Traditional Chinese medicine composition granules and industrial preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to traditional Chinese medicine composition particles and an industrial preparation method thereof. The traditional Chinese medicine composition granules are prepared from the following medicinal raw materials in parts by mass: 580 to 640 parts of radix astragali seu hedysari, 350 to 400 parts of fried semen descurainiae, 350 to 400 parts of rhizoma chuanxiong, 200 to 260 parts of cassia twig processed by glycerol, 200 to 260 parts of salted rhizoma alismatis, 130 to 160 parts of radix platycodonis and 60 to 90 parts of fructus ziziphi jujubae. According to the technical scheme, a step-by-step extraction strategy that ligusticum wallichii and cassia twig are decocted together and then decocted with other medicinal materials is adopted, and the medicine effect is further guaranteed. According to the technical scheme, the technical problem that the content of key functional components such as ferulic acid, cinnamaldehyde and gentiobioside in a product in the prior art needs to be further increased can be solved. The technical scheme has outstanding industrialization advantages, takes cost and feasibility into account, and has clear clinical value and industrial prospect.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, specifically to a traditional Chinese medicine composition granule and its industrial preparation method. Background Technology

[0002] Chronic pulmonary heart disease (CPHD) is a common and serious chronic disease. Its pathogenesis mainly involves pulmonary hypertension caused by lesions in the lung tissue, thoracic cage, or pulmonary artery system, which then progresses to or is accompanied by right heart failure. This disease is prevalent among middle-aged and elderly people, and its prevalence increases significantly with age, severely impacting patients' quality of life and posing a significant threat to their health. In the clinical diagnosis and treatment of CPHD, the disease progression is typically divided into acute exacerbations and chronic remission. The remission period is a crucial stage for long-term disease management, and its treatment effectiveness directly determines the frequency of acute exacerbations, the rate of deterioration in cardiac function, and long-term survival. Therefore, the development of precise treatment plans for the remission period of CPHD has significant clinical value.

[0003] Traditional Chinese medicine has accumulated rich practical experience in the treatment of pulmonary heart disease. With the development of modern pharmaceutical technology, the precision and industrialization of TCM compound prescriptions have become a research hotspot. Existing technologies include patents that disclose drugs for the treatment of pulmonary heart disease. For example, the invention patent with authorization announcement number CN114010707B discloses a pharmaceutical composition for treating pulmonary heart disease. This composition consists of 24 parts Astragalus membranaceus, 15 parts Lepidium apetalum, 9 parts Psoralea corylifolia, 15 parts Ligusticum chuanxiong (processed with wine), 9 parts Alisma plantago-aquatica (processed with salt), 6 parts Platycodon grandiflorus, and 3 parts Ziziphus jujuba. Specifically, Lepidium apetalum is selected from Lepidium apetalum, Psoralea corylifolia is processed with salt, Ligusticum chuanxiong is processed with wine, and Alisma plantago-aquatica is processed with salt. This prescription is prepared into oral formulations such as active pharmaceutical ingredients and granules through processes such as water decoction or ethanol reflux extraction of Astragalus membranaceus and Ligusticum chuanxiong. Clinical applications have shown that it can effectively improve the symptoms of right heart failure during the remission period of chronic cor pulmonale, increase the partial pressure of blood oxygen, reduce plasma fibrinogen content and blood viscosity, and has a definite curative effect on lung and kidney qi deficiency syndrome. It successfully solves the problems of high cost, ambiguous syndrome types and difficulty in measuring efficacy of traditional Chinese medicine complex prescriptions, and provides a simplified and targeted treatment plan for clinical practice.

[0004] To further optimize the therapeutic effect of traditional Chinese medicine in treating pulmonary heart disease, our company has conducted in-depth research based on the aforementioned existing technology. The relevant improvements are documented in a prior patent application (application number: CN202511424584X, invention title: A pharmaceutical composition and its preparation method and application). The improvements of this prior patent compared to the existing technology are: optimizing the origin and processing method of Lepidium apetalum in the pharmaceutical composition, using stir-fried southern Lepidium apetalum instead of the original northern Lepidium apetalum; adjusting the processing specifications of Ligusticum chuanxiong, using raw Ligusticum chuanxiong for formulation; and replacing Psoralea corylifolia in the original formula with Cinnamomum cassia. Through the above formula optimization, this traditional Chinese medicine composition exhibits a more ideal comprehensive efficacy in treating pulmonary heart disease, providing a new technical direction for disease treatment.

[0005] However, in the process of industrializing the above-mentioned optimized traditional Chinese medicine composition into granules, it was found that the content of key active ingredients such as ferulic acid, cinnamaldehyde, and gentianoside in the granule products obtained by existing preparation processes still did not reach the ideal level. The content of these ingredients is directly related to the efficacy of the drug, and their insufficient content limits further improvement in therapeutic effect. Therefore, how to develop an industrialized preparation method that can effectively improve the retention rate of key active ingredients in the optimized traditional Chinese medicine composition has become an urgent technical problem to be solved, and is of great significance for promoting the clinical translation and application of this traditional Chinese medicine composition. Summary of the Invention

[0006] The present invention aims to provide an industrial-scale preparation method for granules of traditional Chinese medicine composition, in order to solve the technical problem that the content of key active ingredients such as ferulic acid, cinnamaldehyde, and gentian disaccharide in existing products needs to be further improved.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: A traditional Chinese medicine granule composition, by weight, is made from the following medicinal raw materials: 580-640 parts of Astragalus membranaceus, 350-400 parts of stir-fried Lepidium apetalum, 350-400 parts of Ligusticum chuanxiong, 200-260 parts of cinnamon twig processed with glycerol, 200-260 parts of Alisma plantago-aquatica (processed with salt), 130-160 parts of Platycodon grandiflorus, and 60-90 parts of jujube.

[0008] Furthermore, cinnamon twigs processed with glycerol are prepared by the following method: take tender cinnamon twigs, slice them, then add glycerol solution, mix well and let them sit for a long time, and dry them in an oven until the moisture content is ≤5% to obtain cinnamon twigs processed with glycerol.

[0009] Furthermore, the mass percentage of solute in the glycerol solution is 1-3%.

[0010] Furthermore, the temperature of the oven is 50–60°C.

[0011] Furthermore, the mass ratio of cinnamon twigs to glycerol solution is 100:10-15.

[0012] This technical solution also provides a method for preparing granules of a traditional Chinese medicine composition, comprising the following steps performed sequentially: Preparation of S1 extract: First, chuanxiong and cinnamon twigs processed with glycerol were decocted in water to extract the first filtrate and a mixture of chuanxiong and cinnamon twig residue. The mixture of chuanxiong and cinnamon twig residue was then mixed with astragalus, stir-fried southern lepidium seed, salt-processed alisma, platycodon, and jujube, and decocted in water again to extract the second filtrate. The first and second filtrates were combined, concentrated, and dried to obtain a dry extract. Preparation of S2 composition granules: The dry extract was granulated by wet granulation to obtain the traditional Chinese medicine composition granules.

[0013] Furthermore, in S1, the cinnamon twigs processed with chuanxiong and glycerol are decocted and extracted with water at a ratio of 1 kg: 10-14 L, and the decoction is carried out for 1-2 hours; the medicinal materials are soaked for 1-2 hours before the decoction.

[0014] Further, in S1, the mixed residue of Ligusticum chuanxiong and Cinnamomum cassia is mixed with Astragalus membranaceus, stir-fried Lepidium apetalum, salt-processed Alisma plantago-aquatica, Platycodon grandiflorus, and Ziziphus jujuba, and then decocted in water for extraction; the material-to-liquid ratio is 1kg:10-14L, and the decoction is performed 3 times, each time for 1-2 hours.

[0015] Further, in S2, the pulverized dry paste is mixed with the filler to obtain a total mixture; then an ethanol solution is added to the total mixture to wet it, followed by shaking granulation and boiling drying, and then granulation, mixing and packaging to obtain the finished product.

[0016] This technical solution also provides the application of traditional Chinese medicine composition granules in the preparation of a drug for treating chronic pulmonary heart disease.

[0017] The technical principle of this technical solution is as follows: This invention is based on the principles of reducing toxicity and enhancing efficacy in traditional Chinese medicine formulations, and optimizes existing formulas to address their shortcomings: First, it replaces Psoralea corylifolia with Cinnamomum cassia twig, thus avoiding the depletion of Psoralea corylifolia resources and potential hepatotoxicity risks, while utilizing the medicinal properties of Cinnamomum cassia twig to improve therapeutic effects. Second, it replaces Lepidium apetalum with Lepidium apetalum with Lepidium apetalum, enhancing the efficacy of the principal herb. Addressing the volatile nature of cinnamaldehyde in Cinnamomum cassia twig, this invention innovatively uses glycerol solution to process the twig, sealing the volatilization pathways of cinnamaldehyde on both physical and chemical levels. Combined with low-temperature drying (moisture content controlled ≤5%), it further reduces the loss of volatile components during drying, laying the foundation for component retention in subsequent extraction stages. Furthermore, the proprietary processing technology for Lepidium apetalum, through precise control of roasting temperature and time, breaks down the cell walls of the herb while preventing the hydrolysis of gentianoside, significantly enhancing its dissolution potential. This product uses salted Alisma plantago-aquatica. The purpose of this is that the Alisma plantago-aquatica is moistened with salt water before being stir-fried, which can greatly reduce the nephrotoxicity and hepatotoxicity of Alisma plantago-aquatica and improve the safety of the product.

[0018] This invention employs a stepwise extraction strategy of "decocting Chuanxiong and Guizhi together first, then mixing them with other medicinal materials for decoction," significantly improving the transfer rate of active ingredients such as ferulic acid and cinnamaldehyde. The inventors believe this is because ferulic acid in Chuanxiong and cinnamaldehyde in Guizhi are both readily reactive components. Pre-decocting them together quickly transfers these two types of components to the extract, preventing subsequent complexation reactions with polysaccharides and saponins in herbs like Huangqi and Jiegeng, thus reducing the loss of active ingredients. Simultaneously, the entire formula utilizes water extraction instead of the ethanol reflux extraction used in the original patent. This reduces production costs while aligning with the dissolution characteristics of water-soluble active ingredients, avoiding the potential irritation to the liver and kidneys from residual organic solvents during ethanol extraction.

[0019] The beneficial effects of this technical solution are as follows: (1) Safety is significantly improved, and the risk of toxicity is resolved. This invention addresses the toxicity issues of the original formula through a dual approach: first, it replaces toxic medicinal materials by using non-hepatotoxic cinnamon twigs instead of psoralea corylifolia, completely avoiding the risk of liver damage caused by psoralen-like components, while also solving the industrial problem of increasingly depleted psoralea corylifolia resources; second, it optimizes the processing technology by using salt-processed alisma plantago-aquatica combined with the whole formula's water extraction process to reduce organic solvent residues, thereby significantly reducing the risk of hepatotoxicity and nephrotoxicity and fundamentally improving the safety of medication.

[0020] (2) Enhanced content of active ingredients and therapeutic effect Through the synergistic effects of formula optimization, specialized processing, and step-by-step extraction, this invention achieves efficient retention of key active ingredients and enhanced therapeutic efficacy. For example, the transfer rates of marker components such as gentiopicroside from stir-fried Lepidium apetalum, cinnamaldehyde from Cinnamomum cassia, and ferulic acid from Ligusticum chuanxiong have been effectively improved. Pharmacological studies have shown that this composition can effectively alleviate the pathological symptoms of a chronic cor pulmonale model.

[0021] (3) It has prominent industrialization advantages and takes into account both cost and feasibility. This invention optimizes the process to meet industrialization needs: it replaces alcohol extraction with water extraction, eliminating the cost of ethanol recovery and explosion-proof equipment. The stepwise extraction process is fully compatible with existing equipment in traditional Chinese medicine granule production lines, such as tank mixers, swing granulators, and fluidized bed dryers, requiring no additional specialized equipment and facilitating industrial transformation.

[0022] (4) The content of the marker components cinnamaldehyde and ferulic acid was significantly increased. The combination of glycerol-processed cinnamon twig and chuanxiong-cinnamon twig decoction is a novel approach, demonstrating significantly better retention of cinnamaldehyde and ferulic acid than existing technologies. Regarding extraction methods, a priority water extraction of cinnamon twig and chuanxiong is employed, increasing the transfer rate of key components. These improvements not only address several technical issues of existing technologies but also possess clear clinical value and industrial potential. Attached Figure Description

[0023] Figure 1 Ultrasound examination results of the effects of different treatments in Experiment 1 on right ventricular function in a lily-induced pulmonary heart disease model in SD rats (normal control group).

[0024] Figure 2 Ultrasound examination results of the effects of different treatments in Experiment 1 on right ventricular function in a lily-induced pulmonary heart disease model in SD rats (model control group).

[0025] Figure 3 Ultrasound examination results of the effects of different treatments in Experiment 1 on right ventricular function in a lily-induced SD rat model of pulmonary heart disease (positive control group).

[0026] Figure 4 Ultrasound examination results of the effects of different treatments in Experiment 1 on right ventricular function in a pulmonary heart disease model induced by lily alkaloids in SD rats (low-dose group of test drug granules).

[0027] Figure 5 Ultrasound examination results of the effects of different treatments in Experiment 1 on right ventricular function in a pulmonary heart disease model induced by lily alkaloids (medium dose group of test drug granules).

[0028] Figure 6 Ultrasound examination results of the effects of different treatments in Experiment 1 on right ventricular function in a pulmonary heart disease model induced by lily alkaloids in SD rats (high-dose group of test drug granules).

[0029] Figure 7 mPAP test results of the effect of different treatments in Experiment 1 on pulmonary artery pressure in a lily alkaloid-induced SD rat model of pulmonary heart disease (normal control group).

[0030] Figure 8 mPAP test results of the effect of different treatments in Experiment 1 on pulmonary artery pressure in a lily alkaloid-induced SD rat model of pulmonary heart disease (model control group).

[0031] Figure 9 mPAP test results of the effect of different treatments in Experiment 1 on pulmonary artery pressure in a lily alkaloid-induced SD rat model of pulmonary heart disease (positive control group).

[0032] Figure 10 mPAP test results of the effect of different treatments in Experiment 1 on pulmonary artery pressure in a leucorrhizal alkaloid-induced SD rat model of pulmonary heart disease (low-dose group of test drug particles).

[0033] Figure 11 mPAP test results of the effect of different treatments in Experiment 1 on pulmonary artery pressure in a leucorrhizal alkaloid-induced SD rat model of pulmonary heart disease (medium dose group of test drug particles).

[0034] Figure 12 mPAP test results of the effect of different treatments in Experiment 1 on pulmonary artery pressure in a leucorrhizal alkaloid-induced SD rat model of pulmonary heart disease (high dose group of test drug particles).

[0035] Figure 13 HE staining results of pulmonary arterioles in SD rats with pulmonary heart disease induced by lily alkaloid under different treatments in Experiment Example 1 (magnification: ×200; A: normal control group; B: model control group; C: positive control group; D: low-dose test drug granules group; E: medium-dose test drug granules group; F: high-dose test drug granules group).

[0036] Figure 14 Masson staining results of lungs in SD rats with pulmonary heart disease induced by lily alkaloid under different treatments in Experiment Example 1 (magnification: ×200; A: normal control group; B: model control group; C: positive control group; D: low-dose test drug granules group; E: medium-dose test drug granules group; F: high-dose test drug granules group).

[0037] Figure 15 Masson staining results of myocardium in a pulmonary heart disease model of SD rats induced by lily alkaloid under different treatments in Experiment Example 1 (magnification: ×200; A: normal control group; B: model control group; C: positive control group; D: low-dose test drug granules group; E: medium-dose test drug granules group; F: high-dose test drug granules group). Detailed Implementation

[0038] The following embodiments are only used to more clearly illustrate the technical solutions of the present invention, and are therefore only examples, not intended to limit the scope of protection of the present invention. The specific embodiments listed in the present invention are only examples of the present invention, and the present invention is not limited to the specific embodiments described below. For those skilled in the art, any equivalent modifications and substitutions to the embodiments described below are also within the scope of the present invention. Therefore, all equivalent transformations and modifications made without departing from the spirit and scope of the present invention should be covered within the scope of the present invention. To better illustrate the present invention, numerous specific details are given in the following specific embodiments. Those skilled in the art should understand that the present invention can be implemented without certain specific details. In some other embodiments, methods, means, equipment, and steps well known to those skilled in the art are not described in detail in order to highlight the main points of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Unless otherwise specified, the units used in this specification are all International Standard Units (SI), and the numerical values ​​and ranges appearing in the present invention should be understood to include systematic errors that are unavoidable in industrial production.

[0039] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the materials, reagents, or instruments used, unless otherwise specified by the manufacturer, are all commercially available; and the conditions not specified in the examples are all performed under conventional conditions or conditions recommended by the manufacturer. Furthermore, this invention does not limit the source of the raw materials used; unless otherwise specified, the raw materials used in this invention are all commercially available products commonly found in this technical field. Unless otherwise specified, the "ratio" referred to in the following examples refers to a ratio of parts by mass.

[0040] Example 1 (1) Formula composition This invention provides a traditional Chinese medicine composition granule, which is made from the following medicinal raw materials in parts by weight: 580-640 parts of Astragalus membranaceus, 350-400 parts of stir-fried Lepidium apetalum, 350-400 parts of Ligusticum chuanxiong, 200-260 parts of Cinnamomum cassia (processed with glycerol), 200-260 parts of Alisma plantago-aquatica (processed with salt), 130-160 parts of Platycodon grandiflorus, and 60-90 parts of Ziziphus jujuba.

[0041] In our prior patent (202511424584X, a pharmaceutical composition and its preparation method and application), compared with the prior art, the traditional Chinese medicine composition granule formulation optimizes the origin and processing method of Lepidium apetalum (using stir-fried Lepidium apetalum) and the compatibility with raw Ligusticum chuanxiong, and replaces Psoralea corylifolia in the original formula with Cinnamomum cassia twig. This composition exhibits ideal comprehensive efficacy in treating pulmonary heart disease. This technical solution further studies the preparation process of the traditional Chinese medicine composition granules in the improved formulation. Specifically, Cinnamomum cassia twig undergoes a special processing treatment, namely, cinnamon twig processed with glycerol.

[0042] More specifically, *Descurainiae Semen lepidii* Semen is a plant belonging to the Brassicaceae family, specifically *Descurainiae Semen*. Descurainia sophia (L.)Webb. ex Prantl.) or Solo Dishes ( Lepidium apetalum The dried, mature seeds of *Lepidium apetalum* (commonly known as "Southern Lepidium" and "Northern Lepidium"). The plants are harvested in summer when the fruits are ripe, dried, and the seeds are extracted by rubbing and removing impurities to obtain the raw product. The stir-fried Southern Lepidium seeds used in this invention are prepared according to the stir-frying method described in "Medicinal Materials and Processed Slices" of the *Chinese Pharmacopoeia (2025 Edition)*: Cleaned Lepidium seeds are stir-fried according to the stir-frying method (General Rule 0213 of the *Chinese Pharmacopoeia (2025 Edition)*) until popping sounds are heard. More specifically, the following processing method can be used: Take southern lepidium seeds, place them in a stir-frying machine, set the temperature to 78-82℃, and stir-fry until popping sounds are heard. Remove and let cool. Northern lepidium seeds stir-fried at this temperature have the most stable color and content. Higher temperatures will cause them to burn, while lower temperatures will result in them not being cooked thoroughly.

[0043] The Alisma plantago-aquatica (ALISMATIS RHIZOMA) used in this technical solution is salt-processed Alisma plantago-aquatica. It is prepared according to the salt-processing method described in "Part I: Medicinal Materials and Processed Slices" of the Chinese Pharmacopoeia (2025 Edition): Take Alisma plantago-aquatica slices and dry them according to the salt water processing method (General Rule 0213 of the Chinese Pharmacopoeia (2025 Edition)). More specifically, the following processing method can be used: Take fresh Alisma plantago-aquatica stems, remove impurities, soak in water for 4-8 hours until fully moistened, cut into thick slices (2-4 mm), dry at 75-85℃ to obtain Alisma plantago-aquatica slices, then add salt water (1-2 kg of salt per 100 kg of Alisma plantago-aquatica slices, the salt water is a saturated sodium chloride solution), mix well, let it sit until fully moistened, place in a stir-frying machine, stir-fry until dry, remove and let cool.

[0044] Unlike our prior patent, this solution involves a special glycerol-based processing of cinnamon twig (Cinnamomi RAMULUS), the specific process of which is as follows: Take tender cinnamon twigs, cut them into thick slices (2-4 mm), then add a 1-3% glycerol solution (10-15 kg of glycerol solution per 100 kg of cinnamon twig slices; glycerol is glycerin, conforming to the standard for pharmaceutical excipients glycerin in Part IV of the Chinese Pharmacopoeia (2025 Edition)), mix well, and let it sit thoroughly. Then, dry it in an oven at 50-60℃ until the moisture content is below 5%, thus obtaining glycerol-processed cinnamon twigs.

[0045] The *Chuanxiong Rhizoma* used in this prescription is the raw *Chuanxiong*, not the wine-processed *Chuanxiong*, and meets the relevant standards for processed medicinal materials in the "Part I: Medicinal Materials and Processed Slices" section of the *Chinese Pharmacopoeia (2025 Edition)*. In addition, the raw medicinal materials such as *Astragalus membranaceus*, *Platycodon grandiflorus*, and *Jujube* all meet the relevant standards for processed medicinal materials in the "Part I: Medicinal Materials and Processed Slices" section of the *Chinese Pharmacopoeia (2020 Edition)*.

[0046] (2) Preparation process Secondly, the present invention further provides a method for preparing the aforementioned pharmaceutical composition, which is prepared by the following method: Preparation of S1 extract: Take sliced ​​Sichuan lovage rhizome and sliced ​​cinnamon twig (cinnamon twig prepared with glycerol according to the aforementioned method), place them in a decoction pot, add 12 times the amount of water (the material-to-liquid ratio can be 1kg:10-14L, preferably 1kg:12L), soak for 1-2 hours (preferably 1 hour), decoct once (1 hour, optional range 1-2 hours), filter, pump the filtrate into a storage tank, and then add the remaining medicinal slices to the decoction pot (fried southern lepidium seed should be decocted in 2-3kg bags to prevent clogging of the filter and making filtration difficult). Boil three times, adding 12 times the amount of water each time (the material-to-liquid ratio can be 1kg:10-14L, preferably 1kg:12L), for 1 hour each time (optional range 1-2 hours). Filter, and continue to pump the filtrate into the storage tank. Then, concentrate all the collected filtrates under reduced pressure at a temperature not exceeding 80℃ to an extract with a relative density of 1.18-1.22 (50℃). Dry under pulsating reduced pressure at a temperature not exceeding 70℃ until the moisture content does not exceed 5%. Crush the dried material (dry extract) through an 80-100 mesh sieve for later use.

[0047] Preparation of S2 composition particles (wet granulation): Granulation and drying: Dextrin (or soluble starch) is added based on the difference between the batch yield and the amount of dried extract obtained. Batch yield refers to the total weight of qualified Chinese medicine granules to be obtained in a single production batch. The amount of dried extract obtained refers to the actual weight of the dried extract (dry paste) obtained after extraction, concentration, and drying of the Chinese medicine raw materials; it is the main carrier of the active ingredients. Dextrin / soluble starch are commonly used inert excipients in Chinese medicine granulation (they do not react with the active ingredients and do not affect efficacy), serving as both fillers and binders. Batch yield - amount of dried extract obtained = amount of excipients (dextrin / soluble starch) to be added. By adding excipients, the final product weight is precisely controlled, ensuring that the concentration of active ingredients in each batch of granules meets the standard and avoiding uneven efficacy due to fluctuations in the amount of dried extract. The moderate viscosity of dextrin / soluble starch can adjust the binding properties of the dried extract, making the granulation process easier to control. With the active ingredient carrier (dry extract) as the core, by calculating the difference between the batch production and the actual amount of dry extract, excipients (dextrin or soluble starch) with both filling and binding functions are precisely added. This ensures that the final product weight meets the preset standard and solves the technical problem of poor dry extract formability, thereby achieving stable efficacy and controllable process of Chinese medicine granules.

[0048] After adding dextrin (or soluble starch), mix with a tank mixer for 20-30 minutes to obtain a total mixture. Add 25%-30% of the total mixture's weight of 85-95% (preferably 90%) ethanol to wet the mixture, stir until evenly wetted, and granulate using a vibrating granulator (16-mesh sieve). Dry with a fluidized bed desiccant: set the inlet air temperature to 80±10℃, maintain the material temperature at 50-60℃, and dry until the moisture content is within acceptable limits (moisture content ≤ 4.0%). Stop the machine and discharge the material after it cools to room temperature.

[0049] Whole grains: The material is first granulated using a granulator with a 16-mesh screen, and then granulated again using a high-efficiency sieving machine. The granules are passed through 10-mesh and 80-mesh stainless steel screens respectively. Particles that can pass through 10-mesh but not 80-mesh are collected as qualified packaging particles.

[0050] mix: All sieved granules were fed into a cone mixer and mixed for 20 minutes (50 Hz). The mixture was then discharged into a sealed bag. The intermediate was sampled and tested for quality; those that passed the test were used for repackaging.

[0051] Package: The DXDK40Ⅵ automatic granule packaging machine is used for packaging. When the automatic granule packaging machine is turned on, each bag contains 13g and the packaging speed is about 80 bags / min.

[0052] (3) Uses of Chinese herbal medicine granules This product has the functions of replenishing qi and promoting blood circulation, warming yang and resolving phlegm, and promoting diuresis and reducing swelling. It is used for patients with chronic pulmonary heart disease in remission who, according to traditional Chinese medicine diagnosis, have deficiency of heart and lung qi, with symptoms such as shortness of breath, palpitations or anxiety, chest tightness, fatigue, spontaneous sweating, which worsens with exertion, or cough, sputum production, puffy face, susceptibility to colds, pale or purplish tongue, white tongue coating, and weak or deep and thready or slightly hesitant or intermittent pulse.

[0053] This product is used to treat chronic pulmonary heart disease (CPHD), and details can be found in our prior patent "202511424584X A pharmaceutical composition and its preparation method and application".

[0054] (4) Specific preparation method The specific formula is as follows: A traditional Chinese medicine composition granule, by weight, is made from the following medicinal raw materials: 615 parts of Astragalus membranaceus, 385 parts of stir-fried Lepidium apetalum, 385 parts of Ligusticum chuanxiong, 231 parts of cinnamon twig processed with glycerol, 231 parts of salt-processed Alisma plantago-aquatica, 154 parts of Platycodon grandiflorus, and 77 parts of jujube.

[0055] Fried Lepidium apetalum seeds are prepared by the following method: Take Lepidium apetalum seeds, place them in a frying machine, set the temperature to about 80℃, fry until popping sounds are heard, remove and let cool.

[0056] Salted Alisma is prepared by the following method: Take fresh Alisma stems, remove impurities, soak briefly, moisten for about 6 hours until fully moistened, cut into thick slices (about 3mm), dry at about 80℃ to obtain Alisma slices, then add salt water (1.5kg of salt per 100kg of Alisma slices), mix well, let it sit, place in a stir-frying machine, stir-fry until dry, take out, and let cool.

[0057] Glycerol-processed cinnamon twigs are prepared by the following method: take tender cinnamon twigs, cut them into thick slices (about 3mm), place them in a container, add 1% glycerol solution (12kg of glycerol solution for every 100kg of cinnamon twig slices), mix well, let them sit, and dry them in an oven at about 55℃ until the moisture content is less than 5%, thus obtaining glycerol-processed cinnamon twigs.

[0058] The granule preparation process is as follows: Preparation of S1 extract: Take sliced ​​chuanxiong and cinnamon twig (cinnamon twig prepared with glycerol according to the aforementioned method), place them in a decoction pot, add 12 times the amount of water, soak for 1 hour, decoct once for 1 hour, filter, and pump the filtrate into a storage tank. Then add the remaining medicinal slices (fried lepidium seed is decocted in 2-3 kg bags to prevent clogging of the filter screen and making filtration difficult), decoct 3 times, adding 12 times the amount of water each time, 1 hour each time, filter, and continue to pump the filtrate into a storage tank. Then concentrate all the collected filtrates under reduced pressure at a temperature not exceeding 80°C to an extract with a relative density of about 1.20 (50°C), and dry under pulsating reduced pressure at a temperature not exceeding 70°C until the moisture content is not more than 5%. Crush the dried material (dry extract) through a 100-mesh sieve for later use.

[0059] Preparation of S2 composition particles: Granulation and drying: Add dextrin based on the difference between the batch yield and the amount of dried paste obtained, and mix for 30 minutes using a tank mixer to obtain the total mixture. Add 25% of the total mixture weight of 90% ethanol to wet the mixture, stir until evenly wetted, and granulate using a swing granulator (16-mesh sieve). Dry using a fluidized bed desiccant: set the inlet air temperature to 80±10℃, maintain the material temperature at around 55℃, and dry until the moisture content is within acceptable limits (moisture content ≤ 4.0%). Stop the machine and discharge the material after the temperature drops to room temperature.

[0060] After routine granulation, mixing, and packaging, the finished product of the Chinese herbal medicine composition granules is obtained.

[0061] Example 2 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1. The difference is in the formula and the method of processing cinnamon twigs with glycerol.

[0062] The formula is as follows: 580 parts Astragalus membranaceus, 350 parts stir-fried Lepidium apetalum, 350 parts Ligusticum chuanxiong, 200 parts Cinnamomum cassia, 200 parts salt-processed Alisma plantago-aquatica, 130 parts Platycodon grandiflorus, and 60 parts Jujube.

[0063] Glycerol-processed cinnamon twigs are prepared by the following method: take tender cinnamon twigs, cut them into thick slices (about 3mm), place them in a container, then add 3% glycerol solution (10kg of glycerol solution for every 100kg of cinnamon twig slices), mix well, let them sit, and dry them in an oven at about 60℃ until the moisture content is less than 5%, thus obtaining glycerol-processed cinnamon twigs.

[0064] Example 3 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1. The difference is in the formula and the method of processing cinnamon twigs with glycerol.

[0065] The formula is as follows: 640 parts Astragalus membranaceus, 400 parts stir-fried Lepidium apetalum, 400 parts Ligusticum chuanxiong, 260 parts Cinnamomum cassia, 260 parts salt-processed Alisma plantago-aquatica, 160 parts Platycodon grandiflorus, and 90 parts Jujube.

[0066] Glycerol-processed cinnamon twigs are prepared by the following method: take tender cinnamon twigs, cut them into thick slices (about 3mm), place them in a container, then add 2% glycerol solution (15kg of glycerol solution for every 100kg of cinnamon twig slices), mix well, let them sit, and dry them in an oven at about 50℃ until the moisture content is less than 5%, thus obtaining glycerol-processed cinnamon twigs.

[0067] Comparative Example 1 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1. The difference is that: the cinnamon twig is not processed and commercially available cinnamon twig slices are used directly, which meet the relevant slice standards in “Part I Medicinal Materials and Slices” of the Chinese Pharmacopoeia (2025 edition).

[0068] Comparative Example 2 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1. The difference is that the cinnamon twigs are prepared as follows: take the tender twigs of cinnamon, cut them into thick slices (about 3mm), place them in a container, and then add 4% glycerol solution (12kg of glycerol solution for every 100kg of cinnamon twig slices), mix well, let them sit, and dry them in an oven at about 55°C until the moisture content is less than 5%, and the cinnamon twigs prepared with glycerol can be obtained.

[0069] Comparative Example 3 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1. The difference is that the cinnamon twigs are prepared as follows: take the tender twigs of cinnamon, cut them into thick slices (about 3mm), place them in a container, and then add 1% glycerol solution (12kg of glycerol solution for every 100kg of cinnamon twig slices), mix well, let them sit, and dry them in an oven at about 65°C until the moisture content is less than 5%, and the cinnamon twigs prepared with glycerol can be obtained.

[0070] Comparative Example 4 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1. The difference is that the cinnamon twigs are prepared as follows: take the tender twigs of cinnamon, cut them into thick slices (about 3mm), place them in a container, and then add 1% glycerol solution (12kg of glycerol solution for every 100kg of cinnamon twig slices), mix well, let them sit, and dry them in an oven at about 45℃ until the moisture content is less than 5%, and the cinnamon twigs prepared with glycerol can be obtained.

[0071] Comparative Example 5 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1, except that an equal amount of 1,2-propanediol is used instead of glycerol.

[0072] Comparative Example 6 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1, except that: an equal amount of sorbitol is used instead of glycerol.

[0073] Comparative Example 7 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1, except that: an equal amount of polyethylene glycol 200 is used instead of glycerol.

[0074] Comparative Example 8 This embodiment is basically the same as the content of “(4) Specific preparation method” in Embodiment 1, except that: an equal amount of maltitol is used instead of glycerol.

[0075] Comparative Example 9 This embodiment is basically the same as the content of "(4) Specific preparation method" in Embodiment 1, except that the "Preparation of S1 extract" step is as follows: Take all the medicinal materials, add 12 times the amount of water, soak for 1 hour, decoct 4 times, 1 hour each time, filter, and pump the filtrate into a storage tank. Then, concentrate all the collected filtrates under reduced pressure at a temperature not exceeding 80℃ to an extract with a relative density of about 1.20 (50℃), and dry under pulsating reduced pressure at a temperature not exceeding 70℃ until the moisture content is not more than 5%. Crush the dried material (dry extract) through a 100-mesh sieve for later use. That is, all the medicinal materials are extracted together, without first extracting Chuanxiong and Guizhi.

[0076] Experimental Example 1: Animal Experiment of Pulmonary Heart Disease Model (1) Test methods (1.1) Model Establishment One hundred qualified SPF-grade male SD rats, weighing 205.6g–245.7g, were selected as the normal control group. Rats temporarily numbered M01–M14 were used as the normal control group. The remaining rats (M15–M100) were used as the model group. The model was induced by intraperitoneal injection of 45mg / kg of 2% lily alkaloid solution (prepared using a mixture of anhydrous ethanol and physiological saline (volume ratio 2:8)). The dosage volume was 2.25mL / kg. The normal control group received an equal volume of the anhydrous ethanol and physiological saline (volume ratio 2:8) mixture intraperitoneally, as a single administration. The animals were observed for 4 weeks. At the beginning of week 4, two animals from the model group (M15 and M16) and two animals from the normal control group (M13 and M14) were selected for cardiac function tests, including mean arterial pressure (mPAP) and pulmonary function. Lung and heart tissues were also collected for histopathological examination to comprehensively determine the success of the model.

[0077] (1.2) Grouping and administration After confirming the successful model, 50 rats weighing between 253.1g and 447.6g were selected and randomly divided into 5 groups according to their weight: a model control group, a positive control group, low-, medium-, and high-dose groups of the drug granules prepared in Example 1 of this protocol (hereinafter referred to as: test drug), and a normal group. Except for the model control group (9 animals), each of the other groups had 10 animals. Rats in all groups except the normal control group and the model control group were administered different doses of the test drug or Bufei Huoxue capsule solution orally at 10mL / kg. The normal control group and the model control group were given an equal volume of pure water. The administration was once a day for 28 consecutive days. Considering the numerous animal indicator tests and dissection procedures at the end of the drug administration period, drug administration was staggered over two days (except for the normal control group and the model control group, animals 01-05 in all other groups were defined as the first batch of animals and administered the drug first; animals 06-10 were defined as the second batch of animals and administered the drug the day after the first batch; in the normal control group, animals 01-05 were defined as the first batch and animals 06-12 as the second batch; in the model control group, animals 01-06 were defined as the first batch and animals 07-13 as the second batch). The normal control group initially included 12 rats, with a final sample size of 10 used for data analysis, after which 2 were excluded; the model control group initially included 13 rats, with a final sample size of 9 used for data analysis, after which 4 were excluded. Rats excluded due to death during the experiment were not included in the final statistical analysis to ensure the accuracy, reliability, and statistical significance of the results.

[0078] (1.3) Dosage design Positive control drug dosage: Bufei Huoxue Capsules (National Drug Approval Number Z20030063) are packaged at 0.35g per capsule. The clinical dosage is: oral administration. Take 4 capsules three times a day, i.e., 4.2g / day. Based on the body surface area method, the equivalent dose in rats is approximately 4.2g × 0.018 / 0.2kg ≈ 0.38g / kg. Therefore, 0.38g / kg was designed as the positive control drug dosage in this experiment.

[0079] Test drug dosage: The intended clinical dosage of this composition granules is 81g crude drug / day. Converted to rat equivalent dosage based on body surface area, this is approximately 81g crude drug × 0.018 / 0.2 kg ≈ 7.29g crude drug / kg. This experiment designed low, medium, and high dose groups of the test drug granules at 3.65g crude drug / kg, 7.29g crude drug / kg, and 14.58g crude drug / kg, respectively, equivalent to 0.5, 1, and 2 times the intended clinical dosage for humans (adult weight calculated as 70kg). See Table 1 for details. The test drug used in this experiment was prepared using the method and process of Example 1. The "preparation of S2 composition granules" in the preparation process is a conventional granulation method in the prior art. The improvement of this scheme compared to the prior art mainly lies in the "preparation of S1 extract," especially the processing method of cinnamon twig. The finished granules in this experiment were dissolved and dispersed according to the specified dosage before administration. The content of crude drugs in the test drug particles prepared in Example 1 was detected and calculated to be approximately 4.12 g crude drug / g dry extract powder. Here, dry extract powder refers to the powdery substance obtained by pulverizing the dried material (dry extract) through a 100-mesh sieve during the "Preparation of S1 Extract," which is the active ingredient of the drug; crude drugs refer to Astragalus membranaceus, stir-fried Lepidium apetalum, Ligusticum chuanxiong, Cinnamomum cassia (processed with glycerol), Alisma plantago-aquatica, Platycodon grandiflorus, and Ziziphus jujuba in the formula; the amount of crude drugs refers to the total mass of Astragalus membranaceus, stir-fried Lepidium apetalum, Ligusticum chuanxiong, Cinnamomum cassia (processed with glycerol), Alisma plantago-aquatica, Platycodon grandiflorus, and Ziziphus jujuba according to the formula ratio. Based on the dosage of each group of rats in Table 1 (calculated as crude drug), combined with the drug content of 4.12g crude drug / g dry extract powder and the proportion of dry extract powder in the finished product granules under batch production, calculate the required dosage of finished product granules (test drug) for each group, accurately weigh them, fully dissolve and disperse them evenly, and administer them by gavage according to the rat's body weight.

[0080] Table 1: Grouping and Dosage Design

[0081] (2) Detection indicators (2.1) Urine output test After the last administration, all animals were placed in metabolic cages for 24-hour urine output monitoring.

[0082] (2.2) Cardiac function test The day after the last administration, hair removal cream was used to remove the hair on the chest of each group of rats to fully expose the sternum and thorax. Then, 60 mg / kg of Shutai 50 was injected intraperitoneally to anesthetize the rats, and they were fixed to the rat board. Doppler ultrasound was used to examine the heart of each group of rats, and cardiac function and structural indicators such as right ventricular outflow tract diameter, aortic and pulmonary artery diameter, EF (ejection fraction), LVIDd (left ventricular diameter at end-diastole), IVSd (interventricular septum thickness at end-diastole), and LVPWd (left ventricular posterior wall thickness at end-diastole) were detected and recorded.

[0083] (2.3) Lung function test The day after the echocardiogram, rats in each group were anesthetized by intraperitoneal injection of 60 mg / kg of Serta-50, followed by tracheotomy. Pulmonary function was then assessed using a small animal pulmonary function testing (PFT) system to measure femoral expiratory volume (FEV1). 200 (Forced expiratory volume in 200 milliseconds), FVC (forced vital capacity), PEF (peak expiratory flow rate), FEV 0.2 Lung function-related indicators such as FVC (forced expiratory ratio), VT (tidal volume), and Cpyn (dynamic lung compliance) are included.

[0084] (2.4) Hemodynamic testing After the pulmonary function test was completed, a disposable intravenous infusion needle was connected to the pressure transducer, and heparinized saline was injected into the connection to expel air. The needle was inserted into the right ventricle approximately 0.5 cm above the point of strongest heartbeat and about 0.2 cm from the midclavicular line. The computer screen was observed simultaneously. When a specific waveform appeared, it indicated that the needle had entered the right ventricle. The right ventricular systolic pressure was recorded for 5 seconds, and the mPAP (mean pulmonary artery pressure) was calculated: mPAP (mmHg) = 0.61 × right ventricular systolic pressure + 2.

[0085] (2.5) Blood gas analysis After the hemodynamic tests were completed, blood was immediately drawn from the abdominal aorta of each group of rats to test arterial blood PaO2 and PaCO2.

[0086] (2.6) Right ventricular hypertrophy index After the above procedures were performed, the rats in each group were euthanized by exsanguination of the abdominal aorta. The heart was removed, the blood was absorbed with filter paper, the atria and the roots of the great vessels were removed along the atrioventricular groove, and the RV (right ventricle) and LV+S (left ventricle and interventricular septum) were separated along the edge of the interventricular septum. The filter paper was wiped dry, and the rats were weighed separately. The right ventricular hypertrophy index was calculated as RV / (LV+S)×100%.

[0087] (2.7) Pathological examination of heart and lung tissues After weighing, heart tissue was fixed in 10% neutral formaldehyde. Rat lungs were perfused with 10% neutral formaldehyde and then fixed, followed by dehydration, fixation, and paraffin embedding. Subsequently, HE and Masson staining were performed, and the pathological morphological changes of lung and heart tissues were observed under a microscope. Fiji software was used to perform batch analysis of collagen volume in Masson stained images. Microscopic image analysis software was used to measure the inner diameter (D1) and outer diameter (D2) of pulmonary arterioles, and the percentage of pulmonary arteriole wall thickness (WT%) was calculated: WT% = (D2 - D1) / D2 × 100%.

[0088] (3) Data processing and statistical analysis The significant figures of the experimental data were rounded to the nearest whole number. Quantitative data are expressed as mean ± standard deviation. This indicates that the normality and homogeneity of variance are tested. If the normality is satisfied ( P If the variance is greater than 0.05, perform statistical analysis using one-way ANOVA, and choose LSD (homogeneous variance) or Tamhane's T2 (unequal variance) for comparison based on the homogeneity of variance; or use the Independent-Samples T Tests for pairwise comparisons. If normality is not satisfied ( P If the result is ≤0.05, then the Nonparametric Tests are used. Statistical results are expressed as α. = 0.05 is the test threshold, where P ≤ 0.05 indicates statistical significance. P ≤ 0.01 indicates that the difference being tested is highly significant.

[0089] (4) Experimental results (4.1) Effects on animal body weight As shown in Table 2 below, compared with the normal control group, the body weight of the animals in the model control group was significantly reduced during the drug administration period. P (≤0.01); Compared with the model control group, the body weight of rats in each drug administration group showed an increasing trend, but the difference was not statistically significant.

[0090] Table 2: Effects of the test drug on body weight during the administration period of the lily alkaloid-induced pulmonary heart disease model in SD rats ( )

[0091] Note: ++ indicates comparison with the normal control group. P ≤ 0.01; W1 indicates the first week of dosing, and so on.

[0092] (4.2) Effects on animal urine output As shown in Table 3 below, compared with the normal control group, the urine output of the animals in the model control group was significantly reduced 24 hours after the last administration ( P ≤ 0.05); compared with the model control group, the urine output of rats in each treatment group was significantly increased 24 h after the last administration ( P ≤0.05, P ≤ 0.01); compared with the positive control group, the urine output 24 h after the last administration was significantly increased in both the low- and high-dose groups of the test drug particles ( P ≤ 0.05, P ≤ 0.01).

[0093] Table 3: Effects of the test drug on 24-hour urine output in a styrax rat model of pulmonary heart disease induced by lily alkaloids ( )

[0094] Note: + indicates comparison with the normal control group. P ≤ 0.05; This indicates a comparison with the model control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.05; ## indicates comparison with the positive control group P ≤ 0.01; # indicates comparison with the positive control group P ≤ 0.05.

[0095] (4.3) Effects on cardiac function in animals As shown in Table 4, Figure 1-6 As shown, compared with the normal control group, the diameter of the main pulmonary artery and the diameter of the right ventricular outflow tract were significantly increased in the model control group rats. P ≤ 0.01); compared with the model control group, the right ventricular outflow tract diameter of rats in each drug administration group was significantly reduced ( P ≤ 0.05, P ≤ 0.01), the diameter of the main pulmonary artery in rats in both the positive control group and the high-dose test drug group was significantly reduced ( P ≤ 0.01).

[0096] Table 4: Effects of the test drug on the diameter of the main pulmonary artery and the inner diameter of the right ventricular outflow tract in a stomatine-induced pulmonary heart disease model in SD rats ( )

[0097] Note: ++ indicates comparison with the normal control group. p ≤ 0.01; This indicates a comparison with the model control group. p ≤ 0.01, This indicates a comparison with the model control group. p ≤ 0.05.

[0098] As shown in Table 5, compared with the normal control group, the left ventricular EF% of rats in the model control group was significantly reduced ( P ≤ 0.01); Compared with the model control group, the left ventricular EF% of rats in the positive control group and the medium-dose group of the test drug granules was significantly increased ( P ≤0.05, P ≤ 0.01).

[0099] Table 5: Effects of the test drug on cardiac function indicators in a lily alkaloid-induced SD rat model of pulmonary heart disease ( )

[0100] Note: ++ indicates comparison with the normal control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.05.

[0101] (4.4) Effects on lung function and blood gas parameters in animals As shown in Table 6, under the FEV detection mode, compared with the normal control group, the FVC and FEV of the rats in the model control group were significantly different. 200 PEF, FEV 0.2 / FVC both decreased significantly ( P ≤ 0.05, P ≤ 0.01). Compared with the model control group, the FVC of rats in the positive control group and the high-dose test drug granule group was significantly increased ( P ≤ 0.05, P ≤ 0.01); FEV1 in rats of the positive control group, medium and high dose groups of test drug granules 200 PEF, FEV 0.2 / FVC both increased significantly ( P ≤ 0.05, P ≤ 0.01).

[0102] Table 6: Effects of the test drug on respiratory parameters of the FEV mode in a lily-inducing SD rat model of pulmonary heart disease (i.e., lipoicine-induced pulmonary heart disease). )

[0103] Note: ++ indicates comparison with the normal control group. P ≤ 0.01; + indicates comparison with the normal control group. P ≤ 0.05; This indicates a comparison with the model control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.05.

[0104] As shown in Table 7, under TB detection mode, compared with the normal control group, the PEF, Vt, and Cpyn levels in the model control group rats were all decreased to varying degrees, but the differences were not statistically significant. Compared with the model control group, the PEF, Vt, and Cpyn levels in each drug-treated group rats were all increased to varying degrees, and the increases were dose-related, but the differences were not statistically significant.

[0105] Table 7: Effects of the test drug on respiratory parameters of the TB mode of pulmonary function in a lily-induced SD rat model of pulmonary heart disease (TB mode) )

[0106] As shown in Table 8, compared with the normal control group, the arterial blood PaO2 of rats in the model control group was significantly reduced ( P ≤0.01). Compared with the model control group, the arterial blood PaO2 of rats in the positive control group, the medium- and high-dose groups of the test drug granules was significantly increased ( P ≤ 0.05, P ≤ 0.01).

[0107] Table 8: Effects of the test drug on blood gas analysis results in a lily alkaloid-induced SD rat model of pulmonary heart disease ( )

[0108] Note: ++ indicates comparison with the normal control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.05.

[0109] (4.5) Effects on mean pulmonary artery pressure and right ventricular hypertrophy index As shown in Table 9, Figure 7-12 As shown, compared with the normal control group, the mPAP level in the model control group rats was significantly increased ( P ≤0.01). Compared with the model control group, the mPAP levels in rats in the positive control group, the medium-dose group, and the high-dose group of the test drug granules were significantly reduced ( P ≤0.01).

[0110] Table 9: Effects of the test drug on pulmonary artery pressure in a lily alkaloid-induced SD rat model of pulmonary heart disease ( )

[0111] Note: ++ indicates comparison with the normal control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.01.

[0112] As shown in Table 10, compared with the normal control group, the right ventricular hypertrophy index of rats in the model control group was significantly increased ( P ≤0.01). Compared with the model control group, the right ventricular hypertrophy index of rats in the positive control group, the medium- and high-dose groups of the test drug granules was significantly reduced ( P ≤ 0.01).

[0113] Table 10: Effects of the test drug on the right ventricular hypertrophy index in a lily alkaloid-induced SD rat model of pulmonary heart disease ( )

[0114] Note: ++ indicates comparison with the normal control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.01.

[0115] (4.6) Histopathological examination (4.6.1) HE staining results The grading and statistical results of the lesions found in the heart and lung histology of each group of animals are shown in Table 11 below.

[0116] Normal control group: SD rats showed focal chronic inflammatory cell infiltration in the myocardium (7 / 10). Lungs showed alveolar wall thickening (1 / 10), peribronchiolar chronic inflammatory cell infiltration (1 / 10), and perivascular chronic inflammatory cell infiltration (5 / 10).

[0117] Model control group: In SD rats, the heart showed myocardial fiber necrosis (9 / 9), interstitial fibrous connective tissue hyperplasia (8 / 9), and chronic inflammatory cell infiltration (9 / 9). In the lungs, the pulmonary artery walls were thickened and / or the lumen was narrowed (6 / 9), with perivascular chronic inflammatory cell infiltration (7 / 9), peribronchiolar chronic inflammatory cell infiltration (1 / 9), foam cell infiltration in the alveolar cavities (2 / 9), and multinucleated giant cell infiltration in the alveolar cavities (1 / 9).

[0118] Positive control group: In SD rats, myocardial fiber necrosis (4 / 10), interstitial fibrous connective tissue hyperplasia (4 / 10), chronic inflammatory cell infiltration (7 / 10), and hemorrhage (2 / 10) were observed in the heart. In the lungs, thickening of the pulmonary artery walls and / or narrowing of the lumen (4 / 10), chronic inflammatory cell infiltration around the vessels (6 / 10), foam cell infiltration in the alveolar cavities (1 / 10), and multinucleated giant cell infiltration in the alveolar cavities (1 / 10) were observed.

[0119] In the low-dose test drug group: SD rats showed myocardial fiber necrosis (5 / 10), interstitial fibrous connective tissue hyperplasia (5 / 10), and chronic inflammatory cell infiltration (8 / 10) in the heart. In the lungs, there was thickening of the pulmonary artery walls and / or narrowing of the lumen (6 / 10), chronic inflammatory cell infiltration around the vessels (8 / 10), and thickening of the alveolar walls (1 / 10).

[0120] In the experimental drug medium-dose group: SD rats showed myocardial fiber necrosis (5 / 10), interstitial fibrous connective tissue hyperplasia (5 / 10), and chronic inflammatory cell infiltration (6 / 10) in the heart. In the lungs, pulmonary artery wall thickening and / or lumen narrowing (5 / 10), perivascular chronic inflammatory cell infiltration (8 / 10), peribronchiolar chronic inflammatory cell infiltration (1 / 10), and alveolar wall thickening (1 / 10).

[0121] In the high-dose test drug group: SD rats showed myocardial fiber necrosis (5 / 10), interstitial fibrous connective tissue hyperplasia (5 / 10), and chronic inflammatory cell infiltration (8 / 10) in the heart. In the lungs, pulmonary artery wall thickening and / or lumen narrowing (5 / 10), perivascular chronic inflammatory cell infiltration (9 / 10), and peribronchiolar chronic inflammatory cell infiltration (1 / 10).

[0122] Table 11: Statistics of Major Lesions in Lung and Heart Tissue

[0123] Note: "-" indicates that the incidence of lesions is zero in the corresponding range. The fractions in the table represent the incidence of lesions. For example, "1 / 10" means that 1 out of 10 animals in this group has the corresponding lesion, and so on.

[0124] The percentage of pulmonary arteriolar wall thickness in each group of animals is shown in Table 12 below. Figure 13 Compared with the normal control group, the percentage of pulmonary arteriolar wall thickness in the model control group rats was significantly increased ( P ≤ 0.05); compared with the model control group, the percentage of pulmonary arteriolar wall thickness in rats in the medium-dose group of the test drug granules was significantly reduced ( P ≤ 0.05).

[0125] Table 12: Effect of test drugs on the percentage of pulmonary arterial wall thickness in a lily alkaloid-induced SD rat model of pulmonary heart disease ( )

[0126] Note: + indicates comparison with the normal control group. P ≤ 0.05; This indicates a comparison with the model control group. P ≤ 0.05.

[0127] (4.6.1) Masson staining results As shown in Table 13, Figure 14 , Figure 15 As shown, compared with the normal control group, the collagen volume of the lungs and heart of the rats in the model control group was significantly increased ( P ≤ 0.01). Compared with the model control group, the lung collagen volume of rats in the high-dose group of the test drug granules was significantly reduced ( P (≤ 0.05), although the collagen volume of the lungs and heart of the animals in the other dose groups decreased to varying degrees, the differences were not statistically significant.

[0128] Table 13: Effect of test drug particles on Masson staining collagen volume in a lily alkaloid-induced SD rat model of pulmonary heart disease ( )

[0129] Note: ++ indicates comparison with the normal control group. P ≤ 0.01; This indicates a comparison with the model control group. P ≤ 0.05.

[0130] Based on the above experimental data, it can be seen that: (1) The low, medium and high doses of the test drug (3.65, 7.29 and 14.58 g crude drug / kg) could significantly increase the 24-hour urine output of rats with pulmonary heart disease. The low and high doses of the test drug (3.65 and 14.58 g crude drug / kg) had a better diuretic effect than the positive control drug Bufei Huoxue Capsule.

[0131] (2) High doses of the test drug (14.58 g crude drug / kg) significantly increased the pulmonary function FVC value and decreased the lung collagen volume in rats with pulmonary heart disease. Medium and high doses of the test drug granules (7.29 and 14.58 g crude drug / kg) significantly increased the pulmonary function FEV200, PEF, FEV0.2 / FVC value and arterial blood PaO2 in rats with pulmonary heart disease. These results suggest that the intervention of the test drug can improve the respiratory function of rats with pulmonary heart disease and slow down the progression of pulmonary fibrosis.

[0132] (3) The high dose of the test drug (14.58 g crude drug / kg) significantly reduced the diameter of the main pulmonary artery in rats with pulmonary heart disease. The low, medium, and high doses of the test drug (3.65, 7.29, and 14.58 g crude drug / kg) significantly reduced the right ventricular outflow tract diameter in rats with pulmonary heart disease. The medium dose of the test drug (7.29 g crude drug / kg) significantly reduced the percentage of pulmonary arteriolar wall thickness in rats with pulmonary heart disease. The medium and high doses of the test drug (7.29 and 14.58 g crude drug / kg) significantly reduced the mPAP and right ventricular hypertrophy index in rats with pulmonary heart disease. These results suggest that the test drug can alleviate the right ventricular load in rats with pulmonary heart disease, improve their right ventricular related functional indicators, and slow the progression of right ventricular hypertrophy.

[0133] (4) The medium dose of the test drug (7.29 g crude drug / kg) can significantly increase the left ventricular EF% in rats with pulmonary heart disease model, and can alleviate the compensatory damage to the left ventricle caused by pulmonary heart disease.

[0134] Experimental Example 2: Detection of Marker Component Content All detection methods were formulated based on high performance liquid chromatography (General Chapter 0512 of the Chinese Pharmacopoeia). They were used to quantitatively detect ferulic acid from Ligusticum chuanxiong, cinnamaldehyde from Cinnamomum cassia, and quercetin-3-O-β-D-glucose-7-O-β-D-gentioside (hereinafter referred to as "gentioside") from Lepidium apetalum in Chinese herbal medicine granules. This ensured the accuracy and reliability of the detection results and determined the content of active ingredients in the finished granules under different preparation process conditions.

[0135] (1) Detection of ferulic acid (1.1) Chromatographic conditions and system suitability Filler: Octadecylsilane-bonded silica gel is used as the stationary phase; Mobile phase: A mixture of methanol and 1% acetic acid solution in a volume ratio of 30:70 is used. Before use, the mixture must be filtered through a 0.45μm filter membrane and degassed by ultrasonication. Detection wavelength: set to 321nm; System suitability requirements: The theoretical plate number calculated based on the ferulic acid peak should be no less than 4000, and the separation degree between the ferulic acid peak and adjacent impurity peaks should meet the requirements (no less than 1.5).

[0136] (1.2) Preparation of reference solution Accurately weigh an appropriate amount of ferulic acid reference standard onto an analytical balance, transfer it to a brown volumetric flask (ferulic acid is susceptible to light and must be stored away from light), add 70% methanol as solvent, dissolve thoroughly, and dilute to volume to prepare a standard solution containing 20 μg of ferulic acid per mL. The solution should be used immediately after preparation. If short-term storage is required, it should be stored at 4°C in the dark for no more than 24 hours.

[0137] (1.3) Preparation of test solution Sampling and pretreatment: Take the Chinese medicine granule sample, grind it and pass it through a No. 4 sieve (pore size about 250μm). Take about 0.5g of the sieved powder, weigh it accurately on an analytical balance, and transfer it to a stoppered conical flask. Extraction process: Accurately add 50 mL of 70% methanol to the conical flask, seal it tightly, weigh it, and place it in a constant temperature water bath for reflux for 30 min (reflux temperature controlled at 70-80℃). Subsequent processing: After the heating and reflux were completed, the conical flask was removed and cooled to room temperature. The weight was weighed again, and the weight lost during heating was replenished with 70% methanol. After thorough shaking, the mixture was allowed to stand. The supernatant was filtered through a 0.45 μm organic phase filter membrane, and the filtrate was collected as the test solution.

[0138] (1.4) Determination method Turn on the high-performance liquid chromatograph (HPLC). After the instrument baseline stabilizes, accurately pipette 10 μL each of the reference solution and the test solution and inject them sequentially into the HPLC, recording the chromatograms. Qualitative analysis is performed using the retention time of the ferulic acid reference standard, and the content of ferulic acid in the test sample is calculated using the peak area according to the external standard method. Each batch of samples should be determined in triplicate, and the average value should be used as the final result. The relative standard deviation (RSD) should not exceed 2.0%.

[0139] (2) Detection of cinnamaldehyde (2.1) Chromatographic conditions and system suitability Filler: Octadecylsilane-bonded silica gel is used as the stationary phase; Mobile phase: Acetonitrile-water mixture with a volume ratio of 32:68. It must be filtered through a 0.45μm filter membrane and degassed by ultrasonication before use. Detection wavelength: set to 290nm; System suitability requirements: The theoretical plate number, calculated based on the cinnamaldehyde peak, should be no less than 3000, and the separation degree between the cinnamaldehyde peak and adjacent impurity peaks should meet the requirements (no less than 1.5).

[0140] (2.2) Preparation of reference solution Accurately weigh an appropriate amount of cinnamaldehyde reference standard onto an analytical balance, transfer it to a volumetric flask, add methanol as a solvent, dissolve thoroughly, and dilute to volume to prepare a standard solution containing 10 μg of cinnamaldehyde per mL. Cinnamaldehyde is volatile, so the preparation process should be rapid. After the solution is prepared, it should be sealed and stored at 4°C. The shelf life is no more than 12 hours.

[0141] (2.3) Preparation of test solution Sampling and pretreatment: Take the Chinese medicine granule sample, grind it and pass it through a No. 4 sieve. Take about 0.5g of the sieved powder, weigh it accurately on an analytical balance, and transfer it to a stoppered conical flask. Extraction process: Accurately add 25 mL of methanol to the conical flask, seal it tightly, weigh it, place it in an ultrasonic extractor, set the power to 250 W and the frequency to 40 kHz, and ultrasonically treat for 30 min. Subsequent processing: After sonication, remove the conical flask and let it cool to room temperature. Weigh it and replenish the weight lost during sonication with methanol. Shake well and filter through a 0.45μm organic phase filter membrane. Accurately measure 1mL of the filtrate and place it in a 25mL volumetric flask. Add methanol to the mark and shake well to obtain the test solution.

[0142] (2.4) Determination method After the baseline of the high-performance liquid chromatography (HPLC) instrument has stabilized, accurately pipette 10 μL each of the reference solution and the test solution and inject them into the chromatograph, recording the chromatograms. Qualitative identification is performed using the retention time of the cinnamaldehyde reference standard, and the content of cinnamaldehyde in the test sample is calculated using the external standard method based on peak area. Each batch of samples should be determined in triplicate, and the average value is the final result. The RSD should be controlled within 2.0%.

[0143] (3) Detection of gentiopicroside (3.1) Chromatographic conditions and system suitability Filler: Octadecylsilane-bonded silica gel is used as the stationary phase; Mobile phase: Acetonitrile-0.1% acetic acid solution is used as a mixed system with a volume ratio of 11:89. It needs to be filtered through a 0.45μm filter membrane and degassed by ultrasonication before use. Detection wavelength: set to 254nm; System suitability requirements: The theoretical plate number, calculated based on the gentiopicroside peak, should be no less than 5800, and the resolution between the gentiopicroside peak and adjacent impurity peaks should meet the requirements (no less than 1.5).

[0144] (3.2) Preparation of reference solution Accurately weigh an appropriate amount of quercetin-3-O-β-D-glucose-7-O-β-D-gentioside reference standard onto an analytical balance, transfer it to a volumetric flask, add 30% methanol as solvent, dissolve thoroughly, and dilute to volume to prepare a standard solution containing 20 μg of gentioside per mL. The solution should be stored protected from light after preparation and can be stored at 4°C for 48 hours.

[0145] (3.3) Preparation of test solution Sampling and pretreatment: Take the Chinese medicine granule sample, grind it and pass it through a No. 4 sieve. Take about 1g of the sieved powder, weigh it accurately on an analytical balance, and transfer it to a stoppered conical flask. Extraction process: Accurately add 50 mL of 70% methanol to an Erlenmeyer flask, seal tightly, weigh, and place in a constant temperature water bath for reflux for 1 hour (reflux temperature controlled at 75-85℃). Subsequent processing: After heating and reflux, cool to room temperature, weigh, replenish the lost weight with 70% methanol, shake thoroughly, filter through a 0.45μm organic phase filter membrane, and collect the filtrate as the test solution.

[0146] (3.4) Determination method After the parameters of the high-performance liquid chromatography (HPLC) instrument have stabilized, accurately pipette 25 μL each of the reference solution and the test solution and inject them into the chromatograph, recording the chromatograms. Qualitative analysis is performed using the retention time of the gentiopicroside reference standard, and the content of gentiopicroside in the test sample is calculated using the external standard method based on peak area. Each batch of samples should be measured in triplicate, and the average value should be calculated. The RSD should not exceed 2.0% to ensure the precision of the detection results.

[0147] The test results are detailed in Table 14. The contents of ferulic acid, cinnamaldehyde, and gentiopicroside are calculated in "mg / bag". Each bag contains 13g of traditional Chinese medicine composition granules.

[0148] Table 14: Detection results of ferulic acid, cinnamaldehyde, and gentiopicroside content (13g / bag specification)

[0149] Note: The experimental results are the average of 10 repeated trials; The t-test compared to Example 1 showed a significant difference (P < 0.05).

[0150] In this experiment, ferulic acid, cinnamaldehyde, and gentiopicroside were used as key quality control indicators for the granules of the traditional Chinese medicine composition. Cinnamaldehyde was the indicative effective component of cinnamon twig, ferulic acid was the indicative effective component of chuanxiong rhizome, and gentiopicroside was the characteristic component reflecting the overall extraction efficiency of the composition.

[0151] (1) Effect of glycerol processing on the content of effective ingredients in cinnamon twig (Examples 1-3 vs. Comparative Example 1) Comparative Example 1 uses commercially available cinnamon twig slices without any processing, following conventional methods. Examples 1-3 all use the glycerol-specific processing method of this invention for cinnamon twigs, with other raw materials, extraction, and preparation processes being basically the same. The results show extremely significant differences: Cinnamaldehyde content: Examples 1-3 showed 42.14-48.61 mg / bag, while Comparative Example 1 showed only 32.12 mg / bag. Processing with glycerol increased the cinnamaldehyde content by 31.3%-51.3%, demonstrating that glycerol processing significantly promotes the dissolution and retention of key components in cinnamon twigs. The inventors analyzed that the reason might be that after glycerol enters the cinnamon twig tissue, it improves the overall wettability of the medicinal material, softens the cell walls, and increases porosity, which is beneficial for improving the dissolution effect of cinnamaldehyde. Further increasing the glycerol concentration did not significantly increase the transfer rate of cinnamaldehyde and ferulic acid; therefore, from a cost-saving perspective, a concentration that meets the extraction requirements is sufficient.

[0152] Ferulic acid content: Examples 1-3 showed 6.69-7.42 mg / bag, while Comparative Example 1 showed only 2.11 mg / bag. The ferulic acid content increased by 217.0%-252.1% after processing with glycerol, indicating that glycerol processing of cinnamon twigs can synergistically enhance the transfer rate of ferulic acid from chuanxiong. This technical solution prioritizes the co-extraction of chuanxiong and glycerol-processed cinnamon twigs, which is beneficial for simultaneously increasing the content of cinnamaldehyde and ferulic acid in the finished product. Ferulic acid belongs to the phenolic acid class, is heat-sensitive, and easily oxidized and degraded, and is also one of the components lost most in traditional water extraction processes. The inventors analyzed that the reason why this solution can achieve a significant increase in the ferulic acid content in the finished product is that the tissue structure of cinnamon twigs becomes looser after processing with glycerol, which is conducive to co-extraction. When cinnamon twigs are co-extracted with chuanxiong, due to the effect of glycerol processing, cinnamon twigs will not compete for the adsorption of ferulic acid in chuanxiong, allowing ferulic acid to be fully released and dissolved from chuanxiong.

[0153] Gentianoside content: The entire process has no significant impact on the gentianoside content, and the transfer rates of the examples and comparative examples are basically the same.

[0154] In summary, the processing of cinnamon twigs with glycerol is not a simple treatment of medicinal slices, but a key process that can simultaneously increase the content of characteristic components of cinnamon twigs, chuanxiong rhizome, and the whole formula, thus solving the problem of low dissolution of effective components caused by conventionally unprocessed cinnamon twigs.

[0155] (2) Requirements for the process parameters of glycerol-processed cinnamon twigs (Examples 1-3 vs Comparative Examples 2-4) The processing method for cinnamon twigs in this technical solution is as follows: Take tender cinnamon twigs, cut them into thick slices (2-4 mm), then add a 1-3% glycerol solution (10-15 kg of glycerol solution per 100 kg of cinnamon twig slices), mix well, and let it steep thoroughly. Then, dry in an oven at 50-60℃ until the moisture content is below 5%, thus obtaining glycerol-processed cinnamon twigs. This invention optimizes and screens the glycerol concentration and drying temperature for glycerol processing, as detailed below: Glycerol concentration: In Example 1 (glycerol concentration 1%), the contents of all three components were high. After the glycerol concentration was increased to 4% (Comparative Example 2), there was no effect on the content of gentiopicroside, and no significant increase in cinnamaldehyde and ferulic acid. This indicates that 1-3% (further preferred 1-2%) is the optimal processing concentration of glycerol. Excessively high concentrations do not significantly increase the transfer rate of cinnamaldehyde and ferulic acid, but instead increase production costs. Therefore, 1-3% is selected.

[0156] Drying temperature: The present invention uses 50~60℃ for drying (Examples 1-3, preferably 50~55℃). If the drying temperature is increased to 65℃ (Comparative Example 3), the content of ferulic acid and cinnamaldehyde will decrease. If the drying temperature is reduced to 45℃ (Comparative Example 4), there is no effect on the content of ferulic acid and cinnamaldehyde, but the drying time is longer, which affects the production efficiency.

[0157] The above results indicate that the synergistic control of glycerol concentration and drying temperature is key to ensuring the processing effect.

[0158] (3) Analysis of the irreplaceability of glycerol as a processing solvent (Example 1 vs Comparative Examples 5-8) Before deciding to use glycerol, the inventors conducted extensive trials, experimenting with conventional polyols and sugar alcohol solvents to improve the product's efficacy. Comparative Examples 5-8 used 1,2-propanediol, sorbitol, polyethylene glycol 200, and maltitol respectively to replace glycerol, with the remaining processes identical to Example 1. 1,2-propanediol, sorbitol, polyethylene glycol 200, maltitol, and glycerol are all hydrophilic polyols or sugar alcohol pharmaceutical excipients, containing multiple hydroxyl groups in their molecular structure. They possess good water solubility, hygroscopicity, moisturizing properties, and chemical stability, exhibiting low toxicity and good biocompatibility. They can all be used as solvents, moisturizers, stabilizers, and plasticizers in traditional Chinese medicine preparations, with similar functional properties. However, in the specific application environment of this scheme (processing cinnamon twigs), glycerol showed unexpected technical effects. Experimental results showed that the cinnamaldehyde content in Comparative Examples 5-8 was significantly lower than in Example 1, and the ferulic acid content in the finished products of Comparative Examples 5-8 was also much lower than in Example 1. Experiments have shown that only glycerol can enhance the processing of cinnamon twigs, while other commonly used solvents cannot achieve the same technical effect.

[0159] (4) Synergistic effect of glycerol-processed cinnamon twig and stepwise extraction process (Example 1 vs Comparative Example 9) This invention employs a step-by-step extraction process, first extracting *Ligusticum chuanxiong* and *Cinnamomum cassia* processed with glycerol, followed by the extraction of other medicinal ingredients. Comparative Example 9 involved a whole-herb mixed extraction; testing of the finished product revealed a significant decrease in the content of ferulic acid and cinnamaldehyde in the granules. The inventors analyzed that this was because the mixed extraction of *Ligusticum chuanxiong* and *Cinnamomum cassia* with other components resulted in significant incompatibility reactions. Even though the *Cinnamomum cassia* was processed with glycerol, it was difficult to offset the impact of the mixed extraction on the extraction efficiency of ferulic acid and cinnamaldehyde. Example 1, by co-extracting *Cinnamomum cassia* processed with glycerol with *Ligusticum chuanxiong*, minimized the destruction of active ingredients and maximized component retention.

[0160] In summary, the glycerol-processed cinnamon twigs of this invention significantly increase the content of two key active ingredients, cinnamaldehyde and ferulic acid, far exceeding the effect of conventionally unprocessed cinnamon twigs. Furthermore, the processed cinnamon twigs reduce the compatibility reaction with chuanxiong (Ligusticum striatum), allowing for preferential co-extraction of both and ensuring the simultaneous preservation of cinnamaldehyde and ferulic acid content in the finished product. During the development of this solution, it was discovered that if all medicinal materials were mixed and decocted for extraction, the content of ferulic acid and cinnamaldehyde in the finished product needed further improvement. The inventors then separated chuanxiong and cinnamon twigs, the corresponding medicinal materials for ferulic acid and cinnamaldehyde, from the other medicinal materials for separate extraction. However, experimental results showed that extracting these two medicinal materials alone was insufficient to effectively address the issue of ferulic acid and cinnamaldehyde content. In trying different cinnamon twig processing methods, an appropriate processing method was found to simultaneously address the problem of low ferulic acid and cinnamaldehyde content in the finished product. Using glycerol to process cinnamon twigs effectively increased the content of ferulic acid and cinnamaldehyde in the finished product, achieving unexpected technical results.

[0161] The above description is merely an embodiment of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solution of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A traditional Chinese medicine composition granule, characterized in that, Based on the mass fractions, it is made from the following medicinal raw materials: 580-640 parts Astragalus membranaceus, 350-400 parts stir-fried Lepidium apetalum, 350-400 parts Ligusticum chuanxiong, 200-260 parts cinnamon twig processed with glycerol, 200-260 parts salt-processed Alisma plantago-aquatica, 130-160 parts Platycodon grandiflorus, and 60-90 parts jujube.

2. The traditional Chinese medicine composition granules according to claim 1, characterized in that, Glycerol-processed cinnamon twigs are prepared by the following method: take tender cinnamon twigs, slice them, then add glycerol solution, mix well and let them sit for a long time, and dry them in an oven until the moisture content is ≤5% to obtain glycerol-processed cinnamon twigs.

3. The traditional Chinese medicine composition granules according to claim 2, characterized in that, The mass percentage of solute in the glycerol solution is 1-3%.

4. The traditional Chinese medicine composition granules according to claim 3, characterized in that, The temperature of the oven is 50-60℃.

5. The traditional Chinese medicine composition granules according to claim 4, characterized in that, The mass ratio of cinnamon twigs to glycerol solution is 100:10-15.

6. A method for preparing a traditional Chinese medicine composition granule according to any one of claims 1-5, characterized in that, The steps are as follows, performed sequentially: Preparation of S1 extract: First, chuanxiong and cinnamon twigs processed with glycerol were decocted in water to extract the first filtrate and a mixture of chuanxiong and cinnamon twig residue. The mixture of chuanxiong and cinnamon twig residue was then mixed with astragalus, stir-fried southern lepidium seed, salt-processed alisma, platycodon, and jujube, and decocted in water again to extract the second filtrate. The first and second filtrates were combined, concentrated, and dried to obtain a dry extract. Preparation of S2 composition granules: The dry extract was granulated by wet granulation to obtain the traditional Chinese medicine composition granules.

7. The method for preparing a traditional Chinese medicine composition granule according to claim 6, characterized in that, In S1, chuanxiong and cinnamon twigs processed with glycerol were extracted by decoction with water at a ratio of 1 kg: 10-14 L, and the decoction was carried out for 1-2 hours; the medicinal materials were soaked for 1-2 hours before the decoction.

8. The method for preparing a traditional Chinese medicine composition granule according to claim 7, characterized in that, In S1, the mixed residue of Ligusticum chuanxiong and Cinnamomum cassia is mixed with Astragalus membranaceus, stir-fried Lepidium apetalum, salt-processed Alisma plantago-aquatica, Platycodon grandiflorus, and Ziziphus jujuba, and then extracted by decoction in water; the material-to-liquid ratio is 1kg:10-14L, and the decoction is performed 3 times, each time for 1-2 hours.

9. The method for preparing a traditional Chinese medicine composition granule according to claim 6, characterized in that, In S2, the pulverized dry paste is mixed with filler to obtain a total mixture; then an ethanol solution is added to the total mixture to wet it, followed by shaking granulation and boiling drying, and then granulation, mixing and packaging to obtain the finished product.

10. The use of a traditional Chinese medicine composition granule according to any one of claims 1-5 in the preparation of a medicament for treating chronic pulmonary heart disease.

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