Use of a composition as an enhancer of antidepressant drugs

Abstract

The application discloses application of a composition in a synergist of a medicine for treating depression, wherein the composition is made of Rubia cordifolia, Taxillus delavayi, Pyrrosia lingua, Oldenlandia diffusa and Achyranthes bidentata, and the medicine for treating depression is made of Astragalus membranaceus, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, prepared Aconitum (black smooth tablet), Cornus officinalis, Salvia miltiorrhiza and Motherwort. The medicine combination prepared from the composition and the medicine for treating depression can significantly improve the depressive behavior of a depressive mouse, relieve the symptom of interest deficiency, and increase the content of a neurotransmitter in the brain of the depressive mouse. Further clinical tests find that the medicine combination has a significant clinical curative effect on various Chinese medical syndrome types of depression, 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, and kidney deficiency and liver depression type, and shows a good anti-depression effect, so the medicine combination 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 an 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, anhedonia, and despair, accompanied by anxiety, insomnia, slowed reaction times, and decreased learning and memory abilities. 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 developed many animal models for depression. Currently, the Chronic Unpredictable Mild Stress (CUMS) model is considered the most classic and commonly used animal model of depression, with a high degree of consistency with human depression.

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

[0004] With advantages such as mild effects and minimal side effects, Traditional Chinese Medicine (TCM) antidepressants are gaining widespread attention both domestically and internationally. However, TCM syndrome differentiation for depression is complex. The "Guidelines for the Integrated Diagnosis and Treatment of Depression with TCM and Western Medicine," published by the Chinese Society of Integrated Traditional Chinese and Western Medicine, the Chinese Association of Traditional Chinese Medicine, and the Chinese Medical Association, recommends the following TCM syndrome differentiations for depression: liver depression and qi stagnation, liver depression and spleen deficiency, liver depression transforming into fire, heart and spleen deficiency, kidney deficiency and liver depression, and phlegm and qi stagnation. Existing TCM herbal remedies for depression also have a limited scope of application. For example, Zishui Qinggan Yin is only indicated for depression characterized by kidney deficiency and liver depression, Guipi Tang is only indicated for depression characterized by heart and spleen deficiency, and Xiaoyao San combined with Banxia Houpo Tang is only indicated for depression characterized by liver depression and spleen deficiency. This narrow treatment scope is not only accompanied by a highly specialized and complex TCM syndrome differentiation process, but also by the frequent occurrence of incorrect syndrome differentiations. This leads to inappropriate medications for the condition, resulting in both wasteful use and significant suffering 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-mentioned defects and deficiencies 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 drugs for treating depression.

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

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

[0010] A composition is used as a synergist for a drug for treating depression. The composition comprises, by weight, 28-32 parts by weight of herba pyrifera, 23-27 parts by weight of herba loranthus, 17-21 parts by weight of herba pyrifera, 40-44 parts by weight of herba hedyotis diffusae, and 14-18 parts by weight of herba cyperi.

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

[0012] Preferably, the depression treatment drug comprises, by weight, 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 leaching, boiling, frying and other methods.

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

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

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

[0018] More preferably, the neurotransmitter comprises norepinephrine, dopamine and / or serotonin.

[0019] The invention discloses a use of a composition in preparing an antidepressant drug. The composition comprises, by weight, 48-52 parts by weight of astragalus, 28-32 parts by weight of leucanthemum, 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 aconite (Heishun 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 mistletoe, 17-21 parts by weight of pyrrosia, 40-44 parts by weight of oldenlandia diffusa and 14-18 parts by weight of chyranthes bidentata.

[0020] Preferably, the composition comprises, by weight, 50 parts by weight of Astragalus, 30 parts by weight of Herba Lycopodii, 19 parts by weight of Atractylodes, 19 parts by weight of Poria, 19 parts by weight of Codonopsis, 8 parts by weight of Processed Aconite (Heishunpian), 15 parts by weight of Cornus officinalis, 28 parts by weight of Salvia miltiorrhiza, 51 parts by weight of Leonurus, 25 parts by weight of Morus alba, 19 parts by weight of Pyrola, 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 symptoms of loss of interest.

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

[0023] More preferably, the neurotransmitter comprises norepinephrine, dopamine and / or serotonin.

[0024] Preferably, the depression includes 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 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 present invention discloses a composition for use as a synergist for depression treatment drugs, wherein the composition is prepared from Herba Hedyotis diffusae, Herba Mori Parasiticae, Herba Schizonepetae, Herba Hedyotis diffusae and Herba Achyranthis Bidentatae, and the depression treatment drugs are prepared from Herba Astragali, Herba Atractylodes Macrocephalae, Herba Poriae, Herba Codonopsis Pilosulae, Herba Aconiti Lateralis Preparata (Heishun Pian), Herba Corni Fructus, Herba Salviae Miltiorrhizae and Herba Leonurus. The drug combination prepared from the composition and the depression treatment drugs can significantly improve the depressive-like behavior of depressed mice, alleviate the symptoms of anhedonia and increase the neurotransmitter content in the brains 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 transformation 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 good antidepressant effect and having broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The effect of the whole Chinese medicine composition and its separate 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 effect of different ratios 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 compositions 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 ratios 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 effect of different formulas 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] Figure 9 The effect of different formulas 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 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, which, however, are not intended to limit the present invention in any way. 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, all reagents and materials used in the following examples were commercially available.

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

[0040] 1. Experimental Methods

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

[0042] Full recipe: Take 50 parts of Astragalus, 30 parts of Herba Lucidiellae, 19 parts of Atractylodes, 19 parts of Poria, 19 parts of Codonopsis, 19 parts of Radix Codonopsis, 8 parts of Aconite (Heishun Pian), 15 parts of Fructus Corni, 25 parts of Herba Mori Parasitici, 28 parts of Salvia miltiorrhizae, 51 parts of Herba Leonuri, 19 parts of Pyrrosiae, 42 parts of Herba Hedyotis diffusae, and 16 parts of Radix Achyranthis Bidentatae. Soak the herbs in water for 30 minutes, then decoct three times with 7-fold, 5-fold, and 5-fold water additions, decocting for 30 minutes each time. Combine the three decoctions for later use.

[0043] Recipe 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, and 51 parts of Leonurus. Soak the herbs in water for 30 minutes, then decoct three times with 7 times, 5 times, and 5 times the amount of water, respectively. Decoction for 30 minutes each time. Combine the three decoctions for later use.

[0044] Recipe 2: Take 30 parts of Herba Lycopodii, 25 parts of Herba Violae, 19 parts of Herba Selaginellae, 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 respectively. Decoction for 30 minutes each time and combine the three medicinal solutions for later use.

[0045] 2. Animal Grouping and Modeling

[0046] SPF male C57BL / 6 mice, weighing 22 ± 2 g, were purchased from the Guangdong Provincial Laboratory Animal Center. Mice were randomly divided into 12 groups, with 8 mice in each group: normal group, model group, fluoxetine group, high-dose unmixed prescription group (1), medium-dose unmixed prescription group (1), low-dose unmixed prescription group (1), high-dose unmixed prescription group (2), medium-dose unmixed prescription group (2), low-dose unmixed prescription group (2), high-dose whole prescription group (1), medium-dose whole prescription group (1), and low-dose whole prescription group (1).

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

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

[0049] 3. Dosage Method

[0050] Fourteen days after modeling, the mice in the drug group were given corresponding doses of drugs by gavage. 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 daily administration, the open field test and tail suspension test were performed to evaluate the behavior of the 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 (only squares stepped into by all four limbs were counted as horizontal movement scores) and the number of hind limbs upright (two front paws were in the air or climbing 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. A quiet and softly lit experimental environment was maintained during the experiment, 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, measuring 50 cm × 50 cm × 30 cm, was placed on its side, with black walls and bottom. The operator used non-stick adhesive to suspend the mouse's tail at the tip of one-third of the box, with its head facing the camera and approximately 10 cm from the bottom of the box. A video camera was used to record the duration of the animal's immobility for 6 minutes and then 4 minutes. Immobility refers to the animal's inaction, with the body suspended and not twisting. Each mouse was tested only once, and excrement and odor were removed after each test to prevent contamination of the subsequent test results.

[0057] Data analysis: Statistical analysis was performed using Prism 10 software, and t-tests were used to analyze the differences between groups. 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 the split-prescription 1, and the high-, medium- and low-dose groups of the full prescription were significantly reduced (P < 0.01), and the split-prescription 1 and the full prescription reduced the tail suspension immobility time of depressed mice in a dose-effect relationship; compared with the corresponding dose groups of the full prescription, the tail suspension immobility time of mice in the dose groups of the split-prescription 1 and the dose groups of the split-prescription 2 were significantly increased (P < 0.01).

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

[0061] These results indicate that using separate formula 1 alone can effectively increase the activity level, interest in exploring the outside world, and ability to explore, in depression-model mice, while using separate formula 2 alone has no such effect. However, when separate formulas 1 and 2 are used together, the resulting full formula can significantly improve the depressive-like behavior of depressed mice, significantly improving the therapeutic effect and significantly surpassing the effect of separate formula 1.

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

[0063] 1. Experimental Methods

[0064] The preparation method of the whole Chinese medicine composition and its separated prescriptions, animal grouping and modeling, and administration method are the same as those 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 Compared with the model group, the fluoxetine group, the high-dose and medium-dose groups of split formula 1, and the high-, medium-, and low-dose groups of the full formula significantly increased the sugar preference index of mice (P < 0.01). Split formula 1 and the full formula increased the sugar preference index of depressed mice in a dose-response relationship. Compared with the corresponding dose groups of the full formula, the sugar preference index of mice in the split formula 1 and split formula 2 dose groups was significantly reduced (P < 0.01).

[0069] These results indicate that using separate formula 1 alone can effectively increase the depressed model mice's interest in sugar water, while using separate formula 2 alone has no such effect. However, when separate formulas 1 and 2 are used together, the resulting full formula can significantly improve the symptoms of depressed mice's lack of interest in sugar water, with a significantly improved therapeutic effect, which is significantly better than the effect of separate formula 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 separated prescriptions, animal grouping and modeling, and administration method are the same as those in Example 1.

[0073] On day 21 of continuous daily dosing, mice were rapidly sacrificed under isoflurane anesthesia 1 hour after the last dose. The brains were removed by decapitation, and the cerebellum was carefully removed. The remaining brain tissue was stored at -80°C until further use. ELISA kits were used to measure the levels of the neurotransmitters norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in the brain tissue.

[0074] 2. Experimental Results

[0075] The neurotransmitter levels 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 fluoxetine group, the high-dose and medium-dose groups of Split Formula 1, and the high-, medium-, and low-dose groups of the full formula all significantly increased 5-HT, NE, and DA levels in the brains of mice treated with the fluoxetine group, the full formula, and the high-, medium-, and low-dose groups (P < 0.01). Split Formula 1 and the full formula also increased neurotransmitters in the brains of depressed mice in a dose-response relationship. Compared with the corresponding full formula dose groups, the brain 5-HT, NE, and DA levels in the mice treated with the split Formula 1 and split Formula 2 dose groups were significantly decreased (P < 0.01).

[0076] These results indicate that using separate formula 1 alone can effectively increase neurotransmitter levels in the brains of depression model mice, while using separate formula 2 alone has no such effect. However, when separate formulas 1 and 2 are used together, the resulting full formula can significantly increase neurotransmitter levels in the brains of depression model mice, and is significantly more effective than separate formula 1.

[0077] Table 2 Effects of the whole Chinese medicine composition and its separate prescriptions on the neurotransmitter content 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 ratios of the Chinese medicine composition are shown in Table 3, specifically:

[0085] Recipe 1: Each 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 Herba Pyriferae is changed from 19 parts by weight to 25 parts by weight, the weight of Herba Hedyotis diffusae is changed from 42 parts by weight to 48 parts by weight, and the weight of Herba Cyathulae is changed from 16 parts by weight to 12 parts by weight, while the weight of the other medicinal ingredients remain unchanged;

[0088] Recipe 4: 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 Atractylodes macrocephala is changed from 19 parts by weight to 25 parts by weight, the weight of Poria 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 root (Heishun tablets) 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 Salvia miltiorrhiza is changed from 28 parts by weight to 23 parts by weight, and the weight of Leonurus japonicus is changed from 51 parts by weight to 45 parts by weight, while the weights of the 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 Lucidum 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 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 root (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 decoct them three times with 7 times, 5 times and 5 times the amount of water respectively. Decoction for 30 minutes each time, and combine the three medicinal solutions for later use.

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

[0092]

[0093] 2. Animal Grouping and Modeling

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

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

[0096] 3. Dosage Method

[0097] Fourteen days after modeling, the mice in the drug group were given corresponding doses of drugs by gavage. 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 effects of the Chinese herbal composition of this embodiment on depression model mice, the method of Example 2 was used to detect the effects of the Chinese herbal composition of this embodiment on the sugar water preference of depression model mice, and the method of Example 3 was used to detect the effects of the Chinese herbal composition of this embodiment on neurotransmitters in the brains of depression model mice.

[0102] 2. Experimental Results

[0103] The behavioral results of mice in each group are shown in Figure 4 and Figure 5 .Depend on Figure 4 It can be seen that compared with the model group, the tail suspension immobility time of mice in fluoxetine group, prescription 1 group, prescription 2 group, prescription 3 group, prescription 4 group, and prescription 5 group was significantly reduced (P < 0.01); compared with prescription 1 group, the tail suspension immobility time of mice in prescription 3 group, prescription 4 group, and prescription 5 group was significantly increased (P < 0.01). Figure 5 Compared with the model group, the open field test scores of mice in the fluoxetine, Formula 1, Formula 2, Formula 3, Formula 4, and Formula 5 groups were significantly increased (P < 0.01); compared with Formula 1, the open field test scores of mice in the Formula 3, Formula 4, and Formula 5 groups were significantly decreased (P < 0.01). The results indicate that Formula 1, Formula 2, Formula 3, Formula 4, and Formula 5 can significantly increase the activity level, interest in exploring external objects, 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 Compared with the model group, the sugar preference index of mice in the fluoxetine, Recipe 1, Recipe 2, Recipe 3, Recipe 4, and Recipe 5 groups was significantly increased (P < 0.01); compared with Recipe 1, the sugar preference index of mice in Recipe 3, Recipe 4, and Recipe 5 groups was significantly decreased (P < 0.01). The results indicate that Recipe 1, Recipe 2, Recipe 3, Recipe 4, and Recipe 5 can all significantly increase the interest of depression model mice in sugar water, but the effect of Recipe 3, Recipe 4, and Recipe 5 on improving the preference for sugar water in depression mice is weaker than that of Recipe 1.

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

[0106] To sum up, 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 neurotransmitter content in mouse brain (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 different TCM syndrome types of depression

[0111] 1. Experimental Methods

[0112] 1. Research subjects

[0113] Two senior TCM physicians performed a TCM syndrome differentiation classification based on the TCM syndrome criteria for depression documented in the "Guidelines for the Diagnosis and Treatment of Depression with Integrated Traditional Chinese and Western Medicine," developed by the Chinese Society of Integrated Traditional Chinese and Western Medicine, the Chinese Association of Traditional Chinese Medicine, and the Chinese Medical Association. The syndromes included 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 to moderate depression were included, with 20 patients in each syndrome type.

[0114] Inclusion criteria: ① Patients with mild to moderate depression who met the Western medicine diagnostic criteria for depression in the "Guidelines for the Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Depression." ② Patients with symptoms consistent with the TCM diagnostic criteria for depression in the "Guidelines for the Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Depression." ③ Hamilton Depression Rating Scale-17 (HAMD-17) score of 8 or less and <24 points. ④ Gender was acceptable, age ≥18 and ≤65 years. ⑤ All patients had primary depressive symptoms. ⑥ Patients were not taking any medications or psychotherapy at the time of study inclusion.

[0115] Exclusion criteria: ① Depression secondary to other medical conditions. 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 cardiac, hepatic, or renal dysfunction, metabolic disorders, or other serious physical illnesses. ⑥ Patients prone to infection and bleeding. ⑦ Pregnant or breastfeeding women. ⑧ Patients with contraindications to treatment medications. ⑨ Patients with severe suicidal tendencies.

[0116] 2. Dosage Method

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

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

[0119] Morinda officinalis oligosaccharide capsules, specifications: each capsule contains 0.3 grams (containing Morinda officinalis oligosaccharide 150mg), produced by Tong Ren Tang Pharmaceutical Factory, Beijing Tong Ren Tang Co., Ltd. Take one Morinda officinalis oligosaccharide capsule orally, one capsule in the morning and one 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] Markedly effective: 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 considered markedly effective;

[0124] Effective: The patient's depressive symptoms and accompanying symptoms have improved compared to 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 test. 2 P < 0.05 was considered significant.

[0128] 2. Experimental Results

[0129] As shown in Table 6: there was no statistically significant difference in the HAMD-17 scores of the patients in each group before treatment (P>0.05); compared with before treatment, after treatment with the full 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 decreased significantly (P<0.05), and the HAMD-17 scores of the other groups did not decrease significantly (P>0.05); compared with after 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 full prescription of Example 1 all decreased significantly (P<0.05).

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

[0131]

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

[0133] As shown in Table 7, the total effective rate of Example 1 in treating depression of different TCM syndromes was 90%, which was significantly higher than that of Morinda officinalis oligosaccharide capsule (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 capsule has significant clinical efficacy only 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 compositions 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 capitata in the whole prescription of Example 1 to obtain Prescription 6:

[0141] In parts by weight, take 50 parts of Astragalus, 30 parts of Herba Luyezi, 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 miltiorrhiza, 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, then decoct them three times with 7 times, 5 times, and 5 times the amount of water, respectively. Decoction 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 was replaced by Radix Ginseng, the Atractylodes Macrocephala was replaced by Dioscorea opposita, and the Salvia miltiorrhiza was replaced by Carthamus tinctorius to obtain Recipe 7:

[0143] In parts by weight, take 50 parts of ginseng, 30 parts of herba gypsophila, 19 parts of yam, 19 parts of poria, 19 parts of codonopsis, 8 parts of processed aconite (black shunpian), 15 parts of cornus officinalis, 25 parts of mistletoe, 28 parts of safflower, 51 parts of motherwort, 19 parts of pyrrosia, 42 parts of oldenlandia diffusa, and 16 parts of cyathula. Soak the medicinal materials 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 standby use.

[0144] (3) In the whole recipe of Example 1, the Radix Astragali was replaced with Radix Ginseng, the Atractylodes Macrocephala was replaced with Dioscorea Opposita, the Salvia miltiorrhiza was replaced with Carthamus tinctorius, the Morus Parasitica was replaced with Cortex Acanthopanacis, and the Achyranthes Bidentata was replaced with Cyathula cuneata, to obtain Recipe 8:

[0145] In parts by weight, take 50 parts of ginseng, 30 parts of herba gypsophila, 19 parts of yam, 19 parts of poria, 19 parts of codonopsis, 8 parts of processed aconite (black shunpian), 15 parts of cornus officinalis, 25 parts of acanthopanax bark, 28 parts of safflower, 51 parts of motherwort, 19 parts of pyrrosia, 42 parts of oldenlandia diffusa, and 16 parts of cyathula. Soak the medicinal materials 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 standby use.

[0146] 2. Animal Grouping and Modeling

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

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

[0149] 3. Dosage Method

[0150] Fourteen days after modeling, the mice in the drug group were given corresponding doses of drugs by gavage. 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 behavioral effect of the Chinese medicine composition of this comparative example on depression model mice was detected according to the method of Example 1, the effect of the Chinese medicine composition of this comparative example on the sugar water preference of depression model mice was detected according to the method of Example 2, and the effect of the Chinese medicine composition of this comparative example on neurotransmitters in the brain of depression model mice was detected according to the method of Example 3.

[0155] 2. Experimental Results

[0156] The behavioral results of mice in each group 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 the fluoxetine group, the 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 the 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 full prescription group, prescription 6 group, prescription 7 group and prescription 8 group were significantly increased (P < 0.01); compared with the full 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 full prescription group, prescription group 6, prescription group 7 and prescription group 8 can significantly increase the activity, interest in exploring external things and exploration ability of depression model mice, but the effect of prescription group 6, prescription group 7 and prescription group 8 on improving the depressive-like behavior of depressed mice is weaker than that of the full prescription group.

[0159] The results of sugar water preference of each group of mice are shown in Figure 9 .Depend on Figure 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 show that the full prescription group, prescription group 6, prescription group 7 and prescription group 8 can significantly increase the interest of depression model mice in 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 is weaker than that of the full 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 5-HT, NE, and DA contents in the brains of mice in the full prescription group, prescription group 6, prescription group 7, and prescription group 8 were significantly increased (P < 0.01); compared with the full prescription group, the 5-HT, NE, and DA contents 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 full 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 on increasing the neurotransmitter content in the brain of depression model mice is stronger than that of the full 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 ** ]]> Full-face group <![CDATA[92.56±7.85 ** ]]> <![CDATA[136.10±13.11 ** ]]> <![CDATA[407.93±26.46 ** ]]> Group 7 <![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 considered as equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. Use of a pharmaceutical composition in the preparation of a drug for treating depression, characterized in that: The composition is prepared by weight from 28-32 parts of herba schizonepetae, 23-27 parts of mistletoe, 17-21 parts of pyrrosia, 40-44 parts of oldenlandia diffusa, 14-18 parts of chyranthes bidentata, 48-52 parts of astragalus, 17-21 parts of atractylodes, 17-21 parts of poria, 17-21 parts of codonopsis pilosula, 6-10 parts of heishunpian, 13-17 parts of cornus officinalis, 26-30 parts of salvia miltiorrhiza and 49-53 parts of motherwort.

2. The use according to claim 1, characterized in that The composition is prepared by weight from 30 parts of herba schizonepetae, 25 parts of mistletoe, 19 parts of pyrrosia, 42 parts of oldenlandia diffusa, 16 parts of cyperus rotundus, 50 parts of astragalus, 19 parts of atractylodes, 19 parts of poria, 19 parts of codonopsis pilosula, 8 parts of heishunpian, 15 parts of cornus officinalis, 28 parts of salvia miltiorrhiza and 51 parts of motherwort.

3. The use according to claim 1, characterized in that The depression includes 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 depression.

4. The use according to claim 1, characterized in that The dosage forms of the drug include but are not limited to tablets, capsules, granules, pills, powders, and mixtures.

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