Application of Dongwan Cough-Relieving Granules in the Preparation of Drugs for Treating Cough Variant Asthma

Abstract

This invention discloses the application of Dongwan Zhike Granules in the preparation of drugs for treating cough-variant asthma, belonging to the field of traditional Chinese medicine technology. This invention induces a rat model of cough-variant asthma using an ovalbumin-aluminum hydroxide suspension, and then verifies the ameliorative effect of Dongwan Zhike Granules on this rat asthma model. Experiments demonstrate that Dongwan Zhike Granules, at low, medium, and high doses, have a certain ameliorative effect on the ovalbumin-aluminum hydroxide suspension-induced cough-variant asthma rat model. This invention provides a new application for Dongwan Zhike Granules and also provides important evidence for its application in the prevention and treatment of cough-variant asthma.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and more specifically, to the application of Dongwan Zhike Granules in the preparation of drugs for treating cough variant asthma. Background Technology

[0002] Cough variant asthma (CVA) is a special type of asthma, characterized by chronic cough as the main clinical manifestation. In traditional Chinese medicine, it falls under the categories of asthma and wheezing syndrome. It is an immune hypersensitivity disease characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. The pathogenesis of CVA is complex, with airway inflammation and airway hyperresponsiveness playing crucial and closely related roles in its development. Long-term inflammatory stimulation leads to damage to the airway mucosa, increased exudation in the mucosal layer and submucosa, and the action of various inflammatory mediators and cytokines on smooth muscle cells, resulting in enhanced tracheal contraction and airway hyperresponsiveness. The airway inflammatory response involves the release of chemokines from the airway, causing effector cells such as neutrophils, eosinophils, and T lymphocytes to aggregate and release cytokines such as interleukin (IL)-4 and IL-5, which participate in adaptive immune responses. Serum IL-4 in vivo promotes the proliferation and activation of B cells, enhances the chemotaxis of inflammatory cells, and promotes the release and spread of inflammatory factors, thereby triggering a local inflammatory response. In addition, IL-4 can promote the production of IgE. When its secretion is abnormal, it will lead to excessive production of IgE. IgE binds to inflammatory cells, damages airway epithelial cells, and causes airway hyperresponsiveness, which in turn causes smooth muscle contraction, airway spasm, mucosal edema, and exacerbates the inflammatory response of the airway, which may trigger airway inflammation and lead to asthma attacks.

[0003] Currently, corticosteroids, leukotriene receptor antagonists, and bronchodilators are commonly used in clinical practice to treat CVA. However, symptoms tend to recur after discontinuation of these medications, and long-term use can lead to significant side effects. Traditional Chinese medicine, on the other hand, is increasingly being used to treat CVA due to its fewer side effects and better long-term efficacy.

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

[0005] The purpose of this invention is to address the shortcomings of existing technologies by providing the application of Dongwan cough-relieving granules in the preparation of drugs for treating cough-variant asthma.

[0006] The Dongwan cough-relieving granules used in this invention were originally used for wind-cold attacking the lungs syndrome, and have the effects of dispelling wind and cold, clearing the lungs and relieving cough. Wind-cold attacking the lungs syndrome in Traditional Chinese Medicine is commonly seen in diseases such as cough, pediatric bronchitis, and acute tracheobronchitis. This syndrome is mostly caused by external wind-cold pathogens, leading to impaired lung function. During the experimental process, the inventors of this invention unexpectedly discovered that Dongwan cough-relieving granules can also be used to treat cough-variant asthma, which has a different pathogenesis than ordinary cough. Specifically, it improves lung volume, ventilation, and airway resistance, and reduces some edema and airway immune inflammatory response. Histopathological examination mainly shows improvement in bronchial mucosal necrosis and shedding, bronchial mucosal thickening, and peribronchial (bronchiolar) inflammatory cell infiltration. Based on the above experimental results, the technical solution of this invention was derived.

[0007] This invention is implemented as follows:

[0008] In a first aspect, the present invention provides the application of Dongwan cough-relieving granules in the preparation of drugs for treating asthma.

[0009] In some embodiments, the aforementioned asthma includes cough variant asthma.

[0010] In some embodiments, the aforementioned asthma includes cough-variant asthma caused by airway inflammation and / or airway hyperresponsiveness.

[0011] This invention demonstrates through animal model experiments that administration of Dongwan Zhike Granules significantly reduces the lung coefficient, total white blood cell count and differential count (MONO / LYMPH) in bronchoalveolar lavage fluid, and serum IgE levels in model animals, thereby alleviating some edema and airway immune inflammatory responses. Histopathological examination also shows that Dongwan Zhike Granules improve bronchial mucosal necrosis and shedding, bronchial mucosal thickening, and peribronchial (bronchiolar) inflammatory cell infiltration in model animals. These experimental results prove that Dongwan Zhike Granules can improve airway inflammation. Furthermore, the detection of airway stenosis index and other indicators demonstrates that Dongwan Zhike Granules can improve airway hyperresponsiveness symptoms to a certain extent.

[0012] In some embodiments, the raw materials of the above-mentioned Dongwan cough granules include ephedra, ginger, asarum, aster, coltsfoot flower, prepared pinellia, magnolia flower and cocklebur.

[0013] Ephedra is the herbaceous stem of *Ephedra sinica*, *Ephedra equisetifolia*, or *Ephedra intermedium*, belonging to the Ephedraceae family. It is pungent, slightly bitter, and warm in nature. It enters the Lung and Bladder meridians. It has the effects of inducing sweating to relieve exterior syndromes, clearing the lungs and relieving asthma, and promoting diuresis and reducing edema. It is mainly used to treat typhoid fever with exterior excess, fever and chills without sweating, headache, nasal congestion, and joint pain; cough and asthma; edema due to wind-dampness, difficulty urinating; stubborn wind-evil numbness, skin numbness, and itchy rashes.

[0014] Ginger is the fresh rhizome of the ginger plant (Zingiber officinale). It is pungent and slightly warm in nature, and enters the lung, spleen, and stomach meridians. Its main functions are to release exterior pathogens, dispel cold, stop vomiting, and resolve phlegm. It is used to treat colds due to wind-cold, vomiting, phlegm retention, cough with wheezing, abdominal distension, and diarrhea; it also detoxifies the poisons of Pinellia ternata, Arisaema heterophyllum, and the meat of fish, crabs, birds, and animals.

[0015] Asarum is the whole herb, including the root, of Asarum heterotropoides or Asarum sieboldii, both belonging to the Aristolochiaceae family. It is pungent and warm in nature, and enters the heart, lung, and kidney meridians. It has the effects of relieving exterior syndromes and dispelling cold, dispelling wind and relieving pain, clearing the nasal passages, warming the lungs and resolving phlegm. It is used for common cold due to wind-cold, headache, toothache, nasal congestion and runny nose, rhinitis, sinusitis, rheumatic pain, and cough with phlegm.

[0016] Aster tataricus is the root and rhizome of the plant Asteraceae family. It is bitter and warm in nature, and enters the lung meridian. It has the effects of warming the lungs, lowering qi, resolving phlegm, and relieving cough. It is used to treat cough and asthma due to wind-cold, cough with purulent sputum and blood due to deficiency, sore throat, and difficulty urinating.

[0017] Coltsfoot flower is the flower bud of the coltsfoot plant in the Asteraceae family. It is pungent and slightly sweet in taste, warm in nature, and enters the lung meridian. It has the effects of moistening the lungs and lowering qi, resolving phlegm and relieving cough, and treating cough, wheezing and sore throat.

[0018] Prepared Pinellia is the tuber of Pinellia ternata, a plant in the Araceae family. It is a processed product of Pinellia ternata and has a pungent and warm nature. It enters the spleen, stomach, and lung meridians. It can dry dampness and resolve phlegm, relieve nausea and vomiting, and when used raw, it can reduce boils and swellings. It is mainly used to treat cough with excessive phlegm, nausea, and vomiting. Externally, it is used to treat acute mastitis and acute and chronic suppurative otitis media.

[0019] Magnolia biondii is the dried flower bud of Magnolia denudata, Magnolia simonii, or Magnolia wudangensis, all belonging to the Magnoliaceae family. It is pungent and warm in nature, and enters the lung and stomach meridians. It has the effects of dispersing wind-cold and clearing nasal passages, and is mainly used to treat colds due to wind-cold, nasal congestion, and sinusitis.

[0020] Xanthium sibiricum is the fruit of the Xanthium sibiricum plant (including its involucre) in the Asteraceae family. It is bitter, sweet, pungent, warm in nature, and slightly toxic. It enters the lung and liver meridians. It is used to treat headaches due to wind-cold, sinusitis, toothache, wind-cold-dampness arthralgia, limb spasms and pain, scabies, and itching.

[0021] The formula of Dongwan Cough Relief Granules consists of ephedra, ginger, asarum, prepared pinellia, aster, coltsfoot flower, magnolia flower, and cocklebur. Ephedra is the principal ingredient, dispersing wind-cold and promoting lung qi to stop coughing; ginger is the assistant ingredient, dispersing wind-cold, warming the lungs, and stopping coughing; asarum dispels wind-cold, warms the lungs, and clears the nasal passages; prepared pinellia dries dampness, resolves phlegm, and warms and transforms cold phlegm; aster and coltsfoot flower are adjuvant ingredients, warming and moistening lung qi, resolving phlegm, and stopping coughing; magnolia flower and cocklebur disperse wind-cold and clear the nasal passages, achieving a simultaneous treatment of the lungs and nose, and a bidirectional regulatory effect in stopping coughing.

[0022] Through the synergistic effect of the above components, Dongwan Cough-Relieving Granules can also improve cough-variant asthma. Furthermore, experiments have shown that the improvement effect of Dongwan Cough-Relieving Granules on cough-variant asthma exhibits a dose-response relationship.

[0023] In some embodiments, the raw materials used in Dongwan Cough Relief Granules are as follows, by weight: Ephedra 30-45 parts, Ginger 35-50 parts, Asarum 8-20 parts, Aster tataricus 35-45 parts, Coltsfoot Flower 40-55 parts, Pinellia ternata 20-45 parts, Magnolia biondii 30-55 parts, and Xanthium sibiricum 40-50 parts.

[0024] In some embodiments, the dosage of Dongwan cough granules for treating asthma is 0.1–1 g / kg / day.

[0025] Secondly, the application of Dongwan cough granules in the preparation of drugs for improving respiratory function.

[0026] In this invention, respiratory function includes inspiratory time, tidal volume, relaxation time, inspiratory volume per minute, and airway stenosis index. Experiments have shown that Dongwan cough granules can significantly increase inspiratory time, tidal volume, relaxation time, and inspiratory volume per minute, and significantly reduce airway stenosis index, thus proving that Dongwan cough granules can improve respiratory function.

[0027] In some embodiments, the raw materials of the above-mentioned Dongwan cough granules include ephedra, ginger, asarum, aster, coltsfoot flower, prepared pinellia, magnolia flower and cocklebur.

[0028] The ingredients of Dongwan Cough Relief Granules are as follows by weight: Ephedra 30-45 parts, Ginger 35-50 parts, Asarum 8-20 parts, Aster tataricus 35-45 parts, Coltsfoot Flower 40-55 parts, Pinellia ternata 20-45 parts, Magnolia biondii 30-55 parts, and Xanthium sibiricum 40-50 parts.

[0029] In some embodiments, the dosage of Dongwan cough granules for improving respiratory function is 0.1–1 g / kg / day.

[0030] The present invention has the following beneficial effects:

[0031] This invention induces a rat model of cough-variant asthma using an ovalbumin-aluminum hydroxide suspension, and then verifies the ameliorative effect of Dongwan Zhike Granules on this rat asthma model. Experiments demonstrate that Dongwan Zhike Granules, at low, medium, and high doses, have a certain ameliorative effect on the ovalbumin-aluminum hydroxide suspension-induced cough-variant asthma rat model. This invention provides a new application for Dongwan Zhike Granules and also provides important evidence for its application in the prevention and treatment of cough-variant asthma. Attached Figure Description

[0032] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation of the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.

[0033] Figure 1 It is a comparison diagram of the results after HE staining of the lungs of animals in each group in the experimental examples. Detailed implementation manners

[0034] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. For those not specified in the embodiments, the conventional conditions or the conditions recommended by the manufacturer are followed. For the reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase. <00000�5>The features and performance of the present invention will be further described in detail below in combination with the embodiments.

[0036] 1. Test drugs

[0037] The Dongwan Zhike Granules are composed of Ephedrae Herba, Zingiberis Rhizoma Recens, Asari Radix et Rhizoma, Asteris Radix, Tussilaginis Flos, Pinelliae Rhizoma Praeparatum, Magnoliae Flos, and Xanthii Fructus, and are provided by Jiangzhong Pharmaceutical Co., Ltd. (batch number: 23010003); 6.75 g, 13.5 g, and 27.0 g of the Dongwan Zhike Granules are respectively weighed and placed in a mortar, an appropriate amount of 0.5% CMC-Na solution is added, and after grinding evenly, it is transferred to a graduated cylinder and made up to 50 mL to prepare medicinal solutions with concentrations of 0.135 g / mL, 0.27 g / mL, and 0.54 g / mL respectively.

[0038] Dexamethasone Acetate Tablets are purchased from Zhejiang Xianju Pharmaceutical Co., Ltd. (batch number: LB2370). Take 7 Dexamethasone Acetate Tablets (5.25 mg), add an appropriate amount of 0.5% CMC-Na solution, grind and stir evenly, then transfer to a graduated cylinder and make up to 48.6 mL to prepare a solution with a concentration of 0.108 mg / mL, and use it immediately after preparation.

[0039] 2. Test animals

[0040] 66 male SD rats at 5 - 6 weeks of age, weighing 180 ± 20 g, are purchased from Hunan Slack Jingda Experimental Animal Co., Ltd., and the license number is SCXK(Xiang)2019 - 0004. The experiments of the present invention have been approved by the Guangdong Provincial Experimental Animal Ethics Committee, and the approval number is: IA-PD2023019-01. The experimental animals are raised in a SPF-level animal environment and are allowed to freely eat and drink water.

[0041] After one week of adaptive feeding, animals were randomly divided into 6 groups according to their body weight: blank control group A, model control group B, dexamethasone acetate tablet group C, low-dose Dongwan cough granules group D, medium-dose Dongwan cough granules group E, and high-dose Dongwan cough granules group F, with 11 animals in each group.

[0042] 3. Reagents

[0043] OVA was purchased from Sigma (lot number: SLCH2414); aluminum hydroxide was provided by Guangdong Guanghua Technology Co., Ltd. (lot number: 20220811); IgE and IL-4 were purchased from R&D (lot number: E20230901A).

[0044] 4. Instruments

[0045] Fully automated blood and body fluid analyzer (Sysmex Medical Electronics Co., Ltd., model: XN-1000[B3]); enzyme-linked immunosorbent assay (ELISA) analyzer (Berten Instruments, Inc., model: ELx808); ultrasonic nebulizer (Omron Healthcare Co., Ltd., model: NB-150U); rat lung function monitoring system (EMKA, France, model: EMKA WBP).

[0046] Example

[0047] This example verifies the effect of Dongwan Zhike Granules on a rat model of cough-variant asthma, as detailed below:

[0048] 1. CVA model establishment and drug administration

[0049] Sensitization: On days 1 and 8, animals in the model control group, dexamethasone acetate tablet group, and low, medium, and high dose groups of Dongwan Zhike Granules were subcutaneously injected with a 1% OVA solution + aluminum hydroxide (10mg) suspension at 10 different locations, including the paws, groin, waist, back, and neck. 0.05mL was injected at each location. Then, each animal was injected intraperitoneally with 0.5mL of the suspension. Animals in the blank control group were injected subcutaneously / intraperitoneally with an equal volume of 0.9% sodium chloride injection. Challenge: On day 16, rats in each group were placed in a sealed container of about 4L. Then, 1% OVA + aluminum hydroxide (10mg) suspension was sprayed into the container at a constant pressure of about 400mmHg using an ultrasonic nebulizer once a day for 20min / time for 21 consecutive days. The blank control group was sprayed with 0.9% sodium chloride injection for 20min / time daily. The drugs were administered by gavage 30 minutes after nebulization stimulation from D23 to D36. The dosage of dexamethasone acetate tablets was 1.08 mg / kg; the dosage of Dongwan cough granules was 1.35 g / kg, 2.70 g / kg, and 5.40 g / kg once a day for 14 consecutive days. The blank control group and the model control group were given the same dose of 0.5% CMC-Na solution.

[0050] 2. Monitoring of respiratory function indicators in rats

[0051] The WBP rat pulmonary function monitoring system was used to measure the airway responsiveness indicators of each group of animals, including inspiratory time (TI), maximum inspiratory volume (PIF), tidal volume (TV), relaxation time (RT), inspiratory volume per minute (MV), respiratory rate (F), and airway stenosis index (Penh).

[0052] 3. Detection of serum IL-4 and IgE levels by ELISA

[0053] After the experiment, the animals were euthanized, blood was collected and serum was separated and stored at -20℃. The IL-4 and IgE levels were determined according to the kit requirements.

[0054] 4. Lung coefficient

[0055] After blood collection, the animal's lungs are quickly dissected and weighed to calculate the lung coefficient. Lung coefficient = lung weight / body weight.

[0056] 5. Collect bronchoalveolar lavage fluid to detect the total white blood cell count and inflammatory cell differential count.

[0057] The bronchi and left lung were ligated and lavaged. The bronchoalveolar lavage fluid was collected to detect the total white blood cell count and the differential count of inflammatory cells.

[0058] 6. HE staining for lung tissue pathological examination

[0059] The right lung was harvested, fixed with 10% formalin, and then subjected to histopathological examination.

[0060] 7. Data processing and statistical analysis

[0061] Data were processed by ECGAUTO software and then imported into EXCEL for statistical analysis. The mean ± standard deviation (s) of each group's measurement data were calculated. The Student-T test (paired T test) was used to compare each experimental group with the pre-drug administration data. Before comparing between groups, an analysis of variance (F-test) was performed. When the variances between groups were homogeneous, the Student-T test (unpaired T test) was used for statistical analysis. When the variances between groups were unequal, a corrected Student-T test was used for statistical analysis.

[0062] 8. Test Results

[0063] (1) The monitoring results of respiratory function indicators of rats are shown in Table 1:

[0064] Table 1. Effects of Dongwan Zhike Granules on respiratory function indicators in CVA model rats after 14 days of administration (±s, n=11)

[0065]

[0066] Note: Compared with the model control group, *P<0.05, **P<0.01 (the same applies below).

[0067] A: Blank control, B: Model control, C: Dexamethasone acetate tablets 1.08mg / kg, D: Dongwan cough granules low dose 1.35g / kg, E: Dongwan cough granules medium dose 2.70g / kg, F: Dongwan cough granules high dose 5.40g / kg.

[0068] The results of respiratory function index measurements on day 14 after drug administration are shown in Table 1. Compared with the blank control group, the TI, TV, RT, MV, and F of the animals in the model control group were significantly decreased (P<0.05 or P<0.01), while Penh was significantly increased (P<0.01). Compared with the model control group, the TI and RT of the dexamethasone acetate tablet group and the low, medium, and high dose groups of Dongwan Zhike granules were significantly increased (P<0.05 or P<0.01), while Penh was significantly decreased (P<0.05 or P<0.01). The TV and MV of the low, medium, and high dose groups of Dongwan Zhike granules were significantly increased (P<0.05 or P<0.01). There were no significant differences in respiratory function indexes among the other groups (P>0.05).

[0069] (2) The results of the effect on the lung coefficient of CVA model rats are shown in Table 2:

[0070] Table 2. Effects of Dongwan Zhike Granules on Lung Coefficient in CVA Model Rats

[0071]

[0072] A: Blank control, B: Model control, C: Dexamethasone acetate tablets 1.08mg / kg, D: Dongwan cough granules low dose 1.35g / kg, E: Dongwan cough granules medium dose 2.70g / kg, F: Dongwan cough granules high dose 5.40g / kg.

[0073] Fourteen days after administration, the body weight of animals in each group was measured. Animals were euthanized using isoflurane anesthesia combined with abdominal aortic blood sampling. After bronchial ligation, the lungs of the animals were dissected and weighed to calculate the lung coefficient. Table 2 shows that, compared with the blank control group, the lung weight and lung coefficient of animals in the model control group were significantly increased (P<0.05). Compared with the model control group, the lung coefficient of animals in the low, medium and high dose groups of Dongwan Zhike Granules was significantly decreased (P<0.05 or P<0.01), the body weight and lung weight of animals in the dexamethasone acetate tablet group were significantly decreased (P<0.01), and the lung weight of animals in the medium dose group of Dongwan Zhike Granules was significantly decreased (P<0.05).

[0074] (3) The effects on the total number of white blood cells and the number of differentially expressed cells in the bronchoalveolar lavage fluid of CVA model rats are shown in Table 3:

[0075] Table 3. Effects of Dongwan Granules on Total White Blood Cell Count and Differential Cell Count in Bronchoalveolar Lavage Fluid of CVA Model Rats

[0076]

[0077] A: Blank control, B: Model control, C: Dexamethasone acetate tablets 1.08mg / kg, D: Dongwan cough granules low dose 1.35g / kg, E: Dongwan cough granules medium dose 2.70g / kg, F: Dongwan cough granules high dose 5.40g / kg.

[0078] After weighing the lungs, the bronchi and left lung were ligated and lavaged. The total white blood cell count and differential count of the bronchoalveolar lavage fluid were measured. Table 3 shows that, compared with the blank control group, the levels of WBC, LYMPH, and MONO in the bronchoalveolar lavage fluid of the model control group animals were significantly increased (P<0.05 or P<0.01). Compared with the model control group, the levels of WBC and MONO in the bronchoalveolar lavage fluid of the dexamethasone acetate tablet group, the medium- and high-dose Dongwan Zhike granules group were significantly decreased (P<0.05 or P<0.01), the levels of LYMPH in the bronchoalveolar lavage fluid of the dexamethasone acetate tablet group and the high-dose Dongwan Zhike granules group were significantly decreased (P<0.05 or P<0.01), and the levels of EO in the bronchoalveolar lavage fluid of the dexamethasone acetate tablet group and the low-dose Dongwan Zhike granules group were significantly increased (P<0.05 or P<0.01).

[0079] (4) The effects on serum IgE and IL-4 levels in CVA model rats are shown in Table 4:

[0080] Table 4. Effects of Dongwan Zhike Granules on serum IgE and IL-4 levels in CVA model rats

[0081]

[0082] A: Blank control, B: Model control, C: Dexamethasone acetate tablets 1.08mg / kg, D: Dongwan cough granules low dose 1.35g / kg, E: Dongwan cough granules medium dose 2.70g / kg, F: Dongwan cough granules high dose 5.40g / kg.

[0083] Blood was collected from the abdominal aorta of each group of animals, and serum was separated to determine the levels of IgE and IL-4. The results in Table 4 show that, compared with the blank control group, the levels of IgE and IL-4 in the serum of animals in the model control group were significantly increased (P<0.05 or P<0.01); compared with the model control group, the levels of IgE in the serum of animals in the dexamethasone acetate tablet group and the low, medium and high dose groups of Dongwan Zhike granules were significantly decreased (P<0.01).

[0084] (5) Pathological examination results of lung tissue, as follows: Figure 1 The pathological results are shown in Table 5:

[0085] Table 5. Distribution of lung histological pathological severity in each group of animals

[0086]

[0087] Note: The degree of histological changes is indicated by -, ±, +, ++, and +++ to represent normal, slight, mild, moderate, and severe, respectively.

[0088] A: Blank control, B: Model control, C: Dexamethasone acetate tablets 1.08mg / kg, D: Dongwan cough granules low dose 1.35g / kg, E: Dongwan cough granules medium dose 2.70g / kg, F: Dongwan cough granules high dose 5.40g / kg.

[0089] from Figure 1 Based on the results in Table 5, the bronchial structures of all levels in the blank control group were normal, with no dilation or shrinkage of alveolar cavities and no inflammatory cells observed. No dilation or stenosis of interstitial vessels was observed, nor was any inflammatory cell infiltration. In the model group, mild bronchial mucosal necrosis and sloughing were observed, along with moderate thickening of the bronchial mucosa and mild inflammatory cell infiltration around the bronchi (bronchioles). In the dexamethasone acetate tablet group, slight bronchial mucosal necrosis and sloughing were observed, along with mild thickening of the bronchial mucosa. In the low-dose group of Dongwan Zhike Granules, slight bronchial mucosal necrosis and sloughing were observed, along with mild thickening of the bronchial mucosa and mild inflammatory cell infiltration around the bronchi (bronchioles). In the medium-dose group of Dongwan Zhike Granules, mild thickening of the bronchial mucosa was observed. In the high-dose group of Dongwan Zhike Granules, slight bronchial mucosal necrosis and sloughing were observed, along with mild inflammatory cell infiltration around the bronchi (bronchioles).

[0090] In this experiment, animals were sensitized through multiple intraperitoneal injections of ovalbumin solution and challenged with nebulization to establish a respiratory model. On day 14 of drug administration, the effects of the drug on respiratory function indicators in CVA model rats were examined. The results showed that after 14 days of administration of dexamethasone acetate tablets and low, medium, and high doses of Dongwan Zhike granules, the respiratory function of CVA model rats was significantly improved by enhancing airway resistance (judged by RT and Penh) and ventilation (judged by TV and MV). The effects of the drug on lung coefficient, total white blood cell count and differential count, and serum IgE level in CVA model rats were also examined. After 14 days of administration of dexamethasone acetate tablets and low, medium, and high doses of Dongwan Zhike granules, the lung coefficient, total white blood cell count and differential count (MONO / LYMPH) in bronchoalveolar lavage fluid, and serum IgE level in the model animals were significantly reduced, thereby alleviating some edema and airway immune inflammatory response in the model animals. Histopathological examination results showed that, under the conditions of this experiment, the dexamethasone acetate tablet group and the low, medium and high dose groups of Dongwan Zhike granules all had a certain ameliorative effect on bronchial mucosal necrosis and shedding, bronchial mucosal thickening and peribronchial (bronchiolar) inflammatory cell infiltration in CVA model rats, and the ameliorative effect of Dongwan Zhike granules showed a dose-response relationship.

[0091] In summary, different doses of Dongwan cough-relieving granules in this invention have a certain ameliorative effect on the CVA rat model induced by OVA compound aluminum hydroxide suspension. The main effects are improved lung volume, ventilation and airway resistance in the model animals, and reduced edema and airway immune inflammatory response in the model animals. In terms of histopathological examination, the main effects are improved bronchial mucosal necrosis and shedding, bronchial mucosal thickening and peribronchial (bronchiolar) inflammatory cell infiltration in the model rats, and a dose-response relationship is shown.

[0092] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. The application of a traditional Chinese medicine composition in the preparation of a medicament for treating cough-variant asthma, characterized in that, The amounts of raw materials used in the traditional Chinese medicine composition by weight are as follows: 30-45 parts of ephedra, 35-50 parts of ginger, 8-20 parts of asarum, 35-45 parts of aster, 40-55 parts of coltsfoot flower, 20-45 parts of prepared pinellia, 30-55 parts of magnolia flower and 40-50 parts of cocklebur.

2. The application according to claim 1, characterized in that, The asthma mentioned is cough-variant asthma caused by airway inflammation.

3. The application according to claim 2, characterized in that, The asthma mentioned is cough-variant asthma caused by airway hyperresponsiveness.

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