A pharmaceutical composition containing pyruvate, and its preparation method and application

Abstract

The present invention belongs to the field of pharmaceutical technology and specifically relates to a pharmaceutical composition containing pyruvate, its preparation method, and its use. The pharmaceutical composition comprises the following raw materials, by mass percentage: 0.05-0.1% Compound I, 0.1-0.2% sodium pyruvate, 0.05-0.1% sodium dihydrogen phosphate, 0.05-0.1% sodium dihydrogen phosphate, 3-5% glycerol, and the balance being saline. The structural formula of Compound I is shown below, #imgabs0#. This pharmaceutical composition alleviates the symptoms of stress-induced rhinitis by reducing nasal secretions, downregulating the expression of TE4, IgE, and IL-4, and lowering the number of eosinophils.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and particularly relates to a pharmaceutical composition containing pyruvate, a preparation method thereof, and an application thereof. Background Art

[0002] Allergic rhinitis (AR), also known as allergic rhinitis, is an allergic disease of the nasal mucosa. It is characterized by increased nasal mucosal reactivity, typically triggered by exposure to specific allergens, such as inhaled allergens like pollen, dust mites, and animal hair, or food allergens like nuts, peanuts, eggs, and milk. Once these allergens enter the body, the immune system triggers an allergic response, leading to nasal inflammation. Furthermore, genetic factors also play a significant role in the development of allergic rhinitis. Allergic rhinitis is a common and widespread disease. Understanding its etiology, clinical manifestations, and treatments is crucial for improving patients' quality of life and reducing the burden of the disease.

[0003] Prior art discloses sodium pyruvate / normal saline nasal sprays that relieve symptoms of allergic rhinitis such as itching, sneezing, runny nose, and nasal congestion by cleaning the nasal cavity and neutralizing harmful substances generated by external inhalation and the nasal cavity's own inflammatory response. These nasal sprays are easy to use and highly safe. However, these nasal sprays cannot fundamentally cure allergic rhinitis, and their therapeutic effect is limited for patients with severe symptoms.

[0004] Vitamin B6 is an essential micronutrient for maintaining healthy growth and normal physiological function in the human body. It possesses anti-inflammatory, antioxidant, neuromodulatory, and anti-tumor properties, making it crucial for maintaining a healthy nervous system, skin, and immune system. However, its effectiveness in treating rhinitis is limited. Therefore, it is crucial to modify natural, harmless vitamin B6 and further develop its therapeutic combination with pyruvate for the treatment of rhinitis. Summary of the Invention

[0005] In order to overcome the deficiencies of the prior art, one of the objectives of the present invention is to provide a pharmaceutical composition containing pyruvate, which can treat allergic rhinitis.

[0006] A second object of the present invention is to provide a method for preparing a pharmaceutical composition containing pyruvate, which has simple preparation steps.

[0007] A third object of the present invention is to provide an application of a pharmaceutical composition containing pyruvate, which has broad application prospects.

[0008] One of the purposes of the present invention is achieved by the following technical solution:

[0009] A pharmaceutical composition containing pyruvate, comprising the following raw materials, calculated by mass percentage: 0.05-0.1% compound I, 0.1-0.2% sodium pyruvate, 0.05-0.1% sodium dihydrogen phosphate, 0.05-0.1% sodium dihydrogen phosphate, 3-5% glycerol, and the balance being normal saline; the structural formula of compound I is shown below:

[0010] .

[0011] Furthermore, the preparation method of the compound I is as follows:

[0012]

[0013] (1) Sodium carbonate and (4S)-4-hydroxy-L-proline methyl ester were added to acetonitrile, and then succinic anhydride was added to react, and intermediate 1 was obtained after purification;

[0014] (2) The intermediate 1 of step (1) and N,N'-dicyclohexylcarbodiimide were added to dichloromethane, stirred at 5-10°C for 10-15 minutes, and then (2,2,8-trimethyl-4H-[1,3]dioxadiene[4,5-C]pyridin-5-yl)methanol and 4-dimethylaminopyridine were added, and the stirring was continued for 30-45 minutes, and then the temperature was raised to react, and the intermediate 2 was obtained after purification;

[0015] (3) adding the intermediate 2 of step (2) to acetonitrile, and then adding hydrochloric acid to react, and obtaining the intermediate 3 after purification;

[0016] (4) The intermediate 3 of step (3) was added to DMF, and then cesium carbonate and tetrabutylammonium iodide were added to react, and compound I was obtained after purification.

[0017] Furthermore, in step (1), the ratio of sodium carbonate, (4S)-4-hydroxy-L-proline methyl ester, and succinic anhydride is (5-8):10:(10-12)l; and the reaction time is 30-60 min.

[0018] Furthermore, in step (2), the molar ratio of the intermediate 1, N,N'-dicyclohexylcarbodiimide, (2,2,8-trimethyl-4H-[1,3]dioxadiene[4,5-C]pyridin-5-yl)methanol, and 4-dimethylaminopyridine is 10:(11-13):(11-13):(8-10).

[0019] Furthermore, the temperature of the temperature-raising reaction in step (2) is 25-35° C., and the reaction time is 3-5 h.

[0020] Furthermore, in step (3), the usage ratio of the intermediate 2, acetonitrile, and hydrochloric acid is (10-12) mmol: (10-12) mL: (40-50) mL; the concentration of the hydrochloric acid is 3-4 mol / L; and the reaction time is 1-2 h.

[0021] Furthermore, in step (4), the ratio of the intermediate 3, cesium carbonate and tetrabutylammonium iodide is 10:(10-12):(1-2).

[0022] Furthermore, the reaction temperature in step (4) is 38-42° C., and the reaction time is 3-4 h.

[0023] The second object of the present invention is achieved by adopting the following technical solution:

[0024] The method for preparing the above-mentioned pharmaceutical composition containing pyruvate comprises the following steps:

[0025] The raw materials can be compounded according to the mass percentage.

[0026] The third object of the present invention is achieved by adopting the following technical solution:

[0027] Use of the above-mentioned pharmaceutical composition containing pyruvate in the preparation of a medicine for treating rhinitis.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The present invention's pharmaceutical composition containing pyruvate includes Compound I and sodium pyruvate. Experimental results indicate that the combination of Compound I and sodium pyruvate can alleviate the symptoms of nasal inflammation by reducing nasal secretions, downregulating the expression of TE4, IgE, and IL-4, and decreasing the number of eosinophils. DETAILED DESCRIPTION

[0030] The present invention will be further described below in conjunction with specific embodiments. It should be noted that, under the premise of no conflict, the various embodiments described below or the various technical features can be arbitrarily combined to form new embodiments. Specific conditions not specified in the embodiments are carried out according to conventional conditions or conditions recommended by the manufacturer. All reagents or instruments used are conventional products obtained through commercial channels unless otherwise specified.

[0031] 1. Example

[0032] Example 1

[0033] This embodiment provides a pharmaceutical composition containing pyruvate, which is composed of the following raw materials, calculated by mass percentage: 0.08% of Compound I, 0.15% of sodium pyruvate, 0.06% of sodium dihydrogen phosphate, 0.06% of sodium hydrogen phosphate, 4% of glycerol, and the balance of normal saline. The structural formula of Compound I is shown below:

[0034] .

[0035] The preparation method of the above compound I is as follows:

[0036]

[0037] (1) Sodium carbonate and (4S)-4-hydroxy-L-proline methyl ester (CAS: 81102-38-7) were added to acetonitrile according to the ratio of sodium carbonate, (4S)-4-hydroxy-L-proline methyl ester, acetonitrile, and succinic anhydride in the amount of 7 mmol:10 mmol:10 mL:11 mmol, and succinic anhydride was slowly added. The reaction was carried out at room temperature for 50 min to obtain a reaction solution. The reaction solution was concentrated and the solvent was removed under reduced pressure. The residue was dissolved in water and acidified with 1 mol / L hydrochloric acid to adjust the pH to 6. The aqueous phase was extracted with ethyl acetate. After separation, the ethyl acetate phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain intermediate 1.

[0038] The characterization results of intermediate 1 are as follows:

[0039] 1 HNMR (C 10 H 15 NO6,400MHz, d 6 -DMSO)δ12.15(s,1H),4.77-4.75(m,1H),3.66(s,3H),3.58(t,1H),3.12-2.87 (m,2H),2.71(t,2H),2.52(t,2H),2.31-2.06(m,3H); MS(ESI)m / z=245.09[M+H] + , found 245.09; the above results confirmed that the target product was obtained.

[0040] (2) According to the molar ratio of the intermediate 1, N,N'-dicyclohexylcarbodiimide (DCC), (2,2,8-trimethyl-4H-[1,3]dioxadiene-[4,5-C]pyridin-5-yl)methanol (CAS: 1136-52-3), and 4-dimethylaminopyridine (DMAP) of 10:12:12:9, the intermediate 1 of step (1) and N,N'-dicyclohexylcarbodiimide were added to dichloromethane and stirred at 8°C for 12 minutes. While stirring, (2,2,8-trimethyl-4H-[1,3]dioxadiene-[4,5-C]pyridin-5-yl)methanol were added in sequence. 4H-[1,3]dioxolane[4,5-c]pyridin-5-yl)methanol and 4-dimethylaminopyridine were stirred for 40 minutes, and then the mixture was heated to room temperature and reacted for 4 hours. After completion of the reaction, a reaction solution was obtained; the reaction solution was concentrated and the solvent was removed under reduced pressure. The residue was dissolved in water and then acidified with 1M hydrochloric acid to adjust the pH to 7. The aqueous phase was extracted with ethyl acetate. After separation, the ethyl acetate phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (the eluent consisted of n-heptane and ethyl acetate in a volume ratio of 3:1) to obtain intermediate 2;

[0041] The characterization results of intermediate 2 are as follows:

[0042] 1 HNMR (C 21 H 28 N2O8,400MHz, d 6 -DMSO)δ8.37(s,1H),5.37(s,2H),5.05(s,2H),4.77-4.75(m,1H),3.66(s,3H),3.58(t,1H),3.12-2.87( m,2H),2.73(t,2H),2.64(t,2H),2.52(s,3H),2.31-2.06(m,2H),1.49(s,6H); MS(ESI)m / z=437.18[M+H] + , 437.18 was found; the above results confirmed that the target product was obtained.

[0043] (3) According to the amount ratio of intermediate 2, acetonitrile and hydrochloric acid of 10 mmol:10 mL:45 mL, intermediate 2 of step (2) was added to acetonitrile at 0°C, and then 3 mol / L hydrochloric acid was added dropwise. The reaction was carried out at room temperature for 1.5 h to obtain a reaction solution. The reaction solution was diluted with ethyl acetate and washed three times with saturated sodium bicarbonate aqueous solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to obtain intermediate 3. MS (ESI) of intermediate 3 was m / z = 397.15 [M+H] + , found 397.15.

[0044] (4) The intermediate 3 of step (3) was added to DMF according to the amount ratio of the intermediate 3, DMF, cesium carbonate, and tetrabutylammonium iodide of 10 mmol: 20 mL: 11 mmol: 1.5 mmol, and then cesium carbonate and tetrabutylammonium iodide were added. The reaction was carried out at 40°C for 3.5 h. After the reaction was completed, a reaction solution was obtained. The reaction solution was quenched with a saturated aqueous sodium bicarbonate solution, and the aqueous phase was extracted with ethyl acetate. The ethyl acetate phases were combined and extracted with saturated brine, dried over sodium sulfate, filtered, concentrated, and purified by column chromatography (the eluent consisted of a mixture of dichloromethane and alcohol in a volume ratio of 3:1, and the alcohol mixture consisted of a mixture of 3 parts of methanol and 2 parts of ethanol by volume) to obtain compound I.

[0045] The characterization results of compound I are as follows:

[0046] 1 HNMR (C 17 H 22 N2O8,400MHz, d 6 -DMSO)δ12.39(s,1H),9.58(s,1H),8.37(s,1H),5.39(s,2H),5.27(s,1H),5.05(s,2H),4.77-4.75(m,1H),3.62(t,1H) ),3.12-2.87(m,2H),2.74-2.72(m,2H),2.65-2.63(m,2H),2.52(s,3H),2.19-1.94(m,3H); MS(ESI)m / z=383.14[M+H] + , 383.14 was found; the above results confirmed that the target product was obtained.

[0047] This embodiment also provides a method for preparing the above-mentioned pharmaceutical composition, which is as follows:

[0048] The raw materials can be compounded according to the mass percentage.

[0049] Example 2

[0050] This embodiment provides a pharmaceutical composition containing pyruvate, which is composed of the following raw materials, calculated by mass percentage: 0.05% Compound I, 0.1% sodium pyruvate, 0.05% sodium dihydrogen phosphate, 0.05% sodium hydrogen phosphate, 3% glycerol, and the balance being normal saline; the structural formula of Compound I is the same as that of Example 1.

[0051] The preparation method of the above compound I is as follows:

[0052] (1) Sodium carbonate and (4S)-4-hydroxy-L-proline methyl ester were added to acetonitrile in a ratio of 5 mmol:11 mmol:12 mL:10 mmol to sodium carbonate, (4S)-4-hydroxy-L-proline methyl ester, acetonitrile, and succinic anhydride, and succinic anhydride was slowly added. The mixture was reacted at room temperature for 30 min to obtain a reaction solution. The reaction solution was concentrated and the solvent was removed under reduced pressure. The residue was dissolved in water and acidified with 1 mol / L hydrochloric acid to adjust the pH to 6. The aqueous phase was extracted with ethyl acetate. After separation, the ethyl acetate phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain intermediate 1. 1 HNMR and MS (ESI) m / z were consistent with those in Example 1;

[0053] (2) According to the molar ratio of the intermediate 1, N,N'-dicyclohexylcarbodiimide, (2,2,8-trimethyl-4H-[1,3]dioxadiene-[4,5-c]pyridin-5-yl)methanol and 4-dimethylaminopyridine of 10:11:11:8, the intermediate 1 of step (1) and N,N'-dicyclohexylcarbodiimide were added to dichloromethane and stirred at 5°C for 10 minutes. While stirring, (2,2,8-trimethyl-4H-[1,3]dioxadiene-[4,5-c]pyridin-5-yl)methanol and 4-dimethylaminopyridine were added in sequence. The mixture was stirred for 30 minutes, and then heated to 30°C for 3 hours to obtain a reaction solution. The reaction solution was concentrated and the solvent was removed under reduced pressure. The residue was dissolved in water and then acidified with 1M hydrochloric acid to adjust the pH to 7. The aqueous phase was extracted with ethyl acetate. After separation, the ethyl acetate phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (the eluent consisted of n-heptane and ethyl acetate in a volume ratio of 3:1) to obtain intermediate 2. 1 HNMR and MS (ESI) m / z were consistent with those in Example 1;

[0054] (3) According to the amount ratio of intermediate 2, acetonitrile and hydrochloric acid of 11 mmol:12 mL:40 mL, intermediate 2 of step (2) was added to acetonitrile at 0°C, and then 4 mol / L hydrochloric acid was added dropwise. The mixture was reacted at room temperature for 1 h to obtain a reaction solution. The reaction solution was diluted with ethyl acetate and washed three times with saturated sodium bicarbonate aqueous solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to obtain intermediate 3. The MS (ESI) m / z of intermediate 3 was consistent with that of Example 1.

[0055] (4) According to the amount ratio of the intermediate 3, DMF, cesium carbonate, and tetrabutylammonium iodide of 10mmol:20mL:10mmol:1mmol, the intermediate 3 of step (3) was added to DMF, and then cesium carbonate and tetrabutylammonium iodide were added, and the reaction was carried out at 38°C for 4h. After the reaction was completed, a reaction solution was obtained; the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution, and the aqueous phase was extracted with ethyl acetate. The ethyl acetate phases were combined and extracted with saturated brine, dried with sodium sulfate, filtered, concentrated, and purified by column chromatography (the eluent was composed of a mixture of dichloromethane and alcohol in a volume ratio of 3:1, and the alcohol mixture was a mixture of 3 parts of methanol and 2 parts of ethanol by volume fraction) to obtain compound I. Compound I 1 HNMR and MS (ESI) m / z were consistent with those in Example 1.

[0056] This embodiment also provides a method for preparing the above-mentioned pharmaceutical composition, which is as follows:

[0057] The raw materials can be compounded according to the mass percentage.

[0058] Example 3

[0059] This embodiment provides a pharmaceutical composition containing pyruvate, which is composed of the following raw materials, calculated by mass percentage: 0.1% Compound I, 0.2% sodium pyruvate, 0.1% sodium dihydrogen phosphate, 0.1% sodium hydrogen phosphate, 5% glycerol, and the balance being normal saline; the structural formula of Compound I is the same as that of Example 1.

[0060] The preparation method of the above compound I is as follows:

[0061] (1) Sodium carbonate and (4S)-4-hydroxy-L-proline methyl ester were added to acetonitrile in a ratio of 8 mmol:12 mmol:15 mL:12 mmol, and succinic anhydride was slowly added. The mixture was reacted at room temperature for 60 min to obtain a reaction solution. The reaction solution was concentrated and the solvent was removed under reduced pressure. The residue was dissolved in water and acidified with 1 mol / L hydrochloric acid to adjust the pH to 6. The aqueous phase was extracted with ethyl acetate. After separation, the ethyl acetate phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain intermediate 1. 1 HNMR and MS (ESI) m / z were consistent with those in Example 1;

[0062] (2) According to the molar ratio of the intermediate 1, N,N'-dicyclohexylcarbodiimide, (2,2,8-trimethyl-4H-[1,3]dioxadiene[4,5-c]pyridin-5-yl)methanol and 4-dimethylaminopyridine of 10:13:13:10, the intermediate 1 of step (1) and N,N'-dicyclohexylcarbodiimide were added to dichloromethane and stirred at 10°C for 15 minutes. While stirring, (2,2,8-trimethyl-4H-[1,3]dioxadiene[4,5-c]pyridin-5-yl)methanol and 4-dimethylaminopyridine were added in sequence. The mixture was stirred for 45 minutes, and then heated to 35°C for 5 hours to obtain a reaction solution. The reaction solution was concentrated and the solvent was removed under reduced pressure. The residue was dissolved in water and then acidified with 1M hydrochloric acid to adjust the pH to 7. The aqueous phase was extracted with ethyl acetate. After separation, the ethyl acetate phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (the eluent consisted of n-heptane and ethyl acetate in a volume ratio of 3:1) to obtain intermediate 2. 1 HNMR and MS (ESI) m / z were consistent with those in Example 1;

[0063] (3) According to the amount ratio of intermediate 2, acetonitrile and hydrochloric acid of 12 mmol:11 mL:50 mL, intermediate 2 of step (2) was added to acetonitrile at 0°C, and then 3 mol / L hydrochloric acid was added dropwise. The mixture was reacted at room temperature for 2 h to obtain a reaction solution. The reaction solution was diluted with ethyl acetate and washed three times with saturated sodium bicarbonate aqueous solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to obtain intermediate 3. The MS (ESI) m / z of intermediate 3 was consistent with that in Example 1.

[0064] (4) According to the amount ratio of the intermediate 3, DMF, cesium carbonate, and tetrabutylammonium iodide of 10mmol:25mL:12mmol:2mmol, the intermediate 3 of step (3) was added to DMF, and then cesium carbonate and tetrabutylammonium iodide were added, and the reaction was carried out at 42°C for 3h. After the reaction was completed, a reaction solution was obtained; the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution, and the aqueous phase was extracted with ethyl acetate. The ethyl acetate phases were combined and extracted with saturated brine, dried with sodium sulfate, filtered, concentrated, and purified by column chromatography (the eluent was composed of a mixture of dichloromethane and alcohol in a volume ratio of 3:1, and the alcohol mixture was a mixture of 3 parts of methanol and 2 parts of ethanol by volume fraction) to obtain compound I. Compound I 1 HNMR and MS (ESI) m / z were consistent with those in Example 1.

[0065] This embodiment also provides a method for preparing the above-mentioned pharmaceutical composition, which is as follows:

[0066] The raw materials can be compounded according to the mass percentage.

[0067] 2. Comparative Example

[0068] Comparative Example 1

[0069] The difference between Comparative Example 1 and Example 1 is that vitamin B6 is used instead of Compound I, and the rest is the same as Example 1.

[0070] 3. Test example

[0071] (1) Experimental animals

[0072] 60 guinea pigs, with a male-female ratio of 1:1 and weighing 350-400 g, were randomly divided into Example 1-3 groups, Comparative Example 1 group, blank control group, and model group, with 10 guinea pigs in each group.

[0073] (2) Model construction

[0074] Prepare suspension: add 0.5 mg of ovalbumin and 30 mg of aluminum hydroxide powder to 1 mL of normal saline to obtain a suspension for later use.

[0075] The blank control group received an equal volume of saline intraperitoneally. Guinea pigs in all other groups, except the blank control group, were sensitized with the suspension intraperitoneally every other day for a total of seven injections. Four days after sensitization, the guinea pigs were placed in a head-down position and challenged with 50 μL of a 2% ovalbumin solution in each nasal cavity every other day for a total of five injections, each challenge being performed 1 hour after the first intranasal administration of the day.

[0076] Behavioral indices were evaluated for the number of sneezing, nasal scratching, and runny nose of guinea pigs within 30 minutes after each bilateral ovalbumin nasal drop challenge. The total score was calculated using the superposition method. A total score ≥ 5 points indicated a successful model establishment. The behavioral evaluation criteria are shown in Table 1.

[0077] Table 1

[0078]

[0079] (3) Method of administration

[0080] The drug was administered on the second day after sensitization, with 50 μL dripped into each nostril three times a day using a micropipette. The model group and the blank control group were given an equal amount of normal saline nasal drops, and the Example 1-3 group and the comparative example 1 group were given the corresponding pharmaceutical composition, and the administration was continued for 12 days.

[0081] (4) Detection indicators and methods

[0082] On the 1st, 3rd, and 5th day of administration, 30 minutes after stimulation with ovalbumin solution, a 2 mm × 30 mm filter paper strip was placed in the nasal cavity with one end fixed outside the nasal cavity for 5 minutes. After the filter paper strip was removed, the amount of nasal secretions was weighed. The results are shown in Table 2.

[0083] After treatment, the animals were fasted overnight and sacrificed the next day for blood collection. Serum leukotriene E4 (LTE4), immunoglobulin E (IgE), and IL-4 levels were assayed according to the kit instructions. The results are shown in Table 3. The nasal concha and septal mucosa of the sacrificed guinea pigs were fixed in 10% formalin, embedded in paraffin, and sectioned for observation under a light microscope. Five fields (10 × 40 pixels) were observed on each section, and the number of eosinophils was counted. The results are shown in Table 3.

[0084] Table 2

[0085]

[0086] Table 3

[0087]

[0088] As shown in Tables 2-3, the use of the pharmaceutical composition containing pyruvate of the present invention significantly reduced nasal secretion volume, LTE4, IgE, IL-4 levels, and eosinophil counts. This indicates that the pharmaceutical composition containing pyruvate of the present invention is effective in treating inflammatory rhinitis.

[0089] Compared to Examples 1-3, the drug obtained in Comparative Example 1 using vitamin B6 instead of Compound I can alleviate rhinitis symptoms, but the effect is less than optimal. These results demonstrate that the combination of Compound I obtained by the present invention and sodium pyruvate can alleviate the symptoms of stress-induced rhinitis by reducing nasal secretions, downregulating the expression of TE4, IgE, and IL-4, and decreasing the number of eosinophils.

[0090] The above embodiments are only preferred embodiments of the present invention and cannot be used to limit the scope of protection of the present invention. Any non-substantial changes and replacements made by technicians in this field on the basis of the present invention fall within the scope of protection required by the present invention.

Claims

1. A pharmaceutical composition containing pyruvate, characterized in that: The invention is composed of the following raw materials in the following mass percentages: 0.05-0.1% compound I, 0.1-0.2% sodium pyruvate, 0.05-0.1% sodium dihydrogen phosphate, 0.05-0.1% sodium hydrogen phosphate, 3-5% glycerol, and the balance being normal saline. The structural formula of the compound I is shown below: 。 2. The pharmaceutical composition containing pyruvate according to claim 1, wherein: The preparation method of compound I is as follows: (1) Sodium carbonate and (4S)-4-hydroxy-L-proline methyl ester were added to acetonitrile, and then succinic anhydride was added to react, and intermediate 1 was obtained after purification; (2) The intermediate 1 of step (1) and N,N'-dicyclohexylcarbodiimide were added to dichloromethane, stirred at 5-10°C for 10-15 minutes, and then (2,2,8-trimethyl-4H-[1,3]dioxadiene[4,5-C]pyridin-5-yl)methanol and 4-dimethylaminopyridine were added, and the stirring was continued for 30-45 minutes, and then the temperature was raised to react, and the intermediate 2 was obtained after purification; (3) adding the intermediate 2 of step (2) to acetonitrile, and then adding hydrochloric acid to react, and obtaining the intermediate 3 after purification; (4) The intermediate 3 of step (3) was added to DMF, and then cesium carbonate and tetrabutylammonium iodide were added to react, and compound I was obtained after purification.

3. The pharmaceutical composition containing pyruvate according to claim 2, wherein: In step (1), the ratio of sodium carbonate, (4S)-4-hydroxy-L-proline methyl ester, and succinic anhydride is (5-8):10:(10-12); and the reaction time is 30-60 min.

4. The pharmaceutical composition containing pyruvate according to claim 2, wherein: The molar ratio of the intermediate 1, N,N'-dicyclohexylcarbodiimide, (2,2,8-trimethyl-4H-[1,3]dioxadiene[4,5-c]pyridin-5-yl)methanol, and 4-dimethylaminopyridine in step (2) is 10:(11-13):(11-13):(8-10).

5. The pharmaceutical composition containing pyruvate according to claim 2, wherein: The temperature of the temperature-raising reaction in step (2) is 25-35° C., and the reaction time is 3-5 h.

6. The pharmaceutical composition containing pyruvate according to claim 2, wherein: In step (3), the ratio of the intermediate 2, acetonitrile, and hydrochloric acid is (10-12) mmol: (10-12) mL: (40-50) mL; the concentration of the hydrochloric acid is 3-4 mol / L; and the reaction time is 1-2 h.

7. The pharmaceutical composition containing pyruvate according to claim 2, wherein: In step (4), the ratio of the intermediate 3, cesium carbonate and tetrabutylammonium iodide is 10:(10-12):(1-2).

8. The pharmaceutical composition containing pyruvate according to claim 2, wherein: The reaction temperature in step (4) is 38-42°C, and the reaction time is 3-4 hours.

9. The method for preparing the pharmaceutical composition containing pyruvate according to any one of claims 1 to 8, wherein: The following steps are involved: The raw materials can be compounded according to the mass percentage.

10. Use of the pharmaceutical composition according to any one of claims 1 to 8 supplemented with pyruvate in the preparation of a medicament for treating allergic rhinitis.

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