Application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicines, and discloses application of a traditional Chinese medicine composition. Effective effect verification is carried out on a depression animal model by using active ingredients of a traditional Chinese medicine compound consisting of radix aucklandiae, fructus aurantii, betel nut and radix linderae, and in the results of a sweet water preference test, an open field test, a forced swimming test and a tail suspension test, the depression animal model shows a relatively good activity state after administration; the active ingredients of the traditional Chinese medicine composition can improve depression behaviors of model animals, show good anti-depression activity and are integrally superior to first-line medicine fluoxetine.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to an application of a traditional Chinese medicine composition. Background Art

[0002] Depression is a common mental illness in modern society. The WHO predicts that depression will become the world's largest disease burden in 2030. However, facing such high morbidity and mortality, effective treatments for depression are very scarce.

[0003] At present, SSRI (Selective Serotonin Reuptake Inhibitor, selective 5-hydroxytryptamine (5-HT) reuptake inhibitor) and SNRI (selective 5-hydroxytryptamine and norepinephrine reuptake inhibitor) are the first-line drugs for clinical antidepressants. SSRIs include fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram and escitalopram. SNRIs include venlafaxine, duloxetine, milnacipran, etc. However, about 1 / 3 of patients with depression lack responsiveness to existing antidepressants, and 1 / 2 of patients experience recurrence of the disease after 6-12 months of treatment. After receiving first-line drug treatment, less than 15% of patients with severe depression have their symptoms relieved. In addition, most antidepressants have gastrointestinal adverse reactions. SSRI and SNRI drugs can cause sexual dysfunction, cardiovascular system problems (hypertension, QT interval prolongation), etc. In recent years, the emergence of ketamine, a rapid antidepressant, has brought hope to patients with depression, but it has the risk of addiction and its safety needs to be evaluated. Therefore, safe and effective antidepressant drugs are urgently needed in clinical practice. Summary of the invention

[0004] In view of this, the purpose of the present invention is to provide a new application of a Chinese medicine composition, so that the Chinese medicine composition has a significant effect on improving depression, is superior to the first-line antidepressant fluoxetine, and can be used in the preparation of drugs for treating depression.

[0005] In order to solve the above technical problems, the present invention provides the use of a traditional Chinese medicine composition in the preparation of a drug for treating depression, wherein the traditional Chinese medicine composition is an extract of costusroot, fructus aurantii, areca catechu, and lindera strychnifolia.

[0006] Optionally, the Chinese medicine composition is an extract and water extract of aromatic components of costusroot, fructus aurantii, areca catechu and lindera strychnifolia.

[0007] Further optionally, the Chinese medicine composition is extracted according to the following method:

[0008] Extract aromatic components from costusroot, fructus aurantii, areca catechu and lindera strychnifolia by steam distillation and store for later use;

[0009] The medicinal liquid is filtered, the medicinal residue is decocted with water, and filtered to obtain a first filtrate; the first filtrate is concentrated under reduced pressure to obtain a clear paste, precipitated with alcohol, and filtered to obtain a second filtrate; the second filtrate is taken to recover ethanol until there is no alcohol taste, water is added to mix, and filtered to obtain a third filtrate; the third filtrate is taken and the aromatic component is added to obtain the Chinese medicine composition.

[0010] Optionally, by weight, 10-25 parts of costusroot, 20-30 parts of fructus aurantii, 10-25 parts of areca catechu, and 20-30 parts of lindera. Further optionally, the weight ratio of costusroot, fructus aurantii, areca catechu, and lindera is 1:1:1:1.

[0011] Optionally, the drug for treating depression includes tablets, capsules, granules, powders and oral solutions.

[0012] The present invention uses the active ingredients of the traditional Chinese medicine compound consisting of costus root, fructus aurantii, areca catechu and lindera stalk to verify the efficacy of depression animal models. In the results of saccharide preference test, open field test, forced swimming test and tail suspension test, the depression animal model shows a better activity state after administration. The active ingredients of the traditional Chinese medicine composition can improve the depressive behavior of the model animals, show good antidepressant activity, and are overall better than the first-line drug fluoxetine. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art are briefly introduced below.

[0014] Figure 1 Shown is a flow chart of the verification experiment of the present invention;

[0015] Figure 2 The figure shows the effect of Simotang oral solution on the sugar water preference of CUMS model animals; compared with the blank control group, *** P<0.001; compared with the CUMS group, ### P < 0.001;

[0016] Figure 3 The figure shows the effect of Simo decoction on the opening behavior of CUMS model animals (the time the animals stayed in the central area in the opening test); compared with the blank control group, * P<0.05; compared with the CUMS group, # P < 0.05;

[0017] Figure 4 The figure shows the effect of Simo decoction on the forced swimming behavior of CUMS model animals; (A) The immobility time of animals in the forced swimming test; (B) The swimming time of animals in the forced swimming test; Compared with the blank control group, ** P<0.01, ***P<0.001; compared with the CUMS group, # P<0.05, ## P<0.01, ### P < 0.001;

[0018] Figure 5 The figure shows the effect of Simo decoction on the tail suspension behavior of CUMS model animals; (A) The immobility time of animals in the tail suspension test; (B) The struggling time of animals in the tail suspension test; Compared with the blank control group, *** P<0.001; compared with the CUMS group, # P<0.05, ## P<0.01, ### P<0.001. DETAILED DESCRIPTION

[0019] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0020] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein may be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and are not intended to limit the content of this application.

[0021] Hansen Pharmaceuticals' Simotang oral liquid improves the traditional Chinese medicine compound based on the traditional Simotang, removes ginseng and agarwood, adds Citrus aurantium and costus root, and develops an improved Simotang Chinese medicine preparation. Simotang oral liquid is extracted from costus root, Citrus aurantium, areca nut, and Linderae strychnifolia (1:1:1:1), mainly including aromatic components and water-extracted active ingredients, each 10mL, each 1mL contains 0.15g of decoction pieces. Simotang oral liquid can smooth the qi and reduce adverse reactions, eliminate accumulation and relieve pain, and is mainly used to treat gastrointestinal system diseases, but there are no reports that it can be used to improve depression.

[0022] In the present invention, the effect of Simotang oral liquid on improving depression is verified by constructing a CUMS model (chronic unpredictable mild stress model). The CUMS model is a classic animal model of depression. It simulates the core symptoms of human depression, such as lack of pleasure, decreased motor ability, decreased social interaction ability, etc., to study the pathogenesis of depression and drug development. The Simotang oral liquid of the present invention was purchased from Hunan Hansen Pharmaceutical Co., Ltd.; fluoxetine hydrochloride (CAS No.: 56296-78-7; purity> 99%) was purchased from Sigma-Aldrich; SPF mice were purchased from Nanjing Annuokang Biotechnology Co., Ltd.

[0023] The present invention randomly divides the model group animals into a model control group, a Simotang group (low / medium / high dose) and a positive drug fluoxetine group, with 10 animals in each group. According to the group, Simotang oral liquid concentrate (raw drug amount 1.35 / 2.7 / 5.4g / kg / d) or fluoxetine (10mg / kg / d) was gavaged for 6 consecutive weeks, and the gavage volume was 10mL / kg. CUMS modeling was performed synchronously during the administration. After 6 weeks of administration, the sugar water preference test, open field test, forced swimming test and tail suspension test were used to evaluate whether Simotang had an improving effect on the depressive-like behavior of the model animals (see the experimental process). Figure 1 ).

[0024] In certain embodiments of the present invention, the sucrose preference test (SPT) method is:

[0025] Mice were housed in individual cages and adapted to 1% (w / v) sucrose water in advance. Before the formal experiment began, they were deprived of water and food for 24 hours. Then, a bottle of 1% (w / v) sucrose water and a bottle of ordinary water were placed in each cage, weighed separately, and switched every 12 hours to reduce experimental errors caused by position preference. The animals' intake of sucrose water and ordinary water within 24 hours was tested to calculate the preference for sugar water. Sucrose water intake ratio = sucrose water intake / (sucrose water intake + pure water intake)*100%. All experimental data are expressed as mean ± standard error, with 10 animals in each group. The experimental results were statistically analyzed using one-way ANOVA.

[0026] Figure 2 The results showed that after 6 consecutive weeks of CUMS modeling and administration of Simotang (1.35 / 2.7 / 5.4g / kg / d), behavioral tests found that Simotang could significantly increase the sucrose preference of CUMS model mice (CUMS: 40.2±8.04, CUMS+SMT1.35: 61.45±5.10, CUMS+SMT2.7: 66.16±5.04, CUMS+SMT5.4: 63.14±5.54), and the improvement effect of Simotang on sugar water preference was better than that of the positive drug fluoxetine (CUMS+Flu: 57.91±6.94).

[0027] In certain embodiments of the present application, the method of open field test (OFT) is:

[0028] Debug the test equipment in advance to ensure the clarity of the camera image. Set the software parameters and define the central and surrounding areas. At the beginning of the experiment, place the mice in the central area, monitor and count the time they stay in the central area within 10 minutes. After each animal is finished, clean the equipment to prevent the odor from affecting the subsequent test animals. Use one-way variance to perform statistical analysis on the experimental results.

[0029] Simotang oral solution (5.4 kg / d) can significantly increase the time that CUMS model mice stay in the central area in the open field test ( Figure 3 ; CUMS:8.24±4.99s, CUMS+SMT5.4:16.67±7.46s), the improvement effect was significantly better than that of the positive drug fluoxetine.

[0030] In certain embodiments of the present application, the forced swimming test (FST) method is:

[0031] Pour 25±2℃ water into a smooth container with a depth of 10-15cm. 24h in advance, put the mice into the water-filled container to pre-swim for 15min, take them out and wipe off the water, and put them back into the preheated cage. On the day of the experiment, debug the forced swimming equipment to ensure that the camera image is stable and clear, and debug the software parameters to analyze the state of the animals in the forced swimming test (immobility, swimming). After the experiment started, the mice were placed in 25±2℃ water to swim for 6min, and the images were collected and the data were statistically analyzed at the same time. After the forced swimming test, the mice were taken out of the water, wiped off the water with a towel, and put back into the preheated cage. All experimental data are expressed as mean ± standard error, with 10 animals in each group. The experimental results were statistically analyzed using one-way variance.

[0032] Simotang oral solution can significantly reduce the immobility time of CUMS model mice in forced swimming ( Figure 4 A; CUMS: 236.61±56.65s, CUMS+SMT1.35: 160.25±21.71s, CUMS+SMT2.7: 129.71±38.94s, CUMS+SMT5.4: 122.39±21.97s), and the effect of Simotang (2.7kg / d and 5.4kg / d) was better than that of the positive drug fluoxetine (141.66±61.22s). At the same time, Simotang oral solution can increase the swimming time of CUMS model mice in the forced swimming test ( Figure 4 B), and the effect is also better than the positive drug fluoxetine.

[0033] In certain embodiments of the present application, the tail suspension test (TST) method is:

[0034] Debug the tail suspension test equipment to ensure that the camera image is stable and clear, and debug the software parameters to analyze the state of the animal in the tail suspension test (immobility, struggle). Stick tape on the mouse's tail at about 2 / 3 and hang it on the instrument, about 15 cm from the ground. The camera collects the movement state of the mouse within 5 minutes of tail suspension, and the software is used to perform statistical analysis on the data. After the end, remove the mouse and put it back in the cage. All experimental data are expressed as mean ± standard error, with 10 animals in each group. The experimental results were statistically analyzed using one-way variance.

[0035] Simotang oral solution can significantly reduce the immobility time of CUMS model mice in the tail suspension test ( Figure 5 A; CUMS: 196.90±30.24s, CUMS+SMT1.35: 143.58±33.45s, CUMS+SMT2.7: 133.61±33.62s, CUMS+SMT5.4: 115.14±30.67s), and the effect of Simotang (2.7kg / d and 5.4kg / d) was better than that of the positive drug fluoxetine (139.52±36.12). At the same time, Simotang oral solution can increase the struggling time of CUMS model mice in the tail suspension test ( Figure 5 B), and the effect of Simo decoction (5.4kg / d) was better than that of the positive drug fluoxetine.

[0036] The core symptom of depression is anhedonia, and sugar water preference is used to evaluate anhedonia behavior. The immobility time in the forced swimming test and the tail suspension test is used to evaluate the antidepressant activity of the drug. The present invention found that Simotang oral liquid can significantly increase the sugar water preference of CUMS model animals, reduce the immobility time of CUMS model animals in the forced swimming test and the tail suspension test, and improve the depressive-like behavior of CUMS model animals, indicating that Simotang oral liquid has good antidepressant activity.

[0037] Based on the above excellent experimental results, the present invention provides the use of a traditional Chinese medicine composition in the preparation of a drug for treating depression, wherein the traditional Chinese medicine composition is an extract of costus root, fructus aurantii, areca catechu, and lindera strychnifolia.

[0038] According to the preparation method of Simotang oral liquid, the Chinese medicine composition is the aromatic component extract and water extract of costusroot, fructus aurantii, areca catechu and lindera strychnifolia.

[0039] More specifically, the Chinese medicine composition is obtained by extracting according to the preparation method of Simotang oral liquid:

[0040] Extract 300-450ml of aromatic water from costusroot, fructus aurantii, areca catechu and lindera strychnifolia by steam distillation and store in a separate container; filter the medicinal liquid, add water to the medicinal residue and boil it twice, each time for 0.5 hour, filter, combine the three filtrates, and concentrate under reduced pressure to obtain a clear paste, add ethanol to make the alcohol content reach 75-80%, refrigerate for 40-70 hours, filter, recover ethanol from the filtrate until there is no alcohol taste, add appropriate amount of water to stir, refrigerate for 15-30 hours, filter, add the above aromatic water, 240g of fructose syrup and 1.5g of potassium sorbate to the filtrate to dissolve, add water to adjust the volume to 1000ml, stir well, refrigerate for 36 hours, filter, and obtain.

[0041] The Chinese medicine composition comprises 10-25 parts of costusroot, 20-30 parts of fructus aurantii, 10-25 parts of areca catechu, and 20-30 parts of lindera stolonifera. Preferably, the weight ratio of costusroot, fructus aurantii, areca catechu, and lindera stolonifera is 1:1:1:1.

[0042] In the application provided by the present invention, the drug for treating depression can be prepared into any feasible drug dosage form by using the Chinese medicine composition of the present invention alone or in combination with other active ingredients, including but not limited to tablets, capsules, granules, powders and oral liquids.

[0043] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

[0044] The present invention and its implementation methods are described above, which is not restrictive. The drawings are only one of the implementation methods of the present invention, and the actual application is not limited thereto. In short, if ordinary technicians in the field are inspired by it and design methods and embodiments similar to the technical solution without creativity without departing from the purpose of the invention, they should all fall within the protection scope of the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for treating depression, wherein the Chinese medicine composition is an extract of costusroot, fructus aurantii, areca catechu, and lindera strychnifolia.

2. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is the aromatic component extract and water extract of costusroot, fructus aurantii, areca catechu and lindera strychnifolia.

3. The use according to claim 2, characterized in that: The Chinese medicine composition is obtained by extraction according to the following method: Extract aromatic components from costusroot, fructus aurantii, areca catechu and lindera strychnifolia by steam distillation and store for later use; The medicinal liquid is filtered, the medicinal residue is decocted with water, and filtered to obtain a first filtrate; the first filtrate is concentrated under reduced pressure to obtain a clear paste, precipitated with alcohol, and filtered to obtain a second filtrate; the second filtrate is taken to recover ethanol until there is no alcohol taste, water is added to mix, and filtered to obtain a third filtrate; the third filtrate is taken and the aromatic component is added to obtain the Chinese medicine composition.

4. The use according to any one of claims 1 to 3, characterized in that: In parts by weight, the ingredients include 10-25 parts of costusroot, 20-30 parts of fructus aurantii, 10-25 parts of areca catechu, and 20-30 parts of lindera stalk.

5. The use according to claim 4, characterized in that: The weight ratio of costusroot, fructus aurantii, areca catechu and lindera stalk is 1:1:1:

1.

6. The use according to claim 1, characterized in that: The medicine for treating depression includes tablets, capsules, granules, powders and oral liquids.

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