A pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer and a preparation method thereof

Abstract

The present invention relates to the field of medical technology, and more particularly to a pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer and a preparation method thereof. The pyruvate inhalation atomizer comprises the following raw materials in percentage by mass: 0.05-0.08% compound A, 0.05-0.1% sodium pyruvate, 0.2-2% disodium hydrogen phosphate, 0.2-2% sodium dihydrogen phosphate, and the balance normal saline; the structural formula of the compound A is as follows: #imgabs0#. Research results indicate that the pyruvate inhalation atomizer can alleviate the symptoms of malignant pleural effusion caused by lung cancer by reducing the amount of pleural effusion in MPE model mice, as well as upregulating the expression of IL-7 and downregulating the expression of VEGF in serum.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer and a preparation method thereof. Background Art

[0002] Lung cancer is a malignant tumor of the lung tissue. When it develops to a certain stage, cancer cells may invade the pleura, increase pleural permeability, and cause fluid exudation to form pleural effusions. At the same time, lung cancer may also block lymphatic vessels, affecting lymphatic return and exacerbating the effusion. In addition, hypoproteinemia caused by factors such as malnutrition and abnormal liver function, as well as the lung inflammation caused by lung cancer, can also promote pleural inflammation and exudation, further forming malignant pleural effusions. The emergence of this complication usually indicates that lung cancer has progressed to the late stage, and patients will face severe symptoms such as difficulty breathing, chest pain, and coughing. Large amounts of effusions can also compress the lungs, restrict respiratory function, and even affect the circulatory system and nutritional status. If not diagnosed and treated promptly, malignant pleural effusions will seriously threaten the patient's life safety. Therefore, it is crucial for lung cancer patients to pay attention to and manage pleural effusions in a timely manner.

[0003] Chlorogenic acid is widely present in medicinal plants, primarily in plants of the genera Lonicera (Caprifoliaceae) and Eucommia (Eucommia) (Eucommia ulmoides), such as honeysuckle and Eucommia ulmoides. Chlorogenic acid has a solubility of 4% in water at 25°C, with greater solubility in hot water. It is readily soluble in ethanol and acetone, slightly soluble in ethyl acetate, and poorly soluble in chloroform and ether. Studies have shown that chlorogenic acid has therapeutic effects in preventing and treating lung injury, inhibiting the increase in myeloperoxidase activity in lung tissue and the expression of polymorphonuclear leukocytes in bronchoalveolar lavage fluid induced by lipopolysaccharide, while significantly reducing the activity of inducible nitric oxide synthase in lung tissue. However, chlorogenic acid has poor oral bioavailability and unsatisfactory pharmacokinetic parameters, which seriously affect its efficacy. However, the application of chlorogenic acid in malignant pleural effusions caused by lung cancer has not been studied.

[0004] Sodium pyruvate, a common pyruvate salt with the molecular formula C3H3NaO3, is an endogenous small molecule. Both sodium pyruvate and pyruvic acid are naturally present in the human body and participate in metabolism throughout various tissues and organs. It has been used in lung-related diseases such as lung cancer and tuberculosis. However, its application in malignant pleural effusions caused by lung cancer has not been further studied. Therefore, there is an urgent need for a drug that can alleviate tumor cell proliferation and relieve the symptoms of malignant pleural effusions caused by lung cancer. Summary of the Invention

[0005] The first object of the present invention is to provide a pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer, wherein the preparation can alleviate the symptoms of malignant pleural effusion caused by lung cancer.

[0006] The second purpose of the present invention is to provide a method for preparing a pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer, which is simple to prepare.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is:

[0008] A pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer, comprising the following raw materials in percentage by mass: 0.05-0.08% of compound A, 0.05-0.1% of sodium pyruvate, 0.2-2% of disodium hydrogen phosphate, 0.2-2% of sodium dihydrogen phosphate, and the balance being normal saline; the structural formula of compound A is shown below:

[0009] .

[0010] Furthermore, the preparation process of compound A is as follows:

[0011]

[0012] (1) Chlorogenic acid and 4-(2-hydroxyethoxy)-3-methoxybenzaldehyde were added to DMF and stirred for reaction under catalyst conditions; intermediate 1 was obtained after purification and concentration;

[0013] (2) adding the intermediate 1 and 2-aminoethylsulfonamide obtained in step (1) to a mixed solvent, adding acetic acid and stirring for 3-4 hours, then adding sodium cyanoborohydride and continuing to stir the reaction, purifying and concentrating to obtain intermediate 2;

[0014] (3) The intermediate 2,4-cyanophenylboronic acid obtained in step (2) is added to tetrahydrofuran for reaction, and purified to obtain compound A.

[0015] Furthermore, the usage ratio of chlorogenic acid, 4-(2-hydroxyethoxy)-3-methoxybenzaldehyde, catalyst, and DMF in step (1) is 1 mmol: (1.2-1.5) mmol: (0.012-0.015) mmol: (20-25) mL.

[0016] Furthermore, the catalyst in step (1) is p-toluenesulfonic acid; and the stirring reaction time is 16-24 hours.

[0017] Furthermore, in step (2), the usage ratio of the intermediate 1, 2-aminoethylsulfonamide, the mixed solvent, acetic acid, and sodium cyanoborohydride is 5 mmol: (10-15) mmol: (25-35) mL: (0.5-1) mL: (10-15) mmol.

[0018] Furthermore, the mixed solvent in step (2) consists of dichloromethane and methanol in a volume ratio of 1:1.

[0019] Furthermore, the stirring reaction time in step (2) is 12-16 hours.

[0020] Furthermore, in step (3), the ratio of the intermediate 2,4-cyanophenylboronic acid and tetrahydrofuran is 5 mmol: (5-6) mmol: (15-20) mL.

[0021] Furthermore, the reaction temperature in step (3) is 70-80° C., and the reaction time is 12-16 h.

[0022] The method for preparing the pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer comprises the following steps:

[0023] The raw materials can be compounded according to the mass percentage.

[0024] The beneficial technical effects of the present invention are:

[0025] 1. The present invention provides a novel pyruvate inhalation nebulizer. Research results show that the pyruvate inhalation nebulizer can alleviate the symptoms of malignant pleural effusion caused by lung cancer by reducing the amount of pleural effusion in MPE model mice, upregulating the expression of IL-7 in serum and downregulating the expression of VEGF in serum.

[0026] 2. The present invention also provides a method for preparing a pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer. The preparation method is simple and easy to operate and can be easily produced in a factory. DETAILED DESCRIPTION

[0027] The following is a further detailed description of the present invention in conjunction with specific preferred embodiments, and it is not intended that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art of the present invention, without departing from the inventive concept, several simple deductions or replacements can also be made, all of which should be considered to belong to the scope of protection of the present invention. The specific conditions not indicated in the examples are carried out according to conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used, unless otherwise specified, are conventional products obtained through commercial channels.

[0028] Example

[0029] Example 1

[0030] This embodiment provides a pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer. The aerosol is composed of the following raw materials in percentage by mass: 0.06% Compound A, 0.08% sodium pyruvate, 1% disodium hydrogen phosphate, 1% sodium dihydrogen phosphate, and the balance being normal saline. The structural formula of Compound A is shown below:

[0031] .

[0032] The preparation process of compound A is as follows:

[0033]

[0034] (1) Chlorogenic acid and 4-(2-hydroxyethoxy)-3-methoxybenzaldehyde were added to DMF in a ratio of 1 mmol:1.4 mmol:0.014 mmol:20 mL, followed by the addition of p-toluenesulfonic acid, and the mixture was stirred at room temperature for 20 h. The reaction solution was diluted with water, purified by reverse-phase high performance liquid chromatography, and concentrated to obtain intermediate 1.

[0035] The NMR results of intermediate 1 are:

[0036] 1 H-NMR (C 26 H 28 O 12 ,400MHz,d6-DMSO)δ9.61(s,1H),9.46(s,2H),7.56-7.54(d,1H),7.48-7.47(d,1H ),7.35-7.34(d,1H),7.17-7.15(d,1H),7.06-7.04(d,1H),6.82-6.80(d,1H),6.6 7-6.65(dd,1H),6.31-6.30(d,1H),5.87(s,1H),4.62-4.40(m,7H),4.13-4.10(t, 1H),3.85(s,3H),3.54-3.51(t,1H),2.32-1.96(m,4H); MS(ESI)m / z=533.16[M+H] + , 533.16 was found; the above results confirmed that the obtained product was the target product.

[0037] (2) The intermediate 1, 2-aminoethylsulfonamide obtained in step (1) was added to a mixed solvent (dichloromethane and methanol in a volume ratio of 1:1) according to the amount ratio of intermediate 1, 2-aminoethylsulfonamide, mixed solvent, acetic acid, and sodium cyanoborohydride (5 mmol:12 mmol:30 mL:0.6 mL:12 mmol), and acetic acid was added. The mixture was stirred at room temperature for 3.5 h, and then sodium cyanoborohydride was added. The mixture was stirred and reacted at room temperature for 14 h. The reaction solution was concentrated and diluted with dichloromethane. The organic layer was washed with saturated brine and evaporated to obtain a concentrated crude product. The crude product was dissolved in dimethyl sulfoxide and diluted with water. The product was then purified by reverse-phase high performance liquid chromatography and concentrated to obtain intermediate 2.

[0038] The NMR results of intermediate 2 are:

[0039] 1 H-NMR (C 28 H 36 N2O 13 S,400MHz,d6-DMSO)δ9.46(s,2H),7.48-7.46(d,1H),7.12(s,2H),7.06-7.04( d,1H),6.98-6.96(d,1H),6.87-6.80(m,3H),6.67-6.66(dd,1H),6.31-6.30(d, 1H),5.91(s,1H),4.62-4.40(m,7H),4.16-4.13(m,2H),3.76-3.75(d,5H),3.5 4-3.52(q,3H),3.11-3.09(t,2H),2.32-1.96(m,4H); MS(ESI)m / z=641.20[M+H] + , found 641.20; the above results confirmed that the obtained product was the target product.

[0040] (3) The intermediate 2,4-cyanophenylboronic acid obtained in step (2) was added to tetrahydrofuran in a ratio of 5 mmol:5.5 mmol:15 mL of the intermediate 2,4-cyanophenylboronic acid and tetrahydrofuran, and the mixture was reacted at 75°C for 14 h; the reaction solution was filtered while hot, and the filter cake was thoroughly washed with tetrahydrofuran during the filtration process. The filter cake was collected and dried to obtain a crude product. The crude product was evenly dispersed with 5 mL of pure water and 10 mL of acetonitrile and completely dissolved at 75°C. The mixture was then cooled to 40°C. No obvious solid precipitation was observed. 5 mL of n-heptane was added to the mixed solution under stirring. Clear solid precipitation was observed. The mixed system was filtered and the filter cake was dried to obtain compound A.

[0041] The NMR results of compound A are:

[0042] 1HNMR (C 35 H 38 BN3O 13 S,400MHz,d6-DMSO)δ7.93-7.91(d,2H),7.60-7.58(d,2H),7.48-7.47(d,1H),7.12(s,2H),7.01- 6.98(m,2H),6.87-6.86(d,1H),6.80-6.78(dd,1H),6.59-6.58(d,1H),6.52-6.50(d,1H),6.31-6 .30(d,1H),5.91(s,1H),4.62-4.40(m,7H),4.16-4.13(m,2H),3.76-3.75(d,5H),3.54-3.51(q,3H),3.11-3.09(t,2H),2.32-1.96(m,4H); MS(ESI)m / z=751.22[M], found 751.22; the above results confirmed that the obtained product was the target product.

[0043] This embodiment also provides a method for preparing the pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer, which is specifically as follows:

[0044] The raw materials can be compounded according to the mass percentage.

[0045] Example 2

[0046] This embodiment provides a pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer. The aerosol is composed of the following raw materials in percentage by mass: 0.05% Compound A, 0.05% sodium pyruvate, 0.2% disodium hydrogen phosphate, 0.2% sodium dihydrogen phosphate, and the balance being normal saline. The structural formula of Compound A is the same as that of Example 1.

[0047] The preparation process of compound A is as follows:

[0048] (1) Chlorogenic acid and 4-(2-hydroxyethoxy)-3-methoxybenzaldehyde were added to DMF in the ratio of 1 mmol: 1.2 mmol: 0.012 mmol: 25 mL, followed by the addition of p-toluenesulfonic acid. The mixture was stirred at room temperature for 16 h. The reaction solution was diluted with water, purified by reversed-phase high performance liquid chromatography, and concentrated to obtain intermediate 1. 1 H-NMR and MS (ESI) m / z were consistent with those in Example 1.

[0049] (2) The intermediate 1, 2-aminoethylsulfonamide obtained in step (1) was added to a mixed solvent (dichloromethane and methanol in a volume ratio of 1:1) according to the amount ratio of intermediate 1, 2-aminoethylsulfonamide, mixed solvent, acetic acid, and sodium cyanoborohydride (5 mmol:10 mmol:25 mL:0.5 mL:10 mmol), and acetic acid was added. The mixture was stirred at room temperature for 3 h, and then sodium cyanoborohydride was added. The mixture was stirred and reacted at room temperature for 12 h. The reaction solution was concentrated and diluted with dichloromethane. The organic layer was washed with saturated brine and evaporated to obtain a concentrated crude product. The crude product was dissolved in dimethyl sulfoxide and diluted with water. It was then purified by reverse-phase high performance liquid chromatography and concentrated to obtain intermediate 2. 1 H-NMR and MS (ESI) m / z were consistent with those in Example 1.

[0050] (3) Add the intermediate 2,4-cyanophenylboronic acid obtained in step (2) to tetrahydrofuran in a ratio of 5mmol:5mmol:20mL, and react at 70°C for 16h; filter the reaction solution while hot, and wash the filter cake thoroughly with tetrahydrofuran during the filtration process. Collect the filter cake and dry the filter cake to obtain a crude product. Use 5mL of pure water and 10mL of acetonitrile to evenly disperse the crude product and completely dissolve it at 75°C. Then cool it to 40°C. No obvious solid precipitation occurs. Add 5mL of n-heptane to the mixed solution under stirring. There is obvious solid precipitation. Filter the mixed system and dry the filter cake to obtain compound A. 1 H-NMR and MS (ESI) m / z were consistent with those in Example 1.

[0051] This embodiment also provides a method for preparing the pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer, which is specifically as follows:

[0052] The raw materials can be compounded according to the mass percentage.

[0053] Example 3

[0054] This embodiment provides a pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer. The aerosol is composed of the following raw materials in percentage by mass: 0.08% Compound A, 0.1% sodium pyruvate, 2% disodium hydrogen phosphate, 2% sodium dihydrogen phosphate, and the balance being normal saline. The structural formula of Compound A is the same as that of Example 1.

[0055] The preparation process of compound A is as follows:

[0056] (1) Chlorogenic acid and 4-(2-hydroxyethoxy)-3-methoxybenzaldehyde were added to DMF in the ratio of 1 mmol: 1.5 mmol: 0.015 mmol: 25 mL, followed by the addition of p-toluenesulfonic acid. The mixture was stirred at room temperature for 24 h. The reaction solution was diluted with water, purified by reversed-phase high performance liquid chromatography, and concentrated to obtain intermediate 1. 1 H-NMR and MS (ESI) m / z were consistent with those in Example 1.

[0057] (2) The intermediate 1, 2-aminoethylsulfonamide obtained in step (1) was added to a mixed solvent (dichloromethane and methanol in a volume ratio of 1:1) according to the amount ratio of intermediate 1, 2-aminoethylsulfonamide, mixed solvent, acetic acid, and sodium cyanoborohydride (5 mmol: 15 mmol: 35 mL: 1 mL: 15 mmol), and acetic acid was added. The mixture was stirred at room temperature for 4 h, and then sodium cyanoborohydride was added. The mixture was stirred and reacted at room temperature for 16 h. The reaction solution was concentrated and diluted with dichloromethane. The organic layer was washed with saturated brine and evaporated to obtain a concentrated crude product. The crude product was dissolved in dimethyl sulfoxide and diluted with water. It was then purified by reverse-phase high performance liquid chromatography and concentrated to obtain intermediate 2. 1 H-NMR and MS (ESI) m / z were consistent with those in Example 1.

[0058] (3) Add the intermediate 2,4-cyanophenylboronic acid obtained in step (2) to tetrahydrofuran in a ratio of 5mmol:6mmol:20mL, and react at 80°C for 12h; filter the reaction solution while hot, and wash the filter cake thoroughly with tetrahydrofuran during the filtration process. Collect the filter cake and dry the filter cake to obtain a crude product. Use 5mL of pure water and 10mL of acetonitrile to evenly disperse the crude product and completely dissolve it at 75°C. Then cool it to 40°C. No obvious solid precipitation occurs. Add 5mL of n-heptane to the mixed solution under stirring. There is obvious solid precipitation. Filter the mixed system and dry the filter cake to obtain compound A. 1 H-NMR and MS (ESI) m / z were consistent with those in Example 1.

[0059] This embodiment also provides a method for preparing the pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer, which is specifically as follows:

[0060] The raw materials can be compounded according to the mass percentage.

[0061] Comparative Example

[0062] Comparative Example 1

[0063] The difference between Comparative Example 1 and Example 1 is that chlorogenic acid is used instead of Compound A, and the rest is the same as Example 1.

[0064] Comparative Example 2

[0065] The difference between Comparative Example 2 and Example 1 is that sodium pyruvate is used instead of Compound A, and the rest is the same as Example 1.

[0066] Test example

[0067] Test Example 1

[0068] The safety of the pyruvate inhalation aerosol obtained in Example 1 was tested as follows:

[0069] Experimental subjects: Twenty healthy 8-week-old C57BL / 6 mice, weighing 180-220 g, were randomly divided into two groups;

[0070] Experimental groups and dosing regimen:

[0071] Blank control group: 0.9% sodium chloride injection by mass volume percentage was administered by atomization;

[0072] Group 1 of Example 1: The inhalation aerosol obtained in Example 1 was administered by nebulization (the dosage of sodium pyruvate was 8 mg / kg);

[0073] Experimental Procedure: A nebulizer was used for drug inhalation. Each group received the drug once daily for 14 consecutive days at a dose volume of 1 mL / kg. Observation was conducted during the drug administration and recovery periods. All animals were sacrificed 24 hours after the last dose. Following autopsy, the lips, palate, tongue, nose, pharynx, larynx, trachea, and lungs were visually inspected for irritation, including congestion, redness, and swelling. Final evaluation was based on visual observation. The results are shown in Table 1.

[0074] Table 1

[0075]

[0076] As shown in Table 1, under the experimental conditions, after the pyruvate inhalation aerosol of the present invention was administered, no obvious irritation changes were observed in the respiratory system of mice, verifying the safety of the pyruvate inhalation aerosol of the present invention.

[0077] Test Example 2

[0078] 1. Animal Grouping, Lewis Lung Cancer Cell Culture, Modeling, and Drug Administration

[0079] Experimental animals: 90 female C57BL / 6 mice aged 8 weeks, weighing 180-220 g, were adaptively fed for 7 days, of which 10 served as blank control group.

[0080] Lewis cell culture: Lewis lung cancer cells were cultured in DMEM high-glucose medium (containing 10% FBS and 1% double-antibody) at 37°C in a 5% CO2 incubator. Lewis lung cancer cells in the logarithmic growth phase were resuspended in PBS to prepare single-cell suspensions, and cell viability was assessed using trypan blue staining. When cell viability was greater than 90%, the cell concentration was adjusted to 3 × 10 6 / mL, for future use.

[0081] Modeling method: 80 mice were anesthetized with 0.4% sodium pentobarbital. The limbs of the mice were fixed in the supine position. The hair on the anterior chest wall was removed and disinfected with alcohol. A transverse incision was made on the right anterolateral chest wall at the level of the xiphoid process of the mice. The subcutaneous fascia and muscles were separated to expose the ribs. Under direct vision, a single cell suspension (3×10 6 / mL) was injected into the pleural cavity of the mouse. The injection site was disinfected and the muscle and epidermal layers were sutured. After the mouse was fully awake, it was returned to its cage and observed using a small animal in vivo imaging system. Over time, the fluorescence of the mouse chest cavity gradually increased. Thoracic dissection of 10 randomly selected mice indicated a successful model if bloody pleural effusion was found.

[0082] Animal grouping: The mice with successful modeling were randomly divided into a model group, Example 1-3 groups, and Comparative Example 1-2 groups, with 10 mice in each group.

[0083] Administration: Blank control group and model group: administered with equal volume of normal saline once a day for 10 consecutive days;

[0084] Groups of Example 1-3: 3 days after successful modeling, the drug preparations of Example 1-3 were administered by aerosol, with a dose of sodium pyruvate of 0.8 mg / kg, once a day for 10 consecutive days;

[0085] Comparative Example 1-2 Group: 3 days after successful modeling, the drug preparations of Comparative Examples 1-2 were administered by aerosol once a day for 10 consecutive days.

[0086] 2. Detection of pleural effusion volume and serum IL-7 and VEGF levels in each group of mice after drug administration

[0087] The mice in each group were anesthetized with 0.4% sodium pentobarbital, the thoracic cavity was exposed, and pleural effusion was extracted with a syringe. The volume of pleural effusion was recorded. The results are shown in Table 2.

[0088] The levels of IL-7 and VEGF in the serum of mice in each group were detected by enzyme-linked immunosorbent assay. The results are shown in Table 2.

[0089] Table 2

[0090]

[0091] Studies have shown that decreased VEGF levels are associated with the therapeutic efficacy of malignant pleural effusions, while IL-7 expression increases during disease remission by regulating immune cells. Based on this, the present invention examined the effects of the pharmaceutical preparations of Examples 1-3 and Comparative Examples 1-2 on mouse serum IL-7 and VEGF to explore their mechanism of action in alleviating malignant pleural effusions caused by lung cancer.

[0092] As shown in Table 2, compared with the blank control group, the pleural effusion volume and VEGF content of the model group were significantly increased. Compared with the model group, the pleural effusion volume and VEGF content of the mice in the Example 1-3 and Comparative Example 1-2 groups were decreased, and the decrease in the Example 1-3 group was more significant.

[0093] Compared with the blank control group, the IL-7 of the model group mice was significantly reduced. Compared with the model group, the IL-7 of the mice in the Example 1-3 group and the Comparative Example 1-2 group increased, and the increase in the Example 1-3 group was more significant. The above results show that the pyruvate inhalation aerosol obtained in Examples 1-3 of the present invention can effectively relieve the symptoms of malignant pleural effusion caused by lung cancer. However, Comparative Example 1 uses chlorogenic acid instead of Compound A, and Comparative Example 2 uses sodium pyruvate instead of Compound A. Although both groups of inhalation aerosols can relieve the symptoms of malignant pleural effusion caused by lung cancer, the effects are not ideal.

[0094] In summary, the pyruvate inhalation aerosol of the present invention can alleviate the symptoms of malignant pleural effusion caused by lung cancer by reducing the pleural effusion volume of MPE model mice, upregulating the expression of IL-7 in serum and downregulating the expression of VEGF in serum.

[0095] Finally, it should be noted that the above embodiments are intended only to illustrate the technical solutions of the present invention and are not intended to limit the same. The basic principles and main features of the present invention have been described above using specific implementation schemes. Modifications or substitutions may be made based on the present invention, but such modifications or substitutions do not detract from the essence of the corresponding technical solutions from the scope of protection claimed by the present invention.

Claims

1. A pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer, characterized in that: The raw materials include the following percentages by mass: 0.05-0.08% of compound A, 0.05-0.1% of sodium pyruvate, 0.2-2% of disodium hydrogen phosphate, 0.2-2% of sodium dihydrogen phosphate, and the balance is normal saline; the structural formula of compound A is shown below: 。 2. The pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer according to claim 1, characterized in that: The preparation process of compound A is as follows: (1) Chlorogenic acid and 4-(2-hydroxyethoxy)-3-methoxybenzaldehyde were added to DMF and stirred for reaction under catalyst conditions; intermediate 1 was obtained after purification and concentration; (2) adding the intermediate 1 and 2-aminoethylsulfonamide obtained in step (1) to a mixed solvent, adding acetic acid and stirring for 3-4 hours, then adding sodium cyanoborohydride and continuing to stir the reaction, purifying and concentrating to obtain intermediate 2; (3) The intermediate 2,4-cyanophenylboronic acid obtained in step (2) is added to tetrahydrofuran for reaction, and purified to obtain compound A.

3. The pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer according to claim 2, characterized in that: The usage ratio of chlorogenic acid, 4-(2-hydroxyethoxy)-3-methoxybenzaldehyde, catalyst and DMF in step (1) is 1 mmol: (1.2-1.5) mmol: (0.012-0.015) mmol: (20-25) mL.

4. The pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer according to claim 2, characterized in that: The catalyst in step (1) is p-toluenesulfonic acid; the stirring reaction time is 16-24 hours.

5. The pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer according to claim 2, characterized in that: The usage ratio of the intermediate 1, 2-aminoethylsulfonamide, mixed solvent, acetic acid, and sodium cyanoborohydride in step (2) is 5 mmol: (10-15) mmol: (25-35) mL: (0.5-1) mL: (10-15) mmol.

6. The pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer according to claim 2, characterized in that: The mixed solvent in step (2) consists of dichloromethane and methanol in a volume ratio of 1:

1.

7. The pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer according to claim 2, characterized in that: The stirring reaction time in step (2) is 12-16 hours.

8. The pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer according to claim 2, characterized in that: The ratio of the intermediate 2, 4-cyanophenylboronic acid and tetrahydrofuran used in step (3) is 5 mmol: (5-6) mmol: (15-20) mL.

9. The pyruvate inhalation aerosol for treating malignant pleural effusion caused by lung cancer according to claim 2, characterized in that: The reaction temperature in step (3) is 70-80°C, and the reaction time is 12-16 hours.

10. The method for preparing the pyruvate inhalation atomizer for treating malignant pleural effusion caused by lung cancer according to any one of claims 1 to 9, characterized in that: The following steps are involved: The raw materials can be compounded according to the mass percentage.

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