A composition for treating pulmonary fibrosis, its preparation and use

Abstract

This invention belongs to the field of traditional Chinese medicine composition technology, and discloses a composition for treating pulmonary fibrosis, its preparation method, and its application. The weight percentage of the composition is: ginseng 15-25%, Chamaejasminoides 40-60%, tangerine peel 15-30%, Buddha's hand or tangerine peel 12-15%; or ginseng saponin extract 5-15%, ginseng polysaccharide 5-10%, Chamaejasminoides polysaccharide 25-35%, tangerine peel water extract 20-25%, and Buddha's hand water extract with alcohol precipitation 15-25%. The preparation method of the composition includes S1, weighing the raw materials and decocting them with water; S2, filtering and concentrating the raw material solution, then adding alcohol and stirring, allowing it to precipitate overnight, filtering to remove the precipitate, and recovering the ethanol from the supernatant; then concentrating it into a concentrated solution for later use or drying it into a paste and pulverizing it into powder; S3, adding excipients to obtain an oral drug formulation. The composition is used in the preparation of drugs for the prevention and / or treatment of pulmonary fibrosis and / or idiopathic pulmonary fibrosis.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, specifically to a composition for treating pulmonary fibrosis, its preparation method, and its application. Background Technology

[0002] Pulmonary fibrosis (PF) is a common degenerative disease of the lung system in middle-aged and elderly people. Characterized by diffuse inflammatory damage and destruction of tissue structure, PF is an irreversible end-stage disease resulting from most interstitial lung changes. Clinical manifestations mainly include progressive exertional dyspnea, or dry cough, prominent clubbing of the fingers, crackles in both lower lung fields, and imaging abnormalities. Idiopathic pulmonary fibrosis (IPF) is one of the major types of diffuse interstitial lung disease. Its main pathology is fibrosis of lung tissue, leading to loss of normal lung respiratory function, severe respiratory dysfunction, and inability to care for oneself. It is characterized by a long course and low cure rate, severely impacting the patient's quality of life and ultimately leading to respiratory failure and endangering the patient's life.

[0003] Currently, the number of pulmonary fibrosis (PF) patients in my country exceeds 2 million. However, the pathogenesis of this disease is still unclear. Researchers believe that possible risk factors include smoking, environmental exposure (such as metal dust, wood dust, chemical gases, etc.), genetic factors, aging, and viral infections. Therefore, there is currently a lack of effective drugs for treating pulmonary fibrosis. Western medicine routinely uses glucocorticoids and antibiotics for anti-inflammatory and antibacterial treatment. Commonly used drugs in clinical practice are pirfenidone and nintedanib. Although they can alleviate the progression of pulmonary fibrosis to some extent and partially improve symptoms, their overall efficacy is not significant, and they cannot control the progression of the disease. Long-term use is required, but long-term use weakens the efficacy and increases toxicity, resulting in significant side effects and a poor prognosis for patients. Furthermore, these two drugs are expensive, placing a heavy economic burden on patients.

[0004] Traditional Chinese medicine practitioners often categorize pulmonary fibrosis under the terms "pulmonary arthralgia" or "pulmonary atrophy," pointing out that this disease is generally caused by lung deficiency and depletion of fluids and qi, leading to the withering and unusability of the lung lobes. Based on its pathological nature, it can be further divided into lung dryness and fluid depletion, and lung qi deficiency and coldness. Its main causes are prolonged illness damaging the lungs and improper treatment damaging fluids. It can be caused by excessive drinking and sexual activity, leading to arthralgia. External pathogens, especially wind, cold, and dampness, invade the skin and hair, lodging in the lungs, causing the lung qi to lose its ability to disperse and descend, leading to kidney qi deficiency, which in turn leads to lung qi deficiency, kidney essence deficiency, and upward flaring of deficient fire scorching lung fluids. Dietary hot or cold foods and emotional distress can also obstruct the flow of lung qi, causing pathogenic factors to obstruct the lung collaterals and affecting the lung's function of governing the body's qi transformation, resulting in lung qi stagnation and arthralgia, which is a case of deficiency in the root and excess in the branch. This is similar to the pathophysiological changes discovered by modern medicine, which are caused by the prolonged and unhealed lung disease, damage to the alveoli, early deposition of immune complexes causing inflammatory reactions in the pulmonary interstitium, and in the middle and late stages, the exudate becomes organized, fibroblasts and collagen proliferate, increasing the surface tension of the alveoli, reducing the microcirculation function of pulmonary blood vessels, and even more seriously, causing alveolar collapse, resulting in a severe decline in restrictive pulmonary ventilation function.

[0005] Traditional Chinese medicine (TCM) classifies pulmonary fibrosis patients into two main syndromes: deficiency and excess. Clinically, these syndromes are often mixed, resulting in complex conditions, with the most common being Qi deficiency and blood stasis syndrome, representing a deficiency in the root and an excess in the branch. Treatment should focus on tonifying the lungs and replenishing Qi, nourishing Yin and benefiting the lungs, and promoting blood circulation and removing blood stasis. For deficiency syndromes: Yin deficiency with internal heat syndrome, the formula Mai Men Dong Tang combined with Qing Zao Jiu Fei Tang (modified formula) is used to clear the lungs, moisten dryness, resolve phlegm, and stop coughing; for lung Qi deficiency syndrome, Ren Shen Hu Tao Tang combined with Ren Shen Yang Fei Wan (modified formula) is used to tonify lung Qi; for lung and kidney Qi deficiency syndrome, Ren Shen Hu Tao Tang combined with Qi Wei Du Qi Wan (modified formula) is used to tonify the lungs and benefit the kidneys. For excess syndromes: Phlegm obstructing the lungs syndrome, Ban Xia Hou Po Tang combined with San Zi Yang Qin Tang (modified formula) is used to dry dampness and resolve phlegm; for phlegm-heat obstructing the lungs syndrome, Qing Jin Hua Tan Tang combined with Sang Bai Pi Tang (modified formula) is used to clear the lungs and detoxify. For concurrent symptoms such as blood stasis, prescriptions often use herbs like safflower to invigorate blood and remove blood stasis. These prescriptions are clinically safe and effective due to their multi-component, multi-functional, and relatively low-toxicity nature. They can exert anti-inflammatory effects, inhibit the aggregation of inflammatory factors, act as anticoagulants, scavengers of free radicals, block cell signaling pathways leading to fibrosis, reduce collagen production, and inhibit fibroblast proliferation and collagen deposition, thus playing an anti-fibrotic role with significant clinical efficacy. However, these clinical prescriptions are often large prescriptions composed of more than 10 Chinese herbs, with complex compositions, making it difficult to control the quality of the herbs. They also require long-term use, which can easily lead to unstable efficacy. Moreover, there are no readily available preparations, making it inconvenient for patients and easily causing patients to abandon medication midway. Other traditional Chinese medicine preparations for preventing and treating pulmonary fibrosis have even more drawbacks, including large complex formulas, numerous herbs, complex active ingredients, unstable production processes, difficulty in quality control, and difficulty in guaranteeing efficacy. Summary of the Invention

[0006] This invention aims to provide a composition, preparation method, and application for treating pulmonary fibrosis. The composition can effectively prevent and reverse pulmonary fibrosis and restore the normal structure and function of the lungs in patients. The preparation method of the composition is simple, easy to control in terms of quality, and low in cost. When applied to drugs for the prevention and / or treatment of pulmonary fibrosis and / or idiopathic pulmonary fibrosis, it can rapidly improve symptoms, has a short course of treatment, no obvious toxic side effects, and is suitable for long-term, high-dose use until a cure is achieved.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] A composition for treating pulmonary fibrosis, wherein the composition comprises, by weight percentage:

[0009] Ginseng 15-25%, Chamaejasminoides 40-60%, dried tangerine peel 15-30%, Buddha's hand or tangerine peel 10-15%.

[0010] Furthermore, the weight percentage of the composition is: ginseng 16%, chamaegu 50%, dried tangerine peel 24%, and bergamot or tangerine peel 10%.

[0011] A composition for treating pulmonary fibrosis, wherein the composition comprises, by weight percentage:

[0012] Ginsenoside extract 5-15%, ginseng polysaccharide 5-10%, Chamaegu polysaccharide 25-35%, 10-fold concentrated tangerine peel water extract 20-25%, and Buddha's hand water extract with alcohol precipitation 15-25%.

[0013] Further, the composition comprises the following weight percentages: 12% ginsenoside extract, 10% ginseng polysaccharide, 28% Chamaegu polysaccharide, 26% 10x concentrated tangerine peel water extract, and 24% bergamot water-extracted alcohol-precipitated extract.

[0014] A method for preparing the above-mentioned composition for treating pulmonary fibrosis includes the following steps:

[0015] S1. Weigh the raw materials of the composition according to the weight percentage, mix them, and then decoct them with water;

[0016] S2. Filter and concentrate the raw medicinal liquid obtained from step S1 to obtain a clear extract; then add alcohol and stir until the alcohol content is 56% to 58%, let it precipitate overnight, filter to remove the precipitate, take the supernatant to recover the ethanol; then concentrate to a concentrated liquid for later use, or place it in a vacuum drying oven to dry into a dry extract and pulverize it into powder.

[0017] S3. Add medical excipients to obtain oral drug formulations.

[0018] Furthermore, in S1, the raw material is decocted with water three times: after the first boil, it is decocted over high heat for 2 hours; after the second boil, it is decocted over high heat for 1.5 hours; and after the third boil, it is decocted over high heat for 1.0 hour.

[0019] Further, in S2, the raw material solution is filtered at 80°C and concentrated to 1 ml to obtain a clear extract of 1.25 g of raw medicinal material; after recovering ethanol, it is concentrated to a specific gravity of 1.15; and then dried in a vacuum drying oven at 60°C to form a dry extract.

[0020] Furthermore, in S3, the prepared oral drug formulation is one of the following: oral liquid, granules, capsules, concentrated pills, or tablets.

[0021] The above-mentioned composition for treating pulmonary fibrosis is used in the preparation of drugs for the prevention and treatment of pulmonary fibrosis.

[0022] The above-mentioned composition for treating pulmonary fibrosis is used in the preparation of drugs for the prevention and treatment of idiopathic pulmonary fibrosis.

[0023] The principles and beneficial effects of the technical solution are as follows:

[0024] This invention analyzes and studies the main etiologies and pathogenesis of pulmonary fibrosis. Based on the main etiologies, pathogenesis, and pathophysiology of pulmonary fibrosis, it proposes that, under the treatment principles of tonifying the lungs and replenishing qi, nourishing yin and benefiting the lungs, and regulating qi and resolving phlegm, modern biomedical technology can be used to screen and refine a simplified traditional Chinese medicine prescription for the prevention and treatment of pulmonary fibrosis. Modern bio-extraction technology is then used to extract and refine the simplified prescription, removing ineffective impurities and retaining effective components to create a new, quality-assured preparation. This preparation can both block the formation of pulmonary fibrosis and restore the normal structure and function of the lungs, fundamentally curing pulmonary fibrosis, while also being convenient for patients to take.

[0025] The composition provided by this invention uses ginseng as the main ingredient and Chamaejasminoides as the secondary ingredient, combined with dried tangerine peel and Citrus medica (tangerine peel). Ginseng is neutral in nature, sweet and slightly bitter in taste, and slightly warm; it enters the spleen, lung, and heart meridians; it is the principal ingredient, described as "greatly replenishing vital energy, benefiting the lungs, and capable of both tonifying and unblocking." Chamaejasminoides is bitter, sweet, and astringent in taste, and slightly warm in nature; it enters the lung, liver, and kidney meridians; it has the function of tonifying the lungs, benefiting the liver and kidneys, and generating essence, thus it can strengthen kidney qi, strengthen the lungs, and benefit the intestines, serving as the secondary ingredient. It nourishes yin, moistens dryness, and generates fluids, on the one hand moistening the collaterals to facilitate smooth flow, and on the other hand restraining the drying and pungent nature of the principal and secondary ingredients, serving as the adjuvant ingredient; it can supplement the insufficient tonifying effect of ginseng on the stomach and intestines, complementing each other. Dried tangerine peel is bitter and pungent in taste, warm, sweet and astringent; it is neutral in nature and enters the heart, lung, and spleen meridians; its functions are regulating qi, harmonizing the middle jiao, drying dampness, and resolving phlegm. It regulates Qi, strengthens the spleen and stomach, unblocks the meridians, and relieves pain. Tangerine peel and orange peel (Citrus reticulata peel) are both assistant herbs, supplementing ginseng to treat the root cause. Buddha's hand (Citrus medica) is pungent, bitter, sour, and warm; it nourishes Yin, moistens dryness, and generates fluids. On one hand, it moistens the meridians to facilitate unobstructed flow; on the other hand, it restrains the drying and pungent nature of the principal and assistant herbs, acting as an adjuvant (soothing the liver and regulating Qi, harmonizing the stomach, and resolving phlegm. Treats stomach pain, hypochondriac distension, vomiting, esophageal obstruction, phlegm-dampness cough and asthma, and can also relieve alcohol intoxication).

[0026] The composition prepared by this invention is a comprehensive formula that tonifies Qi and benefits the lungs, nourishes the stomach and intestines, regulates Qi and invigorates blood circulation, and harmonizes Yin and Yang, eliminating pathogenic factors without harming the body's vital energy. The combination of various herbs is well-matched to the pathogenesis and symptoms, and the formulation emphasizes both tonification and unblocking, combining movement and stillness, and dispersing and astringing; it benefits the kidneys while also taking care of Yin, tonifies Qi without causing warmth or dryness, and regulates Qi without damaging the collaterals.

[0027] The method for preparing the composition according to the present invention is simple, easy to control in terms of quality, low in cost, and has a definite curative effect on pulmonary fibrosis. It has no obvious toxic side effects and is suitable for long-term, high-dose use until a cure is achieved. Attached Figure Description

[0028] Figure 1 This is a diagram showing the pathological examination results of lung tissue in rats with BLM-induced pulmonary fibrosis using FY in an embodiment of the present invention.

[0029] Figure 2 The effect of FY on the expression of transcription factor Keap1 protein in lung tissue of a rat model of BLM-induced pulmonary fibrosis in this embodiment of the invention (IF, X20);

[0030] Figure 3 The effect of FY on the expression of transcription factors Nrf2 and Kelch-like ECH-related protein 1 (Keap1) in lung tissue of a rat model of BLM-induced pulmonary fibrosis is shown in the embodiments of the present invention (x±s, n=6). Detailed Implementation

[0031] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments:

[0032] A composition for treating pulmonary fibrosis, wherein the weight percentage of the composition is:

[0033] Ginseng 15-25%, Chamaejasminoides 40-60%, dried tangerine peel 15-30%, Buddha's hand or tangerine peel 10-15%.

[0034] Preferably, the weight percentage of the composition is: ginseng 16%, chamaegu 50%, dried tangerine peel 24%, and bergamot or tangerine peel 10%.

[0035] A composition for treating pulmonary fibrosis, wherein the weight percentage of the composition is:

[0036] Ginsenoside extract 5-15%, ginseng polysaccharide 5-10%, Chamaegu polysaccharide 25-35%, 10-fold concentrated tangerine peel water extract 20-25%, and Buddha's hand water extract with alcohol precipitation 15-25%.

[0037] Preferably, the weight percentages of the composition are: 12% ginsenoside extract, 10% ginseng polysaccharide, 28% Chamaegu polysaccharide, 26% 10-fold concentrated tangerine peel water extract, and 24% bergamot water extract.

[0038] A method for preparing the above-mentioned composition for treating pulmonary fibrosis includes the following steps:

[0039] S1. Weigh the raw materials of the composition according to the weight percentage, mix them, add water and decoct 3 times. After the first boil, decoct over high heat for 2 hours, after the second boil, decoct over high heat for 1.5 hours, and after the third boil, decoct over high heat for 1.0 hour.

[0040] S2. Filter the raw medicinal liquid obtained from step S1 at 80°C and concentrate it to 1ml to obtain a clear extract of 1.25g of raw medicinal material; then add alcohol and stir until the alcohol content is 56% to 58%, let it precipitate overnight, filter to remove the precipitate, take the supernatant to recover the ethanol; then concentrate it to a specific gravity of 1.15, and keep the concentrate for later use, or place it in a vacuum drying oven at 60°C to dry into a dry paste, and pulverize it into powder;

[0041] S3. Add a medical excipient to obtain an oral pharmaceutical preparation; the obtained oral pharmaceutical preparation is one of the following: oral liquid, granules, capsules, concentrated pills or tablets.

[0042] The above-mentioned composition for treating pulmonary fibrosis is used in the preparation of drugs for the prevention and treatment of pulmonary fibrosis.

[0043] The above-mentioned composition for treating pulmonary fibrosis is used in the preparation of drugs for the prevention and treatment of idiopathic pulmonary fibrosis.

[0044] Example 1 (Oral Liquid)

[0045] Weigh out 5 kg of red ginseng, 12 kg of Chamaejasminoides, 9 kg of dried tangerine peel, and 5 kg of Buddha's hand. Add 10 times the amount of water and decoct three times. After the first boil, maintain a gentle simmer for 2.0 hours. After the second boil, maintain a gentle simmer for 1.5 hours. After the third boil, maintain a gentle simmer for 1.0 hour. Then combine the decoctions, filter, and concentrate the filtrate at 80°C under reduced pressure to a clear extract with a relative density of 1.25. Combine the filtered decoctions and concentrate them using a double-effect evaporator or an open pot at 95-100°C to approximately 1:1 (1 ml is equivalent to 1 g of medicinal material), resulting in approximately 31 L of concentrated liquid (FY).

[0046] Filling: 10ml / vial, sterilizable brown glass bottle; seal, steam or boil for sterilization. Label.

[0047] Granule preparation: 10L of FY concentrate is placed in a drying oven and dried under reduced pressure at 60℃ until the moisture content is 10% dry paste. The paste is then pulverized, starch is added, and it is moistened with 75% alcohol. Granules are then made and dried separately to obtain approximately 20g / dose of granules. The granules are divided into two packets, one packet at a time, taken after breakfast and dinner.

[0048] Example 2 (Granules)

[0049] Weigh out 5 kg of red ginseng, 10 kg of Chamaejasminoides, 6 kg of dried tangerine peel, and 4 kg of Buddha's hand. Add 10 times the amount of water and decoct three times. After the first boil, maintain a gentle simmer for 2.0 hours; after the second boil, maintain a gentle simmer for 1.5 hours; and after the third boil, maintain a gentle simmer for 1.0 hour. Then combine the decoctions and place them in a stainless steel basin. Concentrate the liquid in a water bath until it becomes viscous, approximately 1 ml of which contains 1.2 g of Chamaejasminoides (about 25 L). After filtration, concentrate the filtrate to a clear extract with a relative density of 1.25 at 80°C under reduced pressure. Place the filtrate in a vacuum drying oven at 60°C to obtain a dry extract with a moisture content of 10%. Grind the extract into a fine powder. Add an appropriate amount of dextrin and starch to the dry extract powder, moisten with 75% alcohol, granulate, dry, sizing, and package into 10 g / packets (each pack contains approximately 25 g of the dry powder).

[0050] It can be made into granules, about 20g per dose, divided into 2 packets. Take 1 packet at a time, after breakfast and dinner.

[0051] Example 3 (Capsule Formulation)

[0052] The drug dry extract powder prepared according to the method of Example 1 was filled into gelatin capsules to make capsules, each capsule containing 250mg.

[0053] Example 4 (tablet)

[0054] The drug granules prepared according to the method in Example 1 were compressed into tablets using conventional methods.

[0055] Example 5 (Concentrated Pills)

[0056] The drug powder prepared according to the method in Example 1 was mixed with an appropriate amount of dextrin and starch using conventional methods to form concentrated pills.

[0057] Example 6 (Control Drug)

[0058] Weigh out 5 kg of red ginseng, 10 kg of dried tangerine peel, and 5 kg of Buddha's hand citron. Add 10 times the amount of water and decoct three times. After the first boil, maintain a gentle simmer for 2.0 hours; after the second boil, maintain a gentle simmer for 1.5 hours; and after the third boil, maintain a gentle simmer for 1.0 hour. Then combine the decoctions, filter, and concentrate the filtrate at 80°C under reduced pressure to a clear extract with a relative density of 1.25, approximately 20 L. Bottle the concentrate in 10 ml / vial (sterilizable brown glass bottle), seal, and sterilize by steam or boiling. Label. (Traditional Chinese Medicine Reference 1).

[0059] Clinical validation

[0060] (I) Clinical Data and Methods

[0061] 1. Diagnostic criteria: The inclusion criteria were based on the relevant standards in the "Chinese Expert Consensus on the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis" (Interstitial Lung Disease Group of the Respiratory Disease Branch of the Chinese Medical Association. Chinese Expert Consensus on the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis [J]. Chinese Journal of Tuberculosis and Respiratory Disease, 2016, 49(6): 427-432), and the results were confirmed by clinical manifestations, high-resolution chest CT, and pulmonary function tests; the diagnosis was based on the 2019 guidelines for the diagnosis and treatment of pulmonary fibrosis recognized at home and abroad (Li Zhenhua. Advances in the diagnosis and treatment of idiopathic interstitial pulmonary fibrosis [J]. Chinese Journal of Practical Internal Medicine, 2020, 40(5): 353-356. Patients diagnosed with pulmonary interstitial fibrosis.

[0062] 2. Exclusion criteria: ① Patients with severe dysfunction of major organs, hematological diseases, or immune system diseases; patients with pulmonary heart disease or acute / chronic infections; ② Patients with tuberculosis, malignant lung tumors, acute interstitial pneumonia, advanced IPF, chronic obstructive pulmonary disease, respiratory failure, or other lung diseases; ③ Patients with respiratory diseases such as dyspnea and dry cough caused by other etiologies; ④ Pregnant and lactating women; ⑤ Patients with interstitial lung disease of known etiologies such as drug toxicity, history of exposure to special occupational environments, or connective tissue diseases; ⑥ Patients with allergic constitutions or allergies to the drugs studied; ⑦ Patients who have recently received other IPF treatments.

[0063] Main symptoms according to Traditional Chinese Medicine: Refer to the guidelines for clinical research of new Chinese herbal medicines.

[0064] 3. Patient source: All cases came from outpatients of the Traditional Chinese Medicine Hospital.

[0065] Patient profile: All cases from 2022 to 2023 were selected from patients who met the diagnostic criteria for pulmonary fibrosis in the respiratory department and were diagnosed by clinical examination. A total of 103 patients were included. Among them, 56 were male and 47 were female; the age ranged from 51 to 76 years, with an average age of 63.1 years. The duration of disease ranged from 1 month to 24 months, with an average duration of 15.5 ± 1.4 months.

[0066] Patients meeting the case selection criteria were randomly assigned to three groups: a treatment group, control group 1, and control group 2.

[0067] Treatment group: 34 cases, 19 males and 15 females; duration of illness: 3 to 12 months, with an average of 15.5 ± 1.4 months; age: 51 to 75 years (57.5 ± 2.4) years.

[0068] Control group 1 (traditional Chinese medicine Qi-tonifying decoction): 35 cases, 19 males and 16 females; disease course 3 to 12 months, average 15.3 ± 1.5 months; age 51 to 76 years (57.1 ± 2.6) years.

[0069] Control group 2 (pirfenidone): 34 cases, 18 males and 16 females; disease duration 3 to 11 months, mean 15.3 ± 1.4 months; age 51 to 75 years (57.3 ± 2.4) years.

[0070] The three groups of cases were statistically comparable, showing no significant differences in gender, disease duration, or age (P > 0.05). All participants were informed and signed informed consent forms.

[0071] 4. Treatment methods

[0072] Treatment group: Take 10ml / vial of the oral solution prepared in Example 1, 1 vial / time, 3 times a day.

[0073] Control group 1: Take 10ml / vial of oral liquid prepared as follows, 1 vial / time, 3 times a day.

[0074] Weigh out 5 kg of red ginseng, 10 kg of dried tangerine peel, and 5 kg of Buddha's hand citron. Add 10 times the amount of water and decoct three times. After the first boil, maintain a gentle simmer for 2.0 hours. After the second boil, maintain a gentle simmer for 1.5 hours. After the third boil, maintain a gentle simmer for 1.0 hour. Then combine the decoctions, filter, and concentrate the filtrate under reduced pressure at 80°C to a clear extract with a relative density of 1.25. Bottle the extract in 10 ml vials to prepare an oral liquid.

[0075] Control group 2: Oral pirfenidone (PFD, 200mg / tablet) treatment, 400-600mg, 3 times / day, individualized according to the patient's condition. The pirfenidone was purchased from Beijing Kaiyin Technology Co., Ltd. (National Drug Approval Number H20193259).

[0076] Each group received 15 days as one course of treatment, and the medication was used for a total of 3 months. During this period, other medications for treating pulmonary fibrosis, anti-inflammatory pulmonary fibrosis, and pulmonary function regulation were discontinued.

[0077] The efficacy was evaluated after 2 weeks, 1, 2, and 3 months of treatment in each group.

[0078] 5. Observation Indicators

[0079] ① Safety monitoring: This includes monitoring general vital signs (blood pressure, heart rate, respiration), complete blood count, urinalysis, cardiac, liver and kidney function tests, and adverse reaction monitoring (excitement, irritability, dry mouth, dry tongue). General vital signs are monitored twice a day. Outpatients are informed of the method and instructed to keep detailed records with their families. Other indicators are monitored once before and once after treatment.

[0080] ②Efficacy observation: Improvement of main symptoms (cough, wheezing, spontaneous respiratory function), signs, and laboratory test indicators (blood inflammatory factors, lung function) before and after treatment.

[0081] The efficacy criteria were assessed using the Unified Pulmary Fibrosis Disease Rating Scale (UPFDRS). The efficacy index was calculated as follows: {(Pre-treatment score - Post-treatment score) / Pre-treatment score × 100%}. ≥85% was considered a cure; 70-84% was considered a significant effect; 20%-69% was considered effective; <20% was considered ineffective.

[0082] ① Clinical cure: (referring to the disappearance of symptoms such as cough, wheezing, and spontaneous respiratory function) and the ability to take care of oneself.

[0083] ②Significant effect: refers to the disappearance of symptoms such as cough, wheezing, and spontaneous respiratory function.

[0084] ③ Effective: refers to improvement in cough, wheezing, and spontaneous respiratory function.

[0085] ④ Ineffective: There was no significant improvement in symptoms such as cough, wheezing, and spontaneous respiratory function before and after treatment.

[0086] The severity of the patient's motor symptoms was assessed using Part III of the Unified Life Cycle Rating Scale (UPFDRS) and the Hoehn-Yahr Scale. The patient's daily living abilities were assessed using Part II of the UPFDRS and the Activities of Daily Living Questionnaire (ADCS-ADL). The patient's mental, behavioral, and emotional state were assessed using Part I of the UPFDRS.

[0087] Changes in the main symptoms and signs observed in Traditional Chinese Medicine (TCM) are included in the comprehensive evaluation, with a focus on changes in motor function.

[0088] Statistical methods: t-test was used for continuous data, chi-square test was used for categorical data, and Ridit test was used for ordinal data.

[0089] 6. Evaluation of therapeutic effect

[0090] 6.1 Imaging-based efficacy assessment

[0091] 6.2 Symptomatology-based efficacy assessment

[0092] Currently, there are no symptom-based efficacy assessment tools specifically designed for patients with pulmonary fibrosis, and further research is needed in this area. The SF-36 Quality of Life Scale and the Activities of Daily Living (ADL) Scale were used to assess quality of life.

[0093] As shown in Table 1, the drug of the present invention can effectively improve the main symptoms and signs of lung disease. According to the recognized efficacy standards, the overall treatment of lung disease has good clinical efficacy, and the difference is statistically significant compared with the control group drug QC1 (P<0.01).

[0094] Table 1. Statistical analysis of the efficacy of pulmonary PF in three groups

[0095]

[0096] Compared with control group 2, ※P<0.05

[0097] Using the sum of clinical cure, significant effect, and effective as the data basis for calculating the total effective rate, the clinical efficacy of the three groups was compared. The total effective rates of the treatment group and control group 1 were 88.24% and 82.86%, respectively, while that of control group 2 was 73.54%. The three groups showed significant differences (P<0.05). The present invention had the best effect, followed by the traditional Chinese medicine control group, while pirfenidone had a relatively poor effect.

[0098] Impact on daily living activities and quality of life of PF patients

[0099] Activities of Daily Living (UPFDRS-II) score: After treatment, the scores of activities of daily living in the traditional Chinese medicine group were significantly improved compared with those in the control group, which was statistically significant (P<0.05, see Table 2-1);

[0100] B. Quality of Life Scale (LCCQ) score: After treatment, the LCCQ score of the Chinese medicine group was significantly improved compared with that of the control group, which was statistically significant (P < 0.05, see Table 2-2).

[0101] C. Adverse reactions after 3 months of treatment are shown in Table 2-3;

[0102] Table 2-1 Changes in Activities of Daily Living (UPFDRS-II) scores before and after treatment (x±s)

[0103] Group n Before treatment One month after treatment 2 months after treatment 3 months after treatment FY treatment group 34 16.8±3.8 15.4±3.1 13.1±2.9 <![CDATA[10.2±1.9* ## ]]> Control group 1 35 16.7±3.7 15.2±3.3 13.9±3.1 <![CDATA[12.1±2.2 # ]]> Control group 2 34 16.7±3.8 16.2±3.6 14.4±3.2 <![CDATA[13.2±2.1 # ]]>

[0104] *Compared with control group 2, P<0.05; compared with before treatment, # P<0.05; ## P<0.05.

[0105] Table 2-3 Changes in Least Daily Life Satisfaction (LSIB) scores before and after treatment (x±s)

[0106] Group n Pre-treatment One month after treatment After 2 months of treatment After 3 months of treatment Treatment group 34 9.5±2.1 11.3±2.4 15.1±2.3 17.9±2.6* Control group 1 35 9.6±2.3 10.5±2.6 <![CDATA[13.0±2.8 # ]]> <![CDATA[15.8±2.5 ## ]]> Control group 2 34 9.5±2.2 9.9±2.3 12.3±3.1 <![CDATA[14.5±2.6 # ]]>

[0107] *Compared with control group 2, P<0.05; compared with before treatment, # P<0.05; ## P<0.05.

[0108] Table 2-3 Adverse reaction report after 3 months of treatment (x±s)

[0109]

[0110] **Compared with control group 2, P<0.01

[0111] The drug described in this invention has a significant effect on improving cough and wheezing in pulmonary fibrosis (PF): As can be seen from Tables 2-1 to 2-3, after 3 courses of treatment with the treatment group, control group 1 and control group 2 (pirfenidone tablets), the scores of daily living activities and quality of life scales of the 103 patients treated with the drug were significantly improved in all three groups (P<0.05), indicating that the drug can eliminate asthma and improve patients' daily living activities and quality of life.

[0112] The effective rates in the treatment group and control group 1 for 34 and 35 cases of pulmonary fibrosis (PF) were 88.24% and 82.86%, respectively, while the effective rate in the pirfenidone control group 2 was 73.53%. Although the clinical cure rates of the drug of this invention were only 38.24% and 11.43%, and the significant efficacy rates were 35.29% and 28.57%, respectively, the efficacy of the drug of this invention is significantly higher than the total effective rate of 73.53% of the commonly used drug pirfenidone tablets (P < 0.05). Furthermore, no obvious toxicity was observed with the drug of this invention, while 16 cases (47.06%) in the pirfenidone group experienced elevated transaminase levels and photosensitivity. Only 3 cases (8.82%) of the drug of this invention experienced general gastrointestinal reactions, indicating that the drug of this invention is a safe and effective preparation. However, the effective rate and scores on various evaluation scales in control group 1 were lower than those in the treatment group; therefore, the treatment group showed the best effect with the drug of this invention.

[0113] 6.3 Laboratory Indicators: Levels of Inflammatory Factors

[0114] II. Animal Experiments

[0115] Two different animal models, bleomycin-induced pulmonary fibrosis in rats and silicon-induced pulmonary fibrosis in mice, were selected to investigate the effects of the drug of this invention and pirfenidone, the preferred drug for treating pulmonary fibrosis in modern medicine. The results showed that the drug of this invention has a greater advantage than pirfenidone, the preferred drug for treating pulmonary fibrosis in modern medicine, in preventing and treating pulmonary fibrosis in both animal models.

[0116] Experiment 1: Effects of FY on bleomycin-induced pulmonary fibrosis in experimental rats

[0117] Experimental materials:

[0118] 1. Animals: Adult male SD rats, weighing 180-220g, 6 weeks old, were purchased from Guangdong Provincial Medical Laboratory Animal Center in Guangzhou, China (certification number: Guangdong SCXK, 2018-0002).

[0119] 2. Reagents and Instruments

[0120] 2.1 Reagents

[0121] Pirfenidone was purchased from Beijing Kaiyin Technology Co., Ltd. (National Drug Approval Number H20193259);

[0122] Pirfenidone capsules (specification: 100mg / box, Beijing Kangtini Pharmaceutical Co., Ltd.);

[0123] FY oral solution (batch number: 2023101) was provided and stored in the laboratory of the Medical College of Kashgar University (Kashgar, Xinjiang, China). The preparation method of FY follows Example 1 of this invention. Bleomycin hydrochloride for injection (Haizheng Pfizer Pharmaceutical Co., Ltd.). Feed was purchased from Guangdong Provincial Medical Laboratory Animal Center (A-M07-D, Guangzhou, China). IL1-, IL6-, TNFα rat interleukin 1β (IL-1β) and IL-6 kits (Shenzhen Xinbosheng Biotechnology Co., Ltd., batch numbers: ERC007.96, ERC003.96). Superoxide dismutase (SOD) and malondialdehyde (MDA) assay kits were purchased from Nanjing Jiancheng Bioengineering Institute. p-AMPKα, AMPKα, p-ACC, ACC and β-actin antibodies were purchased from Cell Signal Technology. Fibronectin (#sc-8422) was obtained from Santa Cruz (Dallas, USA). Type IV collagen (#ab236640) antibody was purchased from Abcam (Cambridge, USA). HE and Masson trichrome staining solution were purchased from Servicebio (G1006). Antibody for fibronectin (#sc-8422) was obtained from Santa Cruz (Dallas, USA). Antibody for type IV collagen (#ab236640) was purchased from Abcam (Cambridge, USA). Nrf2 and Keap1 antibodies (Beijing Bio-Science Co., Ltd., batch numbers: bs-1074R, bs-3648R); immunohistochemistry kit (Beijing Zhongshan Jinqiao Biotechnology Co., Ltd., batch number: PV-9004); sodium carboxymethyl cellulose (CMCNa) was purchased from Shanghai Petrochemical Co., Ltd. (30036365, CAS: 9004-32-4, Shanghai). BCA protein detection kit was purchased from Cowin Biosciences (CW0014, Shanghai, China).

[0124] 2.2 Instruments

[0125] The following equipment was used: WBP-4MR Whole-body Plethysmograph (WBP) animal non-invasive pulmonary function respiratory testing system (Shanghai Tawang Intelligent Technology Co., Ltd.); EG1150 H tissue embedding machine (Leica, Germany); KD3368 paraffin microtome (Zhejiang Jinhua Kedi Co., Ltd.); DP73 optical microscope (OLYMPUS Co., Ltd., Japan); multi-functional microplate reader (MULTISKAN GO); 721B spectrophotometer (Shanghai Xinmao Instrument Co., Ltd.). Other instruments included: Berthold Mithras LB 940 multi-functional microplate reader, Eppendoff high-speed refrigerated centrifuge, and Image-pro plus image acquisition and analysis system.

[0126] 3 Experimental Methods

[0127] 3.1 Animal model establishment, grouping, and dosing design

[0128] Eighty SD rats were randomly divided into four groups: normal control, model control, pirfenidone 70 mg / kg, FY 7.50, and 100 mg / kg (equivalent to 0.5 and 1 times the clinical equivalent dose), with 12 rats in each group. The rats were housed in a standard environment with a relative humidity of 40–70% and a temperature of 20–26°C, and were fed and watered regularly, allowing them to acclimatize for one night. Experimental procedures complied with animal experimental ethics guidelines. All animal experiments were approved by the Animal Experiment Ethics Committee of Guangdong Pharmaceutical University (GDPulac2023180).

[0129] The establishment of a rat model of bleomycin-induced pulmonary fibrosis was based on the experiment of Ding et al. (Ding et al., 2019). Rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (3 mL / kg) (except for the normal control group). After adequate anesthesia, rats in each group were placed in a supine position with their limbs fixed. The rat's tongue was pulled out using the thumb and forefinger. Holding a laryngoscope, a microsyringe was quickly inserted into the trachea. 5 U / kg BLM solution was injected into the trachea of ​​the model group and the drug-treated group, while the control group received an equal volume of physiological saline. The injection was ensured to completely enter the airway without residue. After the infusion was completed, the rats were returned to their cages, and their recovery was monitored continuously. Pulmonary fibrosis began to form one week after BLM induction.

[0130] On the day following intratracheal infusion, rats in the treatment groups were administered FY 100 mg / kg, XF-1 200 mg / kg, and PFD 70 mg / kg by gavage, respectively. The normal control group and the model control group were given 10 mL / kg of physiological saline, while the other groups were given the corresponding drugs, with an administration volume of 10 mL / kg, once daily for 28 days.

[0131] 3.2 Respiratory function test of IPF rats

[0132] Respiratory function was tested 1 hour after the last administration of the drug to the animals. The instrument parameters were set, and the rats were placed in the device for 10 to 15 minutes to adapt. The inspiratory time (Ti), expiration time (Te), and tidal volume (Vt) were monitored and recorded, and statistical analysis was performed.

[0133] 3.3 Specimen Collection

[0134] Eighteen hours after the last administration, rats were weighed, anesthetized with chloral hydrate, and euthanized by blood collection from the abdominal aorta. 10 ml of blood was collected from the abdominal aorta and centrifuged at 3000 rpm for 10 minutes using standard methods to prepare serum, which was then stored at -80℃ for later testing. Rats were then euthanized, and lung tissue was separated and accurately weighed wet. The lung coefficient was calculated as follows: Lung coefficient = Lung wet weight (mg) / Body weight (g). A low lung coefficient indicates mild fibrosis, while a high lung coefficient indicates severe fibrosis.

[0135] Pathological examination

[0136] The lower lobe of the left lung was harvested, cleaned of residual blood with PBS solution, and fixed in 4% paraformaldehyde. Then, it was dehydrated by sucrose gradient, embedded in paraffin, and sectioned to a thickness of 5 μm. The sections were spread, mounted, dried, and incubated overnight at 37°C. The sections were then mounted with neutral resin and stained with HE and Masson staining, respectively. The lung tissue inflammation and fibrosis (collagen proliferation) were observed under an optical microscope.

[0137] The lower lobe of the right lung was used for immunohistochemical detection; the remaining lung tissue was used to prepare tissue homogenate, and the supernatant was frozen at -80℃ for later use in detecting inflammatory factors and hydroxyproline (HYP).

[0138] Scoring: The scoring criteria for alveolar inflammation in stained lung tissue are determined according to the Szapiel pathological evaluation method. 1: No alveolar inflammation, no pulmonary fibrosis; 2: Mild alveolar inflammation, mainly characterized by mononuclear cell infiltration, widened alveolar septa but normal structure, infiltration limited to the pleural region, mild pulmonary fibrosis, lesion extent ≤20% of the entire lung; 3: Moderate alveolaritis, moderate pulmonary fibrosis, lesion extent 20%–50% of the entire lung; 4: Severe alveolaritis, severe pulmonary fibrosis, occasionally with mononuclear cells in the alveolar cavities and hemorrhage causing consolidation. Lesion extent ≥50% of the entire lung, with structural changes.

[0139] Pulmonary fibrosis severity scoring: 1 point for no fibrosis, 2 points for mild, 3 points for moderate, and 4 points for severe pulmonary fibrosis. Mild fibrosis mainly affects the pleura and subpleural interstitium, with disordered alveolar structure and an affected area of ​​less than 20%; moderate fibrosis affects 20% to 50% of the entire lung; severe fibrosis affects more than 50% of the entire lung, with disordered lung parenchyma and fusion, and visible air cysts of varying sizes.

[0140] 3.4 Determination of inflammatory factors, HYP and collagen content in lung tissue

[0141] Lung tissues from rats in the control group, model group, and five different drug administration groups were homogenized, and the contents of inflammatory factors (IL-1β, IL-6, TNF-α), fibrosis-related protein HYP, and collagen in the lung tissues were detected by enzyme-linked immunosorbent assay.

[0142] 3.5 Enzyme-linked immunosorbent assay (ELISA) for detecting IL-1β and IL-6 levels in rat serum: Serum samples were removed from a -80°C freezer and thawed at room temperature. Standards were diluted, samples were added, incubated at 37°C for 30 min, washed 5 times, enzymes were added, incubated again at 37°C for 30 min and washed 5 times, color development was performed, the reaction was terminated, and finally, the absorbance (OD value) was measured. The actual concentration of the sample was calculated according to the manufacturer's instructions.

[0143] 3.6 Detection of SOD activity and MDA content in rat serum

[0144] Serum samples were removed from the -80℃ freezer and left at room temperature for 30 minutes. SOD activity was measured using the WST-1 method (ELISA reader 450nm), and MDA content was measured using the TBA method (visible spectrophotometer 532nm).

[0145] 3.7 Immunohistochemical detection of Nrf2 and Keap1 protein expression in rat lung tissue

[0146] Rat tissue sections were routinely dewaxed, graded-distilled with ethanol, incubated with 3% H2O2 solution at room temperature for 10 min to inactivate catalase, washed with PBS, and incubated with primary antibody (1:100) at 4°C overnight. After washing with PBS, secondary antibody (1:1000) was added and incubated at 37°C for 20 min. The sections were then washed with PBS, developed with DAB, rinsed thoroughly with tap water for 3-5 min, counterstained with hematoxylin, dehydrated stepwise with ethanol, cleared with xylene, and mounted with neutral resin. Nrf2 and Keap1 positive expression appeared as brownish-yellow granules. The average optical density was analyzed using Image Pro-Plus software to reflect the expression levels of the relevant proteins.

[0147] 3.8 The mRNA expression levels of tumor necrosis factor receptor Toll-like receptor 4, nuclear transcription factor-κB p65 (NF-κB p65), IL-1β, and NOD-like receptor 3 (NLRP3) genes in lung tissue were detected by real-time quantitative polymerase chain reaction.

[0148] 3.9 Statistical Methods

[0149] The analysis was performed using the one-way ANOVA module in SPSS 26.0 statistical software. All measurement results are expressed as (x±s). P<0.05 and P<0.01 indicate that the differences between the two groups are statistically significant.

[0150] 4. Results

[0151] 4.1 Effects of FY formula on lung respiratory function in BLM model rats

[0152] After BLMf modeling, the lung respiratory function of rats was significantly weakened. FY formula, control Chinese medicine and pirfenidone (PFD) all had a certain effect on improving the weakened lung respiratory function of BLM model rats. FY formula had the most significant effect, followed by the control Chinese medicine, and PFD had a less significant effect (see Table 4-1).

[0153] This study found that IPF rats with BLM model exhibited respiratory distress based on respiratory function tests. After treatment with traditional Chinese medicine, FY decoction was found to significantly improve the respiratory distress of IPF rats, specifically by shortening Ti and Te and significantly increasing Vt.

[0154] Table 4-1. Effects of FY formula on lung respiratory function in BLM model rats

[0155]

[0156] Compared with the normal group, P < 0.01; compared with the model group, P < 0.01

[0157] 4.2 Effects on the lung coefficient of BLM model rats

[0158] After BLMf modeling, the lung coefficient of rats increased significantly, indicating that lung fibrosis occurred. FY formula, control Chinese medicine and pirfenidone (PFD) all had a certain ameliorative effect on the increase of lung coefficient in BLM model rats. FY formula had the most significant ameliorative effect, followed by the control Chinese medicine, and PFD had a less significant effect (see Table 4-2).

[0159] Table 4-2. Effect of FY formula on lung coefficient in BLM model rats (X±SEM)

[0160] Group Number of animals (n) Lung coefficient normal group 10 0.92±0.36 Model group 10 1.68±0.35** FY50mg / kg 10 <![CDATA[1.48±0.33 ## ]]> FY200mg / kg 10 <![CDATA[1.32±0.31 ## ]]> Control treatment 200mg / kg 10 <![CDATA[1.41±0.35 ## ]]> PFD 70mg / kg 10 <![CDATA[1.43±0.36 ## ]]>

[0161] ** Compared with the normal group, P<0.01; ## Compared with the model group, P<0.01

[0162] 4.3 Effects on pneumonia and fibrosis scores in BLM model rats

[0163] After BLMf modeling, the pneumonia and fibrosis scores of rats increased significantly, indicating that pulmonary fibrosis occurred. FY formula, control Chinese medicine and pirfenidone (PFD) all had a certain ameliorative effect on the increase of pneumonia and fibrosis scores in BLM model rats. FY formula had the most significant ameliorative effect, followed by the control Chinese medicine, and PFD had a less significant effect (see Table 4-3).

[0164] Table 4-3 Effects of FY formula on pneumonia and fibrosis scores in BLM model rats (X±SEM)

[0165]

[0166]

[0167] ** Compared with the normal group, P<0.01; ## Compared with the model group, P<0.01

[0168] HE staining revealed the morphology of lung tissue, PAS staining measured lung tissue thickness, and Masson's trichrome staining determined the percentage of blue collagen fibers in the lung tissue. Sirius red staining determined the percentage of red collagen fibers. Three lung tissue samples were randomly selected, and the area of ​​pulmonary fibrosis was measured using HE and PAS staining. Image-Pro Plus 6.0 software was used to quantify the lung tissue area and the area of ​​blue or red fibrosis.

[0169] like Figure 1 As shown, HE staining and Masson staining were used to examine the morphology of lung tissue. The results showed that lung tissue treated with bleomycin (BLM) had extensive inflammatory cell infiltration, alveolar enlargement, and collagen deposition. After FY treatment, pulmonary fibrosis was reduced, lung structure and interstitium were improved, collagen deposition was reduced, and the pathological damage caused by BLM was significantly alleviated. Simultaneously, immunohistochemical results showed that after PF treatment... D Following treatment, characteristic fibrotic proteins such as α-sma, Collagen, and Fibronecion were highly expressed in lung tissue. In contrast, the expression of these characteristic fibrotic proteins decreased after FY treatment. These results suggest that BLM can induce idiopathic pulmonary fibrosis, and FY can alleviate BLM-induced pulmonary fibrosis.

[0170] Idiopathic pulmonary fibrosis is associated with chronic fibrosis and inflammation induced by the synthesis and release of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1β). Studies have shown that both FY formula and pirfenidone can reduce the accumulation of inflammatory cells induced by various stimuli, and weaken cell proliferation, fibrosis-related protein and cytokine production, and extracellular matrix synthesis and accumulation induced by fibroblast stimulation with cell growth factors such as transforming growth factor-β (TGF-β). Bleomycin-induced pulmonary fibrosis model experiments in rats showed that both FY formula and pirfenidone have anti-fibrotic and anti-inflammatory effects, but the drug FY from this invention exhibits superior activity.

[0171] 4.4 Effects on lung HYP in BLM model rats

[0172] After BLMf modeling, the HYP in the lung tissue of rats increased significantly, indicating an increase in fibrotic proteins in the lung tissue. FY formula, control Chinese medicine and pirfenidone (PFD) all significantly increased HYP and collagen in the lungs of BLM model rats and had a certain improvement effect. FY formula had the most significant improvement effect, followed by the control Chinese medicine, and PFD had a less significant effect (see Table 4-4).

[0173] Table 4-4. Effects of FY formula on lung HYP and collagen content in BLM model rats (X±SEM)

[0174]

[0175]

[0176] ** Compared with the normal group, P<0.01; ## Compared with the model group, P<0.01

[0177] 4.5 Effects on pulmonary oxidative stress in BLM model rats

[0178] After BLMf modeling, the lung tissue of rats showed a significant increase in MDA and a significant decrease in SOD, indicating endoplasmic reticulum oxidative stress in the lung tissue. FY formula, control Chinese medicine and pirfenidone (PFD) all had a certain ameliorative effect on the significant increase in lung MDA and the significant decrease in SOD in BLM model rats. FY formula had the most significant ameliorative effect, followed by the control Chinese medicine, and PFD had a less significant effect (see Table 4-5).

[0179] Table 4-5. Effects of FY formula on oxidative stress in lung tissue of BLM model rats (X±SEM)

[0180] Group Animal number SOD (U / mg) MDA (nmol / mg) normal group 10 160.1±16.5 0.77±0.25 Model group 10 92.5±20.4** 2.15±0.41** FY50mg / kg 10 113.2±25.3 <![CDATA[1.52±0.45 # ]]> FY200mg / kg 10 <![CDATA[138.2±19.3 ## ]]> <![CDATA[1.03±0.35 ## ]]> Control group 200mg / kg 10 <![CDATA[121.4±18.9 # ]]> <![CDATA[1.19±0.38 ## ]]> PFD 70mg / kg 10 <![CDATA[123.6±23.5 # ]]> <![CDATA[1.21±0.26 ## ]]>

[0181] ** Compared with the normal group, P<0.01;

[0182] FY can reduce ROS levels and alleviate endoplasmic reticulum stress. In vivo experiments in mice showed that bleomycin can increase ROS levels and promote endoplasmic reticulum stress.

[0183] like Figure 2 As shown, this was further verified at the cellular level in this experiment, and the mechanism of action of FY in alleviating fibrosis was explored. ROS level detection showed that bleomycin induced ROS generation in rat lung tissue cells, while FY reduced ROS levels in rat lung tissue cells. Western blotting was used to detect the expression levels of endoplasmic reticulum stress proteins; the ratio of endoplasmic reticulum stress protein expression levels was also analyzed. (FY is Lung-Nourishing Decoction; *p; 0.05, **p; 0.01, # Compared with the model group, P<0.05; ## Compared with the model group, P<0.01); RT-qPCR results showed that the endoplasmic reticulum stress genes Caspase-12 and GRP78 in rat lung tissue cells were reduced after FY treatment, suggesting that FY can alleviate endoplasmic reticulum stress induced by BLM. Figure 2 B and Figure 2 C). Western blot results showed that after FY treatment, the expression levels of endoplasmic reticulum stress proteins Caspase-12 and GRP78 were significantly reduced. Figure 2 (D, 2E, 2F). The above experiments further verified that bleomycin can induce cellular oxidative stress, while YF, the control traditional Chinese medicine, and PFD can all reduce the ROS level of rat lung tissue cells, alleviate endoplasmic reticulum stress, and reduce cell damage, but YF has the strongest effect.

[0184] 4.6 Effects on inflammatory factors in lung tissue

[0185] After BLM modeling, the inflammatory factors in the lung tissue of rats increased significantly, indicating a significant inflammatory response in the lung tissue. FY formula, control Chinese medicine and pirfenidone (PFD) all significantly reduced the content of inflammatory factors in the lung tissue of BLM model rats and significantly improved the inflammatory response in the lung tissue. FY formula had the most significant improvement effect, followed by the control Chinese medicine, and PFD had a less significant effect (see Table 4-6).

[0186] Table 4-6. Effects of FY formula on pneumonia factors in BLM model rats (X±SEM, pg / ml)

[0187] Group Animal number IL-1β IL6 TNFα normal group 10 0±1.3 ± 120.5±25.2 Model group 10 48.3±6.5** ± 285.3±42.1 FY50mg / kg 10 <![CDATA[29.3±8.3 ## ]]> ± 212.6±28.5 FY200mg / kg 10 <![CDATA[25.5±6.1 ## ]]> ± 163.1±30.3 Control treatment 200mg / kg 10 <![CDATA[31.6±5.3 ## ]]> ± 190.5±35.1 PFD 70mg / kg 10 <![CDATA[28.1±6.3 ## ]]> ± 208.2±32.5

[0188] ** Compared with the normal group, P<0.01; ## Compared with the model group, P<0.01

[0189] As shown in Table 4-7, the levels of TNF-α, TGF-β, MMP-7, and MCP-1 in the BALF supernatant of rats in the model group were significantly higher than those in the control group; while the levels of TNF-α, TGF-β, MMP-7, and MCP-1 in the lung tissue homogenate supernatant of rats in the drug treatment group were significantly lower than those in the model group.

[0190] Table 4-7 FY levels of TNF-α, TGF-β, MMP-7, and MCP-1 in BALF supernatant of BLM rats (pg / ml)

[0191]

[0192]

[0193] The results of this experiment show that BLM induction significantly increases the release levels of profibrotic and inflammatory factors in BALF, while FY can significantly reduce the secretion of profibrotic and inflammatory factors, thereby effectively alleviating disease progression.

[0194] Compared with the model group, FY1 alleviated the pathological changes in lung tissue, alveolar infiltration, protein exudation, and excessive cytokine release in rats with lung injury; and significantly reduced the mRNA expression level of key genes in the NF-κB / NLRP3 pathway. Conclusion: FY has a significant protective effect against LPS-induced lung injury in mice, and its mechanism may be the regulation of the NF-κB / NLRP3 signaling pathway and the inhibition of pulmonary fibrosis.

[0195] In vivo experiments in rats showed that bleomycin can increase the levels of inflammatory factors and promote intercellular inflammatory responses. These experiments further validated that bleomycin can induce cellular inflammatory responses, while YF can reduce inflammatory factors and alleviate cell damage.

[0196] In this embodiment, respiratory function tests revealed that IPF rats modeled with BLM exhibited dyspnea. Treatment with traditional Chinese medicine (TCM) showed that the modified Bufei Decoction significantly improved dyspnea in IPF rats, specifically by shortening Ti and Te and significantly increasing Vt. HE and Masson staining results showed that collagen deposition in the lungs of IPF rats followed the same trend as the inflammatory response. BLM model rats had a large number of inflammatory cells in their lungs, significantly increased collagen proliferation, and pathological changes in lung tissue structure, with collagen replacing normal alveolar structure, leading to impaired respiratory function. Treatment with FY Decoction improved the pathological condition, specifically by reducing inflammatory infiltration, decreasing collagen levels, and restoring alveolar structure, thus improving ventilation function in IPF rats.

[0197] In vivo experiments in rats have shown that bleomycin can increase the levels of inflammatory factors and promote intercellular inflammatory responses. In this embodiment, this was further verified at the cellular level, and the mechanism of action of FY in alleviating fibrosis was explored. Inflammatory factor level detection showed that bleomycin induced the production of inflammatory factors in BEAS-2B human lung epithelial cells, while FY reduced the level of inflammatory factor S in BEAS-2B human lung epithelial cells.

[0198] like Figure 3 As shown, RT-qPCR results indicated that AKT and GRP78, genes involved in the inflammatory pathway in BEAS-2B human lung epithelial cells, were reduced after FY treatment, suggesting that FY can alleviate bleomycin-induced inflammation. Figure 3 B and Figure 3 C). Western blot results showed that after FY treatment, the expression levels of inflammatory factors IL1β and TNFα were significantly reduced (C). Figure 3 (D, 3E, 3F). The above experiments further verified that bleomycin can induce cellular inflammatory response and endoplasmic reticulum oxidative stress, thereby inducing pulmonary fibrosis in rats; while the drug YF of this invention can reduce inflammatory factors, alleviate cell damage, and reduce pulmonary fibrosis, showing superior effects compared to the drug pirfenidone (PFD).

[0199] The above descriptions are merely embodiments of the present invention, and common knowledge regarding specific technical solutions or characteristics is not elaborated upon here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A composition for treating pulmonary fibrosis, characterized in that, The weight percentage of the composition is: Ginseng 15-25%, Chamaejasminoides 40-60%, dried tangerine peel 15-30%, Buddha's hand or tangerine peel 10-15%.

2. The composition for treating pulmonary fibrosis according to claim 1, characterized in that, The composition is composed of the following weight percentages: ginseng 16%, chamaegu 50%, dried tangerine peel 24%, and citron or tangerine peel 10%.

3. A method for preparing the composition for treating pulmonary fibrosis as described in claim 1 or 2, characterized in that, Includes the following steps: S1. Weigh the raw materials of the composition according to the weight percentage, mix them, and then decoct them with water; S2. Filter and concentrate the raw medicinal liquid obtained from step S1 to obtain a clear paste; then add alcohol and stir until the alcohol content is 56% to 58%, let it precipitate overnight, filter to remove the precipitate, take the supernatant to recover the ethanol; then concentrate to a concentrated liquid for later use, or place it in a vacuum drying oven to dry into a dry paste, and pulverize it into powder. S3. Add medical excipients to obtain oral drug formulations.

4. The method for preparing a composition for treating pulmonary fibrosis according to claim 3, characterized in that, In S1, the raw materials are decocted with water three times. After the first boil, the decoction is boiled over high heat for 2 hours. After the second boil, the decoction is boiled over high heat for 1.5 hours. After the third boil, the decoction is boiled over high heat for 1.0 hour.

5. The method for preparing a composition for treating pulmonary fibrosis according to claim 3, characterized in that, In S2, the raw material solution is filtered at 80°C and concentrated to 1 ml to obtain a clear extract of 1.25 g of raw medicinal material; after recovering ethanol, it is concentrated to a specific gravity of 1.15; and then dried into a dry extract in a vacuum drying oven at 60°C.

6. The method for preparing a composition for treating pulmonary fibrosis according to claim 3, characterized in that, In S3, the prepared oral drug formulation is one of the following: oral liquid, granules, capsules, concentrated pills, or tablets.

7. The use of the composition for treating pulmonary fibrosis according to claim 1 or 2 in the preparation of medicaments for the prevention and treatment of pulmonary fibrosis.

8. The use of the composition for treating pulmonary fibrosis according to claim 1 or 2 in the preparation of medicaments for the prevention and treatment of idiopathic pulmonary fibrosis.

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