Traditional Chinese medicine composition, granule preparation and preparation method thereof for treating carotid atherosclerosis combined with hyperlipidemia

Abstract

The present invention relates to the field of traditional Chinese medicine technology, and in particular to a Chinese medicine composition, granule preparation and preparation method thereof for treating carotid atherosclerosis combined with hyperlipidemia. The Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia is mainly prepared from the following components in parts by weight: 8-12 parts of Chuanxiong, 8-12 parts of red peony root, 3-7 parts of coptis root, 8-12 parts of red yeast rice and 3-7 parts of roasted liquorice. The Chinese medicine composition provided by the present invention can have good therapeutic effects on the patient group with carotid atherosclerosis combined with hyperlipidemia, which is a common and frequently occurring disease in the field of cardiovascular disease prevention and treatment. In addition, the present invention prepares the Chinese medicine composition into a granule preparation in a certain manner, ensuring the molding rate, solubility rate, bulk density, angle of repose and moisture absorption rate of the preparation, thereby ensuring the efficacy of the preparation, extending the storage time of the product, taking into account the patient's acceptance, and easily realizing large-scale production.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition, a granule preparation and a preparation method thereof for treating carotid atherosclerosis combined with hyperlipidemia. Background Art

[0002] Atherosclerosis (AS) is the pathological basis of cardiovascular and cerebrovascular diseases. How to effectively inhibit the formation and rupture of AS plaques and reduce the incidence of cardiovascular events is a major clinical scientific issue and research hotspot. Elevated blood lipids are a major risk factor for AS. The carotid artery is a window into the formation and progression of systemic AS. Patients with cervical AS have a significantly increased risk of stroke, myocardial infarction, and death.

[0003] The primary strategy for preventing and treating atherosclerosis currently is lipid-lowering, with statins being a commonly used lipid-lowering drug. However, intensive statin lipid-lowering therapy is often associated with intolerable side effects. Currently, there is a lack of effective traditional Chinese medicines for patients with carotid atherosclerosis and hyperlipidemia. The development of a traditional Chinese medicine composition that can effectively prevent and treat carotid atherosclerosis and hyperlipidemia has important clinical and scientific significance.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] One object of the present invention is to provide a Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia, which can effectively prevent and treat carotid atherosclerosis combined with hyperlipidemia and has no toxic side effects.

[0006] Another object of the present invention is to provide a Chinese medicine granule preparation for treating carotid atherosclerosis combined with hyperlipidemia.

[0007] Another object of the present invention is to provide a method for preparing a Chinese medicine granule preparation for treating carotid atherosclerosis combined with hyperlipidemia.

[0008] In order to achieve the above-mentioned object of the present invention, the present invention provides a traditional Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia, which is mainly prepared by the following components in parts by weight:

[0009] 8-12 parts of Chuanxiong, 8-12 parts of red peony root, 3-7 parts of coptis root, 8-12 parts of red yeast rice and 3-7 parts of roasted liquorice.

[0010] In a specific embodiment of the present invention, the traditional Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia is mainly prepared from the following components in parts by weight:

[0011] 10 parts of Ligusticum chuanxiong, 10 parts of red peony root, 5 parts of coptis chinensis, 10 parts of red yeast rice and 5 parts of prepared liquorice root.

[0012] In a specific embodiment of the present invention, the traditional Chinese medicine composition further comprises dextrin.

[0013] Another aspect of the present invention provides a Chinese medicine granule preparation for treating carotid atherosclerosis combined with hyperlipidemia, which is prepared using any one of the above-mentioned Chinese medicine compositions for treating carotid atherosclerosis combined with hyperlipidemia.

[0014] Another aspect of the present invention provides a method for preparing any one of the above-mentioned Chinese medicine granule preparations, comprising the following steps:

[0015] (a) Weighing Chuanxiong, Paeonia lactiflora, Coptidis rhizome, Monascus koji, and Radix Glycyrrhizae uralensis by weight to obtain a mixed medicinal material; extracting the mixed medicinal material three times with water, combining the aqueous extracts, filtering, and concentrating to obtain an extract;

[0016] (b) mixing the extract and dextrin in a mass ratio of 1: (1.8-2.2), granulating, drying, and granulating to obtain the Chinese medicine granule preparation;

[0017] The relative density of the extract at 50°C is 1.2-1.25 g / cm 3 In a specific embodiment of the present invention, in the three water extractions, the solid-liquid ratio of the first extraction is 1:(10-12), and the time of the first extraction is 0.5-1h; the solid-liquid ratio of the second extraction is 1:(8-10), and the time of the second extraction is 0.5-1h; the solid-liquid ratio of the third extraction is 1:(8-10), and the time of the third extraction is 0.5-1h.

[0018] In a specific embodiment of the present invention, a fluidized bed is used for the granulation, the material temperature is 80-90° C., the inlet air temperature is 100-110° C., and the feed speed is 280-320 rpm.

[0019] In a specific embodiment of the present invention, the drying is carried out in an oven at 75-85° C., and the drying time is 1-2 hours.

[0020] In a specific embodiment of the present invention, the granules are passed through a 10-60 mesh sieve.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] (1) The Chinese medicine composition provided by the present invention has good therapeutic effects on a patient population with carotid atherosclerosis combined with hyperlipidemia, a common and frequently occurring disease in the field of cardiovascular disease prevention and treatment;

[0023] (2) The present invention prepares the Chinese medicine composition into a granular preparation in a certain manner without changing the efficacy of the Chinese medicine composition, thereby ensuring the molding rate, dissolution rate, bulk density, angle of repose and moisture absorption rate of the preparation, and ensuring the efficacy of the preparation, extending the storage time of the product, taking into account the patient acceptance, and easily realizing large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0025] Figure 1 Pathological HE-stained sections of carotid arteries of mice in each group (×200);

[0026] Figure 2 is the ratio of plaque area to vessel area in carotid artery sections of mice in each group;

[0027] Figure 3 The immunohistochemical staining of CD68 protein in the carotid artery tissue of mice in each group (×400);

[0028] Figure 4 Immunofluorescence expression of CD86 and CD206 in the carotid artery tissues of mice in each group (×200);

[0029] Figure 5 The expression of iNOS, Arg-1, PPARγ, and NF-κB p65 proteins in the carotid artery tissues of mice in each group;

[0030] Figure 6 The comparison results of four blood lipid items between the two groups of patients;

[0031] Figure 7 The comparison results of carotid artery intima-media thickness between the two groups of patients;

[0032] Figure 8 The comparison results of inflammation-related factors between the two groups of patients;

[0033] Figure 9 This is the comparison result of TCM syndrome scores between the two groups of patients;

[0034] Figure 10 This is the comparison result of the efficacy of TCM syndromes between the two groups of patients;

[0035] in, Figures 1 to 5In the table, Normal is the normal group, Model is the model group, Atorvastatin is the statin group, HXJD is the Chinese medicine equivalent dose group, H-HXJD is the Chinese medicine high dose group, and HXJD+Atorvastatin is the combined medication group. DETAILED DESCRIPTION

[0036] The technical scheme of the present invention will be clearly and completely described below in conjunction with specific embodiments, but it will be understood by those skilled in the art that the following described embodiments are part of embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention, and should not be considered as limiting the scope of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work premise belong to the scope of protection of the present invention. Those who do not specify specific conditions in the embodiments are carried out according to normal conditions or the conditions recommended by the manufacturer. Those whose reagents or instruments are not specified by the manufacturer are conventional products that can be purchased commercially.

[0037] In one aspect, the present invention provides a traditional Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia, which is mainly prepared from the following components in parts by weight:

[0038] 8-12 parts of Chuanxiong, 8-12 parts of red peony root, 3-7 parts of coptis root, 8-12 parts of red yeast rice and 3-7 parts of roasted liquorice.

[0039] The Chinese medicine composition provided by the present invention can have good therapeutic effects on a patient group suffering from a frequently occurring and common disease in the field of cardiovascular disease prevention and treatment, namely, carotid atherosclerosis combined with hyperlipidemia.

[0040] Chuanxiong, pungent and warm, enters the liver and gallbladder meridians and can be used to promote blood circulation and qi, dispel wind and relieve pain, and has certain therapeutic effects on headaches, menstrual irregularities, and symptoms such as promoting blood circulation and qi. Red peony root, bitter and slightly cold, enters the liver meridian and has the effects of clearing heat and cooling blood, promoting blood circulation and removing blood stasis. Coptis chinensis, bitter and cold, enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians and has the effects of clearing heat and dampness, purging fire and detoxifying. Red yeast rice, sweet and warm, promotes digestion and soothes the stomach, promotes blood circulation and relieves pain, strengthens the spleen, and dries the stomach. Radix Glycyrrhizae Preparata, neutral and slightly warm, is good at tonifying the spleen and stomach, tonifying the middle and relieving urgency, and replenishing qi and restoring the pulse. The Chinese medicine composition of the present invention is prepared by compounding Chuanxiong, red peony root, coptis root, red yeast rice and roasted liquorice in proportion. Chuanxiong is pungent, fragrant, warm and dry, and has a good mobility. It can not only invigorate blood circulation and dissipate blood stasis, but also promote the flow of qi and relieve stagnation, and can move qi upward to the head and downward to the sea of ​​blood, and relieve depression in the middle. It is a "blood-qi medicine"; red peony root is bitter and cold in nature, can clear away heat and cool blood, invigorate blood circulation and relieve pain, and can control the warm and dry nature of Chuanxiong. The two medicines complement each other in their medicinal properties when used together, and have the effect of invigorating blood circulation and dissipating blood stasis; coptis root is very bitter and cold, can clear away heat, purge fire and detoxify , Coptis chinensis clears away heat from the qi, while red peony root clears away heat from the nutrient fluid. The combination of the two medicines can synergistically enhance the heat-clearing effect; Red yeast rice is sweet and warm in nature, and is good at breaking up blood and activating blood circulation, lowering lipids and clearing turbidity. It has a wide range of pharmacological effects such as lowering blood lipids, blood sugar, and blood pressure. When used together with red peony root and Chuanxiong, they achieve the functions of mutual dependence, mutual assistance, and mutual promotion; Roasted licorice is flat and slightly warm in nature, and can tonify the middle and relieve urgency. The combination of these medicines is good at activating blood circulation and detoxifying, and can achieve the prevention and treatment of carotid atherosclerosis combined with hyperlipidemia.

[0041] For example, in different embodiments, the amounts of each component in the Chinese medicine composition can be as follows, calculated by weight:

[0042] The dosage of Chuanxiong can be 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, or any two of them or a range consisting of any two of them;

[0043] The dosage of red peony root can be 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, or any two of them or a range consisting of any two of them;

[0044] The dosage of Coptis chinensis can be 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, or any two of them or a range consisting of any two of them;

[0045] The amount of red yeast rice can be 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, or any two of them or a range consisting of any two of them;

[0046] The dosage of licorice root can be 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, or any two parts thereof or a range consisting of any two parts.

[0047] In a specific embodiment of the present invention, the Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia is mainly prepared from the following components in parts by weight:

[0048] 10 parts of Ligusticum chuanxiong, 10 parts of red peony root, 5 parts of coptis chinensis, 10 parts of red yeast rice and 5 parts of prepared liquorice root.

[0049] The present invention further optimizes the ratio of Chuanxiong, red peony root, coptis root, red yeast rice and licorice. When the dosage of the five components meets the above conditions, it is more helpful to take into account the content and ratio of the main active ingredients of each traditional Chinese medicine during co-extraction, thereby facilitating the efficacy of the medicine.

[0050] In a specific embodiment of the present invention, the traditional Chinese medicine composition further comprises dextrin.

[0051] For Chinese medicine compositions, whether liquid dosage form or solid dosage form, most still have more obvious bitterness. In order to improve patient acceptance and improve patient medication compliance, some components can be added to eliminate or mask the bitterness to achieve corresponding effects. However, the introduction of other components may affect drug efficacy on the one hand, causing product quality control to be more difficult, and on the other hand, change the drug dissolution situation and affect bioavailability. The present invention, through the introduction of dextrin, further cooperates with the granulation method of granule preparation, takes into account the excellent forming rate, dissolution rate, bulk density, angle of repose and moisture absorption rate of granule preparation, and ensures the stability, drug efficacy and medication compliance of the preparation.

[0052] Another aspect of the present invention provides a traditional Chinese medicine granule preparation for carotid atherosclerosis combined with hyperlipidemia, which is prepared using any one of the above-mentioned traditional Chinese medicine compositions for carotid atherosclerosis combined with hyperlipidemia.

[0053] Another aspect of the present invention provides a method for preparing any one of the above-mentioned Chinese medicine granule preparations, comprising the following steps:

[0054] (a) Weighing Chuanxiong, Paeonia lactiflora, Coptidis rhizome, Monascus koji, and Radix Glycyrrhizae (Glycyrrhizae) by weight to obtain a mixed medicinal material; extracting the mixed medicinal material three times with water, combining the aqueous extracts, filtering, and concentrating to obtain an extract;

[0055] (b) mixing the extract and dextrin in a mass ratio of 1:(1.8-2.2), granulating, drying, and granulating to obtain a Chinese medicine granule preparation;

[0056] The relative density of the extract at 50°C is 1.2-1.25 g / cm 3 .

[0057] The method for preparing a traditional Chinese medicine granule preparation of the present invention has the advantages of easy granulation and scalable production. Furthermore, the prepared granules have suitable forming rate, dissolution rate, bulk density, angle of repose, and moisture absorption rate. Furthermore, the long-term stability of the granule preparation is improved, thereby enhancing the storage stability of the granule preparation and ensuring long-term efficacy.

[0058] The introduction of dextrin can, on the one hand, improve adhesion and enhance drug adhesion when mixed with the extract; on the other hand, it can improve the solubility of the granular preparation in water and, to a certain extent, reduce the bitterness of the pharmaceutical composition. However, studies have found that when the dextrin dosage is too high, the viscosity is too high, the resulting granules are large, and the molding rate is too low. In addition, excessive dextrin introduction can easily lead to increased granule moisture absorption, affecting storage stability. When the dextrin dosage is too low, the viscosity is relatively low, the resulting granules are small, which also leads to a low molding rate. In addition, the dextrin content is relatively low, the bitterness is less masked, and the solubility of the granules is insufficient, affecting the efficacy. In the preparation of the granular preparation of the Chinese medicine composition of the present invention, the mass ratio of the extract to dextrin can be 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, or any point value between them or a range consisting of any two of them. Adjusting the ratio within the above range helps to balance the various properties of the granular preparation.

[0059] Through research, it was found that the viscosity of the concentrated extract has a certain influence on the subsequent granulation process. After concentration, the viscosity of the liquid changes significantly. If the concentration degree of the water extract is too high, the viscosity of the liquid extract obtained is too large, and the size of the prepared particles is larger; if the concentration degree of the water extract is too low, the viscosity of the liquid extract obtained is too small, and the size of the prepared particles is smaller; the forming rate is low. The present invention regulates the relative density of the extract and combines it with a certain proportion of dextrin. It can form particles in one step without adding other substances, which significantly improves production efficiency; at the same time, in the granulation process, it helps to form particles of moderate size, ensure the particle forming rate, and ensure the various properties of the particles. For example, in different embodiments, the relative density of the extract of the present invention at 50°C can be 1.2g / cm 3 , 1.21g / cm 3 , 1.22g / cm 3 , 1.23g / cm 3 , 1.24g / cm 3 , 1.25g / cm 3 Or a range consisting of any two of them.

[0060] The granules of the present invention can be successfully prepared simply by compounding the extract and dextrin, without the addition of additional additives. Furthermore, the compounding of the extract and dextrin not only reduces the dextrin content at the same dosage, making it easier for patients to take, but also shortens the subsequent drying time, preventing loss of the active ingredient, while ensuring granule yield and low hygroscopicity.

[0061] In a specific embodiment of the present invention, in the three water extractions, the solid-liquid ratio of the first extraction is 1:(10-12), and the time of the first extraction is 0.5-1h; the solid-liquid ratio of the second extraction is 1:(8-10), and the time of the second extraction is 0.5-1h; the solid-liquid ratio of the third extraction is 1:(8-10), and the time of the third extraction is 0.5-1h.

[0062] Extraction conditions were investigated based on the content of the target components and the solid yield obtained by extraction, with reference to the relevant test index components in the Chinese Pharmacopoeia. The material-to-liquid ratio and extraction time of the three aqueous extractions of the present invention were adjusted to ensure the active ingredient content of each component, fully realizing the efficacy of the combination while ensuring the solid yield obtained by extraction. It should be noted that the material-to-liquid ratio in this invention is defined as a ratio of g:mL. For example, in different embodiments, the solid-liquid ratio of the first extraction can be 1:10, 1:10.5, 1:11, 1:11.5, 1:12 or a range consisting of any two thereof; the time for the first extraction can be 0.5h, 0.6h, 0.8h, 1h or a range consisting of any two thereof; the solid-liquid ratio of the second extraction can be 1:8, 1:8.5, 1:9, 1:9.5, 1:10 or a range consisting of any two thereof; the time for the second extraction can be 0.5h, 0.6h, 0.8h, 1h or a range consisting of any two thereof; the solid-liquid ratio of the third extraction can be 1:8, 1:8.5, 1:9, 1:9.5, 1:10 or a range consisting of any two thereof; the time for the third extraction can be 0.5h, 0.6h, 0.8h, 1h or a range consisting of any two thereof. Under the extraction conditions of the present invention, if the extraction time is further extended, not only the time cost will be increased, but also the impurities (ineffective ingredients) will increase, the proportion of active ingredients in the extract will be reduced, and the efficacy will be reduced.

[0063] In a specific embodiment of the present invention, a fluidized bed is used for granulation. In the fluidized bed granulation, the material temperature is 80-90° C., the inlet air temperature is 100-110° C., the feed speed is 280-320 rpm, and the atomization pressure is 0.1-0.2 MPa.

[0064] For example, in different embodiments, during fluidized bed granulation, the material temperature can be 80°C, 82°C, 85°C, 88°C, 90°C, or a range consisting of any two thereof; the inlet air temperature can be 110°C, 112°C, 115°C, 118°C, 112°C, or a range consisting of any two thereof; the feed rate can be 280 rpm, 290 rpm, 300 rpm, 310 rpm, 320 rpm, or a range consisting of any two thereof; and the atomization pressure can be 0.1 MPa, 0.12 MPa, 0.15 MPa, 0.18 MPa, 0.2 MPa, or a range consisting of any two thereof. By regulating the fluidized bed granulation conditions within the above ranges and combining them with appropriate material ratios, the granule formation rate and granule properties can be guaranteed.

[0065] In a specific embodiment of the present invention, in step (b), drying is carried out in an oven at 75-85° C. for 1-2 hours.

[0066] In a specific embodiment of the present invention, the granules are sieved through a 10-60 mesh sieve.

[0067] In actual operation, 10 mesh sieve and 60 mesh sieve are used for granulation.

[0068] Example 1

[0069] This embodiment provides a method for preparing a traditional Chinese medicine composition and its granule preparation for treating carotid atherosclerosis combined with hyperlipidemia. The traditional Chinese medicine composition is mainly prepared from the following components in parts by weight:

[0070] 10 parts of Ligusticum chuanxiong, 10 parts of red peony root, 5 parts of coptis chinensis, 10 parts of red yeast rice and 5 parts of prepared liquorice root.

[0071] The preparation method of the granule preparation of the Chinese medicine composition comprises the following steps:

[0072] (1) Chuanxiong, red peony root, coptis root, red yeast rice and licorice root were weighed in proportion and mixed. The mixture was decocted with water at a material-liquid ratio of 1:12 for 1 hour and the water extract was collected. The mixture was then decocted with water at a material-liquid ratio of 1:10 for 1 hour and the water extract was collected. The mixture was then decocted with water at a material-liquid ratio of 1:10 for 1 hour and the water extract was collected. The three water extracts were combined, filtered and concentrated under reduced pressure at a concentration pressure of 0.25 MPa and a concentration temperature of 70°C to obtain an extract. The relative density of the extract at 50°C was 1.22 g / cm 3 .

[0073] (2) The extract and dextrin were mixed evenly in a mass ratio of 1:2; then, granules were made using a fluidized bed with a 12-mesh sieve (during granulation, the material temperature was 85°C, the inlet air temperature was 105°C, the feed rate was 300 rpm, and the atomization pressure was 0.1 MPa). After drying in an oven at 80°C for 1 hour, granules were sieved with a 10-mesh sieve and a 60-mesh sieve. Granules that passed through the 10-mesh sieve but not the 60-mesh sieve were taken as the finished granule preparation.

[0074] Example 2 group

[0075] This example is carried out with reference to Example 1, with the only difference being that the extraction conditions in step (1) are different, as shown below:

[0076] Example 2a: The mixture was boiled and extracted for 0.5 h at a material-liquid ratio of 1:10, and the aqueous extract was collected; the mixture was then boiled and extracted for 0.5 h at a material-liquid ratio of 1:8, and the aqueous extract was collected; the mixture was then boiled and extracted for 0.8 h at a material-liquid ratio of 1:8, and the aqueous extract was collected; and subsequent concentration was the same as in Example 1;

[0077] Example 2b: The mixture was boiled and extracted for 1.5 hours at a material-liquid ratio of 1:12, and the water extract was collected; the mixture was boiled and extracted for 1.5 hours at a material-liquid ratio of 1:10, and the water extract was collected; the mixture was boiled and extracted for 1.5 hours at a material-liquid ratio of 1:10, and the water extract was collected; the subsequent concentration was the same as in Example 1;

[0078] Example 2c: The mixture was boiled and extracted with water at a material-liquid ratio of 1:15 for 1 hour, and the water extract was collected; the mixture was boiled and extracted with water at a material-liquid ratio of 1:12 for 1 hour, and the water extract was collected; the mixture was boiled and extracted with water at a material-liquid ratio of 1:12 for 1 hour, and the water extract was collected; the subsequent concentration was the same as in Example 1;

[0079] Example 2d: The mixture was boiled and extracted with water at a material-liquid ratio of 1:8 for 1 hour, and the water extract was collected; the mixture was boiled and extracted with water at a material-liquid ratio of 1:8 for 1 hour, and the water extract was collected; the mixture was boiled and extracted with water at a material-liquid ratio of 1:8 for 1 hour, and the water extract was collected; the subsequent concentration was the same as in Example 1;

[0080] Example 2e: Add water at a material-liquid ratio of 1:12, decoct and extract for 1 hour, collect the water extract; then add water at a material-liquid ratio of 1:10, decoct and extract for 1 hour, collect the water extract; then add water at a material-liquid ratio of 1:10, decoct and extract for 1 hour, collect the water extract; then add water at a material-liquid ratio of 1:10, decoct and extract for 1 hour, collect the water extract; subsequent concentration is the same as in Example 1.

[0081] By testing the solid yield and index component content in the combined water extracts obtained by different extraction processes in Example 1 and Example 2, it was found that the solid yield and index component content of the water extract obtained by the extraction process of Example 1 were the best, followed by Example 2a, while Examples 2b to 2e could not take into account both the solid yield and index component content, and the effects were not as good as those of Example 1 and Example 2a.

[0082] Specifically, by comparing Example 1 and Example 2b, it can be seen that when the extraction time is extended, the yield of the index component does not change significantly; by comparing Example 1 and Example 2c, it can be seen that when the amount of water is increased, the yield of the index component does not increase significantly. At the same time, due to the increase in the amount of water, the subsequent concentration time is increased, which is more likely to cause the loss of effective ingredients; by comparing Example 1 and Example 2d, it can be seen that when the amount of water is reduced, the yield of the index component decreases; by comparing Example 1 and Example 2e, it can be seen that the yield of the index component does not change significantly when the number of extractions is increased.

[0083] Example 3 group

[0084] This example is carried out with reference to Example 1, with the only difference being that the relative density of the extract obtained by the reduced pressure concentration in step (1) is different, as shown below:

[0085] Example 3a: The relative density of the obtained extract at 50°C is 1.20 g / cm 3 ;

[0086] Example 3b: The relative density of the obtained extract at 50°C is 1.25 g / cm 3 ;

[0087] Example 3c: The relative density of the obtained extract at 50°C is 1.15 g / cm 3 ;

[0088] Example 3d: The relative density of the obtained extract at 50°C is 1.30 g / cm 3 .

[0089] By testing the particle formation rates obtained by granulation using different extract densities in Example 1 and Example 3, it was found that the particle formation rate obtained under the extract density condition of Example 1 was higher, the particle formation rate obtained under the extract density conditions of Examples 3a to 3c was also higher, but the particle formation rate obtained under the extract density condition of Example 3d was lower.

[0090] According to the above test results, the relative density of the extract at 50°C is regulated to be between 1.2 and 1.25 g / cm 3The range of the molding rate of the obtained particles can be guaranteed. Comparing Example 1 and Example 3c, it can be seen that when the relative density of the extract is low, although the molding rate is relatively high, the obtained particles have relatively poor fluidity and are easy to absorb moisture. Comparing Example 1 and Example 3d, it can be seen that when the relative density of the extract is high, although the particles are easy to shape, the viscosity is high and the particle size is large, resulting in a low molding rate.

[0091] Example 4 Group

[0092] This example is carried out with reference to Example 1, with the only difference being that the types or amounts of auxiliary materials used in step (2) are different, as shown below:

[0093] Example 4a: The mass ratio of the extract to dextrin is 1:1.8, and the rest remain unchanged;

[0094] Example 4b: The mass ratio of the extract to dextrin is 1:2.2, and the rest remain unchanged;

[0095] Example 4c: The mass ratio of the extract to dextrin is 1:1.5, and the rest remain unchanged;

[0096] Example 4d: The mass ratio of the extract to dextrin is 1:2.5, and the rest remain unchanged;

[0097] Example 4e: The dextrin in Example 1 was replaced by an equal weight of lactose, and the rest remained unchanged;

[0098] Example 4f: The dextrin in Example 1 was replaced by an equal weight of soluble starch, and the rest remained unchanged;

[0099] Example 4g: The dextrin in Example 1 was replaced by an equal weight of microcrystalline cellulose, and the rest remained unchanged;

[0100] Example 4h: The dextrin in Example 1 was replaced by an equal weight of mannitol, and the rest remained unchanged.

[0101] The finished granule preparations obtained by using different excipients in Example 1 and Example 4 were comprehensively evaluated using moisture absorption rate, forming rate, dissolution rate, bulk density, angle of repose, and economic efficiency as indicators.

[0102] In the calculation method of the comprehensive evaluation index, the comprehensive evaluation index = (20 / maximum formability value) × formability value + (15 / maximum bulk density value) × bulk density value + (minimum angle of repose value × 15) / angle of repose value + (20 / maximum solubility value) × solubility value + (minimum moisture absorption value × 20) / moisture absorption value + (minimum economic value × 10) / economic value.

[0103] Formability: Refer to the double screening method under the granule particle size section of Part 4 of the 2020 edition of the Chinese Pharmacopoeia. The prepared granules are passed through a No. 1 sieve and a No. 5 sieve. Granules that pass through the No. 1 sieve but not the No. 5 sieve are considered acceptable. Formability (%) = (weight of granules per sieve / total number of granules) × 100. Maximum Formability Value: The maximum value among the five measured formation rate values.

[0104] Bulk density: Weigh 4g of each pellet and place it in a graduated cylinder. Vibrate the cylinder up and down until the pellets are compacted. Read the volume in mL near the scale mark, which is the volume. Calculate the bulk density: Bulk density = (pellet weight / particle volume) × 100%. Maximum bulk density: The maximum value among the five measured bulk density values.

[0105] Angle of Repose: Using the tandem funnel method, connect three funnels in series using an iron stand and secure them to a flat graph paper, 1 cm above the graph paper. Pour particles along the walls of the funnels into the highest funnel. Stop when the top of the particle cone on the graph paper touches the bottom of the funnel. Record the diameter of the cone base as 2R and calculate the angle of repose α, α = arctan(H / R). Repeat this measurement five times and calculate the average. Minimum angle of repose is the lowest of the five measured angles of repose.

[0106] Solubility: Dry a 50 mL centrifuge tube to constant weight. Accurately weigh 1 g of pellets into the tube. Add 20 mL of boiling water, stir, and shake. Centrifuge at 4000 rpm for 10 min. Discard the supernatant. Oven-dry the residue at 80°C to constant weight. Accurately weigh the residue and calculate the solubility: Solubility (%) = (mass of dissolved pellets / total pellet mass) × 100%. Maximum solubility value: The maximum value among the five measured solubility values.

[0107] Moisture Absorption Rate: Place a desiccator filled with saturated sodium chloride at room temperature for 48 hours, maintaining a relative humidity of 75%. Accurately weigh 1g of the prepared granules into a constant-weight weighing bottle and dry to a constant weight. Remove the bottle cap and place the granules in a desiccator filled with saturated sodium chloride. After 48 hours, accurately weigh them. Moisture Absorption Rate (%) = (Weight of granules after moisture absorption - Weight of granules before moisture absorption) / Weight of granules before moisture absorption × 100%. Minimum Moisture Absorption Rate: The minimum of the five measured moisture absorption rates.

[0108] Economy: The unit price of 1 kg of each auxiliary material. Minimum economy: The lowest value among the unit prices of the five auxiliary materials.

[0109] According to the above-mentioned comprehensive evaluation index calculation method, the present invention adopts an extract and dextrin in a ratio of 1: (1.8-2.2), which is more helpful to ensure the moisture absorption rate, molding rate, dissolution rate, bulk density, angle of repose and economy of the finished granule preparation. Preferably, an extract and dextrin in a ratio of 1:2 is used.

[0110] Example 5 Group

[0111] This example is carried out with reference to Example 1, with the only difference being that the amounts of Chuanxiong, red peony root, coptis root, red yeast rice and licorice root are different, as shown below:

[0112] Example 5a: comprising, by weight, 8 parts of Chuanxiong, 8 parts of Red Peony Root, 3 parts of Coptis chinensis, 8 parts of Red Yeast Rice and 3 parts of Radix Glycyrrhizae Preparata;

[0113] Example 5b: comprising, by weight, 12 parts of Chuanxiong, 12 parts of red peony root, 7 parts of coptis root, 12 parts of red yeast rice and 7 parts of prepared liquorice root;

[0114] Example 5c: comprising, by weight, 5 parts of Chuanxiong, 10 parts of Red Peony Root, 5 parts of Coptis chinensis, 10 parts of Red Yeast Rice and 5 parts of Radix Glycyrrhizae Preparata;

[0115] Example 5d: comprising, by weight, 15 parts of Chuanxiong, 10 parts of red peony root, 5 parts of coptis root, 10 parts of red yeast rice and 5 parts of prepared liquorice root;

[0116] Example 5e: comprising, by weight, 10 parts of Chuanxiong rhizome, 10 parts of red peony root, 5 parts of coptis root, 5 parts of red yeast rice and 5 parts of prepared liquorice root;

[0117] Example 5f: The composition comprises, by weight, 10 parts of Chuanxiong rhizome, 10 parts of red peony root, 5 parts of coptis root, 15 parts of red yeast rice and 5 parts of prepared liquorice root.

[0118] Experimental Example 1

[0119] The stability of the finished granule preparation of Example 1 was studied by conducting a long-term stability test and an accelerated stability test. The stability test verified that the stability of the finished granule preparation obtained using the granulation conditions of Example 1 of the present invention was significantly better than that of the other Examples 2 to 4.

[0120] Long-term stability testing: The long-term stability test employed a sampling method similar to actual drug storage conditions. Pilot samples of the finished granule preparation were placed in commercially available packaging (polyester / aluminum / polyethylene composite film for pharmaceutical packaging) and stored at room temperature for six months. Samples were collected at 0, 3, and 6 months, for a total of three samplings over a total of six months. The results demonstrated that the pilot samples of the finished granule preparation prepared in Example 1 of the present invention exhibited high long-term stability.

[0121] The finished granule preparations after packaging are brown-yellow granules after 0, 3 and 6 months, with a slight odor and a slightly bitter taste.

[0122] According to the thin layer chromatography method (General Chapter 0502 of Part IV of the 2020 edition of the "Chinese Pharmacopoeia"), after 0, 3, and 6 months of testing, the position and fluorescence of the main spots of the solution prepared from the pilot sample of the finished granule preparation were consistent with those of the paeoniflorin reference substance, Chuanxiong reference medicinal material, Monascus reference medicinal material, berberine hydrochloride reference substance, Coptis chinensis reference medicinal material, and Licorice reference medicinal material, respectively. The standard substances were all purchased from the China Food and Drug Inspection Institute.

[0123] The fill volume variation of finished granule preparations was determined using the following method: 10 bags of granule preparations were randomly selected, the packaging removed, and the contents of each bag accurately weighed. The weight of each bag was then compared to the labeled fill volume. The results showed that the fill volume variation of the three batches of granule preparations was within the specified limits (±5%), meeting the requirements of the pharmacopoeia.

[0124] The particle size is determined according to the particle size and particle size distribution determination method in the "Pharmacopoeia of the People's Republic of China (2020 Edition)"; the moisture content is determined according to the moisture determination method in the "Pharmacopoeia of the People's Republic of China (2020 Edition)"; the total aerobic bacteria, total mold and yeast counts of the finished granule preparation are tested and Escherichia coli are tested according to the method of microbial limit inspection of non-sterile products in Part IV, 1105 of the 2020 edition of the "Chinese Pharmacopoeia".

[0125] The results of the long-term stability study of the granule preparation are shown in Table 1.

[0126] Table 1 Long-term stability test results of granule preparations

[0127] Inspection indicators 0 months 3 months 6 months Temperature (℃) 26 23 25 Humidity (%RH) 30 48 52 Difference in filling volume Comply with regulations Comply with regulations Comply with regulations granularity 1.6％ 1.6％ 1.6％ Moisture 2.3％ 2.3％ 1.8％ Total aerobic bacteria <10cfu / g <10cfu / g <10cfu / g Total mold and yeast count <10cfu / g <10cfu / g <10cfu / g Escherichia coli Not detected Not detected Not detected

[0128] Accelerated stability testing: The accelerated stability test employed a sample retention method under high temperature and high humidity conditions. Pilot samples of the finished granule preparation were placed in commercially available packaging (polyester / aluminum / polyethylene composite film for pharmaceutical packaging) and then placed in a comprehensive pharmaceutical stability testing chamber. The test was conducted at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5% for six months. Samples were collected at 0, 1, 2, 3, and 6 months for a total of five tests, covering a period of six months. The results showed that the finished granule preparation met the specified specifications during the accelerated stability testing period. The properties of the packaged Huoxue Jiedu Optimized Granules remained unchanged after 0, 1, 2, 3, and 6 months, all showing a brownish-yellow granule color with a slight odor and a slightly bitter taste. The location and fluorescence of the main spot of the test sample were consistent with those of the paeoniflorin reference standard, the Chuanxiong reference material, the red yeast rice reference material, the berberine hydrochloride reference material, the Coptis chinensis reference material, and the Glycyrrhiza uralensis reference material, respectively. The results of the testing for fill volume variation, particle size, moisture content, and microbial limits are shown in Table 2.

[0129] Table 2 Accelerated stability test results of granule preparations

[0130]

[0131]

[0132] Experimental Example 2

[0133] The granule preparation of Example 1 was subjected to acute toxicity and chronic toxicity tests.

[0134] SPF SD rats were used as research subjects to conduct acute toxicity tests (single-dose toxicity tests) and long-term toxicity tests (6-month repeated-dose toxicity tests) on the pilot products of the finished granule preparations. Normative experimental research was conducted in accordance with the "Classification and Application Material Requirements for Registration of Traditional Chinese Medicines" for innovative Chinese medicines - traditional Chinese medicine compound preparations.

[0135] Long-term toxicity study: SD rats were randomly divided into a solvent control group, a low-dose group (12.5 times the intended clinical dose), a medium-dose group (25 times the intended clinical dose), and a high-dose group (50 times the intended clinical dose). The drugs were administered continuously for 6 months. Basic conditions, hematological parameters, blood biochemistry, organ tissue indices, and pathological examinations were assessed at 13 and 26 weeks of administration. Recovery of these parameters was also observed after the recovery period. Results: No toxic symptoms or significant abnormalities in the test parameters were observed in the experimental rats, and no abnormalities were found in the pathological sections. Acute toxicity study: The drug was administered twice within 24 hours, equivalent to 134 times the intended clinical dose. No significant toxicity was observed.

[0136] Among them, the proposed clinical dosage is: 40g crude drug / day.

[0137] Experimental Example 3

[0138] Animal experiments

[0139] According to the difference in feeding feed, drug administration and dosage, the experimental animals were divided into normal control group, model group, atorvastatin group, high-dose granule preparation group (referred to as high-dose Chinese medicine group), equivalent dose granule preparation group (referred to as equivalent dose Chinese medicine group), equivalent dose granule preparation combined with atorvastatin group (referred to as combined medication group), and the granule preparation was the granule preparation prepared in Example 1. The corresponding drugs were administered orally for 12 weeks. After one week of adaptive feeding with ordinary basic feed, the normal control group was fed with ordinary basic feed; the remaining groups were fed with high-cholesterol and high-fat feed for 2 weeks. The latter formula is made by adding 0.25% cholesterol and 15% fat to ordinary basic feed and mixing them thoroughly. In the third week of the experiment, all groups of mice except the normal control group were cannulated in the right carotid artery to establish a CAS model, and aseptic operation was maintained throughout the animal modeling process. This experiment was divided into 6 groups: C57BL / 6J mice were used as the normal control group (referred to as the normal group), ApoE - / -Mice were randomly divided into a model group, an atorvastatin group (referred to as the statin group), an equivalent dose of the granule preparation group (referred to as the Chinese medicine equivalent dose group), a high dose of the granule preparation group (referred to as the Chinese medicine high dose group), and an equivalent dose of the granule preparation combined with atorvastatin group (referred to as the combination medication group). Drug intervention began at week 9 and continued for 12 weeks. The intervention measures for each group were as follows:

[0140] (1) Normal group: fed with basic feed and given an equal volume of purified water;

[0141] (2) Model group: fed with high-fat diet and cannulated carotid artery, and given an equal volume of purified water;

[0142] (3) statin group: fed with a high-fat diet and cannulated in the carotid artery, and given atorvastatin calcium (10 mg / kg / d);

[0143] (4) Chinese medicine equivalent dose group: high-fat diet + carotid artery cannula, and granular preparation (5.2 g / kg / d);

[0144] (5) High-dose Chinese medicine group: fed with high-fat diet and cannulated in the carotid artery, and given granular preparation (10.4 g / kg / d);

[0145] (6) Combined medication group: fed with high-fat diet and cannulated in the carotid artery, and given granular preparation (5.2 g / kg / d) and atorvastatin calcium (10 mg / kg / d).

[0146] Index detection

[0147] Specimen preparation and sampling

[0148] Carotid atherosclerotic vessel sampling: After 12 weeks of continuous drug administration, mice were anesthetized with an intraperitoneal injection of 50 mg / kg 1% sodium pentobarbital. Eyeballs were removed and blood was collected. The tubes were left at room temperature for 2 hours. After the blood clots had formed and shrank, the blood was centrifuged at 3000 rpm for 10 minutes. The supernatant was collected in a clean centrifuge tube and stored at -80°C until further use. Following blood sampling, the right common carotid artery was excised along the anterior midline of the neck using tissue scissors. The artery was rapidly rinsed with saline until blood was removed. The cannulated common carotid artery was removed, one-third of which was fixed in 10% formaldehyde solution. The remaining two-thirds were divided into two portions, snap-frozen in liquid nitrogen, aliquoted, and quickly transferred to a -80°C freezer for storage. For this experiment, the 10% formaldehyde-fixed carotid artery was stained with hematoxylin and eosin and oil red staining. The remaining carotid artery tissue was quickly plunged into liquid nitrogen and later transferred to a -80°C freezer for further use.

[0149] General conditions: The survival, physical appearance, behavioral activity, mental state, eating, drinking, fur, breathing, mouth, eyes, nose, urine, and feces of each group of mice were observed daily, and the mice were weighed every 5 days.

[0150] Serological testing:

[0151] Blood lipid determination: The serum lipids (TC, TG, LDL-C, HDL-C) of mice were determined by enzymatic method using a fully automatic biochemical analyzer.

[0152] Elisa method was used to detect the levels of serum inflammation-related factors hs-CRP, TNF-α, TGF-β1, iNOS and Arg-1 in each group of mice.

[0153] HE staining was used to observe the pathological morphology of carotid artery tissue. Immunohistochemistry was used to detect the expression of CD68, a universal protein of mouse carotid macrophages. Immunofluorescence was used to detect the expression of CD86, a marker protein of M1 macrophages, and CD206, a marker protein of M2 macrophages. Western Blot was used to detect the expression of iNOS, Arg-1, PPARγ, and NF-κB p65 proteins in mouse carotid artery tissue.

[0154] The specific results are as follows:

[0155] (1) Blood lipid levels: Compared with the model group, the statin group, high-dose Chinese medicine group, and combination group could reduce TC, TG, and LDL-C levels (P<0.05), while the combination group could increase HDL-C level (P<0.05); the equivalent dose of Chinese medicine group could reduce TG and LDL-C levels (P<0.05).

[0156] (2) HE staining results showed: Figure 1 The carotid artery pathological sections of mice in each group were stained with HE. Figure 2 The ratio of plaque area to blood vessel area in carotid artery sections of mice in each group (Note: *P<0.05 vs. normal group, **P<0.01 vs. normal group; # P<0.05vs. model group, ## P < 0.01 vs. model group; ▲ P < 0.05 vs. statin group). The carotid artery lumen in the normal group was intact, with no plaque deposits. All other groups showed varying degrees of intimal thickening, plaque deposits, and accumulation of numerous monocytes, macrophages, and foam cells on the plaque surface. Plaque rupture, hemorrhage, and thrombosis were even observed. After drug intervention, these symptoms were alleviated to varying degrees compared with the model group. Compared with the model group, the ratio of plaque area to vessel area was reduced in the statin group, the high-dose Chinese medicine group, and the combination group (P < 0.05). Compared with the statin group, the combination group further reduced the ratio of plaque area to vessel area (P < 0.05).

[0157] (3) Elisa detection of serum inflammation-related factors: Compared with the model group, the statin group, high-dose Chinese medicine group, and combined drug group could reduce the levels of hs-CRP, TNF-α, and iNOS (P<0.05), and increase the levels of TGF-β1 and Arg-1 (P<0.05); the equivalent dose of Chinese medicine group could reduce the level of TNF-α (P<0.05) and increase the level of Arg-1 (P<0.05).

[0158] (4) Immunohistochemical staining results showed: Figure 3 The immunohistochemical staining of CD68 protein in the carotid artery tissue of mice in each group; compared with the model group, the expression of CD68 protein in the carotid artery of mice in the statin group, high-dose Chinese medicine group, and combination drug group was significantly decreased (P<0.05); compared with the statin group, the combination drug group could further reduce the CD68 level (P<0.05).

[0159] (5) Immunofluorescence staining results showed: Figure 4 Immunofluorescence analysis of CD86 and CD206 in the carotid artery tissues of mice in each group showed that compared with the model group, CD86 protein expression decreased to varying degrees in the statin group, the equivalent-dose Chinese medicine group, the high-dose Chinese medicine group, and the combination drug group (P<0.05). CD206 immunofluorescence analysis showed that compared with the model group, CD206 expression increased to varying degrees in the statin group, the high-dose Chinese medicine group, and the combination drug group (P<0.05).

[0160] (6) Western Blot results show: Figure 5 The expression of iNOS, Arg-1, PPARγ, and NF-κB p65 proteins in the carotid artery tissues of mice in each group was analyzed. Compared with the model group, the statin group, high-dose Chinese medicine group, and combination group downregulated the expression of iNOS (P<0.05). Compared with the model group, the statin group, equivalent-dose Chinese medicine group, high-dose Chinese medicine group, and combination group upregulated the expression of Arg-1 (P<0.05). Compared with the model group, the statin group, equivalent-dose Chinese medicine group, high-dose Chinese medicine group, and combination group upregulated the expression of PPARγ (P<0.05). Compared with the model group, the statin group, high-dose Chinese medicine group, and combination group downregulated the expression of NF-κB p65 (P<0.05). Compared with the statin group, the combination group further upregulated the expression of Arg-1 and PPARγ (P<0.05).

[0161] Conclusion: This study established a mouse model of carotid atherosclerosis and intervened with the Chinese medicine composition, confirming the effectiveness of the Chinese medicine composition in lowering blood lipids and anti-atherosclerosis. At the same time, relevant indicators such as inflammatory factors, macrophage phenotype and PPARγ / NF-κB signaling pathway were detected. The results showed that the Chinese medicine composition of the present invention may regulate macrophage polarization through the PPARγ / NF-κB signaling pathway, thereby exerting an anti-atherosclerotic effect.

[0162] According to the above method, the granule preparations of Examples 5a to 5f were subjected to animal experiments to verify that Examples 5a to 5b had certain effects of lowering blood lipids and resisting atherosclerosis, but the effects were weaker than those of Example 1; the effects of Examples 5c to 5f were even weaker than those of Examples 5a to 5b.

[0163] Experimental Example 4

[0164] Clinical trials

[0165] 1. Research subjects

[0166] The study subjects were 60 patients (30 in each group) from the outpatient and ward departments of the Department of Cardiology at Xiyuan Hospital, China Academy of Chinese Medical Sciences. They met the diagnostic criteria and inclusion / exclusion criteria for hyperlipidemia and carotid atherosclerosis. They were then randomly divided into two groups. The control group received atorvastatin, while the experimental group received the Chinese medicine composition of Example 1 in addition to the control group's treatment. Both groups were treated for 12 weeks.

[0167] 2. Diagnostic criteria

[0168] (1) Hyperlipidemia: refer to the "Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults (2016 Revised Edition)" published by the Joint Committee for the Revision of the Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults;

[0169] (2) With reference to the "Chinese Consensus on the Diagnosis and Treatment of Head and Neck Atherosclerosis", vascular ultrasound examination confirmed that the diagnosis criteria for carotid atherosclerosis were met;

[0170] (3) Syndrome differentiation and classification: The diagnostic criteria for heat-toxic blood stasis syndrome were formulated with reference to the 2016 “Practical Diagnostic Criteria for Blood Stasis Syndrome” and the 2011 “Quantitative Criteria for Syndrome Differentiation and Diagnosis of Toxic-induced Pathogenesis in Stable Coronary Heart Disease”. The specific diagnostic criteria are as follows:

[0171] Main symptoms: dizziness;

[0172] Secondary symptoms: chest tightness, bitter taste in the mouth, dry and hard stools;

[0173] Tongue: Dark red tongue, or with ecchymosis, yellow fur; sublingual veins are purple or crimson;

[0174] Pulse: The pulse is rough and rapid;

[0175] Complexion: complexion or lips and nails are dark purple.

[0176] Two of these are sufficient for diagnosis.

[0177] Quantitative points are scored based on the presence or absence of symptoms and the severity of the symptoms (mild, moderate, severe), with 0, 3, 6, and 9 points representing no symptoms, mild, moderate, and severe symptoms, respectively. Tongue coating and pulse condition are not scored.

[0178] 3. Inclusion criteria

[0179] (1) 40 years old < age < 75 years old;

[0180] (2) Meet the diagnostic criteria for primary hyperlipidemia, meeting any of the following: TC ≥ 5.2 mmol / L; LDL-C ≥ 3.4 mmol / L; TG ≥ 1.7 mmol / L;

[0181] (3) Vascular ultrasound examination confirmed that the diagnostic criteria for carotid atherosclerosis were met, with carotid intima-media thickness (IMT) and carotid stenosis <50%;

[0182] (4) According to TCM diagnosis, it is a syndrome of blood stasis and toxins;

[0183] (5) Although taking lipid-lowering drugs, they have stopped taking them for 2 weeks or more;

[0184] (6) Voluntarily participate in this study and sign the informed consent.

[0185] 4. Case exclusion criteria

[0186] (1) Patients with a history of coronary heart disease, or combined with uncontrolled hypertension (sitting diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg), or diabetes mellitus (glycosylated hemoglobin (HbA1c) ≥8.5%), or uncontrolled heart failure (NYHA grade ≥III) and arrhythmia with clinical symptoms or hemodynamic disorders;

[0187] (2) Patients with hyperlipidemia caused by drugs (phenothiazines, β-blockers, adrenocortical steroids, and certain contraceptives, etc.), or who are currently taking hormones, thyroid hormone treatment drugs, and other drugs that affect lipid metabolism;

[0188] (3) Combined with major liver, kidney and blood system diseases, major infectious diseases, active rheumatic and immune diseases, malignant tumors and mental illness;

[0189] (4) Those who have suffered severe trauma or major surgery in the past six months, or have a tendency to bleed;

[0190] (5) Pregnant or lactating women, or those who are allergic to the experimental drug or its ingredients;

[0191] (6) Participants in other clinical trials.

[0192] 5. Treatment plan

[0193] (1) Conventional treatment: During the observation period, both the experimental and control groups were given nutritional guidance, exercise advice, and a series of chronic disease management methods such as weight loss, smoking cessation, and alcohol restriction, with reference to the Expert Consensus on Nutritional Prescriptions for Cardiovascular Diseases. Based on their actual conditions, they were given medications related to other complications, such as antihypertensive and blood sugar control.

[0194] (2) Treatment plan for the control group: Oral administration of atorvastatin calcium tablets, 10 mg each time, once a day, taken around 8 pm.

[0195] (3) Treatment regimen for the experimental group: treatment with Chinese herbal medicine granules plus atorvastatin. The experimental group received treatment with Chinese herbal medicine granules in addition to the basic Western medicine treatment with atorvastatin. The Chinese herbal medicine granules (prepared according to the method of Example 1) were taken once in the morning and evening, with 13 g of granules (corresponding to 20 g of the crude drug) taken each time.

[0196] (4) Treatment cycle: The treatment cycle for both groups was 12 weeks.

[0197] During the trial, the use of other lipid-lowering Western medications, Chinese herbal medicine slices, or Chinese patent medicine preparations is prohibited. If concurrent illnesses occur, appropriate treatment may be administered, but this should not affect the efficacy of this study. Researchers must record the reason for medication use, medication name, and dosage in detail on the case observation form.

[0198] 6. Detection indicators

[0199] (1) Baseline characteristics: The patient's demographic data, including age, gender, BMI, blood pressure, and smoking status, were recorded.

[0200] (2) Main efficacy indicators: changes in LDL-C and carotid intima-media thickness (IMT) before and after treatment.

[0201] (3) Secondary efficacy indicators: changes in TC, TG, HDL-C, and TCM symptom scores before and after treatment.

[0202] (4) Inflammation-related factors: changes in serum hs-CRP, TNF-α, iNOS, TGF-β1, and Arg-1 before and after treatment.

[0203] (5) Safety indicators: blood routine, liver and kidney function, urine routine and incidence of adverse reactions.

[0204] 7. Efficacy evaluation criteria

[0205] (1) Criteria for determining the efficacy of TCM syndromes: Refer to the 2013 “General Principles for Clinical Research of New Chinese Medicines” and use the integral method to determine the efficacy of TCM syndromes.

[0206] Therapeutic index (n) = [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%

[0207] Clinical recovery: TCM clinical symptoms and signs disappear or basically disappear, and the syndrome score is reduced by ≥90%.

[0208] Markedly effective: Clinical symptoms and signs of TCM were significantly improved, and the syndrome score was reduced by ≥70%.

[0209] Effective: TCM clinical symptoms and signs improved, and the syndrome score decreased by ≥30%.

[0210] Ineffective: There is no significant improvement in TCM clinical symptoms and signs, or they may even worsen, and the symptom score decreases by less than 30%.

[0211] (2) Hyperlipidemia standards were formulated with reference to the Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China (2016 Revised Edition) and the Guiding Principles for Clinical Research of New Chinese Medicines:

[0212] Markedly effective: LDL-C decreased by ≥20%, TC decreased by ≥40%, or TG decreased by ≥20%, or HDL-C increased by ≥0.26 mmol / L (10 mg / dL);

[0213] Effective: TC decreases by 20% to 40%, or TG decreases by 10% to 20%, or HDL-C increases by 0.104 to 0.26 mmol / L (4 to 10 mg / dL);

[0214] Invalid: The above TG, TC, and HDL-C indicators do not meet the effective standards.

[0215] 8. Statistical methods

[0216] SPSS 20.0 software was used for statistical analysis. For intergroup comparisons of measurement data, normality was first tested. If the data followed a normal distribution, a t-test was used for group design data; if not, a Wilcoxon rank-sum test was used. For intergroup comparisons of enumeration data, a χ2 test was used. A P value of less than 0.05 was considered statistically significant.

[0217] result:

[0218] (1) Comparison of baseline characteristics: There was no statistically significant difference in gender, age, BMI, systolic blood pressure, and diastolic blood pressure between the two groups (P>0.05), indicating that the baseline levels of the two groups were consistent.

[0219] (2) Four blood lipid items: Figure 6 Comparison of the four blood lipids of the two groups of patients (Note: Compared with the group before treatment: # P<0.05, ##P < 0.01; compared with the control group: *P < 0.05, **P < 0.01); compared with pre-treatment, the experimental group had decreased TC, TG, and LDL-C levels (P < 0.05), and increased HDL-C levels (P < 0.05); the control group had decreased TG levels (P < 0.05). Intergroup comparisons showed that the experimental group had lower TC, TG, and LDL-C levels than the control group (P < 0.05).

[0220] (3) Carotid intima-media thickness (cIMT): Figure 7 Comparison of carotid artery intima-media thickness between the two groups of patients (Note: Compared with the group before treatment: # P<0.05, ## Compared with before treatment, the carotid artery intima-media thickness in the experimental group and the control group was significantly decreased (P<0.05).

[0221] (4) Inflammation-related factors: Figure 8 Comparison of inflammatory factors between the two groups of patients (Note: Compared with the group before treatment: # P<0.05, ## P < 0.01; compared with the control group: *P < 0.05, **P < 0.01); compared with pre-treatment, hs-CRP, TNF-α, and iNOS levels decreased in both the experimental and control groups after 12 weeks of treatment (P < 0.05), while TGF-β1 and Arg-1 levels increased (P < 0.05). Intergroup comparisons showed that compared with the control group, the experimental group had lower iNOS levels (P < 0.05) and higher Arg-1 levels (P < 0.05).

[0222] (5) TCM syndrome score: Figure 9 Comparison of TCM syndrome scores between the two groups of patients (Note: Compared with the group before treatment: ## P<0.01; compared with the control group: **P<0.01); compared with before treatment, the TCM syndrome score of the experimental group was significantly reduced (P<0.05); and was better than that of the control group (P<0.05).

[0223] (6) TCM syndrome efficacy: Figure 10 The total effective rate of the experimental group was better than that of the control group (80% vs 42.3%, P<0.05).

[0224] Conclusion: The Chinese medicine composition of the present invention can reduce the thickness of the carotid intima-media, reduce blood lipid levels and the expression of inflammatory factors, regulate lipid metabolism, inhibit inflammatory response, and improve the patient's traditional Chinese medicine symptoms, indicating that the Chinese medicine composition of the present invention exerts anti-AS effects through lipid-regulating and anti-inflammatory effects. During the entire study period, no adverse reactions such as liver and kidney damage and allergies occurred, confirming the clinical effectiveness and safety of the Chinese medicine composition of the present invention in treating carotid atherosclerosis combined with hyperlipidemia.

[0225] The above test results indicate that the Chinese medicine composition provided by the present invention has a good therapeutic effect on a patient population with carotid atherosclerosis combined with hyperlipidemia, a common and frequently occurring disease in the field of cardiovascular disease prevention and treatment. Furthermore, the present invention, without changing the efficacy of the Chinese medicine composition, formulates the Chinese medicine composition into a granular preparation by a certain method, ensuring the formulation's molding rate, solubility rate, bulk density, angle of repose, and moisture absorption rate, thereby ensuring the formulation's efficacy, extending the product's storage time, and taking into account patient acceptance, and facilitating large-scale production.

[0226] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia, characterized in that: The invention is prepared from the following components by weight: 8-12 parts of Chuanxiong rhizome, 8-12 parts of red peony root, 3-7 parts of coptis root, 8-12 parts of red yeast rice and 3-7 parts of roasted liquorice root.

2. The Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia according to claim 1, characterized in that: The invention is prepared from the following components by weight: 10 parts of Chuanxiong, 10 parts of red peony root, 5 parts of coptis root, 10 parts of red yeast rice and 5 parts of prepared liquorice root.

3. The Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia according to claim 1, characterized in that: The traditional Chinese medicine composition also includes dextrin.

4. A Chinese medicine granule preparation for treating carotid atherosclerosis combined with hyperlipidemia, characterized in that: The invention is mainly prepared from the traditional Chinese medicine composition for treating carotid atherosclerosis combined with hyperlipidemia as claimed in any one of claims 1 to 3.

5. The method for preparing the Chinese medicine granule preparation for treating carotid atherosclerosis combined with hyperlipidemia according to claim 4, characterized in that: The steps include: (a) Weighing chuanxiong rhizome, red peony root, coptis root, red yeast rice, and prepared liquorice root according to weight to obtain a mixed medicinal material; extracting the mixed medicinal material three times with water, combining the aqueous extracts, filtering, and concentrating to obtain an extract; (b) mixing the extract and dextrin in a mass ratio of 1:(1.8-2.2), granulating, drying, and granulating to obtain the Chinese medicine granule preparation; The relative density of the extract at 50°C is 1.2-1.25 g / cm 3 .

6. The preparation method according to claim 5, characterized in that In the three water extractions, the solid-liquid ratio of the first extraction is 1:(10-12); the solid-liquid ratio of the second extraction is 1:(8-10); and the solid-liquid ratio of the third extraction is 1:(8-10).

7. The preparation method according to claim 5, characterized in that In the three water extractions, the first extraction time is 0.5 to 1 hour; the second extraction time is 0.5 to 1 hour; and the third extraction time is 0.5 to 1 hour.

8. The preparation method according to claim 5, characterized in that The granulation is carried out in a fluidized bed, the material temperature is 80-90° C., the inlet air temperature is 100-110° C., and the feed speed is 280-320 rpm.

9. The preparation method according to claim 5, characterized in that In step (b), the drying is carried out in an oven at 75-85° C. for 1-2 hours.

10. The preparation method according to claim 5, characterized in that The granules are sieved through a 10-60 mesh sieve.

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