Application of combination of ambroxol and ferulic acid in preparation of preparation for preventing and / or treating radiation-induced lung injury

Abstract

The invention provides application of combination of ambroxol and ferulic acid in preparation of a preparation for preventing and / or treating radiation-induced lung injury, and belongs to the technical field of biological medicine. The ambroxol and the ferulic acid are combined for use, so that a good prevention and treatment effect on radiation-induced lung injury caused by ionizing radiation can be achieved, early-stage acute radiation pneumonitis can be inhibited, a long-term lung function can be improved, and lung fibrosis can be blocked. On the premise of remarkably reducing the administration dosage of ambroxol and ferulic acid, the survival rate of a radiation-induced lung injury model mouse is increased by 55%, expression of TNF-alpha and TGF-beta1 is more effectively inhibited, no toxic or side effect is generated on normal alveolar epithelial cells, and the pharmaceutical composition is suitable for clinical application. The traditional Chinese medicine composition has the advantages of small dosage, excellent prevention and / or treatment effect, no toxic or side effect, no dose dependence and the like.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine, and particularly relates to application of ambroxol combined with ferulic acid in preparation of a preparation for preventing and / or treating radiation-induced lung injury. BACKGROUND

[0002] Radiation-Induced Lung Injury (RILI) is one of the most common serious complications after radiotherapy of chest tumors (such as lung cancer, esophageal cancer, breast cancer, etc.), and its pathophysiological mechanism is complex. The occurrence of RILI is the result of the combined action of direct radiation damage, immune inflammatory response and oxidative stress, and is divided into two stages, namely acute stage (Radiation Pneumonitis) and chronic stage (Radiation Fibrosis). Radiation Pneumonitis occurs 1-3 months after radiotherapy, and the direct radiation damage to lung epithelial cells (alveolar type II cells, bronchial epithelial cells) and vascular endothelial cells releases pro-inflammatory factors (TNF-α, IL-6, IL-1β) and chemotactic factors (CXCL10, CCL2), recruits neutrophils and macrophages to infiltrate, and causes alveolar edema and exudation.

[0003] Amifostine is the first pan-cell protective agent approved for listing by the US FDA, and after continuous research by clinical doctors, it is currently widely used to protect normal cells from damage by radiotherapy and chemotherapy drugs. However, at the same time, the use of amifostine can cause adverse reactions such as gastrointestinal dysfunction, hypotension, and hypocalcemic tetany in the body. Glucocorticoids are the first-line standard drugs for the clinical treatment of acute radiation pneumonitis, and are particularly suitable for patients with symptoms of grade 2 and above. However, the limitations of glucocorticoid therapy are very prominent: first, it is ineffective for lung fibrosis that has already formed and cannot improve the long-term prognosis of the disease; second, long-term use can easily cause a variety of adverse reactions, including increased blood glucose, osteoporosis, gastrointestinal ulcers, and increased risk of infection due to immunosuppression; third, there is a "rebound phenomenon", and symptoms are likely to recur after rapid reduction or discontinuation.

[0004] In addition, the treatment of radiation-induced lung injury in clinical practice also includes symptomatic support measures, such as the use of broad-spectrum antibiotics or antifungal drugs when combined with infection, oxygen therapy or non-invasive ventilation for patients with hypoxemia, and pulmonary rehabilitation training, etc., but these measures can only improve symptoms and reduce complications, and cannot fundamentally block the pathological process. Immunosuppressive agents (such as infliximab and cyclophosphamide) are only used for refractory severe cases, and the benefits and risks need to be strictly weighed due to the higher risk of infection. SUMMARY

[0005] In view of this, the purpose of the present invention is to provide an application of ambroxol combined with ferulic acid in the preparation of a formulation for the prevention and / or treatment of radiation-induced lung injury, so as to solve the problems of strong cytotoxicity, large side effects, poor therapeutic effect and poor therapeutic stability of existing drugs.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides the use of ambroxol in combination with ferulic acid in the preparation of medicaments for the prevention and / or treatment of radiation-induced lung injury.

[0007] Preferably, the radiation-induced lung injury is lung injury caused by ionizing radiation.

[0008] Preferably, the ionizing radiation includes X-ray radiation, gamma-ray radiation, or heavy ion radiation.

[0009] Preferably, the radiation-induced lung injury includes acute radiation-induced pneumonia or radiation-induced pulmonary fibrosis.

[0010] Preferably, the mass ratio of ambroxol to ferulic acid is 2~4:10~30.

[0011] The present invention also provides a pharmaceutical composition for the prevention and / or treatment of radiation-induced lung injury, the pharmaceutical composition comprising ambroxol, ferulic acid, and a pharmaceutically acceptable carrier.

[0012] Preferably, the mass ratio of ambroxol to ferulic acid is 2~4:10~30.

[0013] The present invention also provides the use of the pharmaceutical composition in the preparation of formulations for the prevention and / or treatment of radiation-induced lung injury.

[0014] The present invention also provides the use of the pharmaceutical composition in the preparation of formulations for the prevention and / or treatment of acute radiation pneumonitis.

[0015] The present invention also provides the use of the pharmaceutical composition in the preparation of formulations for the prevention and / or treatment of radiation-induced pulmonary fibrosis.

[0016] Compared with the prior art, the present invention has the following beneficial effects: This invention combines ambroxol and ferulic acid to achieve excellent prevention and treatment effects against radiation-induced lung injury caused by ionizing radiation. It can inhibit early acute radiation-induced pneumonia, improve long-term lung function, and inhibit the occurrence of pulmonary fibrosis. Furthermore, while significantly reducing the dosage of ambroxol and ferulic acid, it increases the survival rate of mice with radiation-induced lung injury by 55%, more effectively inhibits the expression of TNF-α and TGF-β1, and does not produce any toxic side effects on normal alveolar epithelial cells. It has the advantages of low dosage, excellent preventive and / or therapeutic effects, no toxic side effects, and no dose dependence. Attached Figure Description

[0017] Figure 1 It is the cytotoxicity of ambroxol and ferulic acid on the RLE-6TN cell line; Figure 2 These are the HE staining results of lung tissue from mice in each group on day 20 after ionizing radiation; Figure 3 These are Masson staining images showing the lung fibrosis status of mice in each group; Figure 4 This is the survival curve of a mouse model of radiation-induced lung injury. Detailed Implementation

[0018] This invention provides the use of ambroxol in combination with ferulic acid in the preparation of medicaments for the prevention and / or treatment of radiation-induced lung injury.

[0019] In this invention, ambroxol is the active metabolite of the mucolytic agent bromhexine, chemically named trans-4-[(2-amino-3,5-dibromobenzyl)amino]cyclohexanol hydrochloride. It is a commonly used respiratory medication that effectively promotes expectoration by thinning thick sputum in the respiratory tract and reducing sputum retention. Ferulic acid (FA) is the main active ingredient in traditional Chinese medicines such as asafoetida and angelica sinensis. Widely distributed in nature, it is a common phenolic acid found in medicinal plants. To date, FA has been shown to possess various pharmacological effects, particularly antioxidant, anti-inflammatory, anti-allergic, and anticancer effects, and has demonstrated therapeutic efficacy in many disease models, such as acute respiratory infections and cardiovascular diseases. The radiation-induced lung injury is lung injury caused by ionizing radiation; the ionizing radiation includes X-ray radiation, gamma-ray radiation, or heavy ion radiation; the radiation-induced lung injury includes acute radiation-induced pneumonia or radiation-induced pulmonary fibrosis; the mass ratio of ambroxol to ferulic acid is preferably 2~4:10~30, more preferably 2.5~3.5:15~25, and even more preferably 3:20.

[0020] The present invention also provides a pharmaceutical composition for the prevention and / or treatment of radiation-induced lung injury, the pharmaceutical composition comprising ambroxol, ferulic acid, and a pharmaceutically acceptable carrier. In the present invention, the mass ratio of ambroxol to ferulic acid is preferably 2-4:10-30, more preferably 2.5-3.5:15-25, and even more preferably 3:20.

[0021] The present invention also provides the use of the pharmaceutical composition in the preparation of formulations for the prevention and / or treatment of radiation-induced lung injury.

[0022] The present invention also provides the use of the pharmaceutical composition in the preparation of formulations for the prevention and / or treatment of acute radiation pneumonitis.

[0023] The present invention also provides the use of the pharmaceutical composition in the preparation of formulations for the prevention and / or treatment of radiation-induced pulmonary fibrosis.

[0024] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0025] In the reagents of this invention, ambroxol and ferulic acid were purchased from Beijing Solarbio Science & Technology Co., Ltd., amifostine was purchased from Hubei Jianyuan Biochemical Co., Ltd., CCK-8 reagent was purchased from Dojin Chemical Research Institute, Japan, and TUNEL assay kit was purchased from Yisheng Biotechnology (Shanghai) Co., Ltd.

[0026] In the test materials of this invention, the test mice were 6-8 week old C57BL / 6 strain mice, weighing 18-22g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.; the test cell line was rat type II alveolar epithelial cell RLE-6TN cell line (catalog number: Delf-16735), purchased from Hefei Wanwu Biotechnology Co., Ltd.

[0027] Example 1

[0028] Cytotoxicity of ambroxol and ferulic acid

[0029] RLE-6TN cell lines were seeded in DMFM / F12 medium containing 10% fetal bovine serum and cultured at 37°C and 5% CO2 until the logarithmic growth phase. The cells were then seeded into 96-well plates and divided into ambroxol, ferulic acid, and control groups. After 24 hours of further culture, ambroxol was added to the wells of the ambroxol groups to final concentrations of 6.25 μmol / L, 12.5 μmol / L, 25 μmol / L, 50 μmol / L, and 100 μmol / L, respectively. Ferulic acid was added to the culture wells of the ferulic acid group at final concentrations of 6.25 μmol / L, 12.5 μmol / L, 25 μmol / L, 50 μmol / L, 100 μmol / L, and 200 μmol / L, respectively. No reagent was added to the control group. After culturing for 48 hours, CCK-8 reagent was added to each well according to the instructions and incubated for 2 hours. The OD of each well was measured using a microplate reader. 450nm The cell viability is calculated using the following formula: Cell viability (%) = .

[0030] Experimental results: such as Figure 1 As shown, ferulic acid at a final concentration ≤50 μmol / L or ambroxol at a final concentration ≤100 μmol / L did not inhibit the growth and proliferation of the RLE-6TN cell line.

[0031] Example 2

[0032] The preventive and therapeutic effects of ambroxol combined with ferulic acid on radiation-induced lung injury.

[0033] One hundred and eighty C57BL / 6 mice were divided into nine groups: a blank control group, an irradiation-only group, an ambroxol group, a ferulic acid group, a low-dose combination group, a medium-dose combination group, a high-dose combination group, a negative control group, and a positive control group, with 20 mice in each group. One hour before ionizing radiation, mice in the ambroxol group were intraperitoneally injected with 90 mg / kg ambroxol, mice in the ferulic acid group were intraperitoneally injected with 100 mg / kg ferulic acid, mice in the low-dose combination group were intraperitoneally injected with 2 mg / kg ambroxol + 10 mg / kg ferulic acid, mice in the medium-dose combination group were intraperitoneally injected with 3 mg / kg ambroxol + 20 mg / kg ferulic acid, mice in the high-dose combination group were intraperitoneally injected with 4 mg / kg ambroxol + 30 mg / kg ferulic acid, mice in the blank control group were intraperitoneally injected with 0.1 mL of physiological saline, mice in the irradiation-only group and the negative control group were intraperitoneally injected with 0.1 mL of dimethyl sulfoxide, and mice in the positive control group were intraperitoneally injected with 20 mg / kg amifostine. Mice in the simple irradiation group, ambroxol group, ferulic acid group, low-dose combination group, medium-dose combination group, high-dose combination group, and positive control group were administered 50 mg / kg of ambroxol. Mice were anesthetized with 1% sodium pentobarbital solution via intraperitoneal injection and fixed in a supine position. Gamma-ray ionizing radiation was applied to the lungs of each mouse using 60Co as the radiation source at a dose of 30 Gy and a rate of 1 Gy / min. Lead plates were used to shield other parts of the mice to prevent ionizing radiation damage. The blank control and negative control mice were not subjected to ionizing radiation. Bilateral lungs were harvested on days 7, 14, and 20 after ionizing radiation, fixed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE). The lungs were washed with pre-cooled saline, and the fresh wet weight and dried weight were measured. The wet / dry weight ratio was calculated using the formula: wet weight / dried weight. The lung coefficient (%) was calculated as: lung wet weight (g) / body weight (g) × 100%. The apoptosis rate of vascular endothelial cells in the lungs of each mouse was determined using a TUNEL assay kit, following the instructions for use of the TUNEL assay kit. Six months after the ionizing radiation ended, paraffin sections of bilateral lung tissue from mice were collected, dewaxed, stained with potassium dichromate, hematoxylin, Ponceau S, acid fuchsin, phosphomolybdic acid, and aniline blue, then differentiated and dehydrated with glacial acetic acid, and finally cleared, mounted, and photographed.

[0034] Experimental results: HE staining results are as follows Figure 2As shown in the figure, the alveolar tissue of mice in the blank control group was clear and normal, with uniform morphology and distribution. Most alveoli were structurally intact and uniformly round, with thin walls and smooth surfaces. They were mainly composed of a single layer of alveolar epithelial cells and alveolar wall capillaries. The internal structure of the alveolar epithelial cells was clear and translucent, and the capillary walls were thin and elastic. No inflammatory cell infiltration, exudation, or hemorrhage was observed. These characteristics were similar to those of the lung tissue of mice in the negative control group. One to two weeks after radiation treatment, the lung tissue of mice in the radiation-only group showed significant pathological phenomena such as large-scale structural disorder. The alveolar walls were significantly thickened, twisted, deformed, and partially fractured and fused over a large area. The alveolar epithelial cells proliferated significantly, and irregular alveoli collapsed or fused into bullae. Some blood vessels were severely congested or ruptured, and there were many inflammatory cell infiltration components in the pulmonary interstitium. Some alveolar cavities showed a large amount of inflammatory exudate or severe hemorrhage. The treatment effects of the ambroxol group, ferulic acid group, and positive control group were similar. Compared with the radiation-only group, the thickening of lung septa in mice treated with the three single-drug groups was reduced to some extent, the degree of alveolar collapse and fusion was alleviated, and the number and types of inflammatory cell infiltration were reduced to some extent, resulting in a certain degree of restoration of the overall lung tissue structure and integrity. Compared with the three single-drug groups, the low-dose combination group showed a further reduction in lung tissue edema and fracture fusion, but the difference was not significant. The medium-dose combination group showed a significant improvement in the level of lung tissue damage, and the original normal alveolar structure outline was restored to some extent. Although it could not reach the healthy level of normal lung tissue structure, the degree of alveolar wall thickening was no longer severe, inflammatory cell infiltration and interstitial edema were significantly improved, and there was no obvious fusion or adhesion between most alveolar walls. The treatment effect was comparable to that of the high-dose combination group. These data strongly demonstrate the significant synergistic effect of this new strategy of combining two drugs, which is of great significance for improving the treatment effect of radiation-induced lung injury.

[0035] Masson staining results are as follows: Figure 3As shown in the image. Masson staining results showed that the lung tissue of mice in the blank control group had a clear and normal structure, with a small amount of fine and lightly stained collagen fibers. The alveolar walls were thin with no obvious collagen fiber deposition. The elastic fiber tissue in the blood vessel and bronchial walls was sparse and thin, with good integrity and continuity, consistent with the negative control group. Six months after radiation exposure, the lung tissue of mice in the irradiation-only group showed severe fibrotic damage, with significant thickening, fusion, and distortion of the alveolar walls. Diffuse, cord-like, or coarse sheet-like blue collagen fiber bundles were deposited in the alveolar interstitium and atelectasis areas. These fibrous tissues further divided, wrapped, and replaced the lung parenchyma, resulting in significant loss of normal alveolar tissue, locally manifesting as complete fibrotic obstruction, and even pulmonary consolidation. Blue collagen fiber material continuously accumulated around most blood vessels and small bronchi, showing significant thickening and irregular thickening of the vessel walls. Some blood vessel and small bronchial walls experienced decreased elasticity due to excessive accumulation of fibrous connective tissue, exhibiting distortion, damage, or breakage. The degree of fibrosis in the lung tissues of mice in the ambroxol group, ferulic acid group, and positive control group was similar, with some degree of collagen deposition in the alveolar interstitium, blood vessels, and small bronchial walls. However, the overall level of fibrosis was milder than that in the irradiation-only group. Although the low-dose combination therapy group also showed some degree of collagen deposition in the alveolar walls, blood vessels, and peribronchial tissues, the degree of fibrosis and damage was lower than that in the ambroxol group, ferulic acid group, and positive control group. The degree of pulmonary fibrosis in mice treated with the medium-dose combination therapy was significantly improved. Compared with the low-dose combination therapy group, not only was the edema of the alveolar walls further reduced, but the blue collagen deposition in the pulmonary interstitium was also significantly reduced. The therapeutic effect was similar to that of the high-dose combination therapy group. These data indicate that the single administration of ambroxol, ferulic acid, or amifostine can all alleviate radiation-induced pulmonary fibrosis to a certain extent. Compared with the above three single-drug administration methods, the combination of ambroxol and ferulic acid at low doses can improve the therapeutic effect of radiation-induced pulmonary fibrosis within a certain range, initially demonstrating the synergistic effect of anti-fibrosis. The combination of medium-dose and high-dose therapy can significantly improve the efficacy of treating radiation-induced pulmonary fibrosis.

[0036] The results of wet / dry ratio and lung coefficient are shown in Table 1.

[0037] Table 1. Wet / dry weight and lung coefficient of mice in each group.

[0038] The apoptosis rate of vascular endothelial cells is shown in Table 2.

[0039] Table 2 Apoptosis rate of vascular endothelial cells in each group of mice

[0040] Tables 1 and 2 show that compared with the blank control group, the wet / dry ratio of the lungs and the lung coefficient were increased in the irradiation-only group, and the apoptosis rate of vascular endothelial cells was significantly increased, indicating that ionizing radiation can cause serious damage to the blood vessels and other tissues of the lungs in mice, resulting in increased pulmonary hemorrhage. The wet / dry ratio of the lungs, the lung coefficient, and the apoptosis rate of vascular endothelial cells were all decreased in the ambroxol group, the ferulic acid group, the low-dose combination group, the medium-dose combination group, the high-dose combination group, and the positive control group. Furthermore, the medium-dose combination group and the high-dose combination group showed significantly lower values ​​of these parameters. The reduction in the wet / dry ratio of the lungs and the apoptosis rate of vascular endothelial cells in rats was more significant, indicating that ambroxol or ferulic acid alone can prevent radiation-induced lung injury caused by ionizing radiation to a certain extent, and the preventive effect is similar to that of amifostine. However, the combination of ambroxol and ferulic acid has a better preventive effect on radiation-induced lung injury caused by ionizing radiation. The preventive effects of 3 mg / kg ambroxol + 20 mg / kg ferulic acid and 4 mg / kg ambroxol + 30 mg / kg ferulic acid on radiation-induced lung injury are similar.

[0041] Example 3

[0042] Effects of ambroxol combined with ferulic acid on TNF-α and TGF-β1 levels

[0043] Many studies have found that transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) are involved in the early inflammatory response of radiation-induced lung injury and can also affect the later fibrosis process by regulating the proliferation, differentiation, and collagen fiber deposition of fibroblasts. Blood samples from mice in each group described in Example 2 were collected, and the levels of TNF-α and TGF-β1 in plasma were detected by ELISA according to the literature (Zhou Yanping, Qiu Mingyi, Hu Zuowei, et al. Effects of Sha Shen Mai Dong Tang on plasma IL-6, TNF-α, and TGF-β1 in radiation-induced pneumonia rats [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2014.).

[0044] Experimental results are shown in Table 3.

[0045] Table 3. Expression levels of TNF-α and TGF-β1 in mice of each group

[0046] Table 3 shows that the expression levels of TNF-α and TGF-β1 in mice in the irradiation-only group were significantly higher than those in other groups; the expression levels of TNF-α and TGF-β1 in mice in the ambroxol group, ferulic acid group, and positive control group were significantly lower than those in the irradiation-only group, and the differences were not significant with the low-dose combination group; while the expression levels of TNF-α and TGF-β1 in mice in the medium-dose combination group and the high-dose combination group were significantly different from those in the positive control group. This indicates that ambroxol or ferulic acid alone can inhibit the production of TNF-α and TGF-β1 to a certain extent, and the inhibitory effect is comparable to that of amifostine; however, the combination of ambroxol and ferulic acid can more effectively inhibit the expression of TNF-α and TGF-β1, thus effectively preventing radiation-induced lung injury.

[0047] Example 4

[0048] Mouse model of radiation-induced lung injury

[0049] C57BL / 6 mice were anesthetized with an intraperitoneal injection of 50 mg / kg 1% sodium pentobarbital solution and fixed in a supine position. Local gamma-ray ionizing radiation was administered to the chest of the C57BL / 6 mice using 60Co as the radiation source at a dose of 30 Gy and a radiation rate of 200 cGy / min. Lead plates were used to shield other parts of the C57BL / 6 mice to prevent ionizing radiation damage. Following ionizing radiation, the C57BL / 6 mice exhibited acute radiation-induced pneumonia within 1–2 weeks, and bilateral lung fibrosis symptoms appeared within 3–5 weeks, largely consistent with the course of radiation-induced lung injury in humans, indicating a successful establishment of a mouse model of radiation-induced lung injury.

[0050] Example 5

[0051] Effect of ambroxol combined with ferulic acid on survival rate of mice with radiation-induced lung injury

[0052] One hundred mice with radiation-induced lung injury, constructed in Example 4, were randomly divided into five groups: irradiation group, ambroxol group, ferulic acid group, combination therapy group, and positive control group, with 20 mice in each group. Six hours after ionizing radiation, mice in the ambroxol group were intraperitoneally injected with 90 mg / kg ambroxol, mice in the ferulic acid group were intraperitoneally injected with 100 mg / kg ferulic acid, mice in the combination therapy group were intraperitoneally injected with 3 mg / kg ambroxol + 20 mg / kg ferulic acid, and mice in the positive control group were intraperitoneally injected with 20 mg / kg amifostine. These treatments were administered every two days thereafter, while mice in the irradiation group received no treatment. The survival rate of mice in each group was recorded over 20 days.

[0053] Experimental results: such as Figure 4As shown in the figure, mice in the irradiation group began to die on day 5 after ionizing radiation, with a survival rate of only 10% on day 20. Mice in both the ambroxol group and the positive control group died between days 8 and 13. Before day 11, the survival rate of mice in the ambroxol group was higher than that of the positive control group. On day 20, the survival rate of mice in the ambroxol group was 40%, while that of the positive control group was 30%. Mice in the ferulic acid group continued to die until day 15, with a survival rate of 25% on day 20. Mice in the combined treatment group only experienced a small number of deaths between days 8 and 14, with a survival rate of 85% on day 20. This indicates that ambroxol combined with ferulic acid can significantly improve the survival rate of mice with radiation-induced lung injury. Compared with amifostine alone, ambroxol combined with ferulic acid increased the survival rate of mice with radiation-induced lung injury by 55%. Compared with ambroxol or ferulic acid alone, ambroxol combined with ferulic acid significantly reduced the dosage of both ambroxol and ferulic acid.

[0054] As demonstrated by the above embodiments, the combined use of ambroxol and ferulic acid in this invention achieves excellent preventive and therapeutic effects against radiation-induced lung injury caused by ionizing radiation. It can inhibit early acute radiation-induced pneumonia, improve long-term lung function, and inhibit the occurrence of pulmonary fibrosis. Furthermore, while significantly reducing the dosage of ambroxol and ferulic acid, it increases the survival rate of mice with radiation-induced lung injury by 55%, more effectively inhibits the expression of TNF-α and TGF-β1, and does not produce any toxic side effects on normal alveolar epithelial cells. It has the advantages of low dosage, excellent preventive and / or therapeutic effects, no toxic side effects, and no dose dependence.

[0055] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The use of ambroxol in combination with ferulic acid in the preparation of drugs for the prevention and / or treatment of radiation-induced lung injury.

2. The application according to claim 1, characterized in that, The radiation-induced lung injury refers to lung injury caused by ionizing radiation.

3. The application according to claim 2, characterized in that, The ionizing radiation includes X-ray radiation, gamma-ray radiation, or heavy ion radiation.

4. The application according to claim 1, characterized in that, The radiation-induced lung injury includes acute radiation-induced pneumonia or radiation-induced pulmonary fibrosis.

5. The application according to any one of claims 1 to 4, characterized in that, The mass ratio of ambroxol to ferulic acid is 2~4:10~30.

6. A pharmaceutical composition for the prevention and / or treatment of radiation-induced lung injury, characterized in that, The pharmaceutical composition includes ambroxol, ferulic acid, and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition according to claim 6, characterized in that, The mass ratio of ambroxol to ferulic acid is 2~4:10~30.

8. Use of the pharmaceutical composition of claim 6 or 7 in the preparation of formulations for the prevention and / or treatment of radiation-induced lung injury.

9. Use of the pharmaceutical composition of claim 6 or 7 in the preparation of an agent for the prevention and / or treatment of acute radiation pneumonitis.

10. Use of the pharmaceutical composition of claim 6 or 7 in the preparation of formulations for the prevention and / or treatment of radiation-induced pulmonary fibrosis.

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