Cefoperazone sodium and sulbactam sodium composition

Abstract

The invention provides a cefoperazone sodium and sulbactam sodium composition, which comprises the following raw materials in parts by weight: 9-10 parts of cefoperazone sodium, 1 part of sulbactam sodium and 0.05-0.07 part of glutathione. The glutathione is added to the composition, so that the composition has relatively good antibacterial effect. Furthermore, a little of sulbactam sodium is utilized, so that accumulation of the sulbactam sodium in a body is reduced; and the production cost is reduced. In addition, by a novel sulbactam sodium crystal, the composition provided by the invention has relatively good stability.

Description

technical field [0001] The invention belongs to the technical field of medicine and specifically designs a cefoperazone sodium sulbactam sodium composition. Background technique [0002] Cefoperazone sodium (Cefoperazone sodium), its chemical name is: (6R, 7R)-3-[[(1-methyl-1H-tetrazol-5yl)sulfur]methyl]-7-[(R)-2- (4-Ethyl-2,3-dioxo-1-piperazinecarbonamido)-2-p-hydroxyphenyl-acetylamino]-8-oxo-5-thia-1-azabicyclo[ 4.2.0] Oct-2-ene-2-carboxylic acid sodium salt. [0003] Cefoperazone sodium is a representative of the third-generation cephalosporins. It exerts antibacterial effects by inhibiting the synthesis of bacterial cell walls. It belongs to lactam antibiotics and can resist the degradation of various β-lactamases. It has a wide antibacterial spectrum and is effective against Gram-positive All bacteria have effects, such as Staphylococcus aureus (including strains that produce or do not produce penicillin), Streptococcus pneumoniae, most strains of beta-hemolytic strep...

AI Technical Summary

Problems solved by technology

[0005] Because both cefoperazone sodium and sulbactam sodium contain a lactam ring, and cefoperazone sodium is a weak acid strong base salt, the mother nucleus in the chemical structure contains an unstable β-lactam ring, which is easily hydrolyzed and degraded, and its stability is poor, and degradation and degradation often occur. Polymerization reaction, which leads to the decrease of the content of the active ingredients of the drug, the increase of impurities, and is extremely sensitive to acid and alkali. Therefore, it is necessary to strictly control the production conditions, especially after the development of a compound formula, the requirements for the production process are also stricter, otherwise it will be very difficult. It is easy to cause the content of impurities to exceed the standard, leading to the occurrence of side effects

And the storage stability of sulbactam sodium in the prior art is relatively poor, its related substances will increase significantly in the light and humid environment, the long-term storage impurity content is higher, and the use safety is poor, when it is compounded with cefoperazone sodium, it is easy to Affect the stability of the compound

The current commercially available compound preparations of cefoperazone sodium and sulbactam sodium have poor stability and need to be stored in a dry and cold place with strict storage conditions, and the validity period can only reach 24 months

[0006] Publication No. CN104844624A provides a co-crystal of cefoperazone sodium and sulbactam sodium and its preparation method. The co-crystal of cefoperazone sodium and sulbactam sodium in the present invention has a concentrated particle size distribution, and the product has good fluidity, surface gloss and high crystallinity. , good stability, the preparation method of its crystal form has simple process, easy operation, and is suitable for wide-scale popularization and application. The buffer can adjust the pH value, which not only solves the problems of poor uniformity, fluidity and raw material stability of the mixed powder in the preparation, but also avoids the generation of carbonate carbon dioxide gas when the stabilizer is added, and the obtained powder injection dissolves quickly after being diluted by conventional infusion. , no crystallization and degradation products are produced, the clarity of the solution meets the requirements, the pH value of the solution has no obvious change, the content of cefoperazone sodium and sulbactam sodium is stable, although the cefoperazone sodium sulbactam sodium cocrystal prepared by the present invention has improved its stability to a certain extent , but its antibacterial effect is not obvious

[0007] Publication No. CN103110644A provides a powder injection of cefoperazone sodium sulbactam sodium pharmaceutical composition for injection, which relates to the field of pharmaceutical preparations and preparation methods, and mainly solves the problem that the single product preparation of cefoperazone sodium sulbactam sodium and metronidazole in the prior art has a large dosage , the problem of poor therapeutic effect and large side effects after combination, the pharmaceutical composition comprises cefoperazone sodium sulbactam sodium and metronidazole lipid microspheres, the weight of cefoperazone sodium sulbactam sodium and metronidazole lipid microspheres is expressed by metronidazole According to the calculation, the pharmaceutical composition is prepared as injection powder, and the pH value of the aqueous solution of the pharmaceutical composition is 4.5-6.0, but the metronidazole lipid microspheres in the present invention are complicated to prepare, are not suitable for industrial production, and have poor stability. needs improvement

[0008] Publication No. CN101780086A discloses a composition containing cefoperazone sulbactam sodium and lysine. The weight ratio between cefoperazone sodium, sulbactam sodium and lysine is 1-50:1:0.02-1. The inventive composition can increase the renal clearance rate of sulbactam and effectively reduce the accumulation of sulbactam in the body. At the same time, an appropriate pH regulator is added to increase the solubility and stability of the composition, thereby improving its clinical use Efficacy and safety, but its stability needs to be further improved

[0009] In the prior art, the compound preparation of cefoperazone sodium and sulbactam sodium combined at 1:1 or 2:1, the antibacterial activity of the compound preparation is obviously improved, and the drug resistance rate is obviously decreased, and it has been clinically proven to have a good antibacterial effect. In the compound preparation of cefoperazone sodium and sulbactam sodium, because cefoperazone sodium is mainly cleared through the liver, and then cleared through the kidneys, clinical studies have confirmed that in patients with renal impairment, the clearance rate of sulbactam sodium is significantly reduced, which is likely to cause accumulation in the body, and The cost of sulbactam sodium is relatively high. If more sulbactam sodium or its salts are used in compound preparations, the production cost of the drug will be increased, thereby increasing the medical burden of patients

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