Application of combination of amifostine and calycosin in preparation of preparation for preventing and / or treating radiation-induced lung injury

Abstract

The invention provides application of combination of amifostine and calycosin in preparation of a preparation for preventing and / or treating radiation-induced lung injury, and belongs to the technical field of medicines. According to the invention, the amifostine and the calycosin are combined for use, so that the medication side effect caused by independent use of the amifostine in the prior art is effectively solved, and the prevention effect and the treatment stability of the amifostine are improved. According to the pharmaceutical composition disclosed by the invention, the amifostine and the calycosin are combined for use, so that the pharmaceutical composition has a good prevention and treatment effect on radiation-induced lung injury caused by ionizing radiation, and adverse reactions such as hypotension and nausea generated when the amifostine is independently used cannot be generated. And when the administration dosage of the amifostine and the calycosin is low, the survival rate of a radiation-induced lung injury model mouse is remarkably improved, and no toxic or side effect exists.

Description

TECHNICAL FIELD

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

[0002] Radiation-induced lung injury (RILI) is the most common dose-limiting complication of thoracic tumor radiotherapy, with an incidence of 5% to 25%. The clinical manifestations are early radiation pneumonia and late pulmonary fibrosis, and severe cases can lead to respiratory failure. At present, the clinic mainly relies on glucocorticoid treatment, but it is only effective for acute inflammation, and has serious side effects such as immunosuppression and osteoporosis, and has limited effect on the fibrosis stage.

[0003] Amifostine is the first pan-cell protective agent approved by the US FDA, which protects normal cells by removing oxygen free radicals (ROS) and has been used for the protection of chemotherapy nephrotoxicity, radiotherapy xerostomia, etc. However, when it is used alone for radiation-induced lung injury, due to the single mechanism of action, it has serious adverse reactions such as hypotension and severe nausea, and poor tolerance of intravenous administration, which limits its clinical application. Therefore, how to avoid the adverse reactions of amifostine in the prevention and / or treatment of radiation-induced lung injury is a problem that needs to be solved at present. SUMMARY

[0004] Therefore, the purpose of the present application is to provide the application of amifostine combined with calycosin in the preparation of preparations for preventing and / or treating radiation-induced lung injury. By combining amifostine with calycosin, the present application effectively solves the side effects of amifostine used alone in the prior art, and improves the prevention effect and treatment stability.

[0005] In order to achieve the above-mentioned purpose of the application, the present application provides the following technical solutions: The present application provides the application of amifostine combined with calycosin in the preparation of preparations for preventing and / or treating radiation-induced lung injury.

[0006] Preferably, the mass ratio of amifostine to calycosin is 1:1 to 3, wherein the concentration of amifostine is 4 to 6 mg / kg, and the concentration of calycosin is 4 to 18 mg / kg.

[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 pneumonia or radiation-induced pulmonary fibrosis.

[0010] The present invention provides a pharmaceutical composition for the prevention and / or treatment of radiation-induced lung injury, the pharmaceutical composition comprising amifostine, verbascoside, and a pharmaceutically acceptable carrier.

[0011] Preferably, the mass ratio of amifostine to verbascoside is 1:1 to 3, wherein the concentration of amifostine is 4 to 6 mg / kg and the concentration of verbascoside is 4 to 18 mg / kg.

[0012] This invention provides the use of the pharmaceutical composition described herein in the preparation of formulations for the prevention and / or treatment of radiation-induced lung injury.

[0013] This invention provides the use of the pharmaceutical composition described herein in the preparation of preparations for the prevention and / or treatment of acute radiation pneumonitis.

[0014] The present invention also provides the use of the pharmaceutical composition described herein in the preparation of agents for the prevention and / or treatment of radiation-induced pulmonary fibrosis.

[0015] Compared with existing technologies, the present invention has the following beneficial effects: The combined use of amifostatin and verbascoside in this invention can effectively prevent and treat radiation-induced lung injury caused by ionizing radiation, without producing adverse reactions such as hypotension and nausea that occur when amifostatin is used alone. Furthermore, at low doses of amifostatin and verbascoside, the survival rate of mice with radiation-induced lung injury is significantly improved, with no toxic side effects. Attached Figure Description

[0016] Figure 1 The cytotoxicity of amifotin, verbascoside and quercetin on the RLE-6TN cell line; Figure 2 HE staining results of lung tissue from mice in blank, irradiated, single-drug, and negative control groups on day 20 after ionizing radiation; Figure 3 HE staining results of lung tissue from mice in the combination group and control group on day 20 after ionizing radiation. The combination group refers to the group treated with amifostatin combined with verbascoside isoflavone, and the control group refers to the group treated with amifostatin combined with quercetin. Figure 4 Survival curves for a mouse model of radiation-induced lung injury. Detailed Implementation

[0017] This invention provides the use of amifostatin in combination with verbascoside in the preparation of formulations for the prevention and / or treatment of radiation-induced lung injury.

[0018] In this invention, amifostine is a cell protectant primarily used to reduce the toxicity of chemotherapy or radiotherapy to normal tissues and prevent radiation-induced oral mucositis. Verbena isoflavone is a natural plant compound that can be used to regulate estrogen levels, provide antioxidant effects, protect cardiovascular and bone health, and may also have positive effects on alleviating menopausal symptoms and reducing inflammation. The mass ratio of amifostine to verbena is 1:1~3, preferably 1:1.5~2.5, more preferably 1:2; the concentration of amifostine is 4~6 mg / kg, preferably 4.5~5.5 mg / kg, more preferably 5 mg / kg, and the concentration of verbena isoflavone is 4~18 mg / kg, preferably 6.5~14 mg / kg, more preferably 10 mg / kg; 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.

[0019] The present invention provides a pharmaceutical composition for the prevention and / or treatment of radiation-induced lung injury, the pharmaceutical composition comprising amifostine, verbascoside, and a pharmaceutically acceptable carrier.

[0020] In this invention, the mass ratio of amifostine to verbascoside is 1:1 to 3, preferably 1:1.5 to 2.5, and more preferably 1:2; wherein the concentration of amifostine is 4 to 6 mg / kg, preferably 4.5 to 5.5 mg / kg, and more preferably 5 mg / kg, and the concentration of verbascoside is 4 to 18 mg / kg, preferably 6.5 to 14 mg / kg, and more preferably 10 mg / kg.

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

[0022] This invention provides the use of the pharmaceutical composition described herein in the preparation of preparations for the prevention and / or treatment of acute radiation pneumonitis.

[0023] The present invention also provides the use of the pharmaceutical composition described herein in the preparation of agents 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, amifostine was purchased from Hubei Jianyuan Biochemical Co., Ltd., isoflavone and quercetin were purchased from Shanghai Aladdin Biochemical Technology 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 amifotin, verbascoflavonoids and quercetin

[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. Then, they were seeded into 96-well plates and divided into amifostine, verbascoside, quercetin, and control groups. After 24 hours of further culture, amifostine was added to the wells of the amifostine groups 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. Verascoside was added to the wells of the verbascoside groups 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. Quercetin was added to the wells of the quercetin group at concentrations of 0.25 μmol / L, 12.5 μmol / L, 25 μmol / L, 50 μmol / L, 100 μmol / L, and 200 μmol / L, respectively, to 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 h, CCK-8 reagent was added to each well according to the instructions and incubated for 2 h. The OD of each well was measured using a microplate reader. 450nm The values ​​were calculated and cell viability was determined. The results are as follows: Figure 1 As shown. The formula for calculating cell viability is: Cell viability (%) = .

[0030] Depend on Figure 1 It can be seen that when the final concentrations of amifostine, verbascoside, and quercetin are ≤100 μmol / L, amifostine, verbascoside, and quercetin do not inhibit the growth and proliferation of the RLE-6TN cell line.

[0031] Example 2

[0032] The effect of amifotin combined with isoflavones or quercetin on the prevention and treatment of radiation-induced lung injury

[0033] 216 C57BL / 6 mice were divided into 12 groups: blank control group, irradiation group, amifostine group, verbascoside group, quercetin group, low-dose combination of amifostine and verbascoside, medium-dose combination of amifostine and verbascoside, high-dose combination of amifostine and verbascoside, low-dose control group of amifostine and quercetin, medium-dose control group of amifostine and quercetin, high-dose control group of amifostine and quercetin, and negative control group, with 18 mice in each group. One hour before ionizing radiation, mice were intraperitoneally injected with 20 mg / kg amifostine in the amifostine group, 20 mg / kg isoflavone in the verbascoside group, 20 mg / kg quercetin in the quercetin group, 5 mg / kg amifostine + 5 mg / kg verbascoside in the low-dose combination group, 5 mg / kg amifostine + 10 mg / kg verbascoside in the medium-dose combination group, and 5 mg / kg amifostine + 15 mg / kg verbascoside in the high-dose combination group. Verbena isoflavones were administered intraperitoneally to mice in the low-dose amifostine and quercetin combined control group (5 mg / kg amifostine + 5 mg / kg quercetin), the medium-dose amifostine and quercetin combined control group (5 mg / kg amifostine + 10 mg / kg quercetin), the high-dose amifostine and quercetin combined control group (5 mg / kg amifostine + 15 mg / kg quercetin), the blank control group (0.1 mL physiological saline), and the irradiation group and negative control group (0.1 mL dimethyl sulfoxide). Mice were anesthetized with 50 mg / kg 1% sodium pentobarbital solution via intraperitoneal injection and fixed in a supine position. The groups included: irradiation-only group, amifostine group, verbascoside isoflavone group, quercetin group, low-dose combination group, medium-dose combination group, high-dose combination group, low-dose control group of amifostine combined with quercetin, medium-dose control group of amifostine combined with quercetin, and high-dose control group. 60 Co was used as the radiation source to subject the lungs of mice to gamma-ray ionizing radiation at a dose of 30 Gy and a dose rate of 1 Gy / min. Lead plates were used to shield other parts of the mice to prevent ionizing radiation damage. The blank control group and negative control group mice did not receive ionizing radiation. The condition of the mice in each group was observed. After the ionizing radiation, bilateral lungs were harvested on days 7, 14, and 20. The lungs were fixed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE). The results are as follows: Figure 2 and Figure 3 As shown in Table 1, the lungs of each mouse were washed with pre-cooled physiological saline, and the fresh wet weight and the dried weight were weighed. The wet / dry ratio and lung coefficient were calculated according to the formula. The results are shown in Table 2. The apoptosis rate of vascular endothelial cells in the lungs of each mouse was determined using the TUNEL assay kit. The specific steps were followed according to the instructions for use of the TUNEL assay kit. The results are shown in Table 2.

[0034] Wet / dry specific gravity = Fresh wet weight / Dry weight after drying Lung coefficient (%) = Lung wet weight (g) / Body weight (g) × 100%.

[0035] Table 1. Wet / dry weight and lung coefficient of mice in each group.

[0036] Table 2 Apoptosis rate of vascular endothelial cells in each group of mice

[0037] Tables 1 and 2 show that compared with the blank control group, the irradiation group had increased lung wet / dry ratio, lung coefficient, and significantly increased vascular endothelial cell apoptosis rate, indicating that ionizing radiation can cause severe damage to lung blood vessels and other tissues in mice, leading to increased pulmonary hemorrhage. The amifotin group, isoflavone group, quercetin group, low-dose combination group, medium-dose combination group, and high-dose combination group all showed decreased lung wet / dry ratio, lung coefficient, and vascular endothelial cell apoptosis rate. Furthermore, the medium-dose and high-dose combination groups showed decreased... The reduction in the wet / dry weight ratio of the mouse lungs and the apoptosis rate of vascular endothelial cells was more significant, indicating that administration of amifostatin, verbascoside, or quercetin alone can prevent radiation-induced lung injury caused by ionizing radiation to some extent. However, the combination of amifostatin and verbascoside showed better preventative effects against radiation-induced lung injury. The effects of 5 mg / kg amifostatin + 10 mg / kg verbascoside and 5 mg / kg amifostatin + 15 mg / kg verbascoside were similar. In contrast, the control group treated with amifostatin and quercetin, regardless of the concentration (low, medium, or high), showed no difference compared to the irradiation-only group, indicating that the combination of amifostatin and quercetin cannot prevent or treat lung injury caused by ionizing radiation in mice. The reason for this is that although both amifostatin and quercetin, when used alone, can prevent radiation-induced lung damage caused by ionizing radiation, their combined use produces an antagonistic effect, rendering both substances ineffective in preventing radiation-induced lung damage. Consequently, the control group using amifostatin and quercetin showed no difference in results compared to the irradiation-only group. Observation of the mice in each group revealed varying degrees of loss of appetite and lethargy in both the amifostatin group and the control group using amifostatin and quercetin, likely due to side effects of amifostatin. However, the mice in the amifostatin and verbascoside combination group showed no adverse symptoms, possibly because the combination of amifostatin and verbascoside has a synergistic effect, eliminating the side effects of amifostatin.

[0038] Depend on Figure 2 and Figure 3It was found that the lung tissue structure of the blank control group mice was clear and normal, with a large number of uniform, round alveolar tissues composed of a single layer of alveolar epithelial cells and capillaries. The alveolar cavities were uniformly clear and transparent, without pathological features such as hemorrhage and inflammatory exudate. The alveolar walls were thin and fine and without inflammatory cell infiltration. These characteristics were basically consistent with those of the negative control group. After 20 days of ionizing radiation, the lung tissue of the mice in the simple irradiation group and the three groups of mice treated with amifotin combined with quercetin showed significant capillary dilation and congestion, and local alveolar cavity collapse. The lungs exhibit bulging, twisting, deformation, or bullae formation; severe interstitial edema with significant inflammatory cell infiltration; marked widening and thickening of alveolar walls; partial fusion of alveolar walls in patches, compressing surrounding bronchioles and causing them to twist and deform; varying numbers of red blood cells and a certain volume of fibrinous exudate are visible in the alveolar cavities; macrophages in some alveolar cavities have engulfed excessive red blood cells, forming hemosiderin-containing brownish-brown refractive granules; indicating that the combined use of amifostatin and quercetin cannot achieve a therapeutic effect on radiation-induced lung injury. The lung tissue lesions in mice in the amifostatin, verbascoside, and quercetin groups were comparable, all showing some degree of inflammatory exudate and hemorrhagic damage, abnormal proliferation of alveolar epithelial cells, and thickening and fusion of alveolar walls. However, compared to the irradiation-only group, the overall inflammation and edema were milder, and alveolar structures and outlines could be observed. Although mice in the low-dose combination group still had interstitial edema and varying degrees of alveolar wall fusion, the overall degree of inflammation was lower than that in the irradiation-only, amifostatin, verbascoside, and quercetin groups. The degree of lesions in alveolar contours and structures was also reduced. In the lung tissue of mice in the medium-dose combination group, most alveolar cavities had clear structures and contours, alveolar wall thickening was not obvious, pulmonary interstitial edema was not severe, and there was no obvious fusion or adhesion between most alveolar walls. Although it could not completely reach the healthy level of lung tissue structure of mice in the blank control group and negative control group, the degree of inflammation and alveolar wall thickness of most alveoli were significantly lower than those in the amifostatin group, the isoflavone group, and the quercetin group, and the staining results were close to those in the high-dose combination group. This indicates that the amifostatin group, the isoflavone group, and the quercetin group, when administered alone, can all play a certain role in the prevention and relief of radiation-induced lung injury, and there is no significant difference in the prevention and treatment effects of radiation-induced lung injury. The combination of amifostatin and isoflavone at low doses has a certain effect on the prevention and treatment of radiation-induced lung injury, initially demonstrating the synergistic effect of anti-radiation and anti-inflammation; at medium and high doses, it can show significant prevention and treatment effects, and it does not exhibit dose dependence.

[0039] Example 3

[0040] Effects of amifotin combined with isoflavones or quercetin on the levels of TNF-α, TGF-β1 and IL-6

[0041] Many studies have found that transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and IL-6 not only participate in the early inflammatory response of radiation-induced lung injury, but also affect the later fibrotic 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, TGF-β1, and IL-6 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.). The results are shown in Table 3.

[0042] Table 3. Expression levels of TNF-α, TGF-β1, and IL-6 in mice of each group.

[0043] Table 3 shows that the expression levels of TNF-α, TGF-β1, and IL-6 in mice in the irradiation-only group were significantly higher than those in other groups. The expression levels of TNF-α, TGF-β1, and IL-6 in mice in the amifostatin, verbascoside, and quercetin groups were significantly lower than those in the irradiation-only group, and the differences were not significant compared to the low-dose combination group. However, the expression levels of TNF-α, TGF-β1, and IL-6 in the medium-dose and high-dose combination groups were significantly different from those in the amifostatin, verbascoside, and quercetin groups. This indicates that amifostatin, verbascoside, or quercetin alone can inhibit the expression of TNF-α, TGF-β1, and IL-6 to a certain extent; while the combination of amifostatin and verbascoside can more effectively inhibit the expression of TNF-α, TGF-β1, and IL-6, thus effectively preventing radiation-induced lung injury. The control group, using amifostatin in combination with quercetin, showed no difference compared to the irradiation-only group, regardless of whether the concentration was low, medium, or high. This indicates that the combination of amifostatin and quercetin does not inhibit the expression of TNF-α, TGF-β1, and IL-6. The reason for this is that while both amifostatin and quercetin can inhibit the expression of TNF-α, TGF-β1, and IL-6 when used alone, their combination produces an antagonistic effect, causing both substances to lose their inhibitory effect on TNF-α, TGF-β1, and IL-6 expression. This results in no difference between the control group using amifostatin and quercetin and the irradiation-only group. Therefore, not all substances that can inhibit the expression of TNF-α, TGF-β1, and IL-6 retain their inhibitory effect when used in combination with amifostatin.

[0044] Example 4

[0045] Mouse model of radiation-induced lung injury

[0046] C57BL / 6 mice were anesthetized with an intraperitoneal injection of 50 mg / kg 1% sodium pentobarbital solution and fixed in a supine position. 60 Co was used as the radiation source to subject C57BL / 6 mice to localized gamma-ray ionizing radiation at a dose of 30 Gy and a dose rate of 200 cGy / min. Lead plates were used to shield other parts of the C57BL / 6 mice from ionizing radiation damage. Following ionizing radiation, the C57BL / 6 mice exhibited acute radiation-induced pneumonia within 1–2 weeks, and bilateral lung fibrosis within 3–5 weeks, a course largely consistent with human radiation-induced lung injury, indicating a successful establishment of a mouse model of radiation-induced lung injury.

[0047] Example 5

[0048] Effects of amifotin combined with verbascoside or quercetin on survival rate in mice with radiation-induced lung injury.

[0049] 120 mice with radiation-induced lung injury, constructed in Example 4, were randomly divided into 6 groups: irradiation group, amifostine group, vernix caseosaflavonoid group, quercetin group, amifostine and vernix caseosaflavonoid combination group, and amifostine and quercetin control group, with 20 mice in each group. Six hours after ionizing radiation, mice in the amifostine group were intraperitoneally injected with 20 mg / kg amifostine, mice in the vernix caseosaflavonoid group were intraperitoneally injected with 20 mg / kg vernix caseosaflavonoid, mice in the combination group were intraperitoneally injected with 5 mg / kg amifostine + 10 mg / kg vernix caseosaflavonoid, and mice in the amifostine and quercetin control group were intraperitoneally injected with 5 mg / kg amifostine + 10 mg / kg quercetin. The corresponding medications were administered every 2 days thereafter. Mice in the irradiation group received no medication. The survival rate of mice in each group was recorded within 20 days. The results are shown below. Figure 4 As shown.

[0050] Depend on Figure 4It was found that mice in the irradiation group and the control group treated with amifostatin and quercetin began to die on day 5 after ionizing radiation. By day 20, the survival rate of the irradiation group was only 15%, and the survival rate of the control group treated with amifostatin and quercetin was only 10%. Mice in the amifostatin group died from day 8 to 14, and the survival rate of mice on day 20 was 35%. Mice in both the isoflavone group and the quercetin group died from day 7 to 17. The mortality time of mice in the isoflavone group and the quercetin group continued until day 18. By day 20, the survival rate of mice in the isoflavone group and the quercetin group was 30%. Mice in the combined treatment group only experienced a small number of deaths from day 9 to 16, and the survival rate reached 90% by day 20. The results indicate that amifostatin combined with isoflavone significantly improved the survival rate of mice with radiation-induced lung injury. Compared with amifostatin alone, the combination of amifostatin and isoflavone increased the survival rate of mice with radiation-induced lung injury by 55%. Compared with isoflavone or quercetin alone, the combination of amifostatin and isoflavone significantly reduced the dosage of both amifostatin and isoflavone, thus improving the survival rate of mice. There was no significant difference in survival rate between the irradiation group and the group treated with amifostatin combined with quercetin, indicating that the combination of amifostatin and quercetin did not improve the survival rate of mice, suggesting that the combination of amifostatin and quercetin has no preventive or therapeutic effect on radiation-induced lung injury.

[0051] As can be seen from the above examples, the present invention, by combining amifostine and verbascoside, can increase the survival rate of mice with radiation-induced lung injury to 90% while significantly reducing the dosage of amifostine and verbascoside, and effectively inhibits the expression of TNF-α, TGF-β1 and IL-6, thus achieving a good preventive and therapeutic effect on radiation-induced lung injury caused by ionizing radiation.

[0052] 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. Application of amifotin combined with verbascoside in the preparation of formulations for the prevention and / or treatment of radiation-induced lung injury.

2. The application according to claim 1, characterized in that, The mass ratio of amifostine to verbascoside is 1:1 to 3, wherein the concentration of amifostine is 4 to 6 mg / kg and the concentration of verbascoside is 4 to 18 mg / kg.

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

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

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

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

7. The pharmaceutical composition according to claim 6, characterized in that, The mass ratio of amifostine to verbascoside is 1:1 to 3, wherein the concentration of amifostine is 4 to 6 mg / kg and the concentration of verbascoside is 4 to 18 mg / kg.

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

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