Traditional Chinese medicine composition for treating phlegm-blood stasis type hyperlipemia with carotid atherosclerotic plaque as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to a traditional Chinese medicine composition for treating phlegm-blood stasis type hyperlipemia with carotid atherosclerotic plaque as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10-20 parts of ginger processed pinellia; 5-15 parts of pericarpium citri reticulatae; 10-20 parts of poria cocos; 10-20 parts of radix salviae miltiorrhizae; 10 to 20 parts of pollen typhae; 10-20 parts of polygonum cuspidatum; 5-15 parts of rhizoma alismatis; 10-20 parts of lotus leaves; 10 to 20 parts of raw hawthorn; and 4-8 parts of honey-fried licorice root. Compared with the prior art, the traditional Chinese medicine composition modified Erchen pollen typhae decoction is prepared from Erchen decoction through melting and cutting, medicines such as the pollen typhae, the radix salviae miltiorrhizae, the rhizoma polygoni cuspidati, the rhizoma alismatis, the lotus leaves and the raw hawthorn fruits are added on the basis of the Erchen decoction, and the effects of promoting blood circulation to remove blood stasis, lowering lipid and reducing phlegm are enhanced.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type, its preparation method and application. Background Technology

[0002] Er Chen Tang is a classic Chinese medicine formula, originating from the Song Dynasty official compilation, *Taiping Huimin Heji Jufang*. It consists of Pinellia ternata, Citrus reticulata peel, Poria cocos, prepared licorice root, ginger, and dried plum. It has the effects of drying dampness and resolving phlegm, regulating qi and harmonizing the stomach, and is a core formula for the clinical diagnosis and treatment of phlegm-dampness syndrome. Er Chen Tang is a classic Chinese medicine formula, hailed as the "first formula for treating phlegm," and is commonly used to treat diseases caused by internal obstruction of phlegm and dampness.

[0003] Dong Luga [1] and Li Xiaofang [2] Studies by researchers have shown that Er Chen Tang and its modified formulas have certain clinical effects in treating hyperlipidemia, but most observations have focused on hyperlipidemia of the phlegm-dampness obstruction type. (Dong Luga) [1] The study selected a TCM syndrome pattern of phlegm obstructing the heart vessels and did not observe changes in atherosclerotic plaques before and after treatment. (Li Xiaofang) [2] The study did not indicate which TCM syndrome type of hyperlipidemia was most effective for Er Chen Tang, nor did it observe the changes in atherosclerotic plaques before and after treatment.

[0004] With the improvement of people's living standards, dietary structures have undergone significant changes, with high-oil, high-fat, and high-sugar diets becoming increasingly common. Coupled with the expanding sedentary office workforce, this has led to a significant increase in the incidence of hyperlipidemia with atherosclerosis, showing a clear trend towards affecting younger people. Hyperlipidemia with carotid atherosclerosis can be diagnosed in Traditional Chinese Medicine (TCM) based on the main clinical symptoms as "dizziness," "headache," "stroke," and "pulse obstruction," etc. It is often caused by factors such as aging, emotional stress, overwork, internal injury, sedentary lifestyle, and irregular diet, leading to dysfunction of the spleen's function of ascending clear qi and descending turbid qi. This results in the formation of pathological products such as phlegm and blood stasis. Phlegm and blood stasis adhere to the blood vessels, accumulating into lumps that form atherosclerotic plaques. Clinical treatment should follow the principle of treating both phlegm and blood stasis simultaneously. This involves addressing the root cause by resolving phlegm and dampness, clearing turbidity and lowering lipids, while addressing the symptoms by promoting blood circulation, removing blood stasis, and clearing the meridians to eliminate plaques, thus resolving phlegm and blood stasis and restoring unobstructed blood flow. Currently, the main focus of the prescription is on hyperlipidemia or arteriosclerosis caused by phlegm-dampness obstruction. There is an urgent need to find an effective prescription for hyperlipidemia with carotid atherosclerosis caused by phlegm-blood stasis.

[0005] Phlegm-blood stasis type hyperlipidemia with carotid atherosclerosis mainly involves the following groups: people with long-term high-oil, high-fat, and high-sugar diets, people who drink excessively, sedentary office workers, elderly people with very little exercise, people with ischemic dizziness and headaches, obese people, and people with long-term high mental stress.

[0006] Chinese Patent CN102973817A discloses a traditional Chinese medicine compound preparation for treating atherosclerosis and its preparation method. The herbal ingredients of this preparation, by weight, are: 80-120 parts raw Astragalus membranaceus, 20-50 parts deer antler, 80-120 parts Panax notoginseng, 80-120 parts Ligusticum chuanxiong, 30-80 parts Gastrodia elata, 30-60 parts processed Polygonum multiflorum, 20-40 parts Citrus medica, 80-120 parts ginger-processed Pinellia ternata, 90-120 parts Arisaema cum bile, 40-60 parts Psoralea corylifolia, 120-180 parts Rehmannia glutinosa, 30-50 parts Acanthopanax senticosus, 40-60 parts Paeonia lactiflora, 30-60 parts Pueraria lobata, 40-50 parts Angelica sinensis, 280-300 parts Portulaca oleracea, and 40-50 parts Crataegus pinnatifida. This patented preparation can lower serum total cholesterol, triglycerides, and low-density lipoprotein, thereby reducing atherosclerotic plaques. In Traditional Chinese Medicine (TCM), atherosclerosis falls under the categories of "dizziness," "headache," and "pulse obstruction," with diverse syndrome types, such as phlegm-dampness obstruction, liver and kidney yin deficiency, and liver yang hyperactivity. This patent attempts to solve all problems with a single formula, violating the core principle of TCM's "syndrome differentiation and treatment." A patient with liver yang hyperactivity taking a formula containing large amounts of warming and tonifying herbs (deer antler, astragalus) might experience adverse effects. Furthermore, this patent fails to provide direct measurements of the size and number of arterial plaques.

[0007] Chinese patent CN101411851A discloses a traditional Chinese medicine composition for preventing and treating hyperlipidemia and atherosclerosis, belonging to the field of traditional Chinese medicine. The active ingredients of this composition are made from the following raw materials in parts by weight: hawthorn 10-30 parts, alisma plantago-aquatica 5-20 parts, polygonum cuspidatum 5-15 parts, turmeric 12-20 parts, salvia miltiorrhiza 5-20 parts, chuanxiong rhizome 5-15 parts, and scutellaria baicalensis 5-10 parts. Hyperlipidemia and atherosclerosis fall under the categories of "phlegm turbidity," "blood stasis," and "stasis toxin" in traditional Chinese medicine. Their core pathogenesis is often characterized by deficiency of the root and excess of the branch (deficiency of the spleen and kidney as the root, and phlegm and blood stasis as the branch). This patent does not use spleen-tonifying and tonifying drugs, and it does not observe the size, number, or intima-media thickness of arterial plaques before and after treatment. Summary of the Invention

[0008] The purpose of this invention is to provide a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type, its preparation method, and its application. The traditional Chinese medicine composition, modified Er Chen Pu Huang Tang, is derived from Er Chen Tang, with the addition of Pu Huang, Danshen, Hu Zhang, Ze Xie, He Ye, and Sheng Shan Zha, enhancing its effects of promoting blood circulation, removing blood stasis, lowering lipids, and resolving phlegm.

[0009] The objective of this invention can be achieved through the following technical solutions:

[0010] A traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type is made from the following raw materials in parts by weight:

[0011]

[0012]

[0013] Furthermore, the traditional Chinese medicine composition also includes 10-15 parts by weight of stir-fried cassia seeds.

[0014] Furthermore, the traditional Chinese medicine composition is made from the following raw materials in parts by weight:

[0015]

[0016] Furthermore, the traditional Chinese medicine composition is an oral preparation.

[0017] Furthermore, the oral preparation is a powder or oral liquid.

[0018] This invention also provides a method for preparing a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type, the specific steps of which are as follows:

[0019] S1. Mix 10-20 parts by weight of ginger-processed Pinellia ternata, 5-15 parts by weight of dried tangerine peel, 10-20 parts by weight of Poria cocos, 10-20 parts by weight of Salvia miltiorrhiza, 10-20 parts by weight of Typha pollen, 10-20 parts by weight of Polygonum cuspidatum, 5-15 parts by weight of Alisma plantago-aquatica, 10-20 parts by weight of lotus leaf, 10-20 parts by weight of raw hawthorn, and 4-8 parts by weight of prepared licorice root. Add cold water and soak thoroughly.

[0020] S2. Boil the soaked herbs and soaking liquid from step S1 together over high heat. After boiling, simmer over low heat to maintain a gentle boil. Filter to obtain the first decoction and the dregs.

[0021] S3. Mix the dregs obtained in step S2 with water and bring to a boil over high heat. After boiling, simmer over low heat to maintain a gentle boil. Filter to obtain the second decoction and dregs.

[0022] S4. The first decoction obtained in step S2 and the second decoction obtained in step S3 are mixed to obtain a traditional Chinese medicine composition.

[0023] Furthermore, in step S1, the amount of cold water is 5-8 times the amount of medicinal materials.

[0024] Furthermore, in step S1, the soaking time is 30-60 minutes.

[0025] Furthermore, in step S2, the simmering time is 30-60 minutes.

[0026] Furthermore, in step S2, the weight ratio of the medicinal materials to the soaking solution is 1:5-8.

[0027] Furthermore, in step S3, the simmering time is 20-40 minutes.

[0028] Furthermore, in step S3, the weight ratio of the dregs to water is 1:3-4.

[0029] As a preferred technical solution, the dregs obtained in step S2 are put back into the decoction vessel, and water is added to cover the herbs by 2-5 cm. The decoction is brought to a boil quickly over high heat, and then simmered over low heat to maintain a gentle boil. The decoction is then filtered to obtain the second decoction and the dregs.

[0030] Furthermore, in step S4, the volume ratio of the first decoction to the second decoction is 1:1.

[0031] Furthermore, in step S4, the method of taking the traditional Chinese medicine composition is as follows: one dose per day, taken one hour after breakfast and dinner, one packet each time, taken warm, for 16 consecutive weeks.

[0032] The present invention also provides a traditional Chinese medicine preparation for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type, which is made from the above-mentioned traditional Chinese medicine composition.

[0033] Furthermore, the present invention also provides the application of the above-mentioned traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the above-mentioned method in the preparation of a medicament for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type.

[0034] The principle of this invention is as follows:

[0035] The modified Er Chen Pu Huang Tang formula is based on Er Chen Tang, but with the following modifications removed: ginger (this formula uses ginger-processed Pinellia, eliminating the need for ginger for detoxification) and dried plum (the astringent properties of dried plum may affect the removal of phlegm and dampness). The following herbs are added: Salvia miltiorrhiza, Typha pollen, Polygonum cuspidatum, Alisma plantago-aquatica, Nelumbo nucifera leaf, raw hawthorn, and stir-fried cassia seed. In this formula, Pinellia ternata and Citrus reticulata peel work together to improve spleen function and resolve phlegm, thus eliminating dampness. Salvia miltiorrhiza and Typha pollen invigorate blood circulation and remove blood stasis, improving arterial microcirculation and inhibiting platelet aggregation. Together, they reduce the accumulation of phlegm and blood stasis, improve arterial blood circulation, and reduce plaque formation. Nelumbo nucifera leaf and hawthorn resolve phlegm and turbidity, promote fat metabolism, and thus lower blood lipids. Poria cocos and Alisma plantago-aquatica work together to promote diuresis and eliminate dampness, helping to expel dampness through urination and enhancing the spleen-strengthening and dampness-removing effects. The entire formula works to resolve phlegm and dampness, invigorate blood circulation, remove blood stasis, and clear the meridians to eliminate plaque.

[0036] Clinically verified, the optimal ratio of the modified Er Chen Pu Huang Tang (a traditional Chinese medicine formula) of this invention is as follows: 15g of ginger-processed Pinellia ternata, 9g of dried tangerine peel, 15g of cattail pollen, 15g of Poria cocos, 15g of Polygonum cuspidatum, 15g of Alisma plantago-aquatica, 15g of lotus leaf, 15g of raw hawthorn, 12g of stir-fried cassia seed, 15g of Salvia miltiorrhiza, and 6g of prepared licorice root. This invention emphasizes both phlegm-resolving and blood-activating effects: 15g of Pinellia ternata resolves phlegm, while 15g each of cattail pollen and Salvia miltiorrhiza activate blood. This balanced dosage reflects the profound understanding of "treating phlegm without forgetting to treat blood stasis, and treating blood stasis always requires considering phlegm," resulting in a synergistic effect of "1+1>2." The dampness-eliminating drug group effect: 15g each of Poria cocos, Alisma plantago-aquatica, Polygonum cuspidatum, and lotus leaf form a powerful "dampness-eliminating and turbidity-clearing" drug group. Furthermore, through different meridian tropisms and medicinal properties, such as lotus leaf ascending and Alisma plantago-aquatica descending, it comprehensively covers the three jiaos (upper, middle, and lower burners). This invention employs a randomized controlled trial, randomly dividing 98 patients with hyperlipidemia and carotid atherosclerosis of the phlegm-blood stasis type into an observation group and a control group, with 49 patients in each group. The control group was treated with rosuvastatin, while the observation group was treated with rosuvastatin combined with a modified Er Chen Pu Huang Tang formula. Both groups were treated for 16 weeks. The results showed that the above-mentioned ratio was the optimal ratio for treating carotid atherosclerosis of the phlegm-blood stasis type. This ratio can effectively regulate lipid metabolism, reduce lipid deposition in blood vessels, thereby inhibiting the increase of carotid intima-media thickness, reducing carotid plaque area, and lowering the risk of vascular remodeling. It can also protect the vascular endothelial structure, delay the progression of atherosclerosis, and has no significant adverse reactions.

[0037] This invention provides treatment principles and the compatibility relationships between principal, assistant, adjuvant, and guide herbs. It highlights the synergistic effects between certain herbs and the fact that the selection of certain herbs is based on special consideration.

[0038] The treatment principles are as follows:

[0039] The traditional Chinese medicine composition of the present invention follows the principle of treating phlegm and blood stasis simultaneously. It addresses the root cause by resolving phlegm and dampness, eliminating turbidity and lowering lipids, and addresses the symptoms by promoting blood circulation, removing blood stasis, clearing the meridians and eliminating spots. This resolves phlegm and blood stasis, clears the meridians, improves blood lipid metabolism, reduces inflammatory response, and delays the development of atherosclerotic plaques.

[0040] The relationships between the ruler, ministers, assistants, and envoys are as follows:

[0041] The principal herbs are: Pinellia ternata, Citrus reticulata peel, and Typha pollen. Pinellia ternata dries dampness and resolves phlegm, while Citrus reticulata peel regulates qi and strengthens the spleen. Together, they work to dry dampness, resolve phlegm, strengthen the spleen, and regulate qi, thus preventing the spleen from producing phlegm and eliminating its source. Typha pollen excels at promoting blood circulation, removing blood stasis, clearing turbidity, and lowering lipids. The combined use of these three herbs embodies the concept of "treating phlegm and blood stasis simultaneously."

[0042] The main ingredients are: Salvia miltiorrhiza, lotus leaf, raw hawthorn, and stir-fried cassia seed. Salvia miltiorrhiza invigorates blood circulation and removes blood stasis; lotus leaf resolves phlegm and turbidity, invigorates blood circulation and removes blood stasis; raw hawthorn eliminates stagnation and phlegm, promotes qi circulation and removes blood stasis; cassia seed moistens the intestines and promotes bowel movements, helping to eliminate excess lipids from the body.

[0043] The adjuvant herbs are: Poria cocos, Polygonum cuspidatum, and Alisma plantago-aquatica. Poria cocos promotes diuresis and eliminates dampness, strengthens the spleen and stomach; Polygonum cuspidatum clears damp-heat in the stomach and intestines and disperses blood stasis in the meridians; Alisma plantago-aquatica promotes diuresis and eliminates dampness, helping to excrete dampness through urination.

[0044] The guiding herb is roasted licorice root. It harmonizes the effects of other herbs, clears heat and toxins, and enhances the overall efficacy of the formula.

[0045] The formula is divided into three parts: lotus leaf promotes the upward movement of clear qi and descends the downward movement of turbid qi, treating the upper jiao; Er Chen Tang strengthens the spleen and resolves phlegm, treating the middle jiao; Alisma, Polygonum cuspidatum, and Cassia seed promote diuresis and relieve constipation, treating the lower jiao, thus achieving the effects of resolving phlegm and dampness, promoting blood circulation and removing blood stasis, clearing the meridians, promoting diuresis, descending turbid qi, and eliminating fat.

[0046] Synergistic effect:

[0047] Pinellia ternata and dried tangerine peel: When combined, they promote each other, disperse and descend in an orderly manner, so that the spleen can function properly and phlegm can be transformed, and the flow of qi can be smooth and dampness can be eliminated.

[0048] Salvia miltiorrhiza, Typha pollen, and lotus leaf: Salvia miltiorrhiza and Typha pollen can improve arterial microcirculation and inhibit platelet aggregation by promoting blood circulation and removing blood stasis. Lotus leaf can resolve phlegm and reduce turbidity and promote fat metabolism, thereby lowering blood lipids. The two work together to reduce the mutual binding of phlegm and blood stasis, improve arterial blood circulation, and reduce plaque formation.

[0049] Poria cocos and Alisma plantago-aquatica: The two work together to promote diuresis and eliminate dampness, helping to expel dampness through urination and enhancing the spleen-strengthening and dampness-removing effects.

[0050] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0051] The traditional Chinese medicine composition of this invention is mainly used to treat patients with hyperlipidemia of the phlegm-blood stasis type accompanied by carotid atherosclerosis. It can reduce plaque area, reduce carotid intima-media thickness (CIMT), reduce the number of plaques, and lower Crouse score; reduce serum total cholesterol, triglycerides, low-density lipoprotein and uric acid, and increase high-density lipoprotein (HDL-C) level; reduce the levels of hypersensitive CRP and IL-6 inflammatory factors, and significantly improve TCM symptoms such as dull complexion, dizziness, lightheadedness, local stabbing pain, palpitations, poor appetite, chest tightness and excessive phlegm. Detailed Implementation

[0052] The present invention will now be described in detail with reference to specific embodiments. These embodiments are based on the technical solution of the present invention and provide detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is not limited to the following embodiments. Unless otherwise specified, the following embodiments and features can be combined with each other.

[0053] Example 1

[0054] This embodiment provides a modified Er Chen Pu Huang Tang (a traditional Chinese medicine formula) for treating hyperlipidemia with carotid atherosclerotic plaques caused by phlegm and blood stasis, which is made from the following raw materials by weight:

[0055]

[0056]

[0057] In addition, this embodiment also provides a method for preparing a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type, the specific steps of which are as follows:

[0058] S1. Place 15g ginger-processed Pinellia ternata, 9g dried tangerine peel, 15g cattail pollen, 15g salvia miltiorrhiza, 15g poria cocos, 15g polygonum cuspidatum, 9g alisma plantago-aquatica, 15g lotus leaf, 15g raw hawthorn, 12g stir-fried cassia seed, and 6g prepared licorice root into a decoction vessel and mix. Add 6 times the amount of cold water as the medicinal materials and soak for 40 minutes to allow the medicinal materials to fully absorb water, which is conducive to the extraction of effective ingredients.

[0059] S2. Quickly bring the soaked herbs and soaking liquid from step S1 to a boil over high heat. After boiling, simmer over low heat for 40 minutes. Filter to obtain the first decoction and the dregs.

[0060] S3. Mix the dregs obtained in step S2 with 3 times the amount of water and bring to a boil over high heat. After boiling, simmer over low heat for 30 minutes. Filter to obtain the second decoction and dregs.

[0061] S4. Mix the first decoction obtained in step S2 and the second decoction obtained in step S3 in equal volumes to obtain a traditional Chinese medicine composition. Take one dose daily, one hour after breakfast and dinner, one packet warm each time, for 16 consecutive weeks.

[0062] Performance Test Example 1

[0063] This test example provides a method for testing the performance of a traditional Chinese medicine composition. The specific steps are as follows:

[0064] (1) Sample size calculation: The sample size was estimated based on the maximum plaque area, the primary efficacy endpoint, and was calculated using the estimation formula for comparing the means of two samples in differential clinical trials.

[0065]

[0066] Based on previous research [3-4] The mean area of ​​the largest carotid artery plaque in patients with hyperlipidemia treated with Jiawei Erchentang combined with atorvastatin was 29.17 mm with a standard deviation of 7.89 mm, while the mean area in the control group was 34.5 mm with a standard deviation of 7.41 mm. This invention sets the significance level at α = 0.05 and the power at 1-β = 0.9. The required sample size for each group is n = 44 cases. Considering a 10% dropout rate, at least 49 cases should be included in each group, resulting in a total sample size of 98 cases.

[0067] Ninety-eight patients with phlegm-blood stasis type hyperlipidemia complicated with carotid atherosclerosis admitted to Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, between February 2023 and June 2025 were selected. They were randomly divided into an observation group and a control group, with 49 patients in each group. Three patients in the observation group withdrew due to stomach discomfort after taking medication, while one patient in the control group withdrew due to abnormal liver function and one patient withdrew due to violation of the medication regimen. A total of 93 patients were included in the final data analysis: 46 in the observation group and 47 in the control group. There were no statistically significant differences between the two groups in terms of gender, age, disease duration, and comorbidities (P>0.05), indicating comparability (see Table 1). This study protocol was reviewed and approved by the Medical Ethics Committee of our hospital (ethics number 2022107).

[0068] Table 1 Comparison of general information between the two groups of patients

[0069]

[0070] (2) Diagnostic criteria:

[0071] (2-1) Western medicine diagnostic criteria:

[0072] The diagnostic criteria for hyperlipidemia are based on the "Chinese Guidelines for Lipid Management (2023)". [5] Under normal dietary conditions, blood lipid levels measured after at least 12 hours of fasting can be used to diagnose hyperlipidemia if one or more of the following criteria are met: total cholesterol (TC) ≥ 5.2 mmol / L, triglycerides (TG) ≥ 1.7 mmol / L, low-density lipoprotein cholesterol (LDL-C) ≥ 3.4 mmol / L, and high-density lipoprotein cholesterol (HDL-C) ≤ 1.0 mmol / L.

[0073] The diagnostic criteria for carotid atherosclerosis are based on the "Guidelines for Vascular Ultrasound Examination in Stroke in China". [6] When the carotid intima-media thickness (CIMT) is ≥1.5 mm, protruding into the vessel lumen, or when localized intimal thickening exceeds 50% of the peripheral IMT, carotid atherosclerotic plaque formation can be diagnosed. Based on arterial ultrasound signal, plaques that are hypoechoic or isoechoic are considered soft plaques; plaques with linear hyperechoic areas in the superficial layer accompanied by posterior acoustic shadowing (fibrous cap) are called hard plaques; and plaques with varying echogenicity are called mixed plaques.

[0074] (2-2) Diagnostic criteria for TCM syndrome types

[0075] The diagnostic criteria for Traditional Chinese Medicine (TCM) are based on the "Expert Consensus on the Prevention and Treatment of Atherosclerosis with Integrated Traditional Chinese and Western Medicine (2021)".[7] Draft of the "Standards for Diagnosis and Treatment of Dyslipidemia in Traditional Chinese Medicine" [8] Guidelines for Clinical Research of New Traditional Chinese Medicine Drugs (Trial Implementation) [9] The diagnosis is based on the syndrome of phlegm and blood stasis, with the following main symptoms: sallow complexion, dizziness, and lightheadedness; secondary symptoms: localized stabbing pain, numbness in the limbs, palpitations, poor appetite, chest tightness, and excessive phlegm; and tongue and pulse symptoms: a purplish-dark tongue or one with spots, a greasy coating, and a wiry and hesitant pulse. A diagnosis can be made based on the presence of two main symptoms or one main symptom and two secondary symptoms, combined with tongue and pulse examination.

[0076] (3) Inclusion criteria

[0077] ① Meets the diagnostic criteria for hyperlipidemia complicated with carotid atherosclerosis, aged 30-70 years, and all patients are treating for the first time; ② The TCM diagnosis is phlegm and blood stasis syndrome; ③ No medications affecting lipid metabolism have been taken in the past month; ⑤ The patient cooperates with the treatment and provides informed consent.

[0078] (4) Exclusion criteria

[0079] ① Patients with secondary hyperlipidemia; ② Patients who have had acute cerebrovascular disease or acute myocardial infarction within the past 6 months; ③ Patients with severe carotid artery stenosis (70-90%) or complete occlusion requiring stent implantation; ④ Patients with liver or kidney dysfunction or a history of mental illness.

[0080] (5) Treatment methods

[0081] The control group received conventional Western medicine treatment, including rosuvastatin (Cordin, AstraZeneca, 10mg per tablet, National Drug Approval Number: H20160545), one tablet nightly for 16 weeks. The observation group received the same treatment as the control group, plus a modified Er Chen Pu Huang Tang (a traditional Chinese medicine formula prepared in Example 1). The formula consisted of: 15g ginger-processed Pinellia ternata, 9g dried tangerine peel, 15g Poria cocos, 15g Polygonum cuspidatum, 9g Alisma plantago-aquatica, 15g lotus leaf, 15g raw hawthorn, 12g stir-fried cassia seed, 15g Salvia miltiorrhiza, 6g prepared licorice root, and 15g cattail pollen. One dose was administered daily, prepared by Shanghai Tongjitang Pharmaceutical Co., Ltd., and packaged into two packets, each containing approximately 150mL of decoction, stored at 4℃. One packet was taken warm twice daily, in the morning and afternoon, for 16 weeks. Both groups followed a low-fat diet and were advised to abstain from smoking and alcohol. Patients with diabetes or hypertension were instructed to actively control their blood pressure and blood sugar.

[0082] (6) Observation indicators

[0083] (6-1) Carotid artery ultrasound examination

[0084] Carotid intima-media thickness (CIMT) was measured before and after treatment using a color Doppler ultrasound diagnostic instrument (GE Logic E8, USA). The CIMT measurement points were 1.0 cm and 2.0 cm proximal to the bifurcation of both common carotid arteries, and the average of these two measurements was taken. The maximum thickness of each isolated plaque was recorded, with 0 indicating no plaque detected; 1 indicating a unilateral plaque with a thickness ≤2 mm; 2 indicating bilateral plaques with both thicknesses ≤2 mm or a unilateral plaque with a thickness >2 mm; 3 indicating bilateral plaques with at least one thickness >2 mm; and 4 indicating bilateral plaques with both thicknesses >2 mm. The sum of the thicknesses of both carotid arteries was the Crouse score. [10-11] Record the maximum area, number, and size of the carotid artery plaque.

[0085] (6-2) Blood lipid test

[0086] Two ml of venous blood was drawn in the morning before and after treatment on an empty stomach, and TC, TG, HDL-C and LDL-C were detected using a fully automated biochemical analyzer (Beckman Coulter, AU5800, USA).

[0087] (6-3) Inflammatory markers

[0088] Two ml of fasting venous blood was collected before and after treatment. Hypersensitive C-reactive protein (hs-CRP) was detected using a fully automated biochemical analyzer (Beckman Coulter, AU5800, USA), and serum interleukin-6 (IL-6) was detected using a Siemens Immilite 1000 fully automated chemiluminescence system.

[0089] (6-4) Score of Phlegm-Blood Stasis Syndrome

[0090] The patient was scored once before and once after treatment. Each symptom was graded into four levels: none, mild, moderate, and severe. The main symptom was scored as 0, 2, 4, and 6 points, respectively, and the secondary symptom as 0, 1, 2, and 3 points. Tongue coating and pulse were not scored. The scores of all symptoms were added together to obtain the score for the phlegm-blood stasis syndrome.

[0091] (7) Safety evaluation

[0092] Adverse events in both groups of patients were recorded during the study. Safety indicators such as blood and urine routine tests, liver and kidney function tests, creatine kinase tests, and electrocardiograms were measured in both groups before and after treatment.

[0093] (8) Efficacy criteria

[0094] The TCM syndrome differentiation and efficacy criteria are based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines". [9] Specify. The calculation formula is the nimodipine method.

[12] The efficacy index is calculated as follows: (Pre-treatment score - Post-treatment score) / Pre-treatment score × 100%. Significant improvement in TCM clinical symptoms and signs, with a reduction in symptom score ≥70%, is considered markedly effective; improvement in both TCM clinical symptoms and signs, with a reduction in symptom score ≥30%, is considered effective; no significant improvement or worsening of TCM clinical symptoms and signs, with a reduction in symptom score <30%, is considered ineffective. The total effective rate is calculated as: (Number of markedly effective cases + Number of effective cases) / Total number of cases × 100%.

[0095] (9) Statistical methods

[0096] SPSS 26.0 software was used for statistical analysis. Categorical data were expressed as cases or percentages, and chi-square tests or Fisher's exact tests were used. Continuous data conforming to a normal distribution were expressed as mean ± standard deviation. Indications that do not conform to a normal distribution are described using median ± interquartile range. Independent samples t-tests were used for between-group comparisons, and paired t-tests were used for within-group comparisons. A p-value < 0.05 was considered statistically significant.

[0097] The experimental results are shown below.

[0098] (1) Comparison of carotid artery ultrasound results between the two groups of patients:

[0099] As shown in Table 2, before treatment, there were no statistically significant differences in maximum plaque area, IMT, number of plaques, and Crouse score between the two groups (P > 0.05). After treatment, the maximum plaque area, IMT, number of plaques, and Crouse score of both groups were significantly lower than before treatment (P < 0.05), and the observation group was lower than the control group (P < 0.05). This demonstrates that the observation group showed greater improvement in plaque reduction, vascular wall thinning, and total plaque thickness than the control group. Therefore, the traditional Chinese medicine composition provided by this invention can inhibit the increase of carotid intima-media thickness, reduce carotid plaque area, and reduce the risk of vascular remodeling.

[0100] Table 2 Comparison of carotid ultrasound results between the two groups of patients

[0101]

[0102] Note: Compared with the group before treatment, *P<0.05; compared with the control group after treatment, #P<0.05

[0103] (2) Comparison of blood lipid levels between the two groups of patients

[0104] As shown in Table 3, before treatment, there were no statistically significant differences in the levels of TC, TG, LDL-C, and HDL-C between the two groups (P > 0.05). After treatment, the levels of TC, TG, and LDL-C in both groups decreased compared to before treatment (P < 0.05), and the indicators in the observation group were better than those in the control group (P < 0.05). The HDL-C level in the observation group increased significantly compared to before treatment (P < 0.05), and the difference was statistically significant compared to the control group (P < 0.05). This demonstrates that the observation group was significantly more effective than the control group in reducing "bad cholesterol" (TC, TG, LDL-C) and significantly more effective in increasing "good cholesterol" (HDL-C). Therefore, the traditional Chinese medicine composition provided by this invention can effectively regulate lipid metabolism and reduce lipid deposition in blood vessels.

[0105] Table 3 Comparison of blood lipid levels between the two groups of patients

[0106] Note: Compared with the group before treatment, *P<0.05; compared with the control group after treatment, #P<0.05

[0107] (3) Comparison of inflammatory factor levels between the two groups of patients

[0108] As shown in Table 4, before treatment, there was no statistically significant difference in hs-CRP and IL-6 levels between the two groups (P > 0.05). After treatment, hs-CRP and IL-6 levels in both groups were significantly lower than before treatment (P < 0.05), with the observation group showing better results than the control group (P < 0.05). The decrease in inflammatory factors (hs-CRP and IL-6) levels in the observation group was more significant than that in the control group, indicating that the traditional Chinese medicine composition provided by this invention can reduce inflammatory responses, protect vascular endothelial structures, and delay the progression of atherosclerosis.

[0109] Table 4 Comparison of inflammatory factor levels between the two groups of patients

[0110]

[0111] Note: Compared with the group before treatment, *P<0.05; compared with the control group after treatment, #P<0.05

[0112] (4) Comparison of TCM syndrome scores between the two groups of patients

[0113] As shown in Table 5, there was no statistically significant difference in the TCM syndrome scores between the two groups before treatment (P>0.05). After treatment, the control group showed a significant decrease in dizziness, palpitations, poor appetite, and total score compared to before treatment (P<0.05). The observation group showed a more significant decrease in symptoms such as dull complexion, dizziness, lightheadedness, local stabbing pain, palpitations, poor appetite, chest tightness, excessive phlegm, and total score compared to the control group (P<0.05). This demonstrates that the observation group not only improved cardiovascular and cerebrovascular symptoms (dizziness and palpitations) but also comprehensively regulated the overall condition (complexion, digestion, and phlegm-dampness), effectively targeting the two core pathogenesis mechanisms of atherosclerosis in TCM theory—"blood stasis" and "phlegm turbidity." The improvement in dull complexion and local stabbing pain indicates strong blood-activating and stasis-removing effects; the improvement in chest tightness, excessive phlegm, and poor appetite indicates significant effects in resolving phlegm, removing dampness, and strengthening the spleen.

[0114] Table 5 Comparison of TCM syndrome scores between the two groups of patients ( point)

[0115]

[0116] Note: Compared with the group before treatment, *P<0.05; compared with the control group after treatment, #P<0.05

[0117] (5) Comparison of TCM syndrome efficacy between the two groups of patients

[0118] The comparison of TCM syndrome efficacy is a supplement to the comparison of TCM syndrome scores, and it also explains from different perspectives that the observation group can better improve the TCM clinical symptoms of patients.

[0119] As shown in Table 6, after treatment, the total effective rate was 78.60% in the control group and 93.48% in the observation group. The difference in total effective rate between the two groups was statistically significant (P<0.05). This demonstrates that the traditional Chinese medicine composition provided by this invention, when combined with conventional Western medicine, effectively improves the treatment level.

[0120] Table 6 Comparison of TCM syndrome efficacy between the two groups of patients [n(%)]

[0121] Note: Compared with the control group after treatment, #P<0.05

[0122] In summary, the modified Er Chen Pu Huang Tang formula of this invention is an effective traditional Chinese medicine prescription suitable for treating patients with hyperlipidemia of the phlegm-blood stasis type accompanied by carotid atherosclerotic plaques. Its formula is rationally formulated, effectively treating both phlegm and blood stasis, achieving the effects of resolving phlegm and dampness, promoting blood circulation and removing blood stasis, clearing the meridians, eliminating dampness and reducing turbidity, and reducing lipids. Clinical trials have demonstrated that this formula not only regulates lipid metabolism and reduces lipid deposition in blood vessels, thereby inhibiting the increase of carotid intima-media thickness, reducing carotid plaque area, and lowering the risk of vascular remodeling; but also reduces inflammatory response, protects vascular endothelial structure, and delays the progression of atherosclerosis.

[0123] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

[0124] The references are as follows:

[0125] [1] Dong Luga, Wang Faming, Mao Pingan, et al. Effects of modified Er Chen Tang combined with statins on blood lipids, hs-CRP, TNF-α and IL-18 in elderly patients with coronary heart disease and hyperlipidemia [J]. China Journal of Traditional Chinese Medicine Science and Technology, 2021, 28(5):702-768.

[0126] [2] Li Xiaofang, Jia Xiaojiang, Lü Pan. Treatment of 60 cases of hyperlipidemia with modified Er Chen Tang [J]. Inner Mongolia Journal of Traditional Chinese Medicine, 2011, 30(06):14.

[0127] [3] Yin Jihong, Fu Deyu. Clinical observation on the treatment of phlegm-dampness obstruction type hyperlipidemia by combination of modified Er Chen Tang and atorvastatin [J]. Jiangxi Journal of Traditional Chinese Medicine, 2022, 53(473):39-42.

[0128] [4] Yin Jihong, Fu Deyu. Effects of Jiawei Erchentang combined with atorvastatin on inflammatory factors, uric acid and carotid plaque in patients with phlegm-dampness obstruction type hyperlipidemia [J]. China Traditional Chinese Medicine Science and Technology, 2022, 29(4):528-532.

[0129] [5] Joint Expert Committee for the Revision of Chinese Guidelines for Lipid Management. Chinese Guidelines for Lipid Management (2023) [J]. Chinese Journal of Circulation, 2023, 38(3):237-271.

[0130] [6] Hua Yang, Hui Pinjing, Xing Yingqi. Guidelines for vascular ultrasound examination of stroke in China [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2015, 12(8):599-610.

[0131] [7] Cardiovascular Professional Committee of the Chinese Association of Integrated Traditional and Western Medicine, Cardiovascular Disease Branch of the China Association of Traditional Chinese Medicine. Expert consensus on the prevention and treatment of atherosclerosis with integrated traditional Chinese and Western medicine (2021) [J]. Chinese Journal of Integrated Traditional and Western Medicine, 2022, 42(3):287-293

[0132] [8] Zhang Xuezhi. Diagnostic criteria for dyslipidemia in traditional Chinese medicine (draft) [J]. Chinese Journal of Traditional Chinese Medicine, 2008, 23(8):716-719.

[0133] [9] Zheng Xiaoyu. Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial) [M]. Beijing: China Medical Science and Technology Press, 2002: 85-89.

[0134]

[10] Zhang Yanhong, Qin Ying, Shao Gang. Effect of Huatan Tongluo Decoction on the vulnerability of carotid atherosclerotic plaques in hypertension [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2023, 29(19):151-159.

[0135]

[11] Wen Xiaowen, Zhang Hengduan, Li Jianshuang, et al. Clinical efficacy of dispersive therapy for pre-atherosclerotic lesions and its effect on high-density lipoprotein cholesterol [J]. Beijing Journal of Traditional Chinese Medicine, 2024, 43(9): 1001-1004.

[0136]

[12] Chen Xiuwen, He Liren. Clinical observation on the treatment of carotid artery plaque of phlegm and blood stasis type by Qingxiao Tongyi formula [J]. Guangming Journal of Traditional Chinese Medicine, 2024, 39(13):2633-2636.

Claims

1. A traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type, characterized in that, Made from the following raw materials in parts by weight:

2. The traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type according to claim 1, characterized in that, The traditional Chinese medicine composition also includes 10-15 parts by weight of stir-fried cassia seeds.

3. The traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type according to claim 2, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight:

4. A method for preparing a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type as described in any one of claims 1-3, characterized in that, The specific steps are as follows: S1. Mix 10-20 parts by weight of ginger-processed Pinellia ternata, 5-15 parts by weight of dried tangerine peel, 10-20 parts by weight of Poria cocos, 10-20 parts by weight of Salvia miltiorrhiza, 10-20 parts by weight of Typha pollen, 10-20 parts by weight of Polygonum cuspidatum, 5-15 parts by weight of Alisma plantago-aquatica, 10-20 parts by weight of lotus leaf, 10-20 parts by weight of raw hawthorn, and 4-8 parts by weight of prepared licorice root. Add cold water and soak thoroughly. S2. Boil the soaked herbs and soaking liquid from step S1 together over high heat. After boiling, simmer over low heat to maintain a gentle boil. Filter to obtain the first decoction and the dregs. S3. Mix the dregs obtained in step S2 with water and bring to a boil over high heat. After boiling, simmer over low heat to maintain a gentle boil. Filter to obtain the second decoction and dregs. S4. The first decoction obtained in step S2 and the second decoction obtained in step S3 are mixed to obtain a traditional Chinese medicine composition.

5. The method for preparing a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of phlegm-blood stasis type according to claim 4, characterized in that, In step S1, the amount of cold water is 5-8 times the amount of medicinal materials; The soaking time is 30-60 minutes.

6. The method for preparing a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of phlegm-blood stasis type according to claim 4, characterized in that, In step S2, the simmering time is 30-60 minutes; The weight ratio of the medicinal materials to the soaking solution is 1:5-8.

7. The method for preparing a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of phlegm-blood stasis type according to claim 4, characterized in that, In step S3, the simmering time is 20-40 minutes; The weight ratio of the dregs to water is 1:3-4.

8. The method for preparing a traditional Chinese medicine composition for treating hyperlipidemia with carotid atherosclerotic plaques of phlegm-blood stasis type according to claim 4, characterized in that, In step S4, the volume ratio of the first decoction to the second decoction is 1:

1.

9. A traditional Chinese medicine preparation for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type, characterized in that, Made from the traditional Chinese medicine composition according to any one of claims 1-3.

10. The use of a traditional Chinese medicine composition as described in any one of claims 1-3 or a traditional Chinese medicine composition prepared by the method as described in any one of claims 4-8 in the preparation of a medicament for treating hyperlipidemia with carotid atherosclerotic plaques of the phlegm-blood stasis type.

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