Use of etomoxir or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the prevention and treatment of interstitial lung diseases and related lung injuries

Abstract

The present application relates to the application of etomoxir or its pharmaceutically acceptable salt in the preparation of a drug for preventing, improving or treating interstitial lung disease and related lung injury. The present application creatively finds that etomoxir and its pharmaceutically acceptable salt have excellent prevention and treatment effect on interstitial lung disease and related lung injury, which specifically shows that: it can effectively reverse the abnormal growth of lung index, lung function damage of interstitial lung disease mice induced by lipopolysaccharide or irradiation, improve the lung inflammation damage and the degree of pulmonary fibrosis of interstitial lung disease mice induced by lipopolysaccharide or irradiation. It provides a new strategy and theoretical basis for clinical prevention, improvement or treatment of interstitial lung disease.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology and relates to the use of atetomodil or its pharmaceutically acceptable salts in the preparation of drugs for the prevention and treatment of interstitial lung disease and related lung injury. Background Technology

[0002] Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease, is a group of chronic respiratory diseases with complex etiologies and highly heterogeneous pathological manifestations. These diseases primarily affect the lung interstitium, alveolar epithelial cells, pulmonary capillary endothelium, and alveolar spaces, gradually leading to structural destruction of lung tissue and irreversible damage to gas exchange function.

[0003] Interstitial lung diseases include connective tissue disease-associated interstitial lung disease, occupational / environmental exposure-induced pulmonary fibrosis, drug-induced lung injury, and allergic pneumonia. Common clinical features of these diseases include progressively worsening exertional dyspnea and dry cough. Pulmonary function tests often show restrictive ventilatory dysfunction with reduced diffusion capacity. High-resolution chest CT scans reveal diffuse ground-glass opacities, reticular formation, and honeycomb-like interstitial changes in both lungs. Patients experience impaired long-term quality of life, and progressive cases have a high mortality rate.

[0004] Among them, progressive fibrosing interstitial lung disease (PF-ILD) is a clinical phenotype of ILD with extremely poor prognosis. It is not limited by the underlying cause and is characterized by the continuous progression of pulmonary fibrosis on chest imaging and the progressive deterioration of lung function. Patients experience progressive worsening of dyspnea symptoms and a significantly shortened survival period, making it a key focus and challenge in the current clinical diagnosis and treatment of ILD.

[0005] Current clinical treatment for ILD primarily focuses on anti-inflammatory and non-specific anti-fibrotic therapies. While these can slow disease progression in some patients to a certain extent, they are insufficient to completely halt the disease progression in most cases and cannot reverse existing irreversible lung tissue damage. Therefore, developing more medication strategies that can reverse existing irreversible lung tissue damage and effectively halt the progression of ILD is of great significance. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the purpose of this invention is to provide the use of atemotoxin or its pharmaceutically acceptable salt in the preparation of medicaments for the prevention and treatment of interstitial lung disease and related lung injury.

[0007] To achieve this objective, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides the use of iotomod or a pharmaceutically acceptable salt thereof, as shown in formula (I), in the preparation of medicaments for the prevention, improvement or treatment of interstitial lung disease and related lung injury;

[0009] Formula (I).

[0010] This invention creatively discovers that atemotome and its pharmaceutically acceptable salts have excellent preventive and therapeutic effects on interstitial lung disease and related lung injuries. Specifically, they can effectively reverse the abnormal increase in lung index and lung function impairment in mice with interstitial lung disease, and improve lung inflammation and fibrosis. This provides a new strategy and theoretical basis for the clinical prevention, improvement, or treatment of interstitial lung disease.

[0011] Preferably, the interstitial lung disease and related lung injury are lipopolysaccharide-induced interstitial lung disease and related lung injury.

[0012] Preferably, the interstitial lung disease and related lung injury are radiation-induced interstitial lung disease and related lung injury.

[0013] In the above applications, the iotomod or its pharmaceutically acceptable salt reverses the abnormal increase in lung index caused by lipopolysaccharide or irradiation.

[0014] In the above applications, the iotomod or its pharmaceutically acceptable salt improves lung function damage caused by lipopolysaccharide or irradiation.

[0015] In the above applications, atetomod or its pharmaceutically acceptable salts improve inflammatory damage to the lungs.

[0016] In the above applications, atetomod or its pharmaceutically acceptable salts improve the degree of pulmonary fibrosis.

[0017] In the above applications, the drug also includes pharmaceutically acceptable excipients.

[0018] Preferably, the pharmaceutically acceptable excipients include any one or a combination of at least two of the following: carriers, diluents, flavoring agents, binders, fillers, thickeners, disintegrants, solubilizers, suspending agents, lubricants, or buffers.

[0019] The atorvastatin of the present invention can be prepared according to methods known in the art. It can be formulated into any dosage form suitable for human or animal use by combining the atorvastatin of formula (I) of the present invention or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients. The atorvastatin of formula (I) of the present invention is typically present in a pharmaceutical composition at a content of 0.1-95% by weight.

[0020] The route of administration of atorvastatin or a pharmaceutical composition containing it, as shown in Formula (I) of this invention, can be enteric or non-enteric, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum, etc. The dosage form can be liquid, solid, or semi-solid. Liquid dosage forms can be solutions (including true solutions and colloidal solutions), emulsions (including o / w, w / o, and double emulsions), suspensions, injections (including aqueous injections, powder injections, and infusions), eye drops, nasal drops, lotions, and liniments, etc.; solid dosage forms can be tablets (including ordinary tablets, enteric-coated tablets, lozenges, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules (including hard capsules, soft capsules, and enteric-coated capsules), granules, powders, microcapsules, droplets, suppositories, films, patches, aerosols, sprays, etc.; semi-solid dosage forms can be ointments, gels, pastes, etc. The atetomod or its pharmaceutically acceptable salt of the present invention can be formulated into conventional formulations, sustained-release formulations, controlled-release formulations, targeted formulations, and various microparticle delivery systems.

[0021] The dosage of atorvastatin according to formula (I) of this invention can vary widely depending on the nature and severity of the disease to be prevented or treated, the individual circumstances of the patient or animal, the route of administration, and the dosage form. Generally, the appropriate daily dose range of atorvastatin of this invention is 0.01-150 mg / kg body weight, preferably 0.1-100 mg / kg body weight, more preferably 0.1-60 mg / kg body weight, and most preferably 0.3-60 mg / kg body weight. The above dosage can be administered as a single dose unit or divided into several dose units, depending on the physician's clinical experience and the administration regimen, including the use of other treatment methods.

[0022] The atorvastatin of formula (I) of this invention, or a pharmaceutical composition containing it, may be taken alone or in combination with other therapeutic or symptomatic medications. When the atorvastatin of formula (I) of this invention has a synergistic effect with other therapeutic medications, its dosage should be adjusted according to the actual situation.

[0023] In a second aspect, the present invention provides a combination pharmaceutical composition, wherein the active components of the combination pharmaceutical composition include a first component and a second component; the first component is selected from atemotoxin or a pharmaceutically acceptable salt thereof; and the second component is selected from prednisolone acetate or a pharmaceutically acceptable salt thereof.

[0024] The dosage of the first and second components can be rationally selected by those skilled in the art based on the nature and severity of the disease to be prevented or treated, the individual circumstances of the patient or animal, the route of administration, and the dosage form.

[0025] Preferably, the combined pharmaceutical composition is a single compound preparation or a combination of two separate preparations. The combined pharmaceutical composition is a combination of two separate preparations, which are administered simultaneously or sequentially.

[0026] Thirdly, the present invention provides the use of the combined pharmaceutical composition as described in the second aspect in the preparation of a medicament for the prevention, improvement or treatment of interstitial lung disease and related lung injury.

[0027] Preferably, the interstitial lung disease and related lung injury are lipopolysaccharide-induced interstitial lung disease and related lung injury.

[0028] In the above applications, the combined pharmaceutical composition reverses the abnormal increase in the lung index caused by lipopolysaccharide or irradiation.

[0029] In the above applications, the combined pharmaceutical composition improves lung function damage caused by lipopolysaccharide or irradiation.

[0030] In the above applications, the combined pharmaceutical composition improves inflammatory damage to the lungs.

[0031] In the above applications, the combined pharmaceutical composition improves the degree of pulmonary fibrosis.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] This invention creatively discovers that atemotoxin and its pharmaceutically acceptable salts have excellent preventive and therapeutic effects on interstitial lung disease and related lung injuries. Specifically, it can effectively reverse the abnormal increase in lung index and lung function impairment in mice with lipopolysaccharide or irradiation-induced interstitial lung disease, and improve the degree of lung inflammation and fibrosis in these mice. This provides a new strategy and theoretical basis for the clinical prevention, improvement, or treatment of interstitial lung disease. Attached Figure Description

[0034] Figure 1 This is a graph showing the effect of iotomod on the lung index in a lipopolysaccharide-induced mouse interstitial lung disease model;

[0035] Figure 2 This is a graph showing the effect of iotomod on lung function in a mouse model of lipopolysaccharide-induced interstitial lung disease.

[0036] Figure 3 This is a graph showing the effect of iotomod on lung pathological changes in a lipopolysaccharide-induced mouse interstitial lung disease model (HE staining).

[0037] Figure 4 This is a graph showing the effect of iotomodil on lung pathological changes in a lipopolysaccharide-induced mouse interstitial lung disease model (Masson staining results).

[0038] Figure 5 The figure shows the effect of atorvastatin on the lung index of a mouse model of interstitial lung disease induced by lipopolysaccharide and based on prednisolone acetate.

[0039] Figure 6 The figure shows the effect of atorvastatin on lung function in a mouse model of interstitial lung disease induced by lipopolysaccharide and based on prednisolone acetate.

[0040] Figure 7 This is a figure showing the effect of atorvastatin on lung pathological changes in a mouse model of interstitial lung disease induced by lipopolysaccharide and based on prednisolone acetate (HE staining).

[0041] Figure 8 This is a graph showing the effect of atorvastatin on lung pathological changes in a mouse model of interstitial lung disease induced by lipopolysaccharide and based on prednisolone acetate (Masson staining results).

[0042] Figure 9 The figure shows the effect of atorvastatin on serum C-reactive protein levels in a mouse model of interstitial lung disease induced by lipopolysaccharide and based on prednisolone acetate.

[0043] Figure 10 The figure shows the effect of atorvastatin on the serum salivary glycoprotein antigen content in a mouse model of interstitial lung disease induced by lipopolysaccharide and based on prednisolone acetate.

[0044] Figure 11 The figure shows the effect of iotomod on the survival rate of an irradiated mouse model of interstitial lung disease.

[0045] Figure 12 This is a graph showing the effect of iotomod on the lung index in an irradiated mouse model of interstitial lung disease.

[0046] Figure 13 This is a graph showing the effect of iotomod on lung function in an irradiated mouse model of interstitial lung disease.

[0047] Figure 14 This is a graph showing the effect of iotomod on blood cell counts in an irradiated mouse model of interstitial lung disease.

[0048] Figure 15 This is a graph showing the effect of iotomodil on serum C-reactive protein levels in an irradiated mouse model of interstitial lung disease. Detailed Implementation

[0049] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0050] The iotomod used in the following experimental examples is from Beijing Zhaoyan New Drug Research Center Co., Ltd., product model SNT20140425. The drug dosage in all experimental examples is based on the actual effective dose of iotomod in the product.

[0051] Experimental Example 1

[0052] Pharmacodynamic studies of atormode in animal models of lipopolysaccharide-induced interstitial lung disease

[0053] (1) Experimental animals: SPF grade C57BL / 6 mice (6-8 weeks old, weight 20g±2g) were selected and fed with ordinary feed for 7 days in an animal room (room temperature: 24±1℃, humidity: 50±10%, 12-hour light-dark cycle) (free access to food and water).

[0054] (2) Animal grouping: Mice were randomly divided into 7 groups according to their body weight: sham operation group, lipopolysaccharide group (LPS), lipopolysaccharide + prednisolone acetate group (LPS + 5 mg / kg PA), lipopolysaccharide + mycophenolate mofetil group (LPS + 33.3 mg / kg MMF), lipopolysaccharide + iotomod low-dose group (LPS + 0.3 mg / kg iotomod), lipopolysaccharide + iotomod medium-dose group (LPS + 0.6 mg / kg iotomod), and lipopolysaccharide + iotomod high-dose group (LPS + 1.2 mg / kg iotomod), with 10 animals in each group.

[0055] (3) Modeling and administration: Except for the sham-operated group, a lipopolysaccharide-induced interstitial lung disease animal model was established by intratracheal infusion of lipopolysaccharide (5 mg / kg) into mice for 5 consecutive days. The administration was carried out in the above manner starting on the first day of modeling, with the sham-operated group and the lipopolysaccharide group given an equal volume of solvent control (0.5% CMC-Na).

[0056] (4) Indicator detection: The experiment ended on day 15. The pharmacodynamic evaluation of lung inflammation and fibrosis was carried out using lung weight index (lung weight / body weight × 1000), lung function, HE and Masson staining results.

[0057] (4.1) The lung index statistics of each group of mice are as follows: Figure 1 As shown (compared to the sham surgery group), This represents p < 0.001; compared with the lipopolysaccharide group, This means p < 0.001. This means p < 0.01. (p < 0.05). As shown in the figure, all three dose groups of atemotomid significantly reduced the lung index of the model animals. The 0.6 mg / kg atemotomid group showed the best effect, almost approaching the level of the sham-operated group, and was superior to the positive control drugs mycophenolate mofetil and prednisolone acetate.

[0058] (4.2) The statistical results of various lung function indicators of mice in each group are as follows: Figure 2 As shown in the figure, atemotoxin at a dose of 0.6 mg / kg can increase tidal volume and minute ventilation and reduce respiratory interval in mice.

[0059] (4.3) HE staining images and inflammation scores of lung tissue from each group of mice are shown below. Figure 3 As shown (compared to the sham surgery group), This represents p < 0.001; compared with the lipopolysaccharide group, (Representing p < 0.001), as shown in the figure, etanercept can significantly reduce inflammatory damage in the lungs of model animals.

[0060] (4.4) Masson staining images and inflammation scores of lung tissue from each group of mice are shown below. Figure 4 As shown (compared to the sham surgery group), This represents p < 0.001; compared with the lipopolysaccharide group, This means p < 0.01. (Representing p < 0.001), as shown in the figure, atetomod can significantly reduce the degree of fibrosis in the lungs of model animals.

[0061] The above findings suggest that atorvastatin has a significant ameliorative effect on the treatment of lipopolysaccharide-induced interstitial lung disease.

[0062] Experimental Example 2

[0063] Pharmacodynamic study of atorvastatin in an animal model of lipopolysaccharide-induced interstitial lung disease based on prednisolone acetate.

[0064] (1) Experimental animals: SPF grade C57BL / 6 mice (6-8 weeks old, 20g±2g) were selected and fed with ordinary feed for 7 days in an animal room (room temperature: 24±1℃, humidity: 50±10%, 12-hour light-dark cycle) (free access to food and water).

[0065] (2) Animal grouping: Mice were randomly divided into 6 groups according to their body weight: sham operation group, lipopolysaccharide + prednisolone acetate group (LPS + 2.5 mg / kg PA), lipopolysaccharide + prednisolone acetate + mycophenolate mofetil group (LPS + 2.5 mg / kg PA + 50 mg / kg MMF), low-dose lipopolysaccharide + prednisolone acetate + iotomodil group (LPS + 2.5 mg / kg PA + 0.3 mg / kg iotomodil), medium-dose lipopolysaccharide + prednisolone acetate + iotomodil group (LPS + 2.5 mg / kg PA + 0.6 mg / kg iotomodil), and high-dose lipopolysaccharide + prednisolone acetate + iotomodil group (LPS + 2.5 mg / kg PA + 1.2 mg / kg iotomodil), with 10 animals in each group.

[0066] (3) Modeling and administration: Except for the sham-operated group, a lipopolysaccharide-induced interstitial lung disease animal model was established by intratracheal infusion of lipopolysaccharide (5 mg / kg) into mice for 5 consecutive days. The administration was carried out in the above manner starting on the first day of modeling, with the sham-operated group and the lipopolysaccharide group given an equal volume of solvent control (0.5% CMC-Na).

[0067] (4) Indicator detection: The experiment ended on day 15. The pharmacodynamic evaluation of lung inflammation and fibrosis was carried out using lung weight index (lung weight / body weight × 1000), lung function, HE and Masson staining results, as well as the content of C-reactive protein and salivary glycan antigen in serum.

[0068] (4.1) The lung index statistics of each group of mice are as follows: Figure 5 As shown (compared to the sham surgery group), (p < 0.05) As shown in the figure, compared with the model group treated with prednisolone acetate alone and the group treated with prednisolone acetate in combination with mycophenolate mofetil, the combination of iotomodil and prednisolone acetate at doses of 0.3 mg / kg and 0.6 mg / kg both reduced the lung index of mice to some extent.

[0069] (4.2) The statistical results of various lung function indicators of mice in each group are as follows: Figure 6 As shown in the figure, the combined administration at doses of 0.6 mg / kg and 1.2 mg / kg increased tidal volume and minute ventilation in mice, and the 1.2 mg / kg dose group significantly reduced respiratory intervals, showing better effects than mycophenolate mofetil.

[0070] (4.3) HE staining images and inflammation scores of lung tissue from each group of mice are shown below. Figure 7 As shown in the figure, the improvement in lung inflammation in the 0.6 mg / kg dose group was significantly better than that of prednisolone acetate alone, and the effect was comparable to that in normal mice.

[0071] (4.4) Masson staining images and inflammation scores of lung tissue from each group of mice are shown below. Figure 8 As shown (compared to the sham surgery group), This represents p < 0.05; compared to the model group, (p < 0.05). As shown in the figure, the combined administration at doses of 0.6 mg / kg and 1.2 mg / kg significantly reduced the deposition of fibrous collagen in the lungs of mice with interstitial lung disease and alleviated pulmonary fibrosis.

[0072] (4.5) The results of C-reactive protein levels in the serum of mice in each group are as follows: Figure 9 As shown in the figure, the combined administration at doses of 0.6 mg / kg and 1.2 mg / kg reduced C-reactive protein in mouse serum.

[0073] (4.6) The results of the salivary glycan antigen levels in the serum of mice in each group are as follows: Figure 10 As shown in the figure, the combined administration at doses of 0.6 mg / kg and 1.2 mg / kg can reduce the level of salivary glycan antigen in mouse serum.

[0074] The above findings suggest that combining prednisolone acetate with atorvastatin can produce a more effective treatment for ILD.

[0075] Experimental Example 3

[0076] Pharmacodynamic studies of etanercept in animal models of radiation-induced interstitial lung disease

[0077] (1) Experimental animals: SPF grade C57BL / 6 mice (6-8 weeks old, 20g±2g) were selected and fed with ordinary feed for 7 days in an animal room (room temperature: 24±1℃, humidity: 50±10%, 12-hour light-dark cycle) (free access to food and water).

[0078] (2) Animal grouping: Mice were randomly divided into 7 groups according to their body weight: sham operation group, 75Gy irradiation group, 75Gy irradiation + prednisolone acetate group (75Gy + 5mg / kg PA), 75Gy irradiation + mycophenolate mofetil group (75Gy + 33.3mg / kg MMF), 75Gy irradiation + low dose of iotomodil group (75Gy + 0.3mg / kg iotomodil), 75Gy irradiation + medium dose of iotomodil group (75Gy + 0.6mg / kg iotomodil), and 75Gy irradiation + high dose of iotomodil group (75Gy + 1.2mg / kg iotomodil), with 10 animals in each group.

[0079] (3) Modeling and drug administration: Except for the sham-operated group, mice were anesthetized and fixed in a supine position in an irradiator, with the lower left lung exposed. A high-dose 75 Gy concentrated irradiation was performed once to establish an irradiation-induced interstitial lung disease animal model. Drug administration was started 24 h after modeling, with the sham-operated group and the irradiated group receiving an equal volume of solvent control (0.5% CMC-Na).

[0080] (4) Indicator detection: The experiment ended on day 43. The efficacy of the drug was evaluated by lung weight index (lung weight / body weight × 1000), survival rate, lung function and C-reactive protein. The number of white blood cells, lymphocytes, neutrophils and monocytes in the blood of the animals was measured by a fully automated blood cell analyzer.

[0081] (4.1) The lung index statistics of each group of mice are as follows: Figure 11 As shown in the figure, by the end of the experiment on day 43, all mice in the prednisolone acetate group had died, while only 3 animals survived in the model group, mycophenolate mofetil group, and 0.3 mg / kg iotomod group, with a survival rate of 30%. In contrast, the survival rate of the 0.6 mg / kg group reached 70%, and the survival rate of the 1.2 mg / kg group was 50%. High doses of iotomod significantly improved the survival rate of mice.

[0082] (4.2) The lung index statistics of each group of mice are as follows: Figure 12 As shown (compared to the sham surgery group), This represents p < 0.001; compared to the irradiated group, This means p < 0.01. (p < 0.001) As shown in the figure, all three doses of atemotomid significantly reduced the lung weight index of the animals, while the lung weight index of mycophenolate mofetil animals did not show a significant improvement compared to the model group.

[0083] (4.3) The statistical results of various lung function indicators of mice in each group are as follows: Figure 13 As shown in the figure, all three doses of atemotomid can enhance the respiratory rate and reduce the respiratory interval in the model animals, and have a significant improvement in lung function. The lung function indicators of the 1.2 mg / kg group are close to those of the sham-operated group.

[0084] (4.4) The blood cell test results of each group of mice are as follows: Figure 14 As shown (compared to the sham surgery group), This means p < 0.05. This represents p < 0.001; compared to the irradiated group, (p < 0.001). As shown in the figure, all three doses of atemotoxin significantly reduced monocytes, while the low and high doses significantly reduced neutrophils.

[0085] (4.5) The results of plasma C-reactive protein levels in mice in each group are as follows: Figure 15 As shown in the figure, low to medium doses of atemotoxin reduced inflammation in the model animals.

[0086] The above findings suggest that atemotome has a significant effect on the treatment of radiation-induced interstitial lung disease.

[0087] The applicant declares that the technical solution of this invention is illustrated by the above embodiments, but this invention is not limited to the above embodiments, that is, it does not mean that this invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the products of this invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

[0088] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0089] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. The use of iotomod or its pharmaceutically acceptable salt as shown in formula (I) in the preparation of medicaments for the prevention, improvement or treatment of interstitial lung disease and related lung injury; Equation (I).

2. The application according to claim 1, characterized in that, The interstitial lung disease and related lung injury mentioned are lipopolysaccharide-induced interstitial lung disease and related lung injury.

3. The application according to claim 1, characterized in that, The interstitial lung disease and related lung injury mentioned are radiation-induced interstitial lung disease and related lung injury.

4. The application according to any one of claims 1-3, characterized in that, The aforementioned iotomod or its pharmaceutically acceptable salt reverses the abnormal increase in lung index caused by lipopolysaccharide or irradiation.

5. The application according to any one of claims 1-3, characterized in that, The aforementioned iotomod or its pharmaceutically acceptable salt improves lung function damage caused by lipopolysaccharide or radiation.

6. The application according to any one of claims 1-3, characterized in that, The aforementioned iotomod or its pharmaceutically acceptable salt improves inflammatory damage to the lungs.

7. The application according to any one of claims 1-3, characterized in that, The aforementioned iotomod or its pharmaceutically acceptable salts improve the degree of pulmonary fibrosis.

8. The application according to any one of claims 1-3, characterized in that, The drug also includes pharmaceutically acceptable excipients.

9. The application according to claim 8, characterized in that, Pharmaceutically acceptable excipients include any one or a combination of at least two of the following: carriers, diluents, flavoring agents, binders, fillers, thickeners, disintegrants, solubilizers, suspending agents, lubricants, or buffers.

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