CN1698896A - Method for preparing compound beta lactam sodium salt/sodium benemid for injection - Google Patents

Abstract

A method for preparing compound β-lactam sodium salt/probenecid sodium for injection. First, 1-10 parts of probenecid are dissolved in 1-100 parts of water according to the number of parts by mass, and then sodium ion-containing Alkaline solution adjusts the pH to 6-11 to react into a salt; then filter through a microporous membrane, sterilize, and dry aseptically or add 10-100 parts of absolute ethanol or anhydrous acetone after filtering through a microporous membrane Precipitate the solid and dry it aseptically to obtain probenecid sodium; mix β-lactam sodium salt with the obtained probenecid sodium according to the ratio of 10:1-1:10 and dissolve in 1-100 parts Just in water. Because there is a carboxyl group in the probenecid molecule, it is acidic, and can form a salt with an alkali, and then dissolve in water. The present invention uses this characteristic to prepare probenecid sodium, and mix it with the raw material drug for injection of β-lactam sodium salt. Thus the compound β-lactam sodium salt/probenecid sodium for injection was prepared.

Description

Preparation method of compound β-lactam sodium salt/probenecid sodium for injection

technical field

The invention relates to a preparation method of compound β-lactam sodium salt/probenecid sodium for injection.

Background technique

β-lactam antibiotics are widely used clinically. However, its oral administration has low bioavailability, short half-life, and requires multiple doses per day, which affects the clinical application of β-lactam antibiotics.

Probenecid is an organic acid drug, clinically used for the treatment of chronic gout.

In the early 1950s, Boger et al. found that when the anti-chronic gout drug probenecid was combined with penicillin, the blood concentration of the latter could be increased. Kampann et al. found that probenecid also has the effect of increasing the blood concentration of ampicillin and prolonging the half-life of ampicillin. Gibaldi et al. pointed out that the combination of probenecid with β-lactam antibiotics caused significant changes in the latter’s in vivo kinetic parameters: the area under the blood drug time curve (AUC) at the peak blood concentration (C _max ), the biological half-life of the drug and The average residence time in vivo increases with the proportion of probenecid.

β-lactam drugs are secreted and excreted through the renal tubules, and probenecid is also secreted and excreted from the renal tubules. When the two are used in combination, probenecid can competitively inhibit the transport of β-lactam antibiotics in renal tubules, make them retain and redistribute, thereby increasing the blood concentration of β-lactams and prolonging the half-life.

Probenecid is widely used both at home and abroad, and is clinically used to treat chronic gout.

Contents of the invention

An object of the present invention is to provide a preparation method of compound β-lactam sodium salt/probenecid sodium for injection, which can effectively solve the problem of insoluble probenecid in water, and prepare a compound preparation suitable for intravenous injection .

In order to achieve the above-mentioned purpose, the preparation method adopted in the present invention is as follows: firstly, 1 to 10 parts of probenecid are dissolved in 1 to 100 parts of water to prepare a probenecid suspension solution in parts by mass, and then mixed with probenecid Add 0.1-2.5 mol/L alkaline solution containing sodium ions to the suspension solution to adjust the pH to 6-11 to react into a salt; then filter through a 0.22 or 0.45 μm microporous membrane and sterilize at 105-200°C for 30 minutes. and aseptically dry or filter with a 0.22 or 0.45 μm microporous membrane, add 10 to 100 parts of absolute ethanol or anhydrous acetone to precipitate a solid, and after aseptic drying, probenecid sodium is obtained; The amide sodium salt and the obtained probenecid sodium are mixed in a ratio of 10:1 to 1:10 and then dissolved in 1 to 100 parts of water.

Alkali in the present invention is inorganic base or organic base, and inorganic base is NaOH; Said organic base is sodium acetate, sodium bicarbonate, sodium carbonate or sodium lactate; Beta-lactam sodium salt is ampicillin sodium, cefotaxime Sodium, Cefoperazone Sodium, Cefuroxime Sodium, Cloxacillin Sodium, Azlocillin Sodium, Carumonan Sodium, Cloxacillin Sodium, or Cefpiramide Sodium Sterile Powder.

Because there is a carboxyl group in the probenecid molecule, it is acidic, and can form a salt with an alkali, and then dissolve in water. The present invention uses this characteristic to prepare probenecid sodium, and mix it with the raw material drug for injection of β-lactam sodium salt. Thus, compound β-lactam sodium salt/probenecid sodium for injection was prepared.

Detailed ways

Embodiment 1: at first 1 part of probenecid is dissolved in 75 parts of water by mass parts to make probenecid suspension, then add the NaOH solution of 1mol/L in probenecid suspension to adjust pH to 8 react to form a salt, then filter through a 0.22 μm microporous membrane, sterilize at 150°C for 30 minutes, and dry aseptically to obtain probenecid sodium; It can be dissolved in 1 portion of infusion solution after mass ratio, intravenous administration can be divided into slow intravenous injection or intravenous infusion; intravenous infusion, 1 ~ 2g (according to ampicillin sodium), instillation 1/2 ~ 1h, 2 to 4 times/day. For children, 100-150 mg/kg (according to ampicillin sodium) per day, given in divided doses.

Embodiment 2: at first 8 parts of probenecid are dissolved in 80 parts of water by mass parts to make probenecid suspension, then add the sodium acetate solution of 0.8mol/L in probenecid suspension to adjust When the pH reaches 9, react to form a salt, filter through a 0.45 μm microporous membrane, sterilize at 200°C for 30 minutes, and dry aseptically to obtain probenecid sodium; mix cefotaxime sodium with the obtained probenecid sodium at a ratio of 1: The mass ratio of 10 can be dissolved in 100 parts of infusion. Intravenous administration can be divided into slow intravenous injection or intravenous infusion; intravenous infusion, 1 ~ 2g (calculated as cefotaxime sodium) once, instilled for 1/2 ~ 1h, 2 ~ 4 times / day. For children, 100-150 mg/kg per day (based on cefotaxime sodium), given in divided doses.

Embodiment 3: at first 5 parts of probenecid are dissolved in 50 parts of water by mass parts to make probenecid suspension, then add the sodium bicarbonate solution of 2.5mol/L in probenecid suspension Adjust the pH to 10 to react into a salt, filter through a 0.22 μm microporous membrane, sterilize at 105°C for 30 minutes, and dry aseptically to obtain probenecid sodium; mix cefoperazone sodium and the obtained probenecid sodium according to the ratio of 10:1 After mass proportioning, it can be dissolved in 80 parts of water. Adults: 1-2g (calculated as cefoperazone sodium), once every 12 hours; for severe infections, it can be increased to 4g once every 12 hours. Children: 50-200mg/kg per day (based on cefoperazone sodium), divided into 2 doses.

Embodiment 4: at first 3 parts of probenecid are dissolved in 63 parts of water by mass parts to make probenecid suspension, then add the sodium carbonate solution of 0.8mol/L in probenecid suspension to adjust When the pH reaches 10, react to form a salt, filter through a 0.45 μm microporous membrane, sterilize at 160°C for 30 minutes, and dry aseptically to obtain probenecid sodium; mix cefuroxime sodium and the obtained probenecid sodium according to the ratio of 3: After the mass proportion of 9 is dissolved in 60 parts of water, it gets final product. Adults, 0.25-0.75g/time, (calculated by cefuroxime sodium), 3-4 times/day; children, 30-60mg/kg per day, (calculated by cefuroxime sodium), divided into 3-4 times.

Embodiment 5: at first 10 parts of probenecid are dissolved in 40 parts of water by mass parts to make probenecid suspension, then add the sodium lactate solution of 2.5mol/L in probenecid suspension to adjust pH To 7, react to form a salt, filter with a 0.45 μm microporous membrane, and then sterilize at 130°C for 30 minutes to obtain probenecid sodium; mix cloxacillin sodium with the obtained probenecid sodium in a mass ratio of 6:5 Soluble in 40 parts of water. Adults, 2g/day (based on cloxacillin sodium), divided into 4 times. Children take 25-50 mg/kg of body weight per day (based on cloxacillin sodium), divided into 4 times. During intramuscular injection, 0.5% lidocaine can be added to reduce pain.

Embodiment 6: first by mass parts, 1 part of probenecid is dissolved in 1 part of water to make probenecid suspension, then add 0.6mol/L sodium lactate solution in probenecid suspension to adjust pH To 7 reaction into salt, add 10 parts of absolute ethanol after filtering with 0.22 μm microporous membrane to separate out solid, dry aseptically to obtain probenecid sodium; combine azlocillin sodium and obtained probenecid sodium by The mass ratio of 9:2 can be dissolved in 50 parts of water. For adults, 6-10g (according to azlocillin sodium) a day, in severe cases can be increased to 10-16g (according to azlocillin sodium), divided into 2-4 infusions. 75mg/kg per day for children (according to azlocillin sodium), and 100mg/kg per day for infants and newborns, divided into 2 to 4 infusions.

Embodiment 7: at first 2 parts of probenecid are dissolved in 15 parts of water by mass parts to make probenecid suspension solution, then add the sodium carbonate solution of 0.1mol/L in probenecid suspension solution to adjust When the pH reaches 10, react to form a salt, filter through a 0.45 μm microporous membrane, add 50 parts of anhydrous acetone to precipitate a solid, and dry aseptically to obtain probenecid sodium; mix carumonan sodium with the obtained probenecid sodium According to the mass ratio of 7:4, it can be dissolved in 15 parts of infusion. Intravenous injection, adult 1~2g/day (based on Calumonan sodium), divided into 2 times. Intravenous drip, 0.5-2g/time (based on Calumonan sodium), can be dissolved and diluted by adding normal saline or isotonic glucose solution. The infusion time is 30 minutes to 2 hours.

Embodiment 8: first the probenecid suspension solution of 6.2 parts is dissolved in 100 parts of water by mass parts to make probenecid suspension solution, then add the sodium carbonate solution of 0.9mol/L in probenecid suspension solution] Adjust the pH to 6 to react into a salt, filter through a 0.45 μm microporous membrane, sterilize at 160°C for 30 minutes, and dry aseptically to obtain probenecid sodium; After the mass ratio of 8 is dissolved in 100 parts of water. For adults, 2-6g/day (based on cloxacillin sodium); for children, 50-100mg/kg per day (based on cloxacillin sodium), intravenous infusion or slow intravenous injection can be done in divided doses.

Embodiment 9: first by mass parts, 9 parts of probenecid are dissolved in 94 parts of water to make probenecid suspension solution, then add the sodium bicarbonate solution of 1.2mol/L in probenecid suspension solution Adjust the pH to 11 and react to form a salt. After filtering with a 0.45 μm microporous membrane, add 100 parts of anhydrous acetone to separate out the solid, and after aseptic drying, probenecid sodium is obtained; cefpiramide sodium and obtained probenecid sodium are formulated according to the quality of 8:7 After that, it can be dissolved in 94 parts of water. The adult dose is 1-2g/day (based on cefpiramide sodium), divided into 2 doses, intravenous injection or intravenous infusion. For children, 30-80mg/kg per day (based on cefpiramide sodium), divided into 2-3 times. Depending on the condition, it can be increased to 4g/day (calculated by cefpiramide sodium) for adults, and 150mg/kg per day (calculated by cefpiramide sodium) for children. Intravenous infusion is generally completed within 30 to 60 minutes.

Test Data

Prescription of compound ampicillin sodium/probenecid sodium for injection: ampicillin sodium: probenecid sodium (mass ratio) = 25:18

Part I Compound Ampicillin Sodium/Probenecid Sodium for Injection Single/Multiple Pharmacokinetic Tests in Rabbits

Table 1 Compound Ampicillin Sodium/Probenecid Sodium Rabbit Single Intravenous Injection Pharmacokinetic Test Results time (h) Plasma concentration of ampicillin μg·ml ^-1 Ampicillin sodium for injection (mg·kg ^-1 ) Compound Ampicillin Sodium/Probenecid Sodium for Injection (mg·kg ^-1 ) 300 120 50 300 120 50 0.020.080.160.330.51.01.52345 381±130250±201159±10060±4635±1013±276±105±262±561±131±3 175±30127±3481±1630±916±109±95±54±44±3- ^a- 68±2446±1729±1112±68±44±32±3---- 403±26 ^** 286±57192±44154 ^{±13** 135±32** 90} ±40 ^** 65±46 ^** 54±45 ^* 29±2510±133±7 248±125134±9898±3773±50 ^** 61±12 ^** 35±11 ^** 23±16 ^** 16±9 ^** 9±6 ^** 5±4 ^** 2±4 ^** 88±18 ^** 51±1239±12 ^* 26±8 ^** 20±17 ^** 9±6 ^** 4±23±3 ^** 0.4±2.7 ^** 0.2±2-

Interpretation of the results in Table 1: Compared with the ampicillin sodium for injection group, the compound ampicillin sodium/probenecid sodium for injection 300mg·kg ^-1 , 120mg·kg ^-1 and 50mg·kg ^-1 groups had different The plasma concentrations of ampicillin sodium at all time points increased (P<0.05 or P<0.01). The concentration of ampicillin sodium in the 120mg·kg ^-1 and 50mg·kg ^-1 groups for injection could not be detected in the system at 4 hours after injection, but the concentration of ampicillin sodium in the compound ampicillin sodium/probenecid sodium group for injection could still be detected in plasma concentration of ampicillin sodium in

Table 2. Rabbits received multiple intravenous injections of compound ampicillin sodium 120mg kg-1, and the plasma ampicillin sodium concentration at different times at the last time (n=6, x±s, μg ml-1) time (h) Ampicillin Sodium Concentration Ampicillin Sodium Compound Ampicillin Sodium/Probenecid Sodium 00.080.160.330.51.01.52345 260±7082±5359±4229±2216±1811±75±45±32±22±3- 384±126 ^** 257±100 ^** 152±136 ^** 98±32 ^** 92±22 ^** 49±31 ^** 33±19 ^** 14±6 ^** 10±4 ^** 6±34±1 ^**

Interpretation of ^the results in Table 2: Table 2 shows that compared with the ampicillin sodium for injection 120 mg kg ^-1 group, the plasma ampicillin after multiple administrations of compound ampicillin sodium/probenecid sodium for injection The concentration of sodium was significantly increased (P<0.05, P<0.01).

Part II Antibacterial Effects of Compound Ampicillin Sodium/Probenecid Sodium for Injection in Mice

Table 3. Effect of intravenous injection of compound ampicillin sodium/probenecid sodium on the mortality of mice infected with Staphylococcus aureus (n=10) Dosage group (mg·kg ^-1 ) Daily deaths mortality rate(%) d1 d2 d3～7 Normal Saline Compound Ampicillin Sodium/Probenecid Sodium Ampicillin Sodium 600300150300 70033 00001 00000 700 ^* 0 ^* 3040

Exact probability test, compared with the ampicillin sodium injection group, ^* P<0.05

Interpretation of the results in Table 3: Compared with the ampicillin sodium for injection group, compound ampicillin sodium/probenecid sodium 600mg·kg-1 and 300mg·kg-1 can reduce the death rate of mice infected with Staphylococcus aureus (P <0.05).

The third part In vitro antibacterial experiment of rabbits with compound ampicillin sodium/probenecid sodium for injection

Table 4 Antibacterial effect of blood plasma on Staphylococcus aureus by intravenous injection of compound ampicillin sodium at 300 mg kg ^-1 in rabbits (n=5) time (h) Antibacterial zone area (cm ² ) Compound Ampicillin Sodium/Probenecid Sodium Ampicillin Sodium 12345 8.6±1.4 ^* 8.3±0.78.1±1.0 ^** 6.1±1.5 ^** 3.0±0.2 ^** 6.9±0.46.4±2.13.3±0.21.4±0.50.8±0.1

t test, compared with the ampicillin sodium injection group, ^* P<0.05, ^** P<0.01

Interpretation of the results in Table 4: Compound Ampicillin Sodium for Injection/Probenecid Sodium 300mg kg-1 and Compound Ampicillin Sodium for Injection are compared to the bacteriostasis of Staphylococcus aureus cultivated at each time point (P＜ 0.05 or P<0.01).

Table 5 Antibacterial effect of multiple intravenous injections of compound ampicillin sodium/probenecid sodium 120 mg·kg ^-1 on Staphylococcus aureus in rabbits for the first time and last collection of plasma (n=5) time (h) Antibacterial zone area (cm ² ) Compound Ampicillin Sodium/Probenecid Sodium for Injection Ampicillin Sodium 12345252627282930 6.2±0.2 ^** 5.6±1.0 ^** 5.1±0.5 ^** 2.6±0.6** 0.8±0.2 ^** 7.5±0.5 ^** 6.8±0.4 ^** 6.5±0.1 ^** 5.3±0.1 ^** 4.0 ^± 1.0 ^** 2.8±0.5 ^** 4.1±0.52.9±0.20.8±0.1- ^a -3.8±0.53.3±0.42.5±0.11.3±0.2--

t-test, compared with the ampicillin sodium group for injection, ^** P<0.01, where ^a means below the detection limit, 1-5 hours after the first drug collection, and 25-30 hours after the last drug collection

Interpretation of the results in Table 5, Compound Ampicillin Sodium/Probenecid Sodium 120mg·kg-1 administered to rabbits for multiple times compared with Ampicillin Sodium for Injection 120mg·kg-1 for multiple times, plasma was collected at various time points after administration Enhanced inhibitory effect on Staphylococcus aureus (P<0.01)

Table 6 Antibacterial effect of blood plasma on Staphylococcus aureus by intravenous injection of compound ampicillin sodium/probenecid sodium 50mg kg ^-1 in rabbits at different times (n=5) time (h) Antibacterial zone area (cm ² ) Compound Ampicillin Sodium/Probenecid Sodium Ampicillin Sodium 12345 3.3±0.4 ^* 1.3±0.3 ^** 0.8±0.1 ^** -- 2.1±0.10.4±0.2---

t test, compared with the ampicillin sodium group for injection, P<0.05, P<0.01, where ^a means below the detection limit

Interpretation of the results in Table 6: Compound Ampicillin Sodium/Probenecid Sodium for Injection 50 mg·kg ^-1 and Injection

There were significant differences (P<0.05 or P<0.01) in cultured Staphylococcus aureus compared with ampicillin sodium 50 mg·kg ^-1 at each time point.

Table 7 Antibacterial effect of blood plasma on Escherichia coli at different times after intravenous injection of compound ampicillin sodium/probenecid sodium 300mg kg ^-1 in rabbits (n=5) time (h) Antibacterial zone area (cm ² ) Compound Ampicillin Sodium/Probenecid Sodium Ampicillin Sodium 12345 5.1±0.94.4±0.6 ^** 2.7±1.1 ^** 2.0±0.4 ^** 1.2±0.5 ^** 4.7±0.60.7±0.05 ^a --

t-test, compared with the ampicillin sodium group for injection, ^** P<0.01, where ^a means below the detection limit.

Interpretation of the results in Table 7: Compared with the Ampicillin Sodium for Injection 300mg kg ^-1 group, the inhibition zone of the Compound Ampicillin Sodium for Injection/Probenecid Sodium group at each time point was higher than that of the Ampicillin Sodium for Injection group The inhibition zone (P<0.01). However, the 300 mg·kg ^-1 ampicillin sodium for injection group could not detect its antibacterial effect after 3 hours, while the 300 mg·kg ^-1 compound ampicillin sodium/probenecid sodium for injection group could still detect the antibacterial effect.

Table 8 Bacteriostatic effect of blood plasma on Escherichia coli for multiple intravenous injections of compound ampicillin sodium/probenecid sodium 120mg kg ^-1 at different times (n=5) time (h) Antibacterial zone area (cm ² ) Compound Ampicillin Sodium/Probenecid Sodium Ampicillin Sodium 12345252627282930 4.4±1.0 ^** 3.9±1.0 ^** 3.1±0.7 ^** 0.8±0.5 ^** -7.3±0.5 ^** 6.3±0.4 ^** 4.8±0.1 ^** 3.8±0.1 ^** 2±0.9 ^** - 2.1±0.50.6±0.2- ^a --2.3±0.11±0.5----

t-test, compared with the ampicillin sodium group for injection, ^** P<0.01, where ^a means below the detection limit, 1-5h is the plasma collection after the first dose, 25-30h is the plasma collection after the last dose

Interpretation of the results in Table 8, compared with the ampicillin sodium for injection group, compound ampicillin sodium/probenecid sodium for injection 120mg·kg ^-1 , there were significant differences against Escherichia coli at each time point (P<0.01) . Table 9 Bacteriostatic effect of blood plasma on Escherichia coli after intravenous injection of compound ampicillin sodium/probenecid sodium 50mg kg ^-1 in rabbits at different times (n=2) time (h) Antibacterial zone area (cm ² ) Compound Ampicillin Sodium/Probenecid Sodium Ampicillin Sodium 1 2.6±1.3 ^** - 2345 2.2±0 ^** --- ----

t test, compared with the ampicillin sodium injection group, ^* P<0.05, ^** P<0.01

Interpretation of the results in Table 9, compound ampicillin sodium/probenecid sodium for injection 50mg·kg ^-1 single administration to rabbits, no antibacterial effect of ampicillin sodium for injection on Escherichia coli was detected.

Part IV Special Safety Test and General Pharmacological Test of Compound Ampicillin Sodium/Probenecid Sodium for Injection

Both test results show that compound ampicillin sodium/probenecid sodium for injection has obvious vascular stimulation, no obvious allergy and hemolysis; and no obvious effect on the central nervous system and cardiovascular system of mice. Adverse reactions have no obvious effect on the urinary system of rats.

Claims (10)

1. A preparation method for compound β-lactam sodium salt/probenecid sodium for injection, characterized in that: 1) First, dissolve 1 to 10 parts of probenecid in 1 to 100 parts of water according to the number of parts by mass to make a probenecid suspension solution, and then add 0.1 to 2.5 mol/L of probenecid into the probenecid suspension solution The alkaline solution containing sodium ions adjusts the pH to 6-11 and reacts to form a salt; 2) Filter through a microporous membrane of 0.22 or 0.45 μm, sterilize at 105-200°C for 30 minutes, and dry aseptically or add 10 to 100 parts of absolute ethanol after filtering through a microporous membrane of 0.22 or 0.45 μm Or anhydrous acetone precipitates solids, and after aseptic drying, probenecid sodium is obtained; 3) The β-lactam sodium salt and the obtained probenecid sodium are mixed in a ratio of 10:1 to 1:10, and then dissolved in 1 to 100 parts of water. 2. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: said base is an inorganic base or an organic base, and the inorganic base is NaOH; The preferred organic base is sodium acetate, sodium bicarbonate, sodium carbonate or sodium lactate. 3. The injection prepared by the preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: said β-lactam sodium salt is ampicillin sodium, cefotaxime sodium, cefoperazone sodium, cefuroxime sodium, cloxacillin sodium, azlocillin sodium, calumonam sodium, cloxacillin sodium, or cefpiramide sodium sterile powder. 4. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: firstly, 1 part of probenecid is dissolved in 75 parts of water in parts by mass Make a probenecid suspension, then add 1mol/L NaOH solution to the probenecid suspension to adjust the pH to 8 to react into a salt, then filter through a 0.22μm microporous membrane and sterilize at 150°C for 30min , and aseptic drying to obtain probenecid sodium; dissolving ampicillin sodium and obtained probenecid sodium in a mass ratio of 1:1 in 1 portion of infusion solution. 5. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: first, 8 parts of probenecid are dissolved in 80 parts of water according to the number of parts by mass Prepare probenecid suspension, then add 0.8mol/L sodium acetate solution to the probenecid suspension to adjust the pH to 9 to react into a salt, filter through a 0.45μm microporous membrane and sterilize at 200°C 30 minutes, and aseptically dried to obtain probenecid sodium; dissolve cefotaxime sodium and the obtained probenecid sodium in a mass ratio of 1:10 in 100 parts of infusion solution. 6. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: firstly, 5 parts of probenecid are dissolved in 50 parts of water according to the number of parts by mass Prepare probenecid suspension, then add 2.5mol/L sodium bicarbonate solution to the probenecid suspension to adjust the pH to 10 to react into a salt, filter through a 0.22μm microporous membrane and extinguish at 105°C sterilize for 30 minutes, and aseptically dry to obtain probenecid sodium; dissolve cefoperazone sodium and obtained probenecid sodium in a mass ratio of 10:1 and dissolve them in 80 parts of water. 7. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: firstly, 3 parts of probenecid are dissolved in 63 parts of water according to the number of parts by mass Prepare probenecid suspension, then add 0.8mol/L sodium carbonate solution to the probenecid suspension to adjust the pH to 10 to react into a salt, filter through a 0.45μm microporous membrane and sterilize at 160°C 30 minutes, and aseptically dried to obtain probenecid sodium; cefuroxime sodium and the obtained probenecid sodium were dissolved in 60 parts of water according to the mass ratio of 3:9. 8. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: firstly, 10 parts of probenecid are dissolved in 40 parts of water according to the number of parts by mass Prepare probenecid suspension, then add 2.5 mol/L sodium lactate solution to the probenecid suspension to adjust the pH to 7 to react into a salt, filter through a 0.45 μm microporous membrane, and then sterilize at 130°C for 30 minutes Probenecid sodium is obtained; cloxacillin sodium and the obtained probenecid sodium are dissolved in 40 parts of water according to the mass ratio of 6:5. 9. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: firstly, 1 part of probenecid is dissolved in 1 part of water in parts by mass Prepare probenecid suspension, then add 0.6mol/L sodium lactate solution to the probenecid suspension to adjust the pH to 7 to react into a salt, filter through a 0.22 μm microporous membrane and add 10 parts of anhydrous Precipitate the solid with ethanol, dry aseptically to obtain probenecid sodium; dissolve azlocillin sodium and the obtained probenecid sodium in a mass ratio of 9:2 and dissolve them in 50 parts of water. 10. The preparation method of compound β-lactam sodium salt/probenecid sodium for injection according to claim 1, characterized in that: firstly, 2 parts of probenecid are dissolved in 15 parts of water according to the number of parts by mass Make probenecid suspension solution, then add 0.1mol/L sodium carbonate solution in probenecid suspension solution to adjust pH to 10 and react to salt, add 50 parts of no Precipitate solids with water and acetone, and aseptically dry to obtain probenecid sodium; dissolve carumonan sodium and obtained probenecid sodium in a mass ratio of 7:4 and dissolve them in 15 parts of infusion solution.