Pharmaceutical composition and application thereof in preparation of medicine for treating chronic pulmonary heart disease

Abstract

The invention relates to the technical field of biological medicines, in particular to a pharmaceutical composition and application thereof in preparation of a medicine for treating chronic pulmonary heart disease. The pharmaceutical composition consists of 21-27 parts of astragalus membranaceus, 13-17 parts of semen lepidii, 7-10 parts of cassia twig, 21-27 parts of ligusticum wallichii, 7-10 parts of rhizoma alismatis, 5-7 parts of platycodon grandiflorum and 2-4 parts of Chinese dates. Compared with the prior art, the cassia twig is adopted to replace fructus psoraleae in an original formula, and meanwhile, the medicinal material specifications of the fried semen descurainiae, the raw ligusticum wallichii and the salted rhizoma alismatis are preferably selected. The invention also provides three preparation methods of the pharmaceutical composition, namely a water extraction and alcohol precipitation method, an alcohol extraction and water extraction combined method and a crushing and mixing method. Experimental results show that the pharmaceutical composition has remarkable effects on improving heart functions, lung functions, blood-gas indexes, right ventricular hypertrophy and the like of pulmonary heart disease model animals, meanwhile, the hepatotoxicity risk of fructus psoraleae is avoided, and the pharmaceutical composition has a good clinical application prospect.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a pharmaceutical composition and its use in the preparation of a drug for treating chronic pulmonary heart disease. Background Technology

[0002] Chronic pulmonary heart disease (CPHD) is a heart condition caused by chronic lesions in the lung tissue, pulmonary artery system, or thoracic cage, leading to increased pulmonary circulation resistance, pulmonary hypertension, and consequently, right ventricular hypertrophy, enlargement, and even right heart failure. The disease has a long course and is complex, requiring long-term medication, especially during remission, to improve cardiac function and slow disease progression.

[0003] Currently, Western medicine treatment for pulmonary heart disease in remission mainly focuses on symptomatic support, such as diuretics, cardiotonics, and oxygen therapy. However, long-term use can easily lead to drug resistance and side effects. Traditional Chinese medicine, based on syndrome differentiation and treatment, demonstrates unique advantages through multi-component and multi-target holistic regulation.

[0004] Chinese invention patent CN114010707B discloses a pharmaceutical composition for treating pulmonary heart disease, consisting of Astragalus membranaceus, Lepidium apetalum, Psoralea corylifolia, Ligusticum chuanxiong, Alisma plantago-aquatica, Platycodon grandiflorus, and Ziziphus jujuba. This composition has the functions of tonifying qi and warming the kidneys, purging the lungs and relieving asthma. It improves pulmonary heart disease, especially right heart failure during the remission phase of chronic pulmonary heart disease. It can increase blood oxygen partial pressure, reduce plasma fibrinogen levels, reduce blood viscosity, improve myocardial hypertrophy, strengthen the heart, promote diuresis, improve pulmonary edema, and improve vasomotor function. The composition of this invention is rationally formulated, with all the herbs working together to tonify qi and warm the kidneys, purge the lungs and relieve asthma. It has excellent efficacy for lung and kidney qi deficiency syndrome during the remission phase of chronic pulmonary heart disease and has good clinical application prospects. Astragalus membranaceus (Huangqi) in this formula tonifies Qi and raises Yang, promotes diuresis and reduces swelling, primarily tonifying the lung and spleen Qi, thus serving as the principal herb. Lepidium apetalum (Tinglizi) drains lung heat and relieves asthma, promotes diuresis and reduces swelling; Psoralea corylifolia (Salted) warms the kidneys and assists Yang, further enhancing its ability to regulate Qi and relieve asthma. These two herbs together serve as assistant herbs, assisting Astragalus membranaceus in promoting diuresis, reducing swelling, tonifying Qi, and raising Yang. Ligusticum striatum (Zhuxiong) (processed with wine) has a stronger effect in invigorating blood, removing blood stasis, regulating Qi, relieving stagnation, clearing the channels, and relieving pain; Alisma plantago-aquatica (Zexie) (processed with salt) further penetrates the kidneys, promoting diuresis and reducing swelling. These two herbs together serve as adjuvant herbs, firstly assisting the principal herb in tonifying Qi without causing stagnation, and secondly assisting the assistant herbs in draining lung heat and relieving asthma. Platycodon grandiflorus (Jiegeng) guides the herbs upwards, clears the lungs, eliminates phlegm, and invigorates blood; Jujube (Dazao) tonifies the middle Jiao and benefits Qi, its sweet and mild nature serving as the guiding herb. The combined effects of these herbs tonify Qi, warm the kidneys, drain lung heat, and relieve asthma.

[0005] Based on the aforementioned existing technology, the inventors, through in-depth research, discovered room for improvement in the original formulation. Although the pharmaceutical composition disclosed in patent CN114010707B has shown good efficacy in treating pulmonary heart disease, the psoralea corylifolia in its formulation has certain limitations in clinical application. Modern pharmacological studies have shown that while psoralea corylifolia has the effect of warming the kidneys and invigorating yang, its components, such as psoralen, may cause hepatotoxic reactions, and the safety of long-term use warrants attention. Recent clinical reports indicate that some patients have experienced abnormal liver function after using preparations containing psoralea corylifolia, which to some extent limits the long-term application of this formulation. Summary of the Invention

[0006] To address the aforementioned technical problems, the present invention aims to provide a pharmaceutical composition and its application in the preparation of a drug for treating chronic pulmonary heart disease. The invention seeks to provide a pharmaceutical composition with comparable or superior efficacy and higher safety, which is of great significance for advancing the treatment of pulmonary heart disease with traditional Chinese medicine.

[0007] To achieve the above-mentioned technical effects, the present invention adopts the following technical solution:

[0008] First, the present invention provides a pharmaceutical composition for treating pulmonary heart disease, comprising, by weight parts, the following pharmaceutical ingredients: Astragalus membranaceus 21-27 parts, Lepidium apetalum 13-17 parts, Cinnamomum cassia 7-10 parts, Ligusticum chuanxiong 13-17 parts, Alisma plantago-aquatica 7-10 parts, Platycodon grandiflorus 5-7 parts, and Ziziphus jujuba 2-4 parts.

[0009] Preferably, the pharmaceutical composition comprises, by weight parts, the following pharmaceutical raw materials: 24 parts Astragalus membranaceus, 15 parts Lepidium apetalum, 7-10 parts Cinnamomum cassia, 15 parts Ligusticum chuanxiong, 9 parts Alisma plantago-aquatica, 6 parts Platycodon grandiflorus, and 3 parts Ziziphus jujuba.

[0010] Preferably, the pharmaceutical composition comprises, by weight parts, the following pharmaceutical ingredients: 24 parts Astragalus membranaceus, 15 parts Lepidium apetalum, 9 parts Cinnamomum cassia, 15 parts Ligusticum chuanxiong, 9 parts Alisma plantago-aquatica, 6 parts Platycodon grandiflorus, and 3 parts Ziziphus jujuba.

[0011] More preferably, the Lepidium seed in the pharmaceutical composition is stir-fried southern Lepidium seed, the Ligusticum chuanxiong is raw, and the Alisma plantago-aquatica is salted Alisma plantago-aquatica. The specified medicinal materials and processing specifications ensure the stability and consistency of the drug quality.

[0012] Preferably, the pharmaceutical composition is prepared as an active ingredient and further prepared with pharmaceutically acceptable excipients into a clinically acceptable oral formulation.

[0013] More preferably, the dosage form of the oral preparation is one of the following: extract, decoction, powder, pill, tablet, granule, capsule, oral liquid, decoction paste, mixture, syrup, and paste.

[0014] In a second aspect, the present invention further provides a method for preparing the pharmaceutical composition provided in the first aspect, which is prepared by any of the following methods:

[0015] Method 1: Take the above seven raw medicinal materials, add water and decoct, filter to obtain decoction; the obtained decoction can be directly concentrated to obtain the active ingredient; or the obtained decoction can be concentrated first and then precipitated with ethanol, the supernatant can be collected, and then the supernatant can be concentrated to obtain the active ingredient.

[0016] Method 2: Combined alcohol and water extraction method

[0017] Astragalus and Ligusticum were extracted by ethanol reflux, and the extract was filtered and directly concentrated to obtain concentrated extract A; the remaining raw materials were decocted with water, filtered to obtain decoction, and directly concentrated or concentrated after alcohol precipitation to obtain concentrated extract B; concentrated extract A and concentrated extract B were combined to obtain the active ingredient.

[0018] Method 3: Crushing and Mixing Method

[0019] The above seven raw medicinal materials are pulverized and then mixed to obtain the active ingredients;

[0020] The active ingredient prepared by any one of methods one to three can be further prepared with pharmaceutically acceptable excipients to form a clinically acceptable oral formulation.

[0021] Preferably, the decoction in Method 1 specifically involves adding 8-12 times the mass of the medicinal materials in a single batch, decocting 2-3 times in a single batch, and decocting for 1-1.5 hours each time. The mass of the medicinal materials is the sum of the masses of all the medicinal ingredients in the formula.

[0022] As a preferred technical solution, the aforementioned method one is specifically as follows:

[0023] Add 8-12 times the amount of water, decoct 2-3 times, 1-1.5 hours each time, filter, combine the decoctions, and concentrate under reduced pressure at 50-70℃ to obtain an extract with a relative density of 1.25-1.35 (measured at 50-60℃).

[0024] As a preferred technical solution, the aforementioned method one can be as follows: add 8-12 times the amount of water according to the sum of the masses of all the medicinal ingredients in the formula, decoct 2-3 times, each time for 1-1.5 hours, filter, combine the decoctions, and concentrate at 50-70℃ to a relative density of 1.10-1.20 (measured at 50-60℃); add ethanol to make the alcohol content reach 60%-70%, let stand for 12-24 hours, take the supernatant, recover the ethanol, and continue to concentrate to an extract with a relative density of 1.25-1.35 (measured at 50-60℃), which is the final product.

[0025] As a preferred technical solution, the aforementioned method one specifically involves: adding 8-12 times the amount of water based on the sum of the masses of all the medicinal ingredients in the formula, decocting 2-3 times, each time for 1-1.5 hours, filtering, combining the decoctions, and concentrating at 50-70℃ to a relative density of 1.10-1.20 (measured at 50-60℃); adding ethanol to achieve an alcohol content of 60%-70%, allowing it to stand for 12-24 hours, taking the supernatant, recovering the ethanol, and further concentrating to a relative density of 1.25-1.35 (measured at 50-60℃) to obtain the extract.

[0026] As a preferred technical solution, the aforementioned Method 2 is specifically as follows: Based on the sum of the masses of all the medicinal ingredients in the formula, take the prescribed amount of Astragalus membranaceus and Ligusticum chuanxiong, add 8-10 times the amount of 70%-80% ethanol, reflux extract 2-3 times, 1-2 hours each time, filter to obtain the extract, recover the ethanol, and concentrate to a relative density of 1.15-1.25 (measured at 50-60℃) to obtain concentrated extract A; add 8-12 times the amount of water to the remaining five raw materials, decoct 2-3 times, 1-1.5 hours each time, filter to obtain the decoction, concentrate to a relative density of 1.10-1.20 (measured at 50-60℃), add ethanol to make the alcohol content reach 50%-60%, let stand for 12-24 hours, take the supernatant and concentrate to a relative density of 1.25-1.35 (measured at 50-60℃) to obtain concentrated extract B; combine concentrated extract A and concentrated extract B, mix well, and the final product is obtained.

[0027] As a preferred technical solution, the aforementioned method three specifically involves: pulverizing the above seven raw medicinal materials separately, passing them through an 80-100 mesh sieve, accurately weighing them according to the prescription ratio, and mixing them using an equal-incrementing method for 20-30 minutes until uniform, thus obtaining the mixed medicinal powder.

[0028] Extracts prepared by Method 1, Scheme 1 or Scheme 2, combined concentrated extracts obtained by Method 2, or mixed powders obtained by Method 3 can all be used as active pharmaceutical ingredients. With or without pharmaceutically acceptable excipients, these active ingredients can be further prepared into clinically acceptable oral formulations. Specifically, extracts can be used directly as extract preparations; mixed powders can be prepared into powders, or, with the addition of suitable excipients, into pills, tablets, or capsules; extracts can also be mixed with excipients and granulated to prepare granules; or diluted with water to prepare oral liquids.

[0029] Thirdly, the present invention also provides the use of the pharmaceutical composition as described above in the preparation of a medicament for treating chronic pulmonary heart disease, preferably, the chronic pulmonary heart disease being in remission.

[0030] Furthermore, the drug has at least one of the following effects: improving cardiac function, promoting diuresis, improving lung function, and reducing right ventricular hypertrophy.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] The inventors optimized the original formula by replacing Psoralea corylifolia with Cinnamomum cassia, forming a new composition. Cinnamomum cassia warms the Yang, resolves phlegm, and promotes blood circulation. Combined with Astragalus membranaceus and Ligusticum chuanxiong, it synergistically tonifies Qi, invigorates blood, warms the Yang, and promotes diuresis. Experiments show that the new composition significantly improves lung function, reduces pulmonary artery pressure, and alleviates right ventricular hypertrophy, without significant toxic side effects, demonstrating promising clinical application prospects. More specifically:

[0033] This invention replaces the potentially hepatotoxic Psoralea corylifolia with Cinnamomum cassia, fundamentally avoiding the risk of liver damage that may result from long-term medication, significantly improving medication safety, and making it particularly suitable for patients with pulmonary heart disease who require long-term medication during remission. Simultaneously, through systematic formulation optimization, the pharmaceutical composition of this invention exhibits a more comprehensive therapeutic effect in improving multiple key pathological aspects of pulmonary heart disease. Animal experiments have confirmed its effectiveness in improving cardiac function indicators (EF value, LVEDD, IVST, etc.) and pulmonary function parameters (FVC, FEV1). 200 It is superior to the original formula in terms of blood gas analysis indicators (PaO2, PaCO2) and reducing right ventricular hypertrophy, as well as PEF, etc.

[0034] This invention, through extensive experimentation, identified the optimal drug ratio. The preferred ratio (Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamomum cassia twig 9 parts, Ligusticum chuanxiong 24 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Ziziphus jujuba 3 parts) exhibited the best efficacy across all pharmacodynamic indicators, demonstrating superior synergistic effects. This drug composition can be prepared into various dosage forms, including extracts, decoctions, powders, pills, tablets, granules, capsules, or oral liquids, meeting the diverse medication needs of patients and improving the convenience of clinical application. Detailed Implementation

[0035] The following embodiments are only used to illustrate the technical solutions of the present invention more clearly, and are therefore only examples and should not be used to limit the scope of protection of the present invention.

[0036] Those skilled in the art will understand that the present invention can be practiced even without certain specific details. In some other embodiments, methods, means, apparatus, and steps well known to those skilled in the art have not been described in detail in order to highlight the spirit of the 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, all units used in this specification are International Standard Units (SI), and all numerical values ​​and ranges appearing in this invention should be understood to include systematic errors unavoidable in industrial production.

[0037] 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 reagents and materials; the conditions not specified in the examples are all carried out according to conventional conditions or conditions recommended by the manufacturer; at the same time, the present invention does not limit the source of the raw materials used, unless otherwise specified, the raw materials used in the present invention are all commercially available products in this technical field.

[0038] It should be noted that the overall technical solution adopted in this invention is as follows:

[0039] First, the present invention provides a pharmaceutical composition for treating pulmonary heart disease, which is made from the following pharmaceutical raw materials in parts by weight: 21-27 parts of Astragalus membranaceus, 13-17 parts of Lepidium apetalum, 7-10 parts of Cinnamomum cassia, 21-27 parts of Ligusticum chuanxiong, 7-10 parts of Alisma plantago-aquatica, 5-7 parts of Platycodon grandiflorus, and 2-4 parts of Ziziphus jujuba.

[0040] In the aforementioned pharmaceutical composition, the Lepidium seed is stir-fried southern Lepidium seed; the Ligusticum chuanxiong is raw; and the Alisma plantago-aquatica is salted Alisma plantago-aquatica.

[0041] More specifically, the aforementioned *Descurainiae Semen lepidii* seed is the dried, mature seed of *Descurainia sophia* (L.) Webb. ex Prant l., a plant of the Brassicaceae family, commonly known as "Southern *Descurainiae*". In the prior patent CN114010707B (A pharmaceutical composition for treating pulmonary heart disease and its preparation method and use), the *Descurainiae* used is Northern *Descurainiae*, specifically *Lepidium apetalum* Willd., and the raw product is used. The *Descurainiae* used in this invention is prepared according to the stir-frying method described in the "Medicinal Materials and Processed Slices" section of the *Chinese Pharmacopoeia (2020 Edition)*: Cleaned *Descurainiae* seeds are stir-fried according to the stir-frying method (General Rule 0213) until popping sounds are heard.

[0042] This technical solution uses Cinnamon Twig (Cinnamon Twig Ramulus) to replace Psoralea corylifolia in the prior patent CN114010707B.

[0043] The Chuanxiong Rhizoma used in this solution is the raw Chuanxiong Rhizoma, not the wine-processed Chuanxiong Rhizoma of the prior patent CN114010707B.

[0044] The Alisma plantago-aquatica used in this technical solution is salt-processed Alisma plantago-aquatica. It is prepared according to the salt-processing method described in "Medicinal Materials and Processed Pieces" of the Chinese Pharmacopoeia (2020 edition): Take Alisma plantago-aquatica slices and stir-fry them until dry according to the salt water processing method (General Rule 0213).

[0045] In addition, raw medicinal materials such as Astragalus membranaceus, Platycodon grandiflorus, and Jujube all meet the relevant standards for processed medicinal materials in Part I, "Medicinal Materials and Processed Medicinal Materials," of the Chinese Pharmacopoeia (2020 Edition).

[0046] Preferably, the present invention provides a pharmaceutical composition for treating pulmonary heart disease, which is made from the following pharmaceutical raw materials in parts by weight: 24 parts of Astragalus membranaceus, 15 parts of Lepidium apetalum, 9 parts of Cinnamomum cassia, 15 parts of Ligusticum chuanxiong, 9 parts of Alisma plantago-aquatica, 6 parts of Platycodon grandiflorus, and 3 parts of Ziziphus jujuba. This ratio is the optimal pharmaceutical composition and weight ratio.

[0047] Secondly, the present invention further provides a method for preparing the aforementioned pharmaceutical composition, which can be achieved by any of the following methods:

[0048] Method 1: Take the above seven raw medicinal materials, add water and decoct, filter to obtain decoction; the obtained decoction can be directly concentrated to obtain the active ingredient; or the obtained decoction can be concentrated first and then precipitated with ethanol, the supernatant can be collected, and then the supernatant can be concentrated to obtain the active ingredient.

[0049] Method 2: Combined alcohol and water extraction method

[0050] Astragalus and Ligusticum were extracted by ethanol reflux, and the extract was filtered and directly concentrated to obtain concentrated extract A; the remaining raw materials were decocted with water, filtered to obtain decoction, and directly concentrated or concentrated after alcohol precipitation to obtain concentrated extract B; concentrated extract A and concentrated extract B were combined to obtain the active ingredient.

[0051] Method 3: Crushing and Mixing Method

[0052] The above seven raw medicinal materials are pulverized and then mixed to obtain the active ingredients;

[0053] The active ingredient prepared by any one of methods one to three can be further prepared with pharmaceutically acceptable excipients to form a clinically acceptable oral formulation.

[0054] Preferably, the decoction in Method 1 specifically involves adding 8-12 times the mass of the medicinal materials in a single batch, decocting 2-3 times in a single batch, and decocting for 1-1.5 hours each time. The mass of the medicinal materials is the sum of the masses of all the medicinal ingredients in the formula.

[0055] As a preferred technical solution, the aforementioned method one is specifically as follows:

[0056] Add 8-12 times the amount of water, decoct 2-3 times, 1-1.5 hours each time, filter, combine the decoctions, and concentrate under reduced pressure at 50-70℃ to obtain an extract with a relative density of 1.25-1.35 (measured at 50-60℃).

[0057] As a preferred technical solution, the aforementioned method one can also be as follows: add 8-12 times the amount of water according to the sum of the masses of all the medicinal ingredients in the formula, decoct 2-3 times, each time for 1-1.5 hours, filter, combine the decoctions, and concentrate at 50-70℃ to a relative density of 1.10-1.20 (measured at 50-60℃); add ethanol to make the alcohol content reach 60%-70%, let stand for 12-24 hours, take the supernatant, recover the ethanol, and continue to concentrate to an extract with a relative density of 1.25-1.35 (measured at 50-60℃), which is the final product.

[0058] As a preferred technical solution, the aforementioned method one specifically involves: adding 8-12 times the amount of water based on the sum of the masses of all the medicinal ingredients in the formula, decocting 2-3 times, each time for 1-1.5 hours, filtering, combining the decoctions, and concentrating at 50-70℃ to a relative density of 1.10-1.20 (measured at 50-60℃); adding ethanol to achieve an alcohol content of 60%-70%, allowing it to stand for 12-24 hours, taking the supernatant, recovering the ethanol, and further concentrating to a relative density of 1.25-1.35 (measured at 50-60℃) to obtain the extract.

[0059] As a preferred technical solution, the aforementioned Method 2 is specifically as follows: Based on the sum of the masses of all the medicinal ingredients in the formula, take the prescribed amount of Astragalus membranaceus and Ligusticum chuanxiong, add 8-10 times the amount of 70%-80% ethanol, reflux extract 2-3 times, 1-2 hours each time, filter to obtain the extract, recover the ethanol, and concentrate to a relative density of 1.15-1.25 (measured at 50-60℃) to obtain concentrated extract A; add 8-12 times the amount of water to the remaining five raw materials, decoct 2-3 times, 1-1.5 hours each time, filter to obtain the decoction, concentrate to a relative density of 1.10-1.20 (measured at 50-60℃), add ethanol to make the alcohol content reach 50%-60%, let stand for 12-24 hours, take the supernatant and concentrate to a relative density of 1.25-1.35 (measured at 50-60℃) to obtain concentrated extract B; combine concentrated extract A and concentrated extract B, mix well, and the final product is obtained.

[0060] As a preferred technical solution, the aforementioned method three specifically involves: pulverizing the above seven raw medicinal materials separately, passing them through an 80-100 mesh sieve, accurately weighing them according to the prescription ratio, and mixing them using an equal-incrementing method for 20-30 minutes until uniform, thus obtaining the mixed medicinal powder.

[0061] The extracts prepared by Method 1, Scheme 1 or Scheme 2, the combined concentrated extracts obtained by Method 2, or the mixed medicinal powders obtained by Method 3 can all be used as active pharmaceutical ingredients. With this active ingredient, with or without the addition of pharmaceutically acceptable excipients, clinical acceptable oral preparations can be further prepared. Among them, the extract can be directly used as an extract agent; the mixed medicinal powder can be prepared into a powder, or made into pills, tablets, or capsules by adding appropriate excipients; the extract can also be granulated after mixing with excipients to prepare granules; or formulated into oral liquid by adding water.

[0062] The technical solutions of the present invention will be further explained below with specific embodiments:

[0063] It should be particularly noted that in this specific embodiment:

[0064] Animal experiment reagents mainly include: monocrotaline, batch number: C16326857, expiration date: January 2, 2027, manufacturer: Shandong Keyuan Biochemical Co., Ltd.; Zoletil 50, specifications: zolazepam: 125 mg, tiletamine: 125 mg, batch numbers: 9C1RA, 9F68A, expiration dates: June 2025, September 2025, production unit: Virbac S.A.

[0065] Main instrument and equipment include: PFT type pulmonary function detection system (Shanghai TowerView), VINNO 6LAB type Doppler ultrasound imaging system (Fiyeno Technology (Suzhou) Co., Ltd.), BL-420S type biological function experiment system (Chengdu Taimeng Technology Co., Ltd.), BG-800 type blood gas electrolyte analyzer (Shenzhen Maidicong Medical Electronics Co., Ltd.), small animal multi-channel physiological recorder (iWorx, Shanghai Yuyan Scientific Instruments Co., Ltd.).

[0066] It should be particularly noted that the following animal experiments are all carried out according to unified standards, including:

[0067] Source of experimental animals: All SPF-grade SD rats, male, with a body weight of 150.0 g to 180.3 g, were purchased from Hunan Slack Jingda Experimental Animal Co., Ltd. The quality certificate of experimental animals: 430727241103159476, the production license number of experimental animals: SCXK(Hunan)2021-0002, raised in Area B of the barrier environment laboratory, and the license number for the use of experimental animals: SYXK(Hunan)2020-0015.

[0068] Grouping and Drug Administration: In each experiment, 15 rats were randomly selected as the normal control group, and the remaining rats were selected as the model group. Rats in the model group were administered a single intraperitoneal injection of 2% limonene alkaloid solution (prepared using a mixture of anhydrous ethanol and physiological saline (volume ratio 2:8)) at a dose of 45 mg / kg to induce modeling. The administration volume for both groups was 2.25 mL / kg. Rats in the normal control group were administered an equal volume of the solvent (calculated by volume ratio, anhydrous ethanol: physiological saline = 2:8) via a single intraperitoneal injection. The rats were observed for 4 weeks after modeling. At the beginning of week 4, 2 rats from each group were randomly selected for cardiac function (mPAP) and pulmonary function tests to assess the success of model establishment.

[0069] Dosing regimen: Except for the normal control group and the model control group, rats in each group were administered different doses of the test drug solution orally at a dose of 10 mL / 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.

[0070] Dosage design: The intended clinical dose of each composition of the test drug was 81g crude drug / day. The dosage for each group of rats was controlled to be consistent (based on the amount of crude drug, which refers to the amount of raw drug material, including processed and unprocessed raw drug material). The equivalent dose for rats (humans are calculated based on 70kg) was converted according to body surface area using the following formula: 81g crude drug × 0.018 / 0.2kg ≈ 7.29g crude drug / kg. This dose is equivalent to 1 times the intended clinical dose for humans.

[0071] The testing indicators include:

[0072] (1) Urine volume test

[0073] After the last administration, all animals were placed in metabolic cages for 24-hour urine output monitoring.

[0074] (2) Cardiac function test

[0075] 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 thoracic cage. 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 the right ventricular outflow tract diameter, main pulmonary artery diameter, EF, LVIDD, IVST, LVPWd and other cardiac function and structural indicators were detected and recorded.

[0076] (3) Lung function test

[0077] After the echocardiogram, a tracheotomy was performed, and lung function was tested using a small animal pulmonary function testing (PFT) system to measure FEV1. 200 Lung function-related indicators such as FVC, PEF, FEV0.2 / FVC, Vt, and Cypn.

[0078] (4) Blood gas analysis

[0079] After the hemodynamic testing was completed, blood was immediately drawn from the abdominal aorta of each group of rats to test arterial blood PaO2 and PaCO2.

[0080] (5) Right ventricular hypertrophy index

[0081] After the above procedures were completed, the rats in each group were euthanized, the heart was removed, the blood was dried with filter paper, the atria and the roots of the great vessels were removed along the atrioventricular groove, and the RV and LV+S parts were separated along the edge of the interventricular septum. The filter paper was dried, the parts were weighed, and the right ventricular hypertrophy index was calculated as RV / (LV+S)*100%.

[0082] Data Processing and Statistical Analysis: Data in this experiment were rounded to the nearest whole number and statistical analysis was performed according to the center's relevant SOPs. SPSS 23.0 was used for statistical analysis. Quantitative data were expressed as mean ± standard deviation (x ± s) and normality and homogeneity of variance were tested. If normality was satisfied (P < 0.05), one-way ANOVA was used for statistical analysis, and LSD (homogeneous variance) or Tamhane's T² (non-homogeneous variance) was selected for comparison based on the homogeneity of variance; or Independent-Samples T Tests were used for pairwise comparisons. If normality was not satisfied (P < 0.05), Nonparametric Tests were used. The statistical results were set with α = 0.05 as the test limit, where P < 0.05 was considered statistically significant.

[0083] Example 1

[0084] The prior patent CN114010707B used Psoralea corylifolia as one of the drug raw materials, but it has certain shortcomings. These include: Psoralea corylifolia is derived from the dried fruit of the legume Psoralea corylifolia L., and has the effects of tonifying the kidneys and strengthening yang, warming the spleen and stopping diarrhea. It is used to treat various diseases such as kidney deficiency and impotence, lower back pain, and osteoporosis, and is a commonly used tonic in traditional Chinese medicine. However, in recent years, reports of adverse reactions to Psoralea corylifolia and related preparations have been increasing, especially hepatotoxicity, which has become a bottleneck restricting the clinical application of Psoralea corylifolia and related preparations. Ancient texts rarely record safety issues related to Psoralea corylifolia, but modern clinical and basic research indicates that it not only has direct toxicity but also immune-specific toxicity (e.g., Xu Yingjie, Zhan Xiaoyan, Bai Zhaofang, et al. Exploring the safety and rational use of Psoralea corylifolia based on the evolution of efficacy / toxicity records in ancient and modern literature [J]. Acta Pharmaceutica Sinica, 2025, 60(02):314-322. DOI:10.16438 / j.0513-4870.2024-0818.). Meanwhile, animal deaths also occurred in the patented experiments (as described in paragraph

[0095] of the instruction manual, multiple groups experienced animal deaths). Although attributed to operational errors or individual differences, the potential adverse reactions of the drug, especially Psoralea corylifolia, cannot be completely ruled out.

[0085] Based on the above principles, the purpose of this embodiment is to observe whether different drugs can achieve similar effects when replacing psoralea corylifolia. The specific experiment is as follows:

[0086] 1.1 Experimental Grouping

[0087] This embodiment is based on the basic formula (derived from prior patent CN114010707B: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Psoralea corylifolia 9 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, Ziziphus jujuba 3 parts), and the following experimental groups were set up to replace Psoralea corylifolia:

[0088] Group C-1: Replace Psoralea corylifolia with 9 parts cinnamon, i.e., the prescription is: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamon 9 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, Jujube 3 parts;

[0089] Group C-2: Replace Psoralea corylifolia with 9 parts of dried ginger, i.e., the prescription is: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, dried ginger 9 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and jujube 3 parts;

[0090] Group C-3: Replace Psoralea corylifolia with 9 parts Asarum, i.e., the prescription is: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Asarum 9 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Ziziphus jujuba 3 parts;

[0091] Group C-4: The prescription used was 9 parts of Epimedium and 9 parts of Psoralea corylifolia, that is, the prescription was: 24 parts of Astragalus membranaceus, 15 parts of Lepidium apetalum, 9 parts of Epimedium, 15 parts of Ligusticum chuanxiong, 9 parts of Alisma plantago-aquatica, 6 parts of Platycodon grandiflorus and 3 parts of Ziziphus jujuba.

[0092] Group C-5: Replace Psoralea corylifolia with 9 parts of Cinnamomum cassia, i.e., the prescription is: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamomum cassia 9 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Ziziphus jujuba 3 parts.

[0093] Group C-6: The basic formula remains unchanged, that is, the prescription is: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Psoralea corylifolia 9 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Ziziphus jujuba 3 parts.

[0094] According to the prescription composition and specific prescription quantity in the above groups, the following unified preparation standards shall be followed:

[0095] According to the drug composition and mass ratio in the prescription, all the medicinal ingredients in the prescription are pulverized and mixed through an 80-mesh sieve to obtain a drug mixture. Based on the mass of the drug mixture, 8 times the mass of the drug mixture is added to the first decoction and decocted for 1.0 hour. 8 times the mass of the drug mixture is added to the second decoction and decocted for 1.0 hour. 6 times the mass of the drug mixture is added to the third decoction and decocted for 1.0 hour. After each decoction, the mixture is filtered and the filtrate is collected. The filtrates from the multiple decoctions are then combined and concentrated to obtain the active pharmaceutical ingredient. The active pharmaceutical ingredient is prepared into a suspension before administration and administered according to the method described in 1.2 above. The finished products of each group of active pharmaceutical ingredients obtained in this way are recorded according to the group.

[0096] Based on the above groups, experiments were conducted according to the aforementioned unified standards for animal experiments. It should be noted that although the composition and specific mass ratios of the medicinal ingredients differed among the groups, all treatment groups were administered the same amount of raw medicinal material (7.29 g raw medicinal material / kg), ensuring a consistent total amount of raw medicinal material in each dose. This design aimed to eliminate the interference of dosage differences on the experimental results, thereby enabling a more accurate observation and comparison of the differences in the therapeutic effects of different drug combinations on the pulmonary heart disease model, and providing reliable experimental evidence for optimizing drug formulations.

[0097] 1.2 Experimental Results

[0098] Based on the above groups, experiments were conducted according to the aforementioned unified standards for animal experiments, and the experimental results are shown in Tables 1-1 to 1-7:

[0099] Table 1-1 Effects of each group on 24-hour urine output in a lily alkaloid-induced SD rat model of pulmonary heart disease (PCH) n=8)

[0100]

[0101] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05

[0102] The results showed that the 24-hour urine output of the model control group rats was significantly lower than that of the normal control group (P<0.05), indicating that the pulmonary heart disease model was successfully established and accompanied by abnormal water metabolism. All treatment groups increased urine output to varying degrees, with group C-5 (cinnamon twig) showing the most significant increase, indicating that cinnamon twig has a prominent effect on improving water metabolism. While group C-6 (psoralen) also increased urine output, the effect was not as significant as that of the cinnamon twig group.

[0103] Table 1-2 Effects of each group on the diameter of the main pulmonary artery and the diameter of the right ventricular outflow tract in a dinoflagellate-induced pulmonary heart disease model in SD rats.

[0104]

[0105]

[0106] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0107] The results of this experiment showed that the diameter of the main pulmonary artery and the inner diameter of the right ventricular outflow tract were significantly increased in the model control group rats (P<0.05), indicating that pulmonary hypertension and right ventricular enlargement existed in the cor pulmonale model. Among the drug administration groups, groups C-2, C-3, and C-5 significantly reduced the diameter of the main pulmonary artery and the inner diameter of the right ventricular outflow tract, with group C-5 (cinnamon twig) showing the best effect, approaching the level of the normal control group, indicating that cinnamon twig can effectively alleviate pulmonary hypertension and right ventricular remodeling.

[0108] Table 1-3 Effects of each group on cardiac function indicators in a lilacin-induced pulmonary heart disease model in SD rats

[0109]

[0110] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0111] The results of this experiment showed that the EF value of the model control group rats was significantly decreased, while the LVEDD and IVST values ​​were significantly increased (P<0.05), indicating impaired cardiac function and left ventricular enlargement. Among the drug-treated groups, group C-5 (Cinnamon Twig) showed significant improvements in EF, LVEDD, and IVST (P<0.05), with the EF value approaching normal levels, indicating that Cinnamon Twig can effectively improve cardiac function and reduce left ventricular enlargement and interventricular septal thickening. While group C-6 (Psoralea) also improved these indicators, the effect was not as significant as that of the Cinnamon Twig group.

[0112] Table 1-4 Effects of each group on respiratory parameters of pulmonary function (FEV1) in a limonene-induced SD rat model of pulmonary heart disease.

[0113]

[0114] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0115] The experimental results indicate that the FVC and FEV of the model control group rats were significantly lower. 200 PEF and FEV 0.2 Both FVC and FEV1 were significantly reduced (P<0.05), indicating impaired lung function. Among the treatment groups, group C-5 (Guizhi) showed the lowest levels of FVC and FEV1. 200 PEF and FEV 0.2 The FVC index showed significant improvement (P<0.05) and was close to the normal level, indicating that cinnamon twig can effectively restore lung function and improve ventilation capacity.

[0116] Table 1-5 Effects of each group on pulmonary function and respiratory parameters in the TB mode of a limonene-induced SD rat model of pulmonary heart disease.

[0117]

[0118] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0119] The results of this experiment showed that the PEF and Vt of the model control group rats were significantly reduced (P<0.05), indicating impaired respiratory flow and tidal volume. Among the drug-treated groups, group C-5 (Cinnamon Twig) showed significant improvement in both PEF and Vt (P<0.05), approaching normal levels, and the Cpyn value also recovered significantly, indicating that Cinnamon Twig can effectively improve respiratory flow and lung compliance.

[0120] Table 1-6 Effects of each group on blood gas analysis results in the lilacin-induced SD rat model of pulmonary heart disease.

[0121]

[0122] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0123] The results of this experiment showed that the PaO2 of the rats in the model control group was significantly decreased and the PaCO2 was significantly increased (P<0.05), indicating impaired gas exchange and respiratory acidosis. Among the drug-treated groups, group C-5 (Cinnamon Twig) showed significant improvement in both PaO2 and PaCO2 (P<0.05), and was close to normal levels, indicating that Cinnamon Twig can effectively correct hypoxemia and hypercapnia and improve gas exchange.

[0124] Table 1-7 Effects of each group on the right ventricular hypertrophy index in a limonene-induced SD rat model of pulmonary heart disease.

[0125]

[0126] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0127] The results of this experiment showed that the right ventricular hypertrophy index was significantly increased in the model control group rats (P<0.05), indicating right ventricular hypertrophy. Among the drug administration groups, groups C-3 and C-5 significantly reduced the right ventricular hypertrophy index (P<0.05), with group C-5 (cinnamon twig) showing better results, approaching the normal level, indicating that cinnamon twig can effectively alleviate right ventricular hypertrophy.

[0128] The experimental results of this embodiment show that among the different drugs that replace psoralea corylifolia, cinnamon twig (group C-5) showed the best effect in improving urine output, cardiac function, pulmonary function, blood gas parameters, and right ventricular hypertrophy index in rats with pulmonary heart disease. Specifically, cinnamon twig can significantly increase urine output, reduce the diameter of the main pulmonary artery and the diameter of the right ventricular outflow tract, improve cardiac function parameters (such as EF, LVEDD, IVST), and restore pulmonary function parameters (such as FVC, FEV1). 200It improves blood gas parameters (PEF, Vt), corrects abnormal blood gas patterns (increasing PaO2, decreasing PaCO2), and reduces right ventricular hypertrophy. Compared with the original control group (group C-6, Psoralea corylifolia), Cinnamomum cassia showed more comprehensive and significant improvements in most indicators, without the potential risk of hepatotoxicity. Other alternative drugs (such as cinnamon, dried ginger, asarum, and epimedium) also showed some improvement, but their effects were not as good as those of Cinnamomum cassia. Therefore, Cinnamomum cassia is an ideal replacement for Psoralea corylifolia, effectively enhancing the therapeutic effect and safety of the drug combination.

[0129] In this embodiment, due to the appropriate dosage, no experimental animals in group C-6 have died.

[0130] Example 2

[0131] Based on the aforementioned Example 1, the inventors discovered that cinnamon twig has the effects of warming and unblocking the meridians and assisting yang and qi transformation. Furthermore, evidence-based medicine shows that cinnamon twig is widely used in the treatment of pulmonary heart disease, and its warming and unblocking effect helps improve blood circulation and cardiac function in patients with pulmonary heart disease. To systematically evaluate the optimal application of cinnamon twig in prescriptions, this example sets up experimental groups with different cinnamon twig combinations and dosages, as detailed below:

[0132] 1.1 Experimental Grouping

[0133] Group A-1: ​​Add 6g of cinnamon twig to the original prescription. The specific prescription is as follows: 24 parts of astragalus, 15 parts of lepidium seed, 9 parts of psoralea, 15 parts of chuanxiong, 9 parts of alisma, 6 parts of platycodon, 3 parts of jujube and 6 parts of cinnamon twig.

[0134] Group A: Add 9g of cinnamon twig to the original prescription. The specific prescription is as follows: 24 parts of astragalus, 15 parts of lepidium seed, 9 parts of psoralea, 15 parts of chuanxiong, 9 parts of alisma, 6 parts of platycodon, 3 parts of jujube and 9 parts of cinnamon twig.

[0135] Group A-2: Add 12g of cinnamon twig to the original prescription. The specific prescription is as follows: 24 parts of astragalus, 15 parts of lepidium seed, 9 parts of psoralea, 15 parts of chuanxiong, 9 parts of alisma, 6 parts of platycodon, 3 parts of jujube and 12 parts of cinnamon twig.

[0136] Group B: Replace the Lepidium seed in the original prescription with Cinnamon Twig, and use 15 parts. The specific prescription is as follows: Astragalus 24 parts, Cinnamon Twig 15 parts, Psoralea 9 parts, Ligusticum chuanxiong 15 parts, Alisma 9 parts, Platycodon 6 parts, Jujube 3 parts.

[0137] Group C: Replace Psoralea corylifolia with an equal amount of 9 parts of Cinnamomum cassia. The specific prescription is as follows: 24 parts of Astragalus membranaceus, 15 parts of Lepidium apetalum, 9 parts of Cinnamomum cassia, 15 parts of Ligusticum chuanxiong, 9 parts of Alisma plantago-aquatica, 6 parts of Platycodon grandiflorus, and 3 parts of Ziziphus jujuba.

[0138] Group D: Replace Psoralea corylifolia with 6 parts of Cinnamomum cassia. The specific prescription is as follows: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamomum cassia 6 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Ziziphus jujuba 3 parts.

[0139] Group E: Replace Psoralea corylifolia with 12 parts of Cinnamomum cassia. The specific prescription is as follows: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamomum cassia 12 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Ziziphus jujuba 3 parts.

[0140] Group F: Replace Chuanxiong with Guizhi (Cinnamon Twig), add 15 parts Guizhi. The specific prescription is: Astragalus 24 parts, Lepidium 15 parts, Guizhi 9 parts, Guizhi 15 parts, Alisma 9 parts, Platycodon 6 parts, Jujube 3 parts.

[0141] Group G: Replace Alisma plantago-aquatica with Cinnamomum cassia and add 9 parts of Cinnamomum cassia. The specific prescription is as follows: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamomum cassia 9 parts, Ligusticum chuanxiong 15 parts, Cinnamomum cassia 9 parts, Platycodon grandiflorus 6 parts, and Jujube 3 parts.

[0142] According to the prescription composition and specific prescription quantity in the above groups, the following unified preparation standards shall be followed:

[0143] According to the drug composition and mass ratio in the prescription, all the medicinal ingredients in the prescription are pulverized and mixed through an 80-mesh sieve to obtain a drug mixture. Based on the mass of the drug mixture, 8 times the mass of the drug mixture is added to the first decoction and decocted for 1.0 hour. 8 times the mass of the drug mixture is added to the second decoction and decocted for 1.0 hour. 6 times the mass of the drug mixture is added to the third decoction and decocted for 1.0 hour. After each decoction, the mixture is filtered and the filtrate is collected. The filtrates from the multiple decoctions are then combined and concentrated to obtain the active pharmaceutical ingredient. The active pharmaceutical ingredient is prepared into a suspension before administration and administered according to the method described in 1.2 above. The finished products of each group of active pharmaceutical ingredients obtained in this way are recorded according to the group.

[0144] Based on the above groups, experiments were conducted according to the aforementioned unified standards for animal experiments. It should be noted that although the composition and specific mass ratios of the medicinal ingredients differed among the groups, all treatment groups were administered the same amount of raw medicinal material (7.29 g raw medicinal material / kg), ensuring a consistent total amount of raw medicinal material in each dose. This design aimed to eliminate the interference of dosage differences on the experimental results, thereby enabling a more accurate observation and comparison of the differences in the therapeutic effects of different drug combinations on the pulmonary heart disease model, and providing reliable experimental evidence for optimizing drug formulations.

[0145] 2.2 Animal Experiment Results

[0146] Based on the above groups, experiments were conducted according to the aforementioned unified standards for animal experiments, and the experimental results are shown in Tables 1-1 to 2-7:

[0147] Table 2-1 Effects of each group on 24-hour urine output in a limonene-induced pulmonary heart disease model in SD rats

[0148]

[0149] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05

[0150] The results of this experiment showed that the 24-hour urine output of the model control group rats was significantly lower than that of the normal control group (P<0.05). Among the drug administration groups, group C (9 parts of cinnamon twig replacing psoralea corylifolia) showed the most significant effect in improving urine output, and had a clear advantage over other groups.

[0151] Table 2-2 Effects of each group on the diameter of the main pulmonary artery and the inner diameter of the right ventricular outflow tract in a dinoflagellate-induced pulmonary heart disease model in SD rats.

[0152]

[0153]

[0154] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0155] The results showed that the diameter of the main pulmonary artery and the inner diameter of the right ventricular outflow tract were significantly increased in the model control group rats (P<0.05). Among the drug administration groups, group C (9 parts of cinnamon twig replacing psoralea corylifolia) showed the best effect, significantly reducing the diameter of the main pulmonary artery and the inner diameter of the right ventricular outflow tract, bringing them close to normal levels. Groups D and E (non-equal replacement) showed good effects but were not as good as group C.

[0156] Table 2-3 Effects of each group on cardiac function indicators in the lilacin-induced pulmonary heart disease model of SD rats

[0157]

[0158] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0159] The results showed that the EF value of the rats in the model control group was significantly reduced, while LVEDD and IVST were significantly increased (P<0.05). Group C (9 parts of cinnamon twig replacing psoralea corylifolia) showed the best improvement in all cardiac function indicators, with the EF value basically returning to normal levels and LVEDD and IVST significantly reduced compared to the model group, indicating that this combination can effectively improve cardiac function. Groups D and E (non-equal replacement) showed better effects than C.

[0160] Table 2-4 Effects of each group on respiratory parameters of pulmonary function (FEV1) in a limonene-induced SD rat model of pulmonary heart disease.

[0161]

[0162] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0163] The experimental results indicate that the FVC and FEV of the model control group rats were significantly lower. 200 PEF and FEV 0.2 / FVC was significantly reduced (P<0.05). Group C (9 parts of cinnamon twig replacing psoralea corylifolia) showed the most significant improvement in all pulmonary function indicators, approaching normal levels, indicating that this combination can effectively restore pulmonary function.

[0164] Table 2-5 Effects of each group on respiratory parameters of pulmonary function in the TB mode of a limonene-induced SD rat model of pulmonary heart disease.

[0165]

[0166]

[0167] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0168] The results showed that PEF and Vt were significantly reduced in the model control group rats (P<0.05). Group C (9 parts of cinnamon twig replacing psoralea corylifolia) showed the best recovery effect in PEF, Vt and Cpyn indices, indicating that this combination can effectively improve respiratory flow and lung compliance, and this group showed the best performance in improving respiratory function.

[0169] Table 1-6 Effects of each group on blood gas analysis results in the lilacin-induced SD rat model of pulmonary heart disease.

[0170]

[0171] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0172] The results showed that PaO2 was significantly decreased and PaCO2 was significantly increased in the model control group rats (P<0.05). Group C (replacing Psoralea corylifolia with 9 parts of Cinnamomum cassia) showed the most significant improvement in blood gas parameters, with both PaO2 and PaCO2 returning to normal levels. Groups D and E (non-equal replacement) showed better effects than C, while the A series (direct addition of Cinnamomum cassia) showed a weaker improvement.

[0173] Table 2-7 Effects of each group on the right ventricular hypertrophy index in a limonene-induced SD rat model of pulmonary heart disease.

[0174]

[0175]

[0176] Note: Compared with the normal control group + P<0.05; compared with the model control group * P<0.05.

[0177] The results showed that the right ventricular hypertrophy index was significantly increased in the model control group rats (P<0.05). Group C showed the best effect in reducing right ventricular hypertrophy.

[0178] Based on the experimental results of this embodiment, group C (replacing psoralea corylifolia with 9 parts cinnamon twig) showed significant advantages in all test indicators. These advantages were observed in 24-hour urine output, aortic and pulmonary artery diameter, right ventricular outflow tract diameter, cardiac function indicators (EF, LVEDD, IVST), and pulmonary function parameters (FVC, FEV1). 200 In terms of blood gas analysis indicators (PaO2, PaCO2) and right ventricular hypertrophy index, group C showed significantly better improvement than the other groups.

[0179] Of particular note is that Group C showed near-normal control group levels in several key indicators, demonstrating excellent therapeutic efficacy. In contrast, while other formulations also showed some therapeutic effect, the degree of improvement was significantly less than that of Group C. Groups D and E (non-equal substitution) showed the next best effect, while Group A series (direct addition of cinnamon twig) and other substitutions had relatively limited effects. This result is highly consistent with the findings of Group C-5 in Example 1, jointly confirming the significant superiority of the formulation of replacing psoralea corylifolia with cinnamon twig in equal amounts. This formulation, while eliminating the potential hepatotoxicity risk of psoralea corylifolia, fully utilizes the warming and invigorating effects of cinnamon twig in promoting blood circulation and tonifying yang, providing a safer and more effective option for the treatment of pulmonary heart disease.

[0180] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention. Technical aspects, shapes, and structures not described in detail in this invention are all well-known technologies.

Claims

1. A pharmaceutical composition for treating pulmonary heart disease, characterized in that, The ingredients, by weight, include the following raw materials: Astragalus membranaceus 21-27 parts, Lepidium apetalum 13-17 parts, Cinnamomum cassia 7-10 parts, Ligusticum chuanxiong 13-17 parts, Alisma plantago-aquatica 7-10 parts, Platycodon grandiflorus 5-7 parts, and Ziziphus jujuba 2-4 parts.

2. The pharmaceutical composition for treating pulmonary heart disease as described in claim 1, characterized in that, The ingredients, by weight, include the following raw materials: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamomum cassia 7-10 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Ziziphus jujuba 3 parts.

3. The pharmaceutical composition for treating pulmonary heart disease as described in claim 1, characterized in that, The ingredients, by weight, include the following medicinal materials: Astragalus membranaceus 24 parts, Lepidium apetalum 15 parts, Cinnamomum cassia 9 parts, Ligusticum chuanxiong 15 parts, Alisma plantago-aquatica 9 parts, Platycodon grandiflorus 6 parts, and Jujube 3 parts.

4. A pharmaceutical composition according to any one of claims 1-3, characterized in that, The Lepidium seed is stir-fried southern Lepidium seed, the Ligusticum chuanxiong is raw, and the Alisma plantago-aquatica is salted Alisma plantago-aquatica.

5. A pharmaceutical composition according to any one of claims 1-3, characterized in that, The pharmaceutical composition is prepared as an active ingredient and further prepared with pharmaceutically acceptable excipients into a clinically acceptable oral formulation.

6. The pharmaceutical composition according to claim 5, characterized in that, The dosage form of the oral preparation is one of the following: extract, decoction, powder, pill, tablet, granule, capsule, oral liquid, decoction paste, mixture, syrup, or paste.

7. A method for preparing a pharmaceutical composition according to any one of claims 1-3, characterized in that, It is prepared by any of the following methods: Method 1: Take the above seven raw medicinal materials, add water and decoct, filter to obtain decoction; the obtained decoction can be directly concentrated to obtain the active ingredient; or the obtained decoction can be concentrated first and then precipitated with ethanol, the supernatant can be collected, and then the supernatant can be concentrated to obtain the active ingredient. Method 2: Combined alcohol and water extraction method Astragalus and Ligusticum were extracted by ethanol reflux, and the extract was filtered and directly concentrated to obtain concentrated extract A; the remaining raw materials were decocted with water, filtered to obtain decoction, and directly concentrated or concentrated after alcohol precipitation to obtain concentrated extract B; concentrated extract A and concentrated extract B were combined to obtain the active ingredient. Method 3: Crushing and Mixing Method The above seven raw medicinal materials are pulverized and then mixed to obtain the active ingredients; The active ingredient prepared by any one of methods one to three is combined with pharmaceutically acceptable excipients to prepare a clinically acceptable oral formulation.

8. The method for preparing a pharmaceutical composition according to claim 7, characterized in that, The specific steps of adding water and decocting in Method 1 are as follows: add 8-12 times the amount of water as the raw material of the medicinal material at one time, decoct 2-3 times at a time, and decoct for 1-1.5 hours each time.

9. The use of the pharmaceutical composition according to any one of claims 1-5 in the preparation of a medicament for treating chronic pulmonary heart disease, preferably, the chronic pulmonary heart disease being in remission.

10. The application as described in claim 9, characterized in that: The drug has at least one of the following effects: improving cardiac function, promoting diuresis, improving lung function, and reducing right ventricular hypertrophy.

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