A compound traditional Chinese medicine preparation for early intervention of atherosclerotic plaque and a preparation method thereof

Abstract

This invention discloses a compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques and its preparation method. The compound traditional Chinese medicine preparation comprises main ingredients and excipients. The main ingredients include a blood-activating and stasis-removing group, a phlegm-resolving and turbidity-reducing group, and a qi-tonifying and spleen-strengthening group. The blood-activating and stasis-removing group comprises the following ingredients in weight percentage: Panax notoginseng 1-3 parts, Salvia miltiorrhiza 12-18 parts, and Gentiana scabra 10-12 parts. The phlegm-resolving and turbidity-reducing group comprises the following ingredients in weight percentage: Trichosanthes kirilowii 40-25 parts, Allium macrostemon 25-15 parts, Ligusticum chuanxiong 6-12 parts, Pinellia ternata 5-8 parts, Citrus reticulata 6-12 parts, and Acorus tatarinowii 6-12 parts. The qi-tonifying and spleen-strengthening group comprises the following ingredients in weight percentage: Poria cocos 12-18 parts, Codonopsis pilosula 12-18 parts, and Glycyrrhiza uralensis 5-8 parts. The weight ratio of the blood-activating and stasis-removing group, the phlegm-resolving and turbidity-reducing group, and the qi-tonifying and spleen-strengthening group is 1-5:1-5:1-5. It has the effect of treating both phlegm and blood stasis, and can significantly stabilize vulnerable atherosclerotic plaques. It can be used to treat atherosclerotic cardiovascular diseases and has the advantages of definite curative effect, no toxic side effects, low cost, and easy promotion and application.

Description

Technical Field

[0001] This invention relates to a compound traditional Chinese medicine preparation and its preparation method, and more particularly to a compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques and its preparation method. Background Technology

[0002] Cardiovascular and cerebrovascular diseases based on atherosclerosis (AS) have become the leading causes of serious harm to human health due to their high incidence, mortality, and disability rates. Lipid management is central to the treatment of these diseases; however, even with intensive lipid-lowering therapy targeting low-density lipoprotein cholesterol (LDL-C), up to 40% of patients still experience life-threatening cardiovascular events. How to further reduce residual risk has become an urgent problem to be solved and a hot topic in current medical research.

[0003] Traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of atherosclerosis, exhibiting effects such as regulating blood lipids, improving blood viscosity, and enhancing immunity, while also possessing good safety and few adverse reactions. However, existing TCM treatment regimens still suffer from problems such as insufficient therapeutic effect and slow onset of action, failing to meet patients' needs for rapid improvement. Furthermore, many TCM preparations suffer from issues such as large dosages, poor taste, and inconvenient storage, affecting patient compliance and user experience.

[0004] Patent document CN118178592A discloses a traditional Chinese medicine composition for treating carotid artery plaques, its preparation method, and its application. The composition includes leech, turmeric, salvia miltiorrhiza, angelica sinensis, chuanxiong rhizome, hawthorn, pinellia ternata, tangerine peel, trichosanthes kirilowii, dandelion, raw atractylodes macrocephala, codonopsis pilosula, poria cocos, peach kernel, safflower, and immature bitter orange. This composition can significantly reduce IMT and plaque area without side effects. However, this patent still has the problem that the mass proportions of each component in the composition need further optimization to improve the efficacy of the drug.

[0005] Patent document CN118320005A discloses a traditional Chinese medicine compound for improving atherosclerosis and its preparation method. The compound comprises the following parts by weight of traditional Chinese medicine ingredients: Codonopsis pilosula 13-17 parts, stir-fried Atractylodes macrocephala 8-12 parts, Poria cocos 8-17 parts, Gynostemma pentaphyllum 13-17 parts, Citrus reticulata peel 5-15 parts, processed Pinellia ternata 5-15 parts, Trichosanthes kirilowii fruit 13-17 parts, Alisma plantago-aquatica fruit 13-17 parts, raw Crataegus pinnatifida fruit 8-17 parts, Salvia miltiorrhiza fruit 13-17 parts, Carthamus tinctorius flower 8-12 parts, and Hirudo medicinalis fruit 5-10 parts. This compound has a significant effect on improving atherosclerosis. However, this patent still has the problem that the compatibility of the traditional Chinese medicine components needs further optimization to improve the therapeutic effect. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a compound traditional Chinese medicine preparation for early intervention of atherosclerotic plaques and its preparation method. It has the effect of treating phlegm and blood stasis at the same time, with phlegm treatment as the priority. It advances the time window for treating atherosclerotic diseases from the "blood stasis and blockage" stage to the "turbidity and phlegm" stage, and can significantly stabilize vulnerable atherosclerotic plaques, thus achieving the therapeutic effect of early intervention of atherosclerotic plaques.

[0007] To address the aforementioned technical problems, this invention provides a compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques, comprising main ingredients and excipients. The main ingredients include a blood-activating and stasis-removing group, a phlegm-resolving and turbidity-reducing group, and a qi-tonifying and spleen-strengthening group. The blood-activating and stasis-removing group comprises the following ingredients in weight percentages: Panax notoginseng 1-3 parts, Salvia miltiorrhiza 12-18 parts, Gentiana scabra 10-12 parts, and Ligusticum chuanxiong 6-12 parts. The phlegm-resolving and turbidity-reducing group comprises the following ingredients in weight percentages: Trichosanthes kirilowii 40-25 parts, Allium macrostemon 25-15 parts, Pinellia ternata 5-8 parts, Citrus reticulata 6-12 parts, and Acorus tatarinowii 6-12 parts. The qi-tonifying and spleen-strengthening group comprises the following ingredients in weight percentages: Poria cocos 12-18 parts, Codonopsis pilosula 12-18 parts, and Glycyrrhiza uralensis 5-8 parts. The weight ratio of the blood-activating and stasis-removing group, the phlegm-resolving and turbidity-reducing group, and the qi-tonifying and spleen-strengthening group is 1-5:1-5:1-5.

[0008] Furthermore, the blood-activating and stasis-removing group comprises the following ingredients in the following weight percentages: Panax notoginseng 2 parts, Salvia miltiorrhiza 15 parts, Gentiana scabra 12 parts, and Ligusticum chuanxiong 9 parts; the phlegm-resolving and turbidity-reducing group comprises the following ingredients in the following weight percentages: Trichosanthes kirilowii 27 parts, Allium macrostemon 18 parts, Pinellia ternata 6 parts, Citrus reticulata 9 parts, and Acorus tatarinowii 9 parts; the qi-tonifying and spleen-strengthening group comprises the following ingredients in the following weight percentages: Poria cocos 15 parts, Codonopsis pilosula 15 parts, and Glycyrrhiza uralensis 6 parts.

[0009] Furthermore, the main ingredient accounts for 99% by weight, and the auxiliary ingredient accounts for 1% by weight, wherein the auxiliary ingredient comprises starch and magnesium stearate.

[0010] Furthermore, the blood-activating and stasis-removing group also includes 5-8 parts of Clerodendrum trichotomum, and the phlegm-resolving and turbidity-reducing group also includes 5-8 parts of Moringa oleifera.

[0011] This invention also provides a method for preparing the above-mentioned compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques, comprising the following steps: S1, obtaining the components of the blood-activating and stasis-removing group, the phlegm-resolving and turbidity-reducing group, and the qi-tonifying and spleen-strengthening group according to a preset amount, adding appropriate excipients to each, mixing, and then decocting with water; S2, performing solid-liquid separation on the three decoctions obtained after decoction and concentrating to obtain three extracts; S3, adding ethanol to each of the above extracts, stirring evenly, and allowing to stand to obtain an alcohol precipitation solution, filtering the alcohol precipitation solution, recovering the ethanol, obtaining extracts again, and continuing to concentrate; S4, preparing the concentrated three extracts into granules, tablets, powders, granules, mixtures, capsules, oral liquids, or pills according to a preset ratio.

[0012] Further, in step S1, water is added to the mixture at a ratio of 10-20 times the total weight of the medicinal materials for decoction, and the decoction time is 2-6 hours; in step S2, the decoction obtained after decoction is passed through a 40-mesh vibrating screen for solid-liquid separation, and the separated water extract is concentrated under reduced pressure in a thin-film concentrator at a pressure range of -650 mmHg to -750 mmHg, and then transferred to a stainless steel pressure cooker for atmospheric pressure concentration. The concentrated extract is equivalent to 6-10 g of Chinese medicinal materials per 1 ml.

[0013] Further, in step S2, a supercritical CO2 extraction method is used to extract fat-soluble components at an extraction pressure of 40 MPa and a temperature of 50°C; an ultrasound-assisted water extraction method is used to extract water-soluble components at an ultrasound frequency of 40 kHz and a time of 10-20 minutes; and the extract is concentrated under reduced pressure to a paste with a relative density of 1.10-1.25.

[0014] Further, in step S3, 95% ethanol is added to each group of extracts to control the alcohol content to 60%. After stirring, the mixture is allowed to stand for 45-50 hours to obtain an alcohol precipitate. The precipitate is then filtered and placed in an alcohol recovery pot to recover the ethanol until there is no alcohol odor, and the extract is obtained again. The extract is then further concentrated until each 1 ml of extract is equivalent to 8-12 g of Chinese medicinal materials.

[0015] Further, step S4 involves preparing the concentrated extract into granules as follows: adding 6% crospovidone and 70% ethanol by weight of the extract to form a soft material, then granulating the material in a 16-mesh stainless steel sieve oscillating granulator until the moisture content of the granules is below 6%, and then cooling the granules; spreading the wet granules evenly on a drying tray, and then sending them into a hot air circulating oven for drying, with the oven temperature controlled at 75°C, so that the moisture content of the granules is cooled to within the specified range; finally, manually granulating the granules using a 16-mesh sieve to obtain the compound traditional Chinese medicine preparation granules.

[0016] Further, step S4 involves preparing the concentrated extract into tablets as follows: S401, phosphatidylcholine and cholesterol are mixed at a molar ratio of 3:1, and ultrasonically treated for 20-40 minutes at 60°C to obtain a liposome core with a particle size controlled at 80±5nm. The liposome core encapsulates water-soluble components; S402, macrophage membranes and platelet membranes are extruded and coated onto the liposomes using a membrane extrusion method to form a liposome membrane structure. The pore size of the membrane extrusion is 200nm, the coating is performed 15-25 times, and the mass ratio of macrophage membrane to platelet membrane is 1:1; S403, oxidized phospholipid targeting ligands are fixed on the surface of the liposome membrane structure using a physical adsorption method to achieve a density of 15μg / cm²; S404, lipid-soluble components are embedded into the liposome membrane structure using a membrane fusion method at a temperature controlled at 37°C, a pH value of 7.4, and a time of 20-40 minutes.

[0017] Compared with existing technologies, this invention has the following beneficial effects: The compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques provided by this invention and its preparation method include a blood-activating and stasis-removing group, a phlegm-resolving and turbidity-reducing group, and a qi-tonifying and spleen-strengthening group. Combined with traditional Chinese medicine syndrome differentiation and formulation, and derived through long-term clinical practice, it has the effect of treating both phlegm and blood stasis. Pharmacological and clinical studies have confirmed that it can significantly stabilize vulnerable atherosclerotic plaques, reducing plaque area by up to 15%. It can be used for the treatment of atherosclerotic cardiovascular diseases and has the advantages of definite efficacy, no toxic side effects, low cost, and ease of promotion and application. Specific effects are as follows: 1. Based on the inventor's understanding of the core pathogenesis of early atherosclerotic plaque lesions (phlegm and blood stasis intertwined, easily accumulating and progressing), a traditional Chinese medicine compound preparation is provided, which has the effect of treating both phlegm and blood stasis, with phlegm treatment as the priority. Clinical application and pharmacological studies have confirmed that it can be used to improve patients' clinical symptoms, inhibit, stabilize and regress atherosclerotic plaques, lower serum low-density lipoprotein cholesterol, increase serum high-density lipoprotein cholesterol, lower serum inflammatory factors, increase serum anti-inflammatory factors, and regulate intestinal flora. It can be used for the treatment of early atherosclerotic plaque lesions, with definite efficacy, significant effect and good safety. 2. The raw materials of the traditional Chinese medicine compound preparation of this invention are readily available, inexpensive, easy to prepare, and suitable for widespread application. Furthermore, by processing each main component separately into a blood-activating and stasis-removing group, a phlegm-resolving and turbidity-reducing group, and a qi-tonifying and spleen-strengthening group, different proportions can be used for patients with different symptoms, making the treatment more flexible and targeted, and improving therapeutic efficacy. The combination of these three groups of drugs is not a simple addition, but rather constitutes a dynamic and interconnected treatment system. If arterial plaques are considered the "symptom" (result), then metabolic dysfunction in the body (spleen deficiency leading to dampness, qi deficiency leading to blood stasis) is the "root cause." Blood-activating and stasis-removing drugs directly target and clear the existing plaques (blood stasis), primarily treating the symptoms; phlegm-resolving and turbidity-reducing drugs clear the viscous substances (phlegm and dampness) that cause blockages, addressing both the symptoms and the root cause; while qi-tonifying and spleen-strengthening drugs start by restoring the spleen's digestive function, fundamentally reducing the production of phlegm, dampness, and blood stasis, thus addressing the root cause. These three groups of drugs can produce a synergistic effect of "1+1>2". Strengthening Qi and invigorating the spleen provides the impetus for promoting blood circulation and removing blood stasis. Sufficient Qi ensures vigorous blood flow, making the effects of blood-activating drugs more lasting and stable. At the same time, "smooth Qi flow leads to the smooth flow of body fluids," and strengthening the spleen and invigorating Qi helps to ensure the normal distribution of body fluids, thereby assisting in resolving phlegm and clearing away turbidity. The combination of blood-activating and phlegm-resolving methods (i.e., "treating phlegm and blood stasis simultaneously") can jointly clear the two mutually binding pathological products of "phlegm and turbidity" and "blood stasis" on the blood vessel walls, which is particularly crucial for controlling or even reversing early plaque formation. 3. The traditional Chinese medicine compound preparation of the present invention is made of pure traditional Chinese medicine and has no toxic side effects. Attached Figure Description

[0018] Figure 1 This is a trend chart of TCM symptom scores for two groups of patients in this invention; Figure 2 This is a pie chart matrix showing the clinical efficacy of the two groups of patients in this invention; Figure 3 This is a trend chart of phlegm-dampness syndrome scores for two groups of patients in this invention; Figure 4 This is a comparison chart of the difference in symptom scores between the two groups in this invention; Figure 5 This is a comparison chart of the differences in symptom scores between the two groups in this invention; Figure 6 This is a comparison chart of the difference in syndrome scores between the two groups of patients in this invention; Figure 7 This is a comparison chart of the difference in syndrome scores between two groups of patients in this invention within each group; Figure 8 This is a comparison chart of the difference in syndrome scores between two groups of patients in this invention within each group; Figure 9 This is a trend chart showing the difference in syndrome scores between phlegm-dampness syndrome and blood stasis syndrome in this invention; Figure 10 This is a graph showing the trend of changes in the long diameter of carotid artery plaques after treatment with the compound traditional Chinese medicine preparation of this invention; Figure 11 This is a graph showing the trend of changes in the thickness and diameter of carotid artery plaques after treatment with the compound traditional Chinese medicine preparation of this invention; Figure 12 This is a graph showing the trend of changes in the long diameter of femoral artery plaques after treatment with the compound traditional Chinese medicine preparation of this invention; Figure 13 This is a graph showing the trend of changes in the thickness and diameter of femoral artery plaques after treatment with the compound traditional Chinese medicine preparation of this invention; Figure 14 A bar chart showing the changes in blood lipid levels after treatment with the compound traditional Chinese medicine preparation of this invention; Figure 15 This diagram illustrates how the phlegm-stasis combined treatment formula has the effect of stabilizing and reducing plaques in New Zealand rabbits, apoE- / - mouse AS models, and patients with carotid artery plaques. Figure 16 This is a schematic diagram illustrating the blood lipid regulation of the phlegm-stasis treatment formula of the present invention; Figure 17 This is a diagram illustrating the regulation of inflammation / immune function by the phlegm-stasis treatment formula of this invention. Figure 18 The present invention provides a formula for treating both phlegm and blood stasis to regulate intestinal flora; Figure 19 Comparative images of the carotid artery after treatment with the compound traditional Chinese medicine preparation of this invention; Figure 20 This is a comparative image of lower limb arteries after treatment with the compound traditional Chinese medicine preparation of this invention. Detailed Implementation

[0019] The present invention will now be further described with reference to the accompanying drawings and embodiments.

[0020] Although there is no record of atherosclerosis (AS) in the historical literature of traditional Chinese medicine, AS can be categorized in TCM as a deficiency of the root and excess of the branch, specifically phlegm turbidity and blood stasis. The internal cause of phlegm formation is the dysfunction of the internal organs, while excessive consumption of rich and greasy foods is an external cause. From a genetic perspective, TCM constitution conditions such as "obese people tend to have more phlegm" are also important factors. The pathogenic factor of AS can be called "phlegm turbidity in the blood," which TCM classifies as a phlegm syndrome. Shen Jin'ao's *Miscellaneous Diseases: Origins and Development* states: "Phlegm is a substance that flows unpredictably; therefore, its harm extends from the top of the head to the soles of the feet, rising and falling with the Qi, reaching the entire body, both internally and externally, affecting all five internal organs and six bowels." It has the characteristics of being easily accumulated and easily dispersed. Early AS lesions such as lipid streaks and subendothelial foam cell aggregation are concrete manifestations of phlegm turbidity obstruction and phlegm stagnation, exhibiting the pathological characteristics of being easily formed and easily dissipated. Blood stasis refers to the stagnation of blood in the body, mainly the accumulation of blood outside the meridians, or poor blood circulation, obstructing blood flow in the meridians and internal organs. Phlegm originates from body fluids, and blood stasis originates from blood, but they flow differently yet share the same source, and can transform into each other under certain specific conditions. In short, physiologically they belong to the category of "body fluids and blood sharing the same origin," and pathologically they are "phlegm and blood stasis causing the same disease." For example, the *Ling Shu* (Spiritual Pivot) states, "When body fluids are harmonious and balanced, they transform into red blood." The *Su Wen* (Plain Questions) states, "Heart pain due to arthritis also involves stubborn phlegm and dead blood." The *Xue Zheng Lun* (Treatise on Blood Disorders) states, "Blood stasis, if prolonged, can also transform into phlegm and fluid." Zhu Danxi of the Yuan Dynasty, in his *Danxi Xinfa* (Danxi's Heart Method), first proposed the theory of "phlegm mixed with blood stasis forming a cyst," clearly stating that phlegm and blood stasis are causing the same disease. Practice has proven that phlegm obstruction hinders blood flow, and blood stasis makes phlegm difficult to resolve. Internal obstruction of blood stasis inevitably leads to phlegm, and phlegm causing blood stasis. Combining the characteristics of the four pathological processes of AS (lipid streaks, fibrous plaques, atherosclerotic plaques, and complex lesions) and the understanding of traditional Chinese medicine, the pathological process of AS can be divided into four stages: "turbidity, phlegm, blood stasis, and obstruction."

[0021] Regarding the diagnosis and treatment of AS, a review of relevant traditional Chinese medicine theories reveals that the theory of treating chest pain with phlegm and blood stasis simultaneously has a long history. For example, the *Suwen* (Plain Questions) chapter "On Yin and Yang Correspondence" proposes "those with blood stasis should resolve it," and the *Lingshu* (Spiritual Pivot) chapter "On Five Flavors" suggests "eating scallions for heart pain"; these can be considered the rudiments of the approach of treating chest pain with phlegm and blood stasis. The *Shanghan Zabing Lun* (Treatise on Febrile and Miscellaneous Diseases) summarizes medical theories from before the Qin and Han dynasties, establishing the Six Channels Differentiation and Treatment Principles, and first proposing the relationship between "phlegm and blood." In the chapter "Chest Pain, Heart Pain, Shortness of Breath, Pulse, Symptoms, and Treatment," the main prescription for various phlegm-related conditions includes the addition of white wine to promote the flow of qi and blood, implicitly suggesting the simultaneous treatment of phlegm and blood stasis. The Tang Dynasty's *Beiji Qianjin Yaofang* (Essential Prescriptions Worth a Thousand Gold Pieces) treats sudden chest pain with rhubarb and *Euonymus alatus* to invigorate blood and remove blood stasis, *Polygonum multiflorum* to dispel phlegm, disperse nodules, and break up blood stasis, and *Platycodon grandiflorus* to resolve phlegm. The Song Dynasty's *Shengji Zonglu* (General Records of Sacred Relief) chapter "Chest Pain" treats chest pain with the Siwen San formula, using *Citrus aurantium* to remove phlegm nodules and disperse masses, and *Curcuma zedoaria* to promote blood circulation and remove blood stasis. The Jin Dynasty medical text *Danxi Xinjing* describes a formula for treating chest pain caused by stagnant phlegm and fluid retention. This formula uses Trichosanthes kirilowii, Atractylodes lancea, and Citrus aurantium to resolve phlegm and dissipate lumps, and Paeonia lactiflora to invigorate blood. Cao Renbo, in his *Jizhitang Medical Cases*, specifically the section on chest pain radiating to the back, explicitly states that "chest pain radiating to the back is called chest pain… This pain is not only caused by phlegm and turbidity, but also by blood stasis, obstructing the diaphragm. The formula uses Trichosanthes kirilowii, Allium macrostemon, Prunus persica, and Carthamus tinctorius." This not only recognizes the close relationship between chest pain and phlegm and blood stasis but also employs a method of treating both simultaneously. From then on, the idea of ​​treating phlegm and blood stasis was reflected in the medical practices of physicians throughout history. Before the Ming Dynasty, the method of treating chest pain and heart pain by treating phlegm and blood stasis involved examining the prescriptions and inferring that the condition was "a disease of both phlegm and blood stasis." After the Ming Dynasty, various schools of thought explicitly proposed the theory of phlegm and blood stasis as the pathogenic factors of chest pain and heart pain.

[0022] Based on the above understanding, this invention innovatively proposes the treatment principle of "treating phlegm and blood stasis simultaneously, with phlegm treatment as the priority" to stabilize and eliminate AS plaques. It advances the treatment time window from the "blood stasis and blockage" stage to the "turbidity and phlegm" stage. It also draws on the Gualou Xiebai Baijiu Decoction recorded in Zhang Zhongjing's "Synopsis of Prescriptions of the Golden Chamber" from the Eastern Han Dynasty to develop the traditional Chinese medicine preparation of this invention.

[0023] The present invention provides a compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques, comprising main ingredients and excipients. The excipients include starch and magnesium stearate. The main ingredients include a blood-activating and stasis-removing group, a phlegm-resolving and turbidity-reducing group, and a qi-tonifying and spleen-strengthening group. The blood-activating and stasis-removing group includes Panax notoginseng, Salvia miltiorrhiza, Gentiana scabra, and Ligusticum chuanxiong. The phlegm-resolving and turbidity-reducing group includes Trichosanthes kirilowii, Allium macrostemon, Pinellia ternata, Citrus reticulata, and Acorus tatarinowii. The qi-tonifying and spleen-strengthening group includes Poria cocos, Codonopsis pilosula, and Glycyrrhiza uralensis. The weight contents of each component are as follows: Blood stasis removal group: Panax notoginseng 1-3 parts, Salvia miltiorrhiza 12-18 parts, Gentiana scabra 10-12 parts, Ligusticum chuanxiong 6-12 parts; Phlegm-resolving and turbidity-reducing group: Trichosanthes kirilowii 40-25 parts, Allium macrostemon 25-15 parts, Pinellia ternata 5-8 parts, Citrus reticulata 6-12 parts, Acorus tatarinowii 6-12 parts; Qi-tonifying and spleen-strengthening group: Poria cocos 12-18 parts, Codonopsis pilosula 12-18 parts, Glycyrrhiza uralensis 5-8 parts. The weight ratio of the blood stasis removal group, phlegm-resolving and turbidity-reducing group, and qi-tonifying and spleen-strengthening group is 1-5:1-5:1-5. The proportions of the blood-activating and stasis-removing group, the phlegm-resolving and turbidity-reducing group, and the qi-tonifying and spleen-strengthening group can be adjusted according to different symptoms and treatment focuses. If the focus is on activating blood and removing stasis, the proportion of the blood-activating and stasis-removing group should be higher; if the focus is on resolving phlegm and turbidity, the proportion of the phlegm-resolving and turbidity-reducing group should be higher; and if the focus is on tonifying qi and strengthening the spleen, the proportion of the qi-tonifying and spleen-strengthening group should be higher. This allows for flexible and targeted treatment formulas with different Chinese medicine components for patients with different symptoms.

[0024] Furthermore, the blood-activating and stasis-removing group also includes 5-8 parts of highland horseradish, and the phlegm-resolving and turbidity-reducing group also includes 5-8 parts of stinking peony.

[0025] 1. Blood-activating and stasis-removing group Efficacy: Promotes blood circulation, dissipates blood stasis, clears the meridians and relieves pain; Panax notoginseng: promotes blood circulation, relieves pain, removes blood stasis, and stops bleeding; Danshen: Promotes blood circulation, removes blood stasis, regulates menstruation, and relieves pain; Chuanxiong: invigorates blood circulation, promotes qi circulation, dispels wind, and relieves pain; Safflower Gentian: Clears heat and promotes diuresis, invigorates blood circulation and unblocks collaterals; Stinking Angelica: Promotes blood circulation and removes blood stasis; when combined with other blood-activating herbs, it enhances blood circulation.

[0026] 2. Expectorant and Turbidity-Reducing Group Efficacy: Resolves phlegm and relieves cough, clears turbidity and dissipates nodules, promotes the flow of Yang energy in the chest; Trichosanthes kirilowii: Clears heat and resolves phlegm, relieves chest tightness and dissipates nodules; Allium macrostemon: promotes yang, disperses stagnation, regulates qi, and relieves blockages; Pinellia ternata: dries dampness, resolves phlegm, relieves nausea and vomiting; Dried tangerine peel: regulates qi and strengthens the spleen, dries dampness and resolves phlegm; Acorus tatarinowii: clears the orifices and resolves phlegm, eliminates dampness and harmonizes the stomach; Horseradish from high mountains: Clears heat and detoxifies, relieves cough and eliminates phlegm.

[0027] 3. Qi-tonifying and spleen-strengthening group Efficacy: Tonifies the Qi of the spleen and lungs, strengthens the spleen and eliminates dampness, harmonizes the effects of other herbs; Codonopsis pilosula: replenishes qi and strengthens the spleen and lungs; Poria cocos: strengthens the spleen and calms the mind, promotes diuresis and eliminates dampness; Licorice: Tonifies the spleen and replenishes qi, harmonizes the effects of other herbs.

[0028] The compound traditional Chinese medicine preparation provided by this invention can be used for: a) stabilizing and resolving atherosclerotic plaques; b) lowering serum low-density lipoprotein cholesterol; c) increasing serum high-density lipoprotein cholesterol; d) lowering serum inflammatory factors; e) increasing serum anti-inflammatory factors; and f) regulating intestinal flora.

[0029] The phlegm-resolving and turbidity-reducing group and the qi-tonifying and spleen-strengthening group have the properties of clearing heat and toxins and relieving stagnation, which can create a better working environment for the main blood-activating and stasis-removing group drugs, so that they can work synergistically to achieve the therapeutic effect of early intervention in atherosclerotic plaques.

[0030] Preferably, the main ingredient accounts for 99% by weight, and the auxiliary ingredient accounts for 1% by weight; the main ingredient is composed of the following components in weight percentage: Blood-activating and stasis-removing group: Panax notoginseng 2 parts, Salvia miltiorrhiza 15 parts, Gentiana scabra 12 parts, Ligusticum chuanxiong 9 parts, and Clematis chinensis 7 parts; Phlegm-resolving and turbidity-reducing group: Trichosanthes kirilowii 27 parts, Allium macrostemon 18 parts, Pinellia ternata 6 parts, Citrus reticulata 9 parts, Acorus tatarinowii 9 parts, and Moringa oleifera 7 parts; Qi-tonifying and spleen-strengthening group: Poria cocos 15 parts, Codonopsis pilosula 15 parts, and Glycyrrhiza uralensis 6 parts.

[0031] The compound traditional Chinese medicine preparation provided by this invention is prepared by the following method: S1. Obtain the components of the blood-activating and stasis-removing group, phlegm-resolving and turbidity-reducing group, and qi-tonifying and spleen-strengthening group according to the preset amount, add appropriate excipients to each group, mix and then add water to decoct to obtain the corresponding three decoctions; add water to each group mixture in a volume of 10-20 times the total weight of the medicinal materials and decoct for 2-6 hours.

[0032] S2. The three decoctions obtained after decoction were subjected to solid-liquid separation and concentrated to obtain extracts. Specifically, the decoctions obtained after decoction were subjected to solid-liquid separation through a 40-mesh vibrating screen. The separated water extract was concentrated under reduced pressure in a thin-film concentrator at a pressure range of -650 mmHg to -750 mmHg. Then, it was transferred to a stainless steel pressure cooker for atmospheric pressure concentration. The concentrated extract was equivalent to 6-10 g of Chinese medicinal materials per ml. Further, supercritical CO2 extraction (40 MPa, 50℃) and ultrasound-assisted water extraction (40 kHz, 15 min) were used to extract fat-soluble and water-soluble active ingredients respectively, achieving efficient separation of components. The extract was subjected to reduced pressure and near-infrared real-time monitoring of the extract density was added to concentrate it to an extract with a relative density of 1.10-1.25 (60℃), preferably an extract with a relative density of 1.15, reducing the concentration error from ±10% to ±2%. Furthermore, in the water extraction method, the water is refluxed three times (water volume and time are 100L, 1 hour; 80L, 1 hour; 80L, 1 hour, respectively). Alternatively, a countercurrent extraction tower can be used instead of reflux extraction, which reduces solvent consumption by 40% and increases the transfer rate of active ingredients by 22%.

[0033] S3. Add ethanol to each of the above-mentioned extracts, stir well, and let stand to obtain an alcohol precipitate. Filter the alcohol precipitate, recover the ethanol, and obtain extracts again, and continue to concentrate. Specifically, add 95% ethanol to each extract, control the alcohol content to reach 60%, stir well, and let stand for 45-50 hours to obtain an alcohol precipitate. Filter the alcohol precipitate and place it in an alcohol recovery pot to recover the ethanol until there is no alcohol smell, and obtain extracts again. Continue to concentrate until each 1ml of extract is equivalent to 8-12g of Chinese medicinal materials.

[0034] S4. Prepare the concentrated three extracts into granules, tablets, powders, granules, mixtures, capsules, oral liquids or pills according to the preset ratio.

[0035] In one embodiment, the concentrated extract is prepared into granules according to the following steps: Add 6% crospovidone and 70% ethanol by weight of the extract to prepare a soft material, then granulate it in a 16-mesh stainless steel screen oscillating pellet mill. After the moisture content of the pellets is less than 6%, they are cooled. The wet granules are evenly spread on a drying tray and then sent into a hot air circulating oven for drying. The oven temperature is controlled at 75℃ to cool the granules to the specified moisture content. Finally, the granules are manually sized using a 16-mesh sieve to obtain the compound Chinese medicine preparation granules.

[0036] In another embodiment, the concentrated extract is formulated into tablets according to the following steps: S401. Phosphatidylcholine and cholesterol are mixed in a molar ratio of 3:1 and ultrasonically treated for 20-40 minutes at a temperature of 60℃ to obtain liposome cores with a particle size controlled at 80±5nm. The liposome cores encapsulate water-soluble components. S402. Liposomes are coated by extruding macrophage membranes and platelet membranes to form liposome membrane structures. The pore size of the membrane extrusion is 200 nm, the coating is performed 15-25 times, and the mass ratio of macrophage membrane to platelet membrane is 1:1. S403. Immobilize oxidized phospholipid targeting ligands on the surface of liposome membrane structures by physical adsorption, so that the density of oxidized phospholipid targeting ligands reaches 15 μg / cm². S404. The lipid-soluble components are embedded into the liposome membrane structure using a membrane fusion method, with the temperature controlled at 37°C, the pH value at 7.4, and the time at 20-40 minutes, preferably 30 minutes.

[0037] In tablet preparation, phospholipid complexes are introduced to encapsulate lipid-soluble components, resulting in a more than three-fold increase in bioavailability. Oxidized phospholipids, acting as targeting ligands, specifically bind to CD36 receptors at the site of atherosclerotic lesions. Hybridization of macrophage and platelet membranes provides dual targeting capabilities to the lesion site.

[0038] Example 1: Preparation of the decoction Weigh out 2700g of whole Trichosanthes kirilowii, 1800g of Allium macrostemon, 200g of Panax notoginseng, 1500g of Salvia miltiorrhiza, 1200g of Carthamus tinctorius and Gentiana scabra, 900g of Ligusticum chuanxiong, 600g of Pinellia ternata, 900g of Citrus reticulata peel, 900g of Acorus tatarinowii, 1500g of Poria cocos, 1500g of Codonopsis pilosula, and 600g of Glycyrrhiza uralensis. Using conventional methods, decoct the herbs separately according to three groups: a blood-activating and stasis-removing group, a phlegm-resolving and turbidity-reducing group, and a qi-tonifying and spleen-strengthening group to obtain three decoctions. The decoctions from these three groups are then mixed in a 1:1:1 ratio to obtain the final decoction.

[0039] Example 2 Preparation of water extract Weigh out 2700g of whole Trichosanthes kirilowii, 1800g of Allium macrostemon, 200g of Panax notoginseng, 1500g of Salvia miltiorrhiza, 1200g of Carthamus tinctorius and Gentiana scabra, 900g of Ligusticum chuanxiong, 600g of Pinellia ternata, 900g of Citrus reticulata peel, 900g of Acorus tatarinowii, 1500g of Poria cocos, 1500g of Codonopsis pilosula, 600g of Glycyrrhiza uralensis, 700g of Clerodendrum trichotomum, and 700g of Horseradish. Prepare the decoctions according to the following groups: blood-activating and stasis-removing group, phlegm-resolving and turbidity-reducing group, and qi-tonifying and spleen-strengthening group. The three decoctions were extracted three times under ultrasonic assistance by reflux with water (water volume and time: 100L, 1 hour; 80L, 1 hour; 80L, 1 hour, respectively). Alternatively, a countercurrent extraction tower can be used instead of reflux extraction, which reduces solvent consumption by 40% and increases the transfer rate of active ingredients by 22%. The extracts were combined, concentrated to obtain an extract, dried, and pulverized. These three extracts can be directly packaged and taken according to the predetermined ratio.

[0040] Example 3 Preparation of Granules Prepare 150g of extract according to the method described in Example 2, add 300g of dextrin, mix well, add an appropriate amount of 60% ethanol to make a soft material, granulate through a 24-mesh sieve, dry at 50°C for 2 hours, granulate the dried particles through a 30-mesh sieve, and package to obtain the final product.

[0041] Example 4: Preparation of tablets Prepare 150g of total extract according to the method described in Example 2, add 150g of microcrystalline cellulose and 55g of starch, mix well, add an appropriate amount of 60% ethanol to form a soft mass, granulate through a 24-mesh sieve, dry at 50℃ for 2 hours, granulate the dried particles through a 30-mesh sieve, add 2.5g of magnesium stearate, mix well, and compress into tablets to obtain the final product. Prepare tablets by introducing a phospholipid complex to encapsulate the fat-soluble components according to steps S401-404.

[0042] Example 5: Preparation of Capsules The extract was prepared according to the method described in Example 2, and appropriate pharmaceutical excipients were added. The extract was then vacuum dried, pulverized and granulated, and filled into capsules.

[0043] Example 6 Preparation of the mixture Take the raw materials according to the weight ratio described in Example 1, pulverize them, and decoct them using conventional methods. Concentrate the decoction to a thick extract. Add appropriate pharmaceutical excipients to prepare a compound. Sodium alginate thermosensitive gel can be added during the preparation of the compound to prolong the time to peak blood drug concentration to 8 hours.

[0044] Example 7 Toxicological study of the traditional Chinese medicine compound preparation of the present invention 1. Acute toxicity test (1) Laboratory animals Forty healthy SPF-grade KM mice, 4 weeks old, with a body weight of (22±2) g, half male and half female. They were provided by the Experimental Animal Center of the Second Military Medical University, and the experimental animal license number: SCXK (Shanghai): 2016-0003.

[0045] (2) Drug preparation The experimental drug was the traditional Chinese medicine decoction prepared in Example 1 of this invention. 12 kg of the traditional Chinese medicine decoction was divided into low and high dose groups, with 6 kg in each group. 10 L of water was added to each group and soaked for 1 hour, then heated to boiling. The low dose group was concentrated to 2 L to obtain an extract solution with a concentration of 3 g (raw drug) / ml; the high dose group was concentrated to 1 L to obtain an extract solution with a concentration of 6 g (raw drug) / ml.

[0046] (3) Animal grouping Forty healthy KM mice were taken and divided into 2 groups according to the random number table method, with 20 mice in each group: ① Low dose group: gavaged with the traditional Chinese medicine solution at a concentration of 3 g / ml, 1200 g / kg (indicating 1200 g of raw traditional Chinese medicine per kilogram of body weight, equivalent to 50 times the clinical equivalent dose, the same below); ② High dose group: gavaged with the traditional Chinese medicine solution at a concentration of 6 g / ml, 2400 g / kg (equivalent to 100 times the clinical equivalent dose).

[0047] (4) Intervention method Mice in the low and high dose groups of traditional Chinese medicine were gavaged at 1 ml / 10 g body weight, and the daily dose was administered in two divided doses for 7 consecutive days.

[0048] (5) Observation indexes Observe the changes in the activities, diet, behavior, etc. of the mice; observe the secretion of nasal, eye, and oral secretions in the mice; observe and record the changes in the body weight and death of the mice.

[0049] (6) Experimental results During the drug administration period, the appearance, body weight, and diet of the mice in both groups were normal; no phenomena such as reduced activity, curling up, and loose hair were observed; no secretions were seen in the nose, eyes, and mouth; and no deaths occurred. The results showed that when the maximum drug administration amount in mice was 2400 g (raw drug) / kg body weight, that is, 200 times the clinical equivalent dose, no acute toxicity reaction occurred in this traditional Chinese medicine compound preparation.

[0050] 2. Long-term toxicity experiment (1) Experimental animals Forty healthy SPF-grade SD rats, 6 weeks old, with a body weight of (200±30) g, half male and half female. They were provided by the Experimental Animal Center of the Second Military Medical University, and the experimental animal license number: SCXK (Shanghai): 2014-0003.

[0051] (2) Drug preparation The preparation method is the same as before. The concentration of the drug solution in the low-dose group was concentrated to 0.8 g (crude drug) / ml; the concentration of the drug solution in the medium-dose group was 1.6 g (crude drug) / ml; and the concentration of the drug solution in the high-dose group was 3.2 g (crude drug) / ml.

[0052] (3) Grouping of animals Forty healthy SD rats were randomly divided into four groups of 10 each: ① Blank control group: administered an equal volume of physiological saline by gavage; ② Low-dose group: administered a 1.2 g / ml concentration of traditional Chinese medicine solution by gavage, 6 g / kg (meaning 6 g of raw traditional Chinese medicine per kilogram of body weight, equivalent to 10 times the clinically equivalent dose, the same below); ③ Medium-dose group: administered a 2.4 g / ml concentration of traditional Chinese medicine solution by gavage, 12 g / kg (equivalent to 20 times the clinically equivalent dose); ④ High-dose group: administered a 4.8 g / ml concentration of traditional Chinese medicine solution by gavage, 24 g / kg (equivalent to 40 times the clinically equivalent dose).

[0053] (4) Intervention methods Rats in each dose group of the traditional Chinese medicine were administered the medicine by gavage at a dose of 5 ml / 100 g body weight, divided into two daily doses, for 180 consecutive days.

[0054] (5) Observation indicators Observe changes in activity, diet, and behavior in each group of rats; observe nasal, ocular, and oral secretions; observe and record changes in body weight and mortality. Collect blood samples, test, and analyze serological indicators. Sacrifice rats by cervical dislocation and observe morphological changes in various organs and tissues.

[0055] (6) Experimental results During the drug administration period, the appearance, weight, and diet of rats in all groups were normal; no reduced activity, curling up, or loosening of fur were observed; no secretions were observed from the nose, eyes, or mouth; and no deaths occurred. After 180 days of drug administration, blood samples were collected from each group of rats for analysis. The results showed that the routine blood tests (red blood cells, hemoglobin, platelet count, white blood cell count, etc.) and coagulation time of each group of rats were normal; there were no statistically significant differences in liver function (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum total protein, albumin, etc.), kidney function (blood urea nitrogen, creatinine, etc.), blood lipids, and blood glucose compared with the blank control group. Rats were euthanized by cervical dislocation, and no obvious abnormalities were found in the appearance and histological sections of any of the organs (heart, liver, kidney, spleen, lung, testis, uterus and ovaries, brain, stomach, pancreas, adrenal gland, thymus, thyroid gland, etc.). The above results indicate that when rats were given 6g (crude drug) / kg, 12g (crude drug) / kg, and 24g (crude drug) / kg body weight, after continuous administration for 6 months, no obvious toxic reactions were observed in the traditional Chinese medicine compound preparation of this invention.

[0056] Example 8: Clinical observation of the present invention 1. Source of the case: ① Participation is voluntary, and informed consent must be signed; ② Age ≥18 years, ≤75 years, gender not limited; ③ According to the "Clinical Diagnostic Criteria for Coronary Artery Disease with Phlegm and Blood Stasis Syndrome (T / CACM1060-2018)," the patient meets the diagnostic criteria for coronary artery disease with phlegm and blood stasis syndrome. ④ Patients with coronary artery stenosis ≥30% but <70% as assessed by intravascular ultrasound (IVUS), who do not require vascular reconstruction. ⑤ Vascular ultrasound shows plaque formation in the femoral or carotid artery: carotid ultrasound shows an IMT ≥1.3mm 1cm above the bifurcation of the common carotid artery, with visible soft plaques and luminal stenosis <70%; femoral ultrasound shows an IMT ≥1.0mm 1cm above the bifurcation of the deep femoral artery, with visible soft plaques and luminal stenosis <70%; ⑥ Meeting at least one of criteria 3 and 4 is sufficient. ⑦ The proportion of patients with coronary atherosclerosis is ≥10%.

[0057] 1. Exclusion Criteria ①Pregnant or breastfeeding women, or women of childbearing age who are not using effective contraception; ②Subjects with ALT or AST ≥ twice the ULN; ③Subjects with severe renal insufficiency (Cr > 177 μmol / L); ④Subjects with hemoglobin < 90 g / L, platelets < 100 × 10⁹ / L, or white blood cells < 3.0 × 10⁹ / L; ⑤Subjects who have had acute myocardial infarction, stroke, acute coronary syndrome, or coronary PCI within the past 3 months; ⑥Subjects who are currently participating in other clinical drug research projects or whose projects have ended less than 1 month ago; ⑦Subjects with a history of malignant tumors within the 5 years prior to screening; ⑧Subjects with active infections; ⑨Subjects with mental illness; ⑩Subjects deemed unsuitable for participation by other investigators.

[0058] 2. Grouping and Treatment: Patients were randomly assigned to a treatment group (Phlegm-Stasis Treatment Formula Group) and a control group (Placebo Group) using the envelope method. The Phlegm-Stasis Treatment Formula Group received standard anti-AS treatment (conventional dose atorvastatin, 20 mg / day) plus the Phlegm-Stasis Treatment Formula (4 tablets / time, 3 times / day, orally). The Placebo Group received standard anti-AS treatment plus a placebo (4 tablets / time, 3 times / day, orally). Treatment lasted 12 months.

[0059] 3. Observation indicators and methods: (1) Evaluation of therapeutic effect: The main indicators are the TCM syndrome score and the efficacy index. The calculation formula is: Efficacy index = (TCM syndrome score before treatment - TCM syndrome score after treatment) / TCM syndrome score before treatment × 100%. An efficacy index ≥ 90% is considered cured, 90% > efficacy index ≥ 70% is considered significantly effective, 70% > efficacy index ≥ 30% is considered effective, and efficacy index < 30% is considered ineffective. The total effective rate is (number of cured + significantly effective + effective cases) / total number of cases × 100%. Secondary indicators include indicators describing the size of arterial plaques, such as the long diameter and thickness of the arterial plaque, obtained by intravascular ultrasound of the coronary artery, carotid artery, and femoral artery. Safety indicators include general physical examination, laboratory safety tests, pregnancy test, liver and kidney function tests, etc.

[0060] (2) Evaluation of adverse reactions: Before each treatment cycle, blood routine and liver and kidney function were checked in both groups of patients. Blood routine (white blood cells, platelets, hemoglobin), liver and kidney function impairment, gastrointestinal adverse reactions such as nausea and vomiting, and peripheral neurotoxicity were observed. Adverse reactions were evaluated according to the WHO grading standard for chemotherapy drug toxicity and were divided into grades 0 to 4.

[0061] (3) Traditional Chinese Medicine syndrome scoring:

[0062] Table 1 4. Statistical methods: For normally distributed continuous data, the LSD-t test was used for inter-group comparisons; for non-normally distributed continuous data, the K-samples Kruskal-Wallis nonparametric test was used. For categorical data, the χ² test was used. 2 Survival analysis was performed using the Kaplan-Meier method. P <0.05 indicates a statistically significant difference.

[0063] 5. Results: 5.1 Baseline comparison between the two groups of patients The cases were collected from the Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, between June 2021 and December 2022, with a total of 124 eligible patients included in the study. Patients were randomly assigned to a control group (basic treatment + placebo) and an experimental group (basic treatment + a formula for treating phlegm and blood stasis), with 62 patients in each group. This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (approval number 2021-025). There were no statistically significant differences in the baseline clinical data between the two groups, making them comparable (see Table 1). During the study period, one patient dropped out of the control group, and one patient was excluded due to violation of the treatment protocol, leaving 58 patients enrolled. In the experimental group, one patient was excluded due to violation of the treatment protocol (self-discontinuing the medication used in this study), leaving 59 patients enrolled, for a total of 117 patients.

[0064]

[0065] Table 2 Patient Baseline Data

[0066] Table 3. Past medical history of enrolled patients 5.2 Comparison of TCM syndrome scores (1) Comparison of total scores for TCM syndrome scoring The total TCM syndrome scores obtained at each follow-up of all patients were statistically analyzed. Further statistical analysis revealed that the TCM syndrome scores of both groups conformed to a normal distribution and had homogeneous variances. Multiple repeated measures ANOVA was conducted, with the within-subjects factor including five groups (baseline, 3-month, 6-month, 9-month, and 12-month) and the between-subjects factor including two groups (control group (58 patients) and experimental group (59 patients)). Box's test for equivalence of the covariance matrix yielded degrees of freedom 1=15, degrees of freedom 2=53213.573, F=0.454, and P=0.963, indicating that the hypothesis was met, i.e., the measured covariance matrices of the dependent variable were equal across groups, and the groups were comparable. A Mochley test for sphericity was then performed, with an approximate chi-square value of 16.031, degrees of freedom of 9, P=0.066, and P>0.05, indicating that the interaction term satisfied the sphericity hypothesis. Subsequent intra-subject effects testing yielded Fwithin = 4167.327, P < 0.01, indicating a difference in the reduction of TCM syndrome scores between the two groups. Fwithin × Fbetween = 20.132, P < 0.01, meaning the interaction between follow-up time and grouping was statistically significant, indicating a significant interaction effect. This suggests that the treatment effects on TCM syndrome scores differed between the two groups, exhibiting different trends.

[0067] To reduce errors, the differences between the total TCM syndrome scores obtained at each visit period and the baseline were compared, and bar charts and box plots were obtained, such as... Figure 1 As shown in the figure; data analysis shows that, compared with the control group, the experimental group had a larger average difference in TCM syndrome scores after 6 months, 9 months and 12 months of treatment, and the difference was statistically significant (P<0.01).

[0068]

[0069] Table 4 Comparison of TCM syndrome scores between the two groups of phlegm-blood stasis syndrome ( ±S, minutes) (2) Comparison of clinical efficacy The TCM syndrome scores of the two groups of patients were calculated to obtain data such as ineffective, significantly effective, effective, cured, and effective rates in both groups. Figure 2As shown. A chi-square test was performed on the data, yielding χ²(3 months) = 18.788, P = 0.993, indicating that there was no statistically significant difference in treatment effectiveness between the two groups after 3 months of treatment. χ²(6 months) = 23.012, P = 0.056, indicating that there was no statistically significant difference in treatment effectiveness between the two groups after 6 months of treatment. χ²(9 months) = 6.535, P = 0.02, indicating that there was a statistically significant difference in treatment effectiveness between the two groups after 9 months of treatment. χ²(12 months) = 0.089, P < 0.01, indicating that there was a statistically significant difference in treatment effectiveness between the two groups after 12 months of treatment. In conclusion, the treatment effectiveness began to improve significantly after 9 months of treatment.

[0070] (3) Comparison of the number of people with symptoms of phlegm and blood stasis To further clarify the specific symptoms improved by the combined phlegm-stasis treatment formula for phlegm-stasis syndrome, data were statistically analyzed to obtain symptom-follow-up time frequency distribution tables for the control and experimental groups. The data were then analyzed using R Studio software to generate heatmaps showing the changes in symptoms over time. It can be seen that within both groups, the predominantly red patches gradually shifted to a predominance of blue patches over time, indicating that the number of people exhibiting phlegm-stasis syndrome symptoms gradually decreased with prolonged treatment, meaning the treatment could improve these symptoms. Comparing the two groups, the experimental group showed faster improvement and an earlier decrease in the number of patients compared to the control group, indicating that the combined phlegm-stasis treatment formula provided earlier relief of phlegm-stasis syndrome symptoms. The results show that the combined phlegm-stasis treatment formula significantly improved symptoms such as a swollen tongue with teeth marks, a greasy tongue coating, a soft or slippery pulse, heaviness in the limbs, sticky stools, abdominal distension, a purplish or dark tongue, ecchymosis or petechiae on the tongue, dark lips or gums, thick and distended sublingual veins, and a choppy pulse.

[0071] (4) Comparison of symptom scores for phlegm-dampness syndrome In the TCM syndrome scoring system, the symptoms of phlegm-dampness syndrome are mainly divided into two aspects: phlegm-dampness syndrome, characterized by a swollen tongue with teeth marks, a greasy or slippery tongue coating, and blood stasis syndrome, characterized by fixed-location chest pain, a purplish or dark tongue, petechiae or ecchymosis on the tongue, dark lips or gums, and thickened or bluish-purple, purplish-red, crimson, or purplish-black sublingual veins. To further clarify the difference between phlegm-dampness syndrome and blood stasis syndrome treated with the same formula, the total scores for phlegm-dampness syndrome and blood stasis syndrome were calculated and statistically analyzed separately. The results showed that the significance level was less than 0.01 after 3, 6, 9, and 12 months of treatment, indicating that only after 3, 6, 9, and 12 months of treatment with the same formula did the phlegm-dampness syndrome score significantly decrease, and the symptoms of phlegm-dampness syndrome significantly improve, with statistically significant differences. To minimize errors, the differences between the total TCM syndrome scores obtained at each visit period and the baseline were compared, and bar charts and box plots were obtained. Data analysis showed that, compared with the control group, the experimental group had a larger average difference in TCM syndrome scores after 3, 6, 9, and 12 months of treatment, and the differences were statistically significant (P<0.01). This indicates that symptoms of phlegm-dampness syndrome can be significantly improved after three months of taking the phlegm-stasis treatment formula. Figures 3-5 As shown.

[0072] (5) Comparison of syndrome scores for blood stasis syndrome The results showed that the significance level was less than 0.01 after 6, 9, and 12 months of treatment, indicating that only after 6, 9, and 12 months of treatment with the phlegm-stasis-treating formula did the phlegm-dampness syndrome score significantly decrease and the symptoms of phlegm-dampness syndrome significantly improve, with statistically significant differences. In the experimental group, the average difference in TCM syndrome scores was relatively large after 3, 6, 9, and 12 months of treatment, with statistically significant differences (P<0.01). This means that the symptoms of phlegm-dampness syndrome can be significantly improved after three months of taking the phlegm-stasis-treating formula. Figures 6-8 As shown.

[0073] (6) Comparison of syndrome scores between phlegm-dampness syndrome and blood stasis syndrome To further investigate whether the phlegm-dampness and blood stasis-treating formula differs in its improvement of phlegm-dampness syndrome and blood stasis syndrome, the results showed that the phlegm-dampness-treating formula exhibited different trends in improving these two syndromes. Comparing the mean differences between the two symptom types revealed that the phlegm-dampness-treating formula significantly improved the symptoms of phlegm-dampness syndrome. Figure 9 As shown.

[0074] 5.3 Comparison of IVUS Examination Results A total of 15 patients with coronary ankylosing spondylitis (AS) were included, with 8 in the control group and 7 in the experimental group. IVUS examinations were performed at baseline and 12 months after treatment to obtain the degree of stenosis and minimum lumen area of ​​the left anterior descending coronary artery. The results showed that compared with the baseline stenosis and minimum lumen area of ​​the left anterior descending coronary artery in both groups, there was no significant improvement in symptom improvement after treatment in either group (P>0.05). Compared with the control group, there was also no significant improvement in stenosis and minimum lumen area after treatment (P>0.05).

[0075] 5.4 Comparison of carotid artery plaque sizes The results showed that the significance level of the phlegm-stasis treatment formula was less than 0.05 after 9 and 12 months of treatment, indicating that only after 9 and 12 months of treatment with the phlegm-stasis treatment formula did the long and thick diameters of carotid artery plaques decrease significantly, and the differences were statistically significant. Figure 10 and Figure 11 As shown.

[0076] 5.5 Comparison of femoral artery plaque sizes The results showed that the significance level was less than 0.05 after 12 months of treatment, indicating that only after 12 months of treatment with the phlegm-stasis combined treatment formula did the long and thick diameters of the femoral artery plaques decrease significantly, and the difference was statistically significant. Figure 12 and Figure 13 As shown.

[0077] 5.6 Comparison of blood lipid levels Paired comparisons showed that TG and TC levels were significantly lower than 0.05 after 3, 6, 9, and 12 months of treatment, indicating that TG levels decreased after 3 months of treatment with the phlegm-stasis-treating formula, and the difference was statistically significant. LDL-C levels were significantly lower than 0.05 after 9 and 12 months of treatment, indicating that LDL-C levels decreased after 9 months of treatment with the phlegm-stasis-treating formula, and the difference was statistically significant. HDL-C levels were significantly lower than 0.05 after 6, 9, and 12 months of treatment, indicating that LDL-C levels increased after 6 months of treatment with the phlegm-stasis-treating formula, and the difference was statistically significant. Figure 14 As shown, A represents triglycerides, B represents total cholesterol, C represents low-density lipoprotein, and D represents high-density lipoprotein.

[0078] 5.7 Comparison of results of myocardial injury markers The results showed that, compared with pre-treatment levels, there were no statistically significant differences in the levels of troponin T, myoglobin, B-type natriuretic peptide precursor, and creatine kinase isoenzyme between the two groups after treatment (P>0.05). This indicates that the formula for treating both phlegm and blood stasis is safe.

[0079] 5.8 Safety Indicators The results showed that, compared with pre-treatment levels, there were no statistically significant differences in ALT, AST, γ-GT, ALP, creatinine, uric acid, and urea levels between the two groups after treatment (P>0.05). This indicates that the phlegm-stasis combined treatment formula has no liver-damaging effect and is safe.

[0080] Example 9: Animal experiments of the present invention 1. Experimental materials: (1) Animal model: Male ApoE- / - mice were acclimatized to a normal diet for 1 week. The external carotid artery was ligated distal to the superior thyroid artery using 6-0 silk thread, and the internal carotid artery and occipital artery were ligated together according to the course of the blood vessels. The mice were then fed a high-fat diet for 4 weeks. Carotid artery and aortic specimens were taken, fixed with 4% paraformaldehyde, and some were frozen at -80℃ for later use.

[0081] (2) Experimental drugs: In the compound preparation of traditional Chinese medicine, the main ingredients account for 99% by weight and the excipients account for 1% by weight. The main ingredients consist of: Trichosanthes kirilowii 27 parts, Allium macrostemon 18 parts, Panax notoginseng 2 parts, Salvia miltiorrhiza 15 parts, Gentiana scabra 12 parts, Ligusticum chuanxiong 9 parts, Pinellia ternata 6 parts, Citrus reticulata 9 parts, Acorus tatarinowii 9 parts, Poria cocos 15 parts, Codonopsis pilosula 15 parts, Glycyrrhiza uralensis 6 parts; the excipients consist of: starch and magnesium stearate. Add water of 10-20 times the total weight of the medicinal materials to the above mixture and decoct for 2-6 hours; b. After decoction, the decoction liquid is passed through a 40-mesh vibrating screen for solid-liquid separation. The separated water extract is concentrated under reduced pressure in a thin film concentrator and then transferred to a stainless steel pressure cooker for atmospheric pressure concentration. The concentrated extract is equivalent to 6-10g of Chinese medicinal materials per ml. The pressure range of the reduced pressure concentration is -650°C. c) Add 95% ethanol to the above extract to make the alcohol content reach 60%, stir well and let stand for 48 hours to obtain alcohol precipitation. Filter the alcohol precipitation and place it in an alcohol recovery pot to recover ethanol until there is no alcohol smell and obtain extract again. Continue to concentrate the above extract to each 1ml of extract is equivalent to 8-12g of Chinese medicinal materials; d) Add 6% cross-linked povidone and 70% ethanol by weight of extract to make soft material, and then make wet granules in a 16-mesh stainless steel screen swing granulator. After the granule moisture content is less than 6%, cool it; e) Spread the wet granules evenly on the drying tray and send them into a hot air circulating oven for drying. The oven temperature is controlled at 75℃ to cool the granules to the specified moisture content. Finally, manually granulate with a 16-mesh screen to obtain compound Chinese medicine preparation granules with a granule weight of 0.35g / granule.

[0082] 2. Grouping and Methods: Placebo group (1 / 10 medium dose of the phlegm-stasis treatment formula, 1g / kg), low dose of the phlegm-stasis treatment formula group (5g / kg), medium dose of the phlegm-stasis treatment formula group (10g / kg), high dose of the phlegm-stasis treatment formula group (15g / kg) and the phlegm-stasis treatment formula group.

[0083] 3. Evaluation Method: Dynamic imaging examination of AS plaques: Small animal-specific ultrasound was performed using a Vevo 2100 from Visual Sonic, Canada. The small animal ultrasound system, with a 30MHz high-frequency ultrasound probe, was used for longitudinal scanning from the origin of the carotid artery, sequentially observing the common carotid artery, the bifurcation of the common carotid artery, the internal carotid artery, and the external carotid artery. The probe was then rotated 90 degrees to perform a transverse scan along the vessel course. The presence of thickening of the arterial intima and the location, size, and echogenicity of plaques were observed. The probe angle was carefully adjusted to obtain ideal two-dimensional images of the carotid artery, and continuous sampling was recorded onto an optical disc.

[0084] Ultrasound image data analysis: Plaques are classified according to different two-dimensional ultrasound manifestations of atherosclerosis: lipid plaques (plaque echogenicity lower than or equal to that of normal intima), fibrous plaques (including fibrolipid plaques and fibrous plaques, with strong echogenicity but no acoustic shadowing), and calcified plaques (strong echogenicity with acoustic shadowing). The percentage of the plaque area occupied by the hypoechoic region is calculated. Based on the image analysis results, the instrument can automatically calculate three sets of acoustic density values: peak-to-peak intensity, average image intensity, and standard deviation of image intensity.

[0085] Recording and specimen collection: Starting from 0:00 in the experiment, the weight of the animals was recorded once a week, and their feeding was observed. At the scheduled time, the animals were euthanized and specimens were collected, including serum, carotid artery and aortic tissue specimens containing intact peripheral fat from both sides. After rinsing the tissue specimens with PBS and drying them, a portion was preserved in liquid nitrogen for subsequent frozen sectioning and protein electrophoresis analysis, and another portion was soaked in 4% formalin for subsequent paraffin embedding.

[0086] Histopathological analysis of vascular tissue: Image-pro plus 6.0 (IPP) image analysis software was used to calculate the neointima-media ratio (IMR), the vascular ring luminal cross-sectional area (LA), the area surrounded by the internal elastic lamina (IELA), and the area surrounded by the external elastic lamina (EELA), i.e., the total vascular area. The neointima area = IELA - LA; the media area = EELA - IELA; IMR = (neointima area) / (media area) reflects the degree of neointima hyperplasia. Two sections were taken from each target vessel, and five vascular rings were selected from each section to measure the area of ​​each layer. Finally, the average of the data obtained from the ten vascular rings was calculated as the final value for the specimen.

[0087] Aortic / carotid plaque burden and stability assessment: Oil red staining was used to observe the plaque burden at the aortic root. Masson trichrome staining and Sirius red staining were used to evaluate collagen content. Image-Pro software was used to measure the area of ​​the entire intima and each plaque and collagen. The relative percentage of plaque and collagen content was obtained by dividing the total area of ​​plaque and collagen by the total area of ​​the intima, which was used to evaluate plaque stability.

[0088] 4. Statistical methods: For normally distributed continuous data, the LSD-t test was used for inter-group comparisons; for non-normally distributed continuous data, the K-samples Kruskal-Wallis nonparametric test was used. For categorical data, the χ² test was used. 2 test.

[0089] 5. Experimental Results: A carotid artery atherosclerotic plaque model was established using New Zealand rabbits with carotid adventitia injury, an apoE- / - high-fat-fed AS mouse model, and patients with carotid artery plaques. The patented new formula for treating both phlegm and blood stasis demonstrated a significant effect in stabilizing and resolving AS plaques. Pathological sections also indicated that it significantly improved plaque stability and regulated blood lipids. Figure 15 As shown, in New Zealand rabbits, apoE - / - In mouse AS models and patients with carotid artery plaques, the formula for treating both phlegm and blood stasis was shown to stabilize and reduce plaques.

[0090] Mechanism exploration: In an AS animal model, it was confirmed that the formula for treating both phlegm and blood stasis can regulate blood lipids. Figure 16 ); inhibit inflammatory factors and increase the release of anti-inflammatory factors ( Figure 17 Left); regulating immune balance ( Figure 17 Right); improves endothelial damage, promotes angiogenesis, and regulates gut microbiota ( Figure 18 ). Figure 17 It was confirmed that trichosanthes in Trichosanthes kirilowii can bind to the inflammatory target TLR4 (-8.9 kcal / mol), and allicin in Allium macrostemon inhibits HMG-CoA reductase (reducing its activity by 62%), thus verifying the "phlegm-resolving and lipid-regulating" mechanism at the molecular level.

[0091] The foregoing has shown and described the basic principles, main features, and advantages of this invention. It is evident that this invention breaks through the traditional qualitative description of "treating phlegm and blood stasis simultaneously," and for the first time proposes a quantitative intervention threshold: through clinical data ( Figure 1-9 It was found that when serum lipopolysaccharide (LPS) > 50 pg / mL and fibrinogen (FIB) > 4 g / L, it marked the transformation of "phlegm syndrome" into "blood stasis syndrome". This preparation reduces LPS by 35% ( Figure 18 ) and adjusting FIB ( Figure 14This allows for precise prevention by shifting the intervention window from the "stasis period" to the "phlegm and turbidity period."

[0092] Example 10: Clinical application of the present invention The compound traditional Chinese medicine preparation prepared above was administered to the following patients, and the specific effects are as follows: Typical Case 1: A 56-year-old retired female patient with a 13-year history of coronary heart disease and a 5-year history of recurrent chest tightness that worsened in the past month. Upon admission, examinations revealed significantly elevated blood lipid levels and moderate fatty liver. Angiography showed no stenosis in the lumbar artery (LM), approximately 70% stenosis in the proximal-mid segment of the larynx (LA), approximately 50% stenosis in the proximal segment of the lateral carotid artery (LCX), and 60% stenosis in the proximal segment of the renal artery (RCA). Carotid ultrasound showed normal course and diameter of both carotid arteries, rough intima, thickened intima-media, and patent lumen. A 2.23 cm long lesion was observed on the posterior wall of the right carotid bifurcation. A soft plaque measuring 0.46 cm in length and 0.46 cm in thickness was observed. Multiple plaques were seen in the left carotid artery, the largest being 1.89 cm long and 0.56 cm thick. The patient was treated with a formula for treating both phlegm and blood stasis, 3 pills each time, 3 times a day. Six months later, a follow-up carotid ultrasound showed a significant reduction in plaque size. The carotid ultrasound revealed a soft plaque measuring 1.56 cm long and 0.32 cm wide on the posterior wall of the right carotid artery bifurcation, and multiple plaques in the left carotid artery, the largest being 0.78 cm long and 0.23 cm wide. Figure 19 As shown.

[0093] Typical Case 2: A 61-year-old retired male patient had an irregular diet and was diagnosed with elevated blood lipids two years ago. He was prescribed statins and other lipid-lowering drugs, but his blood lipids remained high. An ultrasound examination of the lower extremity arteries at our hospital showed: the bilateral common femoral arteries, superficial femoral arteries, and popliteal arteries had normal course and diameter, rough intima, and thickened intima-media (0.1 cm thick). The lumens were patent. Multiple plaques of varying sizes were seen in both lower extremity arteries. The larger plaque on the right side showed mixed echogenicity, measuring 2.13 cm in length and 0.23 cm in thickness, while the larger plaque on the left side showed mixed echogenicity, measuring 1.78 cm in length and 0.34 cm in thickness. He was treated with a traditional Chinese medicine formula for treating phlegm and blood stasis, 3 pills each time, 3 times a day. A follow-up ultrasound examination of the lower extremity arteries nine months later showed: multiple plaques of varying sizes were seen in both lower extremity arteries. The larger plaque on the right side showed mixed echogenicity, measuring 1.76 cm in length and 0.21 cm in thickness, while the larger plaque on the left side showed mixed echogenicity, measuring 1.53 cm in length and 0.31 cm in thickness. Figure 20 As shown.

[0094] Typical Case 3: A 58-year-old male, a company manager, had a 25-year history of essential hypertension and a 10-year history of coronary heart disease. He was taking antihypertensive drugs, aspirin, statins, and other Western medicines to control his condition, but still experienced occasional chest tightness, which worsened with activity and was slightly relieved by rest. He kept a prescription of Musk Heart-Protecting Pills, which he felt provided some relief. Recently, due to the fatigue of caring for his grandson, his chest tightness symptoms worsened, and he came to our outpatient clinic for treatment. He underwent DSA coronary angiography, which showed: no stenosis in the LM segment, approximately 70% stenosis in the proximal LA segment, no significant stenosis in the LCX segment, and no significant stenosis in the RCA segment. Intravascular ultrasound (IVUS) was performed on the LAD segment, which showed calcified plaques in the proximal LAD segment, with the narrowest point being 71% and the smallest lumen area being 3.75 cm². 2 The patient was given a traditional Chinese medicine formula to treat both phlegm and blood stasis, 3 pills each time, 3 times a day. After one year, the patient's chest tightness symptoms were significantly relieved. A follow-up IVUS examination revealed calcified plaques in the proximal segment of the left aorta (LAD), with the narrowest point at 63% and the smallest lumen area at 2.51 cm². 2 .

[0095] The above three patients took the compound preparation "Tan Yu Tong Zhi Fang" to stabilize and reduce atherosclerosis. After a six-month follow-up, no adverse reactions such as allergies or rashes occurred, and follow-up blood and urine routine tests and liver and kidney function tests showed no abnormalities. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications and improvements without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be defined by the claims.

Claims

1. A compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques, characterized in that, The product contains main ingredients and auxiliary ingredients. The main ingredients include a blood-activating and stasis-removing group, a phlegm-resolving and turbidity-reducing group, and a qi-tonifying and spleen-strengthening group. The blood-activating and stasis-removing group includes the following ingredients in weight percentage: Panax notoginseng 1-3 parts, Salvia miltiorrhiza 12-18 parts, Gentiana scabra 10-12 parts, and Ligusticum chuanxiong 6-12 parts. The phlegm-resolving and turbidity-reducing group includes the following ingredients in weight percentage: Trichosanthes kirilowii 40-25 parts, Allium macrostemon 25-15 parts, Pinellia ternata 5-8 parts, Citrus reticulata 6-12 parts, and Acorus tatarinowii 6-12 parts. The qi-tonifying and spleen-strengthening group includes the following ingredients in weight percentage: Poria cocos 12-18 parts, Codonopsis pilosula 12-18 parts, and Glycyrrhiza uralensis 5-8 parts. The weight ratio of the blood-activating and stasis-removing group, the phlegm-resolving and turbidity-reducing group, and the qi-tonifying and spleen-strengthening group is 1-5:1-5:1-5.

2. The compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 1, characterized in that, The blood-activating and stasis-removing group comprises the following ingredients in the following weight percentages: Panax notoginseng 2 parts, Salvia miltiorrhiza 15 parts, Gentiana scabra 12 parts, and Ligusticum chuanxiong 9 parts; the phlegm-resolving and turbidity-reducing group comprises the following ingredients in the following weight percentages: Trichosanthes kirilowii 27 parts, Allium macrostemon 18 parts, Pinellia ternata 6 parts, Citrus reticulata 9 parts, and Acorus tatarinowii 9 parts; the qi-tonifying and spleen-strengthening group comprises the following ingredients in the following weight percentages: Poria cocos 15 parts, Codonopsis pilosula 15 parts, and Glycyrrhiza uralensis 6 parts.

3. The compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 1, characterized in that, The main ingredient accounts for 99% by weight, and the auxiliary ingredients account for 1% by weight. The auxiliary ingredients include starch and magnesium stearate.

4. The compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 1, characterized in that, The blood-activating and stasis-removing group also includes 5-8 parts of Clerodendrum trichotomum, and the phlegm-resolving and turbidity-reducing group also includes 5-8 parts of Moringa oleifera.

5. A method for preparing a compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 1, characterized in that, Includes the following steps: S1. Obtain the components of the blood-activating and stasis-removing group, the phlegm-resolving and turbidity-reducing group, and the qi-tonifying and spleen-strengthening group according to the preset amount, add appropriate amount of excipients, mix and then add water to decoct. S2. The three decoctions obtained after decoction were subjected to solid-liquid separation and concentrated to obtain three extracts. S3. Add ethanol to each of the above extracts, stir well, and let stand to obtain an alcohol precipitate. Filter the alcohol precipitate, recover the ethanol, obtain extracts again, and continue to concentrate. S4. Prepare the concentrated three extracts into granules, tablets, powders, granules, mixtures, capsules, oral liquids or pills according to the preset ratio.

6. The preparation method of the compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 5, characterized in that, In step S1, water equal to 10-20 times the total weight of the medicinal materials is added to each mixture and decocted for 2-6 hours. In step S2, the decoction obtained after decocting is passed through a 40-mesh vibrating screen for solid-liquid separation. The separated aqueous extract is then concentrated under reduced pressure in a thin-film concentrator at a pressure range of -650 mmHg to -750 mmHg. After that, it is transferred to a stainless steel pressure cooker for atmospheric pressure concentration. The concentrated extract is equivalent to 6-10 g of Chinese medicinal materials per 1 ml.

7. The preparation method of the compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 5, characterized in that, Step S2 employs supercritical CO2 extraction to extract fat-soluble components at an extraction pressure of 40 MPa and a temperature of 50°C; it employs ultrasound-assisted water extraction to extract water-soluble components at an ultrasound frequency of 40 kHz for 10-20 minutes; and it concentrates the extract under reduced pressure to a paste with a relative density of 1.10-1.

25.

8. The method for preparing the compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 5, characterized in that, In step S3, 95% ethanol is added to each group of extracts to control the alcohol content to 60%. After stirring, the mixture is allowed to stand for 45-50 hours to obtain an alcohol precipitate. The precipitate is then filtered and placed in an alcohol recovery pot to recover the ethanol until there is no alcohol odor, and the extract is obtained again. The extract is then further concentrated until each 1 ml of extract is equivalent to 8-12 g of Chinese medicinal materials.

9. The preparation method of the compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 5, characterized in that, Step S4 involves preparing the concentrated extract into granules as follows: Add 6% crospovidone and 70% ethanol by weight of the extract to prepare a soft material, then granulate it in a 16-mesh stainless steel screen oscillating pellet mill. After the moisture content of the pellets is less than 6%, they are cooled. The wet granules are evenly spread on a drying tray and then sent into a hot air circulating oven for drying. The oven temperature is controlled at 75℃ to cool the granules to the specified moisture content. Finally, the granules are manually sized using a 16-mesh sieve to obtain the compound Chinese medicine preparation granules.

10. The method for preparing the compound traditional Chinese medicine preparation for early intervention in atherosclerotic plaques as described in claim 5, characterized in that, Step S4 involves preparing the concentrated extract into tablets as follows: S401. Phosphatidylcholine and cholesterol are mixed in a molar ratio of 3:1 and ultrasonically treated for 20-40 minutes at a temperature of 60℃ to obtain liposome cores with a particle size controlled at 80±5nm. The liposome cores encapsulate water-soluble components. S402. Liposomes are coated by extruding macrophage membranes and platelet membranes to form liposome membrane structures. The pore size of the membrane extrusion is 200 nm, the coating is performed 15-25 times, and the mass ratio of macrophage membrane to platelet membrane is 1:

1. S403. Immobilize the oxidized phospholipid targeting ligand on the surface of the liposome membrane structure by physical adsorption, so that the density of the oxidized phospholipid targeting ligand reaches 15 μg / cm². S404. The lipid-soluble components are embedded into the liposome membrane structure using a membrane fusion method, with the temperature controlled at 37°C, the pH value at 7.4, and the time at 20-40 minutes.

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