A traditional Chinese medicine composition for treating bronchiectasis

Abstract

The application belongs to the technical field of medicine, and particularly relates to a traditional Chinese medicine composition for treating bronchiectasis. The traditional Chinese medicine composition is composed of the following traditional Chinese medicines: rhizoma phragmitis, raw semyen of job's tears, winter melon seed, persicae semen, platycodon grandiflorum, semen balsamni, dioscorea, prepared rhizome of rehmannia, radix codonopsis, pinellia ternata, poria cocos and pericarpium citri reticulatae. The traditional Chinese medicine composition is combined together, and through scientific compounding, each medicine plays a synergistic effect, realizes a significant treatment effect on bronchiectasis, has a high clinical application value, and has a wide application prospect.

Description

A traditional Chinese medicine composition for treating bronchiectasis Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a traditional Chinese medicine composition for treating bronchiectasis. Background Technology

[0002] 1.1 Hypersecretion of airway mucus is an important pathophysiological feature of bronchiectasis.

[0003] Bronchiectasis (BE) is caused by recurrent airway infections from various sources, leading to repeated bronchial damage and obstruction, structural remodeling of the bronchial walls, and ultimately, irreversible bronchial dilation. Chronic cough and sputum production are among the main clinical manifestations of BE, with approximately 75%-100% of BE patients experiencing sputum production. Therefore, airway mucus hypersecretion (AMH) is a fundamental pathophysiological and clinical feature of BE. Patients with AMH have reduced airway mucus clearance capacity, causing mucus to accumulate in the airways. This retained mucus obstructs the airways, restricting airflow, and provides favorable conditions for pathogen colonization, resulting in chronic and recurrent respiratory infections. This, in turn, damages the bronchial walls, impacts patients' quality of life, and increases the risk of hospitalization. Therefore, improving AMH status is a crucial aspect of BE treatment and is considered a potential way to break the vicious cycle of BE.

[0004] Bleeding bronchitis (BE) is characterized by airway inflammation due to neutrophil migration and secondary secretion of various inflammatory mediators that cause tissue damage. Neutrophil elastase (NE) is one of the important inflammatory mediators released by neutrophils, which can degrade the extracellular matrix [4], causing damage to bronchopulmonary tissue. NE accounts for about 80% of the total degradative activity of all proteolytic enzymes. In addition to degrading elastin, it can also degrade collagen, proteoglycans, fibronectin, etc. NE promotes the prolongation of inflammation and bacterial infection, and causes a state of hypersecretion of mucus. Its concentration and activity can reflect the activity and severity of the disease. Therefore, some scholars have proposed that comprehensive treatment targeting inflammation, NE, and infection factors should be adopted for BE in order to achieve better results.

[0005] 1.2 Phlegm-heat accumulation in the lungs and deficiency of both spleen and kidney are the main syndrome types in the stable phase of bronchiectasis.

[0006] BE can be categorized under the traditional Chinese medicine terms "lung abscess" and "cough". The "Medical Laws" states: "Lung abscess is caused by the fire accumulated in the five internal organs and the heat stagnating in the stomach, which ascends to the lungs. When the lungs are scorched by the fire and heat, the blood congeals, and the congealed blood forms phlegm, thus forming a small abscess." This indicates that fire and heat are important pathological factors in lung abscess. BE patients often cough up yellow purulent sputum, which is copious and thick, accompanied by fever, sweating, and dry mouth with a thirst. This is a sign of phlegm and heat accumulating in the lungs. This is because of external heat pathogens or emotional distress, which causes qi stagnation and fire, which steams the lung channels and condenses fluids into phlegm. "The lungs are the receptacle for phlegm", thus causing phlegm and heat to accumulate in the lungs. If BE (Behavioral Encephalopathy) has a long course, it is common to see a combination of phlegm-heat accumulation in the lungs and deficiency of both the spleen and kidneys. These patients are more likely to have a long disease course and have repeatedly used antibiotics. Clinical manifestations, in addition to cough and yellow phlegm (symptoms of lung heat), often include fatigue, weight loss, poor appetite, lower back and knee weakness, lethargy, aversion to cold, loose or sticky stools, a swollen tongue, and a greasy tongue coating (symptoms of spleen and kidney deficiency). Prolonged cough leads to lung qi deficiency. Since the lungs are the child organ of the spleen, the child organ steals qi from the mother organ, resulting in spleen deficiency. Spleen deficiency prevents the transformation and transportation of fluids, leading to the accumulation of dampness and phlegm. The kidneys are the root of qi, responsible for the vaporization and transformation of fluids. When phlegm accumulates in the body, it obstructs the warming and transforming functions of kidney yang, eventually leading to kidney deficiency as well. Therefore, a deficiency of both the spleen and kidneys is observed.

[0007] Currently available Chinese herbal medicine products can be summarized as follows: Compound Fresh Bamboo Sap Liquid: Clears heat and resolves phlegm, relieves cough; used for coughs due to phlegm-heat, with thick yellow phlegm. Snake Gallbladder and Fritillaria Liquid: Dispels wind and relieves cough, eliminates phlegm and dissipates nodules. Used for wind-heat cough, excessive phlegm, wheezing, chest tightness, difficulty expectorating phlegm, or persistent cough. Phlegm-Clearing Oral Liquid: Clears the lungs and resolves phlegm. Used for cough, excessive phlegm, and wheezing caused by phlegm-heat obstructing the lungs; also for acute and chronic bronchitis with the above symptoms. Er Chen Wan: Drys dampness and resolves phlegm, regulates qi and harmonizes the stomach. Used for cough, excessive phlegm, chest and abdominal distension, nausea and vomiting caused by phlegm-dampness stagnation. Buckwheat Tablets: Clears heat and detoxifies, drains pus and removes blood stasis, eliminates phlegm, relieves cough and asthma. Used for acute lung abscess, acute and chronic bronchitis, wheezing chronic bronchitis, bronchial asthma, and bacterial dysentery. Symptoms include coughing up foul-smelling purulent bloody sputum or cough with excessive phlegm, wheezing with phlegm, and bloody or purulent stools.

[0008] There are also many traditional Chinese medicine prescriptions for the treatment of bronchiectasis, as follows:

[0009] Chinese Patent CN 113648381 discloses a traditional Chinese medicine composition, the raw materials of which, by weight, include: 10-30 parts of Codonopsis pilosula, 15-45 parts of processed Astragalus membranaceus, 5-15 parts of Bupleurum chinense, 5-15 parts of Peucedanum praeruptorum, 3-9 parts of Coptis chinensis, 5-15 parts of Prunus mume, 15-45 parts of Houttuynia cordata, 5-15 parts of Bletilla striata, 15-45 parts of Coix lacryma-jobi, 5-15 parts of Platycodon grandiflorus, and 3-9 parts of processed Glycyrrhiza uralensis. The invention also provides a method for preparing the traditional Chinese medicine composition and its pharmaceutical uses. This traditional Chinese medicine composition can effectively inhibit Pseudomonas aeruginosa and treat bronchiectasis caused by Pseudomonas aeruginosa colonization.

[0010] Chinese Patent CN 114159533 relates to a traditional Chinese medicine composition for treating multidrug-resistant bacterial infections and its application. The composition is made from the following raw materials in parts by weight: *Pyrola rotundifolia*, *Prunella vulgaris*, *Hedyotis diffusa*, *Astragalus membranaceus*, *Stemona japonica*, *Fagopyrum diffusa*, *Viola yedoensis*, *Lithospermum erythrorhizon*, *Polygonatum sibiricum* (processed), *Atractylodes macrocephala* (stir-fried with wheat bran), *Poria cocos*, and *Bletilla striata*. Its advantages are: it can be used alone or in combination with antibacterial drugs, mainly for treating multidrug-resistant tuberculosis, community-acquired pneumonia, hospital-acquired pneumonia, secondary infections of bronchiectasis, and lung abscess caused by multidrug-resistant bacteria such as *Mycobacterium tuberculosis*, methicillin-resistant *Staphylococcus aureus*, and multidrug-resistant *Pseudomonas aeruginosa*. It can effectively improve the clearance efficiency of pathogenic microorganisms, improve lung pathological damage, stabilize the lung microenvironment, and significantly alleviate clinical symptoms secondary to infection damage, such as cough, sputum production, hemoptysis, fatigue, spontaneous sweating, night sweats, and dry throat.

[0011] Chinese Patent CN 108066663 relates to a traditional Chinese medicine composition for treating lung problems, which is made from the following raw materials in parts by weight: 15-60 parts of reed rhizome, 15-60 parts of coix seed, 10-50 parts of winter melon seed, 3-25 parts of peach kernel, 3-20 parts of platycodon root, 5-45 parts of prepared licorice root, 3-30 parts of codonopsis root, 10-50 parts of ophiopogon root, 5-30 parts of schisandra fruit, 3-45 parts of aster root, 5-35 parts of cinnamon twig, 3-40 parts of poria cocos, 3-30 parts of peony bark, 5-30 parts of peony root, and 1-20 parts of stevia. Compared with the prior art, the beneficial effects of the present invention are as follows: When the various Chinese herbal components of the present invention are combined together, their synergistic effect on the treatment of lung problems is very obvious, which can multiply the effects of promoting blood circulation, clearing the lungs, moistening the lungs, and astringing the lungs, so as to achieve the purpose of treating both the symptoms and the root cause of lung problems; among them, stevia makes the Chinese herbal composition have a taste that is easy for the public to accept to a certain extent, so that the medication can be continued until the lung problems are cured. Summary of the Invention

[0012] The purpose of this invention is to provide a traditional Chinese medicine composition for treating bronchiectasis, the prescription of which is a lung-clearing and phlegm-resolving formula. It has been used in our hospital for many years with definite clinical efficacy, strong patient applicability, and is suitable for further large-scale production.

[0013] Furthermore, the aforementioned traditional Chinese medicine composition comprises the following traditional Chinese medicines: reed rhizome, raw coix seed, winter melon seed, peach kernel, platycodon root, euryale seed, yam, prepared rehmannia root, codonopsis root, pinellia tuber, poria cocos, and tangerine peel.

[0014] Furthermore, the Pinellia ternata mentioned is processed Pinellia ternata. Through optimization of processed Pinellia ternata, ginger-processed Pinellia ternata, and purified Pinellia ternata, the inventors found that using processed Pinellia ternata as a component of traditional Chinese medicine can significantly improve efficacy, superior to ginger-processed Pinellia ternata (Comparative Example 2) and purified Pinellia ternata. The inventors believe that this may be because the step of adding alum and boiling Pinellia ternata together during the preparation process of ginger-processed Pinellia ternata reduces the alkaloids in Pinellia ternata, ultimately leading to a decrease in efficacy; it is also possible that the formula requires only processed Pinellia ternata, and using other types of Pinellia ternata alters the overall structure of the drug, thus reducing efficacy.

[0015] Furthermore, calculated by weight ratio, the following ingredients are included: 3-30 parts by weight of reed rhizome, 10-60 parts by weight of raw coix seed, 5-30 parts by weight of winter melon seed, 3-10 parts by weight of peach kernel, 3-20 parts by weight of platycodon root, 5-30 parts by weight of euryale seed, 5-30 parts by weight of yam, 6-28 parts by weight of prepared rehmannia root, 6-28 parts by weight of codonopsis root, 3-10 parts by weight of prepared pinellia tuber, 6-28 parts by weight of poria cocos, and 5-20 parts by weight of tangerine peel.

[0016] In a preferred embodiment of the present invention, the ingredients are calculated by weight ratio as follows: 18 parts by weight of reed rhizome, 30 parts by weight of raw coix seed, 15 parts by weight of winter melon seed, 5 parts by weight of peach kernel, 11 parts by weight of platycodon root, 15 parts by weight of euryale seed, 15 parts by weight of yam, 15 parts by weight of prepared rehmannia root, 15 parts by weight of codonopsis root, 7 parts by weight of prepared pinellia tuber, 15 parts by weight of poria cocos, and 10 parts by weight of tangerine peel.

[0017] In a preferred embodiment of the present invention, the ingredients are calculated by weight ratio as follows: 20 parts by weight of reed rhizome, 34 parts by weight of raw coix seed, 17 parts by weight of winter melon seed, 6.5 parts by weight of peach kernel, 11.5 parts by weight of platycodon root, 16.5 parts by weight of euryale seed, 17.8 parts by weight of yam, 17 parts by weight of prepared rehmannia root, 17 parts by weight of codonopsis root, 2.6 parts by weight of prepared pinellia tuber, 17 parts by weight of poria cocos, and 12.5 parts by weight of tangerine peel.

[0018] In a preferred embodiment of the present invention, the ingredients are calculated by weight as follows: 20 parts of reed rhizome, 15 parts of raw coix seed, 15 parts of winter melon seed, 6 parts of peach kernel, 10 parts of platycodon root, 20 parts of fox nut, 20 parts of yam, 10 parts of prepared rehmannia root, 10 parts of codonopsis root, 9 parts of prepared pinellia tuber, 10 parts of poria cocos, and 10 parts of tangerine peel.

[0019] Furthermore, the traditional Chinese medicine composition also includes a pharmaceutically acceptable carrier. The carrier includes one or more of fillers, disintegrants, binders, and lubricants. The excipients required for the drug dosage form depend on the dosage form; for example, sweeteners or preservatives can be added to oral liquids.

[0020] Furthermore, the dosage form of the traditional Chinese medicine composition is an oral dosage form. The dosage form includes oral liquid, compound preparation, decoction, pill, capsule, tablet, granule, and powder.

[0021] A second objective of this invention is to provide the use of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for treating bronchiectasis.

[0022] Although the stated application is for bronchiectasis, it can be widely used for complications of bronchiectasis, such as pneumonia, lung abscess, pulmonary gangrene, empyema, and pyopneumothorax caused by bronchiectasis. When extensive fibrosis occurs in the lung tissue and the pulmonary capillary bed is severely damaged, it can lead to increased pulmonary artery resistance, pulmonary hypertension, and chronic cor pulmonale.

[0023] The medicinal parts, properties, and processing methods of the raw materials described in this invention are found in the 2020 edition of the Chinese Pharmacopoeia. For example, in the preparation of processed Pinellia ternata, Pinellia ternata is taken, separated by size, and soaked in water until there is no dry core inside, then removed; a suitable amount of licorice is taken, decocted twice with water, the decoctions are combined, poured into lime solution prepared with an appropriate amount of water, stirred well, and the soaked Pinellia ternata is added, soaked, stirred 1-2 times a day, and the pH value of the soaking solution is kept above 12, until the cross-section is uniformly yellow and there is a slight numbing sensation on the tongue when tasted, then removed, washed, and air-dried or oven-dried to obtain the product.

[0024] Bronchiectasis is often categorized under the traditional Chinese medicine (TCM) concept of "lung abscess." Clinical practice has revealed that long-term bronchiectasis patients often exhibit symptoms of lung heat, such as coughing up yellow or purulent sputum, while also experiencing symptoms of spleen and kidney yang deficiency, such as aversion to cold, abdominal distension, and diarrhea. This often presents as a complex mixture of cold and heat, with an upper excess and lower deficiency. Only by combining cold and heat treatments to clear the upper heat and tonify the lower deficiency can the condition be effectively treated. The disease is primarily characterized by a combination of deficiency and excess, and the TCM theory proposes that "lung and kidney deficiency, with phlegm-heat accumulating in the lungs" is a common pathogenesis in patients with high airway mucus secretion during the stable phase of bronchiectasis. Existing TCM formulas often have a single effect, either clearing the lungs and resolving phlegm or tonifying the spleen and resolving phlegm. Simply clearing heat and resolving phlegm weakens the lower body, while simply tonifying the deficiency exacerbates lung heat, creating a therapeutic contradiction. This invention seeks to target the root cause of phlegm formation, using a combination of cold and heat treatments to treat phlegm from the spleen and kidneys, and clear phlegm from the lungs, thereby improving the state of high airway mucus secretion.

[0025] Compared with the prior art, the beneficial effects achieved by the present invention are as follows:

[0026] 1) The formulation of this invention is based on the mechanism of action and has a clear efficacy. Reed rhizome is the principal herb, specifically used to clear heat and drain pus, thus clearing phlegm from the lungs. Codonopsis pilosula and Coix lacryma-jobi are assistant herbs to strengthen the spleen and replenish qi, clear heat and promote diuresis; Pinellia ternata dries dampness and resolves phlegm; Euryale ferox and Dioscorea opposita tonify the spleen and kidneys; Rehmannia glutinosa nourishes kidney yin. Tangerine peel and Poria cocos are adjuvant herbs to promote qi circulation, diuresis, and strengthen the middle jiao. Winter melon seed, being cold and slippery, is combined with peach kernel to clear heat and invigorate blood, guiding phlegm and heat out of the intestines. Platycodon grandiflorus is the guiding herb to the upper jiao. In this way, phlegm and dampness are eliminated, the middle jiao is strengthened, and the lower jiao is replenished. This not only clears existing phlegm but also prevents the formation of new phlegm, treating both the root cause and the symptoms. It is suitable for patients with bronchiectasis who are in a state of high airway mucus secretion for a long time, with both lung heat and spleen and kidney deficiency, and who have excessive phlegm or difficulty in expectorating.

[0027] 2) This invention uses a combination of Chinese herbal medicines, including reed rhizome, raw coix seed, winter melon seed, peach kernel, platycodon root, euryale seed, yam, prepared rehmannia root, codonopsis root, prepared pinellia tuber, poria cocos, and tangerine peel. Through scientific formulation, each herb exerts a synergistic effect, achieving a significant therapeutic effect on bronchiectasis. It has high clinical application value and broad application prospects.

[0028] the term

[0029] As used herein, the term "pharmaceuticalally acceptable" refers to a substance that is suitable for use in humans and / or animals without excessive adverse side effects (such as toxicity, irritation, and allergic reactions), i.e., a substance with a reasonable benefit / risk ratio.

[0030] As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier used for the administration of therapeutic agents, including various excipients and diluents. This term refers to pharmaceutical carriers that are not essential active ingredients themselves and do not cause excessive toxicity upon administration. Suitable carriers are well known to those skilled in the art.

[0031] As used herein, "parts by weight" can be any fixed weight expressed in milligrams, grams, or kilograms (e.g., 1 mg, 0.1 g, 1 g, 10 g, 1 kg, etc.). For example, a composition consisting of 2 parts by weight of component a and 8 parts by weight of component b can be a composition consisting of 2 g of component a + 8 g of component b, or 20 g of component a + 80 g of component b, etc. In the composition, the percentage content of a certain component = (the number of parts by weight of that component / the sum of the number of parts by weight of all components) × 100%. Therefore, in a composition consisting of 2 parts by weight of component a and 8 parts by weight of component b, the content of component a is 20%, and the content of component b is 80%. Attached Figure Description

[0032] Figure 1: Analysis of cough symptom domain (COUS) scores in the control group and the experimental group; P1, P2, P3, P4, P5, and P6 in the experimental group were all <0.05; P3, P5, and P6 in the control group were all <0.05.

[0033] Figure 2: Analysis of cough influence domain (COUI) scores in the control group and the experimental group; in the experimental group, P1, P2, P3, P5, and P6 were all <0.05, and P4 was >0.05; in the control group, P3 was <0.05, and P1, P2, P4, P5, and P6 were >0.05.

[0034] Figure 3: Analysis of the sputum symptom domain (SPUS) scores of the control group and the experimental group; P1, P2, P3, P4, P5, and P6 in the experimental group were all <0.05; P1 and P5 in the control group were both <0.05, while P2, P3, P4, and P6 were >0.05.

[0035] Figure 4: Analysis of the sputum influence domain (SPUI) scores of the control group and the experimental group; P2, P3, P5, and P6 in the experimental group were all <0.05, while P1 and P4 were >0.05; P1, P3, P4, and P5 in the control group were all <0.05, while P6 was >0.05.

[0036] Figure 5: Analysis of 24-hour sputum volume / ml in the control group and the experimental group; P1, P2, P3, P4, and P5 in the experimental group were all <0.05, and P6 was >0.05; P1, P2, and P3 in the control group were all <0.05, and P4, P5, and P6 were >0.05; the experimental group was significantly lower than the control group at each observation time point in the inter-group comparison, P<0.05.

[0037] Figure 6: Analysis of the total symptom quantitative scores of the control group and the experimental group; P1, P2, P3, P4, P5, and P6 in the experimental group were all <0.05; P1, P2, P3, P4, P5, and P6 in the control group were all <0.05.

[0038] Figure 7: Analysis of airway mucus hypersecretion symptom scores in the control group and the experimental group. In the experimental group, P1, P2, P3, P4, and P5 were all <0.05, and P6 was >0.05; in the control group, P1, P2, P3, and P5 were all <0.05, and P4 and P6 were >0.05.

[0039] Figure 8: WBC (10) of various embodiments 9 ·L -1 The content detection results of Examples 1 and 4 showed significant differences compared with Comparative Example 1 (P<0.05). Examples 1-4 showed significant differences compared with Comparative Examples 3-5 (P<0.05).

[0040] Figure 9: LYM (10) of various embodiments 9 ·L -1 The content detection results of Examples 1 and 4 showed significant differences compared with Comparative Example 1 (P<0.05). Examples 1-4 showed significant differences compared with Comparative Examples 3-5 (P<0.05).

[0041] Figure 10: Pseudomonas aeruginosa counts in each embodiment / 10 8 CFU·L -1 The test results of Examples 1-4 showed significant differences compared with those of Comparative Examples 1-5 (P<0.01).

[0042] Figure 11: Detection results of IL-8 (μg / L) content in each example. Examples 1-4 showed significant differences compared with Comparative Examples 1-5 (P<0.01).

[0043] Figure 12: Detection results of TNF-a (μg / L) content in each example. There were significant differences between Examples 1-4 and Comparative Examples 1-5 (P<0.01). Detailed Implementation

[0044]

[0045] The following detailed description of specific embodiments further illustrates the content of the present invention, but it should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following embodiments. The following embodiments are used to illustrate the technical solutions of the present invention and not to limit the scope of protection of the present invention. Modifications or equivalent substitutions made by those skilled in the art to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention shall still fall within the scope of protection of the present invention.

[0046] Example 1: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0047]

[0048] Take the above-mentioned medicinal materials, add 15 times the amount of water and decoct twice, the first time for 1 hour and the second time for 0.5 hours. Combine the two decoctions, concentrate to about 500ml, filter, and you will get the medicinal liquid. Take it in 1-2 doses.

[0049] Example 2: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0050]

[0051] The preparation process is the same as in Example 1.

[0052] Example 3: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0053]

[0054] The preparation process is the same as in Example 1.

[0055] Example 4: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0056]

[0057] The preparation process is the same as in Example 1.

[0058] Example 5: A granule formulation for bronchiectasis

[0059] Take the raw material according to the weight proportions described in Example 4, add 15 times the amount of water and decoct twice, the first time for 1 hour and the second time for 0.5 hours. Combine the two decoctions and concentrate to about 500 ml. Filter the two decoctions, combine the two filtrates, concentrate to obtain an extract, dry and pulverize the extract to obtain Chinese medicine granules, add 5 times the weight of dextrin to the Chinese medicine granules to obtain granules.

[0060] Example 6: A tablet for bronchiectasis

[0061] Take the raw material according to the weight proportions described in Example 4, add 15 times the amount of water and decoct twice, the first time for 1 hour and the second time for 0.5 hours. Combine the two decoctions and concentrate to about 500 ml. Filter the two decoctions, combine the two filtrates, concentrate to obtain an extract, add 1 weight of sorbitol and 1 weight of microcrystalline cellulose to the extract, vacuum dry, pulverize and granulate, add an appropriate amount of magnesium stearate and compress into tablets.

[0062] Example 7: A capsule for bronchiectasis

[0063] Take the raw material according to the weight proportions described in Example 4, add 15 times the amount of water and decoct twice, the first time for 1 hour and the second time for 0.5 hours. Combine the two decoctions and concentrate to about 500 ml. Filter the two decoctions, combine the two filtrates, concentrate to obtain an extract, add 1 weight of sorbitol and 1 weight of microcrystalline cellulose to the extract, vacuum dry, pulverize and granulate, and fill into capsules.

[0064] Example 8: A compound preparation for bronchiectasis

[0065] Take the raw material according to the weight proportions described in Example 4, add 15 times the amount of water and decoct twice, the first time for 1 hour and the second time for 0.5 hours. Combine the two decoctions and concentrate to about 500 ml. Filter the two decoctions, combine the two filtrates and concentrate to 1.25 times, which is the final product.

[0066] Example 9: An oral liquid for bronchiectasis

[0067] Take the raw material according to the weight proportions described in Example 4, add 15 times the amount of water and decoct twice, the first time for 1 hour and the second time for 0.5 hours. Combine the two decoctions and concentrate to about 500 ml. Filter the two decoctions, combine the two filtrates, concentrate to 1.25 times, and add an appropriate amount of sweetener and sucrose to obtain the final product.

[0068] Example 9: A granule formulation for bronchiectasis

[0069] 20g of reed rhizome, 15g of raw coix seed, 15g of winter melon seed, 6g of peach kernel, 10g of platycodon root, 20g of fox nut, 20g of yam, 10g of prepared rehmannia root, 10g of codonopsis root, 9g of prepared pinellia tuber, 10g of poria cocos, and 10g of dried tangerine peel.

[0070] The preparation process is as follows: add 15 times the amount of water and decoct twice, the first time for 1 hour and the second time for 0.5 hours. Combine the two decoctions and concentrate them to about 500ml. Filter the two decoctions, combine the two filtrates, concentrate them to obtain an extract, dry and pulverize the extract to obtain Chinese medicine granules, add 50% dextrin by weight to obtain granules.

[0071] Comparative Example 1: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0072]

[0073] The preparation process is the same as in Example 1.

[0074] Comparative Example 2: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0075]

[0076] The preparation process is the same as in Example 1.

[0077] Comparative Example 3: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0078]

[0079] The preparation process is the same as in Example 1.

[0080] Comparative Example 4: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0081]

[0082] The preparation process is the same as in Example 1.

[0083] Comparative Example 5: A traditional Chinese medicine composition for bronchiectasis, with the following dosage and composition:

[0084] 30g of reed rhizome, 30g of coix seed, 20g of winter melon seed, 15g of peach kernel, 10g of platycodon root, 25g of prepared licorice root, 10g of codonopsis root, 20g of ophiopogon root, 10g of schisandra fruit, 25g of aster root, 25g of cinnamon twig, 20g of poria cocos, 10g of peony bark, 20g of peony root, and 10g of stevia. The preparation process is the same as in Example 1.

[0085] I. Clinical Trials

[0086] 1.1 General Information

[0087] From March 2022 to March 2024, our team conducted a double-blind, single-dummy clinical trial involving 68 patients with stable bronchiectasis and airway mucus hypersecretion. Patients were randomly assigned to either the experimental or control group, with 34 patients in each group. There were no significant differences in age, symptoms, or other factors between the two groups (P>0.05).

[0088] 1.2 Method of administration

[0089] Experimental group:

[0090] Qingfei Litan granules, one dose per day, divided into two administrations;

[0091] Prescription composition: 20g reed rhizome, 15g raw coix seed, 15g winter melon seed, 6g peach kernel, 10g platycodon root, 20g fox nut, 20g yam, 10g prepared rehmannia root, 10g codonopsis root, 9g prepared pinellia tuber, 10g poria cocos, 10g dried tangerine peel.

[0092] (The granules are provided by Beijing Kangrentang Pharmaceutical Group Co., Ltd. The preparation and production strictly follow the GMP standard requirements for decoction-free Chinese medicine granules, 5g / bag).

[0093] Control group:

[0094] Placebo: dextrin was used as an excipient to make granules, which were taken twice daily at the same time and in the same dosage as the experimental group.

[0095] Basic treatment

[0096] Both groups of patients received carbocysteine ​​oral solution treatment (10 ml each time, 3 times a day, orally), health education, and postural expectoration. Carbocysteine ​​oral solution (Guangzhou Baiyunshan Pharmaceutical Co., Ltd., National Drug Approval Number H20073871).

[0097] The treatment lasts for 3 months, with a telephone visit every month during the period.

[0098] 1.3 Detection Indicators

[0099] 1.3.1 Main therapeutic indicators

[0100] (1) CASA-Q scoring: The Cough and Sputum Assessment Questionnaire (CASA-Q) was used for scoring. Scores in the four domains of the CASA-Q were recorded, and changes in CASA-Q domain scores before and after treatment and before and after visits were compared between groups and within each group. One score was recorded before enrollment, one score was recorded after the end of medication, and one score was recorded every month during the visit period, for a total of 4 times.

[0101] (2) 24-hour sputum volume: The 24-hour sputum volume was obtained by collecting all sputum coughed up by the subject within 24 hours using a graduated measuring cup. It was recorded once before enrollment, once at the end of medication, and once every month during the follow-up period, for a total of 4 times.

[0102] 1.3.2 Secondary efficacy indicators

[0103] (1) Symptom grading and quantitative scoring: recorded once before enrollment, once after medication, and once every month during the visit, for a total of 4 times.

[0104] (2) Sputum mucoprotein 5AC (MUC5AC) level:

[0105] ① Sputum collection process: Try to collect the patient's first sputum in the morning. Provide the patient with a disposable sterile sputum cup. Before collecting the specimen, the patient should rinse their mouth with water at least 3 times to reduce the influence of oral debris and bacteria. Instruct the patient to cough up deep sputum, with a volume of no less than 3ml. Collect the sputum into the sputum cup and cover it for testing.

[0106] ② Sputum Specimen Processing: Using forceps, remove the densest portion of the sputum and place it in a test tube. Add 4 times the volume of 0.1% dithiothreitol (DTT) to the sputum and mix thoroughly (vortex for a few seconds; do not vortex for too long to avoid cell damage). Place the sputum mixture in a 37°C electric thermostatic water bath for 10 minutes, manually shaking occasionally (2-3 times) to accelerate mixing. Remove the test tube and filter the sputum mixture through a 300-mesh nylon filter. Centrifuge the filtrate at 2000 rpm for 7 minutes and place the supernatant in a numbered sterile container. Refrigerate at -80°C. A third-party company will use enzyme-linked immunosorbent assay (ELISA) to test the extracted sputum supernatant. The supernatant will be refrigerated with dry ice during transport to the third-party testing laboratory. Measurements will be taken twice: once before enrollment and once after medication completion.

[0107] (3) Sputum neutrophil elastase (NE) level: The sputum collection and detection methods are the same as above. The sputum was measured once before enrollment and once after medication, for a total of 2 times.

[0108] 1.4 Results Analysis

[0109] The results showed that Qingfei Litan Recipe could improve the scores of the four domains of the Chronic Cough and Sputum Questionnaire (COUS, COUI, SPUS, SPUI) in patients with airway mucus hypersecretion in the stable stage of bronchiectasis (syndrome of phlegm-heat accumulating in the lung and deficiency of both the spleen and kidney), reduce the symptom quantification score, and decrease the 24-hour sputum volume, thus improving the clinical symptoms and quality of life of patients by alleviating the state of airway mucus hypersecretion. See Figures 1-7 for details.

[0110] It could reduce the neutrophil elastase (NE) and mucin 5AC (MUC5AC) in the sputum of patients, as shown in Tables 1-2 below.

[0111] Table 1 Detection of NE content in the experimental group and the control group before and after treatment

[0112]

[0113] Table 2 Detection of mucin 5AC content in the sputum of the experimental group and the control group before and after treatment

[0114]

[0115] It can be seen from Tables 1 and 2 that there was a highly significant difference in the NE content of the experimental group before and after treatment (P<0.01), while there was no significant difference in the NE content of the control group before and after treatment (P>0.05); there was a highly significant difference in the mucin 5AC in the sputum of the experimental group before and after treatment (P<0.01), while there was a significant difference in the mucin 5AC content of the control group before and after treatment (P<0.05). Generally speaking, the treatment effect of the experimental group was better than that of the control group.

[0116] In Figures 1-7: the control group and the experimental group were at 1 before treatment, 2 one month after treatment, 3 two months after treatment, and 4 three months after treatment; P1, P2, and P3 respectively represent the P values of one month, two months, and three months after treatment compared with before treatment, and P4, P5, and P6 respectively represent the P values of two months after treatment compared with one month after treatment, three months after treatment compared with one month after treatment, and three months after treatment compared with two months after treatment.

[0117] II. Pharmacological experiments

[0118] 2.1 Materials

[0119] Animals: SD rats (SPF) about 4 months old, weighing 200-300 g. Provided by the Experimental Animal Center of Xiyuan Hospital, China Academy of Chinese Medical Sciences (Animal No.: SYXK (Beijing) 2023-0053, Jiangsu Experimental Animal Certificate No. 97001).

[0120] Drugs: The drugs of the embodiments of the present invention.

[0121] The reagent, Pseudomonas aeruginosa solution, involves inoculating a standard Pseudomonas aeruginosa strain onto a culture medium and incubating it at 37°C for 24 hours. Several typical colonies are then washed with physiological saline, and the concentration is adjusted to 10 CFUL using a turbidimetric method. -1 Prepare 2 mL of Pseudomonas aeruginosa solution. Use airway tissue homogenate and interleukin-8 (IL-8) and tumor necrosis factor (TNF-α) kits.

[0122] 2.2 Grouping and Administration

[0123] 2.2.1 Grouping

[0124] 110 rats were randomly divided into 11 groups of 10 rats each. There were no significant differences in body weight and health status among the 11 groups before the experiment (P>0.05).

[0125] 2.2.2 Modeling

[0126] Rats were anesthetized by intraperitoneal injection of 2% pentobarbital sodium 30 mg / kg. The rats were fixed in a supine position. A 1 cm longitudinal incision was made 3 cm below the lip, after routine disinfection, to expose the submandibular muscles and longitudinally dissect the trachea. A 2 mm transverse incision was made in the relatively wide tracheal cartilage space below the thyroid cartilage for endotracheal intubation. The self-made endotracheal tube was slowly extended to approximately 3 cm below the sternal angle; resistance was felt, indicating the right basal lobe of the lung. 0.02 mL of Pseudomonas aeruginosa bacterial solution and 1 mL of gas were rapidly injected into the tube using a microsyringe. The tube was quickly removed, and the fixation board was erected to maintain the rat's vertical position to alleviate respiratory distress. After the rat's breathing stabilized, the tracheal incision was sutured longitudinally, and the neck muscles and skin were sutured transversely. Penicillin G 1×10 U / 100 g / d was administered intraperitoneally for 3 days to prevent wound infection. The rats were also administered 50% glucose solution 100 mL / kg / d by gavage for 3 days. Supplementary provisions will be provided for those who die due to operational errors during the model-making process.

[0127] 2.2.3 Administration

[0128] Rats in Examples 1-4 and Comparative Examples 1-5 were administered the solution by gavage twice daily for 28 consecutive days; rats in the model group were administered 5 ml of physiological saline solution by gavage twice daily for 28 consecutive days.

[0129] 2.3 Detection and Results

[0130] 2.3.1 Detection

[0131] The detection method of Wan Yigang et al.'s bronchiectasis formula on airway inflammation and cytokine effects in a bronchiectasis model was followed.

[0132] 2.3.2 Statistical Analysis

[0133] The obtained data were statistically analyzed using GraphPadPrism software. Quantitative data were analyzed using... The value is indicated by P < 0.05.

[0134] Figure 8-12: Detection results of relevant embodiments.

Claims

1. A traditional Chinese medicine composition for treating bronchiectasis due to phlegm-heat accumulation in the lungs and deficiency of both the spleen and kidneys, characterized in that, It is composed of the following Chinese medicinal herbs in parts by weight: 3-30 parts of reed rhizome, 10-60 parts of raw coix seed, 5-30 parts of winter melon seed, 3-10 parts of peach kernel, 3-20 parts of platycodon root, 5-30 parts of euryale seed, 5-30 parts of yam, 6-28 parts of prepared rehmannia root, 6-28 parts of codonopsis root, 3-10 parts of prepared pinellia tuber, 6-28 parts of poria cocos, and 5-20 parts of tangerine peel; the pinellia tuber mentioned is prepared pinellia tuber.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The ingredients, by weight, are: 18 parts reed rhizome, 30 parts raw coix seed, 15 parts winter melon seed, 5 parts peach kernel, 11 parts platycodon root, 15 parts fox nut, 15 parts yam, 15 parts prepared rehmannia root, 15 parts codonopsis root, 7 parts prepared pinellia tuber, 15 parts poria cocos, and 10 parts tangerine peel.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The ingredients, by weight, are: 20 parts reed rhizome, 34 parts raw coix seed, 17 parts winter melon seed, 6.5 parts peach kernel, 11.5 parts platycodon root, 16.5 parts fox nut, 17.8 parts yam, 17 parts prepared rehmannia root, 17 parts codonopsis root, 2.6 parts prepared pinellia tuber, 17 parts poria cocos, and 12.5 parts tangerine peel.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The ingredients, by weight, are: 20 parts reed rhizome, 15 parts raw coix seed, 15 parts winter melon seed, 6 parts peach kernel, 10 parts platycodon root, 20 parts fox nut, 20 parts yam, 10 parts prepared rehmannia root, 10 parts codonopsis root, 9 parts prepared pinellia tuber, 10 parts poria cocos, and 10 parts tangerine peel.

5. The traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, The traditional Chinese medicine composition also includes a pharmaceutically acceptable carrier.

6. The traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, The dosage form of the traditional Chinese medicine composition is oral liquid, decoction, pill, capsule, tablet, granule or powder.

7. The use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicine for treating bronchiectasis caused by phlegm-heat accumulation in the lungs and deficiency of both the spleen and kidneys.

Images