A traditional Chinese medicine composition for treating intractable chronic cough

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly relates to a preparation method of a traditional Chinese medicine composition for intractable chronic cough and application thereof; and particularly discloses a traditional Chinese medicine composition for treating intractable chronic cough, which comprises, by weight fraction, 10-40 parts of Poria cocos, 3-25 parts of fried licorice, 3-20 parts of Schisandra chinensis, 1-20 parts of dried ginger, 1-12 parts of Asarum, 3-20 parts of prepared pinellia, 3-20 parts of bitter apricot kernel, 5-40 parts of white mulberry bark, 3-25 parts of bupleurum, 3-25 parts of wind-protecting plant, 5-40 parts of north-sand peony and 1-5 pieces of centipede. The application is a pure traditional Chinese medicine prescription, has high safety and good efficacy, and can quickly relieve symptoms of intractable chronic cough patients, and is suitable for clinical popularization and application due to wide drug source.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a preparation method of a traditional Chinese medicine composition for refractory chronic cough and application thereof. BACKGROUND

[0002] Cough is a common and frequently-occurring symptom of the respiratory system and a common complaint in the respiratory clinic. Cough itself is a defensive reflex activity when the respiratory system is stimulated, which helps to clear away foreign irritants and secretions in the airway and is a beneficial action, which sometimes also occurs in healthy people. Generally, mild and infrequent cough does not need to be treated with cough suppressants and can be naturally relieved. However, long-term frequent or excessive cough is a pathological reaction, which not only increases the patient's suffering, affects rest and sleep, and increases physical exertion, but also promotes the development of diseases and produces other complications.

[0003] The Chinese "Guidelines for the Diagnosis and Treatment of Cough (2021)" points out that refractory chronic cough (CRC) refers to chronic cough lasting more than 8 weeks, for which the cause remains unknown after recommended standard examinations and treatment; or chronic cough that cannot be alleviated after empirical treatment for known causes of chronic cough; or chronic cough with partial evidence of examination for the cause of chronic cough, but with poor treatment effect and persistent symptoms. Chronic irritative cough is the most common clinical manifestation, accompanied by itching or foreign body sensation in the throat, sensitivity to oil smoke, dust, odors and cold air, or significant cough during speech and mental stress.

[0004] The total incidence of CRC is 5-12%, and the pathogenesis is complex, but the overall basis of pathophysiology is cough hypersensitivity, which is closest to the clinical manifestations of cough variant asthma and allergic cough. At present, there are few effective treatment methods for refractory chronic cough, including drug treatment methods and non-drug treatment methods, and most of the treatment methods often have little effect and are accompanied by varying degrees of adverse reactions. CRC has a serious impact on the work, study and quality of life of patients, and also brings serious health and economic burdens. At present, the effective treatment of CRC from the aspect of Western medicine has become a more difficult problem. However, we found in clinical practice that TCM treatment of CRC has good clinical efficacy.

[0005] Intractable chronic cough belongs to the category of "long-term cough", "stubborn cough", "asthma" or "asthma" in traditional Chinese medicine. Its main pathogenesis is cold phlegm hiding in the lung. It is triggered by external invasion, improper diet, emotional stimulation, physical fatigue and other factors. External evil moves the hidden phlegm, phlegm rises with qi, qi is blocked by phlegm, and they are mutually blocked and congested, causing cough. "Su Wen" points out that "the skin and hair first receive evil qi, and the evil qi follows the combination. Cold food enters the stomach from the lung, and then the lung is cold. The lung is cold, and the internal and external combinations are combined. The evil is caused by the evil, and then the lung coughs. "Five organs are afraid of the lung, and the lung is afraid of cold. "Cold and cold food damage the lung, because the two colds are affected, the inside and outside are damaged, so the qi is reversed and moves upward. "It suggests that cold food hides in the lung, which is the basic pathogenesis of cough. External evil triggers is the triggering factor of cough. This "internal and external combination of evil" leads to cough. "Five internal organs and six viscera all cause cough, not only the lung" (Su Wen · Cough Chapter), which shows that the treatment of cough not only needs to treat the lung, but also needs to consider the five internal organs, such as soothing the liver, calming the heart, invigorating the spleen, and nourishing the kidney.

[0006] There are many studies on traditional Chinese medicine in the treatment of chronic cough in clinic, and the curative effect is definite. However, at present, there are few reports on the treatment of intractable chronic cough. According to the existing literature, the treatment cycle of intractable chronic cough is long, and the curative effect is poor. The present application has accumulated a lot of experience in the treatment of intractable chronic cough in chronic cough, and has formed a set of effective traditional Chinese medicine scheme for treating intractable chronic cough. SUMMARY

[0007] The present application aims to overcome the shortcomings of the existing conditions, and provide a traditional Chinese medicine composition for treating intractable chronic cough.

[0008] In the first aspect, the present application provides a traditional Chinese medicine composition for treating intractable chronic cough, which comprises, by weight fraction: 10-40 parts of Poria cocos, 3-25 parts of fried licorice, 3-20 parts of Schisandra chinensis, 1-20 parts of dried ginger, 1-12 parts of Asarum, 3-20 parts of prepared Rhizoma Pinelliae, 3-20 parts of bitter apricot kernel, 5-40 parts of white mulberry bark, 3-25 parts of Bupleurum, 3-25 parts of Radix Saposhnikoviae, 5-40 parts of North Adenophora and 1-5 pieces of centipede.

[0009] Further, the traditional Chinese medicine composition for treating intractable chronic cough comprises, by weight fraction: 10-35 parts of Poria cocos, 3-20 parts of fried licorice, 3-15 parts of Schisandra chinensis, 1-15 parts of dried ginger, 1-10 parts of Asarum, 3-15 parts of prepared Rhizoma Pinelliae, 3-18 parts of bitter apricot kernel, 10-35 parts of white mulberry bark, 3-20 parts of Bupleurum, 3-20 parts of Radix Saposhnikoviae, 10-35 parts of North Adenophora and 1-4 pieces of centipede.

[0010] Further, the traditional Chinese medicine composition for treating refractory chronic cough comprises, by weight fraction: Poria cocos 10-30 parts, prepared licorice 3-15 parts, Schisandra chinensis 6-15 parts, dried ginger 1-10 parts, Asarum 1-9 parts, prepared Pinellia 6-15 parts, bitter almonds 3-15 parts, mulberry bark 10-30 parts, Bupleurum 3-15 parts, Saposhnikovia 3-15 parts, North Adenophora 10-30 parts, and centipede 1-3.

[0011] Further, the traditional Chinese medicine composition for treating refractory chronic cough comprises, by weight fraction: Poria cocos 10-30 parts, prepared licorice 3-15 parts, Schisandra chinensis 6-15 parts, dried ginger 1-10 parts, Asarum 1-9 parts, prepared Pinellia 6-15 parts, bitter almonds 3-15 parts, mulberry bark 10-30 parts, Bupleurum 3-15 parts, Saposhnikovia 3-15 parts, North Adenophora 10-30 parts, and centipede 1-3.

[0012] In a second aspect, the present application provides a traditional Chinese medicine preparation for treating refractory chronic cough, which is prepared from the following weight fractions of traditional Chinese medicinal materials: Poria cocos 10-40 parts, prepared licorice 3-20 parts, Schisandra chinensis 3-20 parts, dried ginger 1-20 parts, Asarum 1-10 parts, prepared Pinellia 3-20 parts, bitter almonds 3-20 parts, mulberry bark 5-40 parts, Bupleurum 5-20 parts, Saposhnikovia 5-20 parts, North Adenophora 5-40 parts, and centipede 1-5.

[0013] Preferably, the preparation is prepared from the following weight fractions of traditional Chinese medicinal materials: Poria cocos 10-30 parts, prepared licorice 3-15 parts, Schisandra chinensis 3-15 parts, dried ginger 1-15 parts, Asarum 1-9 parts, prepared Pinellia 6-15 parts, bitter almonds 3-15 parts, mulberry bark 10-35 parts, Bupleurum 3-15 parts, Saposhnikovia 3-15 parts, North Adenophora 10-30 parts, and centipede 1-3.

[0014] Preferably, the preparation is prepared from the following weight fractions of traditional Chinese medicinal materials: Poria cocos 10-30 parts, prepared licorice 3-15 parts, Schisandra chinensis 3-15 parts, dried ginger 1-15 parts, Asarum 1-9 parts, prepared Pinellia 6-15 parts, bitter almonds 3-15 parts, mulberry bark 10-35 parts, Bupleurum 3-15 parts, Saposhnikovia 3-15 parts, North Adenophora 10-30 parts, and centipede 1-3.

[0015] Further, the traditional Chinese medicine preparation comprises traditional Chinese medicines for treating refractory chronic cough and pharmaceutically acceptable excipients.

[0016] Further, the preparation includes, but is not limited to, decoction, tablets, pills, powder, capsule granules.

[0017] Further, the preparation is preferably decoction.

[0018] In a third aspect, the present application provides a use of a traditional Chinese medicine composition for treating refractory chronic cough in the preparation of a medicine for treating refractory chronic cough and a combined treatment scheme, wherein the preparation is prepared from the following raw materials by weight: 10-40 parts of Poria cocos, 3-20 parts of prepared licorice, 3-20 parts of Schisandra chinensis, 1-20 parts of dried ginger, 1-10 parts of Asarum, 3-20 parts of Radix Pinelliae praeparata, 3-20 parts of bitter almonds, 5-40 parts of white mulberry bark, 5-20 parts of Bupleurum, 5-20 parts of Saposhnikovia divaricata, 5-40 parts of North Adenophora, and 1-5 pieces of centipede.

[0019] The main effects and pharmacological actions of the raw materials of the traditional Chinese medicines in the present application are as follows:

[0020] Poria cocos: sweet and bland in taste, and enters the heart, spleen and kidney channels, can benefit water and drain dampness, invigorate the spleen and calm the heart, and is used to treat edema, phlegm retention, spleen deficiency diarrhea, palpitation and insomnia; Poria cocos mainly contains polysaccharides, triterpenes, sterols, volatile oils, proteins, etc., and its main active ingredients are triterpenes and polysaccharides, which have curative effects on the urinary system, digestive system, central nervous system and immune system, and have multiple pharmacological actions such as diuresis, liver protection, sedation, immunity enhancement, anti-inflammatory, anti-tumor and blood lipid reduction.

[0021] Prepared licorice: sweet and flat in taste, and enters the heart, lung, spleen and stomach channels, can tonify the spleen and replenish qi, expel phlegm and relieve cough, relieve acute and chronic pain, clear heat and detoxify, and harmonize various drugs, and is used to treat heart qi deficiency, pulse knotting, heart palpitations, spleen qi deficiency, cough and asthma, abdominal pain, four limbs cramping pain, heat disease sores, sore throat, drug and food poisoning, and drug property adjustment; the chemical components of prepared licorice are diverse, mainly including triterpenoid saponins, flavonoids and polysaccharides, etc.; and have pharmacological actions such as anti-tumor, anti-depression, anti-inflammatory, anti-arrhythmia, liver protection, anti-oxidation and immune regulation.

[0022] Schisandra chinensis: sour and sweet in taste, and warm in nature, and enters the lung, kidney and heart channels, has the functions of astringing, tonifying qi and promoting fluid production, tonifying the kidney and calming the heart, and is used for chronic cough, spontaneous perspiration, night sweat, spermatorrhea, chronic diarrhea, thirst, diabetes, palpitation, insomnia and dreaminess; lignans are the main components in Schisandra chinensis, followed by volatile oils and organic acids, and some polysaccharides, amino acids and triterpenes, which have extensive pharmacological activities, especially in protecting the liver, anti-tumor, anti-oxidation and neuroprotection.

[0023] Dried ginger: pungent and hot in nature, and enters the spleen, stomach, kidney, heart and lung channels, can warm the middle, dispel cold, restore yang and unblock the vessels, and warm the lung and resolve fluid, and is commonly used for treating abdominal pain, vomiting, diarrhea, yang deficiency, cold fluid and cough; the chemical components of dried ginger are mainly volatile oils and pungent components (mainly gingerol), in addition to β-sitosterol, palmitic acid, daucin, cyclobutane dicarboxylic anhydride and a small amount of polysaccharides, amino acids, flavonoids, etc., and have the actions of anti-inflammatory, anti-tumor and anti-oxidation.

[0024] Asarum: bitter and warm, it belongs to the lung, heart and kidney channels, and has the functions of relieving the exterior and dispelling cold, dispelling wind and relieving pain, unblocking the orifices, and warming the lung and resolving fluid. It is used to treat phlegm and fluid retention, colds, nasal congestion, rheumatism and arthralgia. Asarum contains various chemical components, among which volatile oil is related to the functions of dispelling cold and relieving fever, relieving pain and inflammation, and anti-allergy. Asarum also contains lignans, flavonoids, amides, alkaloids, and phenanthrenes, which play an important role in regulating immunity, anti-inflammatory and analgesic, and expanding blood vessels. Among them, phenanthrenes are mainly aristolochic acids, such as aristolochic acid IV and aristolochic lactam I, and aristolochic acid IV has significant anti-inflammatory effect.

[0025] Pinellia: bitter and warm, it belongs to the spleen, stomach and lung channels, and has the functions of drying dampness and resolving phlegm, descending adverse qi and stopping vomiting, and dissipating masses. It is used to treat damp phlegm, cold phlegm, vomiting, abdominal mass, chest mass, plum pit qi, goiter, phlegm mass, carbuncle and abscess, and snakebite. Pinellia contains amino acids, volatile oils, alkaloids, Pinellia proteins, organic acids, and steroids, which have the functions of relieving cough and phlegm, stopping vomiting, anti-inflammatory, anti-tumor, antioxidant, and lipid-lowering and blood pressure-lowering.

[0026] Bitter apricot kernel: bitter and slightly warm, it belongs to the lung and large intestine channels, and has the functions of descending qi and relieving cough, moistening the intestines and relieving constipation. It is used to treat cough and asthma, chest fullness and phlegm, and constipation. Bitter apricot kernel contains cyanogenic glycosides, fatty acids, volatile oils, amino acids, flavonoids, and trace elements, which have the functions of relieving cough and asthma, moistening the intestines and relieving constipation, anti-inflammatory and analgesic, and immune regulation.

[0027] White mulberry bark: sweet and cold, it belongs to the lung channel, and has the functions of purging the lung and relieving asthma, and diuresis and swelling. It is used to treat lung heat and cough, edema and swelling, and edema and swelling. The main chemical components of white mulberry bark are flavonoids, stilbenes, glycosides, and other types of compounds. Among them, flavonoids are the main components of white mulberry bark, which have the functions of lowering blood sugar, anti-inflammatory, antioxidant, anti-tumor, heart protection, nerve protection, and immune regulation, as well as anti-depression, lipid-lowering, anti-virus, and diuretic.

[0028] Bupleurum: bitter and slightly cold, it belongs to the liver and gallbladder channels, and has the functions of relieving the exterior and reducing fever, soothing the liver and relieving depression, ascending yang qi, and stopping malaria. It is used to treat fever, less yang syndrome, liver depression and qi stagnation, qi deficiency and prolapse of viscera, and malaria.

[0029] The main chemical components of Bupleurum include saikosaponins, volatile oils, flavonoids, polysaccharides, and coumarins, which have the functions of anti-cancer, anti-depression, anti-inflammatory, antioxidant, heart protection, liver protection, kidney protection, analgesic, anti-fibrosis, and anti-virus.

[0030] Radix Saposhnikoviae: bitter and slightly sweet, warm, liver, bladder, spleen, has the effect of dispelling wind, relieving the exterior, winning wet, stopping convulsion, is often used to treat external syndrome, wind rashes, rheumatism, tetanus, diarrhea, etc.; the chemical composition of Radix Saposhnikoviae mainly includes chromone, coumarin, polysaccharide and volatile oil, has anti-inflammatory, analgesic, anti-allergic or anti-asthma and anti-tumor and other pharmacological activities.

[0031] North Adenophora: bitter and slightly bitter, cold, into the lung, stomach, has the function of nourishing yin and clearing lung, benefiting stomach and generating saliva, is used for treating lung heat cough, labor cough, stomach yin deficiency, heat disease, dry mouth, etc. Lung yin deficiency, stomach yin deficiency; the chemical composition of North Adenophora mainly includes coumarin, lignan, polyacene, etc. Modern pharmacological studies show that it has immunomodulatory, anti-tumor, anti-inflammatory, antioxidant, liver protection and other activities.

[0032] Centipede: bitter and warm, into the liver, has the effect of calming wind and relieving convulsion, attacking toxin and resolving, dredging collaterals and relieving pain, is used for liver wind, convulsions, sores, scrofula, rheumatism, intractable headache, etc.; the chemical composition of centipede is various, mainly including protein, peptide, polysaccharide, fatty acid, quinoline, trace elements, etc., has anti-tumor, anti-thrombosis, anti-myocardial ischemia, antibacterial, analgesic and anti-inflammatory activities.

[0033] The principle in the application is:

[0034] The pathogenesis of intractable chronic cough patients is relatively complex, with cold and dampness hiding in the lung as the main pathogenesis, combined with wind evil disturbing the interior, and internal heat due to fluid loss, with the characteristics of cold and heat mixed, internal and external evil, and deficiency and excess mixed, which needs to be treated with cold and heat, internal and external, and deficiency and excess.

[0035] The application is mainly composed of Lingganweweijingxi decoction and allergic decoction, which can treat intractable chronic cough patients by warming the lung and resolving dampness, dispelling wind and cold, and nourishing yin and clearing heat, especially for intractable chronic cough patients with cold and dampness hiding in the lung, wind evil hiding in the lung and internal heat due to yin deficiency. The most common symptoms are chronic irritating cough, no sputum or a small amount of white sticky sputum, accompanied by itching or foreign body sensation, sensitive to oil smoke, dust, odor and cold air, or coughing is aggravated when talking and mental stress.

[0036] Linggan Wuwei Jiangxin Decoction is from Jin Gui Yao Lue (Essentials of Golden Chamber) · Pulse and Syndrome of Phlegm Retention Cough Disease and Treatment Twelfth, which is composed of five Chinese medicines, including Fuling, Zhigancao, Wuweizi, Ganjiang and Xixin. Fuling is the monarch in the prescription, which can both remove phlegm and stop the source of phlegm. Ganjiang and Xixin are the ministers, in which Ganjiang can both warm the lung and dispel cold to remove phlegm and warm the spleen to remove dampness, and Xixin can disperse and warm the lung. Wuweizi is the assistant, which can stop cough and disperse and collect. Zhigancao is the adjuvant, which can harmonize the other medicines. The whole prescription can remove cold and phlegm. Although the prescription contains five kinds of medicines, the compatibility is strict, which is a good prescription for warming the lung and removing phlegm. Jiafa Banxia Jiangni Zhiwu, Zao Shi Huatan, and Jia Xingren Xuanli Fei Qi Zhi Kou, which is Linggan Wuwei Jiangxin Decoction plus Ganjiang, Xixin and Banxia Xingren Decoction in Jin Gui Yao Lue (Essentials of Golden Chamber) · Pulse and Syndrome of Phlegm Retention Cough Disease and Treatment Twelfth, is aimed at the main pathogenesis of refractory chronic cough, cold phlegm in the lung.

[0037] Gu Jing Decoction is an experienced prescription of Professor ZHU Chen-yu for treating allergic diseases. The original prescription is composed of four medicines, including Fangfeng, Yin Qiehu, Wumei and Wuweizi, which can dispel wind and clear heat, nourish yin and cool blood. Fangfeng can dispel internal and external wind and relieve convulsion and itching. Yin Qiehu can clear virtual heat and cool blood. Wuweizi can astringe and cool the heart. Wumei can astringe the lung, stop cough, astringe the intestine, stop diarrhea and generate saliva to stop thirst. The prescription can be used for treating various cough hypersensitivity syndromes.

[0038] The prescription removes the astringency of Wumei and replaces Yin Qiehu with Qiehu with bitter and pungent flavors and cold nature, which can relieve heat, soothe the liver and lift yang. Cigu added in the prescription can relieve convulsion and relieve bronchial spasm during severe cough. Beishashen can nourish yin and clear the lung. Sangbaipi can clear the lung and relieve asthma.

[0039] The prescription contains 12 medicines, which can warm the lung and remove phlegm, dispel wind and clear heat, and remove cold and phlegm, and can be used for treating refractory chronic cough.

[0040] The dosage and method of the Chinese medicine prescription are as follows: the Chinese medicine prescription is a daily dose, which is decocted into a decoction and taken orally once a day, and is taken twice a day. One week is a course of treatment, and 2-4 courses of treatment are generally needed. During the treatment, the patient should pay attention to the following points: less spicy and cold food, keep warm and maintain appropriate exercise.

[0041] Beneficial effects

[0042] The present application is a pure traditional Chinese medicine prescription, which has mild drug properties, high safety, fast effect and good curative effect, can quickly relieve the symptoms of patients with refractory chronic cough, and is suitable for clinical popularization and application due to wide drug sources. DETAILED DESCRIPTION

[0043] The specific embodiments of the present application are further described below. It should be noted that the description of these embodiments is used to help understand the present application, but does not constitute a limitation on the present application. In addition, the technical features involved in the following described embodiments can be combined with each other as long as they do not conflict with each other.

[0044] The experimental methods in the following examples are all conventional methods unless otherwise specified. The test materials used in the following examples are all commercially available unless otherwise specified.

[0045] Example 1

[0046] The weight ratio of the traditional Chinese medicine prescription is as follows: 20g of Poria cocos, 10g of prepared licorice, 10g of Schisandra chinensis, 3g of dried ginger, 3g of Asarum, 9g of prepared pinellia, 12g of bitter apricot kernel, 20g of mulberry bark, 10g of bupleurum, 10g of wind-preventing, 20g of north sand, and 1 worm.

[0047] Example 2

[0048] The weight ratio of the traditional Chinese medicine prescription is as follows: 15g of Poria cocos, 6g of prepared licorice, 6g of Schisandra chinensis, 3g of dried ginger, 3g of Asarum, 9g of prepared pinellia, 12g of bitter apricot kernel, 15g of mulberry bark, 10g of bupleurum, 10g of wind-preventing, 15g of north sand, and 1 worm.

[0049] Example 3

[0050] The weight ratio of the traditional Chinese medicine prescription is as follows: 30g of Poria cocos, 12g of prepared licorice, 12g of Schisandra chinensis, 9g of dried ginger, 6g of Asarum, 12g of prepared pinellia, 12g of bitter apricot kernel, 30g of mulberry bark, 15g of bupleurum, 15g of wind-preventing, 30g of north sand, and 2 worms.

[0051] Each dose of decoction is first soaked in 1500ml of warm water for half an hour, then boiled for about 5 minutes with high heat, then boiled for 35 minutes with small heat, boiled once, divided into two times, and 200ml is taken twice a day, half an hour after breakfast and dinner.

[0052] Example 4 Clinical efficacy observation

[0053] A clinical observation was conducted on 78 patients with refractory chronic cough in the inpatient ward and outpatient department of TCM of Beijing Chest Hospital from December 2021 to December 2023, which were divided into a traditional Chinese medicine group of 52 cases and a control group of 26 cases. All subjects signed the informed consent form and the clinical case information was recorded in detail.

[0054] 4.1 Diagnostic criteria

[0055] (1) Western medicine diagnostic criteria

[0056] According to the Chinese "Guidelines for the Diagnosis and Treatment of Cough (2021)" and "Chinese Expert Consensus on the Diagnosis and Treatment of Refractory Chronic Cough (2021)", the diagnostic criteria for refractory chronic cough are as follows: ① Cough duration greater than 8 weeks; ② Chronic cough with unknown causes after recommended standard examination and treatment; ③ Chronic cough that cannot be relieved after empirical treatment for known causes of chronic cough; ④ Chronic cough with poor treatment effect and persistent symptoms, with some evidence of examination of chronic cough causes; ⑤ Chronic irritating cough with clinical manifestations such as throat itching or foreign body sensation, sensitivity to oil smoke, dust, odor and cold air, or cough induced by speaking and mental stress.

[0057] (2) TCM syndrome differentiation criteria

[0058] According to "Practical Internal Medicine of Traditional Chinese Medicine", "Expert Consensus on Diagnosis and Treatment of Cough in Traditional Chinese Medicine (2021)", combined with clinical practice, the syndrome differentiation criteria for refractory chronic cough with cold drink hiding in the lung and wind evil disturbing the interior, and fluid damage and internal heat are formulated.

[0059] Main symptoms: cough;

[0060] Secondary symptoms: ① Cough with sputum, ② Throat itching, ③ Cold and hot air induced, ④ Odor induced, ⑤ Speaking induced, ⑥ Dry throat, ⑦ Wheezing.

[0061] With 4 of the 7 secondary symptoms, it can be diagnosed.

[0062] 4.2 Inclusion criteria

[0063] (1) Meet the diagnostic criteria for refractory chronic cough;

[0064] (2) TCM syndrome differentiation belongs to cold drink hiding in the lung and wind evil disturbing the interior, and fluid damage and internal heat;

[0065] (3) Age 15-80 years old, gender not limited;

[0066] (4) No intellectual and mental disorders, normal language expression ability, and judgment ability on general condition;

[0067] (5) Good patient compliance, understanding of treatment process, acceptance and signature of informed consent form.

[0068] 4.3 Exclusion criteria

[0069] (1) Cough duration less than 8 weeks;

[0070] (2) Cough with clear cause and effective treatment according to the cause;

[0071] (3) Patients with severe damage to vital organs such as the heart, lungs, brain, liver, and kidneys.

[0072] 4.4 Treatment Plan

[0073] (1) Control group

[0074] The control group received: (1) Compound methoxyphenamine capsules (Daiichi Sankyo Pharmaceutical (Shanghai) Co., Ltd., Approval No.: H20033669, Specification: Each capsule contains 12.5mg methoxyphenamine hydrochloride, 7mg noscapine, 25mg aminophylline, and 2mg chlorpheniramine maleate) 2 capsules / time, 3 times / day; (2) Montelukast sodium tablets (Organon Pharma (UK) Limited, Approval No.: J20130047, Specification: 10mg) orally, 10mg once / day. One week was one course of treatment, and two consecutive courses of treatment were administered.

[0075] The traditional Chinese medicine group received oral treatment with a decoction. Patients took one dose of the decoction obtained in Example 1 of this invention, twice daily, about half an hour after breakfast and dinner, 200ml each time (decoction method: soak each dose of the decoction in 1500ml of warm water for half an hour, then bring to a boil over high heat for about 5 minutes, then simmer over low heat for 35 minutes; decoct once, divide into two doses, 200ml each time, half an hour after breakfast and dinner). One week constitutes one course of treatment, and two consecutive courses are administered.

[0076] 4.5 Follow-up Design

[0077] Follow-up period: 8 weeks;

[0078] Follow-up frequency: baseline, week 1, week 2, week 4, and week 8, for a total of 5 times.

[0079] 4.6 Efficacy Evaluation Indicators

[0080] (1) Key Indicators

[0081] Overall effective rate of cough improvement: Based on the "Guidelines for the Diagnosis and Treatment of Cough (2021)," the cough severity score scale (CET) was used for scoring, as detailed in Table 1. The overall effective rate was also calculated in accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial Implementation)."

[0082] Calculation formula (nimodipine method): Efficacy index = (Pre-treatment score - Post-treatment score) / Pre-treatment score × 100%. Clinical cure: symptom score reduction ≥ 90%; Significant effect: symptom score reduction ≥ 70%; Effective: symptom score reduction ≥ 30%; Ineffective: symptom score reduction less than 30%.

[0083] Overall effective rate = (number of clinically cured cases + number of cases with significant effect + number of effective cases) / total number of cases in the group × 100%.

[0084] Table 1 Cough severity score table (CET)

[0085]

[0086] Note: Daytime refers to the period from waking up to going to sleep; read the questions in the table and mark the appropriate place with a according to your current coughing condition

[0087] (2) Secondary indicators

[0088] ① Time to cough disappearance

[0089] Criteria: refers to the cough severity score ≤ 1 point, and maintained for 24 hours and more. For example, if the (day + night) cough symptom score on the patient diary card on the 5th and 6th day is 1 point, the time to cough disappearance is recorded as "5 days".

[0090] ② Time to drug effect

[0091] Criteria: after treatment, the patient's cough severity score is reduced by ≥ 1 point compared to baseline, and maintained for 24 hours and more. For example, if the baseline cough severity score minus the cough severity score on the patient diary card on the 5th day is ≥ 1 point, the time to drug effect is recorded as "5 days".

[0092] ③ Recurrence rate: the recurrence of the two groups of patients at the 8th week is counted, and the clinically cured and effective cases are observed. If the relevant symptoms worsen again, it is determined to be recurrence.

[0093] 4.7 Safety evaluation indicators

[0094] Observe the general vital signs (blood pressure, respiration, heart rate, body temperature) of all subjects at baseline, 1st week, 2nd week, and 4th week; blood routine, liver and kidney function, electrocardiogram at baseline and 4th week; adverse events, including abnormal clinical manifestations and detection indicators during the trial, etc.

[0095] 4.8 Study results

[0096] (1) Total effective rate of cough improvement at different follow-up nodes

[0097] After 1 week of treatment, the total effective rate of the traditional Chinese medicine group was (3+12+31) / 52x100%=88.5%, and that of the control group was 12 / 26x100%=46.2%; after 2 weeks of treatment, the total effective rate of the traditional Chinese medicine group was (15+22+12) / 52x100%=94.2%, and that of the control group was (3+13) / 26x100%=61.5%; after 4 weeks of treatment, the total effective rate of the traditional Chinese medicine group was (31+15+4) / 52x100%=96.2%, and that of the control group was (4+8+9) / 26x100%=80.8%. See Table 2 for details.

[0098] Table 2 Total effective rate of cough improvement at different follow-up nodes

[0099]

[0100] (2) Comparison of drug onset time and cough disappearance time

[0101] The drug onset time and cough disappearance time of the traditional Chinese medicine group were shorter than those of the control group, and the differences were statistically significant (P<0.01). See Table 3 for details.

[0102] Table 3 Comparison of drug onset time and cough disappearance time of the two groups

[0103]

[0104]

[0105] (3) Comparison of recurrence rate

[0106] At the 8th week, 2 cases in the traditional Chinese medicine group relapsed, with a recurrence rate of 4.3% (2 / 46); 2 cases in the control group relapsed, with a recurrence rate of 16.7% (2 / 12), and the difference between the two groups was statistically significant (P<0.05).

[0107] (4) Safety analysis

[0108] The general vital signs (blood pressure, respiration, heart rate, body temperature), blood routine, liver and kidney function, and electrocardiogram information of the 78 subjects were collected at baseline, and the safety-related information of 58 patients was collected at the 4th week. No serious adverse events occurred in all subjects during the trial. Four adverse events occurred in the traditional Chinese medicine group, of which 1 case was aggravated, the patient had fever, white blood cell increase, neutrophil percentage increase, chest CT showed left lung patch shadow, combined with positive mycoplasma antibody, considered mycoplasma pneumonia, and improved after treatment with azithromycin; 3 patients had skin rash, skin redness and itching, and all returned to normal after treatment. Five adverse events occurred in the control group, 2 cases of lung infection had fever, 1 case of skin rash had skin redness and itching, 1 case of dizziness, 1 case of arrhythmia with abnormal electrocardiogram and mild blood pressure elevation, but all returned to normal after drug withdrawal. The incidence of adverse events in the traditional Chinese medicine group was significantly lower than that in the control group, and there was a significant difference between the two groups (P<0.05).

[0109] In summary, the effect verification of the present application shows that for patients with refractory chronic cough, the traditional Chinese medicine composition of the traditional Chinese medicine group can quickly reduce the cough severity score compared with the conventional symptomatic treatment of western medicine in the control group, has a fast drug onset time, a short cough disappearance time, a total effective rate of cough improvement of 96.2% at the 4th week, and good safety.

[0110] Typical cases

[0111] Case 1: Huang, female, 50 years old. Initial diagnosis date: March 20, 2023. Complaint: intermittent cough for more than 3 months, aggravated for 2 weeks. Medical history: The patient has had intermittent cough since December 2022 after being infected with the new coronavirus. After treatment by traditional Chinese and Western medicine, there was no significant improvement, and the cough recurred. The patient's cough worsened after being chilled 2 weeks ago, with white sputum, about 15-30 ml per day. Chest CT showed "a small amount of chronic inflammation in both lungs." Current symptoms: cough, cough with white sputum, induced by cold air, strange smell, talking and laughing, slightly short of breath and wheezing after exercise, accompanied by dry throat, throat itching, nasal itching, and cold intolerance, without chest tightness, chest pain, loose stool, normal urination, normal diet and sleep; pale red tongue, yellowish and greasy fur, thin and stringy pulse. Physical examination: pharyngeal hyperemia (±), clear breath sounds in both lungs, no obvious dry or wet rales were heard in both lungs. The patient has a history of "allergic rhinitis". Western medical diagnosis: refractory chronic cough; TCM diagnosis: cough (cold drink hiding in the lung, wind evil disturbing inside, and internal heat due to fluid deficiency). Mainly treat with warming lung and resolving fluid, combined with dispelling wind and cold, nourishing yin and clearing heat. After taking the traditional Chinese medicine formula decoction in Example 3 of the invention for 1 week, the cough was reduced by 60%; after 2 weeks, the cough was reduced by 95%; after 4 weeks of follow-up, there was no cough, and after 8 weeks of follow-up, there was no recurrence.

[0112] Case 2: Cao, male, 62 years old. Initial diagnosis date: August 18, 2023. Complaint: intermittent cough for more than 10 years, aggravated for 2 months. Medical history: The patient was diagnosed with "chronic obstructive pulmonary disease and bronchiectasis" 10 years ago. He had intermittent cough and asthma, and took "Xinbikai" and cough and phlegm relieving drugs for maintenance treatment. Two months ago, his cough worsened after being chilled. After treatment by traditional Chinese and Western medicine, there was no significant improvement, and the cough recurred. Current symptoms: cough, white sputum, induced by cold and hot air, strange smell, talking and laughing, chest tightness and wheezing, more obvious after exercise, accompanied by dry throat, throat itching, no chest pain, excessive sweating, normal diet, sleep, and bowel movements; dark red tongue, yellowish and greasy fur, thin and stringy pulse. Physical examination: pharyngeal hyperemia (±), clear breath sounds in both lungs, no obvious dry or wet rales were heard in both lungs. Western medical diagnosis: refractory chronic cough, chronic obstructive pulmonary disease, and bronchiectasis; TCM diagnosis: cough (cold drink hiding in the lung, wind evil disturbing inside, and internal heat due to fluid deficiency). Mainly treat with warming lung and resolving fluid, combined with dispelling wind and cold, nourishing yin and clearing heat. After taking the traditional Chinese medicine formula decoction in Example 1 of the invention for 1 week, the cough was reduced by 50%; after 2 weeks, the cough was reduced by 90%; after 4 weeks of follow-up, the cough was reduced by 95%, and after 8 weeks of follow-up, there was no recurrence.

[0113] Case 3: A female patient, 42 years old. Initial diagnosis date: September 20, 2023. Complaint: intermittent cough for more than 2 months, aggravated for 1 week. Medical history: The patient had intermittent cough after double infection of influenza A virus and mycoplasma pneumonia for 2 months, dry mouth, and itchy throat. After taking compound methoxy gel capsules, suhuang cough capsules, dextromethorphan syrup, and montelukast tablets, the patient still had a cough. The patient was hospitalized and had chest CT, sinus CT, lung function, blood routine, allergen, esophageal 24h pH detection, and bronchoscopy, all of which were normal. Current symptoms: cough, white sputum, cold and hot air, smell, emotional agitation, dry mouth, itchy throat, sweating, no chest tightness, shortness of breath, normal diet, sleep, and bowel movements; normal menstrual cycle, color, amount, occasional blood clots, small cold abdomen. Tongue body is large with tooth marks, tongue is red, thick white fur, and pulse is thin. Physical examination: negative lung examination. Western medical diagnosis: refractory chronic cough; TCM diagnosis: cough (cold drink hiding in the lung, wind evil disturbing, and internal heat due to fluid damage). Treatment focuses on warming the lung and resolving fluid, combined with dispersing wind and cold, and nourishing yin and clearing heat. After taking the herbal decoction in Example 2 of the invention for 1 week, the cough was reduced by 80%; after 2 weeks, the cough was reduced by 95%; after 4 weeks of follow-up, the cough had disappeared, and after 8 weeks of follow-up, there was no recurrence.

Claims

1. A traditional Chinese medicine composition for treating intractable chronic cough, the traditional Chinese medicine composition being composed of Poria cocos 20 g, prepared licorice 10 g, Schisandra chinensis 10 g, dried ginger 3 g, Asarum 3 g, prepared Pinellia 9 g, bitter apricot kernel 12 g, white mulberry bark 20 g, Bupleurum 10 g, Radix Saposhnikoviae 10 g, North Adenophora 20 g, and centipede 1.

2. A traditional Chinese medicine composition for treating intractable chronic cough, characterized in that, The traditional Chinese medicine composition is composed of Poria cocos 15 g, prepared licorice 6 g, Schisandra chinensis 6 g, dried ginger 3 g, Asarum 3 g, prepared Pinellia 9 g, bitter apricot kernel 12 g, white mulberry bark 15 g, Bupleurum 10 g, Radix Saposhnikoviae 10 g, North Adenophora 15 g, and centipede 1.

3. A traditional Chinese medicine composition for treating intractable chronic cough, characterized in that, The traditional Chinese medicine composition is composed of Poria cocos 30 g, prepared licorice 12 g, Schisandra chinensis 12 g, dried ginger 9 g, Asarum 6 g, prepared Pinellia 12 g, bitter apricot kernel 12 g, white mulberry bark 30 g, Bupleurum 15 g, Radix Saposhnikoviae 15 g, North Adenophora 30 g, and centipede 2.

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