A traditional Chinese medicine composition for treating cough variant asthma

Abstract

This invention provides a traditional Chinese medicine composition for treating cough variant asthma, relating to the field of traditional Chinese medicine technology. The composition includes Aster tataricus, Platycodon grandiflorus, Curcuma longa, Amomum villosum, stir-fried Citrus aurantium, Prunus armeniaca, Fritillaria thunbergii, and Glycyrrhiza uralensis. This invention directly targets the root pathogenesis of cough variant asthma of the wind-heat type, differing from commonly used wind-dispelling and cough-relieving formulas. This compound does not rely on insect-based or ephedra-based wind-dispelling drugs. Aster tataricus is the core herb to disperse chest and lung congestion, combined with Platycodon grandiflorus to promote lung qi and Curcuma longa to regulate qi and dispel stagnation. This addresses the root cause of lung qi stagnation, preventing the continuous generation of internal wind, achieving both symptomatic and root-cause treatment, and significantly reducing the long-term recurrence rate. Platycodon grandiflorus has an ascending and floating medicinal property to open the upper burner, while stir-fried Citrus aurantium and Prunus armeniaca have a descending and reversing effect. This ascending and descending action unblocks the qi mechanism of the entire lung meridian, resolving the core symptoms of chronic cough patients such as lung qi reversal, chest tightness, and itchy and spasmodic throat. Simultaneously, Curcuma longa promotes qi and blood circulation, resolving blood stasis accompanying chronic cough qi stagnation.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating cough variant asthma. Background Technology

[0002] Cough variant asthma (CVA) is a special subtype of asthma characterized by paroxysmal irritating dry cough, itchy throat, and coughing that worsens at night and in the morning. It is triggered by exposure to cold air, fumes, dust, or unusual odors, and has an extremely high incidence rate among people seeking treatment for chronic cough in China. This disease lacks the characteristic signs of typical bronchial asthma, such as wheezing and pulmonary rales, leading to widespread misdiagnosis, missed diagnosis, and mistreatment. Patients are often simply diagnosed with bronchitis or chronic pharyngitis and receive ineffective cough suppressants and anti-infective treatments for extended periods, sometimes lasting from months to years, severely disrupting sleep, daily work, and quality of life.

[0003] Modern medicine has clearly established that persistent chronic allergic inflammation of the airways and macrophage polarization imbalance are the core pathological mechanisms underlying the occurrence and recurrence of CVA. Pulmonary macrophages, as the core effector cells regulating airway inflammation, are divided into two phenotypes: pro-inflammatory M1 and anti-inflammatory / repairing M2. During the course of CVA, the polarization balance of macrophages is disrupted, leading to abnormal activation and proliferation of M1 macrophages, releasing large amounts of... Pro-inflammatory factors such as IL-6 continuously damage the airway epithelial barrier, increase airway hyperresponsiveness, and induce pharyngeal itching and spasmodic dry cough; while the M2 macrophages, which have the functions of mucosal repair and inflammation suppression, are not differentiated enough and cannot reverse chronic airway damage.

[0004] Currently, the standardized clinical treatment regimen in Western medicine is based on inhaled corticosteroids combined with long-acting... While receptor agonists are the primary treatment, short-term intervention can rapidly suppress the release of airway inflammatory mediators and temporarily relieve cough symptoms. However, Western medicine can only temporarily inhibit the secretion of inflammatory factors and cannot correct the underlying immune disorder caused by the imbalance of macrophage M1 / M2 polarization. Once the medication is stopped, airway inflammation rebounds rapidly, and the recurrence rate remains high. Secondly, long-term inhaled hormones have clear adverse reactions, including local irritation symptoms such as oral candidiasis, hoarseness, and dry and sore throat. Long-term systemic absorption of trace amounts of hormones can also induce systemic side effects such as osteoporosis, blood sugar fluctuations, and decreased immunity. Thirdly, Western medicine only controls symptoms and cannot improve the patient's congenital allergic constitution. Long-term continuous use of medication is required, which leads to strong drug dependence and high long-term treatment costs, significantly increasing the medical burden on patients and medical insurance funds.

[0005] The existing TCM formulas for relieving cough and dispelling wind have a one-sided theoretical basis, only treating the symptoms and failing to eradicate the root cause of recurrence. Cough often recurs rapidly after medication is stopped, resulting in poor long-term clinical control. Secondly, mainstream formulas for relieving wind generally combine ephedra and insect-derived wind-dispelling herbs: ephedra contains ephedrine, which can stimulate the sympathetic nervous system, and is strictly contraindicated for patients with hypertension, arrhythmia, insomnia, and coronary heart disease, significantly narrowing the clinically applicable population; insect-derived herbs such as cicada molting, silkworm, and earthworm are rich in foreign proteins, and CVA patients are inherently allergic, which can easily induce allergic reactions such as skin itching, laryngeal edema, and worsening of cough and wheezing after taking them; at the same time, insect-derived herbs are potent, and long-term use can easily damage the spleen and stomach, causing gastrointestinal irritation such as stomach pain, diarrhea, and loss of appetite, making them unsuitable for long-term, standardized use by middle-aged and elderly patients, those with weak constitutions, and those with spleen and stomach deficiencies; thirdly, the treatment methods are singular and cannot cover the complete pathological process of chronic cough. Summary of the Invention

[0006] The purpose of this invention is to provide a traditional Chinese medicine composition for treating cough variant asthma, thereby solving the technical problems existing in the prior art.

[0007] To achieve the above-mentioned objectives, the technical solution adopted by this invention is as follows:

[0008] A traditional Chinese medicine composition for treating cough variant asthma is made from the following raw materials: Aster tataricus, Platycodon grandiflorus, Curcuma longa, Amomum villosum, stir-fried Citrus aurantium, bitter almond, Fritillaria thunbergii, and Glycyrrhiza uralensis.

[0009] Furthermore, the raw materials are in the following weight proportions: 10-20 parts of Aster tataricus, 6-12 parts of Platycodon grandiflorus, 8-16 parts of Curcuma longa, 3-9 parts of Amomum villosum, 6-12 parts of stir-fried Citrus aurantium, 6-12 parts of bitter apricot kernel, 8-16 parts of Fritillaria thunbergii, and 3-9 parts of Glycyrrhiza uralensis.

[0010] Furthermore, the raw materials are in the following weight proportions: 15 parts aster, 9 parts platycodon, 12 parts turmeric, 7 parts cardamom, 10 parts stir-fried immature bitter orange peel, 8 parts bitter almond, 9 parts fritillaria thunbergii, and 5 parts licorice.

[0011] Furthermore, the stir-fried bitter orange peel is stir-fried with wheat bran; the bitter almond is blanched bitter almond; and the licorice is raw licorice.

[0012] Compared with the prior art, the present invention has the following beneficial effects:

[0013] (I) This invention directly targets the fundamental pathogenesis of cough variant asthma caused by wind-heat and spasm. Unlike commonly used wind-dispelling and cough-relieving formulas in clinical practice, this compound does not rely on insect-based or ephedra-based wind-dispelling drugs. It uses Aster tataricus as the core to disperse chest and lung stagnation, combined with Platycodon grandiflorus to promote lung qi and Curcuma longa to regulate qi and dispel stagnation. This relieves lung qi stagnation from the root, prevents the continuous generation of internal wind, achieves both symptomatic and root-cause treatment, and significantly reduces the long-term recurrence rate. Platycodon grandiflorus has an ascending and floating medicinal property to open the upper jiao, while stir-fried Citrus aurantium and bitter apricot kernel sink and descend to relieve adverse qi. The ascending and descending properties of Platycodon grandiflorus can dredge the lung meridians and qi mechanism throughout the body, solving the core symptoms of lung qi disorder, chest tightness, and itchy and spasmodic throat in patients with chronic cough. At the same time, Curcuma longa can promote qi and blood circulation, resolve blood stasis accompanied by qi stagnation in chronic cough, and fully cover the multiple pathological links of chronic cough: stagnation, adverse qi, wind, phlegm, and blood stasis.

[0014] (II) The formula of this invention contains no extremely cold, extremely hot, or toxic medicinal materials, and does not contain ephedra that excites the sympathetic nervous system or insect-derived foreign protein medicinal materials that easily induce allergies. It can be safely used by people with hypertension, arrhythmia, insomnia, middle-aged and elderly people with weak spleen and stomach, allergic constitution, mild liver and kidney dysfunction, children, and pregnant women with mild CVA, thus avoiding the contraindications and allergy risks of existing mainstream cough medicines.

[0015] (III) The compound multi-component synergistic regulation of macrophage polarization balance in this invention: the active ingredients of Aster tataricus and Curcuma longa inhibit IRF3 protein phosphorylation and block the transformation of macrophages into pro-inflammatory M1 type; Platycodon grandiflorus and Glycyrrhiza uralensis inhibit... downregulation of inflammatory signaling pathways This compound contains airway pro-inflammatory factors such as IL-6, and upregulates miR-511-3p expression, promoting the proliferation and differentiation of anti-inflammatory and repair-type M2 macrophages. It can repair airway immune homeostasis and improve patients' allergic constitution. Detailed Implementation

[0016] To make the objectives, technical solutions, and technical effects of this invention clearer, specific embodiments of this invention are described below. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0017] This embodiment provides a traditional Chinese medicine composition for treating cough-variant asthma, comprising the following ingredients: Aster tataricus, Platycodon grandiflorus, Curcuma longa, Amomum villosum, stir-fried Citrus aurantium, Prunus armeniaca, Fritillaria thunbergii, and Glycyrrhiza uralensis. The specific effects are as follows:

[0018] Aster: It disperses the stagnant Qi in the chest and lungs, is warm and moist without being drying, specifically enters the lung meridian, and directly reaches the target point of stagnant lung Qi. It can not only open up the stagnation of lung Qi to cut off the source of internal wind, but also moisten the lungs and lower Qi to relieve chronic cough and dry cough. One medicine can relieve stagnation.

[0019] Platycodon grandiflorus has an ascending and floating medicinal property, opening up and dispersing lung qi, clearing the qi mechanism of the upper jiao, and carrying the medicine upward to reach the lung collaterals; when combined with Aster tataricus, one moistens and the other opens, relieving lung qi stagnation; Platycodon grandiflorus saponins can promote mild secretion of airway mucus, soothe dry and itchy throat, and inhibit the excitability of the cough center.

[0020] Turmeric: Enters the lung and liver meridians, promotes qi circulation and relieves stagnation, invigorates blood and disperses stagnation, and resolves the qi and blood stagnation that accompanies lung qi stagnation; patients with chronic cough will inevitably experience chest tightness and throat obstruction due to lung qi stagnation. Turmeric promotes qi circulation and invigorates blood, eliminates the microscopic pathology of stagnation, and prevents the reversal of qi and the generation of wind.

[0021] Cardamom: Aromatic and warming, it dispels dampness and promotes qi circulation, warms and disperses stagnant cold and dampness in the upper burner; CVA patients with prolonged cough and lung qi stagnation, abnormal fluid metabolism easily leads to phlegm and dampness, which further aggravates lung congestion. Cardamom dispels dampness and turbidity, assists in promoting qi circulation and relieving stagnation; volatile oils soothe airway mucosal congestion and edema, and relieve throat itching;

[0022] Stir-fried Citrus aurantium: It promotes the flow of qi, relieves chest congestion, and relieves rebellious qi in the chest. The descending nature of Citrus aurantium balances the ascending nature of Platycodon grandiflorus. The combination of ascending and descending qi restores the normal rhythm of lung qi circulation. Stir-frying with wheat bran moderates the medicinal properties and avoids damaging qi and the body's vital energy. It is suitable for long-term use by patients with chronic cough and qi deficiency.

[0023] Bitter almonds: bitterness descends and moistens the lungs, clears lung qi, calms upward cough, and specifically relieves paroxysmal choking cough and severe cough at night; blanching removes excessive toxicity of bitter almonds, retains the antitussive activity of amygdalin, and works in harmony with Platycodon grandiflorus to regulate the balance of lung qi.

[0024] Fritillaria thunbergii: Clears heat and resolves phlegm, soothes the throat and dissipates nodules, relieves chronic cough, dry and itchy throat, and small amount of sticky phlegm; Fritillaria thunbergii is mild and moistening without being cold, and will not aggravate lung qi stagnation, while also relieving throat spasms and itching caused by wind-evil, and improving immediate clinical symptoms.

[0025] Licorice: harmonizes the ascending and descending, warming and cooling properties of the whole formula, moistens the lungs and soothes the throat, and relieves airway spasms; glycyrrhizic acid has strong anti-inflammatory and immunomodulatory effects, balances the polarization state of macrophages, and at the same time moderates the strong qi-regulating effects of aster and bitter orange, protects the spleen and stomach, and is suitable for long-term continuous use without gastrointestinal irritation.

[0026] Example 1:

[0027] The raw materials are in the following weight proportions: 10-20 parts of Aster tataricus, 6-12 parts of Platycodon grandiflorus, 8-16 parts of Curcuma longa, 3-9 parts of Amomum villosum, 6-12 parts of stir-fried Citrus aurantium, 6-12 parts of bitter apricot kernel, 8-16 parts of Fritillaria thunbergii, and 3-9 parts of Glycyrrhiza uralensis. In this embodiment, the stir-fried Citrus aurantium is stir-fried with wheat bran; the bitter apricot kernel is blanched bitter apricot kernel; and the licorice is raw licorice.

[0028] S1: Weigh all the raw materials according to the weight proportions, grind them into 20-mesh coarse powder, add 6 times the total weight of the medicinal materials in purified water, and soak at room temperature for 1.5 hours;

[0029] S2: First decoction: After boiling over high heat, simmer over low heat for 60 minutes and separate the first decoction; add 4 times the amount of purified water to the dregs and decoct again for 40 minutes, then combine the two decoctions.

[0030] S3: A clear extract concentrated under reduced pressure to a relative density of 1.15-1.25 at 60℃;

[0031] S4: Add dextrin, sucrose or mannitol to the clear paste, mix to form a soft material, extrude to granulate, dry at a low temperature of 60℃, and granulate to obtain the cough-relieving and soothing granules.

[0032] Directions for use: Take one sachet each time, dissolved in warm water, twice a day, for a course of 4 weeks.

[0033] Example 2:

[0034] The raw materials are in the following weight proportions: 15 parts Aster tataricus, 9 parts Platycodon grandiflorus, 12 parts Curcuma longa, 7 parts Amomum villosum, 10 parts stir-fried Citrus aurantium, 8 parts bitter apricot kernel, 9 parts Fritillaria thunbergii, and 5 parts Glycyrrhiza uralensis.

[0035] S1: Weigh all the raw materials according to the weight parts, grind them into 30-mesh coarse powder, add 8 times the total weight of the medicinal materials in purified water, and soak at room temperature for 2 hours;

[0036] S2: First decoction: After boiling over high heat, simmer over low heat for 60 minutes, then separate the first decoction; add 5 times the amount of purified water to the dregs and decoct again for 40 minutes, then combine the two decoctions.

[0037] S3: Concentrate under reduced pressure to 600ml of concentrated medicine, then divide into 2 bags, each bag containing 300ml.

[0038] Instructions for use: Take one packet warm in the morning and evening, one dose per day, for a course of treatment lasting 4 weeks.

[0039] Example 3:

[0040] The raw materials are in the following weight proportions: 10-20 parts of Aster tataricus, 6-12 parts of Platycodon grandiflorus, 8-16 parts of Curcuma longa, 3-9 parts of Amomum villosum, 6-12 parts of stir-fried Citrus aurantium, 6-12 parts of bitter apricot kernel, 8-16 parts of Fritillaria thunbergii, and 3-9 parts of Glycyrrhiza uralensis.

[0041] S1: Weigh all the raw materials according to the weight parts, grind them into 40-mesh coarse powder, add 10 times the total weight of the medicinal materials in purified water, and soak at room temperature for 3 hours.

[0042] S2: First decoction: After boiling over high heat, simmer over low heat for 60 minutes, then separate the first decoction; add 6 times the amount of purified water to the dregs and decoct again for 40 minutes, then combine the two decoctions.

[0043] S3: A clear extract concentrated under reduced pressure to a relative density of 1.15-1.25 at 60℃;

[0044] S4: The clear extract is spray-dried at a temperature of 160°C and an outlet air temperature of 80°C to obtain a dry extract powder of traditional Chinese medicine; the extract powder is mixed with microcrystalline cellulose and magnesium stearate, and filled into No. 0 empty capsules, each containing the extract of the original medicinal material equivalent to 10g of the original medicinal material.

[0045] Instructions for use: Take 3 capsules orally each time, twice a day, for 4 weeks as one course of treatment.

[0046] Clinical trial implementation

[0047] Complete Implementation Report of 60 Randomized Controlled Clinical Trials

[0048] 1. Research Subjects

[0049] From January 2025 to March 2026, 60 patients with chronic convulsive spasm (CVA) were screened and randomly assigned to two groups at a 1:1 ratio using a random number table: a treatment group of 30 patients (Example 1 of this invention) and a control group of 30 patients (budesonide / formoterol powder inhaler, Symbicort 160 / 4.5). The two groups received two inhalations daily for four consecutive weeks. There were no statistically significant differences in age, disease duration, baseline symptom scores, FeNO, and macrophage indicators between the two groups, and their baselines were comparable.

[0050] 2. Diagnostic criteria

[0051] Western medicine CVA diagnosis: chronic dry cough > 8 weeks, triggered by irritants, worse at night, positive bronchial provocation test, no pulmonary wheezing;

[0052] Traditional Chinese medicine diagnosis of wind-heat spasm syndrome: dry cough with little phlegm, coughing upon itching of the throat, paroxysmal choking and shortness of breath, thin white tongue coating, and wiry pulse.

[0053] 3. Observation indicators and detection points

[0054] At baseline, after 2 weeks of treatment, after 4 weeks of treatment, and after 6 months of drug withdrawal, the patients were followed up.

[0055] ① Traditional Chinese Medicine syndrome score (primary symptoms: cough, itchy throat; secondary symptoms: chest tightness, worsening at night, triggered by stimuli);

[0056] ② Laboratory indicators: FeNO, peripheral blood M1 / M2 macrophage ratio, serum ECP;

[0057] ③ Safety indicators: complete blood count, liver and kidney function tests, and urinalysis;

[0058] ④ Follow-up relapse rate: The percentage of patients whose cough relapses within 6 months of stopping medication.

[0059] 4. Clinical efficacy evaluation criteria

[0060] Cure: Symptom score decreased by ≥90%, FeNO returned to normal, and there was no recurrence of cough;

[0061] Significant effect: Points decrease by 60%–89%;

[0062] Effective: Points decrease by 30%–59%;

[0063] Invalid: Points decreased by less than 30%;

[0064] Overall effective rate = (cured + significantly effective + effective) / total number of cases × 100%.

[0065] 5. Complete clinical data results

[0066] (1) Overall effectiveness after 4 weeks

[0067] Treatment group (this invention): 20 cases were cured, 6 cases showed significant improvement, 2 cases showed improvement, and 2 cases showed no improvement, with a total effective rate of 93.33%;

[0068] Control group (Western medicine hormones): 11 cases were cured, 5 cases showed significant improvement, 5 cases showed improvement, and 9 cases were ineffective, with a total effective rate of 70.00%; P < 0.05, indicating a statistically significant difference.

[0069] (2) Macrophage polarization indices (after 4 weeks of treatment)

[0070] In the treatment group, the baseline percentage of M1 macrophages decreased from 39.4% to 27.0% after treatment, a reduction of 31.7%; the baseline percentage of M2 macrophages decreased from 12.1% to 15.5% after treatment, an increase of 28.4%.

[0071] The baseline M rate in the control group was 38.9% → 34.0% after treatment, a decrease of 12.5%; the baseline M2 rate was 12.3% → 13.5% after treatment, an increase of 9.8%.

[0072] This study confirms that the compound formula has a significantly better effect on regulating macrophage balance than Western medicine.

[0073] (3) Airway inflammatory markers FeNO and ECP

[0074] The treatment group experienced an average decrease of 18.6 ppb in FeNO and a 42.3% decrease in ECP.

[0075] In the control group, FeNO decreased by 11.2 ppb and ECP decreased by 26.1%.

[0076] (4) Relapse rate 6 months after drug withdrawal

[0077] Two patients in the treatment group relapsed, with a relapse rate of 6.67%; 13 patients in the control group relapsed, with a relapse rate of 43.33%; the long-term relapse prevention advantage of this invention is extremely significant.

[0078] (5) Safety observation

[0079] All patients in the treatment group had no abnormalities in blood routine tests and liver and kidney function before and after treatment, and no adverse reactions. In the control group, 9 patients experienced local adverse reactions (6 cases of oral fungal infection and 3 cases of hoarseness), with an adverse reaction rate of 30%.

[0080] 6. Clinical trial conclusions

[0081] The Kaiyu Zhike Decoction of this invention is superior to the standard Western medicine inhaled hormone regimen in short-term clinical efficacy, airway inflammation improvement, macrophage immune regulation, long-term relapse prevention, and medication safety in treating wind-induced spasm syndrome CVA, demonstrating outstanding clinical application value.

[0082] Safety and toxicology test report

[0083] 1. Acute toxicity test

[0084] Rats were administered the compound of Example 1 at the maximum concentration and volume, with a dose of 40 g / kg of raw medicinal materials (equivalent to 20 times the adult clinical dose) by gavage, and were observed for 14 consecutive days. All rats had normal food intake, activity, and feces, with no deaths or toxic reactions. Dissection of the heart, liver, spleen, lungs, and kidneys revealed no pathological damage, confirming that the compound had no acute toxicity.

[0085] 2. Long-term repeated-dose toxicity test

[0086] Rats were administered low, medium, and high doses (5g / kg, 10g / kg, and 20g / kg) by gavage for 90 consecutive days, with blood routine tests and liver and kidney function tests performed every 30 days. At the end of the experiment, the organs were dissected and pathological sections were prepared. Rats in each dose group showed normal growth and development, no abnormal damage to blood biochemistry or organ tissues, and no cumulative toxicity. Long-term continuous administration was safe.

[0087] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating cough-variant asthma, characterized in that: It is made from the following ingredients: Aster tataricus, Platycodon grandiflorus, Curcuma longa, Amomum villosum, stir-fried Citrus aurantium, bitter almond, Fritillaria thunbergii, and Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition for treating cough-variant asthma according to claim 1, characterized in that: The raw materials are in the following weight proportions: 10-20 parts of Aster tataricus, 6-12 parts of Platycodon grandiflorus, 8-16 parts of Curcuma longa, 3-9 parts of Amomum villosum, 6-12 parts of stir-fried Citrus aurantium, 6-12 parts of bitter apricot kernel, 8-16 parts of Fritillaria thunbergii, and 3-9 parts of Glycyrrhiza uralensis.

3. The traditional Chinese medicine composition for treating cough-variant asthma according to claim 2, characterized in that: The raw materials are in the following weight proportions: 15 parts Aster tataricus, 9 parts Platycodon grandiflorus, 12 parts Curcuma longa, 7 parts Amomum villosum, 10 parts stir-fried Citrus aurantium, 8 parts bitter apricot kernel, 9 parts Fritillaria thunbergii, and 5 parts Glycyrrhiza uralensis.

4. The traditional Chinese medicine composition for treating cough-variant asthma according to claim 1, characterized in that: The stir-fried bitter orange peel is stir-fried with wheat bran; the bitter almond is blanched bitter almond; and the licorice is raw licorice.