Qingjin huatan decoction and application thereof in regulating intestinal flora of aecopd patients and improving lung function

Abstract

The application discloses a Qingjin Huatan decoction and application thereof in regulating intestinal flora of AECOPD patients and improving lung function, and belongs to the technical field of traditional Chinese medicine. The Qingjin Huatan decoction is composed of raw medicinal materials in the following mass fractions: Huangqi 10-20 parts, Shanzhizi 6-12 parts, Sangbaipi 6-12 parts, Gualou 10-14 parts, Zhebeimu 6-12 parts, Maidong 6-12 parts, Jiegeng 10-20 parts, Zhimu 6-12 parts, Chenpi 10-20 parts, Fuling 10-20 parts and Zhigancao 4-8 parts. The whole prescription precisely matches the core pathogenesis of the phlegm-heat accumulating in the lung syndrome of acute exacerbation of chronic obstructive pulmonary disease, clears the phlegm-heat evil in the lung, and takes into account the lung yin protection and the protection of the middle-jiao spleen and stomach, attacks the evil without damaging the normal, transforms the phlegm without being too dry to injure the yin, and clears the heat without being too cold to injure the stomach.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a Qingjin Huatan Decoction and its application in regulating the intestinal flora and improving lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Background Technology

[0002] Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory emergency and critical illness in clinical practice. Phlegm-heat accumulation in the lungs is one of the most representative TCM syndromes of this disease. Patients generally have symptoms such as cough and sputum, wheezing and chest tightness, fever and constipation. Poor disease control can easily lead to progressive decline in lung function, significantly increasing the length of hospital stay, long-term readmission rate and clinical mortality risk.

[0003] Currently, the routine clinical intervention for AECOPD mainly involves the combined use of bronchodilators, glucocorticoids, and antibiotics. Although these can quickly relieve acute clinical symptoms, long-term use can easily lead to problems such as intestinal flora imbalance, multiple adverse drug reactions, and increased bacterial resistance. Therefore, it is impossible to simultaneously achieve the treatment goals of regulating the patient's intestinal microecology and improving lung function in the long term, resulting in limited overall clinical benefits.

[0004] Qingjin Huatan Decoction is a commonly used classic formula for treating lung diseases of the phlegm-heat accumulation type. However, in current clinical applications, this formula has defects such as lack of stratified targeting of the formula, inconsistent preparation process parameters, and poor efficacy stability. Furthermore, a standardized application path for it in AECOPD patients has not yet been established, making it difficult to meet the actual needs of precise clinical treatment. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this specification provides one or more embodiments of a Qingjin Huatan Decoction, which, by weight, comprises the following components: 10-20 parts of Scutellaria baicalensis, 6-12 parts of Gardenia jasminoides, 6-12 parts of Morus alba root bark, 10-14 parts of Trichosanthes kirilowii, 6-12 parts of Fritillaria thunbergii, 6-12 parts of Ophiopogon japonicus, 10-20 parts of Platycodon grandiflorus, 6-12 parts of Anemarrhena asphodeloides, 10-20 parts of Citrus reticulata peel, 10-20 parts of Poria cocos, and 4-8 parts of Glycyrrhiza uralensis (processed).

[0006] In some embodiments, the contents of each component by mass parts are as follows: Scutellaria baicalensis 15 parts, Gardenia jasminoides 9 parts, Morus alba root bark 9 parts, Trichosanthes kirilowii 12 parts, Fritillaria thunbergii 9 parts, Ophiopogon japonicus 9 parts, Platycodon grandiflorus 15 parts, Anemarrhena asphodeloides 9 parts, Citrus reticulata peel 15 parts, Poria cocos 15 parts, and Glycyrrhiza uralensis (processed) 6 parts.

[0007] In some embodiments, the dosage form of the Qingjin Huatan Decoction is granules or concentrated pills.

[0008] In some embodiments, the dosage form of Qingjin Huatan Decoction is a decoction of traditional Chinese medicine or a granule of traditional Chinese medicine formula.

[0009] In some embodiments, the dosage form of Qingjin Huatan Decoction is a decoction of traditional Chinese medicine or a granule of traditional Chinese medicine formula.

[0010] This specification also provides one or more embodiments of a method for preparing Qingjin Huatan Decoction, which is prepared by the following steps: S1, the raw material is cleaned to a purity of ≥98%, dried at a constant temperature of 60°C until the moisture content is 8%-10%, pulverized and passed through an 80-mesh sieve to obtain a pretreated raw material; S2, 10 times the amount of purified water is added to the pretreated raw material and soaked for 30-60 minutes, and then decocted using a segmented decoction process: S21, the first decoction is boiled at 100°C over high heat and then the temperature is adjusted to 85°C over low heat and simmered for 30 minutes, wherein the tangerine peel is decocted in the first decoction. Add the first decoction 10 minutes before the end of the decoction; S22, add 8 times the amount of purified water for the second decoction, and simmer at 85℃ for 25 minutes; combine the two decoctions to obtain the original decoction; S3, concentrate the original decoction under reduced pressure at 60℃ and 0.08MPa until it contains 1g of raw herb per milliliter and has a relative density of 1.10-1.15 at 25℃ to obtain the concentrated solution; S4, sterilize the concentrated solution with flowing steam at 100℃ for 30 minutes and then aseptically dispense it into brown glass bottles in a Class A clean area to obtain the Chinese herbal decoction.

[0011] One or more embodiments of this specification also provide the application of Qingjin Huatan Decoction, which is used to prepare a drug for regulating the intestinal flora of patients with acute exacerbation of chronic obstructive pulmonary disease and phlegm-heat accumulation in the lungs.

[0012] One or more embodiments of this specification also provide the application of Qingjin Huatan Decoction, which is used to prepare a drug to improve lung function in patients with acute exacerbation of chronic obstructive pulmonary disease and phlegm-heat accumulation in the lungs.

[0013] Beneficial effects 1. The fixed-ratio basic formula is suitable for the pathogenesis of phlegm-heat accumulation in the lungs during acute exacerbation of COPD. It can clear phlegm-heat, protect lung yin, and safeguard the spleen and stomach, achieving the goal of attacking pathogens without harming the body's vital energy, resolving phlegm without being too harsh, and clearing heat without being too cold.

[0014] 2. Adding houttuynia cordata, forsythia suspensa, and rhubarb (rhubarb added later) to the basic formula enhances its heat-clearing, detoxifying, bowel-regulating, and pathogen-expelling effects. It is suitable for severe patients with excessive heat, accompanied by fever and constipation, balancing the efficacy of the pathogen-expelling herbs with medication safety, and avoiding damage to the body's vital energy.

[0015] 3. The dosage of gardenia and platycodon was reduced and yam and atractylodes were added to optimize the balance of cold and heat and attack and tonify in the prescription, making it suitable for elderly patients with weak constitution, reducing the consumption of vital energy and gastrointestinal intolerance, and improving the safety and compliance of medication.

[0016] 4. The dosage form is set as decoction or formula granules, which retains all the active ingredients of the formula and has stable efficacy, covering use scenarios such as in-hospital and out-of-hospital use, meeting the medication needs of different patients and improving the convenience of medication.

[0017] 5. The raw materials are cleaned, dried, pulverized and sieved to remove ineffective and harmful impurities, protect heat-sensitive components, increase the contact area of ​​the medicinal materials, and facilitate the dissolution of active ingredients.

[0018] 6. Before decocting, soak the herbs in 10 times the amount of purified water for 30-60 minutes to moisten them and promote the dissolution of the components. The time can be adjusted according to the ambient temperature to avoid the herbs deteriorating or not absorbing enough water.

[0019] 7. A segmented decoction process is adopted, which involves boiling over high heat and then simmering over low heat. The decoctions are combined after the two decoctions to promote the release of active ingredients, protect heat-sensitive components, and improve the utilization rate of raw materials. Detailed Implementation

[0020] This specification provides one or more embodiments of a Qingjin Huatan Decoction, which is composed of the following raw materials in parts by weight: Scutellaria baicalensis 10-20 parts, Gardenia jasminoides 6-12 parts, Morus alba root bark 6-12 parts, Trichosanthes kirilowii 10-14 parts, Fritillaria thunbergii 6-12 parts, Ophiopogon japonicus 6-12 parts, Platycodon grandiflorus 10-20 parts, Anemarrhena asphodeloides 6-12 parts, Citrus reticulata peel 10-20 parts, Poria cocos 10-20 parts, and Glycyrrhiza uralensis (processed) 4-8 parts.

[0021] In this formula, Scutellaria baicalensis, Gardenia jasminoides, and Morus alba root bark work together. Scutellaria baicalensis specifically enters the lung meridian to clear away excess heat in the lungs. Gardenia jasminoides clears away stagnant heat in the triple burner and guides the heat evil out through the lower orifices. Morus alba root bark specifically clears away latent heat in the lungs and also has the effect of relieving asthma. The three work together to first clear away the fire and heat evil toxins that cause phlegm and heat to be generated internally, and cut off the core pathological link of heat evil continuously consuming body fluids to generate phlegm and turbidity.

[0022] The combination of Trichosanthes kirilowii, Fritillaria thunbergii, and Platycodon grandiflorus is beneficial. Trichosanthes kirilowii can clear heat and resolve phlegm, relieve chest tightness and dissipate nodules, and also lubricate the intestines to help expel pathogens. Fritillaria thunbergii is good at clearing and resolving accumulated heat and phlegm and dissipating phlegm nodules. Platycodon grandiflorus can promote lung qi, eliminate phlegm and drain pus, and guide the other drugs to ascend directly to the lung collaterals and the diseased area. Together, the three can resolve the phlegm and turbidity that has formed in the lungs, clear the airways blocked by phlegm and turbidity, and restore the normal physiological functions of the lungs in dispersing and descending qi.

[0023] The combination of Anemarrhena asphodeloides, Ophiopogon japonicus, and Citrus reticulata has the following effects: Anemarrhena asphodeloides can clear heat, nourish yin, moisten the lungs and relieve dryness; Ophiopogon japonicus can nourish yin, moisten the lungs and clear residual lung heat. The two can alleviate the drawbacks of the previous bitter and cold heat-clearing drugs that may deplete the yin fluid in the lungs and prevent lung dryness from further aggravating the qi stagnation; Citrus reticulata can regulate qi, dry dampness and resolve phlegm. By regulating the qi of the whole body, it can achieve the effect of qi flowing and phlegm disappearing, preventing phlegm from accumulating further with the stagnation of qi. At the same time, it can also promote the digestion and transformation of the spleen and stomach in the middle jiao and reduce the internal generation of new phlegm.

[0024] Poria cocos and prepared licorice work synergistically. Poria cocos can strengthen the spleen and eliminate dampness. By strengthening the spleen in the middle jiao, it cuts off the path of phlegm production, which is the source of phlegm, and reduces the subsequent generation of phlegm from the root. Prepared licorice can moisten the lungs and stop cough. At the same time, it can harmonize the properties of the other herbs, moderate the bias of bitter, cold and warm herbs in the formula, and avoid the bias of various herbs from damaging the body's vital energy. This allows the whole formula to attack the pathogens without harming the body's vital energy, resolve phlegm without being too dry and damaging to yin, and clear heat without being too cold and damaging to the stomach.

[0025] The formula combines all raw materials in a fixed quality ratio, precisely targeting the core pathogenesis of "phlegm-heat accumulation in the lungs, impaired lung function, and spleen dysfunction" in acute exacerbations of chronic obstructive pulmonary disease. While clearing away phlegm-heat in the lungs, it also nourishes lung yin and protects the function of the spleen and stomach in the middle jiao. It does not excessively attack and damage the body's vital energy. It exerts its therapeutic effect through multiple pathways, such as improving the physiological function of the lungs and reducing the generation of phlegm.

[0026] In some embodiments, the contents of each component of Qingjin Huatan Decoction by weight are as follows: Scutellaria baicalensis 15 parts, Gardenia jasminoides 9 parts, Morus alba root bark 9 parts, Trichosanthes kirilowii 12 parts, Fritillaria thunbergii 9 parts, Ophiopogon japonicus 9 parts, Platycodon grandiflorus 15 parts, Anemarrhena asphodeloides 9 parts, Citrus reticulata peel 15 parts, Poria cocos 15 parts, and Glycyrrhiza uralensis (processed) 6 parts.

[0027] In this embodiment, the components of Qingjin Huatan Decoction are formulated with a fixed mass ratio. This ratio aligns with the core pathogenesis of phlegm-heat accumulation in the lungs during acute exacerbations of chronic obstructive pulmonary disease (COPD), characterized by phlegm-heat obstructing the lungs, impaired lung function, and concurrent intestinal and lung disease. Following the principles of traditional Chinese medicine (TCM) formulation, the components work synergistically to balance their effects: the content of Scutellaria baicalensis and Gardenia jasminoides specifically clears heat from the lungs and the triple burner; the content of Morus alba root bark, Trichosanthes kirilowii fruit, and Fritillaria thunbergii synergistically clears phlegm from the lungs and moistens the intestines, aligning with the patient's concurrent intestinal and lung disease; and the content of Ophiopogon japonicus and Anemarrhena asphodeloides nourishes the lungs. The lung-moistening effect avoids the excessive dryness and heat of heat-clearing and phlegm-resolving herbs, which can deplete the body's fluids. The content of tangerine peel and poria can strengthen the spleen, dry dampness, eliminate phlegm and dissipate nodules, reducing the generation of phlegm from its source. The content of platycodon can carry the medicine upward to guide the effects of other medicines on the lung system. The content of roasted licorice can harmonize the properties of all the herbs, avoiding the conflict between the properties of different herbs. Together, they can achieve the overall effect of clearing heat and resolving phlegm, clearing the lungs and relieving cough, regulating the intestines and stomach. It can not only improve the core lung symptoms such as cough, wheezing and thick yellow phlegm, but also relieve the accompanying intestinal symptoms such as abdominal distension and abnormal bowel movements.

[0028] This fixed ratio serves as the standardized formulation benchmark for Qingjin Huatan Decoction, solving the problems of large fluctuations in formulation dosage and poor uniformity of efficacy between different batches of the medicine in traditional clinical applications. The fixed content of all components ensures that the proportion of active ingredients in Qingjin Huatan Decoction prepared in different batches is stable, and the efficacy will not fluctuate due to the randomness of the weighing of medicinal materials. It not only meets the needs of standardized clinical medication, but also provides a unified formulation basis for subsequent research on the mechanism of action of this formula and the formulation of quality control standards, avoiding deviations in research results or uneven product quality caused by differences in formulation dosage.

[0029] The content of each component in this formulation is set to meet the multi-pathway regulatory requirements of the formula. The dissolution ratio of the effective ingredients of each component is balanced, which can simultaneously act on multiple aspects of intestinal condition regulation and lung function improvement, without the limitation of only improving a single pathological aspect. This provides a stable pharmacodynamic basis for the formula to improve the pathological state of phlegm-heat accumulation in the lungs during the acute exacerbation of chronic obstructive pulmonary disease by regulating the interaction between intestinal flora and improving lung function. It is also suitable for the standardized preparation of different dosage forms such as granules and concentrated pills, which facilitates the promotion and application of the formula.

[0030] In some embodiments, the dosage form of Qingjin Huatan Decoction is a decoction of traditional Chinese medicine or a granule of traditional Chinese medicine formula.

[0031] For the Qingjin Huatan Decoction prescription with complete compatibility, the appropriate dosage form is either a decoction of Chinese medicine or a granule of Chinese medicine formula. The core reason is to match the synergistic effect of multiple components in Chinese medicine compound prescriptions. Both dosage forms use water as the extraction medium for the effective components, which can completely preserve the entire effective material basis formed by the combination of each raw material in the prescription. The compatibility balance of the compound prescription will not be disrupted due to changes in the extraction medium, ensuring that the core therapeutic efficacy of the prescription is stably exerted.

[0032] Among them, the decoction of traditional Chinese medicine is suitable for the use of standardized treatment in hospitals. During the preparation process, the order of feeding and decoction parameters can be adjusted according to the characteristics of different raw materials in the prescription. For raw materials containing volatile components, the feeding can be delayed. For raw materials that are easy to destroy the effective components by prolonged decoction, the decoction time can be controlled. This ensures the full dissolution of various effective components and avoids unnecessary loss of heat-sensitive and volatile components. The prepared decoction can be taken directly with warm water. After the drug enters the gastrointestinal tract, it has high dispersion and fast absorption speed, and can quickly exert its efficacy, which is suitable for the need of patients in the acute exacerbation period to quickly relieve symptoms.

[0033] Traditional Chinese medicine granules are suitable for outpatient administration or use scenarios where decoction is not available. They are made from raw materials that have been pre-extracted and granulated into single herbs, compounded according to the prescription ratio. They can be taken directly with warm water without the need for on-site decoction, which greatly reduces the threshold for prescription use. At the same time, the effective ingredient content of single-herb granules is standardized and controlled to ensure the uniformity of dosage between different batches, reducing the fluctuation of efficacy caused by individual differences in decoction operation. They are suitable for sequential maintenance treatment after patients are discharged from the hospital.

[0034] The two dosage forms cover different clinical use scenarios and can be flexibly matched with Qingjin Huatan Decoction prescriptions for different suitable populations. While fully preserving the therapeutic efficacy of the prescription, they meet the medication needs of different patients at different stages of treatment, effectively improving the convenience of medication and patient medication compliance.

[0035] One or more embodiments of this specification also provide a method for preparing any of the aforementioned Qingjin Huatan Decoction. When the Qingjin Huatan Decoction is a decoction of traditional Chinese medicine, it is prepared by the following steps: S1. The raw material is cleaned to a purity of ≥98%, dried at a constant temperature of 60°C until the moisture content is 8%-10%, pulverized, and passed through an 80-mesh sieve to obtain a pretreated raw material; S2. The pretreated raw material is soaked in 10 times the amount of purified water for 30-60 minutes, and then decocted using a segmented decoction process: S21. The first decoction is boiled at 100°C over high heat, and then the temperature is adjusted to 85°C and simmered over low heat for 30 minutes. In step S22, the tangerine peel is added 10 minutes before the end of the first decoction; in step S3, 8 times the amount of purified water is added to the second decoction, and the mixture is simmered at 85°C for 25 minutes; the two decoctions are combined to obtain the original decoction; in step S4, the original decoction is concentrated under reduced pressure at 60°C and 0.08MPa until it contains 1g of raw herb per milliliter and has a relative density of 1.10-1.15 at 25°C to obtain the concentrated solution; in step S5, the concentrated solution is sterilized by flowing steam at 100°C for 30 minutes and then aseptically dispensed into brown glass bottles in a Class A clean area to obtain the Chinese herbal decoction.

[0036] First, the raw materials are thoroughly cleaned and their purity is controlled to be no less than 98%. This completely removes sand, wood chips, insect-damaged materials, and deteriorated components, preventing ineffective or harmful impurities from entering subsequent preparation processes and ensuring the safety and purity of the finished product. A constant-temperature drying process at 60℃ is used to control the moisture content of the raw materials to 8%-10%. This temperature condition does not damage the heat-sensitive active ingredients in the raw materials and is suitable for the subsequent pulverization process. It avoids excessive moisture content, which can lead to clumping and uneven particle size during pulverization, and also avoids excessive moisture content, which can cause the medicinal materials to become too brittle and generate too much dust during pulverization, resulting in the loss of active ingredients. After pulverization, passing the raw materials through an 80-mesh sieve ensures uniform particle size, significantly increasing the contact area between the medicinal materials and the subsequent decoction solvent, providing a structural basis for the full dissolution of active ingredients.

[0037] Afterwards, add 10 times the amount of purified water to the pretreated raw materials and soak for 30 to 60 minutes. Sufficient purified water can fully moisten the pores inside the medicinal materials, allowing water to gradually penetrate into the cells, making the dried and shrunken cells refilled. This facilitates the smooth diffusion of active ingredients from the cells into the solvent during the subsequent decoction process. Adjusting the soaking time according to the ambient temperature can prevent the medicinal materials from deteriorating due to microbial proliferation during soaking in high summer temperatures, and can also prevent the medicinal materials from not absorbing enough water and affecting the dissolution of active ingredients in low winter temperatures.

[0038] The decoction is then carried out using a segmented decoction process. The first decoction is brought to a boil at 100℃ over high heat, which quickly brings the solvent to a boiling state, destroys the cell wall structure of the medicinal materials, and promotes the release of effective components within the cells. Subsequently, the temperature is adjusted to 85℃ and simmered for 30 minutes. The constant low-temperature decoction state avoids the destruction of heat-sensitive effective components such as baicalin and geniposide by continuous high-temperature boiling, while also reducing the rapid evaporation of the solvent. The tangerine peel is added 10 minutes before the end of the first decoction because the main medicinal components in tangerine peel are volatile oils. Prolonged high-temperature decoction will cause a large amount of volatile oils to escape and be lost. Shortening the decoction time can maximize the retention of volatile effective components in tangerine peel and ensure its efficacy in regulating qi and resolving phlegm.

[0039] After the first decoction, a second decoction is performed. Eight times the amount of purified water is added, and the decoction is simmered at 85°C for 25 minutes. The second decoction allows the deep-seated effective components that were not fully dissolved in the first decoction to be further dissolved, improving the utilization rate of the raw material and avoiding waste of effective components. The decoction concentrate obtained by combining the two decoctions can integrate all the effective components from the two decoctions, ensuring the integrity of the efficacy.

[0040] The decoction was then concentrated under reduced pressure, with the concentration temperature controlled at 60℃ and the pressure at 0.08MPa. This reduced pressure condition lowers the boiling point of water, allowing the decoction to evaporate water at a temperature below the normal boiling point, thus avoiding prolonged high-temperature heating that could damage the structure of the active ingredients. The concentration was reduced to 1g of raw herb per milliliter, with a relative density of 1.10-1.15 at 25℃. This ensures that the concentration of the active ingredients meets the clinical requirements for medication, while avoiding over-concentration that would lead to an overly viscous solution and increased difficulty in subsequent dispensing, and also avoids insufficient concentration that would result in an excessively large single dose and increase the burden on patients.

[0041] After concentration, the product is sterilized with flowing steam at 100℃ for 30 minutes. This sterilization condition can completely kill pathogenic microorganisms in the drug solution, ensuring that the microbial limits of the finished product meet the medication standards, while not excessively damaging the effective components in the drug solution. After sterilization, aseptic packaging is carried out in a Class A clean area to avoid introducing exogenous microbial contamination during the packaging process. Brown glass bottles are used as packaging containers to block light from damaging the photosensitive active ingredients in the drug solution, extending the shelf life of the finished product and ensuring that the efficacy remains stable during the storage period.

[0042] This specification provides one or more embodiments that also provide the application of the Qingjin Huatan Decoction described above, which is used to prepare a drug for regulating the intestinal flora of patients with acute exacerbation of chronic obstructive pulmonary disease and phlegm-heat accumulation in the lungs.

[0043] In some embodiments, the Qingjin Huatan Decoction, based on the traditional Chinese medicine theory of the lung and intestine sharing the same origin, not only exerts its core function of clearing the lungs and resolving phlegm, but also acts on the intestines through the bidirectional regulatory pathway of the gut-lung axis. First, it corrects the intestinal flora disorder in patients with acute exacerbation of chronic obstructive pulmonary disease and phlegm-heat accumulation in the lungs, gradually restoring the diversity of the intestinal flora, optimizing the flora structure, increasing the colonization abundance of beneficial bacteria, and reducing the proportion of pathogenic bacteria. At the same time, it repairs the normal metabolic function of the flora, promotes the synthesis of beneficial metabolites, regulates bile acid metabolism pathways, downregulates the expression of intestinal inflammation-related genes, and reduces local intestinal inflammation. Ultimately, it achieves a targeted regulatory effect on the intestinal flora of this type of patient. After being prepared into a corresponding drug, it can be adapted to the intervention needs of different subtypes of this type of patient, with more ideal overall safety and applicability.

[0044] One or more embodiments of this specification also provide the application of the Qingjin Huatan Decoction described above, which is used to prepare a drug to improve lung function in patients with acute exacerbation of chronic obstructive pulmonary disease and phlegm-heat accumulation in the lungs.

[0045] This specification provides one or more embodiments for the application of the aforementioned Qingjin Huatan Decoction, which is used to prepare a drug to improve lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and phlegm-heat accumulation in the lungs. Based on the traditional Chinese medicine theory of the lung-intestinal homology, and relying on the bidirectional regulatory pathway of the gut-lung axis, this Qingjin Huatan Decoction corrects the patient's gut microbiota dysbiosis and alleviates local intestinal inflammation. It then transmits positive regulatory signals from the gut level to the lungs, first regulating the inflammatory response pathways in the lungs, downregulating abnormal expression related to lung inflammation, reducing airway mucosal congestion and edema, decreasing inflammatory secretion exudation, and alleviating airway obstruction.

[0046] The core function of this Qingjin Huatan Decoction is to clear the lungs and resolve phlegm. It can directly act on the respiratory tract, promote the discharge of phlegm accumulated in the airway, reduce airway resistance, relieve abnormal spasms of airway smooth muscle, improve airway compliance, and gradually restore normal ventilation and gas exchange functions of the airway.

[0047] Differentiated formulas designed for different patient subtypes can further match the individual pathological characteristics of patients. For patients with severe symptoms, the effects of clearing heat and detoxifying, and purging heat can be enhanced to control the progression of lung pathology. For elderly patients with weak constitutions, the stimulation of cold and cooling medicinal properties can be reduced, while also taking into account the benefits of invigorating qi and strengthening the spleen to improve patient tolerance and ensure the stable performance of lung function improvement. After being prepared into corresponding drugs, they can be adapted to the intervention needs of different subtypes of such patients, and the overall safety and applicability are more ideal.

[0048] The method of the present invention will now be described in detail with reference to embodiments, comparative examples and experimental data.

[0049] Example 1 This embodiment provides a Qingjin Huatan Decoction suitable for patients with mild to moderate chronic obstructive pulmonary disease (COPD) acute exacerbation and phlegm-heat accumulation in the lungs with a CAT score of 10-20. The raw materials are composed of the following components by weight: Scutellaria baicalensis 15 parts, Gardenia jasminoides 9 parts, Morus alba root bark 9 parts, Trichosanthes kirilowii 12 parts, Fritillaria thunbergii 9 parts, Ophiopogon japonicus 9 parts, Platycodon grandiflorus 15 parts, Anemarrhena asphodeloides 9 parts, Citrus reticulata peel 15 parts, Poria cocos 15 parts, and Glycyrrhiza uralensis 6 parts. In this embodiment, it is prepared as a decoction of traditional Chinese medicine. The specific preparation process is carried out according to the following steps.

[0050] S1. Weigh each raw material according to the formula and perform a cleaning process to remove impurities such as stones, wood chips, insect-infested and ineffective medicinal materials. Control the purity to be no less than 98%. Place the cleaned and qualified raw materials in a 60℃ constant temperature drying equipment to dry until the moisture content of the raw materials is 9%. Take them out and pulverize the dried raw materials. After all of them are passed through an 80-mesh sieve, the pre-treated raw materials are obtained.

[0051] S2. Add purified water equivalent to 10 times the total mass of the raw material to the obtained pretreated raw material, soak for 45 minutes to allow the medicinal material to fully absorb water and swell, and then complete the decoction operation using a segmented decoction process: S21 is the first decoction step, first heat the system to 100℃ to boil, then adjust the heating temperature to 85℃ and simmer for 30 minutes. During the decoction process, add the tangerine peel to the decoction system 10 minutes before the end of the first decoction to reduce the heating loss of volatile oil effective components in the tangerine peel; S22 is the second decoction step, after the first decoction is completed, filter and separate to obtain the first decoction liquid, add purified water equivalent to 8 times the total mass of the raw material to the remaining residue, simmer at 85℃ for 25 minutes, filter to obtain the second decoction liquid, and combine the liquids from the two decoctions to obtain the decoction stock solution.

[0052] S3. Transfer the obtained decoction to a vacuum concentration device, set the heating temperature to 60℃ and the system pressure to 0.08MPa, and carry out vacuum concentration operation. Stop the concentration when the concentration is 1g of raw drug per milliliter of decoction and the relative density measured at 25℃ is 1.125, and obtain concentrated liquid.

[0053] S4. Sterilize the obtained concentrate with flowing steam at 100℃ for 30 minutes. After sterilization, transfer it to a Class A clean area for aseptic dispensing. Use brown glass bottles as packaging containers to obtain the finished Qingjin Huatan Decoction.

[0054] Example 2 This embodiment provides a Qingjin Huatan Decoction suitable for patients with mild to moderate chronic obstructive pulmonary disease (COPD) acute exacerbation and phlegm-heat accumulation in the lungs with a CAT score of 10-20. The raw materials are composed of the following components by weight: Scutellaria baicalensis 15 parts, Gardenia jasminoides 9 parts, Morus alba root bark 9 parts, Trichosanthes kirilowii 12 parts, Fritillaria thunbergii 9 parts, Ophiopogon japonicus 9 parts, Platycodon grandiflorus 15 parts, Anemarrhena asphodeloides 9 parts, Citrus reticulata peel 15 parts, Poria cocos 15 parts, and Glycyrrhiza uralensis 6 parts. In this embodiment, it is prepared as a decoction of traditional Chinese medicine. The specific preparation process is carried out according to the following steps.

[0055] S1. Weigh each raw material according to the formula and perform a cleaning process to remove impurities such as stones, wood chips, insect-infested and ineffective medicinal materials. Control the purity to be no less than 98%. Place the cleaned and qualified raw materials in a 60℃ constant temperature drying equipment to dry until the moisture content of the raw materials is 9%. Take them out and pulverize the dried raw materials. After all of them are passed through an 80-mesh sieve, the pre-treated raw materials are obtained.

[0056] S2. Add purified water equivalent to 10 times the total mass of the raw material to the obtained pretreated raw material, soak for 45 minutes to allow the medicinal material to fully absorb water and swell, and then complete the decoction operation using a segmented decoction process: S21 is the first decoction step, first heat the system to 100℃ to boil, then adjust the heating temperature to 85℃ and simmer for 30 minutes. During the decoction process, add the tangerine peel to the decoction system 10 minutes before the end of the first decoction to reduce the heating loss of volatile oil effective components in the tangerine peel; S22 is the second decoction step, after the first decoction is completed, filter and separate to obtain the first decoction liquid, add purified water equivalent to 8 times the total mass of the raw material to the remaining residue, simmer at 85℃ for 25 minutes, filter to obtain the second decoction liquid, and combine the liquids from the two decoctions to obtain the decoction stock solution.

[0057] S3. Transfer the obtained decoction to a vacuum concentration device, set the heating temperature to 60℃ and the system pressure to 0.08MPa, and carry out vacuum concentration operation. Stop the concentration when the concentration is 1g of raw drug per milliliter of decoction and the relative density measured at 25℃ is 1.125, and obtain concentrated liquid.

[0058] S4. Sterilize the obtained concentrate with flowing steam at 100℃ for 30 minutes. After sterilization, transfer it to a Class A clean area for aseptic dispensing. Use brown glass bottles as packaging containers to obtain the finished Qingjin Huatan Decoction.

[0059] Example 3 This embodiment provides a Qingjin Huatan Decoction suitable for patients with mild to moderate chronic obstructive pulmonary disease (COPD) acute exacerbation and phlegm-heat accumulation in the lungs with a CAT score of 10-20. The raw materials are composed of the following components by weight: Scutellaria baicalensis 15 parts, Gardenia jasminoides 9 parts, Morus alba root bark 9 parts, Trichosanthes kirilowii 12 parts, Fritillaria thunbergii 9 parts, Ophiopogon japonicus 9 parts, Platycodon grandiflorus 15 parts, Anemarrhena asphodeloides 9 parts, Citrus reticulata peel 15 parts, Poria cocos 15 parts, and Glycyrrhiza uralensis 6 parts. In this embodiment, it is prepared as a decoction of traditional Chinese medicine. The specific preparation process is carried out according to the following steps.

[0060] S1. Weigh each raw material according to the formula and perform a cleaning process to remove impurities such as stones, wood chips, insect-infested and ineffective medicinal materials. Control the purity to be no less than 98%. Place the cleaned and qualified raw materials in a 60℃ constant temperature drying equipment to dry until the moisture content of the raw materials is 9%. Take them out and pulverize the dried raw materials. After all of them are passed through an 80-mesh sieve, the pre-treated raw materials are obtained.

[0061] S2. Add purified water equivalent to 10 times the total mass of the raw material to the obtained pretreated raw material, soak for 45 minutes to allow the medicinal material to fully absorb water and swell, and then complete the decoction operation using a segmented decoction process: S21 is the first decoction step, first heat the system to 100℃ to boil, then adjust the heating temperature to 85℃ and simmer for 30 minutes. During the decoction process, add the tangerine peel to the decoction system 10 minutes before the end of the first decoction to reduce the heating loss of volatile oil effective components in the tangerine peel; S22 is the second decoction step, after the first decoction is completed, filter and separate to obtain the first decoction liquid, add purified water equivalent to 8 times the total mass of the raw material to the remaining residue, simmer at 85℃ for 25 minutes, filter to obtain the second decoction liquid, and combine the liquids from the two decoctions to obtain the decoction stock solution.

[0062] S3. Transfer the obtained decoction to a vacuum concentration device, set the heating temperature to 60℃ and the system pressure to 0.08MPa, and carry out vacuum concentration operation. Stop the concentration when the concentration is 1g of raw drug per milliliter of decoction and the relative density measured at 25℃ is 1.125, and obtain concentrated liquid.

[0063] S4. Sterilize the obtained concentrate with flowing steam at 100℃ for 30 minutes. After sterilization, transfer it to a Class A clean area for aseptic dispensing. Use brown glass bottles as packaging containers to obtain the finished Qingjin Huatan Decoction.

[0064] Comparative Example 1 This comparative example provides a decoction of Qingjin Huatan Decoction, which differs from Example 1 in that the raw material composition does not include mulberry bark, while the dosage and preparation steps of the remaining components are the same as in Example 1.

[0065] Comparative Example 2 This comparative example provides a decoction of Qingjin Huatan Decoction, which differs from Example 1 in that: the amount of Scutellaria baicalensis in the raw materials is 6 parts, while the amount of the remaining components and the preparation steps are the same as in Example 1.

[0066] Comparative Example 3 This comparative example provides a decoction of Qingjin Huatan Decoction, which differs from Example 1 in that: in S1, the dried raw material is pulverized and only passes through a 20-mesh sieve, while the dosage of other components and preparation steps are the same as in Example 1.

[0067] Comparative Example 4 This comparative example provides a decoction of Qingjin Huatan Decoction, which differs from Example 1 in that: in the first decoction step S21, the tangerine peel and other pretreated raw materials are added to purified water for soaking and decoction at the same time, and the materials are not added 10 minutes before the end of the first decoction. The dosage of other components and preparation steps are the same as in Example 1.

[0068] Comparative Example 5 This comparative example provides a decoction of Qingjin Huatan Decoction, which differs from Example 1 in that: the S2 decoction process only performs the first decoction and does not include a second decoction process. After the first decoction is completed, the decoction is directly filtered to obtain the original decoction. The dosage of other components and the preparation steps are the same as in Example 1.

[0069] Comparative Example 6 This comparative example provides a decoction of Qingjin Huatan Decoction, which differs from Example 1 in that: the S3 concentration process uses 100°C atmospheric pressure heating concentration instead of 60°C and 0.08MPa pressure reduced pressure concentration, while the dosage of other components and preparation steps are the same as in Example 1.

[0070] Comparative Example 7 This comparative example provides a decoction of Qingjin Huatan Decoction, which differs from Example 1 in that: the S4 sterilization process uses 121℃ high-pressure steam sterilization for 20 minutes instead of 100℃ flowing steam sterilization for 30 minutes, while the dosage of other components and preparation steps are the same as in Example 1.

[0071] The products corresponding to the above embodiments and comparative examples were tested using the following methods: Intensity of volatile oil odor: Ten evaluators with olfactory sensitivity calibrated were recruited. In a closed evaluation room at 25℃ with no odor, 10 mL of the sample to be tested was placed in an odorless 50 mL glass sample bottle. After opening the bottle, the sample was smelled from 2 cm away from the bottle opening. The evaluators scored the sample according to a scale of 0 to 10, where 0 was no volatile oil odor and 10 was extremely strong volatile oil odor. The arithmetic mean of the scores given by all evaluators was taken as the volatile oil odor intensity value.

[0072] Precipitation grade of the drug solution after 24 hours of standing: Take 50 mL of the mixed drug solution and transfer it to a colorless, transparent, stoppered glass graduated cylinder. After sealing, place it in a light-protected environment at 25℃ for 24 hours. Observe the precipitation state and match it with the corresponding grade: Grade 0 is no visible precipitation, Grade 1 is only a trace amount of misty precipitation, Grade 2 is a small amount of flocculent precipitation, Grade 3 is a large amount of flocculent or granular precipitation, and Grade 4 is a large amount of blocky precipitation. Record the matched grade, which is the precipitation grade of the drug solution after 24 hours of standing.

[0073] Concentration process time: The time is recorded from the moment when all the concentrated liquid is pumped into the concentration equipment and the equipment is officially started and running until the concentration of the concentrated liquid reaches the standard concentration required by the preset process and the concentration equipment stops running. The duration of this period is the concentration process time, and the unit is h or min.

[0074] Improvement in CAT score after medication: Before medication and seven days after medication, patients were instructed to independently complete the questionnaire according to the requirements of the official Chronic Obstructive Pulmonary Disease Assessment Test (CAT) and calculate the corresponding CAT score. Improvement in CAT score after medication = CAT score before medication - CAT score after medication.

[0075] Table 1 Performance Test Results ; Experimental Results Analysis The Qingjin Huatan Decoction prepared in Example 1 was formulated according to the preset plan in terms of raw material composition and preparation process. It was used for patients with mild to moderate chronic obstructive pulmonary disease acute exacerbation of phlegm-heat accumulation in the lungs with a CAT score of 10-20. The volatile oil odor intensity was measured to be 8.8, the precipitation grade of the decoction after standing for 24 hours was grade 1, the concentration process took 45 minutes, and the improvement value of the CAT score after medication was 7.2. All indicators showed good performance.

[0076] The Qingjin Huatan Decoction prepared in Example 2 had the same raw material formulation and preparation process as in Example 1. It was used for patients with mild to moderate chronic obstructive pulmonary disease (COPD) with acute exacerbation of phlegm-heat accumulation in the lungs and a CAT score of 15. The volatile oil odor intensity was measured to be 8.7, the precipitation grade of the decoction after standing for 24 hours was grade 1, the concentration process took 45 minutes, and the improvement value of the patient's CAT score after medication was 7.3. There were no significant differences between the indicators and those in Example 1, showing good process stability.

[0077] The Qingjin Huatan Decoction prepared in Example 3 had the same raw material formulation, preparation process, and applicable population as in Example 1. The volatile oil odor intensity was measured to be 8.8, the precipitation grade of the decoction after standing for 24 hours was grade 1, the concentration process took 45 minutes, and the improvement value of the CAT score of patients after medication was 7.2. All indicators were basically the same as those in Examples 1 and 2, which verified the reproducibility of the formulation and process.

[0078] The Qingjin Huatan Decoction prepared in Comparative Example 1 did not contain mulberry bark in its raw materials. The rest of the formulation and preparation process were the same as in Example 1. The volatile oil odor intensity was measured to be 8.6, the precipitation grade of the decoction after standing for 24 hours was grade 1, and the concentration process took 45 minutes. The physicochemical and process-related indicators were similar to those in Example 1. However, the improvement value of the CAT score after the patient took the medicine was only 3.5, which was much lower than that in Example 1. This indicates that the absence of mulberry bark will significantly reduce the therapeutic effect of the drug on the target indication population.

[0079] In Comparative Example 2, the dosage of Scutellaria baicalensis in the raw materials was adjusted to 6 parts, while the rest of the formulation and preparation process were the same as in Example 1. The volatile oil odor intensity was measured to be 8.7, the precipitation grade of the decoction after standing for 24 hours was grade 1, and the concentration process took 45 minutes. The physicochemical and process-related indicators were not significantly different from those in Example 1. However, the improvement value of the CAT score after the patient took the medicine was only 4.1, which was much lower than that in Example 1. This indicates that the dosage of Scutellaria baicalensis below the preset value will significantly weaken the therapeutic effect of the drug.

[0080] The Qingjin Huatan Decoction prepared in Comparative Example 3 was prepared by pulverizing the raw materials after drying and passing them through a 20-mesh sieve. The rest of the formulation and preparation process were the same as in Example 1. The volatile oil odor intensity was measured to be 7.9, the precipitation grade of the decoction after standing for 24 hours was grade 3, the concentration process took 45 minutes, and the improvement value of the CAT score of the patient after taking the medicine was 5.3. Compared with Example 1, the volatile oil odor intensity was reduced, the precipitation of the decoction was significantly increased, and the therapeutic effect was also reduced. This indicates that the excessively large particle size of the raw materials is not conducive to the dissolution of the effective ingredients, the improvement of the stability of the decoction, and the efficacy.

[0081] In Comparative Example 4, the Qingjin Huatan Decoction was prepared by soaking and decocting tangerine peel and other raw materials simultaneously, but the tangerine peel was not added 10 minutes before the end of the first decoction. The rest of the formula and preparation process were the same as in Example 1. The volatile oil odor intensity was measured to be 3.2, the precipitation grade of the decoction after standing for 24 hours was grade 1, the concentration process took 45 minutes, and the improvement value of the CAT score of the patient after medication was 4.8. Compared with Example 1, the volatile oil odor intensity was significantly reduced, and the therapeutic effect was also significantly reduced. This indicates that the process of delaying the addition of tangerine peel can effectively reduce the loss of volatile oil components in tangerine peel and ensure the efficacy of the drug.

[0082] The Qingjin Huatan Decoction prepared in Comparative Example 5 only underwent a first decoction and did not include a second decoction step. The rest of the formula and preparation process were the same as in Example 1. The volatile oil odor intensity was measured to be 8.5, the sedimentation grade of the decoction after standing for 24 hours was 0, the concentration process took 45 minutes, and the improvement value of the patient's CAT score after medication was 5.0. Compared with Example 1, the therapeutic effect was significantly reduced, indicating that the two-stage decoction process can more fully extract the effective components from the medicinal materials and improve the therapeutic effect.

[0083] The Qingjin Huatan Decoction prepared in Comparative Example 6 was prepared by heating and concentrating at 100℃ under normal pressure instead of vacuum concentration at 60℃ and 0.08MPa. The rest of the formulation and preparation process were the same as in Example 1. The volatile oil odor intensity was measured to be 4.5, the precipitation grade of the decoction after standing for 24 hours was grade 2, the concentration process took 90 minutes, and the improvement value of the CAT score of the patient after medication was 4.5. Compared with Example 1, the concentration time was significantly prolonged, the loss of volatile oil was obvious, the precipitation of the decoction increased, and the therapeutic effect was significantly reduced. This shows that the low temperature vacuum concentration process can reduce the destruction of effective ingredients, improve the stability of the decoction, shorten the production time, and ensure the efficacy.

[0084] The Qingjin Huatan Decoction prepared in Comparative Example 7 was sterilized with 121℃ high-pressure steam for 20 minutes instead of 100℃ flowing steam for 30 minutes. The rest of the formulation and preparation process were the same as in Example 1. The volatile oil odor intensity was measured to be 5.1, the precipitation grade of the decoction after standing for 24 hours was grade 3, the concentration process took 45 minutes, and the improvement value of the CAT score after the patient took the medicine was 4.2. Compared with Example 1, the loss of volatile oil was obvious, the precipitation of the decoction was increased, and the therapeutic effect was significantly reduced. This shows that the 100℃ flowing steam sterilization process can reduce the destruction of effective ingredients, improve the stability of the decoction and ensure the efficacy.

[0085] In summary, the Qingjin Huatan Decoction tested in this experiment, using a pre-defined specific ratio of raw materials, combined with a preparation process involving pulverizing the raw materials and passing them through an 80-mesh sieve, adding tangerine peel 10 minutes before the end of the first decoction, two decoctions, vacuum concentration at 60℃ and 0.08MPa, and sterilization with flowing steam at 100℃ for 30 minutes, effectively preserves the volatile oil components, ensures the stability of the decoction, shortens the concentration process time, and achieves the optimal therapeutic effect when applied to patients with mild to moderate chronic obstructive pulmonary disease (COPD) acute exacerbation and phlegm-heat accumulation in the lungs with a CAT score of 10-20. The formulation and dosage, preparation process parameters, and the selection of the target population all significantly affect the final product quality and efficacy. Arbitrary adjustments to the formulation or dosage, omissions or alterations to the preparation process steps, or use of the medication outside the target population range will lead to a decline in product quality or reduced efficacy.

[0086] The applicant declares that the detailed process flow of this invention is illustrated by the above embodiments, but this invention is not limited to the above detailed process flow, that is, it does not mean that this invention must rely on the above detailed process flow to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the product of this invention, addition of auxiliary components, and selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

Claims

1. A decoction for clearing heat and resolving phlegm, characterized in that, The product comprises the following components by weight: Scutellaria baicalensis 10-20 parts, Gardenia jasminoides 6-12 parts, Morus alba root bark 6-12 parts, Trichosanthes kirilowii 10-14 parts, Fritillaria thunbergii 6-12 parts, Ophiopogon japonicus 6-12 parts, Platycodon grandiflorus 10-20 parts, Anemarrhena asphodeloides 6-12 parts, Citrus reticulata peel 10-20 parts, Poria cocos 10-20 parts, and Glycyrrhiza uralensis (processed) 4-8 parts.

2. The Qingjin Huatan Decoction according to claim 1, characterized in that, The contents of each component by mass are as follows: Scutellaria baicalensis 15 parts, Gardenia jasminoides 9 parts, Morus alba root bark 9 parts, Trichosanthes kirilowii 12 parts, Fritillaria thunbergii 9 parts, Ophiopogon japonicus 9 parts, Platycodon grandiflorus 15 parts, Anemarrhena asphodeloides 9 parts, Citrus reticulata peel 15 parts, Poria cocos 15 parts, and Glycyrrhiza uralensis (processed) 6 parts.

3. The Qingjin Huatan Decoction according to claim 1, characterized in that, The dosage form of the Qingjin Huatan Decoction is granules or concentrated pills.

4. The Qingjin Huatan Decoction according to claim 1, characterized in that, The dosage form of Qingjin Huatan Decoction is a decoction of traditional Chinese medicine or a granule of traditional Chinese medicine formula.

5. A method for preparing a Qingjin Huatan Decoction, characterized in that, It is prepared by the following steps: S1. The raw material is cleaned to a purity of ≥98%, dried at a constant temperature of 60℃ until the moisture content is 8%-10%, pulverized and passed through an 80-mesh sieve to obtain the pretreated raw material; S2. Add 10 times the amount of purified water to the pretreated raw material and soak for 30-60 minutes. Then, decoct using a segmented decoction process: S21. After boiling at 100°C over high heat, adjust the temperature to 85°C and simmer for 30 minutes. Add the dried tangerine peel 10 minutes before the end of the first decoction. S22. Add 8 times the amount of purified water to the second decoction and simmer at 85°C for 25 minutes. Combine the two decoctions to obtain the original decoction. S3. The decoction is concentrated under reduced pressure at 60°C and 0.08MPa until it contains 1g of raw medicinal material per milliliter and has a relative density of 1.10-1.15 at 25°C, thus obtaining a concentrated solution. S4. The concentrated liquid is sterilized by flowing steam at 100°C for 30 minutes and then aseptically dispensed into brown glass bottles in a Class A clean area to obtain the traditional Chinese medicine decoction.

6. The application of the Qingjin Huatan Decoction according to any one of claims 1 to 4, characterized in that, The Qingjin Huatan Decoction is used to prepare a drug for regulating the intestinal flora of patients with acute exacerbation of chronic obstructive pulmonary disease and phlegm-heat accumulation in the lungs.

7. The application of the Qingjin Huatan Decoction according to any one of claims 1 to 4, characterized in that, The Qingjin Huatan Decoction is used to prepare a drug to improve lung function in patients with acute exacerbation of chronic obstructive pulmonary disease and phlegm-heat accumulation in the lungs.