A traditional Chinese medicine composition for treating reflux cough and application thereof

Abstract

This invention relates to a traditional Chinese medicine composition for treating reflux cough, the composition being made from the following raw materials in parts by weight: Coptis chinensis 1-5 parts, Evodia rutaecarpa 1-5 parts, Gardenia jasminoides (processed) 10-14 parts, Fritillaria thunbergii 7-11 parts, Sepia esculenta 18-22 parts, Pinellia ternata (processed) 10-14 parts, Belamcanda chinensis 7-11 parts, Ephedra sinica (processed) 4-8 parts, Asarum heterotropoides 1-5 parts, Schisandra chinensis 1-5 parts, and Zingiber officinale (dried). This invention also provides the application of the traditional Chinese medicine composition. This formula utilizes the heat-clearing and reversing effects of Zuo Jin Wan, the acid-neutralizing and pain-relieving effects of Wu Bei San, the heat-clearing and acid-suppressing effects of Gardenia jasminoides, and the lung-warming and phlegm-resolving effects of Zingiber officinale, Asarum heterotropoides, and Schisandra chinensis from She Gan Ma Huang Tang. The combined effects of these herbs treat both the lungs and stomach, employing both warming and cooling methods to achieve the combined effects of clearing heat, reversing reversal, and relieving cough. The formula is meticulously crafted, with each herb acting in tandem to harmonize and regulate the body, effectively addressing the underlying pathogenesis. Its rigorous formulation has yielded remarkable clinical efficacy. This invention's traditional Chinese medicine compound for treating reflux cough has achieved good clinical results, effectively improving the clinical symptoms and quality of life of patients with reflux cough, while also demonstrating good safety.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and more specifically, to a traditional Chinese medicine composition for treating reflux cough and its application. Background Technology

[0002] Gastroesophageal reflux-related cough (GERC) is a clinical syndrome characterized by cough as the prominent symptom caused by the reflux of gastric acid and / or other gastric contents into the esophagus. It is an extraesophageal syndrome of gastroesophageal reflux disease (GERD). The main clinical manifestations are chronic cough or nocturnal choking cough, with or without typical GERD symptoms such as reflux and heartburn, as well as pharyngeal symptoms such as throat discomfort and foreign body sensation.

[0003] Treatment options for GERC include antireflux medication and surgery. Medication primarily involves acid suppression, with proton pump inhibitors (PPIs) recommended as the first-line treatment. However, reflux cough can be categorized into three types: acid reflux (pH ≤ 4), weak acid reflux (4 < pH ≤ 7), and non-acid reflux (pH > 7). Acid suppression is significantly effective for acid reflux, moderately effective for weak acid reflux, and almost ineffective for non-acid reflux. Therefore, different studies have yielded inconsistent results regarding the efficacy of PPIs in treating GERC, and the overall benefit remains controversial. While PPIs have some efficacy in treating GERC, long-term use has numerous side effects, such as acid rebound after discontinuation, vitamin B12 deficiency, osteoporosis and fractures, gastric fundic gland polyps, and gastrointestinal tumors. Furthermore, surgical treatment carries certain risks, hindering widespread clinical application. The long-term effects of endoscopic antireflux surgery require further clarification, and some techniques have not yet been introduced to China.

[0004] Chinese patent document CN104997989A discloses a traditional Chinese medicine for treating gastroesophageal reflux cough. This medicine consists of the following herbs in parts by weight: Inula japonica 8-16 parts, Pinellia ternata 5-13 parts, Coptis chinensis 8-16 parts, Scutellaria baicalensis 8-16 parts, Cynanchum paniculatum 5-13 parts, Peucedanum praeruptorum 5-13 parts, Platycodon grandiflorus 5-13 parts, Magnolia officinalis 5-13 parts, Areca catechu 5-13 parts, Sepia esculenta 5-13 parts, Calcined oyster shell 8-16 parts, Perilla frutescens 5-13 parts, Cannabis sativa 8-16 parts, Citrus medica 5-13 parts, Citrus medica 5-13 parts, Prunus mume 4-8 parts, and Glycyrrhiza uralensis 4-8 parts. This medicine can significantly improve symptoms, reduce recurrence, and improve the quality of life of patients, achieving good clinical efficacy.

[0005] Chinese patent document CN116115726A discloses a traditional Chinese medicine composition for treating gastroesophageal reflux cough and its application. The composition is made from the following raw materials in parts by weight: 9-15 parts of Inula japonica, 12-18 parts of Hematite, 6-12 parts of Bupleurum chinense, 9-15 parts of Citrus aurantium, 6-12 parts of Gardenia jasminoides (charred), 6-12 parts of Melia toosendan, 1-6 parts of Coptis chinensis, 1-6 parts of Evodia rutaecarpa, 9-15 parts of Pseudostellaria heterophylla, 1-6 parts of Zingiber officinale, and 3-9 parts of Glycyrrhiza uralensis. Its advantages are: the traditional Chinese medicine composition of this invention, verified by pharmacodynamic experiments, can effectively inhibit reflux, reduce the occurrence of airway neurogenic inflammation, improve respiratory inflammatory response, and achieve the purpose of treating gastroesophageal reflux cough. Clinical efficacy is definite, with no obvious adverse reactions observed, and it has significant prospects for new drug transformation and application.

[0006] There are many traditional Chinese medicine compositions for treating reflux cough, but they all have some drawbacks, such as too many ingredients, difficulty in sourcing materials, high prices, and unclear efficacy and poor treatment results. Therefore, there is an urgent need for a traditional Chinese medicine composition that is effective in treating reflux cough, has fewer ingredients, is practical, has high compliance, and is safe and effective. Summary of the Invention

[0007] The purpose of this invention is to address the shortcomings of existing technologies by providing a traditional Chinese medicine composition for treating reflux cough and its application.

[0008] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating reflux cough, the traditional Chinese medicine composition being made from the following raw materials in parts by weight: Coptis chinensis 1-5 parts, Evodia rutaecarpa 1-5 parts, Gardenia jasminoides 10-14 parts, Fritillaria thunbergii 7-11 parts, Sepia esculenta 18-22 parts, Pinellia ternata 10-14 parts, Belamcanda chinensis 7-11 parts, Ephedra sinica 4-8 parts, Asarum heterotropoides 1-5 parts, Schisandra chinensis 1-5 parts, and Zingiber officinale 1-5 parts.

[0009] As a preferred example, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 2-4 parts Coptis chinensis, 2-4 parts Evodia rutaecarpa, 11-13 parts Gardenia jasminoides (processed), 8-10 parts Fritillaria thunbergii, 19-21 parts Cuttlebone, 11-13 parts Pinellia ternata (processed), 8-10 parts Belamcanda chinensis, 5-7 parts Ephedra sinica (processed), 2-4 parts Asarum heterotropoides, 2-4 parts Schisandra chinensis, and 2-4 parts Zingiber officinale (dried).

[0010] As another preferred embodiment, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 3 parts Coptis chinensis, 3 parts Evodia rutaecarpa, 12 parts Gardenia jasminoides (roasted), 9 parts Fritillaria thunbergii, 20 parts Cuttlebone, 12 parts processed Pinellia ternata, 9 parts Belamcanda chinensis, 6 parts processed Ephedra sinica, 3 parts Asarum heterotropoides, 3 parts Schisandra chinensis, and 3 parts dried ginger.

[0011] As another preferred example, the medicine composition is in the form of tablets, capsules, granules, oral liquids, or syrups.

[0012] Secondly, the present invention provides the application of traditional Chinese medicine compositions in the preparation of drugs for treating reflux cough.

[0013] As a preferred example, the reflux cough is a reflux cough due to liver and stomach heat stagnation.

[0014] Thirdly, the present invention provides a pharmaceutical composition for treating reflux cough, the pharmaceutical composition comprising rabeprazole and a traditional Chinese medicine composition.

[0015] Fourthly, the present invention provides the use of the pharmaceutical composition in the preparation of a medicament for treating reflux cough.

[0016] As a preferred example, the reflux cough is a reflux cough due to liver and stomach heat stagnation.

[0017] The advantages of this invention are: the herbal composition of this invention clears heat and relieves nausea, promotes lung function and stops cough. The herbal composition includes: Coptis chinensis, Evodia rutaecarpa, Gardenia jasminoides (processed), Fritillaria thunbergii, Cuttlebone, Pinellia ternata (processed), Belamcanda chinensis, Ephedra sinica (processed), Asarum heterotropoides, Schisandra chinensis, and Zingiber officinale (dried).

[0018] Coptis chinensis: [Source] This product is the dried rhizome of Coptis chinensis, Coptis triangularis, or Coptis yunnanensis, all belonging to the Ranunculaceae family. These three are commonly known as "Wei Lian," "Ya Lian," and "Yun Lian," respectively. Harvested in autumn, the fibrous roots and soil are removed, and the remaining fibrous roots are removed by rubbing. [Taste and Properties] Bitter, cold. [Meridians Entered] Heart, Spleen, Stomach, Liver, Gallbladder, Large Intestine. [Functions and Indications] Clears heat and dries dampness, drains fire and detoxifies. Used for damp-heat fullness, vomiting and acid regurgitation, diarrhea, jaundice, high fever with delirium, excessive heart fire, restlessness and insomnia, hematemesis due to blood heat, red eyes, toothache, thirst, carbuncles and boils; externally used for eczema, damp sores, and ear discharge. Wine-processed Coptis chinensis effectively clears heat from the upper burner. Used for red eyes and mouth sores. Ginger-processed Coptis chinensis clears the stomach and stops vomiting. Used for alternating chills and fever, damp-heat obstruction, fullness, and vomiting. Cornus-processed Coptis chinensis soothes the liver and stomach and stops vomiting. Used for liver and stomach disharmony, vomiting and acid regurgitation.

Dosage and Administration

Excerpt

[0019] Evodia rutaecarpa: [Source] The immature fruit of Evodia rutaecarpa, Evodia rutaecarpa var. rubrophylla, and Evodia rutaecarpa var. rubrophylla. Harvest 3 years after planting, early-maturing varieties in early July, late-maturing varieties in early August, when the fruit is tea-green and the carpels have not separated. Pick the whole bunch of fruit before the dew dries, being careful not to break the fruit branches. Dry in the sun, rub by hand to remove the fruit stalks, and winnow clean. If it rains, use a low fire to prevent drying. [Properties] Pungent; bitter; hot; slightly toxic [Meridians] Liver; Stomach; Spleen; Large Intestine; Kidney [Functions and Indications] Dispels cold and relieves pain; soothes the liver and lowers qi; warms the middle and dries dampness. Mainly used for cold pain in the epigastrium and abdomen; headache in the Jueyin meridian; hernia pain; swelling and pain in the beriberi; vomiting and acid regurgitation; diarrhea due to cold and dampness. [Dosage and Administration] For internal use: decoct 1.5-5g; or make into pills or powders. For external use: appropriate amount, grind into powder and apply, or decoct in water for washing. [Excerpt] "Chinese Materia Medica".

[0020] Gardenia jasminoides (Fructus Gardeniae):

Source

Properties

Meridians

Functions and Indications

Dosage and Administration

Caution

Excerpt

[0021] Fritillaria thunbergii:

Source

Taste and Properties

Meridians Entered

Functions and Indications

Dosage and Administration

Caution

Excerpt

[0022] Cuttlebone: [Source] The inner shell of various cuttlefish species, including the needleless cuttlefish, the scorpion cuttlefish, the needle cuttlefish, the white-spotted cuttlefish, the tiger-spotted cuttlefish, and the pseudo-order cuttlefish. From April to August, the cuttlebone is collected from the seashore or accumulated on the beach, impurities are removed, it is rinsed with fresh water and then dried; or around May, when groups of cuttlefish migrate to the vicinity of islands to spawn, large quantities are caught, the soft parts are removed, the cuttlebone is collected, washed, and dried. [Meridians Entered] Liver; Kidney [Functions and Indications] Astringent and hemostatic; strengthens essence and stops leukorrhea; neutralizes acid and relieves pain; astringes and heals sores. Used for hematemesis; vomiting blood; metrorrhagia; hematochezia; epistaxis; traumatic bleeding; seminal emission due to kidney deficiency; leukorrhea; stomach pain and heartburn; belching and acid reflux; eczema and ulcers. [Dosage and Administration] For internal use: decoction, 10-30g; powder, 1.5-3g. For external use: Apply appropriate amount as powder; or mix and apply topically; or blow into the ears or nose. [Caution] Those with yin deficiency and excessive heat should not take too much; prolonged use may cause constipation, and it can be used in combination with appropriate laxatives. [Excerpt] *Chinese Materia Medica*.

[0023] Prepared Pinellia: [Source] The tuber of Pinellia ternata (Araceae family). Seed propagation takes 3 years; bulbil propagation takes 2 years; tuber propagation is harvested from late September to November of the same year after spring planting. Dig up the tubers, sift out the soil, separate them into large, medium, and small sizes, place them in baskets, and pound them under running water with a stick to remove the skin. Alternatively, a Pinellia peeling machine can be used. Wash clean and sun-dry or oven-dry. [Properties and Flavors] Pungent; warm; toxic. [Meridians Entered] Spleen; Stomach; Lung. [Functions and Indications] Dries dampness and resolves phlegm; relieves nausea and vomiting; dissipates lumps and nodules. Used for cough and asthma with excessive phlegm; vomiting and nausea; chest and epigastric fullness, headache and dizziness; restlessness at night; goiter and phlegm nodules; carbuncles and boils. [Dosage and Administration] For internal use: decoct 3-9g; or make into pills or powders. For external use: appropriate amount, grind the raw product into powder, mix with water and apply, or mix with wine or vinegar and apply.

Caution

Excerpt

[0024] Belamcanda chinensis: [Source] The rhizome of Belamcanda chinensis, a plant of the Iridaceae family. Harvested 2-3 years after planting. The rhizomes are dug up in spring and autumn, washed clean of soil, sun-dried, the fibrous roots rubbed off, and then sun-dried until completely dry. Impurities are removed, the rhizome is washed clean with water, soaked briefly, drained, moistened thoroughly, sliced, and sun-dried; the fibrous roots and debris are sifted out. [Properties] Bitter; cold; bitter. [Meridians] Lung; Liver. [Functions and Indications] Clears heat and detoxifies; resolves phlegm and soothes the throat; dissipates blood stasis and nodules. Used for sore throat; cough and asthma; scrofula; malaria; carbuncles and boils. [Dosage and Administration] For internal use: decoct 5-10g; make into pills or powders; or juice fresh. For external use: appropriate amount, or grind into powder and blow into the throat; or pound and apply. [Caution] Contraindicated in cases without actual heat, spleen deficiency with loose stools, and in pregnant women. [Excerpt] *Chinese Materia Medica*.

[0025] Processed Ephedra:

Source

Properties

Meridians

Functions and Indications

Dosage and Administration

Caution

[0026] Asarum: [Source] The whole herb with roots of Asarum heterotropoides, Asarum sieboldii, and Asarum sieboldii of the Aristolochiaceae family. Transplanted plants grow for 3-5 years, while direct-seeded plants grow for 5-6 years before harvesting. In mid-September, dig up the entire root system, remove the soil, bundle 1-2 kg into bunches, air-dry in a cool place, and then pack and store. Remove impurities, spray with water, cut into sections promptly, and air-dry. [Properties] Pungent; warm; slightly toxic. [Meridians] Lung; Kidney; Heart; Liver; Gallbladder; Spleen. [Functions and Indications] Dispels cold and wind; relieves pain; warms the lungs and resolves phlegm; opens the orifices. Used for wind-cold syndrome; headache, toothache; rheumatic pain; cough and asthma due to phlegm; nasal congestion; sinusitis; oral ulcers. [Dosage and Administration] For internal use: decoct 1.5-9g; grind into powder 1-3g. For external use: appropriate amount, grind into powder and blow into the nose, plug the ears, apply to the navel; or decoct and gargle.

Caution

Excerpt

[0027] Schisandra chinensis: [Source] The fruit of Schisandra chinensis or Schisandra chinensis, both belonging to the Schisandraceae family. It bears fruit 4-5 years after planting, from late August to early October, when the fruit turns purplish-red. Harvest as it ripens, sift out ash and impurities, steam thoroughly, and then sun-dry. Alternatively, stir-fry the cleaned Schisandra chinensis over low heat until it puffs up and turns purplish-brown. [Properties] Sour; warm. [Meridians] Lung; Heart; Kidney. [Functions and Indications] Astringent and consolidating; replenishing qi and generating fluids; calming the mind and soothing the nerves. Used for cough and wheezing; nocturnal emission and spermatorrhea; frequent urination and enuresis; chronic diarrhea; spontaneous sweating and night sweats; thirst due to fluid depletion; palpitations and insomnia. [Dosage and Administration] For internal use: decoct 3-6g; grind into powder; 1-3g each time; make into a paste; or make into pills or powders. For external use: grind into powder and apply; or decoct for washing.

Caution

Excerpt

[0028] Dried Ginger:

Source

Properties

Meridians

Functions and Indications

Dosage and Administration

Caution

Excerpt

[0029] This formula is derived from Zuojin Pill, Wubei Powder, and Shegan Mahuang Decoction. It is one of the series of formulas in the "unblocking," "transforming," "dispersing," and "balancing" diagnostic and treatment system for spleen and stomach diseases at the Research Base of Chen Cunren's Academic Thought of the Ding Family Internal Medicine School of Shanghai-style Traditional Chinese Medicine. The chief herbs in the formula are Coptis chinensis and Evodia rutaecarpa. Coptis chinensis clears heart fire, preventing heart fire from overpowering lung metal. Lung metal, not being overpowered, can restrain liver wood, and wood, restrained by metal, is not unruly. Evodia rutaecarpa addresses phlegm, guides heat downward, and is pungent, warm, and unblocking, opening up stagnation and dispersing nodules. The two herbs together open up with pungent and descend with bitter, clearing liver heat, harmonizing the stomach and relieving nausea, hitting the key to the pathogenesis. The assistant herbs are Gardenia jasminoides, Fritillaria thunbergii, Sepia officinalis, and Pinellia ternata, which clear heat, resolve phlegm, neutralize acid, and relieve nausea. The adjuvant herbs are Shegan, Ephedra sinica, Asarum heterotropoides, Schisandra chinensis, and Zingiber officinale, which warm the lungs, resolve phlegm, disperse lung heat, and stop cough. This formula combines the heat-clearing and reversing effects of Zuojin Pill, the acid-neutralizing and pain-relieving effects of Wubei Powder, the heat-clearing and acid-suppressing effects of Gardenia, and the lung-warming and phlegm-resolving effects of Dried Ginger, Asarum, and Schisandra from Shegan Mahuang Decoction. The combined effects of these herbs treat both the lungs and stomach, using both warming and cooling herbs to achieve the combined effects of clearing heat, reversing reversal, and relieving cough. The entire formula is well-structured, with each herb acting in a harmonious and synergistic manner, precisely targeting the pathogenesis. Its rigorous formulation has yielded remarkable clinical efficacy. This traditional Chinese medicine compound formula for treating reflux cough has achieved good clinical results, effectively improving the clinical symptoms and quality of life of patients with reflux cough, and demonstrating good safety. Detailed Implementation

[0030] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the description of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0031] Example 1: A traditional Chinese medicine composition for treating reflux cough according to the present invention (I)

[0032] Coptis chinensis 3 parts, Evodia rutaecarpa 3 parts, Gardenia jasminoides 12 parts, Fritillaria thunbergii 9 parts, Cuttlebone 20 parts, Pinellia ternata 12 parts, Belamcanda chinensis 9 parts, Ephedra sinica 6 parts, Asarum heterotropoides 3 parts, Schisandra chinensis 3 parts, Zingiber officinale 3 parts.

[0033] Example 2: A traditional Chinese medicine composition for treating reflux cough according to the present invention (II)

[0034] Coptis chinensis 3 parts, Evodia rutaecarpa 2 parts, Gardenia jasminoides 13 parts, Fritillaria thunbergii 7 parts, Cuttlebone 22 parts, Pinellia ternata 12 parts, Belamcanda chinensis 8 parts, Ephedra sinica 7 parts, Asarum heterotropoides 1 part, Schisandra chinensis 5 parts, Zingiber officinale 3 parts.

[0035] Example 3: A traditional Chinese medicine composition for treating reflux cough according to the present invention (III)

[0036] Coptis chinensis 2 parts, Evodia rutaecarpa 4 parts, Gardenia jasminoides 10 parts, Fritillaria thunbergii 11 parts, Cuttlebone 20 parts, Pinellia ternata 11 parts, Belamcanda chinensis 10 parts, Ephedra sinica 4 parts, Asarum heterotropoides 5 parts, Schisandra chinensis 3 parts, Zingiber officinale 2 parts.

[0037] Example 4: A traditional Chinese medicine composition for treating reflux cough according to the present invention (IV)

[0038] Coptis chinensis 4 parts, Evodia rutaecarpa 1 part, Gardenia jasminoides 14 parts, Fritillaria thunbergii 9 parts, Cuttlebone 19 parts, Pinellia ternata 13 parts, Belamcanda chinensis 7 parts, Ephedra sinica 8 parts, Asarum heterotropoides 3 parts, Schisandra chinensis 2 parts, Zingiber officinale 4 parts.

[0039] Example 5: A traditional Chinese medicine composition for treating reflux cough according to the present invention (V)

[0040] Coptis chinensis 1 part, Evodia rutaecarpa 5 parts, Gardenia jasminoides 12 parts, Fritillaria thunbergii 8 parts, Cuttlebone 21 parts, Pinellia ternata 10 parts, Belamcanda chinensis 11 parts, Ephedra sinica 6 parts, Asarum heterotropoides 2 parts, Schisandra chinensis 4 parts, Zingiber officinale 1 part.

[0041] Example 6: A traditional Chinese medicine composition for treating reflux cough according to the present invention (VI)

[0042] Coptis chinensis 5 parts, Evodia rutaecarpa 3 parts, Gardenia jasminoides 11 parts, Fritillaria thunbergii 10 parts, Cuttlebone 18 parts, Pinellia ternata 14 parts, Belamcanda chinensis 9 parts, Ephedra sinica 5 parts, Asarum heterotropoides 4 parts, Schisandra chinensis 1 part, Zingiber officinale 5 parts.

[0043] Example 7: A traditional Chinese medicine composition for treating reflux cough according to the present invention (VII)

[0044] Coptis chinensis 3 parts, Evodia rutaecarpa 4 parts, Gardenia jasminoides 10 parts, Fritillaria thunbergii 11 parts, Cuttlebone 20 parts, Pinellia ternata 11 parts, Belamcanda chinensis 10 parts, Ephedra sinica 4 parts, Asarum heterotropoides 5 parts, Schisandra chinensis 3 parts, Zingiber officinale 2 parts.

[0045] Example 8: A traditional Chinese medicine composition for treating reflux cough according to the present invention (VIII)

[0046] Coptis chinensis 2 parts, Evodia rutaecarpa 1 part, Gardenia jasminoides 14 parts, Fritillaria thunbergii 9 parts, Cuttlebone 19 parts, Pinellia ternata 13 parts, Belamcanda chinensis 7 parts, Ephedra sinica 8 parts, Asarum heterotropoides 3 parts, Schisandra chinensis 2 parts, Zingiber officinale 4 parts.

[0047] Example 9: A traditional Chinese medicine composition for treating reflux cough according to the present invention (IX)

[0048] Coptis chinensis 4 parts, Evodia rutaecarpa 5 parts, Gardenia jasminoides 12 parts, Fritillaria thunbergii 8 parts, Cuttlebone 21 parts, Pinellia ternata 10 parts, Belamcanda chinensis 11 parts, Ephedra sinica 6 parts, Asarum heterotropoides 2 parts, Schisandra chinensis 4 parts, Zingiber officinale 1 part.

[0049] Example 10: A traditional Chinese medicine composition for treating reflux cough according to the present invention (X)

[0050] Coptis chinensis 1 part, Evodia rutaecarpa 3 parts, Gardenia jasminoides 11 parts, Fritillaria thunbergii 10 parts, Cuttlebone 18 parts, Pinellia ternata 14 parts, Belamcanda chinensis 9 parts, Ephedra sinica 5 parts, Asarum heterotropoides 4 parts, Schisandra chinensis 1 part, Zingiber officinale 5 parts.

[0051] Example 11 A traditional Chinese medicine composition for treating reflux cough according to the present invention (XI)

[0052] Coptis chinensis 5 parts, Evodia rutaecarpa 2 parts, Gardenia jasminoides 13 parts, Fritillaria thunbergii 7 parts, Cuttlebone 22 parts, Pinellia ternata 12 parts, Belamcanda chinensis 8 parts, Ephedra sinica 7 parts, Asarum heterotropoides 1 part, Schisandra chinensis 5 parts, Zingiber officinale 3 parts.

[0053] Example 12 Clinical Trial

[0054] 1. Diagnostic criteria

[0055] 1.1 Western Medicine Diagnostic Criteria:

[0056] Refer to the "Guidelines for the Diagnosis and Treatment of Cough (2021)" [1] And the "2020 Chinese Expert Consensus on Gastroesophageal Reflux Disease" [2] .

[0057] (1) Clinical symptoms: Patients present with chronic cough as their chief complaint, with a course of disease ≥8 weeks. The cough is significantly related to eating or body position, such as coughing after meals, coughing while eating, or coughing while lying flat. It may or may not be accompanied by typical GERD symptoms such as reflux and heartburn.

[0058] (2) Clinical questionnaire survey: Gastroesophageal reflux disease questionnaire (Gerd Q), with a Gerd Q score ≥8 points, and Hull airway reflux questionnaire (HARQ), with a HARQ score ≥24 points, which is helpful for the diagnosis of GERC.

[0059] (3) Confirmation of reflux, meeting any one of the following criteria: ① Multichannel intraluminal impedance and pH monitoring (MII-pH) shows acid exposure time (AET) > 6% and symptom association probability (SAP) ≥ 95%; ② PPI test: cough significantly reduced or disappeared after anti-reflux treatment; ③ Electronic gastroscopy and esophageal pathology results show inflammation. According to the criteria of the World Congress of Gastroenterology held in Los Angeles, USA in 1996, the endoscopic diagnosis of reflux esophagitis is divided into four grades: A, B, C, and D.

[0060] 1.2 Traditional Chinese Medicine Diagnostic Criteria:

[0061] Refer to the "Guidelines for the Diagnosis and Treatment of Cough (2021)" [1] Expert Consensus on Traditional Chinese Medicine Diagnosis and Treatment of Gastroesophageal Reflux Disease (2017) [3] According to the TCM diagnostic criteria, the syndrome is diagnosed as liver and stomach heat stagnation.

[0062] Main symptoms: ① Chronic cough or paroxysmal choking cough; ② Symptoms worsen when lying down or after a full meal;

[0063] Secondary symptoms: ① distending pain in the hypochondrium or stomach; ② belching with a foul odor, acid reflux, heartburn, or burning pain; ③ irritability and anger; ④ dry mouth and bitter taste; ⑤ throat discomfort and a feeling of a foreign body. Tongue and pulse characteristics include ① red tongue with yellow coating; ② wiry or wiry-rapid pulse.

[0064] A comprehensive analysis of two primary symptoms, two secondary symptoms, and tongue and pulse characteristics can lead to a diagnosis of GERC of the liver-stomach stagnation and heat type.

[0065] 2. Inclusion, Exclusion, Removal, and Termination Criteria

[0066] 2.1 Inclusion criteria

[0067] (1) Meets the diagnostic criteria for reflux cough in both traditional Chinese and Western medicine.

[0068] (2) Meets the diagnostic criteria for liver and stomach heat stagnation syndrome in traditional Chinese medicine.

[0069] (3) Patients aged between 18 and 70 years were included, regardless of gender.

[0070] (4) The subjects were informed and voluntarily signed the informed consent form.

[0071] 2.2 Exclusion Criteria

[0072] (1) Common diseases that can cause chronic cough include cough variant asthma (CVA), upper airway cough syndrome (UACS) / postnasal drip syndrome (PNDS), eosinophilic bronchitis (EB), and atopic cough (AC).

[0073] (2) Other lung diseases that can cause chronic cough, such as malignant lung tumors, chronic obstructive pulmonary disease, tuberculosis, interstitial pneumonia, etc.

[0074] (3) Chronic cough caused by drugs, such as long-term use of angiotensin-converting enzyme inhibitors (ACEIs).

[0075] (4) Patients with gastric diseases, such as gastric malignant tumors, gastroduodenal ulcers, pyloric obstruction, rumination syndrome, etc.

[0076] (5) Patients with organic esophageal diseases, such as esophageal malignant tumors, Barrett's esophagus, eosinophilic esophagitis, etc.

[0077] (6) Patients with esophageal functional disorders, such as achalasia, gastroesophageal junction obstruction, etc. (7) Patients with serious primary diseases of important systems such as the cardiovascular, nervous, liver, kidney, blood and endocrine systems that have not been effectively controlled; and patients with severe mental illness.

[0078] (8) Individuals who are allergic to any component of the Western medicine rabeprazole or the traditional Chinese medicine used in this study.

[0079] (9) Women who are trying to conceive, pregnant or breastfeeding.

[0080] (10) Individuals who have participated in or are currently participating in other clinical trials one month prior to enrollment.

[0081] 2.3 Rejection Criteria:

[0082] (1) Cases in which subjects were found to be ineligible for inclusion criteria during the trial after enrollment;

[0083] (2) If a prohibited treatment method specified in this protocol is used, such as if the patient takes a potassium-competitive acid blocker on their own during the treatment process, the patient shall be excluded.

[0084] (3) Cases that did not receive standard treatment after inclusion should be excluded, such as patients included in this study who did not take medication continuously or did not take medication as required by the trial.

[0085] (4) Missing case data affects the evaluation of treatment efficacy.

[0086] The reasons for exclusion of cases must be noted, and their case report forms must be kept for future reference. Although no efficacy statistical analysis will be performed, cases that have received at least one treatment and have at least one safety record can be included in the adverse reaction analysis.

[0087] 2.4 Termination Criteria

[0088] Terminating a trial means ending all clinical trial activities before the planned completion date. The main objectives are to protect the rights of participants, ensure the quality of the trial, and minimize unnecessary financial losses. Specifically, this includes:

[0089] (1) If a serious safety problem is encountered during the test, the test should be stopped immediately.

[0090] (2) If a serious error is found in the clinical trial protocol that affects the evaluation of treatment effect, or if a well-designed protocol deviates significantly during the execution process, it will be difficult to accurately evaluate the treatment effect if the trial continues.

[0091] (3) Researchers requested to stop the experiment due to reasons such as funding and management.

[0092] (4) In the case where the trial is revoked by the administrative department.

[0093] 3 General Information

[0094] The study included patients who visited Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, between March 2023 and January 2024. These included patients at the Gastroesophageal Reflux Disease Clinic, Gastroenterology Specialist Clinic, General Clinic, and Gastroenterology Inpatient Ward. All participants completed and signed informed consent forms in accordance with ethical review requirements. All researchers involved in the study received standardized clinical physician training.

[0095] 4 Treatment methods

[0096] The subjects in this study were randomly divided into two groups: the treatment group received Xuanjiang Zhike Pills combined with rabeprazole, and the control group received rabeprazole combined with Xuanjiang Zhike Pills as a placebo.

[0097] 4.1 Treatment group: Xuanjiang Zhike Pills combined with rabeprazole.

[0098] This invention relates to Xuanjiang Zhike Pills, composed of 3g Coptis chinensis, 3g Evodia rutaecarpa, 12g Gardenia jasminoides (processed), 9g Fritillaria thunbergii, 20g Cuttlebone, 12g Pinellia ternata (processed), 9g Belamcanda chinensis, 6g Ephedra sinica (processed), 3g Asarum heterotropoides, 3g Schisandra chinensis, and 3g Zingiber officinale (dried). The traditional Chinese medicine dosage form used in this study is pills, manufactured by Shanghai Wanshicheng Pharmaceutical Co., Ltd., batch number 202303201, with each bag weighing 8g.

[0099] Instructions for use: Patients should take one packet of the pills with warm water 30 to 60 minutes after breakfast and dinner each day for 8 consecutive weeks.

[0100] Rabeprazole sodium enteric-coated capsules are supplied by Jiangsu Jichuan Pharmaceutical Co., Ltd., batch number 2307115, with a specification of 20mg / capsule. Patients should take one capsule orally on an empty stomach before breakfast daily for a course of 8 weeks.

[0101] 4.2 Control group: Xuanjiang Zhike Pills placebo combined with rabeprazole.

[0102] Xuanjiang Zhike Pills placebo: Xuanjiang Zhike Pills were diluted to a 10% dose and 90% excipients were added. The Chinese medicine dosage form used in this study was pills, which were commissioned to Shanghai Wanshicheng Pharmaceutical Co., Ltd., with batch number 202303201 and each bag weighing 8 grams.

[0103] Instructions for use: Patients should take one packet of the pills with warm water 30 to 60 minutes after breakfast and dinner each day for 8 consecutive weeks.

[0104] Rabeprazole sodium enteric-coated capsules are supplied by Jiangsu Jichuan Pharmaceutical Co., Ltd., batch number 2307115, with a specification of 20mg / capsule. Patients should take one capsule orally on an empty stomach before breakfast daily for a course of 8 weeks.

[0105] 5 Observation Indicators

[0106] 5.1 Clinical symptom score

[0107] The clinical symptom scoring scale used in this study was based on the diagnostic criteria of the 2017 Expert Consensus on Traditional Chinese Medicine Diagnosis and Treatment of Gastroesophageal Reflux Disease. [3] And in accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs" [4] Proposed:

[0108] The patients' clinical symptoms were classified into four levels according to severity: asymptomatic, mild, moderate, and severe. If the patient reported no symptoms related to reflux cough, they were classified as asymptomatic; symptoms occurred occasionally, no more than once a day, and had no significant impact on work or rest, which was classified as mild; moderate symptoms occurred 1 to 3 times a day, or occurred occasionally; and severe symptoms were characterized by more than 3 times a day, or frequent occurrences, severely interfering with the subjects' normal work, rest, social, and recreational activities. The main symptoms in the TCM syndrome scoring system designed for this study included chronic cough or nocturnal choking cough, heartburn, and reflux, with scores of 0, 2, 4, and 6 points for the asymptomatic, mild, moderate, and severe levels, respectively. Secondary symptoms included flank or epigastric distension and pain, a feeling of belching or acid reflux, stomach discomfort or burning pain, mood swings such as irritability, dry mouth and bitter taste, throat discomfort, a foreign body sensation, and low mood such as anxiety, depression, irritability, and sadness, with scores of 0, 1, 2, and 3 points for the asymptomatic, mild, moderate, and severe levels, respectively. The score ranges from 0 to 45 points, and the severity of clinical symptoms can be determined based on the score.

[0109] 5.2 Cough Visual Analogue Scale (VAS)

[0110] The patient marks 0 according to their own feelings. ～The severity of the cough is indicated by marking corresponding scales on a 10cm straight line. 0 represents no cough, and 10 represents a severe cough that affects the patient's life and work; the higher the score, the more severe the cough. Compared to the cough symptom score, the VAS scoring system has a more detailed gradation, which helps in longitudinally comparing cough severity before and after treatment.

[0111] 5.3 Simple Cough Severity Rating Scale

[0112] The Simplified Cough Severity Rating Scale (CET) comprehensively assesses several key aspects of a patient's cough, including the frequency and severity of daytime coughs, the degree of sleep disturbance caused by nighttime coughs, the severity of coughs, and the impact of cough symptoms on the patient's quality of life and psychological state. It comprises five items, scored on a scale of 1 to 5: asymptomatic, rare, some, frequent, and common. Higher scores indicate more severe clinical symptoms. [5,6] .

[0113] 5.4 Leicester Cough Quality of Life Questionnaire (Chinese Version)

[0114] The Chinese version of the Leicester Cough Quality of Life Questionnaire (LCQ) consists of 19 items, covering three areas: physical condition, mental health, and social functioning. [7] The 19 questions were assessed based on the frequency of the patient's symptoms over the past two weeks, with options categorized into seven levels (① always, ② most of the time, ③ often, ④ sometimes, ⑤ occasionally, ⑥ almost never, ⑦ never), with scores ranging from 1 to 7. Higher scores indicated more severe clinical symptoms. [8,9] The LCQ questionnaire is a short, effective, and widely used health questionnaire for patients with cough, with advantages in practicality, reliability, and repeatability. [7,10] .

[0115] 5.5 Safety Indicator Observation

[0116] Before enrollment, patients underwent routine physical examinations (blood pressure, pulse, respiration, height, weight, and body temperature). Safety indicators were tested once before and after treatment in both groups, including complete blood count, stool routine + occult blood test, urine routine, liver and kidney function tests, and electrocardiogram. Adverse events that occurred during the clinical study were closely observed and recorded.

[0117] 6 Statistical Methods

[0118] SPSS 22.0 statistical analysis software was used to analyze the statistical data: For continuous data, if they conformed to a normal distribution, a t-test was used, and the data were described using mean ± standard deviation; otherwise, a rank-sum test was used, and the data were described using median and interquartile range. For categorical data, a χ² test was used; a p-value < 0.05 indicated statistical significance.

[0119] 7. Results

[0120] 7.1 Baseline Data Comparison

[0121] In this study, 68 patients with GERC of the liver-stomach stagnation-heat type, meeting the diagnostic criteria of both traditional Chinese and Western medicine, were initially screened to participate in the clinical trial. After 8 weeks of treatment, 63 patients completed the trial. During the treatment period, 5 patients discontinued treatment. Among them, 3 patients in the experimental group withdrew from the trial because their cough symptoms did not significantly improve after two weeks of medication. 2 patients dropped out of the control group; one discontinued medication due to a cold, and the other was lost to follow-up due to inability to be contacted. The dropout rate met the criteria (dropout rate ≈ 7.4% < 10%). All 5 patients were dropout cases and were therefore not included in the statistics, as shown in Table 1.

[0122] Table 1. Case details of the two groups (unit: number of cases)

[0123]

[0124] 7.2 Clinical Symptom Score

[0125] Before treatment, the TCM clinical symptom scores of the two groups were compared, and the difference was not statistically significant (P>0.05). After treatment, the TCM clinical symptom scores and efficacy differences between the two groups were compared, and the differences were statistically significant (P<0.05). The TCM clinical symptom scores of the control group after treatment were significantly different from those before treatment (P<0.05). The TCM clinical symptom scores of the experimental group and the control group after treatment were significantly different (P<0.05), and the efficacy differences between the two groups were also significantly different (P<0.05), as shown in Table 2.

[0126] Table 2 Comparison of clinical symptom scores between the two groups [M(P25,P75), points]

[0127]

[0128]

[0129] Note: Z1 and P1 are intra-group comparison results; Z2 and P2 are inter-group comparison results; *** indicates comparison with pre-treatment, P<0.001; # indicates comparison with experimental group, P<0.05.

[0130] 7.3 VAS score comparison

[0131] Before treatment, the visual analog scale (VAS) scores for cough were compared between the two groups, and there was no statistically significant difference (P>0.05), allowing for comparison between the two groups. After treatment, the VAS scores and the difference in treatment efficacy between the two groups were compared, and the differences were statistically significant (P<0.05), as shown in Table 3.

[0132] Table 3 Comparison of VAS scores between the two groups [M(P25,P75), points]

[0133]

[0134] Note: Z1 and P1 are within-group comparison results; Z2 and P2 are between-group comparison results; *** This indicates a comparison with pre-treatment levels, where P < 0.001; # This indicates that compared with the experimental group, P<0.05.

[0135] 7.4 Simple Cough Severity Score

[0136] Before treatment, the Simple Cough Severity Scores (CET) of the two groups were compared, and the difference was not statistically significant (P>0.05), so they could be compared. After treatment, the CET scores and efficacy differences between the two groups were compared within and between groups, and the differences were statistically significant (P<0.05), as shown in Table 4.

[0137] Table 4 Comparison of CET scores between the two groups ( point)

[0138]

[0139]

[0140] Note: t1 and P1 are within-group comparison results; t2 and P2 are between-group comparison results; *** This indicates a comparison with pre-treatment levels, where P < 0.001; # This indicates that compared with the experimental group, P<0.05.

[0141] 7.5 Leicester Cough Quality of Life Questionnaire Score

[0142] Before treatment, the Leicester Cough Quality of Life Questionnaire (LCQ) scores of the two groups were compared, and there was no statistically significant difference (P>0.05), so they could be compared. After treatment, the LCQ scores and the difference in efficacy between the two groups were compared, and the differences were statistically significant (P<0.05), as shown in Table 5.

[0143] Table 5 Comparison of LCQ scores between the two groups ( point)

[0144]

[0145] Note: t1 and P1 are within-group comparison results; t2 and P2 are between-group comparison results; *** This indicates a comparison with pre-treatment levels, where P < 0.001; # This indicates that compared with the experimental group, P<0.05.

[0146] 7.6 Safety Indicator Observation

[0147] During the trial, liver and kidney function were tested before and after treatment, and no significant abnormalities were found, nor were any drug allergies detected.

[0148] 8. Conclusion

[0149] In summary, a traditional Chinese medicine compound for treating reflux cough has achieved good clinical efficacy, effectively improving the clinical symptoms and quality of life of patients with reflux cough, and has good safety.

[0150] References

[0151] [1] Asthma Group of Chinese Society of Respiratory Diseases. Guidelines for the diagnosis and treatment of cough (2021) [J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2022, 45(01):13-46.

[0152] [2] Chinese Society of Gastroenterology. 2020 Chinese Expert Consensus on Gastroesophageal Reflux Disease [J]. Chinese Journal of Gastroenterology, 2020, 40(10):649-663.

[0153] [3] Spleen and Stomach Diseases Branch of China Association of Traditional Chinese Medicine. Expert consensus on TCM diagnosis and treatment of gastroesophageal reflux disease (2017) [J]. Chinese Journal of Integrated Traditional and Western Medicine on Digestion, 2017.

[0154] [4] Zheng Xiaoyu (ed.). Guidelines for Clinical Research of New Traditional Chinese Medicines (Trial) [M]. Beijing: China Medical Science and Technology Press, 2002: 124-129.

[0155] [5] K,HOLZINGER F,TRAUTH J,et al.Clinical practice guideline:Chronic cough[J].Deutsches International, 2022.

[0156] [6]ZHAN W, ZHANG L, JIANG M, et al. A new simple score of chronic cough:cough evaluation test[J]. BMC Pulmonary Medicine, 2020, 20(1).

[0157] [7] Liu Xianbing, Li Fang, Chen Xiaoping, et al. Study on the distribution of etiology and differences in quality of life among young and middle-aged patients with chronic cough [J]. Chinese General Practice, 2015, 18(28):3430-3434.

[0158] [8]MA W,YU L,WANG Y,et al.Changes in health-related quality of lifeand clinical implications in Chinese patients with chronic cough[J].Cough,2009,5:7.

[0159] [9] Zhu Shengliang, Liu Chunfang, Li Li, et al. Clinical observation on the efficacy and quality of life of 64 patients with gastroesophageal reflux cough treated with Tongjiang Hewei Decoction: The 24th National Academic Conference on Spleen and Stomach Diseases of the Chinese Association of Traditional Chinese Medicine [C], Kunming, Yunnan, China, 2012.

[0160]

[10] ANDRES C, IHRLER S, PUCHTA U, et al. Merkel cell polyomavirus isprevalent in a subset of small cell lung cancer: a study of 31patients[J]. Thorax, 2009, 64(11):1007-1008.

[0161] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.

Claims

1. The application of a traditional Chinese medicine composition for treating reflux cough in the preparation of a drug for treating reflux cough, wherein the reflux cough is a reflux cough due to liver and stomach heat stagnation, and the traditional Chinese medicine composition is made from the following raw materials in parts by weight: Coptis chinensis 2-4 parts, Evodia rutaecarpa 2-4 parts, Gardenia jasminoides (fried) 11-13 parts, Fritillaria thunbergii 8-10 parts, Sepia esculenta 19-21 parts, Pinellia ternata (processed) 11-13 parts, Belamcanda chinensis 8-10 parts, Ephedra sinica (processed) 5-7 parts, Asarum heterotropoides 2-4 parts, Schisandra chinensis 2-4 parts, and Zingiber officinale (dried) 2-4 parts.

2. Use according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 3 parts Coptis chinensis, 3 parts Evodia rutaecarpa, 12 parts Gardenia jasminoides (roasted), 9 parts Fritillaria thunbergii, 20 parts Cuttlebone, 12 parts processed Pinellia ternata, 9 parts Belamcanda chinensis, 6 parts processed Ephedra sinica, 3 parts Asarum heterotropoides, 3 parts Schisandra chinensis, and 3 parts dried ginger.

3. Use of a pharmaceutical composition for treating reflux cough in the preparation of a medicament for treating reflux cough, wherein the reflux cough is liver-stomach stagnated heat syndrome reflux cough, characterized in that, The pharmaceutical composition comprises rabeprazole and a traditional Chinese medicine composition, which is made from the following raw materials in parts by weight: Coptis chinensis 2-4 parts, Evodia rutaecarpa 2-4 parts, Gardenia jasminoides (roasted) 11-13 parts, Fritillaria thunbergii 8-10 parts, Sepia esculenta 19-21 parts, Pinellia ternata (processed) 11-13 parts, Belamcanda chinensis 8-10 parts, Ephedra sinica (processed) 5-7 parts, Asarum heterotropoides 2-4 parts, Schisandra chinensis 2-4 parts, and Zingiber officinale (dried) 2-4 parts.

4. Use according to claim 3, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 3 parts Coptis chinensis, 3 parts Evodia rutaecarpa, 12 parts Gardenia jasminoides (roasted), 9 parts Fritillaria thunbergii, 20 parts Cuttlebone, 12 parts processed Pinellia ternata, 9 parts Belamcanda chinensis, 6 parts processed Ephedra sinica, 3 parts Asarum heterotropoides, 3 parts Schisandra chinensis, and 3 parts dried ginger.

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