Lattamoxef sodium injection and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a latamoxef sodium injection and a preparation method thereof. A modified hydroxypropyl methyl cellulose solution, a colloid solution and 3, 4-dihydroxyphenylalanine are mixed, the colloid solution is obtained through condensation reaction of histidine and ricinoleic acid under the emulsification effect of sucrose fatty acid ester, and the prepared stability-maintaining synergistic carrier matrix improves the acting effect of latamoxef sodium; the preparation method comprises the following steps: uniformly dispersing an anti-inflammatory, bacteriostatic and soothing solution into an emulsion solution formed by reaction of echinacea polysaccharide and octanoic acid, and freeze-drying to obtain the long-acting anti-inflammatory, bacteriostatic and soothing freeze-dried powder which can maintain the treatment effect for a long time; the latamoxef sodium nano-particles obtained after freezing nano spray drying are uniformly dispersed in a stability-maintaining basic solution, and the prepared latamoxef sodium nano-injection is high in stability, quick in drug effect, capable of playing a role for a long time and free of damage to an organism after being injected.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and specifically relates to an injection of latamoxef sodium and a preparation method thereof. Background Art

[0002] The main ingredient of latamoxef sodium injection is latamoxef sodium, a new type of semi-synthetic β-lactam broad-spectrum antibiotic. Its main mechanism of action is to bind to penicillin-binding proteins on the bacterial cell membrane, hindering the biosynthesis of the bacterial cell wall, making it impossible for the bacteria to maintain their normal morphology and divide and reproduce, ultimately leading to bacterial death. Latamoxef sodium has a strong antibacterial effect against Gram-negative bacteria and anaerobic bacteria.

[0003] Latamoxef Sodium Injection is mainly used to treat various infections caused by sensitive bacteria, such as sepsis, meningitis and other serious systemic infections, respiratory system infections, digestive system infections, intra-abdominal infections, urinary system and reproductive system infections, skin and soft tissue infections, bone and joint infections and trauma infections.

[0004] At present, the existing preparation technology of latamoxefox sodium injection has the following problems: first, during the preparation process of the existing latamoxefox sodium injection, the latamoxefox sodium is easily affected by moisture during the freeze-drying process, resulting in hydrolysis and opening of the β-lactam ring, which leads to reduced drug stability; second, during the preparation process of the existing latamoxefox sodium injection, the latamoxefox sodium produces a slow drug effect and has a low efficiency in exerting an antibacterial effect; third, during the long-term injection of the existing latamoxefox sodium injection, it will cause damage to the body, cause diarrhea, and damage the liver and kidneys. Summary of the invention

[0005] In view of the above situation, in order to overcome the defects of the prior art, the present invention provides an injection of latamoxefox sodium and a preparation method thereof. In order to solve the problems of low drug stability, slow drug efficacy, diarrhea caused by long-term injection, and damage to the liver and kidneys of the existing latamoxefox sodium injection, the present invention uses a stabilizing and synergistic carrier matrix to adsorb the latamoxefox sodium solution, and then mixes it with a stabilizing basic solution. The prepared nano injection of latamoxefox sodium has strong stability, fast drug efficacy, long-term effect, and does not cause damage to the body after injection.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows: the present invention provides an injection of latamoxef sodium, and the raw materials for preparing the injection of latamoxef sodium specifically include the following components in parts by weight: 1.5-2.5 parts of latamoxef sodium, 6-9 parts of stabilizing and enhancing carrier matrix, 2.8-4.7 parts of long-acting anti-inflammatory, antibacterial and soothing lyophilized powder, 0.5-0.9 parts of mannitol, 8-12 parts of 0.9% sodium chloride solution, and 0.8-1.4 parts of acetic acid-sodium acetate buffer; The pH value of the acetic acid-sodium acetate buffer is 6.0-7.0; The raw materials for preparing the stabilizing and synergistic carrier matrix include the following components in parts by weight: 3-5 parts of hydroxypropyl methylcellulose, 3.6-6.2 parts of adipic anhydride, 0.8-1.3 parts of N,N-dimethylaminopyridine, 1.2-1.4 parts of histidine, 1.3-1.7 parts of ricinoleic acid, 0.5-0.7 parts of sucrose fatty acid ester, and 0.4-0.8 parts of 3,4-dihydroxyphenylalanine; The raw materials for preparing the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder include the following components in parts by weight: 0.6-0.9 parts of paeoniflorin, 0.3-0.7 parts of sinomenine, 0.5-0.8 parts of kaempferol, 0.6-0.8 parts of shikonin, 1.4-1.8 parts of echinacea polysaccharide, and 2-3 parts of caprylic acid.

[0007] Preferably, the method for preparing the stabilizing and synergistic carrier matrix specifically comprises the following steps: S1. Put hydroxypropyl methylcellulose, adipic anhydride, N,N-dimethylaminopyridine and 50% ethanol solution into a reactor with a power of 2.2-2.4 kW, the reaction temperature is 60-70°C, the reaction time is 2.3-3.2 h, the reaction speed is 300-400 r / min, and an esterification reaction is carried out to obtain a modified hydroxypropyl methylcellulose solution; S2, putting histidine and ultrapure water into a stirrer with a power of 1.2-1.6 kW, stirring at a temperature of 25-30°C, stirring for 10-15 min, stirring at a speed of 120-140 r / min, fully dissolving to obtain a histidine solution; S3, placing the histidine solution prepared in S2, ricinoleic acid, and sucrose fatty acid ester into a constant temperature stirring tank with a power of 1.6-1.9 kW, the constant temperature stirring temperature is 120-130°C, the constant temperature stirring speed is 500 r / min, the constant temperature stirring time is 12-14 h, and the reaction is kept warm for 1.2-1.4 h to obtain a colloid solution; S4. Place the colloid solution prepared in S3, the hydroxypropyl methylcellulose solution prepared in S1, and 3,4-dihydroxyphenylalanine into a stirrer with a power of 1.2-1.6 kW, stir at a temperature of 32-37°C, stir for 20-30 min, and stir at a speed of 230-270 r / min to obtain a stabilizing and synergistic carrier matrix.

[0008] Furthermore, in S1, the mass fraction of the hydroxypropyl methylcellulose in the 50% ethanol solution is 5%.

[0009] Furthermore, in S2, the mass fraction of histidine in ultrapure water is 4%.

[0010] Preferably, the method for preparing the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder specifically comprises the following steps: L1. Place paeoniflorin, sinomenine, kaempferol, shikonin and 70% ethanol solution into a stirrer with a power of 1.2-1.6 kW, stir at a temperature of 28-35°C, for 15-22 min, at a stirring speed of 330-380 r / min, and stir to dissolve to obtain an anti-inflammatory, antibacterial and soothing solution; L2, placing Echinacea polysaccharide and ultrapure water in a stirrer with a power of 1.2-1.6 kW, stirring at a temperature of 60-85°C, stirring for 15-22 min, stirring at a speed of 330-380 r / min, stirring to dissolve, and obtaining an Echinacea polysaccharide solution; L3, put the Echinacea polysaccharide solution prepared in L2, caprylic acid and chloroform into a reactor with a power of 2.2-2.4 kW, the reaction temperature is 85°C, the reaction time is 1.5-1.8 h, the reaction speed is 350-390 r / min, the temperature is raised to 160°C and the heating is stopped, and the stirring is continued and cooled to 100°C. After the reaction, the temperature is kept at 85°C for 24 h to obtain an emulsion solution; L4, the anti-inflammatory and antibacterial soothing solution prepared in L1 is mixed with the emulsion solution prepared in L3, and the mixture is placed in an ultrasonic stirrer with a power of 1.8-2.5 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20000 r / min, a stirring temperature of 25-30°C, and a stirring time of 10-15 min to obtain a long-acting anti-inflammatory and antibacterial soothing suspension; L5. Place the long-acting anti-inflammatory, antibacterial and soothing suspension prepared in L4 into a freeze dryer with a power of 1.6-2.2 kW, the freeze drying pressure is 300 Pa, the reduced pressure drying temperature is -45°C, freeze drying for 12 h, heat to -25°C and freeze drying for 8 h, then freeze drying at 15°C for 5 h to obtain a long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder.

[0011] Furthermore, in L1, the mass fraction of the paeoniflorin in the 70% ethanol solution is 16-21%.

[0012] Furthermore, in L2, the mass fraction of the Echinacea polysaccharide in ultrapure water is 18-23%.

[0013] Furthermore, in L3, the mass fraction of the octanoic acid in chloroform is 20-24%.

[0014] The present invention also provides a method for preparing an injection of latamoxefox sodium, which specifically comprises the following steps: Step 1: Put 0.9% sodium chloride solution, mannitol, and long-acting anti-inflammatory and antibacterial soothing freeze-dried powder into a stirrer with a power of 1.2-1.6 kW, stir at a temperature of 20-28°C, stir for 25-30 min, and stir at a speed of 120-150 r / min, and fully dissolve to obtain a stabilizing basic solution; Step 2, placing latamoxef sodium and ultrapure water in a stirrer with a power of 1.2-1.6 kW, stirring at a temperature of 26-30° C., stirring for 18-22 min, stirring at a speed of 320-340 r / min, and stirring to dissolve to obtain a latamoxef sodium solution; Step 3, placing the stabilization and synergistic carrier matrix into the latamoxef sodium solution prepared in step 2, stirring at a temperature of 28-35°C, stirring for 25-35 min, stirring at a speed of 350-400 r / min, and after sufficient adsorption, placing in a vacuum freeze nano spray dryer with a power of 2.3 kW, a vacuum degree of -0.05 MPa, a freeze nano spray drying temperature of -40°C, a freeze nano spray drying particle size of 100 nm, and a freeze nano spray drying time of 2.5 h to obtain latamoxef sodium nanoparticles; Step 4: Place the latamoxef sodium nanoparticles prepared in step 3 and the stabilization basic solution prepared in step 1 in a stirrer with a power of 1.2-1.6 kW, the stirring temperature is 20-28 ° C, the stirring time is 18-26 min, the stirring speed is 100-130 r / min, and after stirring and mixing, add acetic acid-sodium acetate buffer to adjust the pH value to 6.0-7.0, and filter using a 0.22 mm sterile filter membrane to obtain a nano injection of latamoxef sodium.

[0015] Preferably, in step 2, the mass fraction of latamoxef sodium in ultrapure water is 25%.

[0016] The beneficial effects achieved by the present invention are as follows: The present invention adopts hydroxypropyl methylcellulose and adipic anhydride to be dissolved in a 50% ethanol solution. The molecular chain of hydroxypropyl methylcellulose contains hydroxyl groups. Under the catalytic action of N,N-dimethylaminopyridine, the hydroxyl groups and the acyl groups of adipic anhydride undergo nucleophilic substitution reaction to form new ester bonds. After the reaction, the modified hydroxypropyl methylcellulose with high solubility, toughness and strong water absorption is obtained, which can absorb free water. After the histidine solution is mixed with ricinoleic acid and sucrose fatty acid ester, the amino group in the histidine can undergo condensation reaction with the carboxyl group in the ricinoleic acid to form an amide bond. Under the emulsification of sugar fatty acid ester, the viscosity of the system is increased to obtain a colloid with rich pores. The colloid solution is mixed with modified hydroxypropyl methylcellulose solution and 3,4-dihydroxyphenylalanine. Histidine contains a negative charge that can bind to the positive charge on the surface of the bacterial cell wall, and 3,4-dihydroxyphenylalanine can adhere to the peptidoglycan on the cell wall. The prepared stabilizing and synergistic carrier matrix can make latamoxefox sodium more efficiently bind to the penicillin binding protein on the bacterial cell membrane, thereby maintaining the stability of latamoxefox sodium during processing and in vivo transportation. Peony root and penicillin are added to the mixture. The anti-inflammatory and antibacterial soothing solution prepared by dissolving kaempferol, kaempferol and shikonin in 70% ethanol solution has the effects of anti-oxidation, antibacterial and anti-allergy, and can prevent abdominal pain and diarrhea, and repair damaged liver and kidney. Caprylic acid can promote cell permeation. The anti-inflammatory and antibacterial soothing solution is added to the emulsion prepared by the reaction of Echinacea polysaccharide solution and caprylic acid, and the solution is freeze-dried. The long-acting anti-inflammatory and antibacterial soothing freeze-dried powder can prolong the time of the effective components in the anti-inflammatory and antibacterial soothing solution acting in the blood, and can repair the tissues damaged by bacterial infection in a long-term manner, and maintain the efficacy of latamoxefactoside sodium. Therapeutic effect: The latamoxefox sodium solution is fully adsorbed on the stabilizing and synergistic carrier matrix, and after freeze-nano spray drying, the obtained latamoxefox sodium nanoparticles are uniformly dispersed in a stabilizing basic solution containing 0.9% sodium chloride solution, mannitol, and long-acting anti-inflammatory and antibacterial soothing lyophilized powder, and the pH value is adjusted and filtered. The obtained nano-injection of latamoxefox sodium has a fast efficacy, strong stability of latamoxefox sodium during preparation and in vivo function, high bioavailability, no dependence after stopping injection, long-term maintenance of therapeutic effect, and no damage to the body after injection. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the present invention or the technical solutions in the prior art, the following will be described in a clear and understandable manner in conjunction with the accompanying drawings. Obviously, the drawings described below are only for the present invention, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0018] Figure 1 This is a scanning electron microscope image of the internal structure of the stabilizing and synergistic carrier matrix described in Example 1 of the present invention; Figure 2This is a result diagram of the diameter of the inhibition zone of Escherichia coli described in Experimental Example 1 of the present invention; Figure 3 This is a graph showing the diameter of the inhibition zone of Salmonella described in Experimental Example 1 of the present invention; Figure 4 This is a graph showing the results of the rat organ index described in Experimental Example 2 of the present invention. DETAILED DESCRIPTION

[0019] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments; based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0020] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein may be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and are not intended to limit the content of this application.

[0021] The experimental methods in the following examples are conventional methods unless otherwise specified; the experimental materials and test strains used in the following examples are purchased from commercial channels unless otherwise specified.

[0022] Example 1: This example provides an injection of latamoxef sodium and a preparation method thereof. The injection of latamoxef sodium comprises the following components in parts by weight: 1.5 parts of latamoxef sodium, 6 parts of stabilizing and enhancing carrier matrix, 2.8 parts of long-acting anti-inflammatory, antibacterial and soothing lyophilized powder, 0.5 parts of mannitol, 8 parts of 0.9% sodium chloride solution, and 0.8 parts of acetic acid-sodium acetate buffer; The pH value of the acetic acid-sodium acetate buffer is 6.0; The raw materials for preparing the stabilizing and enhancing carrier matrix include the following components in parts by weight: 3 parts of hydroxypropyl methylcellulose, 3.6 parts of adipic anhydride, 0.8 parts of N,N-dimethylaminopyridine, 1.2 parts of histidine, 1.3 parts of ricinoleic acid, 0.5 parts of sucrose fatty acid ester, and 0.4 parts of 3,4-dihydroxyphenylalanine; The raw materials for preparing the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder include the following components in parts by weight: 0.6 parts of paeoniflorin, 0.3 parts of sinomenine, 0.5 parts of kaempferol, 0.6 parts of shikonin, 1.4 parts of echinacea polysaccharide, and 2 parts of caprylic acid.

[0023] The preparation method of the stabilizing and synergistic carrier matrix specifically comprises the following steps: S1. Put hydroxypropyl methylcellulose, adipic anhydride, N,N-dimethylaminopyridine and 50% ethanol solution into a reactor with a power of 2.2 kW, the reaction temperature is 60°C, the reaction time is 2.3 h, the reaction speed is 300 r / min, and an esterification reaction is carried out to obtain a modified hydroxypropyl methylcellulose solution; S2, put histidine and ultrapure water into a stirrer with a power of 1.2 kW, stir at a temperature of 25°C, stir for 10 min, and stir at a speed of 120 r / min, fully dissolve to obtain a histidine solution; S3, the histidine solution prepared in S2, ricinoleic acid, and sucrose fatty acid ester were placed in a constant temperature stirring tank with a power of 1.6 kW, the constant temperature stirring temperature was 120°C, the constant temperature stirring speed was 500 r / min, the constant temperature stirring time was 12 h, and the reaction was kept warm for 1.2 h to obtain a colloidal solution; S4. Put the colloid solution prepared by S3, the hydroxypropyl methylcellulose solution prepared by S1, and 3,4-dihydroxyphenylalanine into a stirrer with a power of 1.2 kW. The stirring temperature is 32°C, the stirring time is 20 min, and the stirring speed is 230 r / min. Stir and mix to obtain a stabilizing and synergistic carrier matrix.

[0024] In S1, the mass fraction of the hydroxypropyl methylcellulose in the 50% ethanol solution is 5%.

[0025] In S2, the mass fraction of histidine in ultrapure water is 4%.

[0026] The preparation method of the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder specifically comprises the following steps: L1. Put paeoniflorin, sinomenine, kaempferol, shikonin and 70% ethanol solution into a 1.2 kW stirrer at a stirring temperature of 28°C for 15 min at a stirring speed of 330 r / min, and stir to dissolve to obtain an anti-inflammatory, antibacterial and soothing solution; L2, put Echinacea polysaccharide and ultrapure water into a stirrer with a power of 1.2 kW, stir at a temperature of 60°C, stir for 15 min, stir at a speed of 330 r / min, stir and dissolve to obtain an Echinacea polysaccharide solution; L3, put the Echinacea polysaccharide solution prepared in L2, caprylic acid and chloroform into a reactor with a power of 2.2 kW, the reaction temperature is 85°C, the reaction time is 1.5 h, the reaction speed is 350 r / min, the temperature is raised to 160°C and the heating is stopped, and the stirring is continued and cooled to 100°C. After the reaction, the temperature is kept at 85°C for 24 h to obtain an emulsion solution; L4, the anti-inflammatory and antibacterial soothing solution prepared in L1 and the emulsion solution prepared in L3 were mixed, and the mixture was placed in an ultrasonic stirrer with a power of 1.8 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min to obtain a long-acting anti-inflammatory and antibacterial soothing suspension; L5. Place the long-acting anti-inflammatory, antibacterial and soothing suspension prepared in L4 into a freeze dryer with a power of 1.6 kW, the freeze drying pressure is 300 Pa, the reduced pressure drying temperature is -45°C, freeze drying for 12 h, heat to -25°C and freeze drying for 8 h, then freeze drying at 15°C for 5 h to obtain a long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder.

[0027] In L1, the mass fraction of the paeoniflorin in the 70% ethanol solution is 16%.

[0028] In L2, the mass fraction of the Echinacea polysaccharide in ultrapure water is 18%.

[0029] In L3, the mass fraction of octanoic acid in chloroform is 20%.

[0030] This embodiment also provides a method for preparing an injection of latamoxef sodium, which specifically comprises the following steps: Step 1: Put 0.9% sodium chloride solution, mannitol, and long-acting anti-inflammatory and antibacterial soothing freeze-dried powder into a 1.2kW stirrer at a stirring temperature of 20°C, a stirring time of 25 min, and a stirring speed of 120 r / min, and fully dissolve to obtain a stabilizing basic solution; Step 2, putting latamoxef sodium and ultrapure water into a stirrer with a power of 1.2 kW, stirring at a temperature of 26° C., stirring for 18 min, stirring at a speed of 320 r / min, and stirring to dissolve to obtain a latamoxef sodium solution; Step 3, placing the stabilization and synergistic carrier matrix into the latamoxefox sodium solution prepared in step 2, stirring at a temperature of 28 ° C, stirring for 25 min, stirring at a speed of 350 r / min, and after sufficient adsorption, placing it in a vacuum freeze nano spray dryer with a power of 2.3 kW, a vacuum degree of -0.05 MPa, a freeze nano spray drying temperature of -40 ° C, a freeze nano spray drying particle size of 100 nm, and a freeze nano spray drying time of 2.5 h to obtain latamoxefox sodium nanoparticles; Step 4: Place the latamoxef sodium nanoparticles prepared in step 3 and the stabilizing basic solution prepared in step 1 in a stirrer with a power of 1.2 kW, the stirring temperature is 20 ° C, the stirring time is 18 min, the stirring speed is 100 r / min, and after stirring and mixing, add acetic acid-sodium acetate buffer to adjust the pH value to 6.0, and filter using a 0.22 mm sterile filter membrane to obtain a nano injection of latamoxef sodium.

[0031] In step 2, the mass fraction of latamoxef sodium in ultrapure water is 25%.

[0032] Example 2: This example provides an injection of latamoxef sodium and a preparation method thereof. The nano injection of latamoxef sodium comprises the following components in parts by weight: 2 parts of latamoxef sodium, 7 parts of stabilizing and enhancing carrier matrix, 3.2 parts of long-acting anti-inflammatory, antibacterial and soothing lyophilized powder, 0.6 parts of mannitol, 10 parts of 0.9% sodium chloride solution, and 1 part of acetic acid-sodium acetate buffer; The pH value of the acetic acid-sodium acetate buffer is 6.5; The raw materials for preparing the stabilizing and enhancing carrier matrix include the following components in parts by weight: 4 parts of hydroxypropyl methylcellulose, 5.3 parts of adipic anhydride, 1 part of N,N-dimethylaminopyridine, 1.3 parts of histidine, 1.5 parts of ricinoleic acid, 0.6 parts of sucrose fatty acid ester, and 0.6 parts of 3,4-dihydroxyphenylalanine; The raw materials for preparing the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder include the following components in parts by weight: 0.7 parts of paeoniflorin, 0.5 parts of sinomenine, 0.6 parts of kaempferol, 0.7 parts of shikonin, 1.6 parts of echinacea polysaccharide, and 2.5 parts of caprylic acid.

[0033] The preparation method of the stabilizing and synergistic carrier matrix specifically comprises the following steps: S1. Put hydroxypropyl methylcellulose, adipic anhydride, N,N-dimethylaminopyridine and 50% ethanol solution into a reactor with a power of 2.3 kW, the reaction temperature is 65°C, the reaction time is 3 h, the reaction speed is 300 r / min, and an esterification reaction is carried out to obtain a modified hydroxypropyl methylcellulose solution; S2, put histidine and ultrapure water into a stirrer with a power of 1.4 kW, stir at a temperature of 28°C, stir for 13 min, and stir at a speed of 130 r / min, fully dissolve to obtain a histidine solution; S3, the histidine solution prepared in S2, ricinoleic acid, and sucrose fatty acid ester were placed in a constant temperature stirring tank with a power of 1.7 kW, the constant temperature stirring temperature was 120°C, the constant temperature stirring speed was 500 r / min, the constant temperature stirring time was 13 h, and the reaction was kept warm for 1.3 h to obtain a colloidal solution; S4. Put the colloid solution prepared by S3, the hydroxypropyl methylcellulose solution prepared by S1, and 3,4-dihydroxyphenylalanine into a stirrer with a power of 1.4 kW. Stir at a temperature of 34°C, for 25 min, at a speed of 250 r / min, and stir to obtain a stabilizing and synergistic carrier matrix.

[0034] In S1, the mass fraction of the hydroxypropyl methylcellulose in the 50% ethanol solution is 5%.

[0035] In S2, the mass fraction of histidine in ultrapure water is 4%.

[0036] The preparation method of the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder specifically comprises the following steps: L1. Put paeoniflorin, sinomenine, kaempferol, shikonin and 70% ethanol solution into a 1.4 kW stirrer at a stirring temperature of 32°C, a stirring time of 18 min, and a stirring speed of 360 r / min, and stir to dissolve to obtain an anti-inflammatory, antibacterial and soothing solution; L2, put Echinacea polysaccharide and ultrapure water into a stirrer with a power of 1.4 kW, stir at a temperature of 75°C, stir for 18 min, stir at a speed of 360 r / min, stir and dissolve to obtain an Echinacea polysaccharide solution; L3, put the Echinacea polysaccharide solution prepared in L2, caprylic acid and chloroform into a reactor with a power of 2.3 kW, the reaction temperature is 85°C, the reaction time is 1.6 h, the reaction speed is 370 r / min, the temperature is raised to 160°C and the heating is stopped, and the mixture is cooled to 100°C with continued stirring. After the reaction, the mixture is kept at 85°C for 24 h to obtain an emulsion solution; L4, the anti-inflammatory and antibacterial soothing solution prepared in L1 and the emulsion solution prepared in L3 were mixed, and the mixture was placed in an ultrasonic stirrer with a power of 2.2 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 28°C, and a stirring time of 13 min to obtain a long-acting anti-inflammatory and antibacterial soothing suspension; L5. Place the long-acting anti-inflammatory, antibacterial and soothing suspension prepared in L4 into a freeze dryer with a power of 1.9 kW, the freeze drying pressure is 300 Pa, the reduced pressure drying temperature is -45°C, freeze drying for 12 h, heat to -25°C and freeze drying for 8 h, then freeze drying at 15°C for 5 h to obtain a long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder.

[0037] In L1, the mass fraction of the paeoniflorin in the 70% ethanol solution is 19%.

[0038] In L2, the mass fraction of the Echinacea polysaccharide in ultrapure water is 20%.

[0039] In L3, the mass fraction of octanoic acid in chloroform is 22%.

[0040] This embodiment also provides a method for preparing an injection of latamoxef sodium, which specifically comprises the following steps: Step 1: Put 0.9% sodium chloride solution, mannitol, and long-acting anti-inflammatory and antibacterial soothing freeze-dried powder into a 1.4kW stirrer at a stirring temperature of 25°C, a stirring time of 27 min, and a stirring speed of 130 r / min, and fully dissolve to obtain a stabilizing basic solution; Step 2, putting latamoxef sodium and ultrapure water into a stirrer with a power of 1.4 kW, stirring at a temperature of 28° C., stirring for 20 min, stirring at a speed of 330 r / min, and stirring to dissolve to obtain a latamoxef sodium solution; Step 3, placing the stabilization and synergistic carrier matrix into the latamoxef sodium solution prepared in step 2, stirring at a temperature of 32 ° C, stirring for 30 min, stirring at a speed of 380 r / min, and after sufficient adsorption, placing it in a vacuum freeze nano spray dryer with a power of 2.3 kW, a vacuum degree of -0.05 MPa, a freeze nano spray drying temperature of -40 ° C, a freeze nano spray drying particle size of 100 nm, and a freeze nano spray drying time of 2.5 h to obtain latamoxef sodium nanoparticles; Step 4: Place the latamoxef sodium nanoparticles prepared in step 3 and the stabilization basic solution prepared in step 1 in a stirrer with a power of 1.5 kW, the stirring temperature is 25 ° C, the stirring time is 22 min, the stirring speed is 120 r / min, and after stirring and mixing, add acetic acid-sodium acetate buffer to adjust the pH value to 6.5, and filter using a 0.22 mm sterile filter membrane to obtain a nano injection of latamoxef sodium.

[0041] In step 2, the mass fraction of latamoxef sodium in ultrapure water is 25%.

[0042] Example 3: This example provides a nano injection of latamoxef sodium and a preparation method thereof. The nano injection of latamoxef sodium comprises the following components in parts by weight: 2.5 parts of latamoxef sodium, 9 parts of stabilizing and enhancing carrier matrix, 4.7 parts of long-acting anti-inflammatory, antibacterial and soothing lyophilized powder, 0.9 parts of mannitol, 12 parts of 0.9% sodium chloride solution, and 1.4 parts of acetic acid-sodium acetate buffer; The pH value of the acetic acid-sodium acetate buffer is 7.0; The raw materials for preparing the stabilizing and enhancing carrier matrix include the following components in parts by weight: 5 parts of hydroxypropyl methylcellulose, 6.2 parts of adipic anhydride, 1.3 parts of N,N-dimethylaminopyridine, 1.4 parts of histidine, 1.7 parts of ricinoleic acid, 0.7 parts of sucrose fatty acid ester, and 0.8 parts of 3,4-dihydroxyphenylalanine; The raw materials for preparing the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder include the following components in parts by weight: 0.9 parts of paeoniflorin, 0.7 parts of sinomenine, 0.8 parts of kaempferol, 0.8 parts of shikonin, 1.8 parts of echinacea polysaccharide, and 3 parts of caprylic acid.

[0043] The preparation method of the stabilizing and synergistic carrier matrix specifically comprises the following steps: S1. Put hydroxypropyl methylcellulose, adipic anhydride, N,N-dimethylaminopyridine and 50% ethanol solution into a reactor with a power of 2.4 kW, the reaction temperature is 70°C, the reaction time is 3.2 h, the reaction speed is 400 r / min, and an esterification reaction is carried out to obtain a modified hydroxypropyl methylcellulose solution; S2, put histidine and ultrapure water into a stirrer with a power of 1.6 kW, stir at a temperature of 30°C, stir for 15 min, and stir at a speed of 140 r / min, fully dissolve to obtain a histidine solution; S3, the histidine solution prepared in S2, ricinoleic acid, and sucrose fatty acid ester were placed in a constant temperature stirring tank with a power of 1.9 kW, the constant temperature stirring temperature was 130°C, the constant temperature stirring speed was 500 r / min, the constant temperature stirring time was 14 h, and the reaction was kept warm for 1.4 h to obtain a colloidal solution; S4. Put the colloid solution prepared by S3, the hydroxypropyl methylcellulose solution prepared by S1, and 3,4-dihydroxyphenylalanine into a stirrer with a power of 1.6 kW. The stirring temperature is 37°C, the stirring time is 30 min, and the stirring speed is 270 r / min. Stir and mix to obtain a stabilizing and synergistic carrier matrix.

[0044] In S1, the mass fraction of the hydroxypropyl methylcellulose in the 50% ethanol solution is 5%.

[0045] In S2, the mass fraction of histidine in ultrapure water is 4%.

[0046] The preparation method of the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder specifically comprises the following steps: L1. Put paeoniflorin, sinomenine, kaempferol, shikonin and 70% ethanol solution into a 1.6 kW stirrer at a stirring temperature of 35°C, a stirring time of 22 min, and a stirring speed of 380 r / min, and stir to dissolve to obtain an anti-inflammatory, antibacterial and soothing solution; L2, placing Echinacea polysaccharide and ultrapure water in a stirrer with a power of 1.6 kW, stirring at a temperature of 85°C, a stirring time of 22 min, a stirring speed of 380 r / min, stirring and dissolving to obtain an Echinacea polysaccharide solution; L3, put the Echinacea polysaccharide solution prepared in L2, caprylic acid and chloroform into a reactor with a power of 2.4 kW, the reaction temperature is 85°C, the reaction time is 1.8 h, the reaction speed is 390 r / min, the temperature is raised to 160°C and the heating is stopped, and the mixture is cooled to 100°C with continued stirring. After the reaction, the mixture is kept at 85°C for 24 h to obtain an emulsion solution; L4, the anti-inflammatory and antibacterial soothing solution prepared in L1 and the emulsion solution prepared in L3 were mixed, and the mixture was placed in an ultrasonic stirrer with a power of 2.5 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 30°C, and a stirring time of 15 min to obtain a long-acting anti-inflammatory and antibacterial soothing suspension; L5. Place the long-acting anti-inflammatory, antibacterial and soothing suspension prepared in L4 into a freeze dryer with a power of 2.2 kW, the freeze drying pressure is 300 Pa, the reduced pressure drying temperature is -45°C, freeze drying for 12 h, heat to -25°C and freeze drying for 8 h, then freeze drying at 15°C for 5 h to obtain a long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder.

[0047] In L1, the mass fraction of the paeoniflorin in the 70% ethanol solution is 21%.

[0048] In L2, the mass fraction of the Echinacea polysaccharide in ultrapure water is 23%.

[0049] In L3, the mass fraction of octanoic acid in chloroform is 24%.

[0050] This embodiment also provides a method for preparing an injection of latamoxef sodium, which specifically comprises the following steps: Step 1: Put 0.9% sodium chloride solution, mannitol, and long-acting anti-inflammatory and antibacterial soothing freeze-dried powder into a 1.6kW stirrer at a stirring temperature of 28°C for 30 min at a stirring speed of 150 r / min, and fully dissolve to obtain a stabilizing basic solution; Step 2, putting latamoxef sodium and ultrapure water into a stirrer with a power of 1.6 kW, stirring at a temperature of 30° C., stirring for 22 min, stirring at a speed of 340 r / min, and stirring to dissolve to obtain a latamoxef sodium solution; Step 3, placing the stabilization and synergistic carrier matrix into the latamoxefox sodium solution prepared in step 2, stirring at a temperature of 35 ° C, stirring for 35 min, stirring at a speed of 400 r / min, and after sufficient adsorption, placing it in a vacuum freeze nano spray dryer with a power of 2.3 kW, a vacuum degree of -0.05 MPa, a freeze nano spray drying temperature of -40 ° C, a freeze nano spray drying particle size of 100 nm, and a freeze nano spray drying time of 2.5 h to obtain latamoxefox sodium nanoparticles; Step 4: Place the latamoxef sodium nanoparticles prepared in step 3 and the stabilizing basic solution prepared in step 1 in a stirrer with a power of 1.6 kW, the stirring temperature is 28 ° C, the stirring time is 26 min, the stirring speed is 130 r / min, and after stirring and mixing, add acetic acid-sodium acetate buffer to adjust the pH value to 7.0, and filter using a 0.22 mm sterile filter membrane to obtain a nano injection of latamoxef sodium.

[0051] In step 2, the mass fraction of latamoxef sodium in ultrapure water is 25%.

[0052] Comparative Example 1: This comparative example provides a latamoxefox sodium injection and a preparation method thereof, which is different from Example 1 only in that the added stabilizing and synergistic carrier matrix does not contain a colloid solution, and the remaining components, component contents, and method steps are the same as those in Example 1.

[0053] Comparative Example 2: This comparative example provides a latamoxefox sodium injection and a preparation method thereof, which is different from Example 1 only in that the added anti-inflammatory and antibacterial soothing suspension does not contain an anti-inflammatory and antibacterial soothing solution, and the remaining components, component contents, and method steps are the same as those in Example 1.

[0054] Experimental Example 1: Drug efficacy stability determination test.

[0055] The steps of the drug efficacy determination test of the injection of latamoxef sodium prepared in Examples 1-3 of the present invention are as follows: (1) The nanometer injection of latamoxef sodium prepared in Example 1-3, the latamoxef sodium injection prepared in Comparative Example 1-2, and the commercially available latamoxef sodium injection in the control group (purchased from Zhejiang Huidisen Pharmaceutical Co., Ltd., prepared by mixing 1.5 g of latamoxef sodium for injection with 8 mL of 0.9% sodium chloride solution) were measured by using a paper diffusion method. At 35°C, each group of injections was incubated with Escherichia coli and Salmonella for 18 h. The diameters of the inhibition zones produced by Escherichia coli and Salmonella were measured. Three parallels were set for each group, and the average values ​​were recorded. (2) The nano-injection of latamoxef sodium prepared in Example 1-3, the latamoxef sodium injection prepared in Comparative Example 1-2, and the commercially available latamoxef sodium injection in the control group (purchased from Zhejiang Huidisen Pharmaceutical Co., Ltd., prepared by mixing 1.5 g of latamoxef sodium for injection with 8 mL of 0.9% sodium chloride solution) were placed at high temperature of 60°C and light of 4500Lx for 2 days, and then the paper diffusion method was used again to determine the diameter of the inhibition zone produced by each group of injections against Escherichia coli and Salmonella after incubation for 18 hours at 35°C. Three parallels were set for each group, and the average value was recorded. Effect judgment: the inhibition zone diameter ≥ 20mm is extremely sensitive; 20mm>inhibition zone diameter ≥ 15mm is highly sensitive; 15mm>inhibition zone diameter ≥ 10mm is moderately sensitive; the inhibition zone diameter < 10mm is lowly sensitive or ineffective.

[0056] Result analysis: Figure 1 This is a scanning electron microscope image of the internal structure of the stabilization and synergistic carrier matrix described in Example 1 of the present invention. Figure 2 This is a result diagram of the diameter of the inhibition zone of Escherichia coli described in Experimental Example 1 of the present invention. As shown in the figure, the nano-injection of latamoxef sodium prepared in Examples 1-3 was incubated with Escherichia coli for 18 h at 35°C by the paper diffusion method. The diameters of the inhibition zones of Escherichia coli were 20.68 mm, 21.44 mm, and 22.54 mm, respectively. After being placed at a high temperature of 60°C and an illumination of 4500Lx for 2 d, the measurement was performed again. The diameters of the inhibition zones of Escherichia coli were 20.17 mm, 21.06 mm, and 22.11 mm, respectively. The latamoxef sodium injection prepared in Comparative Example 1 was incubated with Escherichia coli for 18 h at 35°C by the paper diffusion method. The diameters of the inhibition zones of Escherichia coli were 18.37 mm, and the diameters of the inhibition zones of Escherichia coli were placed at a high temperature of 60°C and an illumination of 4500Lx for 2 d. d later, the measurement was performed again, and the diameter of the inhibition zone for Escherichia coli was 17.25 mm. The prepared latamoxef sodium injection of comparative example 2 was incubated with Escherichia coli for 18 h at 35°C by the disc diffusion method, and the diameter of the inhibition zone for Escherichia coli was 20.3 mm. After being placed at high temperature of 60°C and 4500Lx for 2 d, the measurement was performed again, and the diameter of the inhibition zone for Escherichia coli was 20.11 mm. The commercially available latamoxef sodium injection of the control group was incubated with Escherichia coli for 18 h at 35°C by the disc diffusion method, and the diameter of the inhibition zone for Escherichia coli was 17.51 ​​mm. After being placed at high temperature of 60°C and 4500Lx for 2 d, the measurement was performed again, and the diameter of the inhibition zone for Escherichia coli was 12.34 mm. Figure 3The result diagram of the Salmonella inhibition zone diameter of Experimental Example 1 of the present invention is as follows. The nanometer injection of latamoxef sodium prepared in Examples 1-3 was incubated with Salmonella for 18 h at 35°C by the disc diffusion method. The diameters of the inhibition zones of Salmonella were 21.51 mm, 22.58 mm, and 23.57 mm, respectively. After being placed at a high temperature of 60°C and an illumination of 4500Lx for 2 d, the diameters of the inhibition zones of Salmonella were 21.01 mm, 22.09 mm, and 23.05 mm, respectively. The latamoxef sodium injection prepared in Comparative Example 1 was incubated with Salmonella for 18 h at 35°C by the disc diffusion method. The diameters of the inhibition zones of Salmonella were 20.23 mm. After being placed at a high temperature of 60°C and an illumination of 4500Lx for 2 d, the diameters of the inhibition zones of Salmonella were 18.91 mm, respectively. mm, the prepared latamoxef sodium injection in comparative example 2 was incubated with Salmonella for 18 h at 35°C using the disc diffusion method, and the diameter of the inhibition zone for Salmonella was 21.16 mm. After being placed at high temperature of 60°C and 4500Lx for 2 days, the inhibition zone diameter for Salmonella was measured again, and the diameter of the inhibition zone for Salmonella was 20.82 mm. The commercially available latamoxef sodium injection in the control group was incubated with Salmonella for 18 h at 35°C using the disc diffusion method, and the diameter of the inhibition zone for Salmonella was 18.16 mm. After being placed at high temperature of 60°C and 4500Lx for 2 days, the inhibition zone diameter for Salmonella was measured again, and the diameter of the inhibition zone for Salmonella was 13.14 mm, indicating that the nano injection of latamoxef sodium prepared by the present invention is extremely sensitive to Escherichia coli and Salmonella, produces a rapid drug effect, has strong stability of the effective components in the process of exerting its effect in the body, has high bioavailability, and exerts its effect for a long time.

[0057] Experimental Example 2: Irritation measurement test.

[0058] The irritation test steps of the nano injection of latamoxef sodium prepared in Examples 1-3 of the present invention are as follows: (1) Sixty male SD rats, each weighing 220 g (purchased from Chengdu Dashuo Animal Co., Ltd.), were randomly divided into six groups of 10 rats. The rats were housed in separate cages, which were kept clean and dry at a temperature of 24°C and a humidity of 50%. The rats were fed with free access to food and water. (2) The nano-injection of latamoxef sodium prepared in Example 1-3 was used to inject the rats in Example 1-3, once a day, 1.5 mL each time for 15 days; the latamoxef sodium injection prepared in Comparative Example 1-2 was used to inject the rats in Comparative Example 1-2, once a day, 1.5 mL each time for 15 days; the commercially available latamoxef sodium injection (purchased from Zhejiang Huidisen Pharmaceutical Co., Ltd., prepared by mixing 1.5 g of latamoxef sodium for injection with 8 mL of 0.9% sodium chloride solution) was used to inject the rats as the control group, once a day, 1.5 mL each time for 15 days; the diarrhea rate of the rats on the 15th day was observed and recorded, and the average value was taken. The diarrhea rate of the rats was calculated according to the formula, rat diarrhea rate (%) = number of rats with diarrhea in each group / total number of rats in each group × 100%; (3) Rats were killed by cervical dislocation. The kidneys and livers were separated and rinsed with 0.9% saline. The surface moisture was then dried with filter paper and weighed immediately. The organ index (%) = weight of a certain organ / rat body weight × 100%. An increase in the organ index indicated organ congestion, edema, or hyperplasia, while a decrease in the organ index indicated organ atrophy and other degenerative changes. The results were recorded.

[0059] Table 1. Diarrhea rate determination table of rats

[0060] Results Analysis Figure 4 This is the rat organ index result diagram described in Experimental Example 2 of the present invention, as shown in Figure 2As shown in Table 1, the nano-injection of latamoxef sodium prepared in Examples 1-3 was used to inject rats in Groups 1-3 of Examples, once a day, 1.5 mL each time for 15 consecutive days. The liver indexes of rats in Groups 1-3 of Examples were 0.45, 0.54, and 0.54, respectively, and the kidney indexes were 1.04, 1.07, and 1.10, respectively. The latamoxef sodium injection prepared in Comparative Example 1 was used to inject rats in Group 1 of Comparative Example 1, once a day, 1.5 mL each time for 15 consecutive days. The liver index of rats in Group 1 of Comparative Example 1 was 0.43, and the kidney index was 1.01. The latamoxef sodium injection prepared in Comparative Example 2 was used to inject rats in Group 2 of Comparative Example 2, once a day, 1.5 mL each time for 15 consecutive days. The liver index of rats in Group 2 of Comparative Example 2 was 0.72, and the kidney index was 1.09. The commercially available latamoxef sodium injection was used to inject rats as a control group, once a day, 1.5 mL each time. mL was continuously injected for 15 d, the liver index of the rats in the control group was 0.83, and the kidney index was 1.42. The liver index and kidney index of the rats in the control group and the comparative example 2 group were higher, and the diarrhea rates of the rats in the Example 1-3 groups and the comparative example 1 group were 0% after continuous injection for 15 d, indicating that the nano injection of latamoxef sodium prepared by the present invention does not cause damage to the body after long-term injection, and effectively repairs liver and kidney damage caused by bacterial infection.

[0061] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

[0062] The present invention and its implementation methods are described above, which is not restrictive. The drawings are only one of the implementation methods of the present invention, and the actual application is not limited thereto. In short, if ordinary technicians in the field are inspired by it and design methods and embodiments similar to the technical solution without creativity without departing from the purpose of the invention, they should all fall within the protection scope of the present invention.

Claims

1. An injection of latamoxef sodium, characterized in that: The nano injection of latamoxef sodium specifically comprises the following components in parts by weight: 1.5-2.5 parts of latamoxef sodium, 6-9 parts of stabilizing and enhancing carrier matrix, 2.8-4.7 parts of long-acting anti-inflammatory, antibacterial and soothing lyophilized powder, 0.5-0.9 parts of mannitol, 8-12 parts of 0.9% sodium chloride solution, and 0.8-1.4 parts of acetic acid-sodium acetate buffer; The pH value of the acetic acid-sodium acetate buffer is 6.0-7.0; The raw materials for preparing the stabilizing and synergistic carrier matrix include the following components in parts by weight: 3-5 parts of hydroxypropyl methylcellulose, 3.6-6.2 parts of adipic anhydride, 0.8-1.3 parts of N,N-dimethylaminopyridine, 1.2-1.4 parts of histidine, 1.3-1.7 parts of ricinoleic acid, 0.5-0.7 parts of sucrose fatty acid ester, and 0.4-0.8 parts of 3,4-dihydroxyphenylalanine; The raw materials for preparing the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder include the following components in parts by weight: 0.6-0.9 parts of paeoniflorin, 0.3-0.7 parts of sinomenine, 0.5-0.8 parts of kaempferol, 0.6-0.8 parts of shikonin, 1.4-1.8 parts of echinacea polysaccharide, and 2-3 parts of caprylic acid.

2. The injection of latamoxef sodium according to claim 1, characterized in that: The preparation method of the stabilizing and synergistic carrier matrix specifically comprises the following steps: S1, mixing hydroxypropyl methylcellulose with adipic anhydride, N,N-dimethylaminopyridine and 50% ethanol solution, and reacting to obtain a modified hydroxypropyl methylcellulose solution; S2, dissolving histidine in ultrapure water to obtain a histidine solution; S3, mixing the histidine solution prepared in S2 with ricinoleic acid and sucrose fatty acid ester, and then keeping the mixture warm for 1.2-1.4 h to obtain a colloidal solution; S4, stirring and mixing the colloid solution prepared in S3, the modified hydroxypropyl methylcellulose solution prepared in S1, and 3,4-dihydroxyphenylalanine to obtain a stabilizing and synergistic carrier matrix.

3. The injection of latamoxef sodium according to claim 2, characterized in that: In S1, the mass fraction of the hydroxypropyl methylcellulose in the 50% ethanol solution is 5%.

4. The injection of latamoxef sodium according to claim 3, characterized in that: In S2, the mass fraction of histidine in ultrapure water is 4%.

5. The injection of latamoxef sodium according to claim 4, characterized in that: The preparation method of the long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder specifically comprises the following steps: L1, stirring and dissolving paeoniflorin, sinomenine, kaempferol and shikonin in 70% ethanol solution to obtain an anti-inflammatory and antibacterial soothing solution; L2, fully dissolving Echinacea polysaccharide in ultrapure water to obtain an Echinacea polysaccharide solution; L3, mixing the Echinacea polysaccharide solution prepared in L2, caprylic acid and chloroform, reacting the mixture, and then keeping the mixture at 85° C. for 24 h to obtain a milky solution; L4, uniformly dispersing the anti-inflammatory and antibacterial soothing solution prepared in L1 in the emulsion solution prepared in L3 to obtain a long-acting anti-inflammatory and antibacterial soothing suspension; L5. Freeze-dry the long-acting anti-inflammatory, antibacterial and soothing suspension prepared in L4 to obtain a long-acting anti-inflammatory, antibacterial and soothing freeze-dried powder.

6. The injection of latamoxef sodium according to claim 5, characterized in that: In L1, the mass fraction of the paeoniflorin in the 70% ethanol solution is 16-21%.

7. The injection of latamoxef sodium according to claim 6, characterized in that: In L2, the mass fraction of the Echinacea polysaccharide in ultrapure water is 18-23%.

8. The injection of latamoxef sodium according to claim 7, characterized in that: In L3, the mass fraction of octanoic acid in chloroform is 20-24%.

9. A method for preparing the injection of latamoxef sodium according to any one of claims 1 to 8, characterized in that: The specific steps include: Step 1: Stir and mix 0.9% sodium chloride solution, mannitol, and long-acting anti-inflammatory and antibacterial soothing lyophilized powder, and fully dissolve them to obtain a stabilizing basic solution; Step 2, dissolving latamoxef sodium in ultrapure water to obtain a latamoxef sodium solution; Step 3, placing the stabilizing and synergistic carrier matrix into the latamoxefox sodium solution prepared in step 2, stirring for sufficient adsorption, and then performing vacuum freeze nano spray drying to obtain latamoxefox sodium nanoparticles; Step 4: Stir and mix the latamoxef sodium nanoparticles prepared in step 3 and the stabilization base solution prepared in step 1, add acetic acid-sodium acetate buffer to adjust the pH value to 6.0-7.0 after mixing, and filter using a 0.22 mm sterile filter membrane to obtain a nano injection of latamoxef sodium.

10. The method for preparing the injection of latamoxef sodium according to claim 9, characterized in that: In step 2, the mass fraction of latamoxef sodium in ultrapure water is 25%.

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