A traditional Chinese medicine composition for improving breast cancer-related dyslipidemia, its preparation method and application

Abstract

This invention relates to the field of traditional Chinese medicine, specifically a traditional Chinese medicine composition for improving breast cancer-related dyslipidemia and its application. The composition comprises the following raw materials in parts by weight: Astragalus membranaceus 6-30 parts, Rhodiola rosea 6-30 parts, Curcuma zedoaria 3-15 parts, Polygonatum sibiricum 3-15 parts, and Actinidia chinensis root 1.5-9 parts. This traditional Chinese medicine composition precisely addresses the pathogenesis of qi deficiency and blood stasis after breast cancer surgery, with the entire formula working synergistically to invigorate qi, strengthen the body, and promote blood circulation. Animal experiments have demonstrated that this invention significantly reduces liver index, serum TG, TC, and LDL-C levels in hyperlipidemic mice, with effects comparable to statins. Clinical trials have also confirmed that this invention improves lipid indicators in breast cancer patients with mild dyslipidemia, and has a high safety profile.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, specifically to a traditional Chinese medicine composition for improving breast cancer-related dyslipidemia, its preparation method, and its application. Background Technology

[0002] Malignant breast cancer is one of the most common malignant tumors among women (Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. Journal of the National Cancer Center, 2024, 46(3):221-231.). With the improvement of diagnosis and treatment, the survival time of breast cancer patients has been effectively extended. Dyslipidemia is a common comorbidity of breast cancer. Studies have shown that the incidence of dyslipidemia in patients newly diagnosed with primary breast cancer is as high as 43.0%, and it is not concentrated in a certain type of breast cancer patient population, but is widely distributed in all molecular subtypes of breast cancer patients (Li X, Liu ZL, Wu YT, et al. Status of lipid and lipoprotein in female breast cancer patients at initial diagnosis and during chemotherapy[J]. Lipids Health Dis, 2018, 17(1):91. Li Ruiqing, Chen Jiejing, Du Jialing, et al. Correlation analysis of blood lipid levels in triple-negative and hormone receptor-positive breast cancer patients[J]. Chinese Journal of Cancer Prevention and Treatment, 2018, 25(11):799-802. Lü Hongying, Nie Xianli, Wang Song, et al. Discussion on the correlation between blood lipid levels and molecular subtypes of invasive breast cancer[J], 2021, 28(3):336-340.). Recent studies have found that dyslipidemia is not only related to the occurrence of breast cancer, but also closely linked to its recurrence and progression (Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of Serum Lipid Profile on the Risk of Breast Cancer: Systematic Review and Meta-Analysis of 1,628,871 Women[J]. J Clin Med, 2022, 11(15): 4503). T, Mortensen ES, Nalwoga H, et al. Impact of pre-diagnostictriglycerides and HDL-cholesterol on breast cancer recurrence and survival bybreast cancer subtypes[J]. BMC Cancer, 2018, 18(1):654.). Total cholesterol (TC) and its metabolite 27-hydroxycholesterol (27HC) can promote the proliferation and migration of breast cancer cells, and are also potentially related to the development of drug resistance (Nelson ER, Wardell SE, Jasper JS, et al. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology[J]. Science, 2013, 342(6162):1094-1098. Baek AE, Krawczynska N, Das Gupta A, et al. The Cholesterol Metabolite 27HC Increases Secretion of Extracellular Vesicles Which Promote Breast Cancer Progression[J]. Endocrinology, 2021, 162(7):bqab095.). In addition, the risk of death from cardiovascular disease related to dyslipidemia remains high among breast cancer patients (Kong Lingquan, Wu Kainian, Li Hongyuan. Cardiology of Breast Tumors [M]. Beijing: Science Press, 2018: 147-288.). Although dyslipidemia may not have obvious symptoms in its early stages, it should be taken seriously. Early detection and intervention are of great clinical significance for the prognosis of breast cancer patients.

[0003] Dyslipidemia typically refers to an elevation in any one of the following: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and / or a decrease in high-density lipoprotein cholesterol (HDL-C) (Zhu Junren, Gao Runlin, Zhao Shuiping, et al. Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults (2016 Revised Edition) [J]. Chinese Journal of Circulation, 2016, 31(10):937-953.). LDL-C plays a central role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD), therefore, various guidelines advocate lowering serum LDL-C levels to control the risk of ASCVD. Statins, as first-line lipid-lowering drugs, are currently the preferred drugs for treating breast cancer-related dyslipidemia (Joint Expert Committee for the Revision of Chinese Guidelines for Lipid Management, Li Jianjun, Zhao Shuiping, et al. Chinese Guidelines for Lipid Management (2023) [J]. Chinese Journal of Circulation, 2023, 38(3):237-271. Expert Group on Multidisciplinary Management of Endocrine Therapy for Breast Cancer in China. Chinese Expert Consensus on the Management of Dyslipidemia in Postmenopausal Early Breast Cancer Patients [J]. Chinese Journal of Oncology, 2017, 39(1):6. Working Committee of the China Cholesterol Education Program, Atherosclerosis and Thrombosis Prevention and Control Branch of the China International Exchange and Promotion Association for Medical and Health Care, Cardiovascular Disease Branch of the Chinese Gerontology and Geriatrics Society, et al. Expert Recommendations on Lipid-Lowering Therapy to Reduce Cardiovascular Events under the China Cholesterol Education Program (2019) [J]. Chinese Journal of Internal Medicine, 2020, 59(1):18-22.), with a large amount of RCT evidence. However, the general population has poor tolerance to this drug, especially when using high doses (atorvastatin 80mg / day, simvastatin 40mg, pravastatin 20mg, rosuvastatin 95mg / day), which commonly causes severe muscle toxicity, liver damage, gastrointestinal reactions, and other adverse drug reactions (Gao Kun, Cheng Feng, Li Hao. Analysis of adverse reactions of statins based on FAERS database mining [J]. Chinese Journal of Hospital Pharmacy, 2022, 42(22):2383-2387.), reducing medication adherence and making intermittent use a common occurrence. The clinically advocated long-term, low-dose statin therapy has no significant benefit evidence for low-risk patients, and it is difficult to achieve ideal efficacy for intermediate- and high-risk patients. It can be seen that Western medicine treatment has certain limitations, and there is a need to develop an effective and low-toxicity lipid-lowering treatment plan and drug as a supplement to statins to improve quality of life and reduce the survival risk of patients.

[0004] Currently, there are numerous traditional Chinese medicine compound formulas used clinically to lower lipids, but there are no lipid-lowering drugs specifically for patients with breast cancer. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition for improving breast cancer-related dyslipidemia, its preparation method, and its application.

[0006] To achieve the above objectives, a first aspect of the present invention provides a traditional Chinese medicine composition for improving breast cancer-related dyslipidemia, comprising the following raw materials in parts by weight: Astragalus membranaceus 6-30 parts, Rhodiola rosea 6-30 parts, Curcuma zedoaria 3-15 parts, Polygonatum sibiricum 3-15 parts, and Actinidia chinensis root 1.5-9 parts. In this composition, Astragalus membranaceus and Rhodiola rosea are the principal herbs; Curcuma zedoaria and Polygonatum sibiricum are the assistant herbs; and Actinidia chinensis root is the adjuvant herb.

[0007] Furthermore, the traditional Chinese medicine composition for improving breast cancer-related dyslipidemia is composed of the following raw materials in parts by weight: Astragalus membranaceus 6-12 parts, Rhodiola rosea 6-12 parts, Curcuma zedoaria 3-6 parts, Polygonatum sibiricum 3-6 parts, and Actinidia chinensis root 2-3 parts.

[0008] As one of the preferred embodiments of the present invention, the traditional Chinese medicine composition for improving breast cancer-related dyslipidemia is composed of the following raw materials in parts by weight: 6 parts Astragalus membranaceus, 6 parts Rhodiola rosea, 3 parts Curcuma zedoaria, 3 parts Polygonatum sibiricum, and 1.5 parts Actinidia chinensis root.

[0009] As one of the preferred embodiments of the present invention, the traditional Chinese medicine composition for improving breast cancer-related dyslipidemia is composed of the following raw materials in parts by weight: 12 parts Astragalus membranaceus, 12 parts Rhodiola rosea, 6 parts Curcuma zedoaria, 6 parts Polygonatum sibiricum, and 3 parts Actinidia chinensis root.

[0010] As one of the preferred embodiments of the present invention, the traditional Chinese medicine composition for improving breast cancer-related dyslipidemia is composed of the following raw materials in parts by weight: 30 parts Astragalus membranaceus, 30 parts Rhodiola rosea, 15 parts Curcuma zedoaria, 15 parts Polygonatum sibiricum, and 9 parts Actinidia chinensis root.

[0011] Analysis of Traditional Chinese Medicine Symptoms of Breast Cancer and Dyslipidemia and the Mechanism of Action of This Invention:

[0012] Traditional Chinese medicine (TCM) theory considers breast cancer to be a condition of "deficiency in the root and excess in the branch," where "pathogenic factors linger, and qi, blood, phlegm, and toxins stagnate and cause harm," accumulating in the breast area or the internal organs and meridians. It often manifests externally as "phlegm and blood stasis," but its root cause lies in "deficiency of vital qi" leading to "deficiency of both the spleen and kidneys." Professor Lu Deming, a nationally renowned TCM master and inheritor of the "Gu Family Surgery" lineage, believes that breast cancer patients often exhibit deficiency after surgery, radiotherapy, and chemotherapy, with few cases of excess. Therefore, he uses "strengthening the body's resistance while eliminating pathogenic factors" as the basic treatment principle. Years of clinical practice and experimental research have confirmed that this approach can improve patients' quality of life, reduce recurrence and metastasis, and prolong survival.

[0013] There is no precise TCM name for dyslipidemia, but based on its physiology, pathology, and common complications, it can be diagnosed and treated by referring to concepts such as dampness obstruction, phlegm retention, blood stasis, chest pain, and dizziness. TCM theory holds that dyslipidemia is related to "spleen dysfunction." Blood lipids, like nourishing blood and body fluids, are the refined substances transformed from food and water, distributed throughout the body, flowing through the blood vessels, warming the skin, and nourishing the internal organs. Once the spleen fails to function properly, it cannot ascend the clear qi, and the stomach cannot descend the turbid qi. Without proper separation of clear and turbid fluids, dampness accumulates, leading to stagnation of body fluids, which in turn forms turbidity, which then accumulates into phlegm. Phlegm enters the blood vessels, and phlegm and blood stasis combine, depositing in the vessels, thus forming hyperlipidemia. Therefore, dyslipidemia is often seen in people who overeat fatty and sweet foods, are obese, and lack exercise—those with an "imbalanced diet and activity." However, clinical observations have shown that even thin breast cancer patients often have dyslipidemia, and the "purgative method" represented by commonly used lipid-lowering drugs—such as lotus leaf, hawthorn, and alisma—is not very effective. This is because breast cancer patients often present with "qi deficiency and blood stasis." The byproducts of inadequate metabolism of food and water, namely "blood lipids," and the byproducts of tumor disease, namely "blood stasis," intertwine in the blood vessels. The mixture of lipids and blood increases blood viscosity, causing stagnation in the blood vessels and exacerbating blood stasis. Furthermore, breast cancer itself is inherently a deficiency of qi, which weakens the body's ability to propel blood circulation. Therefore, breast cancer patients are more prone to abnormal blood lipids, and over time, this can lead to atherosclerosis, vascular stenosis, coronary heart disease, angina pectoris, and other ASCVD (atherosclerotic cardiovascular disease) symptoms. Thus, abnormal blood lipids in breast cancer patients originate in the blood and stem from the spleen; therefore, treatment primarily focuses on tonifying the spleen qi, while also promoting blood circulation and unblocking the meridians. In the traditional Chinese medicine composition of this invention, Astragalus membranaceus invigorates the spleen and replenishes qi, while Rhodiola rosea invigorates qi, promotes blood circulation, and relieves pain. The two herbs work together to regulate qi and blood, serving as the principal herbs. Curcuma zedoaria promotes qi circulation, breaks up blood stasis, eliminates stagnation, and relieves pain, while Polygonatum sibiricum invigorates the spleen and benefits the kidney essence. The two herbs work together to both attack and tonify, serving as the assistant herbs. Actinidia chinensis root clears heat, detoxifies, invigorates blood, and reduces swelling, preventing prolonged stagnation from transforming into heat, serving as the adjuvant herbs. All the herbs work together to strengthen the body's resistance, consolidate the foundation, and promote the elimination of blood stasis.

[0014] Modern pharmacology has found that Rhodiola rosea can lower blood lipids by affecting cholesterol absorption, transport, and antioxidation. Its ethanol extract can significantly reduce TC, TG, and LDL-C in hyperlipidemic model mice and increase HDL-C content (Zhang Qianqian, Li Siqian, Zhou Lihong, et al. Research progress on the auto-oxidation and polymerization mechanism of small molecule phenolic acid components such as caffeic acid and their pharmacological activities [J]. Modern Chinese Materia Medica, 2021, 23(3):555-561.). Rhodiola rosea extract can effectively reduce the body weight of rats and improve blood glucose, blood pressure and blood lipid disorders in rats. After intervention with Rhodiola rosea extract, the expression of liver peroxisome proliferator-activated receptors (PPAR-α mRNA, PPAR-γ mRNA) increased. Since PPAR-γ is closely related to adipocyte differentiation, lipid metabolism, glucose metabolism, and inflammatory response, the effect of Rhodiola rosea extract in improving glucose and lipid metabolism disorders in metabolic syndrome may be related to the activation of PPAR-α and PPAR-γ receptors (Bremer AA, Mietus-Snyder M, Lustig R). H. Toward a unifying hypothesis of metabolic syndrome[J]. Pediatrics, 2012, 129(3): 557-570.). Curcuma zedoaria can achieve lipid-lowering and vascular-protective effects through multiple pathways. Among them, Curcuma zedoaria oil also has the effect of lowering blood lipids and inflammatory factors (Kim M, Kim Y. Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet[J]. Nutrition Research & Practice, 2010, 4(3): 191-195.). Polysaccharide of Polygonatum sibiricum can regulate the expression of lipid metabolism-related genes and proteins to lower lipids and reduce serum inflammatory factors IL-6 and TNF-α (Wang Li, Ji Zhe, Dong Li, et al. Regulatory effect of curcumin and / or aerobic exercise on intestinal function in rats with dyslipidemia[J]. Chinese Journal of Experimental Animals, 2022, 30(2): 208-215.). The root of *Actinidia chinensis* improves hyperlipidemia by increasing serum NO levels and decreasing ET levels, which indirectly confirms that these four herbs can intervene in dyslipidemia (Liu Xin, Niu Huimin, Gao Jie, et al. Effects of Curcuma zedoaria oil on blood lipids and inflammatory factors in atherosclerotic rats [J]. Modern Journal of Integrated Traditional and Western Medicine, 2016, 25(20): 2183-2185).

[0015] A second aspect of the present invention provides a method for preparing the traditional Chinese medicine composition as described above, comprising the following steps:

[0016] (1) Wash the Astragalus membranaceus, Rhodiola rosea, Curcuma zedoaria, Polygonatum sibiricum and Actinidia chinensis root separately, then dry, pulverize and sterilize them for later use;

[0017] (2) Weigh each raw material according to the weight proportions and mix them to obtain the Chinese medicine composition.

[0018] Furthermore, in step (1), the material is pulverized to 200 mesh and then sterilized for later use.

[0019] In a third aspect, the present invention provides the use of the traditional Chinese medicine composition as described above in the preparation of a medicament for improving breast cancer-related dyslipidemia.

[0020] Furthermore, the breast cancer-related dyslipidemia mentioned above refers to mild dyslipidemia, that is, the population for whom the guidelines recommend only exercise and lifestyle interventions without the need for statin treatment.

[0021] In a fourth aspect, the present invention provides a pharmaceutical preparation in which the traditional Chinese medicine composition described above is used as an active ingredient, wherein the pharmaceutical preparation is prepared in accordance with conventional methods for preparing traditional Chinese medicine to form a clinically acceptable conventional pharmaceutical preparation.

[0022] Furthermore, the dosage form of the pharmaceutical preparation is a decoction, pill, tablet, mixture, capsule, granule, powder, paste, or tea.

[0023] Furthermore, the pharmaceutical preparation also includes pharmaceutically acceptable conventional carriers or excipients.

[0024] Furthermore, the pharmaceutically acceptable conventional carriers or excipients include emulsifiers, fillers, binders, humectants, disintegrants, absorption enhancers, flavoring agents, colorants, and solubilizers.

[0025] In a fifth aspect, the present invention provides the use of the traditional Chinese medicine composition as described above in the preparation of foods, beverages, food additives, seasonings or health products that improve breast cancer-related dyslipidemia.

[0026] In a sixth aspect, the present invention provides a food, beverage, food additive or health product in which the traditional Chinese medicine composition described above is used as an active ingredient.

[0027] The advantages of this invention are:

[0028] 1. The traditional Chinese medicine composition of this invention precisely addresses the pathogenesis of qi deficiency and blood stasis after breast cancer surgery, with the entire formula working synergistically to invigorate qi, strengthen the body's resistance, and promote blood circulation. Animal experiments have demonstrated that the traditional Chinese medicine composition of this invention significantly reduces liver index, serum TG, TC, and LDL-C levels in hyperlipidemic mice, with effects comparable to statins. Clinical trials have also confirmed that the traditional Chinese medicine composition of this invention improves lipid indicators in patients with breast cancer and mild dyslipidemia, with high safety.

[0029] 2. The traditional Chinese medicine composition of the present invention has the effect of improving breast cancer-related dyslipidemia. It can be used to prepare various foods, beverages, seasonings, health products or medicines that improve dyslipidemia. It has no side effects, is well tolerated by patients, and is safe and effective.

[0030] 3. It is simple to prepare, inexpensive, and has excellent therapeutic effects, making it suitable for breast cancer patients at all stages of treatment to drink and consume. Attached Figure Description

[0031] Figure 1 Example 8: Schematic diagram of the research process for the clinical trial.

[0032] Figure 2 Liver index of mice in each group during animal experiments; Note: *: P < 0.05; **: P < 0.01.

[0033] Figure 3 Levels of TG, TC, DLD-C, and HDL-C in mice of different groups during animal experiments; Note: *: P < 0.05; **: P < 0.01; ***: P < 0.001; ****: P < 0.0001.

[0034] Figure 4 Lipid deposition in the liver tissue of mice in each group during animal experiments (Oil Red O staining, ×10).

[0035] Figure 5 The pathological morphology of liver tissue stained with HE in each group of mice in animal experiments (HE staining, ×20).

[0036] Figure 6 Changes in blood lipids in the two groups of patients in the clinical trial at weeks 0, 6, and 12; Note: ns: no statistically significant difference between the two groups at this time point; *: P < 0.05 between the two groups at this time point; △: P < 0.01 between the two groups at this time point.

[0037] Figure 7 Changes in body composition in the two groups of patients in the clinical trial at weeks 0, 6, and 12; Note: ns: no statistically significant difference between the two groups at this time point. Detailed Implementation

[0038] The specific implementation methods provided by the present invention will be described in detail below with reference to the embodiments.

[0039] Example 1: The Traditional Chinese Medicine Composition of the Present Invention (I)

[0040] It is composed of the following raw materials in parts by weight: Astragalus membranaceus 30 parts, Rhodiola rosea 30 parts, Curcuma zedoaria 15 parts, Polygonatum sibiricum 15 parts, and Actinidia chinensis root 9 parts.

[0041] Example 2: The Traditional Chinese Medicine Composition of the Present Invention (II)

[0042] It is composed of the following raw materials in parts by weight: Astragalus membranaceus 20 parts, Rhodiola rosea 20 parts, Curcuma zedoaria 10 parts, Polygonatum sibiricum 10 parts, and Actinidia chinensis root 6 parts.

[0043] Example 3: The Traditional Chinese Medicine Composition of the Present Invention (III)

[0044] It is composed of the following raw materials in parts by weight: 10 parts Astragalus membranaceus, 10 parts Rhodiola rosea, 6 parts Curcuma zedoaria, 6 parts Polygonatum sibiricum, and 3 parts Actinidia chinensis root.

[0045] Example 4: The Traditional Chinese Medicine Composition of the Present Invention (IV)

[0046] It is composed of the following raw materials in parts by weight: Astragalus membranaceus 6 parts, Rhodiola rosea 6 parts, Curcuma zedoaria 3 parts, Polygonatum sibiricum 3 parts, and Actinidia chinensis root 1.5 parts.

[0047] Example 5: The Traditional Chinese Medicine Composition of the Present Invention (V)

[0048] It is composed of the following raw materials in parts by weight: Astragalus membranaceus 12 parts, Rhodiola rosea 12 parts, Curcuma zedoaria 6 parts, Polygonatum sibiricum 6 parts, and Actinidia chinensis root 3 parts.

[0049] Example 6: Preparation of the herbal decoction of the present invention

[0050] Weigh each raw material according to the weight ratio described in any of Examples 1-5, pulverize them, add an appropriate amount of water, and decoct them using conventional methods.

[0051] Example 7: Preparation of the herbal tea composition of the present invention

[0052] Weigh each raw material according to the weight ratio described in any of Examples 1-5, mix them, pulverize them into coarse powder (use a 10-mesh sieve with a pore size of 1.74 mm during pulverization to reduce powder leakage from the filter and affect the taste) and make them into tea bags.

[0053] Instruct the patient to first steep the herbs in boiling water, let it stand for 30 seconds, then discard the tea (this is to remove impurities from the herbs). Next, steep the herbs in 400ml of boiling water, covering and letting it steep for 20-30 minutes while keeping warm (root and stem herbs require a longer steeping time to extract their active ingredients). The tea should be clear and orange-brown in color. The dosage is two cups per day, totaling 800ml, and can be taken at any time. Continue this treatment for 12 weeks, drinking it daily. During this period, the patient should not drink other teas (such as black tea, green tea, etc.).

[0054] Example 8: Animal experiments on the traditional Chinese medicine composition of the present invention

[0055] 1. Materials

[0056] 1.1 Laboratory Animals

[0057] Four SPF-grade female C57BL / 6 wild-type mice, C57BL / 6-APOC3 TG Twelve mice, 6 weeks old, weighing (20±2)g, were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., Animal Production License No.: SCXK(Su)2018-0008, and housed at the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine. The room temperature was (23±2)℃, the relative humidity was (60±5%)%, and the day and night cycle was 12h.

[0058] 1.2 Reagents and Instruments

[0059] Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) assay kits (Shanghai Enzyme-Link Biotechnology Co., Ltd., catalog number: ml076636); microplate reader, high-speed low-temperature centrifuge (Thermo Fisher Scientific, USA), upright biological microscope, and EG1150H+C embedding machine were all purchased from Leica, Germany; transmission electron microscope Talos L120CG2 (Bio-Rad, USA); KZ-III-FP high-speed low-temperature tissue homogenizer (Wuhan Saive Biotechnology Co., Ltd.).

[0060] 1.3 Drugs and Preparation

[0061] The traditional Chinese medicine composition of this invention (composed of 30g Astragalus membranaceus, 30g Rhodiola rosea, 15g Curcuma zedoaria, 15g Polygonatum sibiricum, and 9g Actinidia chinensis root) was purchased from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, affiliated with Shanghai University of Traditional Chinese Medicine. It was prepared using conventional methods: first, soaking the herbs in 10 times their volume of water for 30 minutes, then bringing to a boil over high heat and simmering for 40 minutes. The decoction was filtered through gauze, and then 8 times their volume of water was added, followed by another boil over high heat and simmering for 40 minutes. The decoction was then filtered through gauze. The two decoctions were combined, and the mixture was concentrated in a water bath to a concentration of 1.98g / ml of the original medicinal materials. The concentrate was then dispensed into 50mL centrifuge tubes and stored at 4°C. Atorvastatin calcium tablets (Lipitor, National Drug Approval Number J20171062, Pfizer Pharmaceuticals Co., Ltd., batch number H20051408) were also used.

[0062] 2 methods

[0063] 2.1 Modeling, grouping, and drug administration

[0064] After one week of free access to food and water, all mice were fed a normal diet for 8 weeks, followed by C57BL / 6 wild-type mice. TGMice were fed a high-fat diet (consisting of basal diet, 21% fat, and 0.15% cholesterol, purchased from Shanghai SLAC Laboratory Animal Co., Ltd.) for 8 weeks and then randomly divided into a model group, a treatment group using the traditional Chinese medicine composition of this invention, and a statin treatment group, with 4 mice in each group. The equivalent dose of the traditional Chinese medicine composition in the treatment group was determined according to the body surface area conversion between humans and animals and the guidance of the "Chinese Pharmacopoeia". The equivalent dose for mice is equivalent to 9.1 times that for humans, so the clinical equivalent dose of the traditional Chinese medicine composition of this invention administered to mice by gavage was 12.9 g / kg / d. The statin treatment group was administered atorvastatin 5 mg / kg / d by gavage. The normal group and the model group were administered an equal volume of physiological saline by gavage.

[0065] 2.2 Collection of serum and tissue specimens

[0066] After the intervention in mice, they were fasted for 12 hours before sampling, but given normal water intake. They were anesthetized with 2-3% isoflurane before sampling, and maintained with a 1.5-2% isoflurane mask for 2-3 minutes. Blood was collected by enucleation, allowed to stand at room temperature for 2 hours, and then centrifuged at low temperature (3000 rpm, 15 minutes, centrifugation radius 7 cm). The supernatant was collected for analysis. After the mice were euthanized, the abdominal cavity was opened with ethanol-sterilized surgical scissors, and the intact liver tissue was quickly removed, along with the gallbladder. A 6mm × 6mm liver tissue sample from the mid-segment of the hepatic lobe was placed in 4% paraformaldehyde fixative and stored at room temperature for HE staining and Oil Red O staining.

[0067] 2.3 Measurement of mouse body weight and liver index

[0068] During the experiment, the changes in mouse body weight were recorded every 4 days. After the experiment, the final body weight and liver weight of the mice were weighed, and the liver index was obtained according to the following formula: Liver index (%) = Liver weight (g) / Body weight (g) × 100%.

[0069] 2.4 Serum lipid assay

[0070] According to the kit instructions, the contents of TC, TG, LDL-C and HDL-C were detected using a fully automated biochemical analyzer.

[0071] 2.5 Hematoxylin and eosin (HE) staining and Oil Red staining for observing liver pathology

[0072] Mouse liver tissue fixed in 4% paraformaldehyde fixative was used to make paraffin sections (6μm) and frozen sections (8μm). The sections were stained with HE and Oil Red O, and the staining was observed under a microscope. The results were photographed and recorded.

[0073] 3 Results

[0074] 3.1 Effects of the traditional Chinese medicine composition of the present invention on body weight and liver index in hyperlipidemic mice

[0075] The liver index was calculated based on the body weight and liver tissue weight of the mice. The results showed that the liver index of the mice treated with the traditional Chinese medicine composition of this invention was significantly lower than that of the mice in the high-fat model group (P < 0.05), and comparable to that of the statin group (see Table 1). Figure 2 ).

[0076] Table 1 shows the body weight, liver weight, and liver index of mice in each group.

[0077]

[0078] 3.2 The traditional Chinese medicine composition of the present invention reduces serum lipid levels in hyperlipidemic mice.

[0079] The serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels of all mice were detected using a fully automated biochemical analyzer. The results showed that the blood lipid levels in the model group were significantly higher than those in the normal group (P < 0.05), indicating a successful establishment of a hyperlipidemia model. Simultaneously, compared to the model group, the TG, TC, and LDL-C levels in the treatment group using the traditional Chinese medicine composition of this invention were significantly reduced (P < 0.05), with efficacy similar to that of the statin group (see Table 2). Figure 3 ).

[0080] Table 2. Levels of TG, TC, DLD-C, and HDL-C in mice of each group.

[0081]

[0082]

[0083] 3.3 Comparison of lipid deposition in the livers of mice in different groups

[0084] Oil Red O staining results showed that no orange-red lipid droplets were observed in the hepatocytes of normal mice, while a large number of orange-red lipid droplets were deposited in the model group, indicating significant fatty degeneration. The statin group showed the most significant reduction in intrahepatic lipid droplets. The orange-red lipid droplets in the hepatocytes of mice treated with the herbal composition of this invention were also significantly reduced compared to the model group (see...). Figure 4 ).

[0085] 3.4 Comparison of liver morphology and HE staining in different groups of mice

[0086] In the normal group of mice, the liver lobule structure was clear and intact, cells were neatly arranged, nuclei were located centrally, cells showed no fatty degeneration, and no inflammatory cell infiltration was observed. In the model group of mice, cells were swollen and deformed, fatty degeneration was observed, vacuoles of varying sizes were seen, nuclei were located at the periphery, and inflammatory cell infiltration was visible. Compared with the liver tissue of the model group, the traditional Chinese medicine composition of this invention restored the liver lobule structure, and significantly reduced vacuolar degeneration and inflammatory cell infiltration (see...). Figure 5 ).

[0087] Example 9: Clinical Trial of the Traditional Chinese Medicine Composition of the Present Invention

[0088] 1. Materials and Methods

[0089] 1.1 Research Subjects

[0090] This study included 120 breast cancer patients with mild dyslipidemia admitted to the outpatient and inpatient departments of the Department of Breast Disease at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, between March and December 2023. All included cases were histologically or cytologically diagnosed with breast cancer. The staging criteria conformed to the 8th edition of the American Joint Committee on Cancer (AJCC) staging criteria for tumors. The diagnosis of mild dyslipidemia can be referenced in the following references: "Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults (2016 Revised Edition)" (Zhu Junren, Gao Runlin, Zhao Shuiping, et al. Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults (2016 Revised Edition) [J]. Chinese Journal of Circulation, 2016, 31(10): 937-953.), "ACC / AHA Cholesterol Guidelines (2018 Edition)" (Stone NJ, Greenland P, Grundy S M. Strin Usage in Primary Prevention - Comparing the USPSTF Recommendations With the AHA / ACC / Multisociety Guidelines [J]. JAMA Cardiology, 2022, 7(10): 997-999.), and "Expert Recommendations on Lipid-Lowering Therapy to Reduce Cardiovascular Events under the China Cholesterol Education Program (2019)" (China Cholesterol Education Program Working Committee, China International Exchange and Promotion Association for Medical and Health Care, Atherosclerosis and Thrombosis Prevention and Control Branch, Chinese Gerontology and Geriatrics Society Cardiovascular Disease Branch, et al.). al. Expert recommendations from the China Cholesterol Education Program on lipid-lowering therapy to reduce cardiovascular events (2019) [J]. Chinese Journal of Internal Medicine, 2020, 059(001):18-22.), individuals without ASCVD (including acute coronary syndrome, stable coronary artery disease, post-revascularization, ischemic cardiomyopathy, ischemic stroke, transient ischemic attack, peripheral artery atherosclerosis, etc.) and diabetic patients aged 40 years and above, who meet one of the following criteria, can be diagnosed with mild dyslipidemia: 1. TG ≥ 1.7 mmol / L and < 5.6 mmol / L; 2. TC ≥ 5.2 mmol / L and < 7.2 mmol / L; 3. LDL-C ≥ 3.4 mmol / L and < 4.9 mmol / L; 4. HDL-C < 1.0 mmol / L.

[0091] 1.2 Discharge Standards

[0092] 1.2.1 Inclusion Criteria

[0093] ① Female, aged ≥18 years and ≤70 years; ② Post-breast cancer surgery with histopathological confirmation of malignant breast tumor; ③ Expected to maintain the same breast cancer-related treatment regimen during the study (e.g., chemotherapy from enrollment to the end of intervention); ④ Meeting the diagnostic criteria for mild dyslipidemia after fasting blood test; ⑤ Discontinued lipid-lowering medication for more than two weeks if previously receiving such medication; ⑥ Patients must understand and agree to participate in this study and sign an informed consent form.

[0094] 1.2.2 Exclusion Criteria

[0095] ① Patients with severe circulatory, respiratory, digestive, hematologic, urinary, nervous, or endocrine system diseases, such as acute myocardial infarction, heart failure, renal insufficiency, acute cerebral infarction, lupus erythematosus, etc., whose other systemic diseases researchers believe will affect the results of this study; ② Patients with diseases affecting lipid metabolism, such as thyroid disease, gout, diabetes, etc.; ③ Patients who have taken drugs affecting lipid metabolism such as β-blockers, corticosteroids, thiazide diuretics, statins, fibrates, etc. in the past two weeks; ④ Patients who have been regularly taking other traditional Chinese medicines in the past two weeks; ⑤ Patients with distant metastases of breast cancer; ⑥ Patients with any other malignant tumors; ⑦ Patients with a family history of hyperlipidemia; ⑦ Patients who are allergic to the traditional Chinese medicine composition of this invention, including Rhodiola rosea, Polygonatum sibiricum, Curcuma zedoaria, or Actinidia chinensis root; ⑧ Patients with mental illness, speech disorders, or who are unable to cooperate with the study or refuse blood draws for other reasons; ⑨ Patients who participated in other clinical trials within two weeks prior to or during the same period of enrollment; ⑩ Patients who are pregnant or breastfeeding.

[0096] 1.3 Intervention Measures

[0097] All enrolled patients were randomly assigned to the intervention group and the control group at a 1:1 ratio. The specific intervention measures are as follows:

[0098] ① Intervention Group: Patients continued their breast cancer-related treatment and received the herbal composition of this invention. The herbal composition of this invention consists of 6 parts Astragalus membranaceus, 6 parts Rhodiola rosea, 3 parts Curcuma zedoaria, 3 parts Polygonatum sibiricum, and 1.5 parts Actinidia chinensis root, provided uniformly by the pharmacy of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine. The above-mentioned herbal raw materials were processed into coarse powder (a 10-mesh sieve with an aperture of 1.74 mm was used during pulverization to reduce powder leakage from the filter and affect the taste) and made into tea bags. Instruct the patient to first steep the herbs in boiling water, let it stand for 30 seconds, then discard the tea (to remove impurities from the herbs). Next, steep the herbs in 400ml of boiling water and drink it as a tea substitute. Keep the tea warm and cover for 20-30 minutes (root and stem plants should be steeped for a longer time to extract the active ingredients). The tea should be clear and orange-brown in color. The dosage is 2 cups per day, with a total water volume of 800ml. It can be taken at any time and should be continued for 12 weeks. During this period, the patient should not drink other teas (such as black tea, green tea, etc.) and should record the daily consumption.

[0099] ② Control group: Patients continued to receive breast cancer-related treatment without other drug interventions.

[0100] Both groups of patients will receive health education twice during the observation period, once upon enrollment and once at the follow-up examination 6 weeks after treatment. The education will cover diet and exercise, and will be conducted by members of the research team. All members will study the education content in advance.

[0101] Health education is defined as follows:

[0102] According to the "Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults (2016 Revised Edition)," patients are advised to maintain a reasonable dietary structure, ensure nutritional balance, and guarantee the intake of vegetables, fruits, and legumes. Eggs should be consumed in moderation, and fat intake should be controlled. It is recommended that daily cholesterol intake be less than 300mg, and daily cooking oil intake less than 30g. Fat intake should prioritize foods rich in n-3 polyunsaturated fatty acids (such as deep-sea fish, fish oil, and vegetable oil). Daily carbohydrate intake should account for 50%-65% of total energy. Choose carbohydrates rich in dietary fiber and with a low glycemic index to replace saturated fatty acids. Daily diet should include 25-40g of dietary fiber (7-13g of which should be water-soluble). Carbohydrate intake should mainly consist of grains, tubers, and whole grains. Added sugar intake should not exceed 10% of total energy. Avoid high-sugar and fried foods, such as fried chicken, desserts, and other processed foods. Limit alcohol consumption (10-20g per day) and smoking. For individuals with a BMI exceeding 23.9, it is advised to reduce daily total energy intake by 300-500kcal. Meanwhile, considering the patient's individual condition, it is recommended that they engage in appropriate aerobic and anaerobic exercise, such as yoga, dance, brisk walking, and fitness exercises. It is suggested that they engage in moderate-intensity metabolic exercise for 30 minutes, 5-7 days a week. During this period, patients are advised not to self-medicate with lipid-lowering drugs, including but not limited to statins and traditional Chinese medicine (such as Xuezhikang). Mild dyslipidemia can often be regulated by adjusting diet, increasing exercise, and improving lifestyle habits.

[0103] 1.4 Research Steps

[0104] Following the inclusion and exclusion criteria of this study, after obtaining written informed consent from patients, randomization was completed. Patients in the intervention group received oral Chinese herbal tea treatment on day 1 after enrollment, with a treatment course of 12 weeks. Both groups received health education. Fasting blood samples were collected before treatment, and at weeks 6 and 12 after treatment, according to the study design (patients should have fasted for at least 8 hours before blood collection). Blood lipids and inflammatory markers were measured to assess the risk stratification of ASCVD. Patients' body mass index (BMI) and body fat data were measured. Patients' diet and exercise status were followed up. During the study, basic patient information and test results were collected according to the study design.

[0105] 1.4.1 General Data Collection

[0106] Demographic information collected includes patient name, gender, phone number, ID number, and age. Information on chronic diseases, menstrual history, and breast cancer details (including surgical procedure, pathological stage, and pathological type) is collected from the medical history system. Face-to-face surveys are conducted to investigate education level, dietary habits, and exercise. Dietary inquiries include the frequency and types of meat, fish, eggs, vegetables, fruits, and legumes consumed weekly. Exercise surveys include the type of exercise (e.g., Tai Chi, square dancing, walking), duration, and frequency. According to the relevant standards of the "Healthy China Action (2019-2030)," those who exercise 3 or more times per week, for 30 minutes or more each time, for 1 year or more, are considered to have a regular exercise habit.

[0107] 1.4.2 Blood Sample Collection and Processing

[0108] All patients were required to maintain a light diet the day before testing, and to abstain from food and drink after 8 PM. Fasting blood samples were collected the following day. Heparin sodium anticoagulant blood collection tubes were mixed thoroughly and sent for testing immediately. If immediate testing was not possible, the samples were stored at 4°C and sent for testing within 24 hours. Any remaining samples after testing were disposed of according to biological sample handling regulations.

[0109] 1.4.3 Blood Sample Testing

[0110] All peripheral blood samples underwent testing for lipid levels, safety indicators, and ENPP1 and PTPN11.

[0111] The specific lipid indicators are as follows: TC is detected using an enzymatic method; TG is detected using the GPO·POD method; LDL-C and HDL-C are detected using a direct method; small dense low-density lipoprotein cholesterol (sdLDL-C) is detected using a peroxidase method; apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and apolipoprotein E (ApoE) are detected using immunoturbidimetry; and lipoprotein(a) (Lp(a)) is detected using latex immunoturbidimetry. Safety indicators include: complete blood count and liver and kidney function tests.

[0112] 1.4.4 Human body composition analysis

[0113] The Fitpro intelligent human body analyzer (model: GS6.5B) was used, which complies with the "Quality Control Specifications for Human Composition Analysis Technology in Health Examinations (Trial)". Height and weight data were collected to calculate BMI. The calculation formula is: BMI = weight (kg) / height squared (m2). Body fat, body fat percentage, waist-to-hip ratio, subcutaneous fat percentage, and visceral fat index were calculated through contact electrodes and multi-frequency bioelectrical impedance analysis technology.

[0114] 1.4.5 Electrocardiogram and echocardiography

[0115] ① Electrocardiogram (ECG): The patient remains supine, and an ECG machine is used to capture the changes in the patient's heartbeat over 30 seconds. ② Echocardiography: The patient lies supine or on their left side, and a radiologist performs a standard transthoracic echocardiogram, switching the machine probe to the cardiac probe to examine the heart in various planes and assess overall cardiac contractile function.

[0116] 1.5 Observation Indicators

[0117] 1.5.1 Key Observation Indicators

[0118] The overall effective rate in the criteria for evaluating the efficacy of lipid-improving treatment is as follows: TC, TG, and LDL-C reduction rate = (before medication - after medication) / before medication × 100%; HDL-C increase rate = (after medication - before medication) / before medication × 100%; and the overall effective rate = (number of cases with significant effect + number of cases with effect) / total number of cases included × 100%.

[0119] 1.5.2 Secondary observation indicators

[0120] ① Changes in blood lipid levels, including TC, TG, LDL-C, HDL-C, sdLDL-C, ApoA1, ApoB, ApoE, and Lp(a). ② Changes in ENPP1 and PTPN11 levels and their correlation with blood lipid indicators. ③ BMI, body fat, body fat percentage, waist-to-hip ratio, subcutaneous fat percentage, and visceral fat index.

[0121] 1.5.3 Security Indicators:

[0122] Complete blood count, liver and kidney function tests, electrocardiogram, and echocardiogram.

[0123] 1.6 Efficacy Evaluation Criteria

[0124] According to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs in the Treatment of Hyperlipidemia" (Zheng Xiaoyu. Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs: Trial Implementation [M]. Beijing: China Medical Science and Technology Press, 2002: 77-85.), the criteria for judging the efficacy of lipid-lowering drugs are as follows:

[0125] ① A significant effect can be defined as the achievement of any of the following blood lipid tests after treatment: TC decrease ≥20%; TG decrease ≥40%; HDL-C increase ≥0.26mmol / L; LDL-C decrease ≥20%.

[0126] ② The treatment is considered effective if any of the following blood lipid tests are achieved after treatment: TC decreases by <20% and ≥10%; TG decreases by <40% and ≥20%; HDL-C increases by <0.26mmol / L and ≥0.104mmol / L; LDL-C decreases by <20% and ≥10%.

[0127] ③ Ineffective: Those whose blood lipid levels do not meet the above standards after treatment.

[0128] 1.7 Statistical Methods

[0129] All collected data were processed using SPSS 26.0 statistical software. Quantitative data were first tested for normality; if the data conformed to a normal distribution, the mean ± standard deviation was used. This indicates that repeated measures analysis and independent samples t-tests are used when homogeneity of variance is satisfied. In repeated measures ANOVA, if the Mauchly test does not meet the sphericity assumption, the data corrected by the Greenhouse-Geisser method are used; if there is no interaction effect between time and the intervention factor, the main effect test is used; if there is an interaction effect, further individual effect analysis is performed. If the distribution does not conform to normality, the median (25th percentile, 75th percentile) is used to describe the data, and generalized estimating equations (GEE) analysis and nonparametric tests are used. In GEE analysis, if there is no interaction effect between time and the intervention factor, the main effect test is used; if there is an interaction effect, further individual effect analysis is performed. For correlation analysis between two groups of quantitative indicators, Pearson product-moment correlation coefficient or Spearman rank correlation coefficient is used; for categorical data, the number of cases and percentages are used to describe the data; and the chi-square test is used for comparisons between groups. A p-value > 0.05 indicates no statistical significance, and a p-value < 0.05 indicates a statistically significant difference.

[0130] 2. Research Results

[0131] 2.1 Comparison of lipid-lowering efficacy before and after treatment

[0132] In the control group, 33 cases showed significant improvement, 10 cases showed improvement, and 17 cases showed no improvement, with a total effective rate of 71.67%. In the intervention group, 43 cases showed significant improvement, 10 cases showed improvement, and 7 cases showed no improvement, with a total effective rate of 88.33% (see Table 3). Pearson's card test showed a statistically significant difference between the two groups in improving blood lipid levels (P = 0.020 < 0.050), with the total effective rate in the intervention group being significantly higher than that in the control group, indicating that the traditional Chinese medicine composition of this invention has the effect of improving blood lipid levels.

[0133] Table 3 Comparison of lipid-lowering efficacy before and after treatment in the two groups [n(%)]

[0134]

[0135] 2.2 Comparison of blood lipid levels before and after treatment

[0136] Normality and homogeneity of variance tests were performed on various lipid indicators at different time points in both groups of patients. TG and Lp(a) did not meet the normal distribution requirement, while all other indicators met the requirements of normal distribution and homogeneity of variance. TC, LDL-C, HDL-C, and sdLDL-C did not meet the sphericity test, so the results corrected in the Greenhouse-Geisser model were used. ApoA1, ApoB, and ApoE met the sphericity test. TG and Lp(a) were determined based on the model effect test results. The time effect, between-group effect, and interaction effect results for all lipid indicators are shown in Table 4. The interaction effects of TC, TG, LDL-C, sdLDL-C, ApoA1, and ApoB were significant (P < 0.05), so separate effect analyses were performed.

[0137] HDL-C levels showed no significant changes in either group at any time point (Ftime = 0.548, P = 0.562), and there was no difference in HDL-C between the two groups (Fbetween = 1.194, P = 0.277). Lp(a) levels showed a decreasing trend in both groups (Ftime = 6.95, P = 0.031), however, there was no difference in the effect on reducing Lp(a) between the two groups (Fbetween = 0.357, P = 0.55). ApoE levels showed a decreasing trend in both groups (Ftime = 4.035, P = 0.019), and there was a difference in the effect on reducing ApoE between the two groups, but the difference was not significant (Fbetween = 4.198, P = 0.043).

[0138] Simple effect analysis between groups showed that: (1) the TC levels in the control group were 5.77±0.55 mmol / L and 5.33±0.67 mmol / L at weeks 6 and 12 after intervention, respectively, while those in the intervention group were 5.57±0.64 mmol / L and 5.12±0.82 mmol / L. The decrease in TC in the intervention group after 12 weeks of intervention was statistically different from that in the control group, with a more significant decrease in TC (P<0.05); (2) the TG levels in the control group were 1.52 (1.10, 2.01) mmol / L and 1.43 (1.17, 2.02) mmol / L at weeks 6 and 12 after intervention, respectively. The intervention group had 1.47 (1.08, 2.02) mmol / L and 1.27 (1.06, 1.62) mmol / L, respectively. The intervention group showed a statistically significant difference in the degree of decrease compared with the control group after 12 weeks of intervention, with a more significant decrease in TG in the intervention group (P<0.05); (3) The control group had 4.07±0.50 mmol / L and 3.94±0.53 mmol / L at weeks 6 and 12 after intervention, respectively, while the intervention group had 3.88±0.51 mmol / L and 3.57±0.69 mmol / L, respectively. The intervention group showed a statistically significant difference in the degree of decrease compared with the control group at different time points. The decrease in LDL-C was more significant in the intervention group (P<0.05); (4) The sdLDL-C levels in the control group were 1.16±0.34mmol / L and 1.20±0.28mmol / L at weeks 6 and 12 after intervention, respectively, while those in the intervention group were 1.10±0.43mmol / L and 0.94±0.34mmol / L. The decrease in sdLDL-C in the intervention group after 12 weeks of intervention was statistically different from that in the control group, with a more significant decrease in sdLDL-C in the intervention group (P<0.05); (5) The ApoA1 levels in the control group were 1.30±0.31g / L and 1.30±0.28g / L at weeks 6 and 12 after intervention, respectively. The ApoA1 levels in the intervention group were 1.31±0.27 g / L and 1.17±0.31 g / L, respectively. The decrease in ApoA1 levels in the intervention group after 12 weeks of intervention was statistically different from that in the control group, with a more significant decrease in ApoA1 levels in the intervention group (P<0.05). (6) The ApoB levels in the control group were 1.15±0.20 g / L and 1.12±0.20 g / L in the 6th and 12th weeks after intervention, respectively, while those in the intervention group were 1.13±0.19 g / L and 1.02±0.20 g / L, respectively. The decrease in ApoB levels in the intervention group after 12 weeks of intervention was statistically different from that in the control group, with a more significant decrease in ApoB levels in the intervention group (P<0.05), as shown in Table 5.

[0139] The Bonferroni method was used to compare data at three time points in both the intervention and control groups. Simple effect analysis within the groups showed that: (1) Total TC (TC) decreased over time in both groups. The decrease in TC in the control group was not significant between 6 and 12 weeks after intervention (P>0.05), while the decrease in TC in the intervention group was statistically significant at all time points (P<0.01); (2) There was no statistically significant change in total TG (TG) over time in the control group (P>0.05), while the decrease in TG in the intervention group after 12 weeks of intervention was statistically significant compared to the previous two time points (P<0.05); (3) There was no statistically significant change in LDL-C over time in the control group (P>0.05), while the decrease in TG in the intervention group was statistically significant at 12 weeks after intervention compared to the previous two time points (P<0.05); (3) The decrease in sdLDL-C after 12 weeks of intervention was statistically significant compared with the first two time points (P<0.05); (4) There was no statistically significant difference in sdLDL-C over time in the control group (P>0.05), while the decrease in sdLDL-C in the intervention group was statistically significant at each time point (P<0.05); (5) There was no statistically significant difference in ApoA1 over time in the control group (P>0.05), while the decrease in ApoA1 after 12 weeks of intervention was statistically significant compared with the decrease after 6 weeks of intervention (P<0.05); (6) There was no statistically significant difference in ApoB over time in the control group (P>0.05), while the decrease in ApoB in the intervention group was statistically significant at each time point (P<0.01).

[0140] In summary, both groups showed a decreasing trend in TC, TG, LDL-C, sdLDL-C, ApoA1, ApoB, ApoE, and Lp(a) over time. The intervention group demonstrated superior improvement in TC, TG, LDL-C, sdLDL-C, ApoA1, ApoB, and ApoE compared to the control group. Neither group showed significant improvement in HDL-C. Figure 6 .

[0141] Table 4. Results of repeated measurements of blood lipid levels

[0142]

[0143] Table 5. Changes in blood lipid levels at different time points in the two groups of patients.

[0144]

[0145]

[0146] Table 5 (continued) shows the changes in blood lipid levels at different time points in the two groups of patients.

[0147]

[0148] Note: *: The change in this indicator compared to the previous time point is P < 0.05; △: The change in this indicator compared to the previous time point is P < 0.01.

[0149] 2.3 Human body composition analysis

[0150] Normality and homogeneity of variance tests were performed on all body composition indicators at each time point for both groups of patients. BMI and subcutaneous fat percentage did not meet the normal distribution requirement, while all other indicators met both. Weight, body fat percentage, body fat mass index, visceral fat index, and waist-to-hip ratio did not meet the sphericity test; therefore, the results corrected in the Greenhouse-Geisser model were used. BMI and subcutaneous fat percentage were determined based on model effect tests. The time effects, between-group effects, and interaction effects of all body composition indicators are shown in Table 6. The interaction effect of subcutaneous fat percentage was significant (P < 0.001), therefore a separate effect analysis was performed, as shown in Table 6.

[0151] The time effect of subcutaneous fat percentage was significant in both groups (P<0.001), indicating a difference in the change of subcutaneous fat percentage between the two groups at different time points. The time and inter-group effects of waist-to-hip ratio were not significant (P>0.05), indicating no statistically significant differences between or within the two groups at any time point (P>0.05). There were no significant changes in body fat percentage and waist-to-hip ratio in either group at any time point (P>0.05), and no statistically significant differences were found between the two groups (P>0.05). Weight, BMI, body fat, subcutaneous fat percentage, and visceral fat index all showed a decreasing trend over time in both groups (P<0.05), but there were no statistically significant differences between the two groups (P>0.05). (See Table 7). Figure 7 .

[0152] In conclusion, the intervention group showed no significant advantage over the control group in terms of improvement in body composition.

[0153] Table 6 Results of Repeated Measurements of Human Body Composition

[0154]

[0155] Table 7 Changes in body composition at different time points in the two groups of patients.

[0156]

[0157]

[0158] Table 7 (Continued) shows the changes in body composition of the two groups of patients at different time points.

[0159]

[0160] Note: *: The change in this indicator compared to the previous time point is P < 0.05; △: The change in this indicator compared to the previous time point is P < 0.01.

[0161] 2.4 Security Analysis

[0162] During this study, blood routine tests, liver and kidney function, electrocardiogram, echocardiogram and other indicators were evaluated for all enrolled patients before and after treatment. No adverse reactions such as allergies, chest tightness, palpitations, nausea and vomiting, acute liver and kidney damage or cardiac damage occurred in any of the patients, indicating that the traditional Chinese medicine composition of the present invention is safe for treating patients with breast cancer and mild dyslipidemia (see Table 8).

[0163] Table 8 Clinical safety evaluation [cases (%)]

[0164]

[0165] 3 Discussion

[0166] Breast cancer is one of the most common malignant tumors among women. The pathogenesis of breast cancer is closely related to estrogen. After estrogen binds to ER, it further activates downstream signaling pathways by regulating the transcription of specific target genes, ultimately inducing the differentiation and proliferation of breast cancer cells. Multiple studies have shown that hyperlipidemia is closely related to the recurrence and progression of breast cancer, and the risk of cardiovascular disease death induced by dyslipidemia is also high in breast cancer patients (Li Ruiqing, Chen Jiejing, Du Jialing, et al. Correlation analysis of blood lipid levels in triple-negative and hormone receptor-positive breast cancer patients [J]. Chinese Journal of Cancer Prevention and Treatment, 2018, 25(11):799-802.). Although dyslipidemia has no obvious symptoms in its early stages, it should be taken seriously. Early detection and intervention have considerable clinical significance for the prognosis of breast cancer patients.

[0167] Indicators related to lipid metabolism mainly include serum lipids and lipoproteins. Serum lipids include total cholesterol (TC), triglycerides (TG), phospholipids, and free fatty acids (FFA). Lipoproteins are the forms in which blood lipids exist, are transported, and are metabolized. Among them, high-density lipoprotein (HDL) is the group of lipoproteins with the highest particle density in serum. Its main function is to transport cholesterol from tissues outside the liver to the liver for metabolism. Increased HDL levels are beneficial for peripheral tissues to clear cholesterol, while low-density lipoprotein (LDL) is a cholesterol-rich lipoprotein. The protein portion of lipoproteins is called apolipoprotein. Apolipoprotein A is the main structural protein of HDL, and apolipoprotein B is the most abundant protein in LDL. Research results show that after intervention with the traditional Chinese medicine composition of this invention, the blood lipid levels were significantly lower than those of the control group, especially the levels of TC, LDL-C, and sdLDL-C. After health education alone, although the patients' blood lipid indicators improved compared to before, the improvement was not significant, including TG, sdLDL-C, and apolipoproteins. Therefore, the traditional Chinese medicine composition of this invention can effectively reduce the overall blood lipid levels in breast cancer patients.

[0168] Dietary control and increased exercise are important interventions for the prevention and treatment of cardiovascular diseases. The National Cholesterol Education Program (NCEP) in the United States recommends that diet and exercise therapy should be the first line of treatment for patients with dyslipidemia. Diet control combined with exercise therapy has a significant therapeutic effect on 90% of patients with dyslipidemia. (Bard-Chapeau EA, Li S, Ding J, et al. Ptpn11 / Shp2acts as a tumor suppressor in hepatocellular carcinogenesis[J]. Cancer Cell, 2011, 19(5): 629-639. Qiao S, Wang T, Wang H. Dysregulated ceramides metabolism via PTPN11 exposes a metabolic vulnerability to breast cancer metastasis[J]. Med Oncol, 2023, 40(11): 310. Jamshidi Y, Gooljar SB, Snieder H, et al. SHP-2 and PI3-kinase genes PTPN11 and PIK3R1 may influence serum apoB and LDL cholesterol levels in normalwomen[J].Atherosclerosis,2007,194(2):e26-33). A large amount of clinical data and epidemiological surveys show that lack of physical exercise or a sedentary lifestyle is closely related to the occurrence of cardiovascular diseases. Lack of physical activity is one of the important risk factors for coronary heart disease. Less physical activity or a poor level of physical activity is associated with a higher incidence and mortality of coronary heart disease.Exercise can affect lipid metabolism through multiple pathways and mechanisms (Hendriks WJ, Pulido R. Proteinyrosine phosphatase variants in human hereditary disorders and diseasesusceptibilities[J]. Biochim Biophys Acta, 2013, 1832(10): 1673-1696. Libby P, Bornfeldt KE, Tall AR. Atherosclerosis: Successes, Surprises, and Future Challenges[J]. Circ Res, 2016, 118(4): 531-534.). Based on general patient information, most women with breast cancer and dyslipidemia are currently in the perimenopausal period and lack awareness of the importance of exercise. Health education can help strengthen self-management and improve treatment adherence in patients with dyslipidemia, which is beneficial for regulating lipid levels (Herrington W, Lacey B, Sherliker P, et al. Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease[J]. Circ Res, 2016, 118(4): 535-546.). The combination of health education and medication is currently the main approach to lowering lipids.

[0169] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

Claims

1. A traditional Chinese medicine composition for improving breast cancer complicated with mild dyslipidemia, characterized in that, It is composed of the following ingredients in parts by weight: Astragalus membranaceus 6-30 parts, Rhodiola rosea 6-30 parts, Curcuma zedoaria 3-15 parts, Polygonatum sibiricum 3-15 parts, and Actinidia chinensis root 1.5-9 parts.

2. The traditional Chinese medicine composition for improving breast cancer complicated with mild dyslipidemia according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: Astragalus membranaceus 6-12 parts, Rhodiola rosea 6-12 parts, Curcuma zedoaria 3-6 parts, Polygonatum sibiricum 3-6 parts, and Actinidia chinensis root 2-3 parts.

3. The traditional Chinese medicine composition for improving breast cancer complicated with mild dyslipidemia according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: Astragalus membranaceus 6 parts, Rhodiola rosea 6 parts, Curcuma zedoaria 3 parts, Polygonatum sibiricum 3 parts, and Actinidia chinensis root 1.5 parts.

4. The traditional Chinese medicine composition for improving breast cancer complicated with mild dyslipidemia according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 12 parts Astragalus membranaceus, 12 parts Rhodiola rosea, 6 parts Curcuma zedoaria, 6 parts Polygonatum sibiricum, and 3 parts Actinidia chinensis root.

5. The traditional Chinese medicine composition for improving breast cancer complicated with mild dyslipidemia according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: Astragalus membranaceus 30 parts, Rhodiola rosea 30 parts, Curcuma zedoaria 15 parts, Polygonatum sibiricum 15 parts, and Actinidia chinensis root 9 parts.

6. The use of a traditional Chinese medicine composition as described in any one of claims 1-5 in the preparation of a medicament for improving breast cancer complicated with mild dyslipidemia.

7. A pharmaceutical preparation in which the traditional Chinese medicine composition as described in any one of claims 1-5 is used as the active ingredient, characterized in that, The pharmaceutical preparation described herein is prepared according to conventional methods for the preparation of traditional Chinese medicine, resulting in a clinically acceptable conventional pharmaceutical preparation.

8. The pharmaceutical preparation according to claim 7, characterized in that, The dosage forms of the pharmaceutical preparations are decoctions, pills, tablets, mixtures, capsules, granules, powders, ointments, and teas.

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