight of Leonurus japonicus.

4. The use according to claim 1, characterized in that: The depression treatment drug is a drug that improves depressive-like behavior, alleviates anhedonia symptoms and / or increases the content of neurotransmitters in brain tissue.

5. The use according to claim 4, characterized in that: The neurotransmitters include norepinephrine, dopamine and / or serotonin.

6. Use of a composition in the preparation of an antidepressant drug, characterized in that: By weight, the composition comprises 48-52 parts by weight of Astragalus, 28-32 parts by weight of Herba Lycopi, 17-21 parts by weight of Atractylodes, 17-21 parts by weight of Poria, 17-21 parts by weight of Codonopsis, 6-10 parts by weight of Heishun Pian, 13-17 parts by weight of Cornus officinalis, 26-30 parts by weight of Salvia miltiorrhiza, 49-53 parts by weight of Leonurus japonicus, 23-27 parts by weight of Viscum album, 17-21 parts by weight of Pyrrosia, 40-44 parts by weight of Hedyotis diffusa and 14-18 parts by weight of Achyranthes bidentata.

7. The use according to claim 6, characterized in that: The antidepressant drug is a drug that improves depressive-like behavior, relieves anhedonia symptoms and / or increases the content of neurotransmitters in brain tissue.

8. The use according to claim 7, characterized in that: The neurotransmitters include norepinephrine, dopamine and / or serotonin.

9. The use according to claim 6, characterized in that: The depression includes depression of liver depression and qi stagnation type, liver depression transforming into fire type, liver depression and spleen deficiency type, phlegm and qi stagnation type, heart and spleen deficiency type and / or kidney deficiency and liver depression type.

10. The use according to claim 6, characterized in that: The dosage form of the drug includes but is not limited to tablets, capsules, granules, pills, powders, and mixtures.

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