A traditional Chinese medicine composition for treating cough, and a preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating acute and subacute cough and a preparation method and application thereof. The composition is composed of Ephedra, bitter apricot kernel, licorice, gypsum, radix peucedani, platycodon grandiflorum, belamcanda and euphorbia helioscopia seed, is aimed at cough caused by lung qi stagnation, evil heat blocking the lung and phlegm turbidity obstruction, and on the basis of the MA XING SHI GAN decoction for promoting lung and clearing heat, radix peucedani and euphorbia helioscopia seed are added to strengthen qi and phlegm, and platycodon grandiflorum and belamcanda are added to strengthen the lung and relieve the throat. The weight ratio is preferably 5:10:6:20:10:10:10:10. The preparation comprises the following steps: first decocting the raw gypsum, twice water extraction, combining the filtrates, reducing pressure concentration, auxiliary material deployment, filling and sterilization. The composition has clear levels, can improve symptoms such as cough, expectoration, itching of the throat, shortness of breath and the like, and is suitable for acute and subacute cough of the wind-heat invading the lung syndrome or the phlegm-heat blocking the lung syndrome.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and particularly relates to a traditional Chinese medicine composition for treating cough, as well as a preparation method and application thereof. Background Art

[0002] Cough is one of the most common clinical symptoms of respiratory diseases, and is a defensive reflex generated after the respiratory mucosa is stimulated by physical, chemical or biological factors. According to the course of disease, cough is usually divided into acute cough, subacute cough and chronic cough: acute cough refers to a course of less than 3 weeks, subacute cough refers to a course of 3 to 8 weeks, and chronic cough refers to a course of more than 8 weeks. Acute cough is commonly seen in common cold and acute tracheobronchitis, and subacute cough is commonly seen in post-infectious cough, upper airway cough syndrome, cough variant asthma, etc. Recurrent or protracted cough can affect the sleep, work efficiency and daily life quality of patients, and may be accompanied by problems such as chest and abdominal muscle pain and anxiety.

[0003] At present, the treatment of acute and subacute cough mainly includes symptomatic Western medicine treatment, syndrome differentiation treatment with classic traditional Chinese medicine prescriptions, and treatment with commercially available Chinese patent medicines. Western medicine treatment often selects antitussives, expectorants, bronchodilators or antihistamines according to manifestations such as dry cough, expectoration or airway hyperresponsiveness; the classic traditional Chinese medicine prescriptions are represented by Maxing Shigan Decoction, which is mainly used for lung heat cough and asthma; commercially available Chinese patent medicines such as Jizhi Syrup and Suhuang Zhike Capsule focus on clearing heat and resolving phlegm, or dispelling wind and relieving cough respectively. The above solutions can relieve symptoms within their corresponding applicable scopes, but for patients with concurrent symptoms such as cough, sticky phlegm that is difficult to expectorate, itchy or sore throat, and shortness of breath, the following deficiencies still exist: First, the coverage of existing solutions for compound pathogenesis and multi-dimensional symptoms is still insufficient. Conventional Western medicine treatment mainly focuses on inhibiting cough reflex, improving sputum excretion or reducing airway hyperresponsiveness; Maxing Shigan Decoction has a simplified composition of medicinal materials, and is good at ventilating the lung, clearing heat and relieving asthma, but lacks special compatibility for resolving phlegm, lowering qi and soothing the throat for manifestations such as sticky phlegm that is difficult to expectorate, itchy and sore throat; existing Chinese patent medicines such as Jizhi Syrup and Suhuang Zhike Capsule each have their own functional focuses, and when lung qi stagnation, pathogenic heat stagnating in the lung and phlegm turbidity obstruction occur simultaneously, a standardized compound that takes into account ventilating the lung, clearing heat, lowering qi, resolving phlegm and soothing the throat is still needed.

[0004] Second, existing treatment solutions still need further balance among curative effect, compliance and applicable scope. Some antitussives may cause drowsiness, dizziness or gastrointestinal discomfort, and codeine-based drugs also have a dependence risk; some traditional Chinese medicine prescriptions or Chinese patent medicines have a relatively single applicable syndrome, and for patients with concurrent cough, expectoration, throat discomfort and shortness of breath, multiple drugs may need to be used in combination or modified according to syndromes, which is not conducive to the formation of preparations with clear composition, stable process and convenient promotion. Therefore, it is necessary to provide a traditional Chinese medicine composition with a clear composition hierarchy, targeting the above compound symptoms and facilitating standardized preparation. Contents of the Invention

[0005] (a) Technical problems to be solved In view of the above-mentioned shortcomings of the prior art, the present invention provides a traditional Chinese medicine composition for treating cough, its preparation method and application, aiming to solve the problems that existing classic prescriptions do not cover the symptoms of sticky phlegm that is difficult to expectorate, itchy and sore throat, and impaired lung qi circulation, as well as the problems that existing treatment plans cannot simultaneously address the issues of lung qi circulation, heat clearing, qi regulation, phlegm resolution and throat soothing.

[0006] (II) Technical Solution To achieve the above objectives, the present invention provides the following technical solution: A traditional Chinese medicine composition for treating cough, comprising eight raw materials: ephedra, bitter almond, licorice, gypsum, angelica dahurica, platycodon grandiflorus, belamcanda chinensis, and lepidium apetalum, with each raw material formulated in a fixed weight ratio. Among them, the weight parts of ephedra are 5 to 15 parts, the weight parts of bitter almond are 8 to 15 parts, the weight parts of licorice are 5 to 10 parts, the weight parts of gypsum are 15 to 30 parts, the weight parts of angelica dahurica are 8 to 15 parts, the weight parts of platycodon grandiflorus are 8 to 15 parts, the weight parts of belamcanda chinensis are 8 to 15 parts, and the weight parts of lepidium apetalum are 8 to 15 parts. The weight parts are a fixed weight ratio unit between each active pharmaceutical ingredient, and the weight parts of each active pharmaceutical ingredient use the same weight measurement unit.

[0007] Preferably, the fixed weight ratio of each raw material is: 5 parts ephedra, 10 parts bitter almond, 6 parts licorice, 20 parts gypsum, 10 parts angelica dahurica, 10 parts platycodon grandiflorus, 10 parts belamcanda chinensis, and 10 parts lepidium apetalum. The processing specifications for each raw material are as follows: ephedra is processed ephedra, bitter almond is stir-fried bitter almond, gypsum is raw gypsum, and licorice is raw licorice or processed licorice.

[0008] Preferably, the composition is prepared as an oral compound dosage form, and excipients that meet pharmaceutical standards may be added to the compound, including flavoring agents and preservatives. Flavoring agents are made of sucrose or steviol glycosides, and the amount added shall not exceed 20% of the total weight of the mixture; Sodium benzoate or potassium sorbate are used as preservatives.

[0009] Preferably, the composition can be used in combination with antitussive and expectorant chemical drugs, such as dextromethorphan or ambroxol.

[0010] A method for preparing a traditional Chinese medicine composition for treating cough, the method comprising the following steps: Step 1: Weigh each raw material according to the set weight ratio, mix all raw materials evenly, add purified water for soaking, and after soaking, perform the first decoction. After the decoction, perform solid-liquid separation to obtain the filtrate from the first decoction and the residue after decoction. Step 2: Add purified water to the obtained filter residue for a second decoction. After the decoction is completed, perform solid-liquid separation to obtain the filtrate from the second decoction. Step 3: Combine the filtrate obtained from the first decoction with the filtrate obtained from the second decoction and stir them thoroughly. Concentrate the combined filtrate, add the prescribed pharmaceutical excipients, and adjust the volume to obtain the intermediate mixture. Step four: The intermediate compound is filled into containers, and sterilization is performed after filling to finally obtain the finished Chinese medicine composition for treating cough.

[0011] Preferably, in step one, the weight of purified water added is 8 to 12 times the total weight of all raw materials, the soaking time is 0.5 to 1 hour, the first decoction time is 0.5 to 1 hour, and the decoction is kept boiling during the decoction process. In step two, the weight of purified water added should be 6 to 8 times the total weight of all raw materials. The second decoction should last for 0.5 to 1 hour, and the decoction should be kept boiling during the decoction process. Before being mixed and soaked, the raw gypsum in the pharmaceutical raw materials needs to be crushed separately and decocted for 30 minutes before being combined with the other raw materials for subsequent soaking and decoction.

[0012] Preferably, the solid-liquid separation operations in steps one and two are carried out by filter cloth filtration or centrifugation, and the filtrate obtained after separation; The concentration process in step three is carried out by vacuum concentration. The temperature of the concentration process is controlled between 60 degrees Celsius and 80 degrees Celsius. The relative density of the concentrated extract at 60 degrees Celsius is 1.05 to 1.15. In step three, the excipient preparation process requires stirring until all excipients are completely dissolved in the drug solution; The sterilization process in step four uses flowing steam sterilization at 105 to 115 degrees Celsius for 30 to 45 minutes.

[0013] The application of a traditional Chinese medicine composition for treating cough in the preparation of a medicine for treating cough, which is used to treat both acute and subacute coughs; Acute cough refers to a cough lasting less than 3 weeks, including cough caused by the common cold and cough caused by acute tracheobronchitis. Subacute cough refers to cough lasting 3 to 8 weeks, including post-infectious cough, cough caused by upper airway cough syndrome, and cough caused by cough variant asthma. This medicine is also suitable for coughs caused by wind-heat invading the lungs or phlegm-heat obstructing the lungs, with corresponding clinical symptoms including cough, expectoration, itchy throat, shortness of breath, thick yellow phlegm, difficulty expectorating phlegm, and sore throat.

[0014] Preferably, the drug can improve the clinical symptoms of patients with cough, reduce the severity of cough assessment results, and shorten the duration of cough relief and cough disappearance. The cough severity assessment used a clinically accepted cough severity assessment scale, which includes five assessment dimensions: daytime cough frequency, nighttime cough impact on sleep, cough severity, cough impact on daily work and life, and cough-induced anxiety. The drug is administered orally. The dosage is one dose of the drug corresponding to the ratio of the raw material, taken twice a day after meals, morning and evening. A complete course of treatment is 3 to 7 days.

[0015] Preferably, the drug can be used as a monotherapy for the treatment of cough, or as a combination therapy with conventional antitussive Western medicines for the treatment of cough. The combined administration method is suitable for patients with subacute cough. The conventional antitussive Western medicines include centrally acting antitussives, bronchodilators, and antihistamines.

[0016] (III) Beneficial Effects 1. This invention is based on the lung-clearing and heat-reducing formula of Ma Xing Shi Gan Tang. While maintaining the compatibility of ephedra and gypsum, it adds angelica, platycodon, belamcanda, and lepidium to form three synergistic functional units: ephedra-gypsum focuses on clearing lung heat, bitter apricot kernel-angelica-lepidium focuses on descending lung qi, resolving phlegm and relieving asthma, and platycodon-belamcanda focuses on clearing lung qi and soothing the throat; licorice harmonizes the herbs and protects the middle jiao. Compared with classic formulas that only focus on clearing lung heat and relieving asthma, this invention further strengthens the effects of descending qi, resolving phlegm, and soothing the throat, and can simultaneously target symptoms such as cough, sticky phlegm that is difficult to expectorate, itchy and sore throat, and shortness of breath. The formulation hierarchy and applicable symptoms are more clearly defined.

[0017] 2. This invention employs a standardized process involving the pre-decoction of raw gypsum, two decoctions with added water, filtrate merging, vacuum concentration, excipient preparation, filling, and steam sterilization. The pulverization and pre-decoction of raw gypsum for 30 minutes improves the completeness of the extraction; the two water extractions increase the utilization rate of the raw material; vacuum concentration at 60–80°C helps control the concentration process; and steam sterilization at 105–115°C for 30–45 minutes meets microbial control requirements while improving the consistency of the process across different batches, facilitating large-scale preparation.

[0018] 3. The raw materials used in this invention are all commonly used Chinese medicinal herbs in clinical practice, and the formula is relatively simple. No serious adverse reactions clearly related to medication were found during clinical observation. Preferably, after being prepared into an oral compound, patients do not need to decoct it themselves, making it convenient to store, carry, and take; by adding a flavoring agent that meets pharmaceutical standards, the taste can be improved and medication compliance can be enhanced.

[0019] 4. The herbal composition of the present invention can be used alone for mild to moderate acute or subacute cough, or it can be used in combination with conventional antitussive and expectorant drugs according to the patient's symptoms, so as to intervene from different aspects such as clearing lung heat, reducing qi and resolving phlegm and relieving symptoms, thereby expanding the clinical application methods. Attached Figure Description

[0020] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, the preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0021] Figure 1 This is a flowchart illustrating the preparation process of the traditional Chinese medicine composition of the present invention. Figure 2 The effect of the composition of the present invention on the cough latency and the number of coughs within 2 minutes in ammonia-induced cough mice; Figure 3 The effect of the composition of the present invention on the amount of phenol red excreted in the trachea of ​​mice; Figure 4 The effect of the composition of the present invention on xylene-induced ear swelling and swelling inhibition rate in mice; Figure 5 The composition of clinical efficacy and changes in total CET score in 121 clinical observation cases; Figure 6 This study compares the overall effectiveness and cough disappearance time of the composition of the present invention with those of acute bronchitis syrup in a randomized controlled trial. Detailed Implementation

[0022] This application provides a traditional Chinese medicine composition for treating cough, its preparation method, and its application. Based on the traditional Chinese medicine principles of "relieving cough by clearing the lungs, resolving phlegm and heat, and relieving sore throat," the composition adds Peucedanum praeruptorum, Platycodon grandiflorus, Belamcanda chinensis, and Lepidium apetalum to the existing formula of Ephedra sinica, bitter almond, gypsum, and licorice. The weight ratios and preparation process of each raw material are specified to improve symptoms such as cough, phlegm, sore throat, and shortness of breath in patients with acute or subacute cough.

[0023] The present invention will be further described below with reference to specific embodiments. The listed embodiments are used to illustrate the technical solutions of the present invention and do not constitute a limitation on the scope of protection of the present invention.

[0024] Optimal proportions of the traditional Chinese medicine composition in Example 1: This embodiment represents a preferred formulation, with the following weight proportions for each raw material: 5 parts processed ephedra, 10 parts stir-fried bitter almond, 6 parts processed licorice root, 20 parts raw gypsum, 10 parts angelica dahurica, 10 parts platycodon grandiflorus, 10 parts belamcanda chinensis, and 10 parts lepidium apetalum; each part corresponds to the same unit of measurement. Based on 1g per part, the total weight of the raw materials in a single dose is 81g.

[0025] Ephedra (processed) and gypsum (raw) are the principal herbs, with a weight ratio of 1:4. They respectively exert the effects of ventilating the lungs and relieving asthma and clearing lung heat, and mutually restrain each other's medicinal properties. Fried bitter apricot kernel, Peucedanum praeruptorum, and Lepidium apetalum work together to lower qi, stop cough, resolve phlegm, and relieve asthma. Platycodon grandiflorus and Belamcanda chinensis work together to ventilate the lungs, benefit the throat, clear heat, and resolve phlegm. Processed licorice harmonizes all the herbs and also takes into account moistening the lungs, stopping cough, and protecting the spleen and stomach.

[0026] Example 2: Lower limit of the ratio range of the traditional Chinese medicine composition: This embodiment is the lower limit of the active pharmaceutical ingredient ratio scheme. The weight parts of each active pharmaceutical ingredient are as follows: 5 parts of processed ephedra, 8 parts of stir-fried bitter almond, 5 parts of raw licorice, 15 parts of raw gypsum, 8 parts of angelica dahurica, 8 parts of platycodon grandiflorus, 8 parts of belamcanda chinensis, and 8 parts of lepidium apetalum. Each part corresponds to a fixed weight unit of measurement of 1g, and the total weight of a single dose of active pharmaceutical ingredients is 65g.

[0027] Upper limit of the ratio range of the traditional Chinese medicine composition in Example 3: This embodiment represents the upper limit of the formulation range. The weight parts of each raw material are as follows: 15 parts of processed ephedra, 15 parts of stir-fried bitter almond, 10 parts of processed licorice root, 30 parts of raw gypsum, 15 parts of angelica dahurica, 15 parts of platycodon grandiflorus, 15 parts of belamcanda chinensis, and 15 parts of lepidium apetalum. Each part corresponds to the same unit of measurement, calculated as 1g per part, resulting in a total weight of 130g for a single dose of raw materials. This embodiment illustrates the upper limit of the formulation range of the present invention.

[0028] Example 4: Intermediate formulation of the traditional Chinese medicine composition: This embodiment represents an intermediate-value scheme within the specified proportions. The weight proportions of each raw material are as follows: 10 parts raw ephedra, 12 parts stir-fried bitter almond, 8 parts raw licorice, 25 parts raw gypsum, 12 parts angelica dahurica, 12 parts platycodon grandiflorus, 12 parts belamcanda chinensis, and 12 parts lepidium apetalum. Each part corresponds to the same unit of measurement, calculated as 1g per part, resulting in a total weight of 103g for a single dose of raw materials. This embodiment is used to illustrate an intermediate-value scheme within the specified proportions.

[0029] Example 5: Traditional Chinese medicine compositions with different processing specifications: This embodiment illustrates an optional processing method. The weight proportions of each raw material are the same as in Example 1, but the processing specifications are adjusted as follows: 5 parts raw ephedra, 10 parts raw bitter almond, 6 parts raw licorice, 20 parts raw gypsum, 10 parts angelica dahurica, 10 parts raw platycodon grandiflorus, 10 parts belamcanda chinensis, and 10 parts stir-fried lepidium apetalum. Different processing specifications can be selected according to the preparation process and clinical needs.

[0030] Example 6 Preferred preparation process (oral compound): This embodiment uses an optimized ratio of active pharmaceutical ingredients to prepare a commonly used oral compound in clinical practice. The specific steps are as follows: Pretreatment: Weigh each raw material according to the weight proportions, crush the raw gypsum into coarse powder separately, add purified water in an amount of 10 times the total weight of the raw materials, decoct for 30 minutes, and keep the decoction at a gentle boil. First decoction: After mixing the remaining 7 raw materials evenly, add them to the above-mentioned pre-decocted gypsum liquid, add purified water to 10 times the total weight of the raw materials, soak at room temperature for 0.5 hours, then turn on the heat to decoct, keep the liquid at a gentle boil and decoct for 1 hour. After decoction, filter under pressure using a 200-mesh medicinal filter cloth, and collect the first filtrate and the first residue separately. Second decoction: Add purified water to the first filter residue in an amount equal to 8 times the total weight of the raw materials, turn on the heat and decoct for 1 hour while maintaining a gentle boil. After decoction, filter under pressure using a 200-mesh medicinal filter cloth, collect the second filtrate, and discard the filter residue. Concentration and formulation: Combine the first and second filtrates, stir evenly, and transfer to a vacuum concentration tank. Concentrate under reduced pressure at 70℃ and -0.08MPa until the relative density of the concentrated extract at 60℃ is 1.10. Add 10% sucrose as a flavoring agent and 0.1% sodium benzoate as a preservative to the extract. Stir until all excipients are completely dissolved. Add purified water to make up to 400ml and stir evenly to obtain the intermediate of the mixture. Filling and sterilization: After the intermediate of the compound is filtered through a 10μm filter, it is filled into a 100ml brown oral liquid bottle, sealed with a screw cap, and sterilized with flowing steam at 110℃ for 30 minutes. After sterilization, it is inspected by light, labeled, and packaged to obtain the finished compound of the traditional Chinese medicine composition of this invention.

[0031] Example 7: Preparation scheme for lower limit process parameters: This embodiment uses the active pharmaceutical ingredient ratio from Example 2, and the specific steps are as follows: Pretreatment: Weigh each raw material according to the weight proportions, crush the raw gypsum into coarse powder separately, add purified water in an amount of 8 times the total weight of the raw materials, and decoct for 30 minutes. First decoction: Add the remaining raw materials to the gypsum decoction, add purified water to 8 times the total weight of the raw materials, soak at room temperature for 0.5 hours, decoct at a gentle boil for 0.5 hours, centrifuge at 3000 r / min for 10 minutes, and collect the first filtrate and the first filter residue. Second decoction: Add purified water, which is 6 times the total weight of the raw materials, to the first filter residue and decoct for 0.5 hours while maintaining a gentle boil. Centrifuge and separate the residue using the same method, and collect the second filtrate. Concentration and formulation: Combine the two filtrates and concentrate under reduced pressure at 60℃ and -0.08MPa until the relative density of the clear extract at 60℃ is 1.05; add steviol glycosides as a flavoring agent (addition amount is 0.05% of the total weight of the final product) and 0.05% potassium sorbate as a preservative, stir to dissolve and then make up to 300ml to obtain the intermediate of the compound; Filling and sterilization: After fine filtration, the contents are filled into 100ml oral liquid bottles and sterilized with flowing steam at 105℃ for 45 minutes to obtain the finished product.

[0032] Example 8: Preparation scheme for upper limit process parameters: This embodiment uses the active pharmaceutical ingredient ratio from Example 3, and the specific steps are as follows: Pretreatment: Weigh each raw material according to the weight proportions, crush the raw gypsum into coarse powder separately, add purified water in 12 times the total weight of the raw materials, and decoct for 30 minutes. First decoction: Add the remaining raw materials to the gypsum decoction, add purified water to 12 times the total weight of the raw materials, soak at room temperature for 1 hour, then decoct at a gentle boil for 1 hour, filter with a 300-mesh medicinal filter cloth, and collect the first filtrate and the first filter residue. Second decoction: Add purified water at a volume of 7 times the total weight of the raw materials to the first filter residue, maintain a gentle boil and decoct for 1 hour, filter in the same way, and collect the second filtrate; Concentration and formulation: Combine the two filtrates and concentrate under reduced pressure at 80℃ and -0.07MPa until the relative density of the clear extract at 60℃ is 1.15; add 15% sucrose as a flavoring agent and 0.1% sodium benzoate as a preservative, stir to dissolve and then make up to 500ml to obtain the intermediate of the compound. Filling and sterilization: After fine filtration, the contents are filled into 100ml oral liquid bottles and sterilized with flowing steam at 115℃ for 30 minutes to obtain the finished product.

[0033] Example 9: Preparation scheme of traditional Chinese medicine decoction: This embodiment is a decoction preparation scheme for clinical medical institutions, using the raw material ratio of Example 1. The specific steps are as follows: Pretreatment: Weigh each raw material according to the weight proportions, package the raw gypsum separately, and indicate that it should be decocted first; First decoction: Add raw gypsum to the decoction pot, add 800ml of purified water, bring to a boil over high heat, then simmer over low heat for 30 minutes; Combined decoction: Add the remaining 7 raw medicinal materials to the above-mentioned gypsum decoction, add purified water to the total water volume of 1000ml, soak for 30 minutes, bring to a boil over high heat, then simmer over low heat for another 30 minutes, filter to obtain about 400ml of the first decoction; Second decoction: Add 800ml of purified water to the dregs, bring to a boil over high heat, then simmer over low heat for 20 minutes. Filter to obtain about 300ml of the second decoction. Combine the two decoctions, mix them well, and take them warm twice a day after meals, morning and evening, to obtain the Chinese herbal decoction for clinical use.

[0034] Example 10: A compound preparation using ambroxol in combination: This embodiment uses the intermediate prepared in Example 6 to prepare a compound preparation in combination with ambroxol hydrochloride. The specific procedure is as follows: Take 4000ml of the intermediate prepared in Example 6, add 3g of pharmaceutical grade ambroxol hydrochloride, stir until completely dissolved, add purified water to make up to 5000ml, filter, fill and sterilize to obtain the compound preparation; each 10ml of the compound preparation contains 1.62g of the raw herbal composition of the present invention and 6mg of ambroxol hydrochloride, which is suitable for patients with moderate to severe cough with thick sputum and difficulty in expectoration.

[0035] Example 11: A compound preparation used in combination with dextromethorphan: This embodiment uses the intermediate prepared in Example 6 to prepare a compound preparation in combination with dextromethorphan hydrobromide. The specific procedure is as follows: Take 4000ml of the intermediate prepared in Example 6, add 0.75g of pharmaceutical grade dextromethorphan hydrobromide, stir until completely dissolved, add purified water to make up to 5000ml, filter, fill and sterilize to obtain the compound preparation; each 10ml of the compound preparation contains 1.62g of the raw herbal composition of the present invention and 1.5mg of dextromethorphan hydrobromide, which is suitable for patients with acute cough, mainly dry cough, and frequent and severe cough.

[0036] Example 12: Antitussive pharmacodynamic test: Test drugs: The composition of the present invention (the compound prepared in Example 6, with a crude drug concentration of 0.2025 g / ml); Positive control drug 1: Ma Xing Shi Gan Tang decoction (prepared with the classic formula, with a crude drug concentration of 0.2 g / ml); Positive control drug 2: Commercially available acute bronchitis syrup; Positive control drug 3: Commercially available Su Huang Zhi Ke capsules.

[0037] Experimental animals: SPF-grade KM mice, half male and half female, weighing 18-22g, a total of 50 mice, were randomly divided into 5 groups of 10 mice each, namely blank control group, composition of the present invention group, Ma Xing Shi Gan Tang group, Ji Zhi Tang Jiang group, and Su Huang Zhi Ke capsule group.

[0038] Experimental methods: Each group was administered the clinically equivalent dose by gavage once a day for 7 consecutive days. The blank control group was given an equal volume of physiological saline. One hour after the last administration, the mice were placed in a closed cough induction chamber and sprayed with 0.2 mol / L ammonia water with compressed air for 10 seconds. After the spraying was stopped, the cough latency period (the time from the end of the spraying to the first cough) and the number of coughs within 2 minutes were observed and recorded for each mouse.

[0039] Experimental results: Note: Compared with the blank control group, P < 0.001; compared with the Ma Xing Shi Gan Tang group, P < 0.05.

[0040] The experimental results showed that the cough latency period of the composition group of the present invention was prolonged to 46.83±6.75s, and the number of coughs within 2 minutes was reduced to 18.53±3.96 times; the difference was statistically significant compared with the blank control group (P<0.001) and also statistically significant compared with the Ma Xing Shi Gan Tang group (P<0.05). The composition group of the present invention showed good comprehensive antitussive effect in each administration group, as shown in the results below. Figure 2 .

[0041] Example 13 Expectorant Efficacy Test: The test drug, test animals, grouping and dosing regimen are the same as in Example 12.

[0042] Experimental Methods: Thirty minutes after the last administration, each mouse was intraperitoneally injected with 0.5 ml of 0.5% phenol red saline solution. Thirty minutes after injection, the mice were euthanized by cervical dislocation, the trachea was dissected, and a complete tracheal segment was cut from the thyroid cartilage to the tracheal bifurcation. The trachea was flushed three times with 3 ml of saline solution, and the flushing fluids were combined. The mixture was centrifuged at 3000 r / min for 10 minutes, and the absorbance of the supernatant was measured at 546 nm using a UV spectrophotometer. The amount of phenol red secreted from the trachea was calculated based on the phenol red standard curve.

[0043] Experimental results: Note: Compared with the blank control group, P < 0.001; compared with the Ma Xing Shi Gan Tang group, P < 0.01.

[0044] The experimental results showed that the tracheal phenol red excretion rate of the composition of the present invention was 2.27 ± 0.33 μg / ml; the difference was statistically significant compared with the blank control group (P < 0.001) and compared with the Ma Xing Shi Gan Tang group (P < 0.01). These results suggest that the composition of the present invention has the effect of promoting airway secretion and improving sputum expectoration. (See attached figures). Figure 3 .

[0045] Example 14 Anti-inflammatory pharmacodynamic test The test drug, test animals, grouping and dosing regimen are the same as in Example 12.

[0046] Experimental method: One hour after the last administration, 0.05 ml of xylene was evenly applied to both sides of the right ear of each mouse to induce inflammation. The left ear was left untreated as a blank control. One hour after the inflammation was induced, the mice were euthanized by cervical dislocation. Ear pieces from the same location on both ears of the mice were removed using an 8 mm diameter punch, accurately weighed, and the degree of ear swelling (ear swelling = weight of right ear piece - weight of left ear piece) and swelling inhibition rate were calculated.

[0047] Experimental results: Note: Compared with the blank control group, P < 0.001; compared with the other three positive control groups, P < 0.05.

[0048] The experimental results showed that the ear swelling degree of the composition of the present invention was 5.16±1.08 mg, and the swelling inhibition rate was 59.15%. The difference was statistically significant compared with the blank control group (P<0.001) and with the remaining positive control groups (P<0.05). These results suggest that the composition of the present invention has anti-inflammatory effects. (See attached figures.) Figure 4 .

[0049] Example 15 In vitro antibacterial test: Test drug: The composition of the present invention (the mixture prepared in Example 6, sterile filtered and ready for use); Positive control drug: penicillin sodium injection.

[0050] Test strains: Common respiratory pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis, all of which were clinically isolated standard strains.

[0051] Test method: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the composition of the present invention against each strain were determined by the micro-broth dilution method.

[0052] Test results: The MIC of the composition of the present invention against Streptococcus pneumoniae was 15.6 mg / ml and the MBC was 31.2 mg / ml; the MIC against Staphylococcus aureus was 31.2 mg / ml and the MBC was 62.5 mg / ml; the MIC against Haemophilus influenzae was 31.2 mg / ml and the MBC was 62.5 mg / ml; and the MIC against Moraxella catarrhalis was 15.6 mg / ml and the MBC was 31.2 mg / ml.

[0053] The experimental results show that the composition of the present invention exhibits certain in vitro antibacterial activity against Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis under the experimental conditions, which can be used as one of the pharmacodynamic bases for improving respiratory infection-related cough symptoms.

[0054] Example 16 Single-arm clinical trial (121 cases): Case source: Cough patients who visited the outpatient department of the Department of Traditional Chinese Medicine at Peking University People's Hospital between December 2023 and December 2024. After ethical review, 121 eligible cases were ultimately included in this study.

[0055] Diagnostic criteria: Western medicine diagnosis refers to the "Guidelines for the Diagnosis and Treatment of Cough (2021 Edition)", which meets the diagnosis of acute cough (duration <3 weeks) or subacute cough (duration 3-8 weeks), with cough as the main or only symptom, and no obvious abnormalities found in chest imaging examination; Traditional Chinese medicine diagnosis meets the syndrome of wind-heat invading the lungs or phlegm-heat obstructing the lungs.

[0056] Inclusion and exclusion criteria: Patients aged ≥18 years who have signed informed consent forms and have taken medication as prescribed for more than 3 days are included; patients with serious underlying diseases, drug allergies, pregnant or lactating women, and patients with mental illness are excluded.

[0057] Treatment plan: The patient takes the herbal decoction prepared in Example 9 of this invention, one dose per day, divided into two warm doses taken after meals in the morning and evening, for a total of 7 days as one course of treatment.

[0058] Efficacy evaluation criteria: The severity of cough was assessed using the Simplified Cough Evaluation Test (CET). The CET includes five dimensions: daytime cough frequency, impact of nighttime cough on sleep, cough severity, impact of cough on daily work and life, and cough-induced anxiety. Each dimension is scored from 1 to 5, with a higher total score indicating a more severe cough. The efficacy index was calculated using the nimodipine method: Cure was defined as a CET score reduction of ≥95% and near-complete disappearance of cough symptoms; Significant improvement was defined as a CET score reduction of ≥70%; Effective was defined as a CET score reduction of 30%–69%; Ineffective was defined as a CET score reduction of <30%. The overall effective rate was calculated as (number of cured cases + number of cases with significant improvement + number of cases with effectiveness) / total number of cases × 100%. Cough relief time, cough disappearance time, and adverse reactions were also recorded.

[0059] Experimental results: (1) Baseline data: Among the 121 patients, there were 33 males and 88 females, with a mean age of 50.83±13.98 years and a median duration of illness of 7 days. Among them, there were 89 cases of acute cough and 32 cases of subacute cough.

[0060] (2) Clinical efficacy: After one course of treatment, 83 cases (68.59%) were cured, 2 cases (1.65%) showed significant improvement, 25 cases (20.66%) showed improvement, and 11 cases (9.09%) showed no improvement, with a total effective rate of 90.91%. Compared with the preset target effective rate of 73%, the difference was statistically significant (P<0.001).

[0061] (3) Symptom improvement: The median cough relief time was 3 days, and the median cough disappearance time was 6 days; the total CET score on the 3rd day of medication and the 1st week of medication were significantly lower than before treatment (P<0.001). The specific data are as follows, and the results are shown in [link to results]. Figure 5 .

[0062] Note: Compared with before treatment, △P < 0.001.

[0063] (4) Safety results: No serious adverse reactions clearly related to the study drug, such as nausea, vomiting, rash or abnormal liver and kidney function, were found during the observation period.

[0064] Example 17: Randomized controlled clinical trial (compared to Acute Bronchitis Syrup): Case source: 120 patients with acute bronchitis of the phlegm-heat obstructing the lungs were included in the same period and randomly divided into an experimental group and a control group, with 60 patients in each group. There were no statistically significant differences in baseline data between the two groups (P>0.05), and they were comparable.

[0065] Treatment regimen: The experimental group took the compound prepared in Example 6 of this invention, 20 ml each time, 3 times a day; the control group took commercially available acute bronchitis syrup, 30 ml each time, 3 times a day; both groups were treated for 7 consecutive days.

[0066] The efficacy evaluation criteria are the same as in Example 16.

[0067] Results: The total effective rate in the experimental group was 90.91%, while that in the control group was 83.33%. The median cough resolution time was 6 days in the experimental group and 9 days in the control group. The experimental group showed significantly better results than the control group in terms of both total effective rate and cough relief speed (P < 0.05). See attached results. Figure 6 .

[0068] Example 18 Accelerated Stability Test: Three batches of the compound preparation prepared in Example 6 were placed in a constant temperature and humidity chamber and stored for 6 months at 40℃±2℃ and 75%±5% relative humidity. Samples were taken at 0 months, 1 month, 2 months, 3 months and 6 months to test the properties, identification, relative density, pH value, microbial limit and content determination indicators.

[0069] Test results: During the 6-month accelerated test, all test indicators of the three batches of samples showed no significant changes, no stratification, precipitation or mold growth, and the microbial limits were always qualified, indicating that the accelerated stability of the formulation of this invention is good.

[0070] Example 19 Long-term stability test: Three batches of the compound preparation prepared in Example 6 were placed in a constant temperature and humidity chamber and stored for 12 months at 25℃±2℃ and 60%±10% relative humidity. Samples were taken at 0 months, 3 months, 6 months, 9 months and 12 months respectively, and the test items were the same as those for the accelerated stability test.

[0071] Test results: During the 12-month long-term test, all test indicators of the three batches of samples met the quality standard requirements and showed no significant changes, indicating that the formulation of the present invention has good long-term stability and can meet the needs of clinical storage and use.

[0072] Example 20: Detailed information from the clinical observation study Case source: From December 2023 to December 2024, this study included patients with cough who visited the Department of Traditional Chinese Medicine at Peking University People's Hospital and took Xuanfei Zhike Fang (a traditional Chinese medicine formula). Based on the inclusion and exclusion criteria, 121 cases were ultimately included. Basic patient information, medication duration, symptom relief, cough severity scores, and adverse reactions were collected through questionnaires completed under the guidance of physicians. This study was approved by the Ethics Review Committee of Peking University People's Hospital, with ethics approval number 2023PHB420-002.

[0073] Diagnostic criteria: Based on the "Guidelines for the Diagnosis and Treatment of Cough (2021)", the following criteria were established: cough as the main or only symptom; duration of illness not exceeding 8 weeks; and no obvious abnormalities found on chest imaging. Traditional Chinese medicine diagnosis corresponds to either wind-heat invading the lungs or phlegm-heat obstructing the lungs.

[0074] Inclusion criteria: ① Age ≥ 18 years; ② Meets the above Western and Traditional Chinese Medicine diagnostic criteria; ③ Patients are willing to cooperate, have good compliance, understand and abide by all requirements of this study, and sign informed consent; ④ Patients take medication as prescribed for more than 3 days.

[0075] Exclusion criteria: ① Those with other serious or underlying diseases; ② Those who are allergic to or have contraindications to the drug ingredients; ③ Pregnant or lactating women; ④ Those with mental illness.

[0076] Treatment plan: The patient was treated with a lung-clearing and cough-relieving formula from the Department of Traditional Chinese Medicine at Peking University People's Hospital. The formula consists of roasted ephedra, stir-fried bitter almond, raw gypsum (decocted first), licorice root, angelica root, platycodon root, belamcanda rhizome, and lepidium seed, prepared by the Pharmacy Department of Peking University People's Hospital. One dose was taken twice daily, morning and evening, after meals, warm, for seven consecutive days.

[0077] Therapeutic effect evaluation Clinical efficacy rate: Efficacy assessment criteria were developed with reference to the *Standards for Diagnosis and Efficacy Evaluation of Diseases in Traditional Chinese Medicine*, and the severity of cough was evaluated using the simplified cough evaluation test (CET) recommended in the *Guidelines for the Diagnosis and Treatment of Cough (2021)*. The CET questionnaire includes five aspects: daytime cough frequency, the impact of nighttime cough on sleep, cough severity, the impact of cough on daily work and life, and anxiety caused by cough. Each item is scored from 1 to 5 points, with higher scores indicating more severe cough. The efficacy index was calculated using the nimodipine method: Efficacy index = (Total score before treatment - Total score after treatment) / Total score before treatment × 100%. Cure: Cough and related clinical manifestations basically disappeared, and the CET score decreased by more than 95%; Significant effect: CET score decreased by more than 70%; Effective: CET score decreased by 30%–69%; Ineffective: CET score decreased by less than 30%. Total efficacy rate = (Number of cured + Significant effect + Effective) / Total number of cases × 100%.

[0078] Secondary efficacy endpoints: ① Time of cough relief and disappearance (recorded from the start of medication, the time of cough relief and disappearance for follow-up patients); ② Individual scores of five aspects involved in the CET questionnaire: frequency of cough during the day, impact of nighttime cough on sleep, severity of cough, impact of cough on daily work and life, and anxiety caused by cough; ③ Adverse drug reactions (from the start of medication to the end of follow-up).

[0079] Statistical methods: Statistical analysis was performed using SPSS 29.0 software. Normally distributed continuous data were expressed as mean ± standard deviation (x̄ ± s), and paired-samples t-tests were used for comparisons before and after treatment. Non-normally distributed continuous data were expressed as median and interquartile range [M(P25, P75)], and Wilcoxon signed-rank test was used for comparisons before and after treatment. Categorical data were expressed as number of cases and percentages, and chi-square tests were used for comparisons between groups. 2 The statistical significance of the difference was defined as P < 0.05. For the primary efficacy endpoint, the study results were considered clinically significant when the lower limit of its 95% confidence interval was higher than the pre-specified target value and the point estimate met the pre-specified requirements.

[0080] Research findings: This study included 121 patients, of whom 33 were male (27.27%) and 88 were female (72.73%), with a male-to-female ratio of approximately 1:2.7; their ages ranged from 18 to 92 years. Demographic data are shown in Table 1.

[0081] Table 1 Clinical baseline data Key observation indicators: See Table 2. After one week of medication, 83 cases were cured, 2 cases showed significant improvement, 25 cases showed improvement, and 11 cases showed no improvement, with a total effective rate of 90.91%. The preset target effective rate was 73%. Statistical analysis showed that... 2 =13.44, P<0.001, 95% CI 85.8%–96.0%; its lower limit of confidence interval is higher than the preset target value, indicating that the composition of the present invention has a clear clinical efficacy. The results are shown in […]. Figure 5 .

[0082] Table 2 Clinical efficacy Secondary observation indicators: ① Cough relief and disappearance time See Table 3; the median cough relief time for patients was 3 days, and the median cough disappearance time was 6 days.

[0083] Table 3. Time for Cough Relief and Disappearance ② Comparison of CET scores before and after medication See Table 4. On the 3rd day and 1 week of medication, the CET scores and total score of each item were significantly lower than before treatment (P<0.001), and the differences were statistically significant.

[0084] Table 4. CET scores (points) before and after medication. Note: Compared with the pre-treatment values ​​in this group. △ P < 0.001.

[0085] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit the scope of protection of the present invention. All equivalent substitutions, improvements, or other obvious modifications made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

[0086] It should be noted that the above embodiments are merely illustrative of the present invention. Those skilled in the art can make other variations or adjustments without departing from the concept of the present invention; the resulting equivalent technical solutions should also fall within the protection scope defined by the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating cough, characterized in that, The traditional Chinese medicine composition is made from eight raw materials: ephedra, bitter almond, licorice, gypsum, angelica dahurica, platycodon grandiflorus, belamcanda chinensis, and lepidium apetalum. Each raw material is formulated according to the weight proportions. Among them, ephedra is 5 to 15 parts, bitter almond is 8 to 15 parts, licorice is 5 to 10 parts, gypsum is 15 to 30 parts, angelica is 8 to 15 parts, platycodon is 8 to 15 parts, belamcanda is 8 to 15 parts, and lepidium is 8 to 15 parts. The weight parts refer to the relative weight ratio between each active pharmaceutical ingredient, and each active pharmaceutical ingredient uses the same weight measurement unit.

2. The traditional Chinese medicine composition for treating cough according to claim 1, characterized in that, The preferred weight ratio of each raw material is: 5 parts ephedra, 10 parts bitter almond, 6 parts licorice, 20 parts gypsum, 10 parts angelica dahurica, 10 parts platycodon grandiflorus, 10 parts belamcanda chinensis, and 10 parts lepidium apetalum. The processing specifications for the raw materials are as follows: ephedra is processed ephedra, bitter almond is stir-fried bitter almond, gypsum is raw gypsum, and licorice is raw licorice or processed licorice.

3. The traditional Chinese medicine composition for treating cough according to claim 2, characterized in that, The traditional Chinese medicine composition is prepared into an oral compound, which also includes flavoring agents and preservatives that meet pharmaceutical standards. Flavoring agents are made of sucrose or steviol glycosides, and the amount added shall not exceed 20% of the total weight of the mixture; Sodium benzoate or potassium sorbate are used as preservatives.

4. The traditional Chinese medicine composition for treating cough according to claim 2, characterized in that, The traditional Chinese medicine composition can be used in combination with dextromethorphan or ambroxol.

5. A method for preparing a traditional Chinese medicine composition for treating cough according to any one of claims 1 to 4, characterized in that, Includes the following steps: Step 1: Weigh each raw material according to the set weight ratio, crush the gypsum and add purified water to decoct it first, then add the remaining raw materials for soaking and the first decoction; after the decoction is completed, perform solid-liquid separation to obtain the first filtrate and the first residue respectively. Step 2: Add purified water to the first filter residue for a second decoction. After the decoction is completed, perform solid-liquid separation to obtain the second filtrate. Step 3: Combine the first and second filtrates and mix them evenly. Concentrate the combined filtrate, then add pharmaceutical excipients for preparation and volume adjustment to obtain the intermediate preparation. Step four: The intermediate compound is filtered and filled, and then sterilized to obtain the finished traditional Chinese medicine composition for treating cough.

6. The method for preparing the traditional Chinese medicine composition for treating cough according to claim 5, characterized in that, In step one, the weight of purified water added is 8 to 12 times the total weight of all raw materials. The soaking time is 0.5 to 1 hour, and the first decoction time is 0.5 to 1 hour. During the decoction process, the liquid is kept boiling. In step two, the weight of purified water added should be 6 to 8 times the total weight of all raw materials. The second decoction should last for 0.5 to 1 hour, and the decoction should be kept boiling during the decoction process. Before being mixed and soaked, the raw gypsum in the pharmaceutical raw materials needs to be crushed separately and decocted for 30 minutes before being combined with the other raw materials for subsequent soaking and decoction.

7. The preparation method according to claim 5, characterized in that, The solid-liquid separation in steps one and two is achieved by filtration with a filter cloth or centrifugation. The concentration process in step three is carried out by vacuum concentration. The temperature of the concentration process is controlled between 60 degrees Celsius and 80 degrees Celsius. The relative density of the concentrated extract at 60 degrees Celsius is 1.05 to 1.

15. In step three, the excipient preparation process requires stirring until all excipients are completely dissolved in the drug solution; The sterilization process in step four uses flowing steam sterilization at 105 to 115 degrees Celsius for 30 to 45 minutes.

8. The use of the traditional Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for treating cough, characterized in that, The drug is used to treat acute or subacute cough; Acute cough refers to a cough lasting less than 3 weeks, including cough caused by the common cold and cough caused by acute tracheobronchitis. Subacute cough refers to cough lasting 3 to 8 weeks, including post-infectious cough, cough caused by upper airway cough syndrome, and cough caused by cough variant asthma. The medicine is suitable for coughs diagnosed by traditional Chinese medicine as wind-heat invading the lungs or phlegm-heat obstructing the lungs, with clinical manifestations including one or more of the following: cough, expectoration, itchy throat, shortness of breath, thick yellow phlegm, difficulty expectorating phlegm, and sore throat.

9. The application according to claim 8, characterized in that, The drug is used to improve cough-related clinical symptoms, reduce cough severity scores, and shorten cough relief time and cough disappearance time; The cough severity score includes five dimensions: daytime cough frequency, nighttime cough impact on sleep, cough intensity, cough impact on daily work and life, and cough-induced anxiety. The drug is administered orally. The dosage is one dose of the drug corresponding to the ratio of the raw material, taken twice a day after meals, morning and evening. A complete course of treatment is 3 to 7 days.

10. The application according to claim 8, characterized in that, The drug can be used alone to treat cough, or in combination with conventional cough suppressants. The combined medication is suitable for patients with subacute cough, and the conventional antitussive Western medicines include centrally acting antitussives, bronchodilators, or antihistamines.

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