A traditional Chinese medicine composition for relieving stagnation and resolving nodules, a preparation method thereof and application thereof

Abstract

This invention relates to the field of traditional Chinese medicine (TCM) technology, specifically disclosing a TCM composition for relieving depression and dispersing nodules, its preparation method, and its application. The TCM composition comprises the following raw materials in parts by weight: Bupleurum chinense 2-20 parts, Curcuma longa 2-20 parts, Paeonia lactiflora 2-20 parts, Taraxacum mongolicum 5-30 parts, Citrus aurantium 2-20 parts, Citrus aurantium 2-20 parts, Citrus reticulata 2-20 parts, Cremastra appendiculata 2-20 parts, Lobelia chinensis 10-60 parts, Luffa cylindrica 2-20 parts, and Albizia julibrissin bark 5-30 parts. The entire formula prioritizes relieving depression, primarily using heat-clearing, detoxifying, and nodule-dispersing methods, supplemented by promoting blood circulation, regulating qi, and eliminating masses. This allows qi to flow, blood to flow, blood to flow, blood to flow, nodules to disperse, and pathogenic factors to be eliminated, thus restoring balance.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and in particular relates to a traditional Chinese medicine composition for relieving depression and dispersing stagnation, its preparation method and application. Background Technology

[0002] "Stagnation and obstruction" is an important pathological concept in the theoretical system of Traditional Chinese Medicine (TCM). "Stagnation" refers to obstruction and blockage; "obstruction" refers to accumulation and inability to release. Together, "stagnation and obstruction" signifies a pathological state in which the flow of Qi, blood, and body fluids is obstructed, resulting in stagnation and accumulation. Human life depends on free flow; obstruction leads to various diseases. "Stagnation and obstruction" falls under the category of "obstruction" in the *Huangdi Neijing* (Yellow Emperor's Inner Classic). "Stagnation is not a specific name for a single disease, but rather the origin of many diseases," its scope is broad, involving the occurrence and development of various diseases across different clinical departments.

[0003] Breast cancer is one of the most common malignant tumors in women, and its incidence has been rising continuously in recent years, becoming a serious disease threatening women's lives and health. Traditional Chinese medicine (TCM) has certain advantages in the adjuvant treatment of breast cancer, postoperative rehabilitation, reducing the toxic side effects of radiotherapy and chemotherapy, improving clinical symptoms, and regulating the overall state of the body. Furthermore, TCM believes that the occurrence and development of breast cancer are closely related to emotional imbalance, liver dysfunction, spleen deficiency, phlegm stagnation, blood stasis, and internal accumulation of toxins. Among these, depression is one of the common TCM syndromes in breast cancer patients. These patients often present with emotional depression, chest and rib distension, breast pain, poor appetite, fatigue, pale tongue with white coating, and wiry and thready pulse, suggesting that its pathogenesis involves stagnation, phlegm and blood stasis, and deficiency of vital energy.

[0004] However, existing TCM preparations or empirical formulas used for the treatment or adjuvant therapy of breast cancer mainly focus on single aspects such as "anti-cancer," "dispersing nodules," "promoting blood circulation," or "clearing heat and detoxifying." They lack precise intervention targeting specific TCM syndromes of breast cancer, especially the core pathogenesis of patients with "comorbid depression." This often results in a broad treatment scope but insufficient syndrome matching, affecting the stability and specificity of clinical efficacy. Specifically, for breast cancer patients with comorbid depression, using only heat-clearing and detoxifying or blood-activating and nodule-dispersing drugs often fails to address the multiple treatment needs of relieving depression, resolving phlegm and nodules, and strengthening the body's resistance, making it difficult to comprehensively improve the patient's symptoms, physical condition, and long-term recovery quality.

[0005] Therefore, it is necessary to develop a traditional Chinese medicine preparation with the core functions of relieving depression, resolving phlegm and dissipating nodules, and regulating qi and blood, in order to improve the diagnostic and treatment effectiveness and clinical application value for patients with breast cancer complicated by depression. Summary of the Invention

[0006] This invention aims to address at least one of the technical problems existing in the prior art. To this end, this invention proposes a traditional Chinese medicine composition for relieving depression and dissipating nodules, its preparation method, and its application, to solve the problems of insufficient targeted differentiation and inaccurate symptomatic treatment in existing traditional Chinese medicine treatment programs for breast cancer complicated with depression. The traditional Chinese medicine composition of this invention takes into account relieving depression, resolving phlegm and dissipating nodules, promoting blood circulation and detoxification, or strengthening the body's resistance and eliminating pathogenic factors, and can meet the treatment needs of breast cancer patients with depression due to multiple factors and complex pathogenesis.

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for relieving depression and dispersing stagnation, the traditional Chinese medicine composition comprising the following raw materials in parts by weight: Bupleurum 2-20 parts, Curcuma 2-20 parts, Paeonia lactiflora 2-20 parts, Taraxacum mongolicum 5-30 parts, Citrus aurantium 2-20 parts, Citrus aurantium 2-20 parts, Citrus reticulata 2-20 parts, Cremastra appendiculata 2-20 parts, Lobelia chinensis 10-60 parts, Luffa cylindrica 2-20 parts, Albizia julibrissin bark 5-30 parts.

[0008] According to some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Bupleurum chinense 5-20 parts, Curcuma longa 5-20 parts, Paeonia lactiflora 5-20 parts, Taraxacum mongolicum 10-30 parts, Citrus aurantium 5-20 parts, Citrus aurantium 5-20 parts, Citrus reticulata 5-20 parts, Cremastra appendiculata 4-20 parts, Lobelia chinensis 20-40 parts, Luffa cylindrica 5-20 parts, Albizia julibrissin bark 10-30 parts.

[0009] According to some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Bupleurum 10 parts, Curcuma longa 8-12 parts, Paeonia lactiflora 8-12 parts, Taraxacum mongolicum 12-18 parts, Citrus aurantium 8-12 parts, Citrus aurantium 8-12 parts, Citrus reticulata 8-12 parts, Cremastra appendiculata 6-10 parts, Lobelia chinensis 20-40 parts, Luffa cylindrica 8-12 parts, Albizia julibrissin bark 12-18 parts.

[0010] According to some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Bupleurum 10 parts, Curcuma 10 parts, Paeonia lactiflora 10 parts, Taraxacum mongolicum 15 parts, Citrus aurantium 10 parts, Citrus reticulata peel 10 parts, Cremastra appendiculata 8 parts, Lobelia chinensis 30 parts, Luffa cylindrica 10 parts, Albizia julibrissin bark 15 parts.

[0011] In the above formula, Bupleurum, Curcuma, White Peony Root, Green Tangerine Peel, Bitter Orange Peel, and Asarum Seed are key herbs for relieving depression and regulating Qi, which can alleviate breast distension and pain and emotional depression, and are the core components of the formula. Dandelion, Cremastra appendiculata, and Lobelia chinensis work together to clear heat and detoxify, reduce swelling and dissipate nodules, resolve blood stasis and soften hard masses, and have anti-tumor effects. Luffa sponge has the effect of activating blood circulation, clearing the meridians, regulating Qi and dissipating nodules. Albizia bark can relieve depression, calm the mind, and harmonize Qi. The above formula harmonizes the pathogenesis of Qi stagnation, phlegm and blood stasis, and cancer toxin accumulation, and can be used to treat patients with breast cancer, breast hyperplasia, breast nodules, and depression.

[0012] A second aspect of the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition, comprising the following steps: Weigh out the following ingredients according to the formula: Bupleurum, Curcuma longa, Paeonia lactiflora, Taraxacum mongolicum, Citrus aurantium, Citrus reticulata peel, Cremastra appendiculata, Lobelia chinensis, Luffa cylindrica, and Albizia julibrissin bark. After cleaning and mixing, soak in water, decoct and extract, filter, collect the extract, and concentrate to obtain the final product.

[0013] According to some embodiments of the present invention, the decoction extraction includes first adding 8 to 12 times the total weight of the medicinal materials in water, soaking for 30 to 60 minutes, then decocting for 1 to 2 hours, then adding 6 to 10 times the total weight of the medicinal materials in water and decocting for 0.5 to 1.5 hours, combining the two extracts, filtering, and concentrating to a clear extract with a relative density of 1.05 to 1.30 at 60°C.

[0014] In a third aspect, the present invention provides a traditional Chinese medicine preparation for relieving depression and dispersing stagnation, the traditional Chinese medicine preparation comprising the above-mentioned traditional Chinese medicine composition.

[0015] According to some embodiments of the present invention, the traditional Chinese medicine preparation may be a variety of pharmaceutically acceptable dosage forms, including but not limited to: decoctions, granules, powders, tablets, pills, capsules, oral liquids, and pastes. Preferably, decoctions, granules, or capsules are preferred.

[0016] According to some embodiments of the present invention, the traditional Chinese medicine preparation further includes pharmaceutically acceptable excipients.

[0017] In a fourth aspect, the present invention provides the use of the above-mentioned traditional Chinese medicine composition or preparation in the preparation of drugs for relieving depression and / or dispersing nodules.

[0018] In a fifth aspect, the present invention provides the use of the above-described traditional Chinese medicine composition or the above-described traditional Chinese medicine preparation in the preparation of a medicament for treating breast cancer complicated with depression.

[0019] According to some embodiments of the present invention, the traditional Chinese medicine composition or preparation reduces the HAMD-17 score, reduces the TCM syndrome score, increases the FACT-B score, and increases the KPS score.

[0020] According to some embodiments of the present invention, the traditional Chinese medicine composition or preparation improves psychological stress-related behavioral abnormalities.

[0021] According to some embodiments of the present invention, the traditional Chinese medicine composition or preparation alleviates the overactivation of the HPA axis induced by psychological stress, thereby improving the body's stress response.

[0022] According to some embodiments of the present invention, the traditional Chinese medicine composition or preparation reduces psychological stress-related inflammatory responses, for example, by inhibiting the expression of inflammatory factors.

[0023] According to some embodiments of the present invention, the traditional Chinese medicine composition or preparation inhibits tumor growth.

[0024] In a sixth aspect, the present invention provides the use of the above-described traditional Chinese medicine composition or the above-described traditional Chinese medicine preparation in the preparation of a medicament for treating anxiety disorder associated with breast cancer.

[0025] According to some embodiments of the present invention, at least the following beneficial effects are achieved: This invention, based on the principles of traditional Chinese medicine (TCM) syndrome differentiation and treatment, is more targeted than some existing TCM formulas that only focus on clearing heat and detoxifying, promoting blood circulation and resolving stagnation. The formula for relieving depression and resolving stagnation uses Bupleurum, Curcuma, White Peony Root, Green Tangerine Peel, Bitter Orange Peel, and Asarum Seed as core components for relieving depression and regulating Qi; Dandelion, Cremastra appendiculata, and Lobelia chinensis as components for clearing heat and detoxifying, resolving stagnation and reducing swelling; and Luffa sponge as a component for promoting blood circulation, unblocking collaterals, regulating Qi, and resolving stagnation. Albizia bark is also added to relieve depression, calm the mind, and regulate Qi. The combination of each component is rigorous and well-structured, effectively addressing the pathogenesis of breast cancer patients with depression or anxiety, characterized by Qi stagnation, phlegm accumulation, blood stasis, and the mutual accumulation of cancer toxins, accompanied by emotional imbalance.

[0026] This invention has a good overall regulatory effect on common symptoms in breast cancer patients with depression or anxiety, such as emotional distress, breast tenderness, insomnia, poor appetite, and fatigue. The formula for relieving depression and dispersing stagnation can be used as a traditional Chinese medicine treatment for these patients, and can also be used as an adjunct to comprehensive treatments such as surgery, radiotherapy, chemotherapy, and endocrine therapy, demonstrating significant potential for widespread application.

[0027] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0028] The present invention will be further described below with reference to the accompanying drawings and embodiments, wherein: Figure 1 This is a graph showing the saccharide preference index results for each group of mice in Example 3. Compared to the control group, ### P<0.001; compared with the model group, ** P<0.01; compared with the group treated with the Liver-Soothing, Spleen-Strengthening, and Detoxifying Formula, & P<0.05, &&P<0.01; compared with the epirubicin group, △ P<0.05, △△ P < 0.01. The error bar represents the standard error (SE), n = 8.

[0029] Figure 2 This is a graph showing the results of the open field experiment in Example 3, where, compared to the control group, ## P<0.01, ### P<0.001; compared with the model group, ** P<0.01, *** P<0.001; compared with the group treated with the Liver-Soothing, Spleen-Strengthening, and Detoxifying Formula, & P<0.05, && P<0.01; compared with the epirubicin group, △ P < 0.05. The error bar represents the standard error (SE), n = 8.

[0030] Figure 3 These are the results of the elevated cruciate maze experiment for mice in Example 3. Compared to the control group, ## P<0.01, ### P<0.001; Compared with the model group, *P<0.05, **P<0.01, ***P<0.001; Compared with the liver-soothing, spleen-strengthening, and detoxifying formula group, & P<0.05, && P<0.01; compared with the epirubicin group, △ P < 0.05. The error bar represents the standard error (SE), n = 8.

[0031] Figure 4 This is a graph showing the HPA axis-related hormone levels in each group of mice in Example 3. Compared to the control group, ## P<0.01, ### P<0.001; compared with the model group, *** P<0.001; compared with the group treated with the Liver-Soothing, Spleen-Strengthening, and Detoxifying Formula, & P<0.05, && P<0.01; compared with the epirubicin group, △△ P<0.01, △△△ P < 0.001. The error bar represents the standard error (SE), n = 8.

[0032] Figure 5 The graph shows the serum IL-6, IL-1β, and TNF-α levels in mice in each group in Example 3. Compared to the control group, ## P<0.01, ### P<0.001; compared with the model group, ** P<0.01, ***P<0.001; compared with the group treated with the Liver-Soothing, Spleen-Strengthening, and Detoxifying Formula, & P<0.05, && P<0.01; compared with the epirubicin group, △ P<0.05, △△ P < 0.01. The error bar represents the standard error (SE), n = 8.

[0033] Figure 6 These are images showing the changes in tumor volume and the results of tumor removal in each group of mice in Example 3. Compared to the model group, * P<0.05, ** P<0.01; compared with the group treated with the Liver-Soothing, Spleen-Strengthening, and Detoxifying Formula, & P<0.05, && P<0.01. Detailed Implementation

[0034] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0035] The terms "preferred," "more preferably," etc., used in this invention refer to embodiments of the invention that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this invention.

[0036] Unless otherwise specified, "about" in this invention means that the allowable error is within ±2%.

[0037] Unless otherwise specified, "room temperature" in this invention means 25±5 ℃.

[0038] "And / or" is used to indicate that one or both of the described situations may occur, for example, A and / or B includes (A and B) and (A or B).

[0039] Unless otherwise specified, all other conditions in the following examples and comparative examples were performed under conventional conditions or conditions recommended by the manufacturer; reagents or instruments whose manufacturers are not specified were all commercially available products.

[0040] The design concept of this invention is as follows: Based on the theories of "breast cancer" and "breast lumps" in traditional Chinese medicine, this invention believes that the occurrence and development of breast cancer complicated with depression is often related to emotional distress, qi stagnation and phlegm accumulation, and the mutual binding of blood stasis and toxins. This is often due to emotional distress, which in turn affects the spleen, leading to dysfunction of the middle jiao, internal retention of dampness, and the accumulation of phlegm; obstructed qi flow and blood circulation, over time leading to the mutual binding of phlegm and blood stasis, forming lumps in the breast meridians; prolonged illness results in deficiency of vital qi and lingering pathogenic toxins, forming a mixed deficiency and excess syndrome. Based on this, this invention uses the principles of relieving depression, nourishing blood, clearing heat and detoxifying, dispersing lumps and reducing swelling, and promoting blood circulation and unblocking meridians. It creatively combines qi-regulating drugs, heat-clearing and detoxifying drugs, and blood-activating and meridian-unblocking drugs to create a traditional Chinese medicine preparation for relieving depression and dispersing lumps.

[0041] In this formula, Bupleurum, Curcuma, and White Peony are the principal herbs, regulating Qi and relieving stagnation. White Peony nourishes blood, relieves spasms and pain, and together with Bupleurum and Curcuma, they enhance the effects of harmonizing blood and regulating Qi. Anemarrhena, Aurantium, and Green Tangerine Peel are the assistant herbs. Curcuma not only relieves stagnation but also promotes Qi and blood circulation. Dandelion, Cremastra appendiculata, and Lobelia chinensis are the adjuvant herbs. Dandelion clears heat and detoxifies, reduces swelling and dissipates nodules; Cremastra appendiculata resolves phlegm and dissipates nodules and reduces swelling; Lobelia chinensis is a commonly used Chinese herb for clearing heat and detoxifying, reducing swelling and dissipating nodules, and together they strengthen the effects of clearing heat and detoxifying, reducing swelling and dissipating nodules. Luffa sponge unblocks the meridians, dissipates nodules, invigorates the meridians, and relieves pain; Albizia julibrissin bark relieves stagnation and calms the mind, and helps alleviate emotional distress, serving as the guiding herb.

[0042] The entire formula prioritizes relieving depression, focusing on clearing heat, detoxifying, and dispersing nodules, supplemented by promoting blood circulation, regulating qi, and eliminating masses. This allows qi to flow, blood to flow, blood to flow, blood to disperse stagnation, and the meridians to clear blockages, thus restoring balance and eliminating pathogenic factors. The combined effects of these herbs are to relieve depression, nourish blood, clear heat and detoxify, disperse nodules and reduce swelling, and promote blood circulation, making it particularly suitable for breast cancer patients with concurrent depression.

[0043] Example 1 This embodiment provides a formula for relieving depression and dispersing stagnation, the raw materials for which are: Bupleurum 10g, Curcuma longa 10g, Paeonia lactiflora 10g, Taraxacum mongolicum 15g, Citrus aurantium 10g, Citrus reticulata 10g, Cremastra appendiculata 8g, Lobelia chinensis 30g, Luffa cylindrica 10g, Albizia julibrissin bark 15g.

[0044] The preparation method of this formula for relieving depression and dispersing stagnation is as follows: Weigh out the following herbs according to the above weights: Bupleurum, Curcuma, White Peony Root, Dandelion, Prescription of the Rhizome, Bitter Orange Peel, Green Tangerine Peel, Cremastra appendiculata, Lobeliae, Luffa Sponge, and Albizia Bark. Clean and mix them evenly. Add 8 times the amount of water and soak for 30 minutes. Heat and decoct for 1 hour. Filter and collect the first extract. Add 6 times the amount of water to the dregs and heat and decoct again for 1 hour. Filter and collect the second extract. Combine the two extracts, filter, and concentrate under reduced pressure to a clear paste with a relative density of 1.10~1.20 at 60℃ to obtain the extract of the formula for relieving depression and dispersing stagnation.

[0045] Comparative Example 1 This comparative example provides a formula for soothing the liver, strengthening the spleen, and detoxifying, the composition of which is as follows: Bupleurum 10g, Curcuma longa 10g, Paeonia lactiflora 10g, Taraxacum mongolicum 15g, Prunella vulgaris 15g, Vaccaria segetalis 10g, Curcuma zedoaria 8g, Scutellaria barbata 30g, Hedyotis diffusa 30g, Citrus reticulata seed 10g, Glycyrrhiza uralensis 5g, Luffa cylindrica sponge 10g, Albizia julibrissin bark 15g.

[0046] The preparation method of this liver-soothing, spleen-strengthening, and detoxifying formula includes: Weigh out the following herbs according to the above weights: Bupleurum, Curcuma, White Peony Root, Dandelion, Prunella Vulgaris, Vaccaria Semen, Curcuma Rhizoma, Scutellariae Bark, Hedyotis Diffusae, Citrus Seed, Licorice Root, Luffa Sponge, and Albizia Bark. Clean and mix them evenly. Add 8 times the amount of water and soak for 30 minutes. Heat and decoct for 1 hour. Filter and collect the first extract. Add 6 times the amount of water to the dregs and heat and decoct again for 1 hour. Filter and collect the second extract. Combine the two extracts, filter, and concentrate under reduced pressure to a clear paste with a relative density of 1.10~1.20 at 60℃ to obtain the extract of the Liver-Soothing, Spleen-Strengthening, and Detoxifying Formula.

[0047] Example 2 To further evaluate the clinical efficacy of the Jieyu Sanjie formula in Example 1, 64 patients with breast cancer complicated by depression admitted to Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine were selected for clinical observation. All patients were diagnosed with breast cancer based on clinical manifestations, breast imaging examinations, and histopathological examinations. Traditional Chinese medicine diagnosis was based on the relevant standards of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," combined with symptoms such as emotional depression, chest and rib distension or breast pain, frequent sighing, decreased appetite, insomnia, pale red or red tongue, and wiry pulse, and was diagnosed as depression syndrome. Patients were randomly divided into an observation group and a control group, with 32 patients in each group.

[0048] The control group received routine basic treatment for breast cancer (such as surgical resection) and symptomatic supportive treatment; the observation group received the same treatment as the control group, plus the Jieyu Sanjie formula from Example 1, one dose daily, decocted in water and taken in two divided doses, morning and evening. Treatment continued for 4 weeks.

[0049] Changes in Hamilton Depression Rating Scale (HAMD-17), Breast Cancer Patient Quality of Life Assessment Scale (FACT-B), KPS score, and TCM syndrome score were observed in both groups before and after treatment, and safety indicators were recorded.

[0050] The results are shown in Table 1. After treatment, the HAMD-17 scores of both groups decreased compared with those before treatment, while the FACT-B and KPS scores increased. The TCM syndrome scores decreased compared with those before treatment. Moreover, the improvement in the observation group was better than that in the control group, suggesting that the Jieyu Sanjie formula can further improve the emotional state, quality of life and TCM syndrome of breast cancer patients with depression.

[0051] Table 1 Comparison of patients before and after treatment in the two groups (x) ±s, minutes)

[0052] Note: There was no statistically significant difference between the two groups before treatment (P>0.05); there was a statistically significant difference between the two groups after treatment (P<0.01).

[0053] The clinical efficacy comparison between the two groups of patients is shown in Table 2.

[0054] Table 2 Comparison of clinical efficacy between the two groups of patients [n (%)]

[0055] Note: The difference in the overall effective rate between the two groups was statistically significant (P < 0.05).

[0056] During the treatment, no serious adverse reactions were observed in either group, and no significant abnormalities were found in safety indicators such as blood routine tests, liver and kidney function. These results indicate that, based on routine breast cancer treatment, the Jieyu Sanjie formula can further improve the emotional state, TCM syndromes, and quality of life of patients with concurrent depression, demonstrating good clinical application value and safety.

[0057] Example 3 This embodiment examines the effects of the antidepressant and stagnation-relieving formula obtained in Example 1 and the liver-soothing, spleen-strengthening, and detoxifying formula obtained in Comparative Example 1 on mice with triple-negative breast cancer and depression under psychological stress.

[0058] A mouse model of triple-negative breast cancer combined with depression under psychological stress was established using female BALB / c mice purchased from Hunan Slack Jingda Experimental Animal Center. Mice were acclimatized for one week before being used in the experiment. A psychological stress model was established using chronic restraint stress combined with solitary rearing. A tumor-bearing model was established by injecting 4T1-luc triple-negative breast cancer cell suspension into the right abdominal mammary pad, thus constructing a mouse model of triple-negative breast cancer combined with depression under psychological stress. After modeling, a blank control group, a model group, a formula for relieving depression and dispersing stagnation, a formula for soothing the liver, strengthening the spleen, and detoxifying (or the original formula for soothing the liver, strengthening the spleen, and detoxifying), and an epirubicin group were set up. The effects of the formula for relieving depression and dispersing stagnation on mouse behavior, HPA axis-related hormones, inflammatory factors, and tumor growth were observed and compared with those of the formula for soothing the liver, strengthening the spleen, and detoxifying.

[0059] (1) Impact on psychological stress behavior A psychological stress model was established by combining chronic restraint and isolation, and 4T1-luc triple-negative breast cancer cells were injected under the right axillary breast pad to construct a tumor-bearing model.

[0060] The sucrose preference test, open field test, and elevated cruciate maze test were used to evaluate behavioral changes in mice. The sucrose preference test assessed anhedonia, recording sucrose intake and calculating the sucrose preference rate; a decreased sucrose preference rate indicated worsening depressive-like behaviors. The open field test assessed spontaneous activity and exploratory behavior, recording indicators such as total distance traveled; a decrease in total distance traveled indicated decreased activity capacity. The elevated cruciate maze test assessed anxiety-like behaviors, recording the percentage of time spent with arms open and the percentage of times arms were opened; decreases in these indicators indicated worsening anxiety-like behaviors. After drug intervention, an increase in the sucrose preference rate, total distance traveled, percentage of time spent with arms open, and percentage of times arms were opened indicated that the drug had a positive effect on psychological stress-related behavioral abnormalities.

[0061] The results are as follows Figures 1-3 As shown, compared with the control group, the model group mice showed a significant decrease in sucrose preference index, a reduction in total distance traveled in the open field experiment, and a decrease in the percentage of times they entered the elevated cross maze with open arms and the percentage of time they remained in the open arms, indicating that the psychological stress tumor model was successfully established. Compared with the model group, the sucrose preference index of the Jieyu Sanjie formula group mice was significantly increased (see...). Figure 1 The total distance traveled in the open field experiment increased (see...). Figure 2 The percentage of entries into the elevated cross maze and the percentage of time spent in the open arms increased (see...). Figure 3 Compared with the formula group for soothing the liver, strengthening the spleen, and detoxifying, the formula group for relieving depression and dispersing stagnation showed a more significant improvement in the above-mentioned behavioral indicators.

[0062] The results showed that the Jieyu Sanjie formula could significantly improve depressive-like and anxiety-like behaviors caused by psychological stress, suggesting that it has the effect of relieving depression and regulating emotional abnormalities. At the same time, compared with the Shugan Jianpi Jiedu formula, the Jieyu Sanjie formula had a better effect in improving behavioral abnormalities.

[0063] (2) Effects on HPA axis-related hormones The serum levels of CRH, CORT, and NE in mice of each group were detected by ELISA.

[0064] The results are as follows Figure 4 show, Figure 4 The serum levels of CRH, CORT, and NE in each group of mice are shown. Compared with the control group, the serum levels of CRH, CORT, and NE in the model group were significantly increased, indicating that the HPA axis was overactivated under psychological stress. Compared with the model group, the serum levels of CRH, CORT, and NE in the detoxifying and relieving nodules group were significantly decreased; compared with the original liver-soothing, spleen-strengthening, and detoxifying formula group, the decrease in the above indicators was more significant in the relieving nodules and relieving stagnation formula group.

[0065] The results showed that the formula for relieving depression and dispersing stagnation could alleviate the overactivation of the HPA axis induced by psychological stress, thereby improving the body's stress response; at the same time, its regulatory effect on HPA axis-related hormones was better than that of the original formula for soothing the liver, strengthening the spleen, and detoxifying.

[0066] (3) Effects on inflammatory factors The serum levels of IL-6, IL-1β and TNF-α in mice of each group were detected by ELISA.

[0067] The results are as follows Figure 5 As shown, compared with the control group, the serum levels of IL-6, IL-1β, and TNF-α in the model group mice were significantly increased, indicating that psychological stress can induce an enhanced inflammatory response in the body. Compared with the model group, the serum levels of IL-6, IL-1β, and TNF-α in the detoxifying and dispersing-nodus formula group were significantly decreased; compared with the original liver-soothing, spleen-strengthening, and detoxifying formula group, the levels of inflammatory factors in the relieving-detoxifying and dispersing-nodus formula group were further reduced. The results indicate that the relieving-detoxifying and dispersing-nodus formula has the effect of reducing psychological stress-related inflammatory responses, and is superior to the original liver-soothing, spleen-strengthening, and detoxifying formula in inhibiting the expression of inflammatory factors.

[0068] (4) Effects on tumor growth During modeling and drug administration, the long and short diameters of the tumor were measured periodically, and the tumor volume was calculated. After the experiment, the tumor was dissected and weighed, and the tumor inhibition rate was calculated.

[0069] The results are as follows Figure 6 As shown, compared with the model group, the tumor volume growth rate and tumor weight of the Jieyu Sanjie formula group were slower, indicating a more significant tumor-suppressing effect. Compared with the original Shugan Jianpi Jiedu formula group, the Jieyu Sanjie formula group performed better in reducing the tumor volume growth rate and tumor weight. The results indicate that the Jieyu Sanjie formula, while improving psychological stress, also has a good inhibitory effect on tumor growth, and its overall effect is superior to the original Shugan Jianpi Jiedu formula.

[0070] The above experimental results show that the Jieyu Sanjie formula can not only inhibit tumor growth in mice with triple-negative breast cancer and depression under psychological stress, but also improve depression-like and anxiety-like behaviors, regulate HPA axis-related hormone levels and reduce inflammatory factor expression, demonstrating the therapeutic characteristics of emphasizing both anti-tumor and Jieyu Sanjie treatment.

[0071] Example 4 To clarify the chemical basis of this formula for relieving depression and dispersing stagnation, mass spectrometry analysis was performed, and the detected components were classified, statistically analyzed, and ranked by relative content. The results showed that, ranked by relative content, the top 10 components in the formula mainly included: betaine, cis-4-hydroxy-D-proline, D-galactose, N-α-acetyllysine, Chrysoeriol, homologous acids, pyroglutamic acid, tryptophan, salicylic acid, and L-tyrosine. Based on the relative total amount of the aforementioned top 10 components, betaine accounted for 38%, cis-4-hydroxy-D-proline for 27%, D-galactose for 8%, N-α-acetyllysine for 6%, Chrysoeriol for 5%, homologous acids for 4%, pyroglutamic acid for 4%, tryptophan for 3%, salicylic acid for 3%, and L-tyrosine for 2%.

[0072] The above results suggest that the main chemical components of the Detoxifying and Stasis-Dispersing Formula include amino acids and their derivatives, organic acids, sugars, and flavonoids. Betaine, a typical small-molecule active substance, has functions such as regulating osmotic pressure, participating in methyl metabolism, antioxidation, and cell protection. Chrysoeriol, a flavonoid, has been shown to possess anti-inflammatory, antioxidant, and certain anti-tumor activities. Organic acids such as salicylic acid, homologous acids, and pyroglutamic acid may be related to the anti-inflammatory, anti-stress, and metabolic regulatory effects of the Detoxifying and Stasis-Dispersing Formula. Amino acids such as L-tyrosine or their derivatives may participate in cell metabolism, neuroendocrine regulation, and stress-related pathway regulation. Combined with the animal experimental results of this invention, it is suggested that the above-mentioned multiple components may collectively constitute the material basis for the Detoxifying and Stasis-Dispersing Formula's effects on anti-breast cancer, regulation of hypoxia-related signaling pathways, intervention in energy metabolism, and improvement of psychological stress.

[0073] In summary, the formula for relieving depression and dispersing stagnation of this invention has a complex composition and a wide distribution of chemical categories, mainly enriched in carboxylic acids and their derivatives, fatty acyls, benzene and its substituted derivatives, etc. Its high-abundance components are represented by betaine, cis-4-Hydroxy-D-proline, and D-galactose, while also containing flavonoids, organic acids, and amino acids as active ingredients. Its clear chemical basis can provide a foundation for its quality evaluation, pharmacodynamic material basis research, and subsequent elucidation of its mechanism of action.

[0074] The above description, in conjunction with specific embodiments, provides a detailed explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.

Claims

1. A traditional Chinese medicine composition for relieving depression and dispersing stagnation, characterized in that, The preparation raw materials include the following parts by weight: Bupleurum 2-20 parts, Curcuma 2-20 parts, Paeonia lactiflora 2-20 parts, Taraxacum mongolicum 5-30 parts, Citrus aurantium 2-20 parts, Citrus aurantium 2-20 parts, Citrus reticulata 2-20 parts, Cremastra appendiculata 2-20 parts, Lobelia chinensis 10-60 parts, Luffa cylindrica 2-20 parts, Albizia julibrissin bark 5-30 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The preparation raw materials include the following parts by weight: Bupleurum chinense 5-20 parts, Curcuma longa 5-20 parts, Paeonia lactiflora 5-20 parts, Taraxacum mongolicum 10-30 parts, Citrus aurantium 5-20 parts, Citrus aurantium 5-20 parts, Citrus reticulata 5-20 parts, Cremastra appendiculata 4-20 parts, Lobelia chinensis 20-40 parts, Luffa cylindrica 5-20 parts, Albizia julibrissin bark 10-30 parts.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The preparation raw materials include the following parts by weight: Bupleurum 10 parts, Curcuma longa 8-12 parts, Paeonia lactiflora 8-12 parts, Taraxacum mongolicum 12-18 parts, Citrus aurantium 8-12 parts, Citrus aurantium 8-12 parts, Citrus reticulata 8-12 parts, Cremastra appendiculata 6-10 parts, Lobelia chinensis 20-40 parts, Luffa cylindrica 8-12 parts, Albizia julibrissin bark 12-18 parts.

4. The method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, Includes the following steps: Weigh out the following ingredients according to the formula: Bupleurum, Curcuma longa, Paeonia lactiflora, Taraxacum mongolicum, Citrus aurantium, Citrus reticulata peel, Cremastra appendiculata, Lobelia chinensis, Luffa cylindrica, and Albizia julibrissin bark. After cleaning and mixing, soak in water, decoct and extract, filter, collect the extract, and concentrate to obtain the final product.

5. The preparation method according to claim 4, characterized in that, The decoction extraction process involves first adding 8 to 12 times the total weight of the medicinal materials in water, soaking for 30 to 60 minutes, then decocting for 1 to 2 hours, then adding 6 to 10 times the total weight of the medicinal materials in water and decocting for 0.5 to 1.5 hours. The two extracts are combined, filtered, and concentrated to a clear extract with a relative density of 1.05 to 1.30 at 60°C.

6. A traditional Chinese medicine preparation for relieving depression and dispersing stagnation, characterized in that, The traditional Chinese medicine composition included in any one of claims 1 to 3.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, The dosage form of the traditional Chinese medicine preparation is selected from decoction, granules, powder, tablets, pills, capsules, oral liquid or paste.

8. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine preparation according to claims 6 and 7 in the preparation of drugs for relieving depression and / or dispersing nodules.

9. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine preparation according to claims 6 and 7 in the preparation of a medicament for treating breast cancer complicated with depression.

10. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine preparation according to claims 6 and 7 in the preparation of a medicament for treating anxiety disorder associated with breast cancer.

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