An antidepressant traditional Chinese medicine composition and application thereof

Abstract

The application belongs to the technical field of traditional Chinese medicine, and particularly relates to an antidepressant traditional Chinese medicine composition and application thereof. The antidepressant traditional Chinese medicine composition is composed of raw medicinal materials in the following mass fractions: 3-11 parts of yujin, 8-15 parts of danshen, 3-10 parts of chuanqiong, 4-12 parts of dangui, 7-15 parts of sangshen, 8-15 parts of suanzhiren, 1-10 parts of zhizhi, 4-12 parts of yuzhu, 4-10 parts of zhizi, 4-9 parts of zhidouzi and 4-12 parts of zhimu, and is prepared into granules for treating depression, especially depression of yin deficiency and blood stasis type, solving important pathogenesis of depression disorder and improving the clinical cure rate of depression. Meanwhile, the application provides strong evidence-based medical evidence for treating depression by traditional Chinese medicine. The antidepressant mechanism of the antidepressant traditional Chinese medicine composition is clear and the composition is convenient to take, and the effectiveness and persistence of long-term treatment of patients can be improved, and the technical problem that there is no traditional Chinese medicine composition for preventing and treating depression, especially depression of yin deficiency and blood stasis type, and convenient to take, is solved.

Description

Technical Field

[0001] This application belongs to the field of traditional Chinese medicine technology, specifically relating to an antidepressant traditional Chinese medicine composition and its application. Background Technology

[0002] Depression is a serious mood disorder with a high prevalence, persistently high relapse rate, and significant risks of disability and suicide. Its core symptoms include persistent low mood, slowed thinking, and diminished willpower and behavior, often accompanied by physical symptoms such as memory loss, sleep disturbances, constipation, pain, sexual dysfunction, and amenorrhea. The relapse rate is as high as 75%–90%, and severely affected patients may even exhibit self-harm or suicidal tendencies, seriously impacting their work capacity and social functioning; therefore, it is known as the "silent killer" of human mental health. According to epidemiological statistics, depression has become the fourth leading cause of disease burden globally and the second leading cause of loss of healthy life expectancy due to disability worldwide.

[0003] Currently, first-line antidepressants in clinical practice are mainly SSRIs (supervised intravenous drug regimens), with representative drugs including fluoxetine hydrochloride, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram. However, these drugs generally have limitations such as delayed onset of action, easy development of drug tolerance, significant gastrointestinal and nervous system adverse reactions, and obvious withdrawal reactions, making them difficult to meet the needs of long-term treatment. Traditional Chinese medicine (TCM) has certain advantages in the treatment of depression, but existing TCM compound prescriptions are mostly aimed at common syndromes such as liver qi stagnation and deficiency of both heart and spleen. However, clinical surveys show that patients with persistent and recurrent depressive disorders, especially those with long-term illness, the elderly, or postpartum women, often have a complex pathogenesis of yin deficiency and blood stasis. Yin deficiency and blood stasis syndrome accounts for an important proportion of treatment-resistant depression. Unfortunately, there is currently a lack of effective TCM preparations specifically targeting this syndrome on the market; at the same time, existing TCM treatments for depression are mostly used in the form of decoctions, which have practical problems such as cumbersome decoction preparation, inconvenient portability, and poor patient compliance.

[0004] Therefore, developing a novel traditional Chinese medicine composition that is both effective for depression of the Yin deficiency and blood stasis type and convenient to take has become a technical challenge that urgently needs to be overcome in this field. This invention is based on the aforementioned clinical gaps and dosage form requirements, aiming to provide a traditional Chinese medicine composition with definite efficacy and convenient use, in order to offer a new and effective solution for the treatment of depression, especially the Yin deficiency and blood stasis type. Summary of the Invention

[0005] To address the lack of readily available and convenient traditional Chinese medicine (TCM) compositions for the prevention and treatment of depression, particularly Yin deficiency and blood stasis syndrome, in existing technologies, this application provides an antidepressant TCM composition and its application. This composition is particularly effective in treating depression of the Yin deficiency and blood stasis syndrome type, addressing a key pathogenesis of depressive disorders and improving the clinical cure rate. Furthermore, it will provide strong evidence-based medical support for TCM treatment of depression. The specific technical solution is as follows: An antidepressant traditional Chinese medicine composition, characterized in that it is composed of the following raw materials in parts by weight: 3-11 parts of Curcuma longa, 8-15 parts of Salvia miltiorrhiza, 3-10 parts of Ligusticum chuanxiong, 4-12 parts of Angelica sinensis, 7-15 parts of Morus alba, 8-15 parts of Ziziphus jujuba var. spinosa, 1-10 parts of Polygala tenuifolia, 4-12 parts of Polygonatum odoratum, 4-10 parts of Gardenia jasminoides, 4-9 parts of Hovenia dulcis, and 4-12 parts of Anemarrhena asphodeloides.

[0006] Furthermore, the raw materials are in the following proportions by weight: 6-10 parts of turmeric, 9-13 parts of salvia miltiorrhiza, 5-9 parts of chuanxiong rhizome, 5-11 parts of angelica sinensis, 8-12 parts of mulberry fruit, 9-13 parts of jujube seed, 3-6 parts of prepared polygala tenuifolia root, 5-10 parts of polygonatum odoratum rhizome, 5-8 parts of gardenia fruit, 5-7 parts of jujube fruit, and 5-8 parts of anemarrhena rhizome.

[0007] Furthermore, the raw materials are in the following proportions by weight: 10 parts turmeric, 9 parts salvia miltiorrhiza, 6 parts chuanxiong rhizome, 7 parts angelica sinensis, 8 parts mulberry fruit, 9 parts jujube seed, 3 parts prepared polygala tenuifolia, 7 parts polygonatum odoratum, 7 parts gardenia fruit, 6 parts jujube fruit, and 6 parts anemarrhena rhizome.

[0008] Furthermore, the dosage form of the traditional Chinese medicine composition is granules.

[0009] Furthermore, the preparation method of the traditional Chinese medicine composition includes the following steps: S1. Add 8-12 times the amount of water to the raw materials by total mass, soak for 0.5-1 hour, decoct 2-3 times, 1-2 hours each time, combine the decoctions, and filter. S2. At 60-70℃, the filtrate is concentrated to an extract with a relative density of 1.10-1.15, an appropriate amount of excipients are added, the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain the final product.

[0010] Furthermore, the excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0011] Furthermore, the application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0012] Compared with the prior art, the beneficial effects of this application are as follows: 1. The antidepressant traditional Chinese medicine composition of this application is used to treat depression, especially for depression of the Yin deficiency and blood stasis type, which has a better therapeutic effect, solves the important pathogenesis of depressive disorders, and improves the clinical cure rate of depression.

[0013] 2. The antidepressant traditional Chinese medicine composition of this application is based on the combination of three classic prescriptions (Zhang Zhongjing's Suanzaoren Decoction in "Synopsis of Prescriptions of the Golden Chamber", Baijin Pill in "Universal Relief Prescriptions" compiled by Zhu Su et al. in the Song Dynasty, and Sansangshen Paste in "Collection of Prescriptions from the Crane Pavilion" written by Ling Huan in the Qing Dynasty) with modifications and additions. The composition strictly follows the core pathogenesis of Yin deficiency and blood stasis and emotional distress in traditional Chinese medicine. The core treatment principle is "nourishing Yin and clearing heat, promoting blood circulation and removing blood stasis, relieving depression and calming the mind". The combination of principal, assistant, adjuvant and guide herbs is logically clear and suitable for the entire pathogenesis of depression, especially the Yin deficiency and blood stasis syndrome type of depression.

[0014] 3. The antidepressant traditional Chinese medicine composition of this application is in granule form, which is convenient to take and can improve the sustainability and effectiveness of long-term treatment for patients.

[0015] 4. Previous animal pharmacodynamic and mechanism-of-action studies have shown that the antidepressant traditional Chinese medicine composition of this application has good antidepressant effects and a clear mechanism of action. Attached Figure Description

[0016] Figure 1 The figure shows the experimental results of the effect of JYAG10 on ptosis and rectal temperature in reserpine-induced acute depression mice. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 2 The figure shows the experimental results of the effect of JYAG10 on the levels of 5-HT and 5-HIAA in the hippocampus of mice with reserpine-induced acute depression. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 3The figure shows the experimental results of the effect of JYAG10 on serum IL-6 and IL-1β levels in reserpine-induced acute depression mice. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 4 The figure shows the experimental results of the effect of JYAG10 on the behavior of CUMS mice. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 5 The figure shows the experimental results of the effect of JYAG10 on the body weight of CUMS mice. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 6The figure shows the experimental results of the effect of JYAG10 on the levels of 5-HT, DA, and NE in the hippocampus of CUMS mice. Among them, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 7 The figure shows the experimental results of the effect of JYAG10 on the HPA axis in CUMS mice. Among them, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 8 The figure shows the experimental results of the effect of JYAG10 on hippocampal injury in CUMS mice. Among them, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 9 The figure shows the experimental results of the effect of JYAG10 on the behavior of LPS-induced acute depression mice. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 10 The figure shows the experimental results of the effect of JYAG10 on the weight loss of LPS-induced acute depression mice 24 hours later. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 11 The figure shows the experimental results of the effect of JYAG10 on hippocampal microglia in LPS-induced depression model mice. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8; Figure 12 The figure shows the results of an experiment in which JYAG10 improves LPS-induced acute depression in mice through the P2X7 / NLRP3 / IL-1β signaling pathway. In the figure, CON: blank control group, MOD: model group, MOD+JY-L: low (225 mg / kg) dose group of JYAG10, MOD+JY-M: medium (450 mg / kg) dose group of JYAG10, MOD+JY-H: high (900 mg / kg) dose group of JYAG10, MOD+FLU: positive control drug (fluoxetine hydrochloride) group, #p<0.05, ##p<0.01 vs. CON group, *p<0.05, **p<0.01 vs. MOD group, n=8. Detailed Implementation

[0017] The technical solution of this application is further explained below, based on the traditional Chinese medicine theory of the antidepressant traditional Chinese medicine composition and pharmacodynamic experiments. It should be noted that JYAG is the abbreviation for the granules of the antidepressant traditional Chinese medicine composition of this application.

[0018] Example 1 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 3 parts Curcuma longa, 8 parts Salvia miltiorrhiza, 3 parts Ligusticum chuanxiong, 4 parts Angelica sinensis, 7 parts Morus alba, 8 parts Ziziphus jujuba var. spinosa, 1 part Polygala tenuifolia, 4 parts Polygonatum odoratum, 4 parts Gardenia jasminoides, 4 parts Hovenia dulcis, and 4 parts Anemarrhena asphodeloides.

[0019] The above-mentioned traditional Chinese medicine composition is made into granules.

[0020] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 8 times the amount of water to the raw materials by total mass, soak for 0.5 hours, decoct twice, 1 hour each time, combine the decoctions, and filter. S2. At 60℃, the filtrate is concentrated to an extract with a relative density of 1.10. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG01.

[0021] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0022] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0023] Example 2 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 6 parts turmeric, 10 parts salvia miltiorrhiza, 6 parts chuanxiong rhizome, 6 parts angelica sinensis, 9 parts mulberry fruit, 10 parts jujube seed, 2 parts prepared polygala tenuifolia root, 8 parts polygonatum odoratum rhizome, 6 parts gardenia fruit, 6 parts jujube fruit, and 6 parts anemarrhena rhizome.

[0024] The above-mentioned traditional Chinese medicine composition is made into granules.

[0025] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 8 times the amount of water to the raw materials by total mass, soak for 0.5 hours, decoct twice, 1 hour each time, combine the decoctions, and filter. S2. At 60℃, the filtrate is concentrated to an extract with a relative density of 1.10. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG02.

[0026] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0027] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0028] Example 3 An antidepressant traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 9 parts turmeric, 13 parts salvia miltiorrhiza, 9 parts chuanxiong rhizome, 8 parts angelica sinensis, 14 parts mulberry fruit, 13 parts jujube seed, 3 parts prepared polygala tenuifolia, 10 parts polygonatum odoratum, 8 parts gardenia fruit, 8 parts jujube fruit, and 10 parts anemarrhena rhizome.

[0029] The above-mentioned traditional Chinese medicine composition is made into granules.

[0030] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 8 times the amount of water to the raw materials by total mass, soak for 0.5 hours, decoct twice, 1 hour each time, combine the decoctions, and filter. S2. At 60℃, the filtrate is concentrated to an extract with a relative density of 1.12. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG03.

[0031] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0032] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0033] Example 4 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 11 parts of Curcuma longa, 15 parts of Salvia miltiorrhiza, 10 parts of Ligusticum chuanxiong, 12 parts of Angelica sinensis, 15 parts of Morus alba, 15 parts of Ziziphus jujuba var. spinosa, 10 parts of Polygala tenuifolia (processed), 12 parts of Polygonatum odoratum, 10 parts of Gardenia jasminoides, 9 parts of Hovenia dulcis, and 12 parts of Anemarrhena asphodeloides.

[0034] The above-mentioned traditional Chinese medicine composition is made into granules.

[0035] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 8 times the amount of water to the raw materials by total mass, soak for 0.5 hours, decoct twice, 1 hour each time, combine the decoctions, and filter. S2. At 60℃, the filtrate is concentrated to an extract with a relative density of 1.12. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG04.

[0036] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0037] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0038] Example 5 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 6 parts turmeric, 9 parts salvia miltiorrhiza, 5 parts chuanxiong rhizome, 5 parts angelica sinensis, 8 parts mulberry fruit, 9 parts jujube seed, 3 parts prepared polygala tenuifolia root, 5 parts polygonatum odoratum rhizome, 5 parts gardenia fruit, 5 parts jujube fruit, and 5 parts anemarrhena rhizome.

[0039] The above-mentioned traditional Chinese medicine composition is made into granules.

[0040] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 10 times the amount of water to the raw materials by total mass, soak for 1 hour, decoct 3 times, 2 hours each time, combine the decoctions and filter. S2. At 60℃, the filtrate is concentrated to an extract with a relative density of 1.14. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG05.

[0041] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0042] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0043] Example 6 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 7 parts Curcuma longa, 10 parts Salvia miltiorrhiza, 6 parts Ligusticum chuanxiong, 6 parts Angelica sinensis, 10 parts Morus alba, 10 parts Ziziphus jujuba var. spinosa, 4 parts Polygala tenuifolia, 6 parts Polygonatum odoratum, 6 parts Gardenia jasminoides, 6 parts Hovenia dulcis, and 6 parts Anemarrhena asphodeloides.

[0044] The above-mentioned traditional Chinese medicine composition is made into granules.

[0045] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 8 times the amount of water to the raw materials by total mass, soak for 0.5 hours, decoct twice, 1 hour each time, combine the decoctions, and filter. S2. At 65℃, the filtrate is concentrated to an extract with a relative density of 1.14. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG06.

[0046] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0047] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0048] Example 7 An antidepressant traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 8 parts turmeric, 11 parts salvia miltiorrhiza, 7 parts chuanxiong rhizome, 7 parts angelica sinensis, 10 parts mulberry fruit, 11 parts jujube seed, 4 parts prepared polygala tenuifolia, 7 parts polygonatum odoratum, 6 parts gardenia fruit, 6 parts jujube fruit, and 7 parts anemarrhena rhizome.

[0049] The above-mentioned traditional Chinese medicine composition is made into granules.

[0050] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 8 times the amount of water to the raw materials by total mass, soak for 0.5 hours, decoct twice, 1 hour each time, combine the decoctions, and filter. S2. At 65℃, the filtrate is concentrated to an extract with a relative density of 1.15. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG07.

[0051] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0052] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0053] Example 8 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 9 parts turmeric, 11 parts salvia miltiorrhiza, 8 parts chuanxiong rhizome, 8 parts angelica sinensis, 12 parts mulberry fruit, 12 parts jujube seed, 4 parts prepared polygala tenuifolia root, 8 parts polygonatum odoratum rhizome, 7 parts gardenia fruit, 7 parts jujube fruit, and 8 parts anemarrhena rhizome.

[0054] The above-mentioned traditional Chinese medicine composition is made into granules.

[0055] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 8 times the amount of water to the raw materials by total mass, soak for 0.5 hours, decoct twice, 1 hour each time, combine the decoctions, and filter. S2. At 65℃, the filtrate is concentrated to an extract with a relative density of 1.15. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG08.

[0056] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0057] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0058] Example 9 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 10 parts of Curcuma longa, 13 parts of Salvia miltiorrhiza, 9 parts of Ligusticum chuanxiong, 11 parts of Angelica sinensis, 12 parts of Morus alba, 13 parts of Ziziphus jujuba var. spinosa, 6 parts of Polygala tenuifolia, 10 parts of Polygonatum odoratum, 8 parts of Gardenia jasminoides, 7 parts of Hovenia dulcis, and 8 parts of Anemarrhena asphodeloides.

[0059] The above-mentioned traditional Chinese medicine composition is made into granules.

[0060] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 12 times the amount of water to the raw materials by total mass, soak for 1 hour, decoct 3 times, 2 hours each time, combine the decoctions and filter. S2. At 70℃, the filtrate is concentrated to an extract with a relative density of 1.13. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG09.

[0061] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

[0062] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0063] Example 10 An antidepressant traditional Chinese medicine composition, comprising the following raw materials in parts by weight: 10 parts turmeric, 9 parts salvia miltiorrhiza, 6 parts chuanxiong rhizome, 7 parts angelica sinensis, 8 parts mulberry fruit, 9 parts jujube seed, 3 parts prepared polygala tenuifolia, 7 parts polygonatum odoratum, 7 parts gardenia fruit, 6 parts jujube fruit, and 6 parts anemarrhena rhizome.

[0064] The above-mentioned traditional Chinese medicine composition is made into granules.

[0065] The method for preparing the granules of the traditional Chinese medicine composition includes the following steps: S1. Add 12 times the amount of water to the raw materials by total mass, soak for 1 hour, decoct 3 times, 2 hours each time, combine the decoctions and filter. S2. At 70℃, the filtrate is concentrated to an extract with a relative density of 1.13. An appropriate amount of excipients is added, and the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain JYAG10.

[0066] The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is a combination of magnesium stearate or talc.

[0067] The application of the above-mentioned traditional Chinese medicine composition in the treatment of depression.

[0068] The pharmacology of each component in the antidepressant traditional Chinese medicine composition provided in this invention embodiment is as follows: Chief herb: Turmeric. Turmeric is cold in nature and bitter in taste, and enters the liver, heart, and lung meridians. Its core functions are to invigorate blood and relieve pain, regulate qi and relieve depression, and clear the heart and cool the blood. Targeting the core pathogenesis of depressive disorders—liver qi stagnation, blood stasis, and disturbance of the mind—it can directly address the root cause of liver qi stagnation and blood stasis, relieve emotional stagnation, and clear the deficiency heat in the heart meridian. This is the core of the entire formula for relieving depression, invigorating blood, clearing the heart, and calming the mind.

[0069] Assistant herbs: Danshen, Chuanxiong, and Danggui. These three herbs work together to assist the principal herb, enhancing its effects of promoting blood circulation, removing blood stasis, nourishing and harmonizing blood, and regulating qi and blood flow. Danshen invigorates blood, cools the blood, clears the heart, and relieves irritability, effectively treating palpitations due to blood stasis, emotional distress, and insomnia. Chuanxiong promotes qi and blood circulation, dispels wind, and unblocks the meridians; as a qi-regulating herb within the blood, it can disperse stagnation, dredge qi and blood, and improve emotional distress. Danggui nourishes and invigorates blood, replenishes deficiency, and moistens dryness, invigorating blood without harming the body's vital energy, addressing the root causes of yin and blood deficiency. The combined use of these three herbs resolves blood stasis without harming yin, and regulates qi without depleting blood, making it suitable for the complex pathogenesis of yin deficiency and blood stasis.

[0070] The adjuvant herbs are: mulberry, jujube seed, prepared polygala, polygonatum, gardenia, jujube fruit, and anemarrhena. Polygala and mulberry nourish yin and generate fluids, tonify the liver and kidneys, specifically addressing the root cause of yin deficiency, relieving symptoms such as hot flashes, dry mouth, and insufficient yin and blood; anemarrhena clears heat and drains fire, nourishes yin and moistens dryness, clears internal heat due to yin deficiency, and prevents mental disturbance caused by deficiency fire; gardenia clears heart fire, cools blood and relieves irritability, specifically targeting stagnant heat in the heart meridian, improving irritability, insomnia, and anxiety; jujube seed and prepared polygala nourish the heart and calm the mind, benefiting intelligence and soothing the heart, effectively improving symptoms of insomnia, restlessness, and low mood in patients with depression; jujube fruit clears heat and relieves irritability, soothes emotions, and assists in harmonizing qi and relieving stagnant heat.

[0071] The combined use of all the herbs in the formula, each with its own function and complementing each other, works together to nourish yin and calm the mind, soothe the liver and promote blood circulation, addressing the core pathogenesis of depressive disorders, especially those with yin deficiency and blood stasis syndrome.

[0072] In this application, the antidepressant traditional Chinese medicine composition granules JYAG10 prepared in Example 10 were used for preliminary animal pharmacodynamic experiments and mechanism of action experiments.

[0073] I. Experimental Preparation 1. Preliminary animal pharmacodynamic experiments and ethics SPF-grade male C57BL / 6 mice, 8 weeks old and weighing 20-22g, were selected. Hulling conditions: temperature (22±2)℃, humidity (50±10)%, 12h light / dark cycle, free access to food and water. Experiments were conducted after one week of acclimatization.

[0074] 2. Test drug and positive control Test drug: JYAG10. Before the experiment, JYAG10 was prepared into a suspension with 0.5% sodium carboxymethyl cellulose (CMC-Na) and administered by gavage (ig), with a volume of 10 mL / kg.

[0075] Positive control: Fluoxetine hydrochloride, dissolved in physiological saline before use, dosage 10 mg / kg.

[0076] Blank and model control groups: were given an equal volume of 0.5% sodium carboxymethyl cellulose (CMC-Na).

[0077] 3. Animal grouping and dosage design There were 6 groups in total, with n=8 in each group: blank control group (CON), model group (MOD), low-dose JYAG10 group (MOD+JY-L): 225mg / kg, medium-dose JYAG10 group (MOD+JY-M): 450mg / kg, high-dose JYAG10 group (MOD+JY-H): 900mg / kg, and positive control group (MOD+FLU): fluoxetine hydrochloride 10mg / kg.

[0078] 4. Establishment of a mouse depression model and drug administration regimen Based on the characteristics of different depression models, the following design was implemented (all medications were administered before or concurrently with modeling): 5. Detection Indicators and Methods 5.1 Behavioral Testing Open field test (OFT): The time the mouse spends in the central area and its average moving speed are recorded within 5 minutes.

[0079] Forced swimming test (FST): Record the immobility time for the last 4 minutes after the initial 6 minutes.

[0080] Suspended tail test (TST): Record the immobility time for the last 4 minutes after the initial 6 minutes.

[0081] 5.2 Physiological and Morphological Indicators Rectal temperature: Measured by inserting a digital thermometer 1.5cm into the rectum.

[0082] Ptosis score: 0-4 points for semi-quantitative assessment (0 = fully open, 4 = fully closed).

[0083] Weight change: The LPS model recorded the weight difference 24 hours before and after modeling; the CUMS model recorded weekly weight.

[0084] 5.3 Biochemical indicators (ELISA method) Hippocampal tissue: testing for 5-HT, 5-HIAA, DA, and NE content.

[0085] Serum: Tests CORT, ACTH, IL-6, and IL-1β levels.

[0086] 5.4 Histopathology and Immunological Detection HE staining: to examine the morphology of neurons in the CA1 region of the hippocampus.

[0087] Immunofluorescence: Count of Iba-1 positive microglia.

[0088] Western Blot: The expression of P2X7, TLR4, NLRP3, ASC, Caspase-1 (p20), iNOS, and IL-1β proteins in hippocampal tissue was detected, with β-actin as an internal control.

[0089] 6. Statistical Analysis Data are expressed as mean ± standard error (Mean ± SEM). One-way ANOVA was performed using SPSS 26.0, and LSD-t tests were used for comparisons between groups. *P < 0.05 was considered statistically significant, and **P < 0.01 was considered highly significant.

[0090] II. Formal Experiment 1. Effects of JYAG10 on reserpine-induced acute depression in mice (1) Effects of JYAG10 on ptosis and rectal temperature in reserpine-induced acute depression mice like Figure 1 As shown, compared with the blank control group, the model group mice showed a significant decrease in body temperature and an increase in eyelid ptosis (P < 0.01, P < 0.01); compared with the model group, the fluoxetine hydrochloride group and the medium and high dose groups of JYAG10 mice showed a significant decrease in eyelid ptosis (P < 0.01, P < 0.05) and a significant increase in body temperature (P < 0.05, P < 0.05). The results indicate that JYAG10 can antagonize reserpine-induced hypothermia and eyelid ptosis symptoms in mice.

[0091] (2) Effects of JYAG10 on hippocampal 5-HT and 5-HIAA levels in depressed mice like Figure 2 As shown, compared with the blank control group, the 5-HT content in the hippocampus of mice in the model group was significantly decreased (P < 0.01), while the 5-HIAA content was significantly increased (P < 0.01). Compared with the model group, the 5-HT content in the hippocampus of mice in the fluoxetine hydrochloride group and the medium and high dose groups of JYAG10 was significantly increased (P < 0.01, P < 0.05), while the 5-HIAA content was significantly decreased (P < 0.01, P < 0.05). Compared with the blank control group, the 5-HIAA / 5-HT level in the model group was significantly increased (P < 0.01), while the levels in the fluoxetine hydrochloride group and the medium and high dose groups of JYAG10 were significantly lower than those in the model group (P < 0.01, P < 0.01). These results indicate that JYAG10 can increase the 5-HT content in the hippocampus of model mice and can reduce the metabolism of 5-HT to 5-HIAA, further increasing the 5-HT content.

[0092] (3) Effects of JYAG10 on serum IL-6 and IL-1β levels in reserpine-induced acute depression mice like Figure 3 As shown, compared with the model group, the serum IL-1β (P<0.01, P<0.01) and IL-6 (P<0.05, P<0.05) levels in mice in the fluoxetine hydrochloride group and the high-dose JYAG10 group were significantly reduced. The results indicate that JYAG10 can reduce serum IL-1β and IL-6 levels in model mice.

[0093] 2. Effects of JYAG10 on a mouse model of chronic unpredictable mild stimulation depression (CUMS). (1) Effects of JYAG10 on the behavior of CUMS mice like Figure 4 As shown, compared with the blank control group, the central dwell time and average movement speed of mice in the model group were significantly reduced (P < 0.01), while the immobility time in the forced swimming and tail suspension tests was significantly increased (P < 0.01). Compared with the model group, the central dwell time and average movement speed of mice in the medium- and high-dose JYAG10 groups and the fluoxetine hydrochloride group were significantly increased (P < 0.01), while the immobility time in the forced swimming and tail suspension tests was significantly reduced (P < 0.01). This indicates that JYAG10 can improve the autonomous activity ability of model mice, reduce the despair level of model mice, and improve the depressive state.

[0094] (2) Effect of JYAG10 on body weight of CUMS mice like Figure 5 As shown, after the modeling began, the weight gain of mice in all groups except the blank group was relatively slow. However, after the administration of the drug by gavage in week 4, the weight gain of mice in the medium and high dose groups of JYAG10 and the fluoxetine hydrochloride group was significantly faster than that of the model group. At the end of week 7, there was a significant difference in weight between the mice and the model group, indicating that JYAG10 can make the weight gain of CUMS mice faster.

[0095] (3) Effects of JYAG10 on the levels of 5-HT, DA, and NE in the hippocampus of CUMS mice like Figure 6 As shown, compared with the blank control group, the levels of 5-HT, DA, and NE in the hippocampus of mice in the model group were significantly decreased (P < 0.01); compared with the model group, the levels of 5-HT, DA, and NE in the hippocampus of mice in the medium- and high-dose JYAG10 groups and the fluoxetine hydrochloride group were significantly increased (P < 0.05), indicating that JYAG10 can increase the level of monoamine neurotransmitters in the brain of CUMS mice and improve the depressive state.

[0096] (4) Effects of JYAG10 on the HPA axis in CUMS mice like Figure 7 As shown, compared with the blank control group, the serum CORT and ACTH levels of mice in the model group were significantly increased (P < 0.01); compared with the model group, the serum CORT and ACTH levels of mice in the medium and high dose groups of JYAG10 and the fluoxetine hydrochloride group were significantly decreased (P < 0.05), indicating that JYAG10 can restore the HPA axis balance in mice by reducing serum CORT and ACTH levels, thereby improving the depressive state.

[0097] (5) Effects of JYAG10 on hippocampal damage in CUMS mice like Figure 8 As shown, under a microscope, the hippocampal cells of mice in the blank control group (A) were arranged tightly and orderly with normal structure and morphology. In the model group (B), the hippocampal cells of mice were arranged disorderly, with loose and enlarged gaps and obvious cell shrinkage, indicating that the hippocampal tissue of mice in the model group had a certain degree of damage. In contrast, the hippocampal cells of mice in the JYAG10 (D), high-dose (E), and fluoxetine hydrochloride (F) groups were arranged neatly and densely, indicating that JYAG10 can reduce the degree of hippocampal damage in CUMS model mice.

[0098] 3. Effects of JYAG10 on LPS-induced acute depression model mice (1) Effects of JYAG10 on the behavior of LPS-induced acute depression mice like Figure 9 As shown, compared with the blank control group, the central dwell time and average movement speed of mice in the model group were significantly reduced (P < 0.01), while the immobility time in the forced swimming and tail suspension tests was significantly increased (P < 0.01). Compared with the model group, the central dwell time and average movement speed of mice in the medium- and high-dose JYAG10 groups and the fluoxetine hydrochloride group were significantly increased (P < 0.01), while the immobility time in the forced swimming and tail suspension tests was significantly reduced (P < 0.01). This indicates that JYAG10 can improve the autonomous activity ability of model mice, reduce the despair level of model mice, and improve the depressive state.

[0099] (2) Effect of JYAG10 on weight loss in LPS-induced acute depression mice 24 h later like Figure 10 As shown, compared with the blank group, the body weight of mice in the model group decreased significantly after LPS modeling (P < 0.05); compared with the model group, the degree of body weight loss in mice in the low, medium, and high dose groups of JYAG10 and the fluoxetine hydrochloride group was significantly reduced (P < 0.05). This indicates that JYAG10 can alleviate the degree of LPS-induced body weight loss in mice.

[0100] (3) Effects of JYAG10 on hippocampal microglia in LPS-induced depression model mice like Figure 11 As shown, immunofluorescence staining results indicated that, compared with the blank control group, the number of Iba-1 positive cells in the hippocampus of mice in the model group was significantly increased; compared with the model group, the number of Iba-1 positive cells in the hippocampus of mice in the JYAG10 medium- and high-dose groups and the fluoxetine hydrochloride group was significantly decreased; Western blot results showed that, compared with the blank control group, the expression of Iba-1 and iNOS proteins in the hippocampus of mice in the model group was significantly upregulated; while compared with the model group, the expression of Iba-1 and iNOS proteins in the hippocampus of mice in the JYAG10 medium- and high-dose groups and the fluoxetine hydrochloride group was significantly downregulated. This indicates that JYAG10 can reduce the degree of neuroinflammation in the brain of LPS-induced acutely depressed mice.

[0101] 4. The mechanism of JYAG10 in preventing and treating depression Stress or LPS can stimulate the production and release of excess glutamate at neuronal synaptic terminals, prompting astrocytes to release large amounts of ATP. Excessive extracellular ATP may activate P2X7R in microglia, leading to a cascade reaction and inducing NLRP3 inflammasome activation. TLR4, a pattern recognition receptor in the innate immune system, is a key mediator of hippocampal microglia activation, influencing immune responses by activating downstream signaling pathways and mediating innate immune responses. The NLRP3 inflammasome is an important downstream signaling molecule of P2X7 and TLR4; NLRP3 activation promotes the release of inflammatory cytokines, leading to neuroinflammation. P2X7 receptor-mediated NLRP3 inflammasome activation plays a crucial role in the development of depression. Modern research indicates that P2X7 antagonists can exert therapeutic effects by inhibiting the P2X7 / NLRP3 / IL-1β signaling pathway, while simultaneously alleviating microglia-mediated neuroinflammation. Figure 12 As shown, compared with the model group, the expression of P2X7, TLR4, NLRP3 and IL-1β pathway-related proteins in the hippocampus of mice in the JYAG10 medium- and high-dose groups and the fluoxetine hydrochloride group showed a significant downregulation trend (P < 0.05), indicating that JYAG10 can improve LPS-induced neuroinflammation and improve the depressive state of mice through the P2X7 / NLRP3 / IL-1β signaling pathway.

[0102] In summary, preliminary animal pharmacodynamic and mechanism-of-action experiments have shown that the antidepressant traditional Chinese medicine composition of this application is comparable in efficacy to the mainstream SSRI fluoxetine hydrochloride. However, clinical trials have demonstrated that the antidepressant traditional Chinese medicine composition of this application has fewer side effects and exhibits significant antidepressant advantages, with a clear mechanism of action for improving depression. The animal experiments of this application verified the common pharmacodynamic mechanism of antidepressants, while the specific efficacy against "Yin deficiency and blood stasis syndrome" has been verified in clinical practice.

Claims

1. A traditional Chinese medicine composition for treating depression, characterized in that, It is composed of the following raw materials in parts by weight: 3-11 parts of Curcuma longa, 8-15 parts of Salvia miltiorrhiza, 3-10 parts of Ligusticum chuanxiong, 4-12 parts of Angelica sinensis, 7-15 parts of Morus alba, 8-15 parts of Ziziphus jujuba var. spinosa, 1-10 parts of Polygala tenuifolia, 4-12 parts of Polygonatum odoratum, 4-10 parts of Gardenia jasminoides, 4-9 parts of Hovenia dulcis, and 4-12 parts of Anemarrhena asphodeloides.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The raw materials are in the following proportions by weight: 6-10 parts of turmeric, 9-13 parts of salvia miltiorrhiza, 5-9 parts of chuanxiong rhizome, 5-11 parts of angelica sinensis, 8-12 parts of mulberry fruit, 9-13 parts of jujube seed, 3-6 parts of prepared polygala tenuifolia root, 5-10 parts of polygonatum odoratum rhizome, 5-8 parts of gardenia fruit, 5-7 parts of jujube fruit, and 5-8 parts of anemarrhena rhizome.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The raw materials are in the following proportions by weight: 10 parts turmeric, 9 parts salvia miltiorrhiza, 6 parts chuanxiong rhizome, 7 parts angelica sinensis, 8 parts mulberry fruit, 9 parts jujube seed, 3 parts prepared polygala tenuifolia, 7 parts polygonatum odoratum, 7 parts gardenia fruit, 6 parts jujube fruit, and 6 parts anemarrhena rhizome.

4. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The dosage form of the traditional Chinese medicine composition is granules.

5. The traditional Chinese medicine composition according to claim 4, characterized in that, The preparation method of the traditional Chinese medicine composition includes the following steps: S1. Add 8-12 times the amount of water to the raw materials by total mass, soak for 0.5-1 hour, decoct 2-3 times, 1-2 hours each time, combine the decoctions, and filter. S2. At 60-70℃, the filtrate is concentrated to an extract with a relative density of 1.10-1.15, an appropriate amount of excipients are added, the mixture is stirred evenly and then spray-dried to obtain a spray-dried powder. S3. Take the spray-dried powder, add an appropriate amount of excipients, mix well, and granulate by dry method to obtain the final product.

6. The traditional Chinese medicine composition according to claim 5, characterized in that, The excipient in S2 is dextrin or a combination of dextrin and maltodextrin; the excipient in S3 is magnesium stearate or talc.

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

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