Sodium pyruvate aerosol inhalation preparation as well as preparation method and application thereof

Abstract

The invention belongs to the field of biological medicine, and particularly relates to a sodium pyruvate aerosol inhalation preparation and a preparation method and application thereof. The aerosol inhalation preparation comprises the following components: sodium pyruvate, modified glycyrrhizic acid, a pH regulator and water for injection, the concentration of the sodium pyruvate is 50-120 mg / mL, the concentration of the modified glycyrrhizic acid is 5-40 mg / mL, and the pH value of the preparation is 6.5-7. By adding the modified glycyrrhizic acid, the stability and bioavailability of the sodium pyruvate can be effectively improved. In addition, sodium pyruvate and modified glycyrrhizic acid in the aerosol inhalation preparation take effect synergistically, and the pulmonary fibrosis process of patients with chronic obstructive pulmonary diseases can be effectively delayed.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and specifically relates to a sodium pyruvate atomized inhalation preparation and a preparation method and application thereof. Background Art

[0002] Pyruvate is an intermediate metabolite of glucose in the body and the final product of glycolysis. It is transported to the mitochondria to participate in the tricarboxylic acid cycle for energy metabolism, provide substrates for mitochondrial energy metabolism, synthesize cholesterol, and is reduced to lactic acid under anaerobic conditions, regenerate nicotinamide adenine dinucleotide, etc. to participate in cell metabolism. Sodium pyruvate is a common endogenous small molecule pyruvate.

[0003] Since the 1940s, no adverse reactions to sodium pyruvate have been found in humans. With the deepening of research, more animal experiments and clinical experimental data have shown that pyruvate has obvious advantages in improving cellular hypoxia / anaerobic tolerance, correcting hypoxic lactic acidosis, anti-inflammatory and antioxidant, and protecting mitochondrial function. Sodium pyruvate also has significant advantages in protecting the heart, brain, liver, kidneys and small intestinal barriers. It can effectively treat patients' symptoms in emergency situations and promote the recovery of chronic diseases.

[0004] Chronic obstructive pulmonary disease (COPD) is a type of chronic bronchitis and / or emphysema with airflow obstruction. It is a common preventable and treatable disease characterized by persistent airflow limitation, which is associated with an enhanced chronic inflammatory response of the airways and lungs to toxic particles or gases. It can further develop into a common chronic disease of cor pulmonale and respiratory failure. It is associated with abnormal inflammatory responses to harmful gases and particles, and has a high disability and mortality rate. Studies have found that sodium pyruvate can relieve the symptoms of chronic obstructive pulmonary disease. Nebulization inhalation is to use high-speed oxygen airflow to form a mist of the drug solution, which is then inhaled through the respiratory tract to achieve the purpose of treatment. The pyruvate preparation commonly used in clinical practice is the original sodium pyruvate preparation, which has problems such as slow efficacy, high dosage, and poor biological activity.

[0005] Licorice is a commonly used Chinese medicine that has been accepted and used by people. The latest generation of licorice preparations, diammonium glycyrrhizinate enteric-coated capsules, are specific therapeutic drugs for various liver inflammations. Licorice contains a variety of chemical components, among which glycyrrhizic acid is one of its main active ingredients, which has detoxification, anti-inflammatory, anti-tumor, and antibacterial effects. At the same time, because the sweetness of glycyrrhizic acid is 150 times that of sucrose, it is also a widely used sweetener.

[0006] Patent CN103156930A (a respiratory drug delivery preparation containing peony and licorice extracts) discloses that licorice extracts can be used for asthma, cough, chronic obstructive pulmonary disease, etc. However, the use of glycyrrhizic acid extract as an active ingredient has biological activity and cannot achieve the expected therapeutic effect. On this basis, how to improve the biological activity of glycyrrhizic acid has become a technical problem that needs to be solved urgently. Summary of the invention

[0007] The first object of the present invention is to provide a sodium pyruvate aerosol inhalation preparation, which can effectively delay the progress of pulmonary fibrosis in patients with chronic obstructive pulmonary disease.

[0008] The second object of the present invention is to provide a method for preparing a sodium pyruvate aerosol inhalation preparation.

[0009] The third object of the present invention is to provide an application of a sodium pyruvate aerosol inhalation preparation.

[0010] In order to achieve the above object, the technical solution adopted by the present invention is: A sodium pyruvate aerosol inhalation preparation, comprising the following components: sodium pyruvate, modified glycyrrhizic acid, sodium chloride, a pH regulator, and water for injection; the concentration of the sodium pyruvate is 50-120 mg / mL, the concentration of the modified glycyrrhizic acid is 5-40 mg / mL, the concentration of the sodium chloride is 0.85-0.95 wt%, and the pH of the aerosol inhalation preparation is 6.5-7; the structural formula of the modified glycyrrhizic acid is as shown in Formula I, .

[0011] Furthermore, the preparation method of the modified glycyrrhizic acid is as follows: (1) Glycyrrhizic acid is mixed with anhydride and pyridine, and stirred to react to obtain intermediate 1; intermediate 1 is then mixed with thionyl chloride and refluxed to obtain intermediate 2; (2) Add a compound having a thiol group or an amino group on the benzene ring to the solution of the intermediate 2 obtained in step (1) at 0-5°C, stir and react for 2-3 hours, then heat to room temperature and continue to react for 20-28 hours to obtain the intermediate 3; (3) Add trimethylsilyl iodide to the solution of the intermediate 3 obtained in step (3) to carry out a deprotection reaction to obtain the modified glycyrrhizic acid.

[0012] Furthermore, in step (2), the molar ratio of the intermediate 2:3-aminobenzenethiol is 1:3-3.5.

[0013] Furthermore, in step (3), the molar ratio of the intermediate 3 to trimethylsilyl iodide is 1:1.2-1.5; the temperature of the deprotection reaction is 20-30° C.; and the ratio of the protective group removed in the deprotection reaction is 60-70%.

[0014] Furthermore, in step (1), the dosage ratio of glycyrrhizic acid, acid anhydride and pyridine is 1 g: 4-6 g: 0.2-0.3 mL; the stirring reaction temperature is 20-30° C. and the time is 24-36 h.

[0015] Furthermore, the acid anhydride is selected from one or two of acetic anhydride, propionic anhydride and butyric anhydride.

[0016] Furthermore, in step (1), the ratio of the intermediate 1 to thionyl chloride is 1 g: 2-3 mL; the temperature of the reflux reaction is 55-65° C., and the time is 4-6 h.

[0017] Furthermore, the pH regulator is selected from one of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer and acetic acid-sodium acetate buffer.

[0018] The preparation method of the sodium pyruvate aerosol inhalation preparation comprises the following steps: according to the above formula, sodium pyruvate, modified glycyrrhizic acid and sodium chloride are dispersed in water for injection, and the pH of the solution is adjusted to 6.5-7 using a pH regulator to obtain the preparation.

[0019] Application of the sodium pyruvate aerosol inhalation preparation in the preparation of products for treating respiratory diseases.

[0020] Compared with the prior art, the beneficial effects of the present invention are mainly: The present invention provides a sodium pyruvate atomization inhalation preparation, wherein modified glycyrrhizic acid and sodium pyruvate are used in combination. The modified glycyrrhizic acid is prepared by esterifying glycyrrhizic acid with an acid anhydride, and then the intermediate is subjected to a nucleophilic substitution reaction with thionyl chloride, and then the obtained product is subjected to a nucleophilic addition reaction with 3-aminothiophenol to generate a compound having an amide group, and finally the modified glycyrrhizic acid is obtained by deprotection under the action of trimethyl iodosilane.

[0021] The modified glycyrrhizic acid added in the present invention has good stability, and can be used synergistically with sodium pyruvate to effectively delay the progress of pulmonary fibrosis in patients with chronic obstructive pulmonary disease.

[0022] The invention also provides a method for preparing a sodium pyruvate atomized inhalation preparation, which is simple to operate, easy to implement and convenient for batch production. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 is the intermediate 1 in Example 1 of the present invention 1 HNMR spectra; Figure 2 is the intermediate 2 in Example 1 of the present invention 1 HNMR spectra; Figure 3 is the intermediate 3 in Example 1 of the present invention 1 HNMR spectra; Figure 4 The modified glycyrrhizic acid of formula I in Example 1 of the present invention 1 HNMR spectrum. DETAILED DESCRIPTION

[0024] 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.

[0025] 1. Implementation Example 1 A sodium pyruvate aerosol inhalation preparation is composed of the following components: sodium pyruvate, modified glycyrrhizic acid, sodium chloride, disodium hydrogen phosphate-sodium dihydrogen phosphate buffer, and water for injection; the concentration of the sodium pyruvate is 80 mg / mL, the concentration of the modified glycyrrhizic acid is 25 mg / mL, the concentration of the sodium chloride is 0.85 wt%, and the pH of the aerosol inhalation preparation is 6.7.

[0026] The preparation process of the modified glycyrrhizic acid is as follows: (1) At 25°C, glycyrrhizic acid and propionic anhydride were first mixed according to the ratio of glycyrrhizic acid, propionic anhydride and pyridine in the amount of 1g:5g:0.25mL, and then pyridine was added, stirred for reaction for 30h, and then column purified to obtain intermediate 1; according to the ratio of intermediate 1 to thionyl chloride in the amount of 1g:2.5mL, thionyl chloride was slowly added dropwise to intermediate 1 at 0°C, and then refluxed at 60°C for 5h. After the reaction, the reaction solution was distilled under reduced pressure to obtain intermediate 2; The NMR results of intermediate 1 are ( Figure 1 shown): 1H-NMR(400MHz,DMSO)δ=0.90-0.95(m,13H),1.13(m,3H),1.24-1.26(d,8H),1.32(m,2 H),1.57(m,6H),1.64(m,2H),1.71-1.75(m,4H),1.91-1.92(m,4H),2.02(s,8H),3.05( The above results confirmed that the product obtained was the target product.

[0027] The NMR results of intermediate 2 are ( Figure 2 shown): 1 H-NMR(400MHz,DMSO)δ=0.90-0.95(m,13H),1.01-1.13(m,5H),1.22-1.26(d,7H),1. 32-1.39(m,4H),1.46(m,1H),1.52-1.57(m,4H),1.64-1.68(m,2H),1.71-1.76(m,2H) ,1.91-2.02(m,12H),3.05(t,1H),3.61(t,1H),4.50-4.52(t,3H),4.78(s,2H),5.00-5.06(m,3H),5.37-5.41(m,2H),5.59-5.61(m,2H),5.78(s,1H). The above results confirmed that the obtained product was the target product.

[0028] (2) According to the molar ratio of intermediate 2 to 3-aminothiophenol of 1:3.2, 3-aminothiophenol was added to the tetrahydrofuran solution of intermediate 2 at 4°C, and the mixture was stirred for reaction for 2.5 hours, then the mixture was heated to room temperature and the reaction was continued for 24 hours. After the reaction, the reaction solution was separated and purified by column chromatography to obtain intermediate 3; The NMR results of intermediate 3 are ( Figure 3 shown): 1H-NMR(400MHz,DMSO)δ=0.90-0.95(m,13H),1.01-1.13(m,5H), 1.25-1.30(m,7H),1.32-1.39(m,4H),1.46(m,1H),1.57(m,3H),1.61-1.64(m,2H),1.71-1.77(m,2 H),1.85(,m1H),1.91(m,1H),2.01-2.03(s,10H),3.05(t,1H),3.41(s,3H),3.61(t,1H),4.50-4.52 (t, 3H), 4.78(s, 1H), 5.09(t, 1H), 5.30-5.37(m, 3H), 5.41(m, 1H), 5.61-5.67(m, 2H), 5.78(s, 1H), 7.03(t, 3H), 7.41(t, 12H), 7.77(t, 3H), 8.22(d, 3H), 9.30(s, 1H), 10.03(s, 2H). The above results confirmed that the product obtained was the target product.

[0029] (3) According to the molar ratio of intermediate 3 to trimethylsilyl iodide of 1:1.3, trimethylsilyl iodide was added to the dichloromethane solution of intermediate 3 at 25°C to carry out a deprotection reaction. After the reaction, the reaction solution was washed with water, and the organic phase was collected and dried. The organic phase was separated and purified by column chromatography to obtain modified glycyrrhizic acid (the structural formula is shown in Formula I).

[0030] The NMR results of modified glycyrrhizic acid are ( Figure 4 shown): 1 H-NMR(400MHz,DMSO)δ=0.90-0.95(m,13H),1.01-1.13(m,5H) 1.25-1.26(m,4H),1.30-1.39(m,8H),1.46(m,1H),1.57-1.64(m,5H),1.71-1.76(m,2H),1.85(m,1 H),1.91-1.93(m,2H),2.01-2.03(m,5H),3.05(t,1H),3.41(s,3H),3.61(t,1H),3.91t(,1H),4.01 (t, 1H), 4.50-4.52(m, 2H), 4.60(m, 1H), 4.71-4.78(m, 6H), 5.41(d, 1H), 5.61(d, 1H), 5.78(s, 1H), 7.03(d, 3H), 7.41(t, 3H), 7.77(m, 3H), 8.22(d, 3H), 9.30(s, 1H), 10.03(s, 2H). The above results confirmed that the product obtained was the target product.

[0031] The preparation method of the above-mentioned sodium pyruvate aerosol inhalation preparation is as follows: According to the above formula, sodium pyruvate, modified glycyrrhizic acid and sodium chloride are dispersed in water for injection, the pH value of the solution is adjusted to 6.7 with disodium hydrogen phosphate-sodium dihydrogen phosphate buffer, and the solution is filled by using an aseptic filling process to obtain the product.

[0032] Example 2 A sodium pyruvate aerosol inhalation preparation is composed of the following components: sodium pyruvate, modified glycyrrhizic acid, sodium chloride, disodium hydrogen phosphate-sodium dihydrogen phosphate buffer, and water for injection; the concentration of the sodium pyruvate is 120 mg / mL, the concentration of the modified glycyrrhizic acid is 40 mg / mL, the concentration of the sodium chloride is 0.95 wt%, and the pH of the aerosol inhalation preparation is 6.5.

[0033] The preparation process of the modified glycyrrhizic acid is as follows: (1) At 20°C, glycyrrhizic acid and butyric anhydride were first mixed according to the ratio of glycyrrhizic acid, butyric anhydride and pyridine in the amount of 1g:4g:0.2mL, and then pyridine was added, stirred for reaction for 24h, and then column purified to obtain intermediate 1; according to the ratio of intermediate 1 to thionyl chloride in the amount of 1g:3mL, thionyl chloride was slowly added dropwise to intermediate 1 at 0°C, and then refluxed at 55°C for 6h. After the reaction, the reaction solution was distilled under reduced pressure to obtain intermediate 2; (2) adding 3-aminothiophenol to a tetrahydrofuran solution of intermediate 2 at a molar ratio of 1:3.5 at 0°C, stirring for 3 h, then heating to room temperature and continuing the reaction for 20 h. After the reaction, the reaction solution was separated and purified by column chromatography to obtain intermediate 3; (3) According to the molar ratio of intermediate 3 to trimethylsilyl iodide of 1:1, trimethylsilyl iodide is added to the dichloromethane solution of intermediate 3 at 30°C to carry out a deprotection reaction. After the reaction is completed, the reaction solution is washed with water, and the organic phase is collected and dried. The organic phase is separated and purified by column chromatography to obtain modified glycyrrhizic acid (the structural formula is shown in Formula I).

[0034] The preparation method of the above-mentioned sodium pyruvate aerosol inhalation preparation is as follows: According to the above formula, sodium pyruvate, modified glycyrrhizic acid and sodium chloride are dispersed in water for injection, the pH value of the solution is adjusted to 6.5 with disodium hydrogen phosphate-sodium dihydrogen phosphate buffer, and the solution is filled by using an aseptic filling process to obtain the product.

[0035] Example 3 A sodium pyruvate aerosol inhalation preparation is composed of the following components: sodium pyruvate, modified glycyrrhizic acid, sodium chloride, acetic acid-sodium acetate buffer, and water for injection; the concentration of the sodium pyruvate is 50 mg / mL, the concentration of the modified glycyrrhizic acid is 5 mg / mL, the concentration of the sodium chloride is 0.85 wt%, and the pH of the aerosol inhalation preparation is 7.

[0036] The preparation process of the modified glycyrrhizic acid is as follows: (1) At 30°C, glycyrrhizic acid, acetic anhydride and butyric anhydride mixture were first mixed according to the ratio of glycyrrhizic acid, acetic anhydride and butyric anhydride mixture to pyridine of 1 g:6 g:0.3 mL, and then pyridine was added, stirred for 36 hours, and then purified by column to obtain intermediate 1; according to the ratio of intermediate 1 to thionyl chloride of 1 g:2 mL, thionyl chloride was slowly added dropwise to intermediate 1 at 0°C, and then refluxed at 65°C for 4 hours. After the reaction, the reaction solution was distilled under reduced pressure to obtain intermediate 2; (2) According to the molar ratio of intermediate 2 to 3-aminothiophenol of 1:3.5, 3-aminothiophenol was added to the tetrahydrofuran solution of intermediate 2 at 5°C, and the mixture was stirred for reaction for 2 hours, then the mixture was heated to room temperature and the reaction was continued for 28 hours. After the reaction, the reaction solution was separated and purified by column chromatography to obtain intermediate 3; (3) According to the molar ratio of intermediate 3 to trimethylsilyl iodide of 1:1.5, trimethylsilyl iodide was added to the dichloromethane solution of intermediate 3 at 20°C to carry out a deprotection reaction. After the reaction, the reaction solution was washed with water, and the organic phase was collected and dried. The organic phase was separated and purified by column chromatography to obtain modified glycyrrhizic acid (the structural formula is shown in Formula I).

[0037] The preparation method of the above-mentioned sodium pyruvate aerosol inhalation preparation is as follows: According to the above formula, sodium pyruvate, modified glycyrrhizic acid and sodium chloride are dispersed in water for injection, the pH value of the solution is adjusted to 7 with acetic acid-sodium acetate buffer, and the solution is filled by using a sterile filling process to obtain the product.

[0038] (II) Comparative Example Comparative Example 1 Comparative Example 1 uses glycyrrhizic acid instead of modified glycyrrhizic acid, and the rest is the same as Example 1.

[0039] Comparative Example 2 Comparative Example 2 uses glycyrrhizic acid monoammonium salt instead of modified glycyrrhizic acid, and the rest is the same as Example 1.

[0040] Comparative Example 3 In Comparative Example 3, no modified glycyrrhizic acid was added, and the rest was the same as in Example 1.

[0041] The performance of the sodium pyruvate aerosol inhalation preparation prepared by the present invention is further described below.

[0042] 1. Biological activity of aerosol inhalation preparations A vibrating mesh nebulizer was used in combination with the nebulized inhalation preparations of Examples 1-3 and Comparative Examples 1-3. The biological activities of the nebulized inhalation preparations of Examples 1-3 and Comparative Examples 1-3 before and after nebulization were detected by cytopathic assay (L929). The results are shown in Table 1.

[0043] Table 1 From Table 1, it is known that there is no significant difference in the biological activity of the aerosol inhalation preparations of Examples 1-3 before and after aerosolization. There is a significant difference in the biological activity of the aerosol inhalation preparation of Comparative Example 3 before and after aerosolization, and there is a slight difference in the biological activity of the aerosol inhalation preparations of Comparative Examples 1 and 2 before and after aerosolization. Analysis shows that Comparative Example 1 uses glycyrrhizic acid instead of modified glycyrrhizic acid, Comparative Example 2 uses monoammonium oxalate instead of modified glycyrrhizic acid, and Comparative Example 3 does not add modified glycyrrhizic acid. From the above, it can be seen that the modified glycyrrhizic acid of the present invention can improve the stability of sodium pyruvate.

[0044] 2. Pharmacological properties of aerosol inhalation preparations The rats were anesthetized with sodium pentobarbital (1%, 40 mg / kg) on ​​the 1st and 14th days of the experiment, and then injected with 0.2 mL of lipopolysaccharide saline solution (200 μg / μL). The rats were then rotated upright to the left and right to evenly distribute lipopolysaccharide in both lungs. From the 2nd to the 28th day (except the 14th day), the rats were divided into groups and placed in a self-made closed modeling box. All experimental rats were smoked for 30 minutes every morning, with 5 cigarettes each time, to establish a chronic obstructive pulmonary disease (COPD) model.

[0045] Grouping and administration method: 50 rats with successful modeling were randomly divided into 5 groups, negative control group: lung function test was performed on rats with successful modeling immediately, and the alveolar lavage fluid of rats was collected, and the concentration of IL-6 and IL-1β was detected by enzyme-linked immunosorbent assay; model group: 0.6 mg / kg of normal saline was administered intragastrically; experimental group: 0.6 g / kg of the preparations of Examples 1-3 and Comparative Examples 1-3 were administered by atomization (i.e., the amount of sodium pyruvate in the atomized inhalation preparation was 0.6 mg / kg); blank control group: 10 healthy rats were taken and 35 mg / kg of normal saline was administered intragastrically. The negative control group was a rat with a lung function test on the first day after successful modeling.

[0046] Drugs or water were continuously administered for 14 days. On the 15th day, the rats in each group were anesthetized, the neck skin was cut, the subcutaneous tissue was bluntly separated to expose the trachea, a small incision was made circularly between the tracheal cartilages, and the endotracheal tube was inserted and tied tightly. The rats were placed in a supine position with their heads down in a closed volume recording box of a small animal pulmonary function tester. One end of the endotracheal tube was connected to the animal ventilator, and after recording a period of quiet breathing, the forced vital capacity (FVC), 0.3s forced expiratory volume (FEV0.3), FEV0.3 / FVC, and peak expiratory flow rate (PEFR) were measured. The results are shown in Table 2.

[0047] The drugs or water were administered continuously for 14 days. On the 15th day, the bronchoalveolar lavage fluid of rats in each group was collected and the concentrations of IL-6 and IL-1β were detected by enzyme-linked immunosorbent assay. The results are shown in Table 3.

[0048] Table 2 Table 3 It can be seen from Table 2 that compared with the blank control group, the lung function parameters FVC, FEV0.3, FEV0.3 / FVC, and PEFR of the rats in the negative control group were significantly reduced, indicating that the rats had airflow obstruction, indicating that the modeling was successful. The experimental data in Table 2 show that after 14 days of treatment with the sodium pyruvate aerosol inhalation preparation of Examples 1-3 of the present invention, the maximum expiratory peak flow rate of the rats was close to that of the negative control group. After 14 days of treatment with the sodium pyruvate aerosol inhalation preparation of Comparative Examples 1-3, the maximum expiratory peak flow rate of the rats was lower than that of the negative control group. It can be seen from the above that the sodium pyruvate and modified glycyrrhizic acid in the sodium pyruvate aerosol inhalation preparation of the present invention work synergistically and can effectively delay the progress of pulmonary fibrosis in patients with chronic obstructive pulmonary disease.

[0049] It can be seen from Table 3 that, compared with the model group, the sodium pyruvate aerosol inhalation preparation of the present invention can effectively inhibit the expression of pulmonary inflammatory factors. Compared with Examples 1-3, the ability of the aerosol inhalation preparation of Comparative Example 1-3 to inhibit the expression of inflammatory factors is reduced. Further analysis shows that the difference between the aerosol inhalation preparation of Comparative Example 1-3 and that of Example 1-3 is that different glycyrrhizic acid is used. In summary, the sodium pyruvate aerosol inhalation preparation prepared by the modified glycyrrhizic acid provided by the present invention has excellent anti-inflammatory effects.

[0050] 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 sodium pyruvate aerosol inhalation preparation, characterized in that: The invention comprises the following components: sodium pyruvate, modified glycyrrhizic acid, sodium chloride, a pH regulator, and water for injection; the concentration of the sodium pyruvate is 50-120 mg / mL, the concentration of the modified glycyrrhizic acid is 5-40 mg / mL, the concentration of the sodium chloride is 0.85-0.95 wt%, and the pH of the atomized inhalation preparation is 6.5-7; the structural formula of the modified glycyrrhizic acid is shown in Formula I, 。 2. The sodium pyruvate aerosol inhalation preparation according to claim 1, characterized in that: The preparation method of the modified glycyrrhizic acid is as follows: (1) Glycyrrhizic acid is mixed with anhydride and pyridine, and stirred to react to obtain intermediate 1; intermediate 1 is then mixed with thionyl chloride and refluxed to obtain intermediate 2; (2) Add a compound having a thiol group or an amino group on the benzene ring to the solution of the intermediate 2 obtained in step (1) at 0-5°C, stir and react for 2-3 hours, then heat to room temperature and continue to react for 20-28 hours to obtain the intermediate 3; (3) Add trimethylsilyl iodide to the solution of the intermediate 3 in step (3) to carry out a deprotection reaction to obtain the modified glycyrrhizic acid.

3. The sodium pyruvate aerosol inhalation preparation according to claim 2, characterized in that: The molar ratio of the intermediate 2:3-aminobenzenethiol in step (2) is 1:3-3.

5.

4. The sodium pyruvate aerosol inhalation preparation according to claim 2, characterized in that: In step (3), the molar ratio of the intermediate 3 to trimethylsilyl iodide is 1:1-1.5; the temperature of the deprotection reaction is 20-30° C.; and the ratio of the protective group removed in the deprotection reaction is 60-70%.

5. The sodium pyruvate aerosol inhalation preparation according to claim 2, characterized in that: In step (1), the dosage ratio of glycyrrhizic acid, acid anhydride and pyridine is 1 g: 4-6 g: 0.2-0.3 mL; the stirring reaction temperature is 20-30° C. and the time is 24-36 h.

6. The sodium pyruvate aerosol inhalation preparation according to claim 5, characterized in that: The acid anhydride is selected from one or two of acetic anhydride, propionic anhydride and butyric anhydride.

7. The sodium pyruvate aerosol inhalation preparation according to claim 2, characterized in that: In step (1), the ratio of the intermediate 1 to thionyl chloride is 1 g: 2-3 mL; the temperature of the reflux reaction is 55-65° C., and the time is 4-6 h.

8. The sodium pyruvate aerosol inhalation preparation according to claim 1, characterized in that: The pH regulator is selected from one of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer and acetic acid-sodium acetate buffer.

9. The method for preparing the sodium pyruvate aerosol inhalation preparation according to any one of claims 1 to 8, characterized in that: The method comprises the following steps: according to the above formula, sodium pyruvate, modified glycyrrhizic acid and sodium chloride are dispersed in water for injection, and a pH regulator is used to adjust the pH of the solution to 6.5-7.

10. Use of the sodium pyruvate aerosol inhalation preparation according to any one of claims 1 to 8 in the preparation of products for treating respiratory diseases.

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