A composition containing pyruvate and its preparation method and application

Abstract

The present invention belongs to the field of biomedicine technology, and specifically relates to a composition containing pyruvate, a preparation method thereof and an application thereof. The composition comprises the following raw materials in parts by weight: 2-3 parts of pyruvate and 3-5 parts of modified tyrosine, and the structural formula of the modified tyrosine is:. The composition can significantly reduce the number of inflammatory cells in the bronchoalveolar lavage fluid of mice with acute lung injury, as well as the W / D ratio of lung tissue and MPO activity. At the same time, the composition is used in a relatively small amount, which can avoid side effects such as liver damage caused by long-term use of hormone drugs and reduce drug resistance. The preparation method provided by the present invention is simple and feasible, and provides a new synthetic idea for preparing drugs for treating acute lung injury.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and in particular relates to a composition containing pyruvate, and a preparation method and application thereof. Background Art

[0002] Acute lung injury (ALI) is the early stage of acute respiratory distress syndrome (ARDS), clinically characterized by severe respiratory distress and hypoxemia. The main cytological features of ALI are the destruction of the alveolar-capillary membrane, excessive migration of neutrophils, and the massive release of proinflammatory and cytotoxic mediators. Although the incidence of ALI is not high, at 86.2 per 100,000 people per year, its mortality rate is as high as 40-60%. There are many factors that lead to ALI, among which lipopolysaccharide (LPS)-induced endotoxemia is one of the common causes.

[0003] Currently, there is no particularly effective treatment for ALI patients. Ventilator therapy can reduce the mortality rate of patients but is prone to mechanical ventilation-induced lung injury; and clinically used anti-ALI drugs, such as dexamethasone and prednisolone, can cause adverse reactions such as coagulation disorders, gastric ulcers, osteoporosis and liver damage. Therefore, it is particularly important to find new effective drugs for ALI.

[0004] The literature Ethyl pyruvate reduces mortality in an endotoxin-induced severe acute lung injury mouse model, Respiratory Research, 2019 disclosed that ethyl pyruvate can reduce the mortality of endotoxin-induced severe acute lung injury mouse model. However, its therapeutic effect is relatively limited. Sodium pyruvate is the most common pyruvate, with a molecular formula of C 3 H 3 NaO 3 , is a class of endogenous small molecules. Sodium pyruvate and pyruvic acid are naturally present in the human body and participate in the metabolism of various tissues and organs throughout the body. However, the prior art has not studied the effect of sodium pyruvate on acute lung injury. Tyrosine is a non-essential amino acid that can improve vitiligo, regulate mood, and promote metabolism.

[0005] The present invention prepares a pharmaceutical composition capable of alleviating acute lung injury by modifying tyrosine and then acting with pyruvate. Summary of the invention

[0006] In order to overcome the deficiencies of the prior art, the primary purpose of the present invention is to provide a composition containing pyruvate, which is prepared by modifying tyrosine and then combining it with pyruvate. The composition can reduce the number of inflammatory cells in the bronchoalveolar lavage fluid of mice with acute lung injury, as well as the W / D ratio and MPO activity of the lung tissue of model mice. At the same time, the composition is used in a relatively small amount, which can avoid the side effects such as liver damage caused by commonly used hormone drugs and reduce drug resistance.

[0007] The second purpose of the present invention is to provide a method for preparing the above-mentioned composition containing pyruvate, which is simple and feasible and provides a new synthetic idea for preparing drugs for treating acute lung injury.

[0008] The third purpose of the present invention is to provide an application of the above-mentioned composition containing pyruvate in the preparation of a drug for treating acute lung injury, thereby providing a new therapeutic drug for treating acute lung injury.

[0009] The purpose of the present invention is achieved through the following technical solutions:

[0010] A composition containing pyruvate, comprising the following raw materials in parts by weight: 2-3 parts of pyruvate, 3-5 parts of modified tyrosine; the structural formula of the modified tyrosine is:

[0011] .

[0012] As a preferred technical solution of the present invention, the preparation process of the modified tyrosine comprises the following steps:

[0013] (1) Under an inert gas atmosphere, Boc-L-tyrosine and an organic base are added to solvent A, and after stirring for 10-20 min, EDC and HOBt are added. After further stirring for 5-10 min, 2-amino-5-nitrobenzimidazole is added to react. The reaction solution is separated and purified to obtain intermediate 1.

[0014] The structural formula of the intermediate 1 is:

[0015]

[0016] (2) Add intermediate 1 to solvent B, add trifluoroacetic acid at 0-3°C and keep warm for reaction, and concentrate the reaction solution to obtain intermediate 2;

[0017] The structural formula of the intermediate 2 is:

[0018]

[0019] (3) Add intermediate 2 and 2-[(2-methyl-4-oxo-4H-pyran-3-yl)oxy]-acetic acid to a mixed solvent, then add triethylamine and N,N'-dicyclohexylcarbodiimide at 0°C, and react at room temperature; separate and purify the reaction solution to obtain the modified tyrosine.

[0020] As a preferred technical solution of the present invention, the molar ratio of Boc-L-tyrosine, organic base, EDC, HOBt and 2-amino-5-nitrobenzimidazole in step (1) is (1.2-1.5): (1.3-1.5): (1.8-2.1): (0.9-1.1): 1; the organic base is N,N-diisopropylethylamine or triethylamine.

[0021] As a preferred technical solution of the present invention, the reaction time in step (1) is 18-24 h.

[0022] As a preferred technical solution of the present invention, the molar ratio of the intermediate 1 to trifluoroacetic acid in step (2) is 1:(45-55).

[0023] As a preferred technical solution of the present invention, the time of the insulation reaction in step (2) is 45-60 min.

[0024] As a preferred technical solution of the present invention, the molar ratio of the intermediate 2, 2-[(2-methyl-4-oxo-4H-pyran-3-yl)oxy]-acetic acid, triethylamine and N,N'-dicyclohexylcarbodiimide in step (3) is 5:(5.0-5.2):(5.2-5.5):(6.5-7.0).

[0025] As a preferred technical solution of the present invention, the reaction time at room temperature in step (3) is 3-5 h; the mixed solvent in step (3) is a mixed solvent of acetonitrile and DMF in a volume ratio of 4:1.

[0026] The preparation method of the composition containing pyruvate is as follows: the pyruvate and modified tyrosine are mixed according to a weight ratio to obtain the composition.

[0027] The above-mentioned composition containing pyruvate is used to prepare a medicine for treating acute lung injury.

[0028] The present invention has the following effects compared with the prior art:

[0029] 1. The present invention provides a composition containing pyruvate, which includes pyruvate and modified tyrosine. Based on long-term research and molecular structure design and improvement of chemical drugs, the inventor modified tyrosine to synthesize a modified tyrosine, and then combined it with pyruvate. The composition can significantly reduce the number of inflammatory cells in the bronchoalveolar lavage fluid of mice with acute lung injury, as well as the W / D ratio and MPO activity of the lung tissue of model mice. At the same time, the dosage of the composition is relatively small, which can avoid side effects such as liver damage caused by long-term use of hormone drugs and reduce drug resistance.

[0030] 2. The present invention also provides a method for preparing the above-mentioned composition containing pyruvate, which is simple and feasible, and provides a new synthetic idea for preparing drugs for treating acute lung injury.

[0031] 3. The present invention also provides a use of the above-mentioned composition containing pyruvate in the preparation of a drug for treating acute lung injury, thereby providing a new therapeutic drug for treating acute lung injury. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 ALT is the level of alanine aminotransferase (ALT) in the serum of mice in the blank control group and Example 1-3 groups in the test examples of the present invention;

[0033] Figure 2 is the level of aspartate aminotransferase (AST) in the serum of mice in the blank control group and Example 1-3 groups in the test examples of the present invention;

[0034] Figure 3 The wet / dry weight ratio of lung tissue of each group of mice in the test example of the present invention;

[0035] Figure 4 These are the results of MPO activity in the lung tissues of each group of mice in the test examples of the present invention. DETAILED DESCRIPTION

[0036] The technical scheme of the present invention is further described below in conjunction with specific embodiments. However, it should be understood by those skilled in the art that the following examples are only used to illustrate the present invention and should not be regarded as limiting the present invention. The specific conditions not specified in the examples are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used, unless otherwise specified, are conventional products obtained through commercial channels.

[0037] Example 1

[0038] A composition containing pyruvate, comprising the following raw materials in parts by weight: 2 parts of sodium pyruvate, 3 parts of modified tyrosine; the structural formula of the modified tyrosine is:

[0039] .

[0040] The specific preparation process of the above modified tyrosine is as follows:

[0041]

[0042] (1) Under nitrogen atmosphere, Boc-L-tyrosine (CAS: 3978-80-1, 12 mmol) and N,N-diisopropylethylamine (DIPEA, 15 mmol) were added to 15 mL DMF and stirred at room temperature for 10 min. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 18 mmol) and 1-hydroxybenzotriazole (HOBt, 9 mmol) were added to the above reaction system and stirred for 5 min. Then 2-amino-5-nitrobenzimidazole (CAS: 6232-92-4, 10 mmol) was added to the mixed system and reacted at room temperature for 18 h. Ethyl acetate was added to dilute the reaction solution, and then washed with 5 wt% hydrochloric acid solution, 5 wt% sodium bicarbonate solution, deionized water, and saturated brine in sequence. After washing, the ethyl acetate phase was dried over anhydrous sodium sulfate, concentrated, and column-filtered (V 二氯甲烷 :V 甲醇 =9:1) and purified to obtain intermediate 1.

[0043] The intermediate 1 1 H NMR( C 21 H 23 N 5 O 6 , 400 MHz, d 6 -DMSO) δ 12.41 (s, 1H), 10.30(s, 1H), 9.06 (s, 1H), 8.39-8.37 (d, 1H), 8.09-8.07 (d, 1H), 7.67-7.66 (d,1H), 7.40 (s, 1H), 6.96-6.94 (d, 2H), 6.68-6.65 (d, 2H), 4.91-4.90 (t, 1H),3.43-3.40 (q, 1H), 3.20-3.18 (q, 1H), 1.40 (s, 9H). The above results confirmed that it was the target product.

[0044] (2) Intermediate 1 (10 mmol) was added to 50 mL of dichloromethane, the reaction solution was cooled to 0°C, and trifluoroacetic acid (450 mmol) was added. The reaction was continued at 0°C for 45 min. The reaction solution was concentrated to obtain intermediate 2.

[0045] HRMS (ESI+ ): [M+H] + Calculated to be 342.11, found to be 342.11; the above results confirmed that the obtained product was the target product.

[0046] (3) Add 2-[(2-methyl-4-oxo-4H-pyran-3-yl)oxy]-acetic acid (CAS: 148115-82-6, 5.0 mmol) and intermediate 2 (5.0 mmol) to 50 mL of a mixed solvent (V 乙腈 :V N,N-二甲基甲酰胺 =4:1), the reaction solution was cooled to 0°C, triethylamine (5.2 mmol) and N,N'-dicyclohexylcarbodiimide (DCC, 6.5 mmol) were added thereto in sequence, the reaction solution was naturally heated to room temperature and reacted for 3 h; the reaction solution was filtered and concentrated, the reaction solution was diluted with ethyl acetate, 1M hydrochloric acid was used to adjust the pH to neutral, water was added thereto until the mixed system was obviously separated, the organic phase was washed with water after separation, and then washed with saturated sodium bicarbonate solution and saturated brine in sequence, dried over anhydrous sodium sulfate, concentrated, and purified by column to obtain modified tyrosine.

[0047] The above modified tyrosine 1 H NMR( C 24 H 21 N 5 O 8 , 400 MHz, d 6 -DMSO) δ 12.41 (s, 1H),10.30 (s, 1H), 9.06 (s, 1H), 8.39 (d, 1H), 8.32 (s, 1H), 8.11-8.09 (dd, 1H),7.74-7.72 (d, 1H), 7.69-7.67 (d, 1H), 6.98-6.96 (d, 2H), 6.70-6.68 (d, 2H), 6.37-6.35 (d, 1H), 4.93-4.91 (t, 1H), 4.85 (s, 2H), 3.46-3.43 (q, 1H), 3.21-3.18 (q, 1H), 2.30 (s, 3H); HRMS (ESI + ): [M+H] + Calculated to be 508.14, found to be 508.14; the above results confirmed that the obtained product was the target product.

[0048] The present invention also provides a method for preparing the above-mentioned composition containing pyruvate, comprising the following steps: according to the above-mentioned weight ratio, sodium pyruvate and modified tyrosine are uniformly mixed to obtain.

[0049] Example 2

[0050] A composition containing pyruvate comprises the following raw materials in parts by weight: 3 parts of sodium pyruvate and 5 parts of modified tyrosine; the structure of the modified tyrosine is the same as that in Example 1.

[0051] The specific preparation process of the above modified tyrosine is as follows:

[0052] (1) Under nitrogen atmosphere, add Boc-L-tyrosine (15 mmol) and triethylamine (13 mmol) to 15 mL DMF and stir at room temperature for 20 min. Add EDC (21 mmol) and HOBt (11 mmol) to the above reaction system and stir for 10 min. Then add 2-amino-5-nitrobenzimidazole (10 mmol) to the mixed system and react at room temperature for 24 h. Add ethyl acetate to dilute the reaction solution, and then wash it with 5 wt% hydrochloric acid solution, 5 wt% sodium bicarbonate solution, deionized water, and saturated brine in sequence. After washing, dry the ethyl acetate phase with anhydrous sodium sulfate, concentrate, and pass through a column (V 二氯甲烷 :V 甲醇 =9:1) to obtain intermediate 1. 1 H NMR was consistent with Example 1.

[0053] (2) Intermediate 1 (10 mmol) was added to 50 mL of dichloromethane, the reaction solution was cooled to 0°C, and trifluoroacetic acid (500 mmol) was added, and the reaction was continued at 3°C ​​for 60 min; the reaction solution was concentrated to obtain intermediate 2. HRMS (ESI + )The results are consistent with those in Example 1.

[0054] (3) Add 2-[(2-methyl-4-oxo-4H-pyran-3-yl)oxy]-acetic acid (5.2 mmol) and intermediate 2 (5.0 mmol) to 50 mL of a mixed solvent (V 乙腈 :V N,N-二甲基甲酰胺 =4:1), cool the reaction solution to 0°C, then add triethylamine (5.5 mmol) and DCC (7.0 mmol) in turn, naturally warm the reaction solution to room temperature and react for 5 h; filter the reaction solution and concentrate it, dilute the reaction solution with ethyl acetate, adjust the pH to neutral with 1 M hydrochloric acid, and then add water until the mixed system is clearly separated. After separation, wash the organic phase with water, then wash with saturated sodium bicarbonate solution and saturated brine in turn, dry with anhydrous sodium sulfate, concentrate, and purify by column to obtain modified tyrosine. 1 H NMR was consistent with Example 1.

[0055] The present invention also provides a method for preparing the above-mentioned composition containing pyruvate, comprising the following steps: according to the above-mentioned weight ratio, sodium pyruvate and modified tyrosine are uniformly mixed to obtain.

[0056] Example 3

[0057] A composition containing pyruvate comprises the following raw materials in parts by weight: 2 parts of sodium pyruvate and 4 parts of modified tyrosine; the structural formula of the modified tyrosine is the same as that of Example 1.

[0058] The specific preparation process of the above modified tyrosine is as follows:

[0059] (1) Under nitrogen atmosphere, add Boc-L-tyrosine (14 mmol) and triethylamine (14 mmol) to 15 mL DMF and stir at room temperature for 15 min. Add EDC (20 mmol) and HOBt (10 mmol) to the above reaction system and stir for 8 min. Then add 2-amino-5-nitrobenzimidazole (10 mmol) to the mixed system and react at room temperature for 20 h. Add ethyl acetate to dilute the reaction solution, and then wash with 5 wt% hydrochloric acid solution, 5 wt% sodium bicarbonate solution, deionized water, and saturated brine in sequence. After washing, dry the ethyl acetate phase with anhydrous sodium sulfate, concentrate, and pass through a column (V 二氯甲烷 :V 甲醇 =9:1) to obtain intermediate 1. 1 H NMR was consistent with Example 1.

[0060] (2) Intermediate 1 (10 mmol) was added to 50 mL of dichloromethane, the reaction solution was cooled to 0°C, and trifluoroacetic acid (470 mmol) was added, and the reaction was continued at 3°C ​​for 50 min. The reaction solution was concentrated to obtain intermediate 2. HRMS (ESI + )The results are consistent with those in Example 1.

[0061] (3) Add 2-[(2-methyl-4-oxo-4H-pyran-3-yl)oxy]-acetic acid (5.0 mmol) and intermediate 2 (5.0 mmol) to 50 mL of a mixed solvent (V 乙腈 :V N,N-二甲基甲酰胺=4:1), cool the reaction solution to 0°C, then add triethylamine (5.4 mmol) and DCC (6.8 mmol) in turn, naturally warm the reaction solution to room temperature and react for 4 h; filter the reaction solution and concentrate it, dilute the reaction solution with ethyl acetate, adjust the pH to neutral with 1M hydrochloric acid, and then add water until the mixed system is clearly separated. After separation, wash the organic phase with water, then wash with saturated sodium bicarbonate solution and saturated brine in turn, dry with anhydrous sodium sulfate, concentrate, and purify by column to obtain modified tyrosine. Modified tyrosine 1 H NMR was consistent with Example 1.

[0062] The present invention also provides a method for preparing the above-mentioned composition containing pyruvate, comprising the following steps: according to the above-mentioned weight ratio, sodium pyruvate and modified tyrosine are uniformly mixed to obtain.

[0063] Test example

[0064] 1. Animal Modeling

[0065] A total of 120 SPF healthy BALB / c mice, weighing 18-22 g, were male and adaptively fed for 2 days. The mice in each group were fasted for 12 h before modeling, and then the mice were anesthetized with 0.5% sodium pentobarbital (60 mg / kg). After anesthesia, the mouse mouth was opened with a mouse opener, and lipopolysaccharide (LPS, dose of 4 mg / kg) solution was injected into the lungs using a lung liquid quantitative nebulizer to establish an acute lung injury model (ALI model).

[0066] 2. Animal grouping and dosing regimen

[0067] The 120 mice with successful modeling were randomly divided into ALI model group, Example 1-3 group, sodium pyruvate group and DEX (dexamethasone) group, and 20 healthy mice were taken as blank control group. The dosing schedule is shown in Table 1.

[0068] Table 1 Dosage regimen for each group

[0069]

[0070] 3. Animal specimen handling and collection

[0071] (1) One hour after administration on the 8th day, the mice were anesthetized with 0.5% sodium pentobarbital (60 mg / kg), and blood was collected from the eyeballs of mice in each group. The collected serum was tilted and allowed to stand, centrifuged at 4°C and 3000 r / min for 20 min, and the serum was separated and frozen at -20°C for detection of serum biochemical indicators.

[0072] (2) After blood collection, the thorax was opened to expose the mouse trachea and lungs, the left main bronchus was ligated, and the bronchoalveoli were lavaged with 4°C phosphate buffer for three consecutive times. The alveolar lavage fluid (BALF) of the mice was collected for the detection of the total number of cells, neutrophils and macrophages in the BALF.

[0073] (3) After collecting blood and BALF, the mice in each group were killed, and the lung tissues were separated and weighed to calculate the wet weight / dry weight (W / D) ratio of lung tissue and MPO activity.

[0074] 4. Test indicators and result analysis

[0075] 4.1 Safety of Compositions Containing Pyruvate on Liver Tissue

[0076] The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of the blank control group and the mice in Example 1-3 groups were determined by enzyme-linked immunosorbent assay (ELISA). The data of each group were expressed as mean ± standard deviation (x ± s). The quantitative data were analyzed by variance analysis, and the differences between the groups were tested by Student T test. The results are shown in Figure 1 and Figure 2 .

[0077] Figure 1 is the level of ALT in the serum of the blank control group and the mice in Examples 1-3, Figure 2 is the level of AST in the blank control group and the mice of Examples 1-3. Figure 1 and Figure 2 It can be seen that the ALT and AST levels of the Example 1-3 groups are almost the same as those of the blank control group, which indicates that the composition containing pyruvate prepared by the present invention will not cause drug-induced liver injury. In the process of treating acute lung injury, the use of the composition containing pyruvate of the present invention can avoid the side effects such as liver damage caused by long-term use of hormone drugs such as dexamethasone.

[0078] 4.2 Therapeutic effect of the composition containing pyruvate on acute lung injury

[0079] (1) The bronchoalveolar lavage fluid of each group of mice was centrifuged at 4°C and 3000 r / min for 10 min. The precipitated cells were resuspended in 100 μL PBS and Diff-Quik staining was used to identify and count the total cells, neutrophils, and macrophages in BALF. The results are shown in Table 2.

[0080] (2) After the mice in each group were killed, the lung tissue was separated and its weight was measured and recorded as the wet weight of the lung tissue. The lung tissue was then dried in a 60°C constant temperature incubator and its weight was measured after 48 hours and recorded as the dry weight of the lung tissue. The ratio of the wet weight of the lung tissue to the dry weight was calculated as the lung tissue wet weight / dry weight (W / D) ratio. The results are shown in Figure 3.

[0081] (3) After measuring the W / D ratio of the lung tissue, the lung tissue was washed with ice-cold saline, the surface moisture was dried with filter paper, and the MPO activity in the lung tissue was detected after homogenization with a grinder. The final data was the average value of each group of mice. The results are shown in Figure 4 .

[0082] Table 2 Numbers of total cells, neutrophils and macrophages in BALF of mice in each group

[0083]

[0084] As can be seen from Table 2, compared with the blank control group, the number of total cells, neutrophils and macrophages in the BALF of mice in the ALI model group increased significantly. Compared with the ALI model group, the number of cells in the BALF of mice in the Example 1-3 group, the DEX group and the sodium pyruvate group was significantly reduced, and the effect of reducing the number of cells in the BALF in the Example 1-3 group was better than that in the sodium pyruvate group and similar to that in the DEX group.

[0085] Measuring the lung W / D ratio is a key indicator for checking the degree of pulmonary edema. Figure 3 The wet weight / dry weight ratio of lung tissue of each group of mice is shown in Table 1. Figure 3 It can be seen that compared with the blank control group, the W / D ratio of the lung tissue of the ALI model group mice was significantly increased. Compared with the ALI model group, the W / D ratio of the lung tissue of the mice in Example 1-3 groups was significantly reduced, and the effect was similar to that of the DEX group and better than that of the sodium pyruvate group.

[0086] Figure 4 The results of MPO activity in lung tissue of mice in each group are shown in Table 1. Figure 4 It can be seen that the MPO activity in the lung tissue of mice in the ALI model group was significantly increased compared with the blank control group. The MPO activity in the lungs of mice in the Example 1-3 group, the DEX group and the sodium pyruvate group was significantly reduced compared with the ALI model group, and there was no significant difference between the Example 1-3 group and the DEX group, which were all better than the sodium pyruvate group.

[0087] In summary, the pyruvate-containing compositions prepared in Examples 1-3 of the present invention can reduce pulmonary edema, inhibit the release of total cells, neutrophils and macrophages into BALF, and increase the MPO activity in lung tissue, thereby effectively inhibiting LPS-induced acute lung injury and inflammation.

[0088] In summary, the present invention provides a composition containing pyruvate, which includes pyruvate and modified tyrosine. The composition can significantly reduce the number of inflammatory cells in the alveolar fluid of mice with acute lung injury, as well as the W / D ratio and MPO activity of the lung tissue of model mice. At the same time, the composition is used in a relatively small amount, which can avoid side effects such as liver damage caused by long-term use of commonly used hormone drugs and reduce drug resistance. The present invention also provides a method for preparing the above-mentioned composition containing pyruvate, which provides a new synthetic idea for preparing drugs for treating acute lung injury.

[0089] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. On the basis of the present invention, some modifications or replacements may be made thereto, but these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of protection claimed by the present invention.

Claims

1. A composition containing pyruvate, characterized in that The invention is composed of the following raw materials in parts by weight: 2-3 parts of pyruvate, 3-5 parts of modified tyrosine; the pyruvate is sodium pyruvate; the structural formula of the modified tyrosine is: 。 2. The composition containing pyruvate according to claim 1, characterized in that The preparation process of the modified tyrosine comprises the following steps: (1) Under an inert gas atmosphere, Boc-L-tyrosine and an organic base are added to N,N-dimethylformamide, and after stirring for 10-20 minutes, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole are added, and after continuing to stir for 5-10 minutes, 2-amino-5-nitrobenzimidazole is added to react; the reaction solution is separated and purified to obtain an intermediate 1; the structural formula of the intermediate 1 is: (2) Add intermediate 1 to dichloromethane, add trifluoroacetic acid at 0-3°C and keep warm for reaction, concentrate the reaction solution to obtain intermediate 2; the structural formula of intermediate 2 is: (3) Adding intermediate 2 and 2-[(2-methyl-4-oxo-4H-pyran-3-yl)oxy]-acetic acid to a mixed solvent consisting of acetonitrile and N,N-dimethylformamide, and then adding triethylamine and N,N'-dicyclohexylcarbodiimide at 0°C, and reacting at room temperature; separating and purifying the reaction solution to obtain the modified tyrosine.

3. The composition containing pyruvate according to claim 2, characterized in that The molar ratio of Boc-L-tyrosine, organic base, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1-hydroxybenzotriazole and 2-amino-5-nitrobenzimidazole in step (1) is (1.2-1.5): (1.3-1.5): (1.8-2.1): (0.9-1.1): 1; the organic base is N,N-diisopropylethylamine or triethylamine.

4. The composition containing pyruvate according to claim 2, characterized in that The reaction time in step (1) is 18-24 h.

5. The composition containing pyruvate according to claim 2, characterized in that The molar ratio of the intermediate 1 to trifluoroacetic acid in step (2) is 1:(45-55).

6. The composition containing pyruvate according to claim 2, characterized in that The insulation reaction time in step (2) is 45-60 min.

7. The composition containing pyruvate according to claim 2, characterized in that The molar ratio of the intermediate 2, 2-[(2-methyl-4-oxo-4H-pyran-3-yl)oxy]-acetic acid, triethylamine and N,N'-dicyclohexylcarbodiimide in step (3) is 5:(5.0-5.2):(5.2-5.5):(6.5-7.0).

8. The composition containing pyruvate according to claim 2, characterized in that The reaction time at room temperature in step (3) is 3-5 h; the mixed solvent in step (3) is a mixed solvent of acetonitrile and N,N-dimethylformamide in a volume ratio of 4:

1.

9. The method for preparing a composition containing pyruvate according to any one of claims 1 to 8, characterized in that: The pyruvate and modified tyrosine are mixed according to a weight ratio to obtain the product.

10. Use of the composition containing pyruvate according to any one of claims 1 to 8, characterized in that: Used for preparing drugs for treating acute lung injury.

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