Novel piperacillin-tazobactam composition

Abstract

The invention discloses a novel piperacillin-tazobactam composition. Pegylation is performed on the piperacillin, so that the good stability is ensured simultaneously when the water-solubility of the drug is improved; the tazobactam is modified to be tazobactam glucuronate, therefore, the characteristic of high hygroscopicity is modified, problems of poor liquidity caused by easy absorption of moisture, non-uniform mixing with piperacillin, easiness in color change and metamorphic degradation and the like can be avoided, while the pototype drug is released after the drug enters human bodies, the antidote, i.e. glucuronic acid, is also released and can be used for treating drug cumulative poisoning and residue caused by large use amount of antibiotic in a long period; after being respectively subjected to molecular modification, the two active ingredients are modified in physicochemical property, greatly improved in stability, ensured in effective content after the drug enters the human bodies; and therefore, the problem of quality stability of the novel composition in production, storage, preparation and infusion processes is basically solved, and the dosage of tazobactam is greatly reduced.

Description

technical field [0001] The invention relates to an antibiotic drug, in particular to a novel piperacillin-tazobactam composition. Background technique [0002] Piperacillin Sodium-Tazobactam Sodium for Injection was successfully developed by Wyeth Corporation of the United States, and its marketed dosage form is powder injection. Piperacillin is a broad-spectrum β-lactam antibiotic. It introduces a heterocyclic substituted amide group on the amino group of ampicillin. It has a strong and rapid effect because it can quickly penetrate the cell membrane of a variety of Gram-positive bacteria. , has an enhanced effect on Pseudomonas aeruginosa, and is a penicillin derivative with a wider antibacterial spectrum, but it is hygroscopic and unstable in room temperature solution, which will lead to the formation of particulate matter. Piperacillin is easily destroyed by β-lactamase, and tazobactam is an irreversible competitive β-lactamase inhibitor, and its inhibitory activity far ...

AI Technical Summary

Problems solved by technology

[0003] In the process of preparing by freeze-drying method, piperacillin sodium and tazobactam sodium are in a solution state during the liquid preparation and drying process, which are prone to degradation and deterioration, resulting in unqualified product quality; and the common preparations on the market have poor stability and cannot Meet the quality requirements within the validity period; the liquid medicine is unstable at room temperature and is easy to form granules, especially after the frozen piperacillin sodium tazobactam sodium solution is re-thawed or the product prepared as freeze-dried powder is reconstituted into a solution The longer the storage time, the more particles will be generated. The particles in the solution for intravenous injection are very harmful to the patient and may cause infusion phlebitis

[0004] Chinese patent CN1802179A discloses that Wyeth of the United States adds ion chelating agent ethylenediaminetetraacetic acid sodium salt (EDTA) and buffering agent sodium citrate to piperacillin sodium and tazobactam sodium, and controls the interaction between the drug and the excipients. Ratio, solves the problem of microparticles formed in the pharmaceutical composition during reconstitution and thawing in the prior art, can be used safely for parenteral administration, the disadvantage is that ion chelating agents, especially ethylenediaminetetraacetic acid (EDTA ) is likely to cause the loss of sodium, potassium, and calcium ions in the bones, resulting in risks such as osteoporosis

[0005] Chinese patents CN101890016A and CN101890015A respectively disclose a microsphere injection and a liposome injection of piperacillin sodium and tazobactam sodium pharmaceutical composition, which can improve the problem of poor stability of common injections to a certain extent

These new injection preparations (liposome injections, microsphere injections) have certain advantages over traditional injections, but they also have low encapsulation efficiency, easy adhesion and aggregation, easy rupture, burst release effect, and possible cause immune response

In addition, the scale-up production of these new dosage forms in China is not mature enough, and the preparation process conditions are very strict, the production is difficult, the process reproducibility is poor, and the production cost is high, which virtually increases the financial burden of patients, so it does not not the best choice

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